Association of gut microbiome with COPD in Japanese male residents: the SESSA study.

Background: Altered gut microbiota may contribute to COPD development or progression. Herein, we investigated the association of gut microorganisms with COPD, taking into account the impact of smoking status. Methods: This cross-sectional observational study was a part of the Shiga Epidemiological Study of Subclinical Atherosclerosis, a population-based cohort study of Japanese men aged 46-76 years, conducted from 2010 to 2016. The gut microbiome, determined using 16S rRNA gene sequencing, was compared among 99 never-smokers, 306 non-COPD ever-smokers and 76 patients with COPD while adjusting for age, body mass index, ethanol consumption and treatment for type 2 diabetes mellitus. Results: The abundance of phylum Firmicutes was comparable between patients with COPD and non-COPD ever-smokers but tended to be higher in never-smokers. Similarly, the α- and ß-diversity analysis showed similarity between patients with COPD and non-COPD ever-smokers, which tended to differ from never-smokers. Discriminant analysis identified the genus [Prevotella] to be more prevalent in patients with COPD than in never-smokers or non-COPD ever-smokers. Post hoc analysis confirmed similarity of gut microbiome between COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I and non-COPD ever-smokers, which was different from GOLD II. Conclusion: Smoking may alter the overall gut microbial composition, but gut microbial composition itself may not play a role in the development of COPD. Rather, specific gut bacteria, such as [Prevotella], could be a risk factor for the development of COPD; this may be a potential therapeutic target.

Changes in enamel hardness, wear resistance, surface texture, and surface crystal structure with glass ionomer cement containing BioUnion fillers.

This study investigated the potential of BioUnion filler containing glass ionomer cement (GIC) to enhance the properties of enamel surrounding restorations, with a specific focus on the effect on hardness. The hardness of the bovine enamel immersed in the cement was measured using Vickers hardness numbers. Following sliding and impact wear simulations, the enamel facets were examined using confocal-laser-scanning microscopy and scanning-electron microscopy. Surface properties were further analyzed using energy-dispersive X-ray spectroscopy and X-ray diffraction (XRD). A significant increase in Vickers hardness numbers was observed in the BioUnion filler GIC after 2 days. Furthermore, the mean depth of enamel facets treated with BioUnion filler GIC was significantly less than that of untreated facets. Characteristic XRD peaks indicating the presence of hydroxyapatite were also observed. Our findings imply that GIC with BioUnion fillers enhances the mechanical properties of the tooth surface adjacent to the cement.

Prophylactic treatment of dacomitinib-induced skin toxicities in epidermal growth factor receptor-mutated non-small-cell lung cancer: A multicenter, Phase II trial.

BACKGROUND: Dacomitinib significantly improves progression-free survival and overall survival (OS) compared with gefitinib in patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR)-activating mutations. However, dacomitinib often causes skin toxicities, resulting in treatment discontinuation. We aimed to evaluate a prophylactic strategy for skin toxicity induced by dacomitinib. METHODS: We performed a single-arm, prospective, open-label, multi-institutional phase II trial for comprehensive skin toxicity prophylaxis. Patients with NSCLC harboring EGFR-activating mutations were enrolled and received dacomitinib with comprehensive prophylaxis. The primary endpoint was the incidence of skin toxicity (Grade ≥2) in the initial 8 weeks. RESULTS: In total, 41 Japanese patients participated between May 2019 and April 2021 from 14 institutions (median age 70 years; range: 32-83 years), 20 were male, and 36 had a performance status of 0-1. Nineteen patients had exon 19 deletions and L858R mutation. More than 90% of patients were perfectly compliant with prophylactic minocycline administration. Skin toxicities (Grade ≥2) occurred in 43.9% of patients (90% confidence interval [CI], 31.2%-56.7%). The most frequent skin toxicity was acneiform rash in 11 patients (26.8%), followed by paronychia in five patients (12.2%). Due to skin toxicities, eight patients (19.5%) received reduced doses of dacomitinib. The median progression-free survival was 6.8 months (95% CI, 4.0-8.6 months) and median OS was 21.6 months (95% CI, 17.0 months-not reached). CONCLUSION: Although the prophylactic strategy was ineffective, the adherence to prophylactic medication was quite good. Patient education regarding prophylaxis is important and can lead to improved treatment continuity.

