The relationship between CPAP and health literacy: A prospective observational study.

Background: We aimed to assess differences in health literacy between those who improved CPAP non-adherent and those who remained non-adherent. Methods: We included patients newly diagnosed with sleep apnea syndrome who had started CPAP therapy between February 2019 and October 2020 with ≥6 follow-up months or who self-interrupted CPAP therapy <6 months. We recorded the CPAP wearing time after 3 and 6 months. Patients were divided into the CPAP adherent (using CPAP for ≥4 h per night) and non-adherent (self-interrupted CPAP therapy/using CPAP for <4 h per night) groups. We compared the European Health Literacy Survey Questionnaire 47 (HLS-EU-Q47) score between those who were CPAP non-adherent after 3 months and become CPAP adherent after 6 months, and those who remained non-adherent after 6 months. Results: At 3 months, 34 patients were CPAP non-adherent. After 6 months, there were 7 and 27 patients in the CPAP adherent and non-adherent groups, respectively. There was a significant difference in the HLS-EU-Q47 score between the patients who became adherent to CPAP and who remained non-adherent after 6 months. Conclusion: Previously non-adherent patients who subsequently became adherent tended to have higher health literacy.

Serum anti-DIDO1, anti-CPSF2, and anti-FOXJ2 antibodies as predictive risk markers for acute ischemic stroke.

BACKGROUND: Acute ischemic stroke (AIS) is a serious cause of mortality and disability. AIS is a serious cause of mortality and disability. Early diagnosis of atherosclerosis, which is the major cause of AIS, allows therapeutic intervention before the onset, leading to prevention of AIS. METHODS: Serological identification by cDNA expression cDNA libraries and the protein array method were used for the screening of antigens recognized by serum IgG antibodies in patients with atherosclerosis. Recombinant proteins or synthetic peptides derived from candidate antigens were used as antigens to compare serum IgG levels between healthy donors (HDs) and patients with atherosclerosis-related disease using the amplified luminescent proximity homogeneous assay-linked immunosorbent assay. RESULTS: The first screening using the protein array method identified death-inducer obliterator 1 (DIDO1), forkhead box J2 (FOXJ2), and cleavage and polyadenylation specificity factor (CPSF2) as the target antigens of serum IgG antibodies in patients with AIS. Then, we prepared various antigens including glutathione S-transferase-fused DIDO1 protein as well as peptides of the amino acids 297-311 of DIDO1, 426-440 of FOXJ2, and 607-621 of CPSF2 to examine serum antibody levels. Compared with HDs, a significant increase in antibody levels of the DIDO1 protein and peptide in patients with AIS, transient ischemic attack (TIA), and chronic kidney disease (CKD) but not in those with acute myocardial infarction and diabetes mellitus (DM). Serum anti-FOXJ2 antibody levels were elevated in most patients with atherosclerosis-related diseases, whereas serum anti-CPSF2 antibody levels were associated with AIS, TIA, and DM. Receiver operating characteristic curves showed that serum DIDO1 antibody levels were highly associated with CKD, and correlation analysis revealed that serum anti-FOXJ2 antibody levels were associated with hypertension. A prospective case-control study on ischemic stroke verified that the serum antibody levels of the DIDO1 protein and DIDO1, FOXJ2, and CPSF2 peptides showed significantly higher odds ratios with a risk of AIS in patients with the highest quartile than in those with the lowest quartile, indicating that these antibody markers are useful as risk factors for AIS. CONCLUSIONS: Serum antibody levels of DIDO1, FOXJ2, and CPSF2 are useful in predicting the onset of atherosclerosis-related AIS caused by kidney failure, hypertension, and DM, respectively.

PAD4 Deficiency Improves Bleomycin-induced Neutrophil Extracellular Traps and Fibrosis in Mouse Lung.

