Safety and effectiveness of additional triamcinolone acetonide with endoscopic radial incision and cutting for benign stenosis of the lower gastrointestinal tract: A pilot study.

Objectives: Radial incision and cutting (RIC) is being investigated as an alternative endoscopic dilation method for lower intestinal tract stenosis, providing a high technical success rate and improving subjective symptoms. However, several patients develop re-stenosis following RIC. In this pilot study, we aimed to evaluate the safety and efficacy of triamcinolone acetonide (TA) addition after RIC. Methods: RIC with TA was performed in 20 patients with lower gastrointestinal tract stenosis. We evaluated the rate of adverse events 2 months after RIC with TA. We investigated the short- and long-term prognoses, as well as the improvement in subjective symptoms, using a visual analog scale. Results: The delayed bleeding rate after RIC was 23.8%. Endoscopic hemostasis was achieved in all patients with delayed bleeding. No perforations were observed. The cumulative re-stenosis-free, re-intervention-free, and surgery-free rates 1 year after RIC were 52.9%, 63.7%, and 85.2%, respectively. Subjective symptoms, including abdominal pain, abdominal bloating, nausea, and dyschezia, significantly improved after RIC with TA. Conclusion: Although additional TA administration after RIC could be safe, additional TA may not be effective on luminal patency after dilation. Further investigation is warranted.

The providing multidisciplinary ILD diagnoses (PROMISE) study - study design of the national registry of Japan facilitating interactive online multidisciplinary discussion diagnosis.

BACKGROUND: Multidisciplinary discussion (MDD), in which physicians, radiologists, and pathologists communicate and diagnose together, has been reported to improve diagnostic accuracy compared to diagnoses made solely by physicians. However, even among experts, diagnostic concordance of MDD is not always good, and some patients may not receive a specific diagnosis due to insufficient findings. A provisional diagnosis based on the ontology with a diagnostic confidence level has recently been proposed. Additionally, we developed an artificial intelligence model to differentiate idiopathic pulmonary fibrosis (IPF) from other chronic interstitial lung diseases (ILD)s, which needs validation in a broader population. METHODS: This prospective nationwide ILD registry has recruited patients with newly diagnosed ILD at the referral respiratory hospitals in Japan and provides rapid MDD diagnoses and treatment recommendations through a central online MDD platform with a 3-year follow-up period. A modified diagnostic ontology is used. If no diagnosis reaches more than 50% certainty, the diagnosis is unclassifiable ILD. If multiple diseases are expected, the diagnosis with a high probability takes precedence. If the confidence levels for the top two possible diagnoses are equal, the diagnosis can be unclassifiable. The registry uses tentative diagnostic criteria for nonspecific interstitial pneumonia with organising pneumonia and smoking-related ILD not otherwise specified as possible new entities. Central MDD diagnosticians review the clinical data, test results, radiology images, and pathological specimens on a dedicated website and conduct MDD diagnoses using online meetings with a cloud-based reporting system. This study aims to (1) provide MDD diagnoses with treatment recommendations; (2) determine the overall ILD rates in Japan; (3) clarify the reasons for unclassifiable ILDs; (4) evaluate possible new disease entities; (5) identify progressive phenotypes and create a clinical prediction model; (6) measure the agreement rate between institutional and central diagnoses in ILD referral and non-referral centres; (7) identify key factors for each specific ILD diagnosis; and (8) create a new disease classification system based on treatment strategies, including the use of antifibrotic drugs. DISCUSSION: This study will provide ILD frequencies, including new entities, using central MDD on dedicated online systems, and develop a machine learning model for ILD diagnosis and prognosis prediction. TRIAL REGISTRATION: UMIN-CTR Clinical Trial Registry (UMIN000040678).

Management of anti-melanoma differentiation-associated gene 5 antibody-induced refractory dermatomyositis complicated by interstitial pneumonia using tofacitinib and its outcomes: a case report.

BACKGROUND: Clinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined. CASE PRESENTATION: A 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient's respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, ßD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis. CONCLUSION: The patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected.

Transesophageal ultrasound-guided bronchoscopic Acquire TBNB versus Vizishot2 TBNA needles for neoplastic lesions: A retrospective study.