Autobullectomy with COVID-19 in a patient with chronic obstructive pulmonary disease.

A 72-year-old man with chronic obstructive pulmonary disease (COPD) was admitted for coronavirus disease 2019 (COVID-19). He was discharged on day 30; however, he was readmitted 6 days later due to a left lung organizing pneumonia secondary to COVID-19. After methylprednisolone treatment, the patient was discharged on day 15. One year later, computed tomography showed shrinkage of emphysematous lesions, and both total lung capacity measured using computed tomography and fraction of low attenuation volume decreased in the left lung compared to that before COVID-19. Here, we report a rare case of autobullectomy with COVID-19 in a patient with COPD.

Inspiratory and Expiratory Computed Tomography Imaging Clusters Reflect Functional Characteristics in Chronic Obstructive Pulmonary Disease.

Purpose: Disease probability measure (DPM) is a useful voxel-wise imaging assessment of gas-trapping and emphysematous lesions in patients with chronic obstructive pulmonary disease (COPD). To elucidate the progression of COPD, we performed a cluster analysis using the following DPM parameters: normal (DPMNormal), gas-trapping (DPMGasTrap), and emphysematous lesions (DPMEmph). Our findings revealed the characteristics of each cluster and the 3-year disease progression using imaging parameters. Patients and Methods: Inspiratory and expiratory chest computed tomography (CT) images of 131 patients with COPD were examined, of which 84 were followed up for 3 years. The percentage of low attenuation volume (LAV%) and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) were quantitatively measured using inspiratory chest CT. A hierarchical cluster analysis was performed using the DPM parameters at baseline. Five clusters were named according to the dominant DPM parameters: normal (NL), normal-GasTrap (NL-GT), GasTrap (GT), GasTrap-Emphysema (GT-EM), and Emphysema (EM). Results: Women were predominantly diagnosed with GT. Forced expiratory volume in 1 s gradually decreased in the following order: NL, NL-GT, GT, GT-EM, and EM. DPMEmph correlated well with LAV%. Four clusters other than NL showed significantly higher values of √Aaw at Pi10 than NL; however, no significant differences were observed among them. In all clusters, DPMEmph increased after 3 years. DPMNormal only increased in the GT cluster. Conclusion: Clusters using DPM parameters may reflect the characteristics of COPD and help understand the pathophysiology of the disease.

Predictors of longitudinal changes in body weight, muscle and fat in patients with and ever-smokers at risk of COPD.

BACKGROUND AND OBJECTIVE: Weight and muscle loss are predictors of poor outcomes in chronic obstructive pulmonary disease. However, to our knowledge, no study has investigated the predictors of longitudinal weight loss or its composition from functional and morphological perspectives. METHODS: This longitudinal observational study with a median follow-up period of 5 years (range: 3.0-5.8 years) included patients with COPD and ever-smokers at risk of COPD. Using chest computed tomography (CT) images, airway and emphysematous lesions were assessed as the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the percentage of low attenuation volume (LAV%). Muscle mass was estimated using cross-sectional areas (CSAs) of the pectoralis and erector spinae muscles, and fat mass was estimated using the subcutaneous fat thickness at the level of the 8th rib measured using chest CT images. Statistical analyses were performed using the linear mixed-effects models. RESULTS: In total, 114 patients were enrolled. Their body mass index remained stable during the study period while body weight and muscle CSA decreased over time and the subcutaneous fat thickness increased. Reduced forced expiratory volume in 1 s and peak expiratory flow (PEF) at baseline predicted the future decline in muscle CSA. CONCLUSION: Severe airflow limitation predicted future muscle wasting in patients with COPD and ever-smokers at risk of COPD. Airflow limitation with a PEF slightly below 90% of the predicted value may require intervention to prevent future muscle loss.

