Opacity Scores Research Articles

Ground-glass opacity score predicts the prognosis of anti-MDA5 positive dermatomyositis: a single-centre cohort study

ObjectiveDermatomyositis (DM) positive with anti-melanoma differentiation-associated gene 5 (anti-MDA5-DM) is a systemic autoimmune disease with high mortality. This study aimed to explore the risk factors of death in anti-MDA5-DM and validate a prediction model for all-cause mortality in anti-MDA5-DM.MethodWe conducted a retrospective study using a single-centre cohort of patients with newly onset anti-MDA5-DM from June 1, 2018 to August 31, 2021. Patients were divided into four groups according to baseline ground-glass opacity (GGO) score: Group A, GGO ≤ 1; Group B, 1 < GGO ≤ 2; Group C, 2 < GGO ≤ 3; Group D, GGO > 3. The primary outcome was death during the follow-up. Secondary outcomes included death within 3, 6, 12 months, severe infection, and remission during the first 12 months.ResultsA total of 200 patients were included in the study. Based on multivariable Cox regression, the prognostic factors at baseline were identified as CRP > 5 mg/L, serum ferritin (SF) > 600ng/ml, positive anti-Ro52 antibody, prophylactic use of compound sulfamethoxazole (SMZ Co), four-category GGO score: GGO ≤ 1, 1 < GGO ≤ 2, 2 < GGO ≤ 3, GGO > 3. The final mortality of four groups was 16.4, 22.2, 48.5, 92.0%, respectively. Compared with Group A, the Hazards Ratio (HR) of Group B was 1.408, (p = 0.408), HR of Group C was 3.433 (p = 0.005), HR of Group D was 4.376 (p = 0.001).ConclusionsGGO score is a reliable predictor for risk stratification in anti-MDA5-DM and may provide guidance for individualized managements of patients.

Carbon Monoxide Releasing Molecule-3 Alleviates Oxidative Stress and Apoptosis in Selenite-Induced Cataract in Rats via Activating Nrf2/HO-1 Pathway

Purpose This study investigated the protective effect of carbon monoxide releasing molecule-3 (CORM-3), the classical donor of carbon monoxide, on selenite-induced cataract in rats and explore its possible mechanism. Methods Sprague-Dawley rat pups treated with sodium selenite (Na2SeO3) were chosen as the cataract model. Fifty rat pups were randomly divided into 5 groups: Control group, Na2SeO3 (3.46 mg/kg) group, low-dose CORM-3 (8 mg/kg/d) + Na2SeO3 group, high-dose CORM-3 (16 mg/kg/d) + Na2SeO3 group, and inactivated CORM-3 (iCORM-3) (8 mg/kg/d) + Na2SeO3 group. The protective effect of CORM-3 was tested by lens opacity scores, hematoxylin and eosin staining, TdT-mediated dUTP nick-end labeling assay, and enzyme-linked immunosorbent assay. Besides, quantitative real-time PCR and western blotting were used for mechanism validation. Results Na2SeO3 induced nuclear cataract rapidly and stably, and the achievement ratio of Na2SeO3 group was 100%. CORM-3 alleviated lens opacity of selenite-induced cataract and attenuated the morphological changes of the rat lens. The levels of antioxidant enzymes GSH and SOD in rat lens were also increased by CORM-3 treatment. CORM-3 significantly reduced the ratio of apoptotic lens epithelial cells, besides, CORM-3 decreased the expression of Cleaved Caspase-3 and Bax induced by selenite and increased the expression of Bcl-2 in rat lens inhibited by selenite. Moreover, Nrf-2 and HO-1 were upregulated and Keap1 was downregulated after CORM-3 treatment. While iCORM-3 did not exert the same effect as CORM-3. Conclusions Exogenous CO released from CORM-3 alleviates oxidative stress and apoptosis in selenite-induced rat cataract via activating Nrf2/HO-1 pathway. CORM-3 may serve as a promising preventive and therapeutic strategy for cataract.

