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We herein report a 48-year-old man with a history of chronic atrial fibrillation (AF) and repeated hemoptysis after radiofrequency ablation. Contrast tomography showed soft tissue thickening of the left hilar region and left pulmonary vein stenosis. We performed bronchial artery embolization, but the hemoptysis did not disappear, and AF was not controlled. We performed left lung lobectomy and maze procedures since we considered surgical removal necessary as radical treatment. After the surgery, hemoptysis and atrial fibrillation did not recur. Refractory hemoptysis after catheter ablation is rare, but occasionally occurs in patients with severe pulmonary vein stenosis.

Rationale: The clinical features and prognosis of nontuberculous mycobacterial (NTM) pleuritis and pleural effusion combined with NTM lung disease remain unclear. Objectives: To investigate the cli...

We herein report a 67-year-old kidney transplant patient who died of COVID-19. He was treated with hydroxychloroquine and azithromycin and received mechanical ventilation that temporarily improved his respiratory status. Despite our efforts, however, he later developed respiratory failure and died 43 days after the disease onset. The autopsy revealed prominent organization of alveoli and alveolar ducts, with a massive accumulation of macrophages in the lungs. A few severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen-positive cells were detected in the lung, suggesting delayed virus clearance owing to his long-term immunosuppressed state, leading to constant lung damage and ultimately respiratory failure.

We assessed the consistency of seropositive results of three rapid immunoassays (Kits A, B, and C) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared to highly accurate serological tests (Abbott and Roche) among healthcare workers in a hospital in Tokyo. The seroprevalence of SARS-CoV-2 immunoglobulin G was 0.41%, 2.36%, and 0.08% using Kits A, B, and C, respectively. Of the 51 samples that were seropositive on any rapid test, all were seronegative on both the Abbott and the Roche assays. Given that the seroprevalence of SARS-CoV-2 immunoglobulin G varied widely according to the choice of rapid test and the rapid test results were inconsistent with the results of highly accurate tests, the diagnostic accuracy of rapid serological tests for SARS-CoV-2 should be assessed before introducing these tests for point-of-care testing or surveillance.

The rapid global spread of the COVID-19 pandemic has posed a significant challenge to various countries in terms of the capacity of hospitals to admit and care for patients during the crisis. To estimate hospital capacity during the COVID-19 pandemic, clinicians working in tertiary hospitals around the world were surveyed regarding available COVID-19 hospital statistics. Data were obtained from 8 tertiary centers in 8 countries including the United States, United Kingdom, Switzerland, Turkey, Singapore, India, Pakistan, and Japan. The correlation between the number of patients with COVID-19 per 1 million population vs. the maximum number of inpatients with COVID-19 in a representative tertiary hospital in each country was determined, as was the correlation between COVID-19 deaths per 1 million population vs. the maximum number of patients with COVID-19 in the intensive care unit (ICU). What was noteworthy was that none of the 8 hospitals reduced emergency room (ER) activity even at the peak of the pandemic although treatment of patients without COVID-19 decreased by 0-70% depending on the extent of the epidemic. Although various measures are being actively implemented to slow the spread of the virus and reduce the strain on the health care system, the reality is that there are still a significant number of hospitals at risk of being overloaded in the event of a future surge in cases.

A 62‐year‐old woman with rheumatoid arthritis and a history of receiving immunosuppressant therapy had a recurrence of lung adenocarcinoma with EGFR L858R mutation. Following 14 months of treatment with erlotinib, computed tomography (CT) findings revealed the presence of small diffuse nodules. Bronchoscopy was performed as metastasis was suspected; however, this was not detected on lung biopsy with forceps. Transbronchial lung cryobiopsy (TBLC) succeeded in detecting metastatic adenocarcinoma, and T790M and L858R gene mutations. Pathological examination revealed a cluster of tumor cells in the intralobular interstitial areas, which was consistent with the CT findings. This report provides important information regarding the role of TBLC in diagnosing metastatic cancer, such as diffuse small miliary nodules, and its genetic mutations., This case report shows that cryobiopsy enables the diagnosis of miliary nodules as adenocarcinoma and its genetic mutations, and is a less invasive procedure than surgical lung biopsy. Cryobiopsy may be used to investigate malignant tumors and their genetic mutation in miliary nodules which liquid biopsy is unable to detect.

Objective To evaluate the efficacy and safety of direct hemoperfusion using a polymyxin B‐immobilized polystyrene column (PMX‐DHP) in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐positive pneumonia patients. Methods This study was a case series conducted at a designated infectious diseases hospital. Twelve SARS‐CoV‐2‐positive patients with partial pressure of arterial oxygen/percentage of inspired oxygen (P/F) ratio