Immune-related aseptic meningitis diagnosed by Cube FLAIR on enhanced magnetic resonance imaging for a lung cancer patient administered atezolizumab: A case report.

Immune checkpoint inhibitors (ICIs) can cause immune-related adverse events (irAEs), such as neurological toxicity. A 46-year-old man was diagnosed with squamous cell lung cancer. Lung cancer recurred 3 years after he experienced left segmental lung rejection. Therefore, he received atezolizumab as fourth-line chemotherapy. He experienced fever, headache, and decreased consciousness 10 days after the first dose of atezolizumab. Plain head computed tomography and cerebrospinal fluid examination showed no significant findings. Magnetic resonance imaging (MRI) with a Gadolinium (Gd)-enhanced Cube fluid-attenuated inversion recovery (FLAIR) sequence showed nodular abnormalities with contrast enhancement. Thus, aseptic meningitis caused by ICIs was suspected. His consciousness level gradually improved with glucocorticoid therapy. Moreover, most nodular abnormalities observed on cerebral MRI disappeared concurrently. Thus, Gd-enhanced Cube FLAIR sequence has the unique ability to reveal immune-related aseptic meningitis.

Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia.

OBJECTIVES: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19. METHODS: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO2). RESULTS: There was no significant difference in the changes in the clinical progression scale between nafamostat with favipiravir and favipiravir alone groups (median, -0.444 vs -0.150, respectively; least-squares mean difference, -0.294; P = 0.364). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group. CONCLUSION: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO2 were observed in the combination group.

Risk factors for pneumonitis in advanced extrapulmonary cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune-mediated pneumonitis has a high mortality rate; however, information regarding the related risk factors remains limited. This study aimed to analyze risk factors for pneumonitis, including smoking and lung metastasis (LM), in patients with extrapulmonary primary tumors. METHODS: Data of 110 patients treated with immune checkpoint inhibitors (ICIs) (nivolumab/pembrolizumab) for treating extrapulmonary primary tumors at the Shiga University of Medical Science Hospital between January 2015 and December 2019 were retrospectively collected. The association between the onset of pneumonitis and treatment-related factors was analyzed by logistic regression. The severity of pneumonitis was graded according to the Common Terminology Criteria for Adverse Events version 5.0. Risk factors, such as the absence or presence of interstitial lung disease (ILD) and LM, or other clinical factors, including smoking status before ICI administration, were analyzed. RESULTS: Multivariate analyses indicated that the amount of smoking was significantly associated with an increase in the development of all-grade pneumonitis types (odds ratio (OR) = 20.33, 95% confidence interval (CI) = 20.03-20.66; p = 0.029). LM and ILD were significantly related to an increase in the development of symptomatic pneumonitis (≥ Grade 2) (OR = 10.08, 95% CI = 1.69-199.81; p = 0.076, and OR = 6.76, 95% CI = 1.13-40.63; p = 0.037, respectively). CONCLUSIONS: Pre-screening for ILD and LM and recognizing patients' smoking history is important for determining the risk of ICI-induced pneumonitis and allowing safe ICI administration.

Age dependence of the maturation of the midpalatal suture in the stability of orthodontic anchoring screws.