Lung Opacity And Coronary Artery Calcium Score: A Combined Tool For Risk Stratification And Outcome Prediction In Covid-19 Patients

Lung Opacity And Coronary Artery Calcium Score: A Combined Tool For Risk Stratification And Outcome Prediction In Covid-19 Patients

Radiological findings based comparison of functional status in patients who have post-covid lung injury or idiopathic pulmonary fibrosis

BackgroundFollowing COVID-19 infection, some patients acquired lung injury and fibrosis. Idiopathic pulmonary fibrosis is characterized by lung fibrosis. Both post-COVID lung injury and idiopathic pulmonary fibrosis cause loss of respiratory function and involvement of the lung parenchyma. We aimed to compare respiratory related functional characteristics and radiological involvement between post-COVID lung injury and idiopathic pulmonary fibrosis.MethodsA single center, cross-sectional study was applied. Patients with post-COVID lung injury and idiopathic pulmonary fibrosis included in the study. All patients underwent the 6-minute walk test, as well as the Borg and MRC scales. Radiological images were evaluated and scored for lung parenchymal involvement. The impact of post-COVID lung injury and idiopathic pulmonary fibrosis on respiratory functions of were compared. The relationship of functional status and radiological involvement, as well as the effect of potential confounding factors were investigated.ResultsA total of 71 patients were included in the study. Forty-eight (67.6%) of the patients were male and the mean age was 65.4 ± 10.3 years. Patients with post-COVID lung injury had greater 6-minute walk test distance and duration, as well as higher oxygen saturations. The MRC and Borg dyspnea scores were comparable. At radiologic evaluation, ground glass opacity scores were higher in patients with post-COVID lung injury, whereas pulmonary fibrosis scores were higher in patients with idiopathic pulmonary fibrosis. However, the total severity scores were similar. While pulmonary fibrosis score was found to have a negative correlation with 6-minute walk test distance, test duration, and pre- and post-test oxygen saturation levels, there was a positive correlation with oxygen saturation recovery time and MRC score. There was no relationship between ground glass opacity and the functional parameters.ConclusionsDespite having equal degrees of radiological involvement and dyspnea symptom severity, PCLI patients exhibited higher levels of functional status. This might be due to different pathophysiological mechanisms and radiological involvement patterns of both diseases.

COVID-19 Severity Prediction from Chest X-ray Images Using an Anatomy-Aware Deep Learning Model.

The COVID-19 pandemic has been adversely affecting the patient management systems in hospitals around the world. Radiological imaging, especially chest x-ray and lung Computed Tomography (CT) scans, plays a vital role in the severity analysis of hospitalized COVID-19 patients. However, with an increasing number of patients and a lack of skilled radiologists, automated assessment of COVID-19 severity using medical image analysis has become increasingly important. Chest x-ray (CXR) imaging plays a significant role in assessing the severity of pneumonia, especially in low-resource hospitals, and is the most frequently used diagnostic imaging in the world. Previous methods that automatically predict the severity of COVID-19 pneumonia mainly focus on feature pooling from pre-trained CXR models without explicitly considering the underlying human anatomical attributes. This paper proposes an anatomy-aware (AA) deep learning model that learns the generic features from x-ray images considering the underlying anatomical information. Utilizing a pre-trained model and lung segmentation masks, the model generates a feature vector including disease-level features and lung involvement scores. We have used four different open-source datasets, along with an in-house annotated test set for training and evaluation of the proposed method. The proposed method improves the geographical extent score by 11% in terms of mean squared error (MSE) while preserving the benchmark result in lung opacity score. The results demonstrate the effectiveness of the proposed AA model in COVID-19 severity prediction from chest X-ray images. The algorithm can be used in low-resource setting hospitals for COVID-19 severity prediction, especially where there is a lack of skilled radiologists.

Therapeutic effects of thalidomide on patients with systemic sclerosis-associated interstitial lung disease.