BACKGROUND: Lung cancer is often diagnosed at an advanced stage; however, it has shown improved therapeutic efficacy with the introduction of molecularly targeted drugs and immune checkpoint inhibitors, necessitating accurate molecular diagnosis for effective treatment planning. Traditional sampling techniques, including endobronchial ultrasound-guided transbronchial needle aspiration, frequently require multiple biopsies to obtain sufficient tissues for multiplex testing, highlighting the need for more efficient methods. Therefore, we explored the diagnostic utility of endoscopic ultrasound with bronchoscope-guided fine-needle biopsy (EUS-B-FNB) versus fine-needle aspiration (EUS-B-FNA) in patients with lung cancer, focusing on tissue sample collection for molecular testing. The introduction of the Franseen needle in EUS-B-FNB, characterized by three beveled edges, allows for more tissue collection in cylinder form. METHODS: We retrospectively analyzed the data of 97 patients who underwent EUS-B-FNB or EUS-B-FNA at Hakodate Goryoukaku Hospital and evaluated diagnostic yields, safety, and nucleic acid concentrations using collected specimens. RESULTS: The diagnostic yields of EUS-B-FNB and EUS-B-FNA were comparable (92.2% vs. 92.3%), with no significant differences in complications. However, EUS-B-FNB provided significantly higher DNA and RNA concentrations (DNA; 41.05 vs. 10.20 ng/mL; P < 0.0001, RNA; 36.80 vs. 11.80 ng/mL; P = 0.0009), essential for comprehensive molecular testing. CONCLUSION: This study highlights the potential of EUS-B-FNB for enhancing the molecular diagnosis of lung cancer by ensuring adequate tissue sample collection for multiplex testing, paving the way for personalized medicine. This technique is comparable in safety and efficacy to traditional methods while offering a substantial improvement in the quality of molecular diagnostics.

Negative-Pressure Pulmonary Edema Induced by Flexible Bronchoscopy: A Case Report.

Negative-pressure pulmonary edema (NPPE) arises from excessive inspiratory effort due to upper airway obstruction, often associated with postoperative laryngospasm and upper airway infections like epiglottitis. We present a case of NPPE during bronchoscopy. A 45-year-old female patient, who was undergoing bronchoscopy for interstitial pneumonia evaluation, was examined using a tracheal tube with a 7.5 mm internal diameter and a bronchoscope with a 5.9 mm external diameter. The patient's respiratory condition gradually worsened after intubation. We continued with the examination, supplying approximately 5 L/min of oxygen through the intubation tube. We performed an alveolar lavage, and the recovered fluid gradually turned pale and bloody. After the examination, the patient continued to expectorate pink and frothy sputum and prolonged respiratory failure. Chest radiography revealed new extensive bilateral infiltrates. We ruled out cardiogenic causes through clinical examination, electrocardiogram (ECG), and transthoracic echocardiography. As a result, we suspected that temporary upper airway obstruction during bronchoscopy led to NPPE. Applying continuous positive airway pressure (CPAP) quickly improved the pulmonary edema. The risk of NPPE during bronchoscopy needs to be acknowledged, especially when using larger bronchoscopes and smaller tracheal tubes.

Therapeutic effect of long-acting muscarinic antagonist for treating uncontrolled asthma assessed using impulse oscillometry.

