Pulmonary cryptococcosis mimicking lung cancer with multiple lung metastases.

The differential diagnosis of a lung mass with multiple pulmonary nodules includes metastases of lung cancer, mycobacterial infections, and pulmonary mycosis. Pulmonary cryptococcosis should be recognized, especially in immunocompromised patients.

A prospective cohort study of periostin as a serum biomarker in patients with idiopathic pulmonary fibrosis treated with nintedanib.

This study investigated the utility of periostin, a matricellular protein, as a prognostic biomarker in patients with idiopathic pulmonary fibrosis (IPF) who received nintedanib. Monomeric and total periostin levels were measured by enzyme-linked immunosorbent assay in 87 eligible patients who participated in a multicenter prospective study. Forty-three antifibrotic drug-naive patients with IPF described in previous studies were set as historical controls. Monomeric and total periostin levels were not significantly associated with the change in forced vital capacity (FVC) or diffusing capacity of the lungs for carbon monoxide (DLCO) during any follow-up period. Higher monomeric and total periostin levels were independent risk factors for overall survival in the Cox proportional hazard model. In the analysis of nintedanib effectiveness, higher binarized monomeric periostin levels were associated with more favorable suppressive effects on decreased vital capacity (VC) and DLCO in the treatment group compared with historical controls. Higher binarized levels of total periostin were associated with more favorable suppressive effects on decreased DLCO but not VC. In conclusion, higher periostin levels were independently associated with survival and better therapeutic effectiveness in patients with IPF treated with nintedanib. Periostin assessments may contribute to determining therapeutic strategies for patients with IPF.

Hypereosinophilic syndrome presenting as eosinophilic gastroenteritis exacerbated by clopidogrel bisulphate.

Clopidogrel is a widely prescribed prodrug with antithrombotic activity that functions by irreversibly inhibiting the P2Y12 receptors on platelets; nevertheless, drug-induced eosinophilia from this drug is rarely reported. An 81-year-old man was diagnosed with cerebral infarction 2 months earlier and was admitted to our hospital with rash, fever, wheezing, and stomach discomfort after being initiated with clopidogrel treatment. Based on his medical history, chest CT, and gastroscopy, we diagnosed him with clopidogrel-induced hypereosinophilic syndrome. After discontinuation of clopidogrel, the eosinophilia and symptoms improved. In cases of drug-induced eosinophilia, it is important to obtain a detailed medical history.

CD47 promotes peripheral T cell survival by preventing dendritic cell-mediated T cell necroptosis.

Conventional dendritic cells (cDCs) are required for peripheral T cell homeostasis in lymphoid organs, but the molecular mechanism underlying this requirement has remained unclear. We here show that T cell-specific CD47-deficient (Cd47 ΔT) mice have a markedly reduced number of T cells in peripheral tissues. Direct interaction of CD47-deficient T cells with cDCs resulted in activation of the latter cells, which in turn induced necroptosis of the former cells. The deficiency and cell death of T cells in Cd47 ΔT mice required expression of its receptor signal regulatory protein α on cDCs. The development of CD4+ T helper cell-dependent contact hypersensitivity and inhibition of tumor growth by cytotoxic CD8+ T cells were both markedly impaired in Cd47 ΔT mice. CD47 on T cells thus likely prevents their necroptotic cell death initiated by cDCs and thereby promotes T cell survival and function.

Cohort study to evaluate prognostic factors in idiopathic pulmonary fibrosis patients introduced to oxygen therapy.

