Effects of Tongue Strength Training on Patients with Mild to Moderate Sleep-disordered Breathing: A Randomized Controlled Trial.

Objectives: : Several studies have reported that oropharyngeal myofunctional therapy (OMT) reduces the severity of obstructive sleep apnea (OSA). However, because OMT protocols are often complicated, they take time and effort to implement. The aim of this study was to determine the therapeutic effect of 8 weeks of simple tongue strength training with a training device. Methods: : Twenty patients with mild to moderate sleep-disordered breathing were randomized to the control group (n=10) or intervention group (n=10). The patients in the intervention group completed 8 weeks of daily tongue strength training using a training device. After 8 weeks, we evaluated each patient for sleep-disordered breathing by portable monitoring. We also evaluated each patient's body mass index (BMI), neck circumference, Epworth Sleepiness Scale (ESS) score, and tongue pressure. Results: No significant difference was found in the change in apnea hypopnea index (AHI) from baseline to 8 weeks between the control and intervention groups (P=0.44). However, the changes in neck circumference (P=0.02) and maximum tongue pressure (P=0.03) from baseline to 8 weeks were significantly different between the two groups. No significant difference was found for changes in BMI and ESS scores from baseline to 8 weeks between the two groups. Conclusions: : Tongue strength training in patients with sleep-disordered breathing did not significantly improve AHI as measured by portable monitoring, although significant changes were observed for increased tongue pressure and reduced neck circumference.

Mechanism of action of adapalene for treating EGFR-TKI-induced skin disorder.

BACKGROUND: Skin disorders are the most common side effect associated with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. It is important to manage skin lesions. Adapalene has been used to treat skin lesions caused by EGFR-TKIs in some cases. The aim of this study was to investigate the functional mechanism of adapalene in erlotinib-induced skin disorder. METHODS: To analyze the effect of adapalene on skin rash, afatinib and adapalene were administered to mice. The relationship between the concentration of adapalene and skin disorders was also examined by analyzing AQP3 expression. A skin lesion model was experimentally established in human skin keratinocytes (HaCaT) by using erlotinib with TNF-α and IL-1ß. We used qRT-PCR to analyze chemokine-induced inflammation and western blotting to analyze the effects of adapalene on the NF-κB signaling pathway. Antimicrobial peptides and adhesion factors were also examined using qRT-PCR. RESULTS: Mice administered 0.01% adapalene had less skin inflammation than mice treated with afatinib alone. The expression level of AQP3 decreased in an adapalene concentration-dependent manner. The mRNA levels of proinflammatory cytokines such as CCL2 and CCL27 in HaCaT cells were significantly reduced by adapalene. The expression of an antimicrobial peptide, hBD3, was upregulated after adapalene treatment. Adhesion factors, such as E-cadherin, were significantly downregulated by EGFR-TKI and significantly upregulated by adapalene treatment. Western blot analysis suggested that erlotinib-induced phosphorylation of p65 was decreased by adapalene. CONCLUSION: We suggest that adapalene may be a possible treatment option for skin disorders induced by EGFR-TKIs.

Real-World Safety and Effectiveness of Benralizumab in Japanese Patients with Severe Asthma: A Multicenter Prospective Observational Study.