Excessive release of neutrophil extracellular traps (NETs) has been implicated in several organ fibrosis, including pulmonary fibrosis. NETs constitute a phenomenon in which decorated nuclear chromatin with cytosolic proteins is released into the extracellular space. PAD4 (peptidylarginine deiminase 4) plays an important role in the formation of NETs. However, the role of NETs in the pathogenesis of pulmonary fibrosis remains undefined. Here, we identified NETs in the alveolar and interstitial lung space of mice undergoing bleomycin (BLM)-induced lung fibrosis, which was suppressed by a pan-PAD inhibitor, Cl-amidine. In vitro, BLM directly induced NETs in blood neutrophils, which was also inhibited by Cl-amidine. Furthermore, Padi4 gene knockout (PAD4-KO) in mice led to the alleviation of BLM-induced NETs and pulmonary fibrosis and to the expression of inflammatory and fibrotic genes. PAD4 deficiency prevented decreases in alveolar epithelial and pulmonary vascular endothelial cell numbers and increases in ACTA2-positive mesenchymal cells and S100A4-positive fibroblasts in the lung. Hematopoietic cell grafts from PAD4-KO mice, not wild-type mice, resolved BLM-induced lung fibrosis and fibrotic gene expression in wild-type and PAD4-KO mice, suggesting that expression of PAD4 in hematopoietic cells may be involved in the development of lung fibrosis. These data suggest that PAD4 deficiency could ameliorate BLM-induced formation of NETs and lung fibrosis, suggesting that this pathway could serve as a therapeutic target for pulmonary fibrosis treatment.

Circulating Anti-Sorting Nexins 16 Antibodies as an Emerging Biomarker of Coronary Artery Disease in Patients with Obstructive Sleep Apnea.

Biomarkers are not available for monitoring the onset and progression of coronary artery disease (CAD) in patients with obstructive sleep apnea (OSA), a major risk factor for arteriosclerotic cardiovascular diseases. This study aimed to test for correlation between circulating anti-Sorting Nexins 16 antibody (SNX16-Ab) levels, CAD history and clinical parameters of patients with OSA. Sixty-four healthy donors, 82 adults with OSA, and 96 with acute coronary syndrome (ACS) were studied. Serum samples were collected at diagnostic polysomnography in the OSA group or at the disease onset in the ACS group. Serum SNX16-Ab levels were measured by amplified luminescence proximity homogeneous assay (AlphaLISA), and correlation between SNX16-Ab levels and clinical parameters was analyzed. SNX16-Ab levels and apnea-hypopnea index (AHI) were weakly correlated. Additionally, logistic regression analyses of OSA group identified that elevated SNX16-Ab level associated with the history of CAD. Circulating SNX16-Ab could increase during CAD pathogenesis in patients with OSA. Further prospective studies are required to prove the predictive potential of SNX16-Ab level in CAD onset of patients with OSA.

S100A12 inhibits fibroblast migration via the receptor for advanced glycation end products and p38 MAPK signaling.

The migration of lung fibroblasts plays a pivotal role in wound repair and fibrotic processes in the lung. Although the receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of lung diseases, its role in lung fibroblast migration is unclear. The current study examined the effect of three different RAGE ligands, namely, high mobility group box 1 (HMGB1), S100A12, and N-epsilon-(carboxymethyl) lysine (CML), on human fibronectin-directed human fetal lung fibroblast (HFL-1) migration. HMGB1 augmented, whereas S100A12 inhibited, HFL-1 migration in a concentration-dependent manner. CML did not affect HFL-1 migration. The effect of HMGB1 was not through RAGE. However, the effect of S100A12 was mediated by RAGE, but not Toll-like receptor 4. S100A12 did not exert a chemoattractant effect, but inhibited HFL-1 chemotaxis and/or chemokinesis. Moreover, S100A12 mediated HFL-1 migration through p38 mitogen-activated protein kinase (MAPK) but not through nuclear factor-kappa B, protein kinase A, phosphatase and tensin homolog deleted on chromosome 10, or cyclooxygenase. In addition, western blot analysis showed that S100A12 augmented p38 MAPK activity in the presence of human fibronectin. In conclusion, S100A12 inhibits lung fibroblast migration via RAGE-p38 MAPK signaling. This pathway could represent a therapeutic target for pulmonary conditions characterized by abnormal tissue repair and remodeling.