While high-level evidence is lacking, numerous retrospective studies have depicted the value of supplemental oxygen in idiopathic pulmonary fibrosis (IPF) and other interstitial lung diseases, and its use should be encouraged where necessary. The clinical course and survival of patients with IPF who have been introduced to oxygen therapy is still not fully understood. The objective of this study was to clarify overall survival, factors associated with prognosis, and causes of death in IPF patients after the start of oxygen therapy. This is a prospective cohort multicenter study, enrolling patients with IPF who started oxygen therapy at 19 hospitals with expertise in interstitial lung disease. Baseline clinical data at the start of oxygen therapy and 3-year follow-up data including death and cause of death were assessed. Factors associated with prognosis were analyzed using univariable and multivariable analyses. One hundred forty-seven eligible patients, of whom 86 (59%) were prescribed ambulatory oxygen therapy and 61 (41%) were prescribed long-term oxygen therapy, were recruited. Of them, 111 died (76%) during a median follow-up of 479 days. The median survival from the start of oxygen therapy was 537 ± 74 days. In the univariable analysis, low body mass index (BMI), low forced vital capacity (FVC), low diffusion capacity (DLCO), resting hypoxemia, short 6 min-walk distance, and high COPD assessment test (CAT) score were significantly associated with poor prognosis. Multivariable analysis revealed low BMI, low FVC, low DLCO, low minimum SpO2 on 6MWT, and high CAT score were independent factors for poor prognosis. The overall survival of IPF patients after starting oxygen therapy is about 1.5 years. In addition to pulmonary function tests, 6MWT and patient reported outcomes can be used to predict prognosis more accurately.Clinical Trial Registration: UMIN000009322.

Infection Dynamics and Genomic Mutations of Hepatitis E Virus in Naturally Infected Pigs on a Farrow-to-Finish Farm in Japan: A Survey from 2012 to 2021.

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans. Pigs are the primary reservoir for zoonotic HEV genotypes 3 and 4 worldwide. This study investigated the infection dynamics and genomic mutations of HEV in domestic pigs on a farrow-to-finish pig farm in Japan between 2012 and 2021. A high prevalence of anti-HEV IgG antibodies was noted among pigs on this farm in 2012, when the survey started, and persisted for at least nine years. During 2012-2021, HEV RNA was detected in both serum and fecal samples, indicating active viral replication. Environmental samples, including slurry samples in manure pits, feces on the floor, floor and wall swabs in pens, and dust samples, also tested positive for HEV RNA, suggesting potential sources of infection within the farm environment. Indeed, pigs raised in HEV-contaminated houses had a higher rate of HEV infection than those in an HEV-free house. All 104 HEV strains belonged to subgenotype 3b, showing a gradual decrease in nucleotide identities over time. The 2012 (swEJM1201802S) and 2021 (swEJM2100729F) HEV strains shared 97.9% sequence identity over the entire genome. Importantly, the swEJM2100729F strain efficiently propagated in human hepatoma cells, demonstrating its infectivity. These findings contribute to our understanding of the prevalence, transmission dynamics, and genetic characteristics of HEV in domestic pigs, emphasizing the potential risks associated with HEV infections and are crucial for developing effective strategies to mitigate the risk of HEV infection in both animals and humans.

Lung CCR6-CXCR3- type 2 helper T cells as an indicator of progressive fibrosing interstitial lung diseases.

Progressive fibrosing interstitial lung diseases (PF-ILDs) have a poor prognosis and may be resistant to corticosteroids and/or immunosuppressants, but antifibrotic therapies such as nintedanib and pirfenidone have been shown to slow the deterioration of lung function. The aim of this study was to identify the characteristic cellular profile of bronchoalveolar lavage fluid at diagnostic bronchoscopy for predicting PF-ILDs, defined as fibrotic diseases on chest high-resolution computed tomography with more than a 5% relative decline in the percent predicted value of forced vital capacity (FVC) over 6 months. The proportions of inflammatory cells, CCR6-CXCR3- T helper type 2 (Th2) cells among conventional CD4+ T cells in bronchoalveolar lavage fluid (BALF) and peripheral blood, were measured by flowcytometry. The proportion of lymphocytes in BALF was significantly higher in non-PF-ILD patients than in PF-ILD patients. The proportion of Th2 cells in BALF, but not in peripheral blood, was significantly higher in PF-ILD patients than in non-PF-ILD patients. Multivariate analysis showed that a greater population of Th2 cells in BALF was the only indicator for PF-ILDs. An increased proportion of Th2 cells in BALF is associated with greater deterioration of lung function in fibrotic interstitial lung diseases.

Allergic Bronchopulmonary Mycosis Complicated with Lung Adenocarcinoma.