To evaluate the clinical efficacy of thalidomide in patients with systemic sclerosis-associated interstitial lung disease. Ninety-six systemic sclerosis-associated interstitial lung disease patients who received basic glucocorticoid treatment and admitted between 2016 and 2020 were included in this study, including 48 cases in the thalidomide group (combination of thalidomide and cyclophosphamide) and 48 cases in control group (cyclophosphamide monotherapy). Evaluation items included clinical symptoms, modified Rodnan skin score, pulmonary function test, chest high-resolution computed tomography scores, and adverse effects between two groups after 24 weeks of treatment. Remarkable improvements in several aspects were found in the thalidomide group, including modified Rodnan skin score, expiratory dyspnea score, cough visual analog scale score, total ground-glass opacity score, and total interstitial lung disease score. Compared to the control group, improvements in the thalidomide group were found, such as significantly decreased cough visual analog scale score and expectoration; increased number of platelets; improved pulmonary fibrosis (p = 0.056), and reduced carbon monoxide diffusing capacity (p = 0.053). There were no statistically significant differences in the expiratory dyspnea score and predicted forced vital capacity between the two groups. Patients who experienced at least one adverse event in the control group and thalidomide group were 33.3% and 64.6% (p = 0.002); while those with serious adverse events were 8.3% versus 12.5% (p = 0.504). Venous thrombosis was found in one case in the thalidomide group. Thalidomide combined with cyclophosphamide can improve the symptoms of cough and expectoration in patients with systemic sclerosis-associated interstitial lung disease, and may slightly delay the progression of pulmonary fibrosis, but with the possibility of an increased risk of adverse events.

Assessment of cardiopulmonary manifestations and its correlation with semi-quantitative scoring of high-resolution computed tomography in patients with autoimmune rheumatic diseases

PurposeAutoimmune rheumatic diseases (ARD) are groups of diseases that are commonly associated with cardiac and pulmonary manifestations and may affect the morbidity and mortality of the patients. The study aimed to the assessment of cardiopulmonary manifestations and their correlation with the semi-quantitative scoring of high-resolution computed tomography (HRCT) in ARD patients.Methods and patients30 patients with ARD were included in the study (mean age 42.2 ± 9.76 years) [10 patients were scleroderma (SSc), 10 patients were rheumatoid arthritis (RA), and 10 patients were systemic lupus erythematosus (SLE)]. They all met the diagnostic criteria of the American College of Rheumatology and underwent spirometry, echocardiography, and chest HRCT. The HRCT was assessed by a semi-quantitative score for parenchymal abnormalities. Correlation between HRCT lung scores and: inflammatory markers, lung volumes in spirometry, and echocardiographic indices has been performed.ResultsThe total lung score (TLS) by HRCT was 14.8 ± 8.78 (mean ± SD), ground glass opacity score (GGO) was 7.20 ± 5.79 (mean ± SD) and fibrosis lung score (F) was 7.63 ± 6.05 (mean ± SD). TLS correlated significantly with ESR (r 0.528, p 0.003), CRP (r 0.439, p 0.015), PaO2 (r -0.395, P 0.031) FVC% (r -0.687, p 0.001), and echocardiographic Tricuspid E (r -0.370, p 0.044), Tricuspid E/è (r -0.397,p 0.03), ESPAP (r 0.459,p 0.011), TAPSE (r -0.405, p 0.027), MPI-TDI (r -0.428, p 0.018) and RV Global strain(r -0.567, p 0.001). GGO score correlated significantly with ESR (r 0.597, p 0.001), CRP (r 0.473, p 0.008), FVC% (r -0.558, p 0.001), and RV Global strain(r -0.496, p 0.005). F score correlated significantly with FVC% (r -0.397, p 0.030), Tricuspid E/è (r -0.445, p 0.014), ESPAP (r 0.402, p 0.028), and MPI-TDI (r -0.448, p 0.013).ConclusionThe total lung score and GGO score in ARD were found to be consistently significantly correlated with FVC% predicted, PaO2, inflammatory markers, and RV functions. Fibrotic score correlated with ESPAP. Therefore, in a clinical setting, most clinicians who monitor patients suffering from ARD should concern with the applicability of semiquantitative HRCT scoring in clinical practice.

Initial clinical, laboratory and radiological features of SARS-CoV-2-infected patients and their impact on the course of the disease.

