Infectious respiratory pathogens among patients with acute exacerbation of idiopathic pulmonary fibrosis during the coronavirus disease 2019 pandemic in Japan.

BACKGROUND: Few studies have investigated the prevalence of pathogens in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), specifically, the interactions between respiratory pathogens and AE-IPF during the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVES: We aimed to analyze pathogens in patients with AE-IPF between September 2020 and December 2022. METHODS: This retrospective observational study was conducted at our hospital between September 2020 and December 2022. In patients with AE-IPF, pre-hospitalization polymerase chain reaction (PCR) tests for respiratory pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were performed using multiplex PCR or Smart Gene assay with nasopharyngeal swab specimens. Microbiological assays, including Gram staining, sputum cultures, blood cultures, and urinary antigen tests for Streptococcus pneumoniae and Legionella pneumophila, were also performed. RESULTS: Forty-nine patients with AE-IPF were included. The median age was 75 years old and 42 (86 %) were male. Only one of the 49 patients (2 %) was positive for SARS-CoV-2. Two of 28 patients (7 %) were positive for human rhinovirus/enterovirus. No bacteria were detected in sputum culture, blood culture, or urinary antigen tests. CONCLUSIONS: The detection frequency of SARS-CoV-2 infection in patients with AE-IPF was lower than that of human rhinovirus/enterovirus. Continuous analysis for the presence of pathogens is necessary for appropriate infection control because respiratory viruses may increase as the coronavirus pandemic subsides.

The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs' histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.

Epidemiologic evaluation of pulmonary paragonimiasis in Japan using a Japanese nationwide administrative database.

BACKGROUND: Paragonimiasis is a parasitic disease primarily contracted through consumption of undercooked freshwater crustaceans or wild boar meat. Large-scale nationwide epidemiological data on paragonimiasis are lacking. In this study, we aimed to investigate the nationwide epidemiology of hospitalized patients with paragonimiasis in Japan using a comprehensive nationwide Japanese administrative database. METHODS: We evaluated the Japanese Diagnosis Procedure Combination (DPC) data of patients diagnosed with pulmonary paragonimiasis between April 1, 2012 and March 30, 2020. The patients' address and information, including age, sex, treatment (medication: praziquantel; surgery: open thoracotomy or intracranial mass extirpation), Japan coma scale, comorbidities, and length of hospital stay, were extracted. RESULTS: Of the 49.6 million hospitalized patients, data were extracted on 73 patients with paragonimiasis, of whom 36 were male and 37 were female. The mean age was 49.7 years and the mean length of stay was 12.5 days. The most frequent comorbidity was pleural effusion (31.5 %), followed by pneumothorax (13.7 %). The sites of ectopic paragonimiasis in organs other than the lung included the liver (5.5 %), skin (4.1 %), and brain (2.7 %). Geographically, most patients were from the Kyushu region (54.8 %), followed by the Kanto region (22.0 %). Fukuoka Prefecture had the highest number of patients (22.0 %) by prefecture. During the study period, an average of 9.1 patients/year were hospitalized with lung paragonimiasis in Japan. CONCLUSION: Paragonimiasis has not completely disappeared in Japan; thus, physicians should be aware of paragonimiasis in the Kyushu region, especially in the Fukuoka Prefecture.

Sarcoidosis Associated with Enlarged Mediastinal Lymph Nodes with the Detection of Streptococcus gordonii and Cutibacterium acnes Using a Clone Library Method.

A 77-year-old Japanese woman with mediastinal lymphadenopathy and uveitis was diagnosed with sarcoidosis. The bacterial flora in biopsied samples from mediastinal lymph nodes was analyzed using a clone library method with Sanger sequencing of the 16S rRNA gene, and Streptococcus gordonii (52 of 71 clones) and Cutibacterium acnes (19 of 71 clones) were detected. No previous study has conducted a bacterial floral analysis using the Sanger method for the mediastinal lymph node in sarcoidosis, making this case report the first to document the presence of S. gordonii and C. acnes in the mediastinal lymph node of a patient with sarcoidosis.