Chest computed tomography (CT) of a 76-year-old woman with bronchial asthma showed multiple lung nodules with high CT densities that were compatible with high-attenuation mucoid (HAM) impactions characteristic of allergic bronchopulmonary mycosis (ABPM). Follow-up chest CT revealed increased sizes of multiple lung nodules. However, a left upper lobe nodule showed lower CT density than the other HAM impactions. A transbronchial lung biopsy of that upper lobe nodule revealed lung adenocarcinoma. Measuring the CT density is important for the differential diagnosis of lung nodules when following ABPM patients. Our patient's increased serum carcinoembryonic antigen levels were associated with peripheral blood eosinophilia. Mucoid impaction in the lung was positively stained with carcinoembryonic antigen and showed the distribution of eosinophilic granules.

Broncholith-associated mucus plug mimicking lung cancer.

A mucus plug caused by bronchial obstruction of a broncholith may mimic lung cancer, and bronchoscopic removal of the broncholith was useful for differential diagnosis.

Lupus-related protein-losing enteropathy associated with pseudo-pseudo Meigs' syndrome and successfully treated with hydroxychloroquine.

We herein report the first case of lupus-related protein-losing enteropathy associated with pseudo-pseudo Meigs' syndrome. Lupus-related protein-losing enteropathy and pseudo-pseudo Meigs' syndrome are extremely rare complications in patients with systemic lupus erythematosus, Both have a similar clinical course characterized by producing marked ascites, and respond to steroids in typical cases. However, in our case, steroid monotherapy was inadequate and the addition of hydroxychloroquine was effective for their treatment. Furthermore, no reports have previously confirmed elevated CA 125 levels with lupus-related protein-losing enteropathy or increased 99mTc-HSA activity with pseudo-pseudo Meigs' syndrome. In addition, we are the first to report an evaluation of the histopathology of lupus-related protein-losing enteropathy. Previously reported cases have been described as being caused by either pseudo-Meigs's syndrome or lupus-related protein-losing enteropathy as the cause of the rare pathology that causes marked pleural effusion and ascites in patients with systemic lupus erythematosus, but it has not been evaluated whether the other is co-occurring. Our case highlights that there is a potential case of overlapping lupus-related protein-losing enteropathy and pseudo-Pseudo-Meigs's syndrome. Furthermore, it is possible that patients with marked ascites with elevated CA 125 levels were mistakenly diagnosed with Meigs's syndrome or pseudo-Meigs's syndrome associated with malignant or benign ovarian tumors and underwent surgery. Clinicians should not forget SLE with pseudo-Pseudo-Meigs's syndrome as one of the differential diagnoses for marked ascites with elevated CA 125 levels.

Anticancer efficacy of monotherapy with antibodies to SIRPα/SIRPß1 mediated by induction of antitumorigenic macrophages.

The interaction of signal regulatory protein α (SIRPα) on macrophages with CD47 on cancer cells is thought to prevent antibody (Ab)-dependent cellular phagocytosis (ADCP) of the latter cells by the former. Blockade of the CD47-SIRPα interaction by Abs to CD47 or to SIRPα, in combination with tumor-targeting Abs such as rituximab, thus inhibits tumor formation by promoting macrophage-mediated ADCP of cancer cells. Here we show that monotherapy with a monoclonal Ab (mAb) to SIRPα that also recognizes SIRPß1 inhibited tumor formation by bladder and mammary cancer cells in mice, with this inhibitory effect being largely dependent on macrophages. The mAb to SIRPα promoted polarization of tumor-infiltrating macrophages toward an antitumorigenic phenotype, resulting in the killing and phagocytosis of cancer cells by the macrophages. Ablation of SIRPα in mice did not prevent the inhibitory effect of the anti-SIRPα mAb on tumor formation or its promotion of the cancer cell-killing activity of macrophages, however. Moreover, knockdown of SIRPß1 in macrophages attenuated the stimulatory effect of the anti-SIRPα mAb on the killing of cancer cells, whereas an mAb specific for SIRPß1 mimicked the effect of the anti-SIRPα mAb. Our results thus suggest that monotherapy with Abs to SIRPα/SIRPß1 induces antitumorigenic macrophages and thereby inhibits tumor growth and that SIRPß1 is a potential target for cancer immunotherapy.