On March 11, 2020, coronavirus disease (COVID-19) was declared a global threat by the World Health Organization (WHO). It quickly became apparent that reducing inpatient mortality rates and early phase prediction of possible deterioration or severe disease course relied on finding more specific biomarkers. This retrospective study assessed initial clinical, laboratory and radiological features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and explored their impact on mortality and the course of the disease. Such efforts aimed to facilitate the identification of high-risk patients and to improve the formulation of treatment plans for these individuals. The cohort comprised 111 consecutive adult inpatients diagnosed with COVID-19 and hospitalized in the Internal Medicine Ward of the University Clinical Center of prof. K. Gibiński of the Medical University of Silesia in Katowice, Poland, a COVID-19 Treatment Unit, between November 16, 2020 and February 15, 2021. All available clinical, laboratory and radiological findings were extracted from electronic records and assessed as possible risk factors for poor prognosis. Clinicasl and radiological features with higher frequency in COVID-19 non-survivors included older age, history of smoking, concomitant cardiovascular diseases, low oxygen saturation (SpO2), and high infection risk assessed on admission as well as high opacity score, percentage of opacity and percentage of high opacity in computed tomography. Non-survivors had decreased serum lymphocytes, monocytes, calcium, magnesium, and hemoglobin oxygen saturation. They also had increased red cell distribution width (RDW), C-reactive protein (CRP), procalcitonin, alkaline phosphatase (ALP), creatinine, blood urea nitrogen (BUN), D-dimer, troponin, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, as well as a base deficit. This retrospective study identified several markers associated with a fatal course of COVID-19. The early assessment of SARS-CoV-2-infected inpatients should consider these markers.

Effects of Pirfenidone on Idiopathic Pulmonary Fibrosis Progression and Safety: Results of Multicenter Prospective Observational Study

The aim of this study was to determine the effectiveness of pirfenidone in patients with idiopathic pulmonary fibrosis (IPF) seen in clinical practice. Fifty-five adults with IPF were enrolled in this multicenter, open-label, non-randomized, non-controlled, interventional clinical study. All patients received pirfenidone 2403 mg/day (three 267 mg capsules three times daily) for 26 weeks. After 26 weeks of treatment, the mean change in absolute forced vital capacity (FVC) was 128.8 mL (95% confidence interval [CI] -26.8, 284.4) and the mean change in relative predicted FVC was -0.10% (95% CI -3.18, 2.99). Stable disease (defined as improvement of ≥0% or a decline of <10% to 0% of the corresponding FVC value) was observed in most patients (relative FVC, 90.9%; absolute FVC, 83.6%). There was no statistically significant change in the mean high-resolution computed tomography fibrosis score or lung opacity score at week 26 compared with baseline. Treatment-emergent adverse events were reported in 80% of patients during the treatment period; most of them were mild or moderate in severity. No serious pirfenidone-related adverse events were observed during the study period. Pirfenidone was generally safe and effective for controlling functional decline and stabilizing disease in patients with IPF encountered in clinical practice in Russia.

The NLRP3 Inflammasome Is Required for Protection Against Pseudomonas Keratitis.

The current study was designed to examine the role of the NLRP3 inflammasome pathway in the clearance of Pseudomonas aeruginosa (PA) infection in mouse corneas. Corneas of wild type and NLRP3-/- mice were infected with PA. The severity of bacterial keratitis was graded on days 1 and 3 post-infection by slit lamp, and then corneas were harvested for: (i) bacterial enumeration, (ii) immune cell analysis by flow cytometry, (iii) immunoblotting analysis of cleaved caspase-1 and IL-1β, and (iv) IL-1β quantification by ELISA. In parallel experiments, severity of keratitis was examined in the wild-type mice receiving a subconjunctival injection of a highly selective NLRP3 inhibitor immediately prior to infection. Compared to wild type mice, NLRP3-/- mice exhibited more severe infection, as indicated by an increase in opacity score and an increase in bacterial load. The hallmark of inflammasome assembly is the activation of proinflammatory caspase-1 and IL-1β by cleavage of their precursors, pro-caspase-1 and pro-IL-1β, respectively. Accordingly, increased severity of infection in the NLRP3-/- mice was associated with reduced levels of cleaved forms of caspase-1 and IL-1β and reduced IL-1β+ neutrophil infiltration in infected corneas. Likewise, corneas of mice receiving subconjunctival injections of NLRP3 inhibitor exhibited increased bacterial load, and reduced IL-1β expression. Activation of NLRP3 pathway is required for the clearance of PA infection in mouse corneas.