Objective New flex‐rigid pleuroscope enables observations with a maximum angle of curvature of 180°, allowing visualization of the area near the insertion site of the pleuroscope. And, it improved the image quality and channel inner diameter. The aim of this study was to evaluate the clinical effectiveness and safety of a new flex‐rigid pleuroscope. Methods A retrospective analysis of patients who were examined with a new flex‐rigid pleuroscope under local anesthesia at our institution was conducted. Pleuroscopy was performed in 33 patients with undiagnosed exudative pleural effusions from December 2016 to March 2019. Results A total of 33 patients (10 women, 23 men); their median age 74 years (range 24‐90) were investigated. Pleuroscopy showed that 18 had malignant pleural disease (54%), and 15 had benign pleural diseases (46%). The top three most frequent causes of pleural disease were pleural metastases of lung carcinoma (30.3%), pyothorax (15.1%), and malignant pleural mesothelioma (12.1%). In 32 cases (97%), observation at the introducer insertion site was possible. It was not possible in one case due to hard adhesions. The diagnostic rate was 100%, and the complication rate was 6.1%. There were no major complications, and minor complications included mild pain (one case) and minor bleeding (one case) that was stanched spontaneously. Conclusions The new flex‐rigid pleuroscope is effective and safe for diagnosing pleural effusions. The improved bending angle is likely to minimize the blind area. The new pleuroscopy fiberscope may improve the diagnostic rate.

Immune checkpoint inhibitors (ICIs) are reportedly effective against many kinds of neoplasm, but may be responsible for several kinds of immune‐related adverse events (irAEs). Among these irAEs, the incidence of myelosuppression due to ICIs is relatively low. Corticosteroids are needed to control most cases of myelosuppression. Here, we report an 88‐year‐old woman with squamous cell lung cancer who was administered pembrolizumab. After five cycles of pembrolizumab, she developed severe pancytopenia. The pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term antitumor efficacy. Key points Significant findings of the study There are several kinds of immune‐related adverse events. We encountered a case of pembrolizumab‐induced pancytopenia with squamous cell lung cancer. What this study adds Corticosteroids are needed to control most cases of myelosuppression induced by ICIs, but pancytopenia induced by pembrolizumab in our case improved without steroids., An 88‐year‐old woman with squamous cell lung cancer was administered pembrolizumab. After 5 cycles of pembrolizumab, she developed severe pancytopenia. Pancytopenia improved under observation without steroid administration after cessation of pembrolizumab. During recovery from this irAE, the patient also maintained long‐term anti‐tumor efficacy.

In early 2020, Japan repatriated 566 nationals from China. Universal laboratory testing and 14-day monitoring of returnees detected 12 cases of severe acute respiratory syndrome coronavirus 2 infection; initial screening results were negative for 5. Common outcomes were remaining asymptomatic (n = 4) and pneumonia (n = 6). Overall, screening performed poorly.

Since the initial report of coronavirus disease (COVID-19) from the City of Wuhan, China in December 2019, there have been multiple cases globally. Reported here are 11 cases of COVID-19 at this hospital; all of the patients in question presented with relative bradycardia. The severity of the disease was classified into four grades. Of the patients studied, 3 with mild COVID-19 and 3 with moderate COVID-19 improved spontaneously. Lopinavir/ ritonavir was administered to 3 patients with severe COVID-19 and 2 with critical COVID-19. Both patients with critical COVID-19 required mechanical ventilation and extracorporeal membrane oxygenation. Both patients with critical COVID-19 had a higher fever that persisted for longer than patients with milder COVID-19. The respiratory status of patients with critical COVID-19 worsened rapidly 7 days after the onset of symptoms. Relative bradycardia may be useful in distinguishing between COVID-19 and bacterial community-acquired pneumonia. In patients who have had a fever for > 7 days, the condition might worsen suddenly.

The recommended daily dose of erlotinib was determined for patients with all types of non-small cell lung cancer (NSCLC). We determined the optimal dose (OD) in patients with NSCLC harboring only epidermal growth factor receptor (EGFR) sensitizing mutations. EGFR-tyrosine kinase inhibitor-naive patients with sensitizing mutations were eligible. Clinical OD was determined in a phase I/II study based on the continual re-assessment method (CRM) of both disease control and dose-limiting toxicity, defined as any toxicity of grade 2 (G2) or higher within 8 weeks. We also determined the pharmacologic OD via a pharmacokinetic (PK) study. Thirty-eight patients were enrolled. Clinical OD was 25 mg/day by the CRM. Median progression-free survival (mPFS) was 9.3 months. In receiver operating characteristic (ROC) analysis of mPFS, the trough concentration ( Cminss ) was ≥ 0.30 μg/mL. The area under the curve (AUC) and Cminss were predicted via population PK (PopPK) or a bootstrap of 100 iterations (PopPK100 ). TOX20 was defined as

BackgroundWhile increasing coverage of effective vaccines against coronavirus disease 2019 (COVID-19), emergent variants raise concerns about breakthrough infections. Data are limited, however, whether breakthrough infection during the epidemic of the variant is ascribed to insufficient vaccine-induced immunogenicity.MethodsWe described incident COVID-19 in relation to the vaccination program among workers of a referral hospital in Tokyo. During the predominantly Delta epidemic, we followed 2,473 fully vaccinated staff (BNT162b2) for breakthrough infection and selected three matched controls. We measured pre-infection neutralizing antibodies against the wild-type, Alpha (B.1.1.7), and Delta (B.1.617.2) strains using live viruses and anti-spike antibodies using quantitative assays, and compared them using the generalized estimating equation model between the two groups.ResultsNo COVID-19 cases occurred 1–2 months after the vaccination program during the fourth epidemic wave in Japan, dominated by the Alpha variant, while 22 cases emerged 2–4 months after the vaccination program during the fifth wave, dominated by the Delta variant. In the vaccinated cohort, all 17 cases of breakthrough infection were mild or asymptomatic and had returned to work early. There was no measurable difference between cases and controls in pre-infection neutralizing antibody titers against the wild-type, Alpha, and Delta, and anti-spike antibody titers, while neutralizing titers against the variants were considerably lower than those against the wild-type.ConclusionsPre-infection neutralizing antibody titers were not decreased among patients with breakthrough infection under the Delta variant rampage. The result points to the importance of infection control measures in the post-vaccination era, irrespective of immunogenicity profile.