Introduction: This study aimed to demonstrate whether benralizumab maintained the safety and effectiveness profiles established in randomized controlled trials among all patients with severe uncontrolled asthma initially prescribed benralizumab in the real-world setting in Japan. Methods: This was a prospective, observational, multicenter post-marketing study (ClinicalTrial.gov, NCT03588546). The safety and tolerability of benralizumab over 1 year were assessed by the incidence of adverse events (AEs), serious AEs, adverse drug reactions (ADRs), and serious ADRs. Patient background characteristics indicating a more frequent onset of ADRs with benralizumab were explored. The main effectiveness assessment was the change in Asthma Control Questionnaire-5 (ACQ-5) score from baseline. Patients with baseline ACQ-5 scores ≥1.5 were defined as having severe uncontrolled asthma. Results: In total, 632 patients were evaluated for safety and 274 for effectiveness; 139 patients were included in the severe uncontrolled asthma subgroup. ADRs were reported in 12.7% and serious AEs in 13.0% of patients. Serious infections occurred in 3.8%, serious hypersensitivity in 0.3%, and malignancy in 0.3% of patients. No helminthic infections occurred. In the effectiveness population, benralizumab improved the mean (standard deviation [95% confidence interval]) ACQ-5 score by -1.16 (1.40 [-1.36, -0.96]) from baseline; forced expiratory volume in 1 second by 0.151 (0.440 [0.09, 0.21]) L; and Mini-Asthma Quality of Life questionnaire score by 1.16 (1.29 [0.94, 1.38]) at the last observation. The annual asthma exacerbation rate was 0.42. A greater ACQ-5 score improvement was observed among patients with eosinophilic asthma characteristics. Conclusion: No new safety concerns were raised, and patients experienced benefits consistent with previous studies of benralizumab, thus supporting the use of benralizumab for the add-on maintenance treatment of patients with eosinophilic severe uncontrolled asthma.

Low-Intensity Pulsed Ultrasound Maintains Bone Mass After Withdrawal of Human Parathyroid Hormone in Ovariectomized Mice.

The intermittent injection of teriparatide, a recombinant fragment of human parathyroid hormone (PTH 1-34), activates anabolic activity on bone turnover. However, the PTH administration period is limited to 2 years. Thus, sequential therapy after discontinuation of PTH is required. Low-intensity pulsed ultrasound (LIPUS) has been widely used for bone fracture healing. In this study, we examined the effects of LIPUS on bone mass after PTH withdrawal in ovariectomized (OVX) model mice. The LIPUS-non-irradiated femoral trabecular bone mineral density (BMD) in the treated after PTH withdrawal was significantly decreased. Meanwhile, the femoral BMD in the OVX + PTH-LIPUS group was remarkably higher than that of the OVX group. Additionally, mRNA expression of Runx2, Osterix, Col1a1, and ALP increased significantly following LIPUS irradiation after PTH withdrawal. These results suggest that LIPUS protected against femoral trabecular BMD loss and up-regulated the osteogenic factors following PTH withdrawal in OVX mice.

Identification of a 17 kDa protein that is a potentially novel antigen of lettuce-associated respiratory allergy in farmers.

BACKGROUND: We have identified and reported a novel antigen, nonprotein-specific secreted EP1-like glycoprotein (51 kDa), for lettuce-related respiratory allergy. OBJECTIVE: We aimed to identify a novel antigen for lettuce-related respiratory allergy that is different from epidermis-specific secreted EP1-like glycoprotein. METHODS: Immunoblotting was performed using an immunoglobulin E-specific antibody. The antigen-antibody reaction was confirmed by means of enzyme-linked immunosorbent assaying. LC-MS/MS analysis was carried out to detect a novel protein found in sera from 3 of 13 patients with lettuce-related respiratory allergy. Finally, we purified a novel protein from Escherichia coli. RESULTS: Immunoblotting assays showed common bands of 17 kDa in the sera of 3 of 13 patients. An enzyme-linked immunosorbent assay confirmed that the patient sera reacted with lettuce latex juice. A 17 kDa protein band that showed antigenic reactivity in 3 of 13 patient sera was identified as a kirola-like protein by LC-MS/MS. In addition, although we purified this protein, we failed to show the inhibitory effect. CONCLUSION: A 17 kDa protein that is a potentially novel antigen of lettuce-associated respiratory allergy was identified. In further studies, we will focus on purifying this novel protein to diagnose lettuce allergy.

In-hospital Mortality among Patients with High-flow Nasal Cannulas in the General Ward.

