Expansion of exhausted CD8+ T cells associates with increased pulmonary fungal infection risk in anti-melanoma differentiation associated gene 5 dermatomyositis.

OBJECTIVES: Anti-MDA5+ dermatomyositis was associated with poor prognosis due to the high incidence of rapid progressive interstitial lung disease, pulmonary infection. The aim of this study is to investigate the abundance and clinical relevance of exhaustion markers on peripheral CD8 T cells from patients with idiopathic inflammatory myopathy (IIM). METHODS: Twenty-nine healthy controls (HCs) and 71 patients with IIM were enrolled, including 42 with anti-MDA5+ and 18 with anti-MDA5- dermatomyositis (DM) and 11 with anti-synthetase syndrome (ASS). Flow cytometry was applied to detect PD-1, TIM-3 and LAG-3 in CD8 T cells. The clinical associations of the CD8 T cell exhaustion phenotype in patients with anti-MDA5+ DM were analysed. RESULTS: CD8 T cells from patients with anti-MDA5+ DM showed significantly increased LAG-3, TIM-3 and PD-1 compared to those from patients with anti-MDA5- IIM (18 with anti-MDA5- DM and 11 with ASS) or HCs (adjusted p all < 0.05). CD8 T cells with distinct exhaustion levels were all significantly increased in anti-MDA5+ DM patients compared with HCs (p all < 0.05). Patients with high level of PD-1+ TIM-3+LAG-3+ CD8+ T cells had a significant higher incidence of pulmonary fungal infections but lower counts of CD4+ and CD8+ T cells. ROC analysis revealed that the frequency of PD-1+TIM-3+LAG-3+CD8+ T cell significantly predicted pulmonary fungal infections (area under the curve: 0.828). CONCLUSIONS: CD8 T cells from patients with anti-MDA5+ DM show significant exhausted phenotype, and increased exhausted CD8 T cells were associated with high risk of pulmonary fungal infection.

IbBBX24 Promotes the Jasmonic Acid Pathway and Enhances Fusarium Wilt Resistance in Sweet Potato.

Cultivated sweet potato (Ipomoea batatas) is an important source of food for both humans and domesticated animals. Here, we show that the B-box (BBX) family transcription factor IbBBX24 regulates the jasmonic acid (JA) pathway in sweet potato. When IbBBX24 was overexpressed in sweet potato, JA accumulation increased, whereas silencing this gene decreased JA levels. RNA sequencing analysis revealed that IbBBX24 modulates the expression of genes involved in the JA pathway. IbBBX24 regulates JA responses by antagonizing the JA signaling repressor IbJAZ10, which relieves IbJAZ10's repression of IbMYC2, a JA signaling activator. IbBBX24 binds to the IbJAZ10 promoter and activates its transcription, whereas it represses the transcription of IbMYC2 The interaction between IbBBX24 and IbJAZ10 interferes with IbJAZ10's repression of IbMYC2, thereby promoting the transcriptional activity of IbMYC2. Overexpressing IbBBX24 significantly increased Fusarium wilt disease resistance, suggesting that JA responses play a crucial role in regulating Fusarium wilt resistance in sweet potato. Finally, overexpressing IbBBX24 led to increased yields in sweet potato. Together, our findings indicate that IbBBX24 plays a pivotal role in regulating JA biosynthesis and signaling and increasing Fusarium wilt resistance and yield in sweet potato, thus providing a candidate gene for developing elite crop varieties with enhanced pathogen resistance but without yield penalty.

Evaluation and validation of the prognostic value of anti-MDA5 IgG subclasses in dermatomyositis-associated interstitial lung disease.

OBJECTIVE: To investigate the association between the anti-melanoma differentiation associated gene 5 (MDA5) IgG subclasses and prognosis of patients with dermatomyositis (DM)-associated interstitial lung disease (ILD). METHODS: This retrospective study included 122 anti-MDA5 positive DM-ILD patients admitted from October 2017 to October 2020 as training cohort, and additional 68 patients from August 2014 to September 2017 as validation cohort. The levels of anti-MDA5 total IgG and IgG subclasses were measured using in-house enzyme-linked immunosorbent assays, and analysed in association with the patient prognosis. RESULTS: In the training cohort, the concentrations of anti-MDA5 IgG1 and IgG3 in non-survivors were significantly higher than in survivors (P < 0.05), whereas there were no significant differences in the IgG2 and IgG4 levels. Kaplan-Meier survival analysis revealed that the levels of anti-MDA5 total IgG, IgG1 and IgG3 were associated with mortality (P < 0.05). Multivariate analysis revealed anti-MDA5 IgG1 >13 U/ml and anti-MDA5 IgG3 >11 U/ml were independent risk factors for death of DM-ILD patients (P < 0.05). Anti-MDA5 IgG1 was confirmed as an independent risk factor in the validation cohort, while anti-MDA5 IgG3 was not. Anti-MDA5 IgG1 showed greater discriminable power for patient prognosis (Youden index 0.494) than anti-MDA5 total IgG, IgG3, or the combination of IgG1 and IgG3 (Youden index 0.356, 0.32 and 0.447, respectively). CONCLUSION: Anti-MDA5 IgG1 and IgG3 are significantly associated with poor prognosis in DM-ILD patients, and anti-MDA5 IgG1 is more efficient as a prognostic biomarker in DM-ILD patients.