Objectives To alleviate the overflow of coronavirus disease 2019 (COVID-19) patients in hospitals, less invasive and simple criteria are required to triage the patients. We evaluated the relationship between COVID-19 severity and fatty liver on plain computed tomography (CT) scan performed on admission. Methods In this retrospective cohort study, we considered all COVID-19 patients at a large tertiary care hospital between January 31 and August 31, 2020. COVID-19 severity was categorized into severe (moderate and severe) and non-severe (asymptomatic and mild) groups, based on the Japanese National COVID-19 guidelines. Fatty liver was detected on plain CT scan. Multivariate logistic regression analysis was performed to evaluate factors associated with severe COVID-19. Results Of 222 patients (median age: 52 years), 3.2%, 58.1%, 20.7%, and 18.0% presented with asymptomatic, mild, moderate, and severe COVID-19, respectively. Although 59.9% had no fatty liver on plain CT, mild, moderate, and severe fatty liver occurred in 13.1%, 18.9%, and 8.1%, respectively. Age and presence of fatty liver were significantly associated with severe COVID-19. Conclusion Our study showed that fatty liver on plain CT scan on admission can become a risk factor for severe COVID-19. This finding may help clinicians to easily triage COVID-19 patients.

Obesity may downregulate vaccine-induced immunogenicity, but the epidemiological evidence for the COVID-19 vaccine is limited, and the sex-associated difference is unknown. It was observed that a higher body mass index was associated with lower titers of spike IgG antibodies against SARS-CoV-2 in men but not in women.

Bronchial Thermoplasty (BT) is an epoch-making treatment that reduces bronchial smooth muscle by using a bronchoscope to reach the basket catheter to the bronchus and directing high-frequency current directly into the bronchi. In GINA Guidelines 2019, BT is considered to be additional treatment at Step V (the most severe), and the evidence level is B. The Japanese guidelines (JGL) also added BT as a treatment for Step 4, but it is reserved because there are still unclear points regarding long-term efficacy and safety. In Japan, as of April 1, 2019, 672 treatments were performed at 123 institutions nationwide. The average age of patients was 54.1 years, but 84 cases were over 70 years old. The average value of %FEV1 was 78.2%, but there were 94 cases less than 60%. There were 32 cases that underwent BT treatment at our institution. Of them, 12 cases with progress up to one year later could be observed. The average age was 56.1 years old, and each of 6 men and women had a %FEV1 of 70.5%. One year later, AQLQ and %FEV1 improved, and the number of exacerbations decreased, but exhaled NO values increased. %FEV1 improvement might be due to poorer lung function (70.5% vs. 77.8%) and more BT activation (average 1.28 times AIR2) compared to the AIR2 trial. In terms of improvement in %FEV1, patients with moderate obstructive disorder from 50 to 80% responded well after BT treatment. In the near future, various new antibody preparations such as IL-4 / 13 antibody and anti-TSLP antibody are expected to be promoted. Therefore, we first consider whether these antibody preparations can be applied to patients with refractory asthma. We consider that BT is indicated only when there is no indication or no expected effect of antibody preparations. In other words, BT treatment is the last resort of intractable asthma, and it is the duty of medical professionals involved in BT treatment to be able to advocate when it is best to give BT to such patients.

IntroductionBronchial thermoplasty (BT) is a bronchoscopic procedure that involves the delivery of thermal radiofrequency energy to the bronchial wall for treating severe asthma. It has been suggested that too many radiofrequency activations could induce serious adverse events (SAEs) at an early stage. We aimed to examine the number of radiofrequency activations at each session and early lung function changes from baseline to determine whether these are related to SAEs.MethodsWe retrospectively investigated 13 consecutive patients who underwent three sessions each of BT for severe asthma from February 2015 to January 2016. Lung function tests were performed on the day before and after each BT procedure. Since we compared the number of activations and lung function changes from baseline after each session, a total of 39 sessions were reviewed. The relationship between the number of radiofrequency activations and each lung function change from baseline was also examined by linear regression analysis.ResultsA total of 10 SAEs (4 of pneumonia, 3 of atelectasis, 2 of bronchial asthma exacerbation and 1 of hemoptysis) were observed following the 39 BT sessions. When we compared sessions with and without SAEs, there were no differences in the number of activations (mean ± SD, 71.5 ± 28.6 times in sessions with SAEs; 66.5 ± 25.1 times in sessions without SAEs;p = 0.772) and lung function changes (mean changes in FVC/%FVC/FEV1/%FEV1/%PEF from baseline; − 0.49 l/− 14.2%/− 0.36 l/− 11.7%/− 9.6% in sessions with SAEs; − 0.43 l/− 13.3%/− 0.34 l/− 12.1%/− 9.4% in sessions without SAEs;p > 0.05 for all the above). Increase in the number of activations correlated with decreased FEV1(R2 = 0.17,p = 0.0088) and %FEV1(R2 = 0.11,p = 0.0357).ConclusionsIncrease in the number of radiofrequency activations during BT is related to a decrease in FEV1and %FEV1from baseline. The number of radiofrequency activations, however, is not associated with SAEs after BT.