Compounded sulfamethoxazole improved the prognosis of dermatomyositis patients positive with anti-melanoma differentiation-associated gene 5.

Mortality of dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM) is alarming, especially during the first several months. Infection is an important cause of early death. As there are no reports regarding the effect of prophylactic use of compounded sulfamethoxazole (coSMZ; each tablet contains 400 mg of sulfamethoxazole and 80 mg of trimethoprim) in anti-MDA5-DM patients, we conducted this study to evaluate the efficacy of coSMZ in reducing the incidence of Pneumocystis jirovecii pneumonia (PJP). Consecutive patients with new-onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for >12 months. They were divided into two groups-coSMZ and non-coSMZ-based on the initial use of prophylactic coSMZ. Mortality and the incidence of severe infection within 12 months were compared between two groups. Compared with the non-coSMZ group (n = 93), the coSMZ group (n = 121) had lower mortality (18.8% vs 51.1%; P < 0.001) and a lower incidence of PJP (6.8% vs 15.2%; P = 0.040) and fatal infection (16.1% vs 3.3%; P = 0.001) during the first 12 months from diagnosis. After adjusting for age, gender, disease duration, peripheral blood lymphocyte count, anti-MDA5 antibody titres, ground-glass opacity scores and treatments, an inverse association was revealed between the prophylactic use of coSMZ and incidence of PJP [adjusted odds ratio 0.299 (95% CI 0.102-0.878), P = 0.028]. Prophylactic use of coSMZ is an effective and safe way to improve the prognosis of anti-MDA5-DM patients by preventing the incidence of PJP.

A radiographic, deep transfer learning framework, adapted to estimate lung opacities from chest x-rays

Chest radiographs (CXRs) are the most widely available radiographic imaging modality used to detect respiratory diseases that result in lung opacities. CXR reports often use non-standardized language that result in subjective, qualitative, and non-reproducible opacity estimates. Our goal was to develop a robust deep transfer learning framework and adapt it to estimate the degree of lung opacity from CXRs. Following CXR data selection based on exclusion criteria, segmentation schemes were used for ROI (Region Of Interest) extraction, and all combinations of segmentation, data balancing, and classification methods were tested to pick the top performing models. Multifold cross validation was used to determine the best model from the initial selected top models, based on appropriate performance metrics, as well as a novel Macro-Averaged Heatmap Concordance Score (MA HCS). Performance of the best model is compared against that of expert physician annotators, and heatmaps were produced. Finally, model performance sensitivity analysis across patient populations of interest was performed. The proposed framework was adapted to the specific use case of estimation of degree of CXR lung opacity using ordinal multiclass classification. Acquired between March 24, 2020, and May 22, 2020, 38,365 prospectively annotated CXRs from 17,418 patients were used. We tested three neural network architectures (ResNet-50, VGG-16, and ChexNet), three segmentation schemes (no segmentation, lung segmentation, and lateral segmentation based on spine detection), and three data balancing strategies (undersampling, double-stage sampling, and synthetic minority oversampling) using 38,079 CXR images for training, and validation with 286 images as the out-of-the-box dataset that underwent expert radiologist adjudication. Based on the results of these experiments, the ResNet-50 model with undersampling and no ROI segmentation is recommended for lung opacity classification, based on optimal values for the MAE metric and HCS (Heatmap Concordance Score). The degree of agreement between the opacity scores predicted by this model with respect to the two sets of radiologist scores (OR or Original Reader and OOBTR or Out Of Box Reader) in terms of performance metrics is superior to the inter-radiologist opacity score agreement.

Association between lung opacities and visceral fat in COVID-19 patients.