BACKGROUND: In recent years, the incorporation of LAMAs into asthma therapy has been expected to enhance symptom control. However, a significant number of patients with asthma continue to experience poorly managed symptoms. There have been limited investigations on LAMA-induced airway alterations in asthma treatment employing IOS. In this study, we administered a LAMA to patients with poorly controlled asthma, evaluated clinical responses and respiratory function, and investigated airway changes facilitated by LAMA treatments using the IOS. METHODS: Of a total of 1282 consecutive patients with asthma, 118 exhibited uncontrolled symptoms. Among them, 42 switched their treatment to high-dose fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) (ICS/LABA/LAMA). The patients were then assessed using AHQ-33 or LCQ and ACT. Spirometry parameters (such as FEV1 or MMEF) and IOS parameters (such as R20 or AX) were measured and compared before and after exacerbations and the addition of LAMA. RESULTS: Of the 42 patients, 17 who switched to FF/UMEC/VI caused by dyspnea exhibited decreased pulmonary function between period 1 and baseline, followed by an increase in pulmonary function between baseline and period 2. Significant differences were observed in IOS parameters such as R20, R5-R20, Fres, or AX between period 1 and baseline as well as between baseline and period 2. Among the patients who switched to inhaler due to cough, 25 were classified as responders (n = 17) and nonresponders (n = 8) based on treatment outcomes. Among nonresponders, there were no significant differences in spirometry parameters such as FEV1 or PEF and IOS parameters such as R20 or AX between period 1 and baseline. However, among responders, significant differences were observed in all IOS parameters, though not in most spirometry parameters, between period 1 and baseline. Furthermore, significant differences were noted between baseline and period 2 in terms of FEV1, %MMEF, %PEF, and all IOS parameters. CONCLUSION: ICS/LABA/LAMA demonstrates superiority over ICS/LABA in improving symptoms and lung function, which is primarily attributed to the addition of LAMA. Additionally, IOS revealed the effectiveness of LAMA across all airway segments, particularly in the periphery. Hence, LAMA can be effective against various asthma phenotypes characterized by airway inflammation, even in real-world cases.

Current challenges in the diagnosis and management of idiopathic pulmonary fibrosis in Japan.

Idiopathic pulmonary fibrosis (IPF) is the archetypal interstitial lung disease. It is a chronic progressive condition that is challenging to manage as the clinical course of the disease is often difficult to predict. The prevalence of IPF is rising globally and in Japan, where it is estimated to affect 27 individuals per 100,000 of the population. Greater patient numbers and the poor prognosis associated with IPF diagnosis mean that there is a growing need for disease management approaches that can slow or even reverse disease progression and improve survival. Considerable progress has been made in recent years, with the approval of two antifibrotic therapies for IPF (pirfenidone and nintedanib), the availability of Japanese treatment guidelines, and the creation of global and Japanese disease registries. Despite this, significant unmet needs remain with respect to the diagnosis, treatment, and management of this complex disease. Each of these challenges will be discussed in this review, including making a timely and differential diagnosis of IPF, uptake and adherence to antifibrotic therapy, patient access to pulmonary rehabilitation, lung transplantation and palliative care, and optimal strategies for monitoring and staging disease progression, with a particular focus on the status in Japan. In addition, the review will reflect upon how ongoing research, clinical trials of novel therapies, and technologic advancements (including artificial intelligence, biomarkers, and genomic classification) may help address these challenges in the future.

Risk factors for severe immune-related pneumonitis after nivolumab plus ipilimumab therapy for non-small cell lung cancer.

BACKGROUND: The efficacy of anti-CTLA-4 antibody (ipilimumab) plus anti-programmed cell death 1 antibody (nivolumab) in treating advanced non-small cell lung cancer (NSCLC) is impeded by an elevated risk of severe immune-related adverse events. However, our understanding of associations among pre-existing fibrosis, emphysematous changes, and objective indicators as predictive factors is limited for severe pneumonitis in NSCLC patients receiving this combination therapy. Thus, we retrospectively investigated these associations, including overall tumor burden, before treatment initiation in the Japanese population. METHODS: We focused on patients (n = 76) with pre-existing interstitial lung disease (ILD) to identify predictors of severe pneumonitis. Variables included age, sex, smoking status, programmed cell death ligand 1 expression, overall tumor burden, chest computed tomography-confirmed fibrosis, serum markers, and respiratory function test results. RESULTS: Severe pneumonitis was more frequent in patients with squamous cell carcinoma, fibrosis, low diffusing capacity for carbon monoxide (%DLCO), and high surfactant protein D (SP-D) level. Notably, squamous cell carcinoma, baseline %DLCO, and SP-D level were significant risk factors. Our findings revealed the nonsignificance of tumor burden (≥85 mm) in predicting severe pneumonitis, emphasizing the importance of pre-existing ILD. Conversely, in cases without pre-existing fibrosis, severe pneumonitis was not associated with %DLCO or SP-D level (93.2% vs. 91.9%, and 63.3 vs. 40.9 ng/mL, respectively) and was more common in patients with a large overall tumor burden (97.5 vs. 70.0 mm). CONCLUSION: Vigilant monitoring and early intervention are crucial for patients with squamous cell carcinoma, high SP-D level, or low %DLCO undergoing ipilimumab plus nivolumab therapy.