Chylothorax is the accumulation of lipid pleural effusion. Few reports have described chylothorax caused by gastric cancer. A 45-year-old woman presented with progressive lymphedema and bilateral chylothorax. Although repetitive thoracentesis was performed to relieve her dyspnea, swelling of her axillary lymph nodes became significant. Positron emission tomography/computed tomography demonstrated the accumulation of 18F-fluorodeoxyglucose in these nodes, and a lymph node biopsy showed signet ring cell carcinoma. The primary site was a 0-IIc type lesion in the gastric body that was only detected by upper gastrointestinal endoscopy. The patient was diagnosed with advanced gastric cancer 3.5 months after presentation for chylothorax.

[ABSTRACT] BACKGROUND: Pulmonary alveolar proteinosis is a disease characterized by abnormal accumulation of surfactant in the alveoli. Most cases are autoimmune and are associated with an autoantibody against granulocyte?macrophage colony-stimulating factor (GM-CSF) that prevents clearing of pulmonary surfactant by alveolar macrophages. An open-label, phase 2 study showed some therapeutic efficacy of inhaled recombinant human GM-CSF in patients with severe pulmonary alveolar proteinosis; however, the efficacy in patients with mild-to-moderate disease remains unclear. METHODS: We conducted a double-blind, placebo-controlled trial of daily inhaled recombinant human GM-CSF (sargramostim), at a dose of 125 μg twice daily for 7 days, every other week for 24 weeks, or placebo in 64 patients with autoimmune pulmonary alveolar proteinosis who had a partial pressure of arterial oxygen (Pao2) while breathing ambient air of less than 70 mm Hg (or, Funded by the Japan Agency for Medical Research and Development and the Ministry of Health, Labor, and Welfare of Japan; PAGE ClinicalTrials.gov number, NCT02835742; Japan Medical Association Center for Clinical Trials number, JMA-IIA00205.

BACKGROUND: We investigated the measurement of end-tidal partial pressure of carbon dioxide (PETCO2) with a capnometer in patients with respiratory failure, and we determined whether this technique could provide an alternative to measurement of PaCO2 using arterial blood gas analysis in the clinical setting. METHODS: We measured PETCO2 in subjects with hypoxemic and hypercarbic respiratory failure using a capnometer. We simultaneously measured PaCO2, venous partial pressure of carbon dioxide (PvCO2), and transcutaneously measured partial pressure PCO2 (PtcCO2). We analyzed agreements among these parameters with Bland-Altman analysis. We obtained 30 samples from subjects with hypoxemic respiratory failure and 30 samples from subjects with hypercarbic respiratory failure. RESULTS: Thirty subjects with hypoxemic respiratory failure and 18 subjects with hypercarbic respiratory failure participated in this study. Significant relationships were found between PETCO2 and PaCO2, between PtcCO2 and PaCO2, and between PvCO2 and PaCO2. Bland-Altman analysis of PETCO2 and PaCO2 in all subjects revealed a bias of 6.48 mm Hg (95% CI 4.93–8.03, P CONCLUSIONS: PETCO2 can be measured simply using a capnometer, and PETCO2 measurements can estimate PaCO2. However, the limits of agreement were wide. Therefore, care providers must pay attention to the characteristics and errors of these devices. These results suggest that measurement of PETCO2 might be useful for screening for hypercarbic respiratory failure in the clinical setting.

Bronchial thermoplasty (BT), which delivers thermal radiofrequency to the bronchial wall, is an effective therapy for patients with severe persistent uncontrolled asthma. We herein report the case of a 47-year-old man who underwent BT for uncontrolled severe asthma. After BT, his asthma control, asthma-related quality of life, and pulmonary function improved. Furthermore, a histologic examination of transbronchial biopsy specimens revealed a decrease in goblet cell hyperplasia and the smooth muscle mass as well as in the subepithelial basement membrane thickness. BT can be effective for patients with severe uncontrolled asthma and mucus hypersecretion.

Background The current gold standard in coronavirus disease (COVID-19) diagnostics is the real-time reverse transcription–polymerase chain reaction (RT-PCR) assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasopharyngeal swab (NPS) samples. Alternatively, nasal swab (NS) or saliva swab (SS) specimens are used, although available data on test accuracy are limited. We examined the diagnostic accuracy of NPS/NS/SS samples for this purpose. Methods Ten patients were included after being tested positive for SARS-CoV-2 RT-PCR in NPS samples according to the National Institute of Infectious Disease guidelines. In comparison with this conventional diagnostic method, NPS/NS/SS samples were tested using the cobas 6800 systems RT-PCR device. To investigate the usefulness of the cobas method and the difference among sample types, the agreement and sensitivity were calculated. Five to six samples were collected over a total period of 5–6 d from each patient. Results Fifty-seven sets of NPS/NS/SS samples were collected, of which 40 tested positive for COVID-19 by the conventional method. Overall, the concordance rates using the conventional method were 86.0%/70.2%/54.4% for NPS/NS/SS samples (cobas); however, for samples collected up to and including on Day 9 after disease onset (22 negative and one positive specimens), the corresponding rates were 95.7%/87.0%/65.2%. The overall sensitivity estimates were 100.0%/67.5%/37.5% for NPS/NS/SS samples (cobas). For samples up to 9 d after onset, the corresponding values were 100.0%/86.4%/63.6%. Conclusions NS samples are more reliable than SS samples and can be an alternative to NPS samples. They can be a useful diagnostic method in the future.

Angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2), two receptors on the cell membrane of bronchial epithelial cells, are indispensable for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. ACE2 receptor is increased among aged, males, and smokers. As smoking upsurges ACE2 expression, chronic obstructive pulmonary disease (COPD) patients are prone to SARS-CoV-2 infection, and are at a higher risk for severe forms of COVID-19 (coronavirus disease 2019) once infected. The expression of ACE2 and TMPRSS2 in asthma patients is identical (or less common) to that of healthy participants. ACE2 especially, tends to be low in patients with strong atopic factors and in those with poor asthma control. Therefore, it could be speculated that asthma patients are not susceptible to COVID-19. Epidemiologically, asthma patients are less likely to suffer from COVID-19, and the number of hospitalized patients due to exacerbation of asthma in Japan is also clearly reduced during the COVID-19 pandemic; therefore, they are not aggravating factors for COVID-19. Related academic societies in Japan and abroad still lack clear evidence regarding asthma treatment during the COVID-19 pandemic, and recommend that regular treatment including biologics for severe patients be continued.

Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) originating in Wuhan, China, has spread globally very rapidly. The number of COVID-19 patients increased in Japan from late March to early April 2020. Since COVID-19 treatment methods with antiviral drugs were not established in March 2020, clinical trials began at a rapid pace worldwide. We participated in a global investigator-initiated clinical trial of the antiviral drug remdesivir. It took approximately two months to prepare for and start patient enrollment, 26 days to enroll all patients in Japan, and 32 days from the end of enrollment to the release of the first report, a fairly quick response overall. In the course of this clinical trial, we found some of the critical issues related to conducting an infectious disease clinical trial in Japan need to be addressed and tackled to support a rapid response. These included such things as the necessity of a research network to promote clinical research, a framework for a rapid review system of clinical trial notification, and better cooperation with outsourced teams. Furthermore, for Japan to take the lead in global collaborative research and development in the field of infectious diseases, it is necessary to develop further human resources and organization on a national basis. It is indispensable for Japan to establish a clinical trial system at the national level to prepare for future emerging and re-emerging infectious diseases.

An 83-year-old man was hospitalized for coronavirus disease 2019 (COVID-19) after a 10-day history of a persistent fever. Chest computed tomography showed extensive non-segmental ground glass opacity. Despite the initiation of lopinavir and ritonavir, respiratory failure progressed. Two days of polymyxin B-immobilized fiber column-direct hemoperfusion (PMX-DHP) with adjunctive corticosteroid prevented his respiratory condition from worsening. For rapidly progressive COVID-19 cases, the early use of PMX-DHP may avoid the need for mechanical ventilation by suppressing local inflammation of the lung.

Supplemental Digital Content is available in the text., Subjects: Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019. Interventions: Not applicable. Measurements and Main Results: This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary β2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low β2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were β2-microglobulin; severe versus moderate + mild: 2,457 μg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 μg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary β2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend. Conclusions: Evaluating urinary biomarkers such as β2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.

Bronchial thermoplasty (BT) is an interventional endoscopic treatment for severe bronchial asthma. Some studies have shown the clinical efficacy of this intervention, but its cost-effectiveness is unclear. The aim of this study was to evaluate the cost-effectiveness of BT. We collected data from the medical records of 16 Japanese patients who were treated with BT between February 2015 and April 2017, and compared asthma-related medical expenses between the year preceding and the year following BT. Four patients were Global Initiative for Asthma (GINA) treatment step 4, and 12 were step 5. In 8 patients who had a successful response to BT, the annual asthma-related medical expenses decreased because of a reduction in hospitalization and emergency outpatient visits due to asthma attacks, and termination of the use of biologics. Most patients in the non-responder group had increased asthma-related medical costs postoperatively. The main reason for the increase in medical costs was the add-on treatment of biologics. BT was cost-effective in the responder group. If its effects continue for more than 10 years, BT will be a cost-effective treatment. Medical costs will be reduced if those who respond to BT can be identified prior to commencement of treatment.