INTRODUCTION: Orthodontic anchoring screws (OASs) have been placed around midpalatal sutures in patients of various ages. Our previous study found that OAS placement more than 1.5 mm from midpalatal suture was more successful than placement directly at the suture. This study aimed to investigate the relationship between age and midpalatal suture maturation, considering factors affecting the failure of OASs using cone-beam computed tomography. METHODS: In total, 150 patients who underwent cone-beam computed tomography were selected. The total depth and sutured depth of the midpalatal suture corresponding area to anterior (interpremolar zone) and posterior region (mesial and distal borders of the first molar) were measured, and the ratio of sutured depth to total depth (sutured ratio) was calculated. RESULTS: The mean sutured ratios at interpremolar zone and mesial and distal borders of the first molar according to age were 40%, 60%, and 63% in the younger group (≤17 years), 46%, 76%, and 76% in the middle group (18-25 years), and 47%, 74%, and 76% in the older group (≥26 years), respectively. The sutured ratio of the anterior region was significantly lower than that of the posterior region (P <0.01). Each mean sutured ratio of the middle and older group was significantly higher than that of the younger group on both sides (P <0.01). According to the cervical vertebral maturation, the mean sutured ratio of cervical vertebral stages 5-6 was significantly higher than cervical vertebral stages 1-3 on the distal side (P <0.05). CONCLUSIONS: Incomplete closure of the midpalatal suture was observed frequently, even in the older group. This might be caused by insufficient calcification of the midpalatal suture, including in elder patients. To prevent OAS placement to the unsutured area, the midpalatal suture should be avoided regardless of age.

Influence of masticating cycles and chewing patterns on inadvertent enamel wear caused by zirconia brackets.

Little information is available about enamel wear caused by zirconia brackets, an inadvertent side effect of orthodontic treatment. The purpose of this study was to examine potential enamel damage induced by contact with zirconia brackets. Sliding and impact wear simulations were performed using bovine enamel specimens positioned at a 25° slant to a zirconium ball to determine wear behaviour. Different chewing patterns, tapping and grinding, were simulated. Specimens were profiled using confocal laser scanning microscopy, and the mean maximum depth and surface roughness were measured. Scanning electron microscopy was also performed. The mean maximum depth of wear values differed according to the number of mastication cycles, with a higher number of cycles producing higher depths of wear. The facet wear depth was significantly greater with the tapping pattern than with the grinding pattern. Scanning electron microscopic observation of the wear facets revealed that surface textures at the edges were rougher than those at the centre of all facets. The results of this study indicated that enamel wear was induced by contact with zirconia brackets during the early period of mastication, and that the patterns and number of cycles of mastication affected the wear progression of enamel.

Influence of pre-drilling diameter on the stability of orthodontic anchoring screws in the mid-palatal area.

PURPOSE: The aim of this study was to investigate the stability of orthodontic anchor screws (OASs) in the mid-palatal area according to pre-drilling diameter. METHODS: The success rate of 161 OASs (83 patients, φ2.0 mm, 6.0 mm in length) placed in a corresponding area to the mesial and distal borders of the first molar (mesial zone and distal zone) was assessed according to placement location and pre-drilling diameter (1.2 and 1.5 mm). Placement torque values from 73 OASs with a pre-drilling diameter of 1.2 mm were compared between success and failure groups. RESULTS: The success rates of OASs pre-drilled with φ1.2 and 1.5 mm were 94.5% and 83.0%, respectively (P < 0.05); corresponding rates in the mesial zone were 100.0% and 77.3% (P < 0.005), and those in the distal zone were 89.2% and 88.6%, respectively. Placement torques of OASs predrilled with φ1.2 mm in the success and failure groups were 25.9 and 19.2 N·cm, respectively (P < 0.05). CONCLUSION: A smaller pre-drilling diameter was associated with a higher success rate of OASs in the mid-palatal area, especially in the mesial zone. When pre-drilling diameter of 1.2 mm was used for φ2.0 mm OAS, greater placement torque was indicative of greater OAS stability.

Pain and removal force associated with bracket debonding: a clinical study.

