Neuropsychiatric Systemic Lupus Erythematosus in a Patient with Pancytopenia and Chronic Schizophrenia Requiring Hospitalisation.

We herein report a patient with systemic lupus erythematosus (SLE) and neuropsychiatric SLE (NPSLE), who had been misdiagnosed with schizophrenia for a long time and presented with pancytopenia. Brain magnetic resonance imaging revealed sporadic punctate hyperintense areas in the cerebral white matter. Single-photon emission computed tomography revealed a clear decrease in blood flow from the parietotemporal association area to the temporal lobe. NPSLE is a serious organ complication that significantly worsens the SLE prognosis. NPSLE symptoms are diverse and difficult to diagnose and differentiate from those of other neuropsychiatric disorders, especially in an early onset.

Usefulness of fat-containing agents: an initial study on estimating fat content for magnetic resonance imaging.

This initial study aimed at testing whether fat-containing agents can be used for the fat mass estimation methods using magnetic resonance imaging (MRI). As an example for clinical application, fat-containing agents (based on soybean oil, 10% and 20%), 100% soybean oil, and saline as reference substances were placed outside the proximal femurs obtained from 14 participants and analyzed by 0.3 T MRI. Fat content was the estimated fat fraction (FF) based on signal intensity (SIeFF, %). The SIeFF values of the femoral bone marrow, including the femoral head, neck, shaft, and trochanter area, were measured. MRI data were compared in terms of bone mineral content (BMC) and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) in the proximal femur. Twelve pig femurs were also used to confirm the correlation between FF by the DIXON method and SIeFF. According to Pearson's correlation coefficient, the SIeFF and total BMC and BMD data revealed strong and moderate negative correlations in the femoral head (r < - 0.74) and other sites (r = - 0.66 to - 0.45). FF and SIeFF showed a strong correlation (r = 0.96). This study was an initial investigation of a method for estimating fat mass with fat-containing agents and showed the potential for use in MRI. SIeFF and FF showed a strong correlation, and SIeFF and BMD and BMC showed correlation; however, further studies are needed to use SIeFF as a substitute for DXA.

A systematic review and meta-analysis of macrolides in the management of adult patients with asthma.

BACKGROUND: The efficacy of macrolides in the management of asthma has been studied but remains controversial. We conducted a systematic review and meta-analysis of macrolides in the management of adult patients with asthma. METHODS: Randomized controlled trials of macrolides used in adult patients with asthma were searched for in MEDLINE, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Igaku Chuo Zasshi databases to evaluate the efficacy and safety of macrolides. RESULTS: Seventeen reports with macrolide treatment durations ranging from 6 to 48 weeks were included. Macrolides did not reduce exacerbations requiring hospitalization, severe exacerbations, or rescue use of short-acting beta-2 agonist inhalers; improve lung function; decrease peripheral blood or sputum neutrophil counts; or decrease fractional exhaled nitric oxide compared to placebo. Macrolides statistically improved asthma control and quality of life but by less than the minimal clinically important difference. Peripheral blood eosinophil counts as well as serum and sputum eosinophilic cationic protein concentrations were significantly decreased with macrolides compared to placebo. The improvement of asthma symptoms and airway hyperresponsiveness varied by study. The safety profile of macrolides was comparable to that of placebo. CONCLUSIONS: Although macrolides have some useful clinical aspects, there is not sufficient evidence to recommend their use in the management of adult patients with asthma.

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.

High-sensitivity Cardiac Troponin T Is a Useful Biomarker for Predicting the Prognosis of Patients with Systemic Sarcoidosis Regardless of Cardiac Involvement.

Objective Cardiac involvement defines the prognosis for patients with systemic sarcoidosis. Despite advancements in techniques for diagnosing cardiac lesions, there remains significant room for improvement in cardiac screening and prognostic prediction. The present study therefore assessed the prognostic factors associated with cardiovascular events in patients with sarcoidosis. Methods We retrospectively studied 132 patients with systemic sarcoidosis and evaluated the clinical data obtained between 2009 and 2022. A Kaplan-Meier survival analysis and Cox proportional hazards models were used to evaluate the associations between cardiovascular events and prognostic factors. Results The median age of the patients at the diagnosis was 64.0 (55.0-71.0) years old. During a mean follow-up period of 6.3±3.2 years, 28 patients suffered from cardiovascular events. Patients in the event group had more severe heart failure symptoms, more frequent ventricular tachycardia, higher serum high-sensitivity cardiac troponin T (hs-cTnT) values [0.025 (0.017-0.044) vs. 0.011 (0.007-0.019) ng/mL, p<0.001], and lower left ventricular ejection fraction values than those in the non-event group. These trends were observed even if the patients were not diagnosed with cardiac involvement at the time of enrollment. A multivariate analysis revealed that hs-cTnT was an independent biomarker for the prediction of cardiac events (hs-cTnT >0.014 ng/mL: HR: 7.31, 95% confidence interval: 2.20 to 24.28, p<0.001). Conclusion Hs-cTnT is a useful biomarker for predicting cardiovascular events in patients with sarcoidosis, even if cardiac involvement is not detected at the initial evaluation.

An Investigation into the Factors Associated with Incorrect Use of a Pressurized Metered-Dose Inhaler in Japanese Patients.

Rationale: Inhalation of the correct dose of a short-acting beta 2 agonist (SABA) from a pressurized metered-dose inhaler (pMDI) is essential for the relief of symptoms in patients with asthma and/or chronic obstructive pulmonary disease. The aim of this study was to evaluate the prevalence and factors associated with the incorrect use of a pMDI. Methods: This study retrospectively assessed the electronic medical records of 161 patients with various respiratory diseases. The patients had never used a pMDI and underwent training by pharmacists educated in the use of a pMDI followed by bronchodilator reversibility testing at our hospital. The patients' characteristics and various lung capacity parameters were evaluated for association with the incorrect use of a pMDI. Results: Thirty-nine of the 161 (24.2%) patients, including 46% of 28 patients older than 80 years, used the pMDI incorrectly, mainly because of incoordination between activation of the device and inhalation (n = 11), inadequate strength to manipulate the device (n = 9), too short duration of inhalation (n = 6), and difficulty in breath holding (n = 3). Advanced age; lower height; and decreased lung volumes, including vital capacity (VC), inspiratory capacity, inspiratory reserve volume (IRV), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow rate, were associated with the incorrect use of a pMDI. Neither the body weight, tidal volume, expiratory reserve volume, %FVC predicted, %FEV1 predicted, nor FEV1% was associated with the incorrect use of a pMDI. Multivariate binomial logistic regression analysis identified decreased IRV as the only independent predictor associated with the incorrect use of a pMDI. Conclusions: Physicians should be aware that elderly patients or patients with decreased IRV might be unable to obtain the correct SABA dose from a pMDI. A large-scale prospective study is required to confirm these findings from our retrospective study with a small group of patients.

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.

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.