Successful Treatment of Mucus Plug Due to Allergic Bronchopulmonary Aspergillosis Using Dupilumab.

Allergic bronchopulmonary aspergillosis (ABPA) often necessitates treatment with systemic steroids and antifungals, which are associated with relapses and side effects. We report an 82-year-old woman with eosinophilic asthma, experiencing sputum production and dyspnea, who was diagnosed with ABPA based on her chest CT, pulmonary function tests, and elevated blood eosinophils and immunoglobulin E. Due to the presence of osteoporosis and diabetes, standard steroid therapy was considered a high risk. Instead, we administered dupilumab, an interleukin 4 receptor alpha (IL4-Rα) antibody targeting Th2 cytokine signaling. Remarkable improvements were observed within two weeks, including reduced sputum and dyspnea. After 12 weeks, significant enhancements in asthma control and lung function, along with decreased fractional exhaled nitric oxide (FeNO) levels were noted, with chest CT showing resolution of most of the mucus plugs. This case demonstrates dupilumab's potential as a viable ABPA treatment alternative, particularly for patients who are unsuitable for systemic steroids. More research on the long-term effectiveness and safety of such biologics is needed.

Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

BACKGROUND: This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies. METHODS: A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status. RESULTS: Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users. CONCLUSIONS: NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

Sputum colour: An indicator of Legionella pneumophila pneumonia.

The sputum colour in patients with severe pneumonia needs to be considered during diagnosis.

A Phase II Clinical Trial to Study the Safety of Triamcinolone after Endoscopic Radial Incision and Cutting Dilatation for Benign Stenosis of the Lower Gastrointestinal Tract: A Study Protocol.

BACKGROUND: Lower gastrointestinal tract stenosis is commonly diagnosed and is typically treated with surgery or endoscopic balloon dilation (EBD). Radial incision and cutting (RIC) is a novel treatment approach that has several benefits compared with EBD and surgery. Although RIC has demonstrated a high technical success rate and has been shown to improve subjective symptoms, previous studies revealed that restenosis after RIC remain unsolved. Herein, we report the design of a prospective, multicenter, single-arm, interventional, phase II trial to evaluate the safety of local triamcinolone acetonide (TA) administration and its feasibility in preventing restenosis after RIC for lower gastrointestinal tract stenosis. METHODS: The major inclusion criteria are age 20-80 years and the presence of benign stenosis in the lower gastrointestinal tract accessible by colonoscope. We will perform RIC followed by local administration of TA to 20 participants. The primary outcome is the safety of local TA administration, which will be assessed by determining the frequency of adverse events of special interest. The secondary outcomes are the technical success rate of RIC, duration of procedure, improvement in subjective symptoms, and duration of hospitalization. The outcomes, improvement in subjective symptoms, and long-term results will be evaluated using descriptive statistics, Student's t-test, and Kaplan-Meier curve, respectively. DISCUSSION: This explorative study will provide useful information regarding the safety of TA administration after RIC, which may contribute to further investigations.

Prognostic significance of immunohistochemical classification utilizing biopsy specimens in patients with extensive-disease small-cell lung cancer treated with first-line chemotherapy and immune checkpoint inhibitors.