An Analysis of the Clinical Benefit of 37 Bronchoalveolar Lavage Procedures in Patients with Hematologic Disease and Pulmonary Complications.

Objective Since pulmonary complications are a major cause of mortality in patients with hematologic diseases, their rapid detection and treatment are essential. Bronchoalveolar lavage (BAL) is widely performed to diagnose pulmonary infiltrates not evident with non-invasive investigations; however, reports on its clinical benefits for patients with hematologic diseases are limited. The aim of our study was to investigate the utility of diagnostic bronchoscopy with BAL for those patients. Methods We retrospectively reviewed the clinical records of 37 consecutive BAL procedures in 33 adult patients with hematological diseases and pulmonary infiltrates with at least 6 months of follow-up between August 2013 and September 2017 (total 747 BAL procedures). The BAL results, ensuing treatment modifications, treatment outcomes, survival times, and adverse events were evaluated. Results Microbiological findings were detected in 11 (29.7%), even though wide-spectrum antibiotics and antifungal drugs had been empirically administered to most patients (>70%) prior to the bronchoscopy procedure. Overall, 25 of the 37 BAL procedures (67.6%) had some impact on the diagnosis of pulmonary diseases. Patients without specific diagnostic findings from BAL had a significantly poorer survival than those with diagnostic findings via BAL (30-day survival: 33.3% vs. 92.0%; 180-day survival: 8.3% vs. 64.0%). Four patients (12.1%) experienced complications associated with bronchoscopy; there were no procedure-related deaths. Conclusion BAL seems still important for diagnosing pulmonary infiltrates and/or excluding some of the important respiratory tract pathogens in patients with hematological diseases; furthermore, negative specific diagnostic findings from BAL may be associated with poor prognoses.

Tocilizumab-effective multicentric Castleman's disease with infiltration of eosinophil and IgG4-positive plasma cells: A case report.

A 67-year-old woman with fever and cough was diagnosed with eosinophilic pneumonia because of eosinophilia and increased eosinophil levels in the bronchoalveolar lavage fluid and transbronchial biopsy lung specimens. However, prednisolone therapy at a previous hospital was ineffective. Histological findings from thoracoscopic lung and lymph node biopsies were consistent with multicentric Castleman's disease (MCD). Since specimens also showed prominent eosinophil and IgG4-positive plasma cell infiltration, it was difficult to distinguish IgG4-related disease (IgG4-RD) from MCD. Administration of prednisolone plus tocilizumab improved the symptoms and lung lesions, and prednisolone administration was successfully reduced and then terminated. The present case highlights the difficulty in diagnosing MCD and IgG4-RD, and suggests that combined administration of tocilizumab and prednisolone might be effective in such a case.

Fetus-in-fetu: parasite or neoplasm? A study of two cases.

INTRODUCTION: Fetus-in-fetu is a rare congenital fetiform mass whose etiology is still controversial. We report two cases of fetus-in-fetu. CASE 1: A fetal retroperitoneal cystic tumor including two masses was detected by ultrasonography at 26 gestational weeks. The masses showed distinctive structures resembling a vertebral axis and were prenatally diagnosed as fetus-in-fetu. A resected specimen revealed two fetiform masses. CASE 2: An intracranial tumor with hydrocephalus was detected by ultrasonography at 19 gestational weeks. The pregnancy was terminated, and a postmortem examination revealed six fetiform masses with immature teratoma. DISCUSSION: The tumors may possibly consist of parasitic monozygotic diamniotic twins or highly differentiated teratomas.