To assess the relationship between the amount of the epigastric visceral fat area and the severity of pneumonia in the course of COVID-19 using chest computed tomography (CT) examinations. 177 patients (54 female), with COVID-19 infection were included. A routine chest CT was performed to assess the severity of pneumonia. The affected lung tissue as well as semi-quantitative scales such as the Chest CT Score and Total Opacity Score were calculated using SyngoVia VB30A CT Pneumonia Analysis software. The epigastric region area of visceral fat (L1) was also determined. The mean value of the visceral adipose tissue area was 196.23 ± 101.36 cm2. The area of adipose tissue significantly correlated with the percentage of the affected lung tissue (r = 0.1476; p = 0.050), the Chest CT Score (r = 0.2086; p = 0.005), and the Total Opacity Score (r = 0.1744; p = 0.200). The mean area of adipose tissue in the age group ≥ 65 years was 216.13 ± 105.19 cm2, while in the group < 65 years, it was 169.18 ± 89.69 cm2. This difference was statistically significant (p = 0.002). The study showed a relationship between the area of visceral adipose tissue and the degree of lung inflammation in COVID-19 disease in patients under 65 years of age.

Predicting the COVID-19 Patients Status Using Chest CT Scan Findings: A Risk Assessment Model Based on Decision Tree Analysis.

The role of chest computed tomography (CT) to diagnose coronavirus disease 2019 (COVID-19) is still an open field to be explored. The aim of this study was to apply the decision tree (DT) model to predict critical or non-critical status of patients infected with COVID-19 based on available information on non-contrast CT scans. This retrospective study was performed on patients with COVID-19 who underwent chest CT scans. Medical records of 1078 patients with COVID-19 were evaluated. The classification and regression tree (CART) of decision tree model and k-fold cross-validation were used to predict the status of patients using sensitivity, specificity, and area under the curve (AUC) assessments. The subjects comprised of 169 critical cases and 909 non-critical cases. The bilateral distribution and multifocal lung involvement were 165 (97.6%) and 766 (84.3%) in critical patients, respectively. According to the DT model, total opacity score, age, lesion types, and gender were statistically significant predictors for critical outcomes. Moreover, the results showed that the accuracy, sensitivity and specificity of the DT model were 93.3%, 72.8%, and 97.1%, respectively. The presented algorithm demonstrates the factors affecting health conditions in COVID-19 disease patients. This model has the potential characteristics for clinical applications and can identify high-risk subpopulations that need specific prevention. Further developments including integration of blood biomarkers are underway to increase the performance of the model.

The feasibility of using acoustic measures for predicting the Total Opacity Scores of chest computed tomography scans in patients with COVID-19

ABSTRACT To study the possibility of using acoustic parameters, i.e., Acoustic Voice Quality Index (AVQI) and Maximum Phonation Time (MPT) for predicting the degree of lung involvement in COVID-19 patients. This cross-sectional case–control study was conducted on the voice samples collected from 163 healthy individuals and 181 patients with COVID-19. Each participant produced a sustained vowel/a/, and a phonetically balanced Persian text containing 36 syllables. AVQI and MPT were measured using Praat scripts. Each patient underwent a non-enhanced chest computed tomographic scan and the Total Opacity score was rated to assess the degree of lung involvement. The results revealed significant differences between patients with COVID-19 and healthy individuals in terms of AVQI and MPT. A significant difference was also observed between male and female participants in AVQI and MPT. The results from the receiver operating characteristic curve analysis and area under the curve indicated that MPT (0.909) had higher diagnostic accuracy than AVQI (0.771). A significant relationship was observed between AVQI and TO scores. In the case of MPT, however, no such relationship was observed. The findings indicated that MPT was a better classifier in differentiating patients from healthy individuals, in comparison with AVQI. The results also showed that AVQI can be used as a predictor of the degree of patients’ and recovered individuals’ lung involvement. A formula is suggested for calculating the degree of lung involvement using AVQI.

Amplified Natural Killer Cell Activity and Attenuated Regulatory T-cell Function Are Determinants for Corneal Alloimmunity in Very Young Mice.

