Carmona, Eva M.

ObjectivesThe aim of this study was to assess bleomycin‐induced pulmonary fibrosis on ex vivo mouse lungs using ultrasound image grading and texture analysis.MethodsExcised mouse lungs were divided into 3 groups: control, mild fibrosis, and severe fibrosis based on the monitored indicators of health. B‐mode ultrasound images were obtained via scanning the mouse lungs ex vivo. The surface smoothness, echo density, and angle of lesions or the lung margin were graded, and the imaging contrast, correlation, homogeneity, and entropy were assessed via texture analysis.ResultsThe grades of surface smoothness, echo density, and angle were statistically higher for the severe fibrosis group compared with those of the control and mild fibrosis groups (P < .05). In addition, statistically significant differences in the contrast, correlation, and homogeneity between mild and severe fibrosis groups were observed (P < .05).ConclusionsThe results obtained in this study suggest that ultrasound image grading and texture analysis are valuable and meaningful methods for assessing pulmonary fibrosis in a bleomycin mouse model.

Pneumocystis jirovecii , the opportunistic fungus that causes Pneumocystis pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the profound deleterious inflammatory effects of the major β-glucan cell wall carbohydrate constituents of Pneumocystis through Dectin-1 engagement and downstream caspase recruitment domain-containing protein 9 (CARD9) immune activation, we sought to determine whether the pharmacodynamic activity of the known CARD9 inhibitor BRD5529 might have a therapeutic effect on macrophage innate immune signaling and subsequent downstream anti-inflammatory activity.

AbstractBackgroundPneumocystis major surface glycoprotein (Msg) is a 120-kD surface protein complex on the organism with importance in adhesion and immune recognition. In this study, we show that Msg significantly impairs tumor necrosis factor (TNF)-α secretion by macrophages induced by Saccharomyces cerevisiae and Pneumocystis carinii (Pc) β-glucans.MethodsMajor surface glycoprotein was shown to greatly reduce β-glucan-induced Dectin-1 immunoreceptor tyrosine-based activating motif (ITAM) phosphorylation. Major surface glycoprotein also down regulated Dectin-1 receptor messenger ribonucleic acid (mRNA) expression in the macrophages. It is interesting that Msg incubation with macrophages resulted in significant mRNA upregulation of both C-type lectin receptors (CLR) Mincle and MCL in Msg protein presence alone but to even greater amounts in the presence of Pc β-glucan.ResultsThe silencing of MCL and Mincle resulted in TNF-α secretions similar to that of macrophages treated with Pneumocystis β-glucan alone, which is suggestive of an inhibitory role for these 2 CLRs in Msg-suppressive effects on host cell immune response.ConclusionsTaken together, these data indicate that the Pneumocystis Msg surface protein complex can act to suppress host macrophage inflammatory responses to the proinflammatory β -glucan components of the organisms.

Abstract Background: Sarcoidosis is a systemic granulomatous disease that may affect the myocardium. This study evaluated the diagnostic and prognostic value of 2-dimensional speckle tracking echocardiography in cardiac sarcoidosis (CS). Methods: Eighty-three patients with extracardiac, biopsy-proven sarcoidosis and definite/probable diagnosis of cardiac involvement diagnosed from January 2005 through December 2016 were included. Strain parameters in early stages of CS, in a subgroup of 23 CS patients with left ventricular ejection fraction (LVEF) within normal limits (LVEF>52% for men: >54% for women, mean value: 57.3%±3.8%) and no wall motion abnormalities was compared with 97 controls (1:4) without cardiac disease. LV and right ventricular (RV) global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain and strain rate (SR) analyses were performed with TomTec software and correlated with cardiac outcomes (including heart failure and arrhythmias). This study was approved by the Mayo Clinic Institutional Review Board, and all patients gave informed written consent to participate. Results: Mean age of CS patients was 53.6±10.8 years, and 34.9% were women. Mean LVEF was 43.2%±12.4%; LV GLS, -12.4%±3.7%; LV GCS, -17.1%±6.5%; LV GRS, 29.3%±12.8%; and RV wall GLS, 14.6%±6.3%. In the 23 patients with early stage CS with normal LVEF and RV systolic function, strain parameters were significantly reduced when compared with controls (respectively: LV GLS, -15.9%±2.5% vs -18.2%±2.7% [ P =.001]; RV GLS, -16.9%±4.5% vs -24.1%±4.0% [ P <.001]). A LV GLS value of -16.3% provided 82.2% sensitivity and 81.2% specificity for the diagnosis of CS (AUC 0.91), while a RV value of -19.9% provided 88.1% sensitivity and 86.7% specificity (AUC 0.93). Hospital admission and heart failure significantly correlated to impaired LV GLS (> -14%). Conclusion: Reduced strain values in the LV GLS and RV GLS can be used in the diagnostic algorithm in patients with suspicion of cardiac sarcoidosis. These values also correlate with adverse cardiovascular events.

Abstract Rationale Prompt diagnosis of invasive fungal infections is important because of the associated morbidity and mortality; however, diagnosis is challenging because of the nonspecific symptoms and radiographic findings. Objectives To conduct a systematic review and meta-analysis of studies that evaluated the diagnostic accuracy of serum and bronchoalveolar lavage (BAL) galactomannan (GM) and serum or BAL polymerase chain reaction (PCR) in patients with suspected invasive aspergillosis (IA), β-d-glucan in critically ill patients at risk for candidiasis or candidemia, and serology testing and antigen detection in patients with endemic mycoses (histoplasmosis, blastomycosis, and coccidioidomycosis). Methods Studies were selected and appraised by pairs of reviewers. Bivariate random effects meta-analysis was used to generate pooled sensitivity, specificity, and diagnostic likelihood ratios. Results Serum GM in patients with impaired immunity suspected of having IA had sensitivity of 0.71 (95% confidence interval [CI], 0.64–0.78) and specificity of 0.89 (95% CI, 0.84–0.92). A cutoff of 1 optical density index yielded optimal sensitivity and specificity. BAL GM in patients with impaired immunity suspected of having IA had sensitivity of 0.84 (95% CI, 0.73–0.91) and specificity of 0.88 (95% CI, 0.81–0.91). Serum or whole-blood PCR in immunocompromised patients with suspected IA had sensitivity of 0.81 (95% CI, 0.73–0.86) and specificity of 0.79 (95% CI, 0.68–0.86). BAL PCR in patients at high risk for IA had high sensitivity of 0.90 (95% CI, 0.77–0.96) and specificity of 0.96 (95% CI, 0.93–0.98) for diagnosing IA. β-d-glucan assay in patients in the intensive care unit at risk for invasive candidiasis or candidemia had sensitivity of 0.81 (95% CI, 0.74–0.86) and specificity of 0.60 (95% CI, 0.49–0.71). Data on diagnostic accuracy of antigen detection and serology testing for endemic mycoses were limited and heterogeneous (varied according to test, patient immunity, and suspected endemic disease). Conclusions The diagnosis of invasive fungal infections remains a challenge. Various serum and BAL markers can aid in diagnosis. This evidence supports the development of clinical practice recommendations by the American Thoracic Society.

Quantitative activity through the TCR-proximal protein network specifies thymic positive versus negative selection.