High-flow nasal cannulas (HFNCs) have become common devices for patients with respiratory failure who are treated in general wards. Few reports have been published on in-hospital mortality associated with the ratio of oxygen saturation (ROX) index, measured by pulse oximetry/fraction of inspired oxygen to respiratory rate, in patients treated with HFNCs. We aimed to examine in-hospital mortality and associated factors in patients who initiated HFNC use in a general ward. Sixty patients who initiated HFNC use in general wards at Kobe University Hospital between December 2016 and October 2020 were retrospectively enrolled. We assessed in-hospital mortality, comorbidities, and ROX index. The in-hospital mortality was 48.3%, and ROX index values were significantly lower in patients who died than in those who did not (at HFNC oxygen therapy initiation; 6.93 [2.73-18.5] vs. 9.01 [4.62-18.1], p = 0.00861). Although the difference was not statistically significant, the change in ROX index values between HFNC initiation and 12 hours after initiation tended to be greater in the patients who died in the hospital (0.732 [-2.84-3.5] vs. -0.35[-4.3-2.6], p = 0.0536). Lower ROX index values may be associated with the in-hospital death of patients who are treated with HFNCs in general wards.

A case of eosinophilic pneumonia induced by lettuce.

A 56-year-old female lettuce farmer was admitted to the hospital with a low-grade fever, worsening cough, and dyspnoea. A blood test revealed eosinophilia and a high serum IgE concentration. The 3-year follow-up showed that her total IgE level increased in December, peaked in May, and suddenly decreased in August. This result was consistent with the lettuce harvest season. A chest x-ray taken on admission showed an infiltrative shadow in the upper lung field. Chest CT revealed patchy ground glass opacity on the upper lung field and thickening of the bronchial wall. The bronchoalveolar lavage fluid contained 8% eosinophils. She was treated with prednisolone, and her symptoms and radiological findings improved. The 37 kDa protein that reacted with the patient's sera was identified by immunoblot analysis.

Nationwide survey of refractory asthma with bronchiectasis by inflammatory subtypes.

RATIONALE: Bronchiectasis and bronchiolitis are differential diagnoses of asthma; moreover, they are factors associated with worse asthma control. OBJECTIVE: We determined clinical courses of bronchiectasis/bronchiolitis-complicated asthma by inflammatory subtypes as well as factors affecting them. METHODS: We conducted a survey of refractory asthma with non-cystic fibrosis bronchiectasis/bronchiolitis in Japan. Cases were classified into three groups, based on the latest fractional exhaled NO (FeNO) level (32 ppb for the threshold) and blood eosinophil counts (320/µL for the threshold): high (type 2-high) or low (type 2-low) FeNO and eosinophil and high FeNO or eosinophil (type 2-intermediate). Clinical courses in groups and factors affecting them were analysed. RESULTS: In total, 216 cases from 81 facilities were reported, and 142 were stratified: 34, 40 and 68 into the type 2-high, -intermediate and -low groups, respectively. The frequency of bronchopneumonia and exacerbations requiring antibiotics and gram-negative bacteria detection rates were highest in the type 2-low group. Eighty-seven cases had paired latest and oldest available data of FeNO and eosinophil counts; they were analysed for inflammatory transition patterns. Among former type 2-high and -intermediate groups, 32% had recently transitioned to the -low group, to which relatively low FeNO in the past and oral corticosteroid use contributed. Lastly, in cases treated with moderate to high doses of inhaled corticosteroids, the frequencies of exacerbations requiring antibiotics were found to be higher in cases with more severe airway lesions and lower FeNO. CONCLUSIONS: Bronchiectasis/bronchiolitis-complicated refractory asthma is heterogeneous. In patients with sputum symptoms and low FeNO, airway colonisation of pathogenic bacteria and infectious episodes are common; thus, corticosteroids should be carefully used.

Cross-sectional study of cholinergic urticaria subtypes and bronchial hyperresponsiveness.