PURPOSE: Although immune checkpoint inhibitors (ICIs), together with cytotoxic chemotherapy (chemoimmunotherapy), have been adapted for the initial treatment of extensive-disease small-cell lung cancer (ED-SCLC), they have achieved limited success. In ED-SCLC, a subtype of SCLC, the expression of immune-related molecules and clinical data are not well understood in relation to ICI treatment efficiency. METHODS: We examined lung biopsy specimens from patients diagnosed with ED-SCLC treated with chemoimmunotherapy or chemotherapy. SCLC subtype, expression of HLA class I, and infiltration of CD8-positive cells were examined using immunohistochemistry (IHC). Subsequently, the association between clinical factors, IHC results, and progression-free survival or overall survival was assessed. RESULTS: Most of the cases showed the achaete-scute homolog 1 (ASCL1) subtype. Among the 75 SCLC cases, 29 expressed high levels of HLA class I, while 46 showed low levels or a negative result; 33 patients were characterized as CD8-high, whereas 42 were CD8-low. In the chemoimmunotherapy cohort, multivariate analysis revealed a correlation between CD8-high and improved survival. Specifically, patients in the CD8-high group of the chemoimmunotherapy cohort experienced enhanced survival compared to those in the chemotherapy cohort, which was attributed to ICI addition. IHC subtype analysis demonstrated a survival advantage in the SCLC-I and SCLC-A groups when ICI was combined with chemotherapy compared to chemotherapy alone. CONCLUSION: Our study highlights the predictive value of IHC-classified subtypes and CD8-positive cell infiltration in estimating outcomes for patients with ED-SCLC treated with chemoimmunotherapy as a first-line therapy. These findings have practical implications for daily clinical assessments and treatment decisions.

Bob1 maintains T follicular helper cells for long-term humoral immunity.

Humoral immunity is vital for host protection, yet aberrant antibody responses can trigger harmful inflammation and immune-related disorders. T follicular helper (Tfh) cells, central to humoral immunity, have garnered significant attention for unraveling immune mechanisms. This study shows the role of B-cell Oct-binding protein 1 (Bob1), a transcriptional coactivator, in Tfh cell regulation. Our investigation, utilizing conditional Bob1-deficient mice, suggests that Bob1 plays a critical role in modulating inducible T-cell costimulator expression and cellular respiration in Tfh cells. This regulation maintains the long-term functionality of Tfh cells, enabling their reactivation from central memory T cells to produce antibodies during recall responses. In a bronchial asthma model induced by house dust mite (HDM) inhalation, Bob1 is observed to enhance HDM-specific antibodies, including IgE, highlighting its pivotal function in Tfh cell regulation. Further exploration of Bob1-dependent mechanisms in Tfh cells holds promise for governing protective immunity and addressing immune-related disorders.

The impact of respiratory reactance in oscillometry on survival in patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Pulmonary function tests (PFTs) aid in evaluating the disease status of IPF. The clinical significance of oscillometry measurements in interstitial lung diseases has recently been reported. Our previous study showed that respiratory reactance (Xrs) measured by oscillometry reflected disease severity and predicted subsequent lung capacity decline in patients with IPF. However, the direct impact of Xrs on survival needs to be determined, and there are currently no reference values in oscillometry to predict prognosis. Therefore, this study aimed to investigate the association between oscillometry measurements, particularly Xrs, and survival in patients with IPF and to determine the cutoff values of Xrs that predict 3-year survival. METHODS: We analyzed the relationship between the measured values of PFT and oscillometry derived from 178 patients with IPF. Univariate and multivariate Cox proportional hazards analyses were performed to investigate the relationships between clinical indices at the time of the first oscillometry and survival. We performed the time-dependent receiver operating characteristic (ROC) curve analysis to set the optimized cutoff values of Xrs for 3-year survival prediction. We examined the discriminating power of cutoff values of Xrs on survival using the Kaplan-Meier method and the log-rank test. RESULTS: Xrs components, especially in the inspiratory phase (In), significantly correlated with the PFT values. In the multivariate analyses, Xrs (all of reactance at 5 Hz [X5], resonant frequency [Fres], and low-frequency reactance area [ALX] in the inspiratory phase) had a significant impact on survival (X5, p = 0.003; Fres, p = 0.016; ALX, p = 0.003) independent of age, sex, and other prognostic factors derived from the univariate analysis. The area under the ROC curve was 0.765, 0.759, and 0.766 for X5 In, Fres In, and ALX In, with cutoff values determined at - 0.98, 10.67, and 5.32, respectively. We found significant differences in survival after dividing patients using each of the cutoff values of Xrs. CONCLUSIONS: In patients with IPF, Xrs measured by oscillometry significantly impacted survival. We also determined the cutoff values of Xrs to discriminate patients with poor prognoses.

Drop finger caused by lung cancer metastasis.

Skeletal muscle metastasis of lung cancer is rare. However, clinicians should be aware that tumour-induced nerve compression symptoms may develop.