Clinical factors associated with viral shedding time of SARS-CoV-2 Omicron variant in Japan.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 exhibits increased infectivity compared with all prior variants, and the timing of quarantine release should be carefully considered. However, to date, only two Chinese studies have analyzed the association between the viral shedding time (VST) and risk factors among patients infected with the Omicron variant. These studies included only limited numbers of severe cases and no analysis of underlying diseases and immunosuppressive drug use. Therefore, the current study aimed to analyze them in Japan. This retrospective observational study was conducted at the University of Occupational and Environmental Health, Japan, from January 2022 to October 2022 and included 87 hospitalized patients and 305 healthcare workers (HCWs) with coronavirus 2019 (COVID-19). In comparison with HCWs, hospitalized patients were significantly older and had a higher proportion of severe COVID-19 cases and significantly longer VST. A simple regression analysis showed that severe, current, or ex-smoking status, cardiovascular diseases, chronic kidney disease, and use of corticosteroids for underlying diseases were significantly correlated with a longer VST. Moreover, multiple linear regression analysis revealed that cardiovascular diseases, chronic kidney disease, and corticosteroid use were significantly associated with a longer VST. Therefore, COVID-19 patients with these underlying diseases may require a longer isolation period and the timing of quarantine release should be carefully considered.

Difficulty differentiating primary mediastinal classical Hodgkin lymphoma from inflammatory myofibroblastic tumor: A case report.

A 20-year-old Japanese man visited our hospital because an enlarged mediastinal shadow had been detected on chest x-ray. Chest computed tomography revealed a large mediastinal mass with multiple lymph node enlargement, pericardial effusion, and bilateral pleural effusion. He was diagnosed with inflammatory myofibroblastic tumor (IMT) based on a thoracoscopic tumor biopsy. Initial corticosteroid and celecoxib treatment was only partially effective; therefore, additional tumor rebiopsy and left axillary lymph node biopsy were performed. Based on the findings, the patient was rediagnosed with classical Hodgkin lymphoma (CHL). To date, there has only been one report of a case initially diagnosed as IMT and rediagnosed as CHL, as in our case, and only three reports of malignant lymphoma mimicking IMT. When IMT is suspected based on pathological findings and subsequently with treatment failure, possible CHL and performing rebiopsy should be considered.

A case of idiopathic multicentric Castleman's disease with secondary autoimmune neutropenia.

A 73-year-old Japanese woman with productive cough and dyspnoea on exertion was admitted, and she showed neutropenia and pulmonary reticular opacities and axial and mediastinal lymphadenopathies on chest computed tomography. The clinical findings and surgical lung and lymph node biopsies were diagnostic for idiopathic multicentric Castleman's disease (iMCD) complicated by secondary autoimmune neutropenia (AIN). iMCD is often complicated with hematologic disorders, however, iMCD complicated with AIN has not been reported; therefore, if iMCD is accompanied by neutropenia, the anti-neutrophil antibodies should be measured.

Plastic bronchitis caused by Haemophilus influenzae.

Plastic bronchitis is characterized by sputum obstructing the bronchus and causing atelectasis. Bronchoscopic removal of the clogged bronchial cast is typically performed, but small-diameter bronchoscopes with narrow suction ports cannot achieve adequate suction. Suction using a bronchoscope as a guide sheath may be effective for treating plastic bronchitis in children.

Acute pneumonitis caused by oral intake of incense.

Incense is typically burned for use, with bronchitis and pneumonia reported as potential side effects. Physicians should be cautious as inappropriate oral ingestion of incense can lead to acute pneumonitis.

Using Video Calls to Reduce Risky Behaviors and Enhance Instruction Understanding of Patients in Acute Care Hospitals During the COVID-19 Pandemic.