Corneal transplantation outcomes are generally less favorable in young children compared with adults. The purpose of this study was to determine the immunological mechanisms underlying this difference. A murine model of allogeneic corneal transplantation was used in the study, and graft survival was determined by evaluating opacity scores for 8 wk. Syngeneic transplantation in the very young host served as a surgical control. The frequencies of total and activated natural killer (NK) cells in cornea posttransplantation were kinetically evaluated using flow cytometry. The regulatory T cell (Treg) frequency and function in naive animals were assessed by flow cytometry and in vitro suppression assays, respectively. Finally, graft survival and immune responses were determined in NK cell-depleted, or adult naive Treg-transferred, young hosts. Corneal allograft survival in the very young recipients was significantly lower than in adult hosts. The frequencies of total NK cells and their interferon gamma-expressing subset in the cornea were significantly higher in the very young mice posttransplantation. In ungrafted mice, frequencies of Treg in draining lymph nodes as well as their capabilities to suppress NK-cell secretion of interferon gamma were lower in the very young compared with adults. In NK cell-depleted or adult Treg--transferred very young recipients, the allograft survival was significantly improved along with the suppressed NK-cell response. Our data demonstrate that amplified activity of NK cells, together with lower suppressive function of Treg, contributes to early rejection of corneal allografts in very young graft recipients.

Changes in anti-MDA5 antibody titres and serum cytokine levels before and after diagnosis of anti-MDA5 antibody-positive dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive DM is characterized by rapidly progressive interstitial lung disease and has a poor prognosis. We aimed to investigate whether anti-MDA5 antibody titres and cytokine levels predict clinical course, and evaluate changes in both parameters before and after diagnosis. This was a retrospective, single-centre study in 38 patients with anti-MDA5 antibody-positive DM. We compared clinical characteristics and laboratory data at diagnosis between patients in the treatment response (n = 23) and non-response (n = 15) groups, and between those in the relapse (n = 5) and non-relapse (n = 24) groups. We also measured serum anti-MDA5 antibody titres and cytokine levels before and after diagnosis. The non-response group was older, had a higher ground-glass opacity score, lower PaO2/FiO2, higher CRP level, and higher anti-MDA5 antibody titre than the response group. No cytokines significantly differed between groups at diagnosis. The relapse group had a significantly higher anti-MDA5 antibody titre than the non-relapse group. In the survivor group, the anti-MDA5 antibody titre and levels of IFN-α, IFN-γ, monocyte chemotactic protein-1 (MCP-1), IL-6, IL-33, CRP, and ferritin were significantly lower 6 months post-treatment than at diagnosis. Macrophage-associated cytokines such as IL-6, IL-8, IL-18 and MCP-1 increased after anti-MDA5 antibody positivity in three patients who were anti-MDA5 antibody-positive before diagnosis. The anti-MDA5 antibody titre at diagnosis may predict the clinical course. Levels of macrophage-associated cytokines significantly declined at 6 months post-treatment, and they may have increased after anti-MDA5 antibody titre positivity.

Predictors of mortality for dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 and optimal treatment.

To explore the risk factors of early death in dermatomyositis patients positive with anti-melanoma differentiation-related gene 5 antibody (anti-MDA5-DM). To explore the optimal treatment regimen for patients with anti-MDA5-DM. Patients with newly onset anti-MDA5-DM from June 2018 to October 2021 in our centre were retrospectively reviewed for 6 months. Patients were divided into five groups based on initial treatments. The major outcome was mortality in 6 months. Secondary outcomes included remission and severe infection. A total of 214 patients were included in the study. During 6 month follow-up, 63 patients (30.14%) died, 112 patients (53.59%) achieved remission, 52 patients (24.88%) experienced serious infection and 5 patients (2.34%) were lost. Independent risk factors of mortality in the first 6 months after diagnosis were as follows: age> 53 years, skin ulcer, peripheral blood lymphocyte count (LYMP)≤ 0.6×109/L, lactate dehydrogenase (LDH) > 500 U/L, C reactive protein (CRP) > 5mg/L, anti-Ro52 antibody and ground-glass opacity (GGO) score> 2. On the contrary, prophylactic use of the compound sulfamethoxazole (SMZ Co) was independent protective factor. The five-category treatment was not an independent influencing factor of early death, but subgroup analysis found that patients with rapidly progressive interstitial lung disease (RPILD) responded better to a triple combination of high-dose glucocorticoids (GC), calcineurin inhibitors (CNI) and cyclophosphamide (CYC) or a triple combibation of GC, CNI and tofacitinib (TOF). Advanced age, skin ulcer, lymphopenia, anti-Ro52 antibody and higher levels of LDH, CRP and GGO score increase the risk of early death for MDA5-DM, while prophylactic use of SMZ Co is protective. Aggressive therapy with combined immunosuppressants may improve the short-term prognosis of anti-MDA5-DM with RPILD.