Detection of fibrosing interstitial lung disease-suspected chest radiographs using a deep learning-based computer-aided detection system: a retrospective, observational study.

OBJECTIVES: To investigate the effectiveness of BMAX, a deep learning-based computer-aided detection system for detecting fibrosing interstitial lung disease (ILD) on chest radiographs among non-expert and expert physicians in the real-world clinical setting. DESIGN: Retrospective, observational study. SETTING: This study used chest radiograph images consecutively taken in three medical facilities with various degrees of referral. Three expert ILD physicians interpreted each image and determined whether it was a fibrosing ILD-suspected image (fibrosing ILD positive) or not (fibrosing ILD negative). Interpreters, including non-experts and experts, classified each of 120 images extracted from the pooled data for the reading test into positive or negative for fibrosing ILD without and with the assistance of BMAX. PARTICIPANTS: Chest radiographs of patients aged 20 years or older with two or more visits that were taken during consecutive periods were accumulated. 1251 chest radiograph images were collected, from which 120 images (24 positive and 96 negative images) were randomly extracted for the reading test. The interpreters for the reading test were 20 non-expert physicians and 5 expert physicians (3 pulmonologists and 2 radiologists). PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was the comparison of area under the receiver-operating characteristic curve (ROC-AUC) for identifying fibrosing ILD-positive images by non-experts without versus with BMAX. The secondary outcome was the comparison of sensitivity, specificity and accuracy by non-experts and experts without versus with BMAX. RESULTS: The mean ROC-AUC of non-expert interpreters was 0.795 (95% CI; 0.765 to 0.825) without BMAX and 0.825 (95% CI; 0.799 to 0.850) with BMAX (p=0.005). After using BMAX, sensitivity was improved from 0.744 (95% CI; 0.697 to 0.791) to 0.802 (95% CI; 0.754 to 0.850) among non-experts (p=0.003), but not among experts (p=0.285). Specificity and accuracy were not changed after using BMAX among either non-expert or expert interpreters. CONCLUSION: BMAX was useful for detecting fibrosing ILD-suspected chest radiographs for non-expert physicians. TRIAL REGISTRATION NUMBER: jRCT1032220090.

Transbronchial cryobiopsy for small peripheral pulmonary lesions using endobronchial ultrasonography and an ultrathin bronchoscope.

BACKGROUND: Transbronchial biopsy using an ultrathin bronchoscope (UTB) has a high diagnostic yield for peripheral pulmonary lesions (PPLs). When combined with peripheral transbronchial needle aspiration (pTBNA), it improves the diagnostic yield of "adjacent to" radial endobronchial ultrasonography (rEBUS) findings. However, pTBNA is a complicated technique, and the specimen volume is often inadequate for diagnostic and multiplex analyses. Recently, transbronchial cryobiopsy (TBCB) using a 1.1-mm cryoprobe that could be inserted into an UTB has been available. We investigated whether TBCB combined with forceps biopsy using a 1.1-mm cryoprobe with an UTB improved the diagnostic yield of "adjacent to" lesions. METHODS: The data of 66 consecutive patients who underwent TBCB and forceps biopsy using UTB (hemostasis using two-scope method) under rEBUS for small PPLs (≤30 mm) were retrospectively analyzed. The histological diagnosis rate using TBCB and forceps biopsy, TBCB alone, or forceps biopsy alone was compared between cases where the rEBUS probe was "within" and "adjacent to" lesions. RESULTS: The diagnosis rate using TBCB and forceps biopsy was 81.8 % for all lesions ("within" vs. "adjacent to" cases: 88.4 % vs. 69.6 %; p = 0.093). The corresponding rate using TBCB alone was 80.3 % (86.0 % vs. 69.6 %; p = 0.19), and that using forceps biopsy alone was 62.1 % (74.4 % vs. 39.1 %; p = 0.008). Bleeding leading to discontinuation of the examination occurred in four (6.1 %) patients; however, in all cases, bleeding could be controlled endoscopically. CONCLUSION: Forceps biopsy with TBCB during ultrathin bronchoscopy for small PPLs improved the diagnostic yield when the lesions were adjacent to the rEBUS probe.