Cholinergic urticaria (CholU) is classified into several subtypes: (1) conventional sweat allergy-type CholU (conventional SAT-CholU), (2) CholU with palpebral angioedema (CholU-PA), 3) CholU with acquired anhidrosis and/or hypohidrosis (CholU-Anhd); 1) and 2) include SAT based on pathogenesis. There have been no studies on differences in the prevalence of bronchial asthma among the subtypes. We analyzed bronchial responsiveness using the methacholine dose indicator Dmin, respiratory symptoms, and exhaled nitric oxide (FeNO). Median log10 Dmin (interquartile range) of patients with conventional SAT-CholU (n = 11), CholU-PA (n = 11), and CholU-Anhd (n = 11) was 0.381 (- 0.829, 1.079), 0.717 (0.249, 0.787), and 1.318 (0.121, 1.699), respectively (p = 0.516). Respiratory symptoms were less frequently observed in CholU-Anhd than in conventional SAT-CholU or CholU-PA. FeNO of patients with conventional SAT-CholU, CholU-PA, and CholU-Anhd was 23 (18.5, 65.0), 39 (32.0, 59.5), and 25 (19.0, 33.0) ppb, respectively (p = 0.237). Nine% of conventional SAT-CholU patients and more than half of CholU-PA patients required treatment for asthma. Log Dmin tended to be lower in patients with SAT-CholU than in those with CholU-Anhd. CholU-PA might be associated with asthma.

The utility of bispectral index monitoring in flexible bronchoscopy: A single-center, retrospective observational study.

BACKGROUND: The desired depth of sedation during flexible bronchoscopy is one in which verbal contact is possible whenever necessary. Although it is common that the depth of sedation is assessed by validated instruments such as the modified observer's assessment of alertness and sedation (MOAA/S) score, the repeated stimulation associated with the assessment can affect the sedation. The bispectral index (BIS) has been widely used for general anesthesia due to its objective and noninvasive nature. However, the utility of BIS monitoring and a target BIS value for use during bronchoscopy have not been fully elucidated. METHODS: We performed a retrospective observational study to assess the utility of the BIS value for monitoring conscious sedation during bronchoscopy at Kobe University Hospital from August 2020 to April 2021. RESULTS: Eighteen patients underwent bronchoscopy with BIS monitoring. The BIS value significantly correlated with the MOAA/S score (r = 0.2, p < 0.01), and the correlation was stronger in sufficiently sedated patients (r = 0.486, p < 0.01). The lowest MOAA/S score during the procedure was highly correlated with the BIS value (r = 0.625, p < 0.01). The BIS monitoring seemed to be more sensitive to changes in the sedation level than the MOAA/S score, heart rate and mean arterial pressure. The median BIS value at an MOAA/S score of 3-4, the desired depth of sedation, was 82.0. CONCLUSIONS: BIS value is useful for monitoring sedation during bronchoscopy. This study suggests that a BIS value of 82 reflects an adequate level of sedation.

Inhaled corticosteroids do not affect the antibody titer against the SARS-CoV-2 spike protein in BNT162b2 mRNA vaccinated patients.

OBJECTIVES: Oral corticosteroids reduce the antibody titer of the BNT162b2 mRNA vaccine against SARS-CoV-2. To date, the effect of inhaled corticosteroids on antibody titers is unknown. STUDY DESIGN: The design of this study is retrospective study. METHODS: We analyzed the relationship between the clinical features and total antibody titers against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein in 320 subjects who had never been infected with Coronavirus disease 2019 (COVID-19) and were vaccinated the second time with the BNT162b2 mRNA vaccine between October 1 to December 28, 2021. RESULTS: Of the 320 subjects, 205 were treated with inhaled corticosteroids. The median antibody titer of patients treated with inhaled corticosteroids was 572 U/mL, which was significantly higher than that of patients treated without inhaled corticosteroids (454U/mL, P = 0.00258). The median antibody titers of smokers, men, and patients aged 65 years and over, were 315.5 U/mL, 385 U/mL, and 425.5 U/mL, respectively. These results are significantly lower than those of patients who never smoked, women, and patients aged less than 64 years (582 U/mL [P < 0.0001], 682.5 U/mL [P < 0.0001], and 717 U/mL [P < 0.0001], respectively). The multivariate analysis revealed that females and age were independent antibody titer-reducing factors (P = 0.0001 and P < 0.0001, respectively). CONCLUSIONS: The use of inhaled corticosteroids did not reduce the antibody titer against SARS-CoV-2 spike protein. Clinicians should continue treatment with inhaled corticosteroids if indicated.