OBJECTIVE: Pain is a problem during bracket removal, and more comfortable treatment is needed. This study examined the association of pain with the removal force required for ceramic brackets, compared with metal and plastic brackets, to determine which removal method resulted in less pain and discomfort. METHODOLOGY: 81 subjects (mean age, 25.1 years; 25 males and 56 females) were enrolled, from whom 1,235 brackets (407 ceramic, 432 plastic, and 396 metal) were removed. Measured teeth were distinguished at six segments. Pain was measured with a visual analogue scale (VAS) during the removal of each bracket. An additional grip was placed on the grips of debonding pliers with right-angled beaks; a mini loading cell sensor pinched by the grips was used to measure removal force during debonding. VAS and force values were statistically analyzed. The Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni correction were performed for multiple comparisons; multiple regression analysis was also performed. RESULTS: Forces in the upper and lower anterior segments were significantly smaller (p<0.05) than those in the other segments. Pain tended to be greater in the upper and lower anterior segments than in the posterior segments. In all segments, the removal force was greater for metal brackets than for plastic or ceramic brackets. Ceramic brackets caused significantly greater pain than plastic brackets for the upper and lower anterior segments. Debonding force was involved in the brackets, following adjustments for pain, upper left segment, age, and sex. CONCLUSIONS: Pain and discomfort are likely to occur during bracket debonding.

Pain and removal force associated with bracket debonding: a clinical study

Abstract Objective: Pain is a problem during bracket removal, and more comfortable treatment is needed. This study examined the association of pain with the removal force required for ceramic brackets, compared with metal and plastic brackets, to determine which removal method resulted in less pain and discomfort. Methodology: 81 subjects (mean age, 25.1 years; 25 males and 56 females) were enrolled, from whom 1,235 brackets (407 ceramic, 432 plastic, and 396 metal) were removed. Measured teeth were distinguished at six segments. Pain was measured with a visual analogue scale (VAS) during the removal of each bracket. An additional grip was placed on the grips of debonding pliers with right-angled beaks; a mini loading cell sensor pinched by the grips was used to measure removal force during debonding. VAS and force values were statistically analyzed. The Kruskal-Wallis test followed by the Mann-Whitney U test with Bonferroni correction were performed for multiple comparisons; multiple regression analysis was also performed. Results: Forces in the upper and lower anterior segments were significantly smaller (p<0.05) than those in the other segments. Pain tended to be greater in the upper and lower anterior segments than in the posterior segments. In all segments, the removal force was greater for metal brackets than for plastic or ceramic brackets. Ceramic brackets caused significantly greater pain than plastic brackets for the upper and lower anterior segments. Debonding force was involved in the brackets, following adjustments for pain, upper left segment, age, and sex. Conclusions Pain and discomfort are likely to occur during bracket debonding.

Prediction of radiation pneumonitis using dose-volume histogram parameters with high attenuation in two types of cancer: A retrospective study.

The constraint values of dose-volume histogram (DVH) parameters for radiation pneumonitis (RP) prediction have not been uniform in previous studies. We compared the differences between conventional DVH parameters and DVH parameters with high attenuation volume (HAV) in CT imaging in both esophageal cancer and lung cancer patients to determine the most suitable DVH parameters in predicting RP onset. Seventy-seven and 72 patients who underwent radiation therapy for lung cancer and esophageal cancer, respectively, were retrospectively assessed. RP was valued according to the Common Terminology Criteria for Adverse Events. We quantified HAV with quantitative computed tomography analysis. We compared conventional DVH parameters and DVH parameters with HAV in both groups of patients. Then, the thresholds of DVH parameters that predicted symptomatic RP and the differences in threshold of DVH parameters between lung cancer and esophageal cancer patient groups were compared. The predictive performance of DVH parameters for symptomatic RP was compared using the area under the receiver operating characteristic curve. Mean lung dose, HAV30% (the proportion of the lung with HAV receiving ≥30 Gy), and HAV20% were the top three parameters in lung cancer, while HAV10%, HAV5%, and V10 (the percentage of lung volume receiving 10 Gy or more) were the top three in esophageal cancer. By comparing the differences in the threshold for parameters predicting RP between the two cancers, we saw that HAV30% retained the same value in both cancers. DVH parameters with HAV showed narrow differences in the threshold between the two cancer patient groups compared to conventional DVH parameters. DVH parameters with HAV may have higher commonality than conventional DVH parameters in both patient groups tested.

Finite element analysis of stress caused by palatal orthodontic anchor screws.