Heme oxygenase-1 as an important predictor of the severity of COVID-19

A cytokine storm is caused by inflammatory cells, including pro-inflammatory macrophage phenotype (M1), and play a critical role in the pathogenesis of COVID-19, in which diffuse alveolar damage occurs in the lungs due to oxidative stress exposure. Heme oxygenase (HO)-1 is a stress-induced protein produced by the anti-inflammatory / anti-oxidative macrophage phenotype (M2), which also produces soluble CD163 (sCD163). In our study, we investigated and determined that serum HO-1 can be a predictive biomarker for assessing both the severity and the outcome of COVID-19 patients. The serum concentrations of HO-1 and sCD163 of COVID-19 patients were measured on admission. The relationship between these biomarkers and other clinical parameters and outcomes were evaluated. Sixty-four COVID-19 patients (11 mild, 38 moderate, and 15 severe cases) were assessed. The serum HO-1 tended to increase (11.0 ng/mL vs. 24.3 ng/mL vs. 59.6 ng/mL with severity). Serum HO-1 correlated with serum lactate dehydrogenase (R = 0.422), C-reactive protein (R = 0.463), and the ground glass opacity (GGO) and consolidation score (R = 0.625) of chest computed tomography. The serum HO-1 showed a better area under the curve (AUC) for predicting ICU admission than the serum sCD163 (HO-1; 0.816 and sCD163; 0.743). In addition, composite parameters including serum HO-1 and the GGO and consolidation score showed a higher AUC for predicting ICU admission than the AUC of a single parameter. Clinically, serum HO-1, reflecting the activation of M2, could be a very useful marker for evaluating disease severity and predicting prognoses for COVID-19 patients. In addition, controlling activated M2 might be a preventative COVID-19 therapeutic target.

Hyperstable EGF-like bleogen derived from cactus accelerates corneal healing in rats.

Corneal scarring reduces corneal transparency, compromises vision, and is a major cause of vision loss worldwide. Epidermal growth factor (EGF), which is the prototypic member of the EGF receptor (EGFR) agonists, is present in tears to provide repair and regeneration. Recently, we discovered bleogen pB1 in the cactus plant Pereskia bleo and showed that it is a non-canonical and hyperstable EGFR agonist with EGF-like wound healing properties for diabetic rats. Here, we apply bleogen pB1 to accelerate corneal wound healing in rats. To assess the corneal healing effects of bleogen pB1, we induced an acute alkali burn to the right eye of male Wistar rats. After five consecutive ophthalmic applications, fluorescein staining and opacity scores of the bleogen pB1-treated, and the positive control EGF-treated groups improved significantly compared to the saline control group. Immunohistochemical analyses revealed that infiltrated CD68+ macrophages and the expression of the myofibroblast marker alpha smooth muscle actin (α-SMA) were significantly decreased in the bleogen pB1- and the EGF-treated groups. By employing a differential gene expression analysis of bleogen pB1- and EGF-treated keratinocytes through RNA-seq, we demonstrated that bleogen pB1 or EGF treatments can affect the expression of genes associated with inflammatory responses and extracellular matrix remodeling. Taken together, our results indicate that the plant-derived EGFR agonist bleogen pB1 can produce similar effects to those of EGF in accelerating corneal wound healing as well as in reducing persistent inflammation and myofibroblast accumulation in the cornea.