Backgrounds During the COVID-19 pandemic, visitor restrictions in healthcare settings adversely affected patients. Video calls have emerged as an essential digital alternative that can decrease patients' anxiety and improve satisfaction. This study investigated whether family-initiated video calls could mitigate delirium symptoms and risky behaviors and enhance patients' comprehension of instructions. Methods This observational study used medical chart data and the Diem Payment System from a single acute care hospital in Fukuoka, Japan. The study involved patients hospitalized between May 2020 and August 2021 who used video chat systems. Patients or their relatives used video calls through Skype. The frequency of video chat use served as the primary exposure. Changes in the patients' risky behaviors and instruction comprehension upon discharge were the primary outcomes. Results A total of 532 patients were included in the study, with an average age of over 70 years. After implementing the inverse probability of treatment weighting adjustment, an improved balance across age, sex, BMI categories, and other variables was observed. The effects of video calls on risky behaviors and instruction comprehension varied. Patients with three or more video calls showed distinct effects compared with those with fewer calls. When hospitalization was limited to three weeks, video calls noticeably influenced risky behaviors (p=0.022, 95% CI:1.08-2.63), but not instruction comprehension (p=0.226, 95% CI:0.43-1.22). Conclusions The use of video calls as a visitation method in acute care hospitals during a pandemic suggests that video calls reduce risky behaviors in patients with a three-week stay. This alternative to physical visitations contributes positively to patient safety and supports ongoing efforts to prevent the spread of COVID-19.

Immune checkpoint inhibitor-induced asthma and chronic obstructive pulmonary disease overlap in patient with adenocarcinoma.

A 67-year-old current smoker Japanese man, with no history of asthma, was diagnosed with lung adenocarcinoma. He received first-line chemotherapy with carboplatin, pemetrexed, ipilimumab, and nivolumab in July 20XX-1, and subsequently a maintenance therapy with nivolumab. In October 20XX, he became aware of wheezy dyspnoea, and chest computed tomography demonstrated worsening bronchial wall thickenings. Eosinophilia was noted, and a pulmonary function test showed obstructive dysfunction insufficiently responding to beta-agonists, with 130 mL increase of forced expiratory volume in one second and high fractional exhaled nitric oxide level (85 ppb). He was clinically diagnosed with asthma and chronic obstructive pulmonary disease overlap, secondary to immune checkpoint inhibitors (ICIs). The inhibition of binding between programmed cell death-protein-1 (PD-1), expressed on T cells, and programmed cell death-ligand-2 (PD-L2), expressed on tumour and dendritic cells, can induce airway hyperresponsiveness. Physicians should be wary of asthmatic symptoms and chest image findings during ICIs therapy.

Pulmonary veno-occlusive disease with vanished pulmonary consolidation.

Pulmonary veno-occlusive disease (PVOD) is an extremely rare cause of pulmonary hypertension. Previously reported computed tomography (CT) findings of PVOD included centrilobular ground-glass opacities, a mosaic pattern, and septal lines; however, chest CT revealing pulmonary consolidation disappearance with repositioning has not been reported.

Pulmonary artery aneurysm induced by lung abscess.

Physicians should consider a pulmonary artery aneurysm complication in patients presenting with hemoptysis during treatment for a pulmonary abscess. Contrast-enhanced CT or angiography is recommended for diagnosis, followed by pulmonary embolization for treatment.

A rare case of double primary lung adenocarcinomas with uncommon complex EGFR G719X and S768I mutations and pleomorphic carcinoma.

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-targeted therapy has emerged as a viable treatment for patients with advanced non-small cell lung cancer with common EGFR mutations. The uncommon G719X and S768I mutations can co-occur as complex mutations in the same tumor. Here we report a case of a 72-year-old male patient with double lung carcinoma, with G719X and S768I complex mutations detected in the right upper lung lobe along with brain metastases. Osimertinib (80 mg/day) was administered as the first-line treatment, and a reduction in the right lobe tumor and brain lesions was achieved. However, the left upper lung lobe mass remained unchanged; histopathological examination via a lobectomy revealed pleomorphic carcinoma. Thus, the patient was diagnosed with multiple primary lung cancers. In conclusion, osimertinib is a viable treatment option for lung cancer with rare EGFR G719X and S768I complex mutations.

COVID-19 associated Bell's palsy.