This study used finite element (FE) analysis to investigate the stability of miniscrews (screws) placed at the median palate. FE models with variable suture maturity and screw-suture distances were used to examine the relationship with screw stability. Four groups were classified by extent of maturation of the midpalatal suture (0%, 60%, 75%, and 100%). The placement position was set at the center of the suture (0.0 mm), or 0.5, 1.0, and 1.5 mm to the side of the suture, and von Mises stress values in bone and screw displacement were compared among models. The stress value for the unsutured model, in which the screw was placed at the center of the suture, was greater than 30 MPa. Stress values for models in which screws were placed to the side (0.5-1.5 mm) were less than 28 MPa. Maximum screw displacement was greater in the 0.0-mm incomplete suture model than at other placement positions. Because bone conditions vary among patients, placement position and suture maturation should be examined on cone beam-computed tomography images, to ensure screw stability.

Final Results from a Phase II Trial of Osimertinib for Elderly Patients with Epidermal Growth Factor Receptor t790m-Positive Non-Small Cell Lung Cancer That Progressed during Previous Treatment.

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are used for treating EGFR-mutated lung cancer, and osimertinib is effective in cases that acquired T790M mutations after treatment with the first- and second-generation EGFR-TKIs. However, no study has evaluated its safety and efficacy in older patients. This phase II trial (jRCTs071180002) evaluated osimertinib in T790M mutation-positive Japanese patients who were ≥75 years old and had experienced relapse or progression after previous EGFR-TKI treatment. Our previous report that enrolled 36 patients showed the overall response rate (58.3%) and disease control rate (97.2%), while this report describes the results for the progression-free survival (PFS), overall survival (OS), and safety analyses. The median PFS was 11.9 months (95% confidence interval (CI): 7.9-17.5), and the median OS was 22.0 months (95% CI: 16.0 months-not reached). The most frequent adverse events were anemia/hypoalbuminemia (27 patients, 75.0%), thrombocytopenia (21 patients, 58.3%), and paronychia/anorexia/diarrhea/neutropenia (15 patients, 41.7%). Pneumonitis was observed in four patients (11.1%), including two patients (5.6%) with Grade 3-4 pneumonitis. These results suggest that osimertinib was relatively safe and effective for non-small cell lung cancer that acquired T790M mutations after previous EGFR-TKI treatment, even among patients who were ≥75 years old.

Effects of composition on the hardness of orthodontic adhesives.

Although there have been improvements in bracket systems precoated with adhesive, removal of adhesive remnants continues to be problematic. This study compared the hardness and maintainability of precoated adhesive with other commercial adhesives. Knoop hardness values were measured after light- or chemical-induced initial curing, immersion in distilled water at 37°C for 24 h and 1,000 and 10,000 thermal cycles after 24 h. Additionally, the forces required to move brackets by 0.5 mm were measured during bracket positioning, and brackets bonded to bovine enamel were examined by field-emission scanning electron microscopy. The Knoop hardness values of the precoated adhesives were lower than those of commercial resin composite adhesives, and hardness was dependent on the amount of filler in the resin matrix. The ability to maintain the device position may depend on the resin matrix composition. Precoated adhesives with less filler and more matrix material are light curable, and remnant resin may be easily removed.

Changes in surface properties of dental alloys with atmospheric plasma irradiation.

Chemical transitions after atmospheric pressure plasma irradiation were investigated by evaluating intermolecular attractions and atomic and molecular reactions. Gold, titanium and stainless-steel alloy samples were ground with #800 grit SiC waterproof paper and nitrogen gas atmospheric plasma irradiation was conducted. The surface free energies of the treated alloys were calculated and compared statistically. X-ray photoelectron spectroscopy analysis was performed.The surface free energies of all metal surfaces treated by plasma irradiation were 1.5-times higher than those of the untreated metals. The energy of the hydrogen bonding component increased, and all alloy surfaces were coated with metal oxide after only a short period of plasma irradiation. The surfaces oxidized by plasma exhibited a high active energy, mainly due to an increase in the hydrogen bonding component. Reactions with oxygen in the air were promoted on the clean surfaces with exposed reactive elements.