Background Osimertinib, a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), can be used as second-line treatment for lung cancer patients harboring the T790M substitution. Although osimertinib is more effective than the first-generation EGFR-TKIs used for first-line treatment, its efficacy with respect to long-term patient survival remains unclear even upon the administration of a complete sequence of EGFR-TKI therapy. Moreover, limited information is available regarding genetic diagnostic approaches after the treatment of EGFR-TKI–naïve patients. This study investigated the clinical characteristics of EGFR-mutated lung cancer patients harboring the T790M substitution resistant to EGFR-TKIs, as well as the advantages of rebiopsy and liquid biopsy for these patients. Methods The medical records of patients screened for EGFR mutations were reviewed. Upon failure of naïve treatment with EGFR-TKIs, except for osimertinib, single-plexus cobas version 2 was repeatedly used to detect the T790M substitution in EGFR via tissue or liquid biopsy. Results From April 2016 through May 2019, 113 patients were found to harbor EGFR mutations. Sixty patients were treated with EGFR-TKIs, among whom 46 underwent tissue or liquid biopsy. Twenty-nine of these 46 (63%) patients harbored the T790M substitution. In total, 141 rebiopsies were performed. The T790M substitution was detected in 24 of 43 tissue biopsies and 11 of 98 liquid biopsies. If patients displayed an EGFR exon 19 deletion, had a new lesion, and were administered gefitinib as first-line therapy, they were suspected to harbor the T790M substitution. Furthermore, the T790M substitution was detected through rebiopsy in patients with coexisting original mutations, brain metastases, tumor enlargement by ≥12 mm, or metastases at minor sites. Conclusion Among patients with positive factors associated with the T790M mutation, repeated tissue or liquid biopsies are useful to maximize the detection rate of the T790M substitution. Furthermore, these biopsies need to be repeated numerous times in order to reduce “detection overlook” among such patients.

To the Editor,A recent report in this journal described the severe nature and potentially fatal outcome of coronavirus disease 2019 (COVID-19) [1]. We here report a severe familial cluster case in ...

An 83‐year‐old woman presented with dyspnoea. Her chest X‐ray showed a right‐sided pleural effusion. Flex‐rigid pleuroscopy was performed and showed a mass in the anterior portion. The mass was biopsied with conventional biopsy forceps, but the mass was solid, and sufficient tissues could not be obtained. Therefore, the mass was biopsied with a cryoprobe. The tip of the probe was attached to the mass, and it was cooled with carbon dioxide once for 5 sec and then for 7 sec in the same place. The tissue size obtained was 2 mm by conventional biopsy forceps, and 5 mm at 5 sec and 12 mm at 7 sec by cryobiopsy. Histological analysis of the conventional biopsy forceps specimen showed cancer cells in the glandular cavity, but it was not sufficient tissue for comprehensive cancer genetic panel (CGP) testing. The cryobiopsy specimens showed cancer cells and sufficient tissue for comprehensive CGP testing., Here, we describe a case of an 83‐year‐old woman in whom insufficient pleural tissue to perform comprehensive cancer genetic panel testing was obtained with biopsy forceps, but sufficient tissue was obtained with cryobiopsy.

Background Severe acute respiratory syndrome–related coronavirus 2 (SARS-CoV-2) was found to be the causative microorganism of coronavirus disease 2019 (COVID-19), which started to spread in Wuhan, China. This study was to evaluate the effectiveness of questionnaire, symptoms-based screening, and polymerase chain reaction (PCR) screening of returnees from COVID-19-endemic areas on a chartered flight, to examine the proportion of infected persons and the proportion of asymptomatic persons among infected persons who returned from Wuhan. Methods A retrospective cohort study was done in 7 tertiary medical institutions in Japan. A total of 566 Japanese who returned from Wuhan participated in the study. Results Overall, 11 of the 566 passengers had a positive SARS-CoV-2 PCR result for pharyngeal swabs and 6 were asymptomatic. Only fever differed between SARS-CoV-2-positive and -negative individuals (P < .043). Six of the 11 PCR-positive individuals were asymptomatic; 4 remained positive on day 10, and 1 asymptomatic person tested positive up to day 27. Two of the 11 were negative on the first PCR test and positive on the second. Conclusions Our results will be important insights on screening returnees from locked-down cities, as well as providing important data on the proportion of asymptomatic individuals infected with SARS-CoV-2. A 13-day observation period and a second round of PCR may be effective to screen patients, including asymptomatic infections.

Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province. Japanese citizens lost a means of transportation to return back to Japan. The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences. A total of five charter flights were dispatched, and the majority of returnees (793/829 [95.7%]) were handled at NCGM. A large number of personnel from various departments participated in this operation; 107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total. Several medical translators were also involved. In this operation, we conducted airborne precautions in addition to contact precautions. Eye shields were also used. The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets. Enhanced hand hygiene using alcohol hand sanitizer was performed. Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34). Of those hospitalized after NCGM triage, 8.3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8.3%] vs. 9/745 [1.2%]: p = 0.0057). NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area. We were able to establish a scheme through this experience that can be used in the future.

The world is facing an unprecedented challenge in every place that is affected by the spreading COVID-19 pandemic. With China recording fewer and fewer cases, Europe and the Americas have become the epicenter of the pandemic since mid-March 2020, respectively accounting for 54.8% (621,407) and 27.8% (315,714) of 1,133,758 confirmed cases globally as of April 5. Moreover, the number of confirmed cases in the US (273,808), Spain (124,736), Italy (124,632), and Germany (91,714) has exceeded the number in China (82,930) so far. International cooperation and coordination are essential to tackling this pandemic in terms of both assistance with emergency medical supplies and medical technical assistance. Coordinated global action has been called for by the World Health Organization (WHO), G7, G20, the World Trade Organization (WTO), and other bodies. More effective actions are urgently needed to protect the most vulnerable, including older people and people with an underlying medical condition, as well as healthcare workers, who are most frequently exposed and who are vital to the response.