Immunotherapy in Advanced Non-Small Cell Lung Cancers: Current Status and Updates.

Non-small-cell lung cancer (NSCLC) is a major health burden, and novel therapeutic options are needed to help solve this problem. One such option is immunotherapy, which targets immune checkpoint molecules that inhibit cancer cells, decreasing immune system activation, for example, immunotherapies target PD-1, its ligand PD-L1, and CTLA-4. There have been major advances in the development of agents that inhibit these molecules, called immune checkpoint inhibitors, and several of them are already approved for usage in NSCLC patients, especially in advanced stages. In this review, the reasons why immune checkpoint inhibitors could be beneficial and the clinical results of studies using these drugs for advanced or recurrent NSCLC patients are discussed, as is the safety profile of the drugs.

Budesonide/glycopyrronium/formoterol fumarate triple therapy prevents pulmonary hypertension in a COPD mouse model via NFκB inactivation.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a health problem that results in death, commonly due to the development of pulmonary hypertension (PH). Here, by utilizing a mouse model of intratracheal elastase-induced emphysema that presents three different phases of COPD, we sought to observe whether budesonide/glycopyrronium/formoterol fumarate (BGF) triple therapy could prevent COPD-PH in addition to ameliorating COPD progression. METHODS: We utilized intratracheal elastase-induced emphysema mouse model and performed experiments in three phases illustrating COPD progression: inflammatory (1 day post-elastase), emphysema (3 weeks post-elastase) and PH (4 weeks post-elastase), while treatments of BGF and controls (vehicle, one-drug, and two-drug combinations) were started in prior to elastase instillation (inflammatory phase), at day 7 (emphysema), or at day 14 (PH phase). Phenotype analyses were performed in each phase. In vitro, A549 cells or isolated mouse lung endothelial cells (MLEC) were treated with TNFα with/without BGF treatment to analyze NFκB signaling and cytokine expression changes. RESULTS: We observed significant reductions in the proinflammatory phenotype observed in the lungs and bronchoalveolar lavage fluid (BALF) 1 day after elastase administration in mice treated with BGF compared with that in mice administered elastase alone (BALF neutrophil percentage, p = 0.0011 for PBS/Vehicle vs. PBS/Elastase, p = 0.0161 for PBS/Elastase vs. BGF). In contrast, only BGF treatment significantly ameliorated the elastase-induced emphysematous lung structure and desaturation after three weeks of elastase instillation (mean linear intercept, p = 0.0156 for PBS/Vehicle vs. PBS/Elastase, p = 0.0274 for PBS/Elastase vs. BGF). Furthermore, BGF treatment prevented COPD-PH development, as shown by improvements in the hemodynamic and histological phenotypes four weeks after elastase treatment (right ventricular systolic pressure, p = 0.0062 for PBS/Vehicle vs. PBS/Elastase, p = 0.027 for PBS/Elastase vs. BGF). Molecularly, BGF acts by inhibiting NFκB-p65 phosphorylation and subsequently decreasing the mRNA expression of proinflammatory cytokines in both alveolar epithelial and pulmonary endothelial cells. CONCLUSION: Our results collectively showed that BGF treatment could prevent PH in addition to ameliorating COPD progression via the inhibition of inflammatory NFκB signaling.