While rare, a diagnosis of Bell's palsy should be considered in young patients who test positive for SARS-CoV-2 infection and who also present with notable neurological facial signs and symptoms suggestive of lower motor neuron-type seventh cranial nerve palsy.

Fatal limbic encephalitis as paraneoplastic neurological syndrome in a patient with lung adenocarcinoma positive for antiamphiphysin antibody after durvalumab treatment.

A 69-year-old Japanese male with advanced lung adenocarcinoma developed neurological symptoms after chemoradiotherapy and durvalumab maintenance therapy. He was positive for serum antiamphiphysin antibody, which is rarely seen in patients with lung adenocarcinoma. Additionally, his brain magnetic resonance images showed limbic encephalitis which led to the diagnosis of classic paraneoplastic neurological syndrome (PNS). Immune checkpoint inhibitors (ICIs) activate T cells and may also activate antineuronal antibodies that cause PNS. Durvalumab, which is an ICI, may have led to antiamphiphysin antibody-positive PNS in our patient. Treatment with systemic high-dose methylprednisolone was unsuccessful and he died 2 months later. PNS should be considered as one of the differential diagnoses in patients with lung cancer and neurological symptoms during, or after, ICI treatment.

Efficacy and safety of once-daily single-inhaler triple therapy for mild-to-moderate chronic obstructive pulmonary disease: a study protocol for a randomised and interventional study.

INTRODUCTION: Bronchodilators, including long-acting muscarinic antagonists (LAMA) and long-acting beta 2 agonists (LABA), are the main treatments for chronic obstructive pulmonary disease (COPD). The efficacy of triple therapy (inhaled corticosteroids/LAMA/LABA) has also been reported. However, the effect of triple therapy on patients with mild-to-moderate COPD has not yet been clarified. This study aims to investigate the safety and efficacy of triple therapy, compared with LAMA/LABA combination therapy, for lung function and health-related quality of life in patients with mild-to-moderate COPD and identify baseline characteristics and biomarkers to predict responders and non-responders to triple therapy. METHODS AND ANALYSIS: This is a multicentre, prospective, open-label, randomised, parallel-group study. Mild-to-moderate patients with COPD will be randomised to receive fluticasone furoate/umeclidinium/vilanterol or umeclidinium/vilanterol for 24 weeks. A total of 668 patients will be enrolled from March 2022 to September 2023 from 38 sites in Japan. The primary endpoint is the change in the trough forced expiration volume in 1 s after 12 weeks of treatment. Secondary endpoints are responder rates based on the COPD assessment test score and the St. George's Respiratory Questionnaire total score after 24 weeks of treatment. The safety endpoint is the occurrence of any adverse events. We will also investigate safety in terms of changes in microbial colonisation in sputum and antimycobacterium avium complex antibodies. ETHICS AND DISSEMINATION: The study protocol and informed consent documents were approved by the Saga University Clinical Research Review Board (approval number: CRB7180010). Written informed consent will be obtained from all patients. Recruitment of the patients began in March 2022. The results will be disseminated through scientific peer-reviewed publications and domestic and international medical conferences. TRIAL REGISTRATION NUMBERS: UMIN000046812 and jRCTs031190008.

Successful Treatment with Crizotinib to Overcome Drug Resistance Possibly Due to Mesenchymal-epithelial Transition Amplification in a Lung Cancer Patient with the Echinoderm Microtubule-associated Protein-like 4-anaplastic Lymphoma Kinase Fusion Gene.

Amplification of the mesenchymal-epithelial transition (MET) gene plays an important role in anticancer drug resistance to anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) in echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged lung cancer cells. We encountered an ALK-rearranged lung cancer patient who developed MET amplification after alectinib treatment and showed an effective response to fifth-line crizotinib. First-line alectinib treatment was effective for 2.5 years; however, liver metastases exacerbated. Liver biopsy specimens revealed MET and human epidermal growth factor receptor 2 (HER2) amplifications. Switching to the MET inhibitor crizotinib improved liver metastases. Crizotinib may be effective in ALK-positive patients with MET amplification.

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.