Lung cancer immunotherapy is an effective treatment option; however, it can be hampered by adverse events, including pancreatitis, associated with excessive immune activation. Here, we report the case of a 70‐year‐old patient who presented with recurrent lung squamous carcinoma and was started with pembrolizumab treatment (200 mg every three weeks). The patient developed pembrolizumab‐induced pancreatitis. After 14 months of pembrolizumab treatment, positron emission tomography–computed tomography showed a tumour‐shaped, highly integrated lesion at the pancreatic head and significantly elevated tumour markers, including carbohydrate antigen 19‐9 (149.3 U/mL), s‐pancreas antigen‐1 (44.7 U/mL), and duke pancreatic monoclonal antigen type 2 (412 U/mL). Pembrolizumab‐induced immune‐related pancreatitis was effectively treated with prednisolone 90 mg (1 mg/kg/day). Four months later, normal levels of the three specific tumour markers were detected, with improved pancreatic enzymes and radiographic findings. To our knowledge, this is the first reported case of immune‐related pancreatitis with elevated pancreatic cancer‐specific markers., We report a case of pembrolizumab‐induced immune‐related pancreatitis with the elevation of pancreatic tumour markers in a patient with squamous cell lung cancer.

Mucormycosis is a life-threatening infectious disease that occurs most commonly in immunocompromised patients such as those with hematological malignancies. Its clinical symptoms and associated radiological findings vary and specific biomarkers and culture characteristics have not been defined. An 85-year-old man who had been treated for myelodysplastic syndrome and tuberculosis for several months presented with subacute fever and worsening left-side chest pain. Contrast-enhanced computed tomography images depicted massive tumor-like consolidation without enhancement, expanding from the left lower lobe. Emboli that did not respond to anticoagulants were detected in the left descending pulmonary artery. Despite intensive treatment he developed multiple organ failure and died 47 days after hospitalization. Gross pathology of a lung autopsy specimen revealed left lower pulmonary arterial emboli and pulmonary infarction, which was concluded to be the direct cause of death. The emboli were histopathologically identified as invasive mycelia in vessels. Mucor sp. was detected via real-time polymerase chain reaction and immunohistopathological analyses revealed that the mold in the blood vessels of lung tissue was partially positive for the mucor antigen. In the present case of Mucor sp. pulmonary emboli in a patient with myelodysplastic syndrome, radiographic findings were hard to distinguish from those typical of a lung abscess.

Lymphoproliferative disease (LPD) is one of the complications of methotrexate (MTX) therapy. In MTX‐associated LPD (MTX‐LPD), LPD lesions limited to the lungs are rare and show various types of opacity. A 75‐year‐old woman with rheumatoid arthritis (RA) presented with myalgia. She had been taking MTX for 11 years. Chest computed tomography (CT) scans showed a nodule in the left lower lobe that had grown significantly and a new nodule in the right lower lobe. 18F‐fluorodeoxyglucose (FDG)/positron emission tomography (PET)/CT revealed significant FDG uptake in these nodules. Transbronchial biopsy specimen showed diffusely distributed CD20‐positive lymphoid cells, and we made a diagnosis of MTX‐LPD. All lung lesions disappeared within months after the immediate discontinuation of MTX. We also had two other patients with MTX‐LPD lung lesions that had high FDG uptake. FDG PET/CT might be a useful diagnostic tool as it may reflect disease progression and help identify separate lesions., Methotrexate (MTX) is one of the key drugs for treating rheumatoid arthritis (RA) and other autoimmune arthritis. Lymphoproliferative disease (LPD) is a complication of low‐dose MTX therapy. We describe three cases of MTX‐LPD where we conducted chest computed tomography (CT) and 18F‐fluorodeoxyglucose (FDG)/positron emission tomography (PET)/CT. This report focuses on the radiological findings of MTX‐LPD, including FDG PET/CT, based on these cases. FDG PET/CT might be a useful diagnostic tool as it may reflect disease progression and help identify separate lesions.

Very recently, a modest but significant efficacy of granulocyte–macrophage colony-stimulating factor (GM-CSF) inhalation therapy for the treatment of mild to moderate autoimmune pulmonary alveolar proteinosis (aPAP) has been reported. As the ability to measure the level of GM-CSF autoantibody (GMAb) in the serum is required to decide the indication for this therapy, we developed a high-performance GMAb testing kit for clinical use. As the kit succeeded in reducing nonspecific IgG binding to the ELISA plate, the predictive performance shown in the training study to discriminate aPAP patients from healthy subjects was perfect, providing a cut-off value of 1.65 U·mL−1 in 78 patients with aPAP and 90 healthy subjects in an operator-blinded manner using logistic regression analysis. As in the validation study, serum samples from another 213 patients with aPAP were also blinded and evaluated in an operator-blinded manner against external 207 samples from patients with other types of PAP and patients exhibiting various ground-glass opacities on chest high-resolution computed tomography that require discrimination from PAP. The logistic regression analysis of these validation data sets revealed values of 97.6% and 100% for specificity and sensitivity, respectively. Thus, this new GMAb testing kit is reliable for the diagnosis of aPAP and differential diagnosis of other lung diseases., Using a newly developed ELISA kit, the cut-off value for serological diagnosis of autoimmune pulmonary alveolar proteinosis can be reset to 1.65 U/mL, which is externally validated against patients with conditions other than autoimmune PAP http://bit.ly/2LgFmKk