Cross-Neutralizing Activity Against Omicron Could Be Obtained in SARS-CoV-2 Convalescent Patients Who Received Two Doses of mRNA Vaccination.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant omicron is now under investigation. We evaluated cross-neutralizing activity against omicron in coronavirus disease 2019 (COVID-19) convalescent patients (n = 23) who had received 2 doses of an mRNA vaccination (BNT162b2 or mRNA-1273). Intriguingly, after the second vaccination, the neutralizing antibody titers of subjects against SARS-CoV-2 variants, including omicron, all became seropositive, and significant fold-increases (21.1-52.0) were seen regardless of the disease severity. Our findings thus demonstrate that 2 doses of mRNA vaccination to SARS-CoV-2 convalescent patients can induce cross-neutralizing activity against omicron.

Randomized single-blind comparative study of the midazolam/pethidine combination and midazolam alone during bronchoscopy.

BACKGROUND: Bronchoscopy can be a distress for the patient. There have been few studies on the combination of sedatives and opioids. The aim of this study was to demonstrate the usefulness and safety of administration of the combination of midazolam and pethidine during bronchoscopy. METHODS: In this prospective randomized single (patient)-blind study, we randomly assigned 100 patients who were scheduled to undergo bronchoscopy biopsy to receive treatment with either the midazolam/pethidine combination (combination group) or midazolam alone (midazolam group) during examinations. After the end of bronchoscopy, patients completed a questionnaire and the visual analogue scale was measured. The primary outcome was the patients' acceptance of re-examination assessed by visual analogue scale. We also assessed pain levels, vital signs, midazolam use, xylocaine use, and adverse events. Univariate analyses were performed using Fisher's exact test for categorical data, and the t-test or Mann-Whitney test was carried out for analysis of numeric data. All P-values were two-sided, and values < 0.05 were considered statistically significant. RESULTS: We analyzed 47 patients in the combination group and 49 patients in the midazolam group. The primary outcome was a good trend in the combination group, but not significantly different (3.82 ± 2.3 in combination group versus 4.17 ± 2.75 in midazolam alone, P = 0.400). In the combination group, the visual analog scale score for pain during bronchoscopy was significantly lower (1.10 ± 1.88 versus 2.13 ± 2.42, P = 0.022), and the sedation level score per the modified observer's assessment of alertness/sedation scale was significantly deeper (3.49 ± 0.98 versus 3.94 ± 1.03, P = 0.031). Maximal systolic blood pressure during testing was significantly lower (162.39 ± 23.45 mmHg versus 178.24 ± 30.24 mmHg, P = 0.005), and the number of additional administrations of midazolam was significantly lower (2.06 ± 1.45 versus 2.63 ± 1.35, P = 0.049). There were also significantly fewer adverse events (30 versus 41, P = 0.036). CONCLUSIONS: The combination uses of midazolam and pethidine for sedation resulted in significant improvements in the pain, blood pressure, additional use of midazolam, and safety during bronchoscopy among patients. TRIAL REGISTRATION: This study was registered in the University Medical Hospital Information Network in Japan (UMINCTR Registration number: UMIN000032230 , Registered: 13/April/2018).

Cross-Neutralizing Breadth and Longevity Against SARS-CoV-2 Variants After Infections.

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the virus responsible for the Coronavirus Disease 2019 (COVID-19) pandemic. The emergence of variants of concern (VOCs) has become one of the most pressing issues in public health. To control VOCs, it is important to know which COVID-19 convalescent sera have cross-neutralizing activity against VOCs and how long the sera maintain this protective activity. Methods: Sera of patients infected with SARS-CoV-2 from March 2020 to January 2021 and admitted to Hyogo Prefectural Kakogawa Medical Center were selected. Blood was drawn from patients at 1-3, 3-6, and 6-8 months post onset. Then, a virus neutralization assay against SARS-CoV-2 variants (D614G mutation as conventional strain; B.1.1.7, P.1, and B.1.351 as VOCs) was performed using authentic viruses. Results: We assessed 97 sera from 42 patients. Sera from 28 patients showed neutralizing activity that was sustained for 3-8 months post onset. The neutralizing antibody titer against D614G significantly decreased in sera of 6-8 months post onset compared to those of 1-3 months post onset. However, the neutralizing antibody titers against the three VOCs were not significantly different among 1-3, 3-6, and 6-8 months post onset. Discussion: Our results indicate that neutralizing antibodies that recognize the common epitope for several variants may be maintained for a long time, while neutralizing antibodies having specific epitopes for a variant, produced in large quantities immediately after infection, may decrease quite rapidly.

Retrospective Analysis of the Starting Dose of Combined ICS/LABA for Cough-variant Asthma and Cough-predominant Asthma.

BACKGROUND/AIM: Although the usefulness of inhaled corticosteroids and long-acting ß2 agonists (ICS/LABA) in cough-variant asthma and cough-predominant asthma has been reported, there is no consensus on its starting dose. The aim of this study is to find the optimal dose of ICS/LABA for cough-variant asthma and cough-predominant asthma. PATIENTS AND METHODS: We analysed 112 patients who visited our clinic from January 2009 to December 2012 with the chief complaint of cough that had continued for more than 3 weeks. Cough-variant asthma (n=30) and cough-predominant asthma (n=7) were treated with ICS/LABA. RESULTS: There was no significant difference in cough duration time from starting ICS/LABA in cough-variant asthma and cough-predominant asthma between medium and high doses (14.3% versus 10.9%, respectively) (p=0.192). Moreover, there was no significant difference in cough duration time from starting ICS/LABA in cough-variant asthma between medium and high doses (13.2% versus 11.5%, respectively) (p=0.433). CONCLUSION: The medium starting dose of ICS/LABA is sufficient for treating cough-variant asthma.

Annexin A10 Expression as a Novel Prognostic Marker in Lung Adenocarcinoma.

BACKGROUND/AIM: Annexin A10 (ANXA10) is a member of the annexin family and a calcium-dependent phospholipid-binding protein. The aim of this study was to clarify the clinical significance of ANXA10 expression in lung adenocarcinoma. MATERIALS AND METHODS: ANXA10 expression was immunohistochemically examined in surgical specimens of lung adenocarcinoma obtained from 74 consecutive patients who underwent complete resection from January 2014 to December 2014. Expression of ANXA10 was down-regulated in A549 cells via siRNA transfection and the effect of ANXA10 on cell migration was assessed by the wound healing assay. Expression of ANXA10 was examined by immunocytochemistry and polymerase chain reaction. RESULTS: High ANXA10 expression was significantly correlated with poor overall survival (p=0.00705). Multivariate analysis with the Cox proportional hazard model demonstrated that ANXA10 expression was an independent prognostic factor. Cell migration was suppressed in ANXA10-down-regulated A549 cell lines. CONCLUSION: ANXA10 has a role in cancer cell migration and high ANXA10 expression is a novel prognostic marker in lung adenocarcinoma.

The Gut Microbiome as a Biomarker of Cancer Progression Among Female Never-smokers With Lung Adenocarcinoma.

BACKGROUND/AIM: The gut microbiome plays an important role in the immune system and has attracted attention as a biomarker of several diseases, including cancer. In this study, we examined the relationship between the gut microbiome and lung cancer progression. PATIENTS AND METHODS: Female never-smokers diagnosed with lung adenocarcinoma were consecutively enrolled between May 2018 and August 2019, and fecal samples were collected. Principal coordinate analyses were performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. RESULTS: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). CONCLUSION: This study identified the gut microbiome as a promising biomarker of lung cancer progression.