Background The British Thoracic Society guidelines for diagnostic flexible bronchoscopy (FB) in adults recommend that intravenous sedation should be offered to patients undergoing bronchoscopy. However, it is difficult to determine the adequate depth of sedation for each patient because of inter-individual variability. Methods This prospective, open-label, single-arm study was conducted in patients undergoing routine bronchus examination with FB. All patients underwent FB under local anesthesia and conscious sedation, with initial administration of 0.03 mg/kg midazolam. The sedation level during FB was objectively assessed using the Ramsay sedation score (RSS). Two hours after the procedure, patients completed a questionnaire about its efficacy and adverse effects using a visual analog scale (VAS). Receiver operating characteristic (ROC) curve analyses were performed to determine the optimal RSS that could improve the subjective efficacy indicated by the VAS. Results This study enrolled 110 consecutive patients between September 2008 and February 2012. The median total amount of midazolam administered was 1.65 mg per patient. In an analysis of ROC curves between RSS and VAS, the area under the ROC curve for an RSS of 4 against the others was 0.66 (95% CI: 0.54 to 0.77, p = 0.014). The area under the ROC curve was not shown to be statistically significant for RSSs other than 4. Conclusions The optimal depth of conscious sedation during FB for conventional examination was achieved at an RSS of 4. The patients’ subjective evaluations indicated that a deep level of conscious sedation does not seem necessary for FB.

Background The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. Method We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. Results The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934–0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929–0.998) and T-SPOT (96.9%; 95% CI, 0.914–0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934–0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. Conclusions The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan.

Development of aspergilloma is common in cases with a fungus ball-like shadow in cavities due to old tuberculosis. Some reports have shown that blood clots tend to appear as a fungus ball-like shadow. A 71-year-old man with a history of pulmonary tuberculosis presented with a fungus ball-like shadow in an old cavity and hemoptysis. There was no evidence of aspergillus infection on various examinations. We confirmed a blood clot and aneurysm of an artery under direct vision by bronchoscopy. A lateral thoracic artery aneurysm was detected by angiography. Transcatheter arterial embolization was performed. After treatment, the artery aneurysm disappeared.

Bronchoscopy is a procedure for diagnosis and treatment decision-making in patients with lung disease, especially those with acute respiratory failure. However, the optimal bronchoscopic method for patients with acute respiratory failure is not known. Therefore, in the real world, we sometimes hesitate to perform bronchoscopy in such patients because of safety and have experienced treating patients without bronchoscopy. To address this problem, we evaluated the usefulness and safety of Jackson mask ventilation, a novel noninvasive method of bronchoscopy performed under mask ventilation using the Jackson Rees circuit, in patients with acute respiratory failure.We retrospectively reviewed patients with acute respiratory failure who underwent bronchoscopy at our institution between January 2015 and May 2018. We compared patients who received Jackson mask ventilation (Jackson group) and those who received conventional oxygen administration (conventional group). Mean percutaneous oxygen saturation (SpO2) and mean oxygen flow rate were compared between the groups by the Wilcoxon signed-rank test. We excluded patients who were intubated and those without acute respiratory failure who received Jackson mask ventilation preventively.Of 1262 patients who underwent bronchoscopy, 12 were classified into the Jackson group and 13 into the conventional group. Proper oxygenation was maintained in the Jackson group, with SpO2 increasing after Jackson mask ventilation (89.4% to 96.8%, P = .03). Mean SpO2 was significantly higher in the Jackson group than in the conventional group (96.8% vs 95.2%, P = .03). Mean oxygen flow rate was significantly lower in the Jackson group (4.0 L/min vs 7.9 L/min, P

Early-onset pulmonary emphysema is uncommon and its pathogenesis is poorly defined. A 30-year-old man was admitted to our intensive care unit with severe respiratory failure. Besides smoking heavily since the 14 years of age, he had habitually inhaled organic solvents, such as toluene, in his adolescence. High-resolution computed tomography showed evident pulmonary emphysema throughout the lung fields. Based on the findings of right heart catheterization, he was diagnosed with an acute exacerbation of chronic obstructive pulmonary disease complicated with pulmonary hypertension. Heavy smoking from a young age and exposure to toluene were the suspected causes of the patient's severe pulmonary emphysema.

Anti-tumor necrosis factor α (anti-TNFα) agents increase the risk of tuberculosis (TB), but cases are rarely fatal. This report concerns a patient who was undergoing treatment with infliximab and presented with acute respiratory distress syndrome due to miliary TB without a miliary shadow. The findings of a pathological autopsy revealed innumerable granulomas in the organs, and the miliary nodules in the lung consisted of more unstructured granulomas. Anti-TNFα agents are unusual in the presentation of TB. It is important, particularly for patients receiving anti-TNFα agents, to constantly consider the possibility of TB and to prepare for appropriate management.