A Novel Petri Nets-Based Modeling Method for the Interaction between the Sensor and the Geographic Environment in Emerging Sensor Networks.

The service of sensor device in Emerging Sensor Networks (ESNs) is the extension of traditional Web services. Through the sensor network, the service of sensor device can communicate directly with the entity in the geographic environment, and even impact the geographic entity directly. The interaction between the sensor device in ESNs and geographic environment is very complex, and the interaction modeling is a challenging problem. This paper proposed a novel Petri Nets-based modeling method for the interaction between the sensor device and the geographic environment. The feature of the sensor device service in ESNs is more easily affected by the geographic environment than the traditional Web service. Therefore, the response time, the fault-tolerant ability and the resource consumption become important factors in the performance of the whole sensor application system. Thus, this paper classified IoT services as Sensing services and Controlling services according to the interaction between IoT service and geographic entity, and classified GIS services as data services and processing services. Then, this paper designed and analyzed service algebra and Colored Petri Nets model to modeling the geo-feature, IoT service, GIS service and the interaction process between the sensor and the geographic enviroment. At last, the modeling process is discussed by examples.

Polycomb regulates circadian rhythms in Drosophila in clock neurons.

Circadian rhythms are essential physiological feature for most living organisms. Previous studies have shown that epigenetic regulation plays a crucial role. There is a knowledge gap in the chromatin state of some key clock neuron clusters. In this study, we show that circadian rhythm is affected by the epigenetic regulator Polycomb (Pc) within the Drosophila clock neurons. To investigate the molecular mechanisms underlying the roles of Pc in these clock neuron clusters, we use targeted DamID (TaDa) to identify genes significantly bound by Pc in the neurons marked by C929-Gal4 (including l-LNvs cluster), R6-Gal4 (including s-LNvs cluster), R18H11-Gal4 (including DN1 cluster), and DVpdf-Gal4, pdf-Gal80 (including LNds cluster). It shows that Pc binds to the genes involved in the circadian rhythm pathways, arguing a direct role for Pc in regulating circadian rhythms through specific clock genes. This study shows the identification of Pc targets in the clock neuron clusters, providing potential resource for understanding the regulatory mechanisms of circadian rhythms by the PcG complex. Thus, this study provided an example for epigenetic regulation of adult behavior.

Association of anti-HMGCR antibodies of the IgM isotype with refractory immune-mediated necrotizing myopathy.

OBJECTIVE: Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) autoantibodies are one of the myositis-specific antibodies which is associated with immune-mediated necrotizing myopathy (IMNM). However, the relationship between anti-HMGCR isotypes and prognosis has not yet been fully investigated. This study was conducted to gain insight into the association between anti-HMGCR isotypes and clinical, and prognosis in IMNM patients who were positive for anti-HMGCR antibodies. METHODS: Levels of anti-HMGCR isotypes (IgG, IgA and IgM) were assessed by enzyme-linked immunosorbent assay (ELISA) in 123 consecutive serum samples obtained from 71 patients who were positive for anti-HMGCR IgG at baseline. Disease activity was assessed by manual muscle testing (MMT) 8, Physician's Global Assessment (PGA) visual analog scale (VAS), and muscle VAS. RESULTS: Baseline anti-HMGCR IgG levels were correlated with PGA VAS (r = 0.24; p = 0.04), muscle VAS (r = 0.32; p < 0.01), and MMT8(r=-0.24; p = 0.04), and baseline anti-HMGCR IgM levels were positively correlated with PGA VAS (r = 0.27, p = 0.02), muscle VAS (r = 0.24, p = 0.04). Anti-HMGCR IgM positive patients had a lower age of onset [29(25,46) vs. 51(33,65), p = 0.006], and a higher proportion of neck weakness (63.5% vs. 34.6%, p = 0.031) compared with anti-HMGCR IgM negative patients. Longitudinal analysis showed that the changes in anti-HMGCR IgG levels were correlated with the changes in the PGA VAS (ß = 3.830; p < 0.0001), muscle VAS (ß = 2.893; p < 0.0001), MMT8 (ß=-19.368; p < 0.0001), and creatine kinase (CK) levels (ß = 3900.05, p < 0.0001). Anti-HMGCR IgM levels were weakly correlated with anti-HMGCR IgA levels at baseline (r = 0.33, p < 0.01), and the variations in anti-HMGCR IgA levels were correlated with the changes in anti-HMGCR IgM levels during follow-up (ß = 0.885; p < 0.0001). There were more patients with anti-HMGCR IgM who showed a refractory course than those who were with anti-HMGCR IgM negative (polycyclic course: 40% vs. 25%; chronic continuous course: 46.7% vs. 20.5%, p = 0.018). CONCLUSION: In anti-HMGCR IgG-positive IMNM patients, the levels of anti-HMGCR IgG are associated with disease activity, and anti-HMGCR IgM is associated with refractory outcome and poor prognosis.

Spontaneous pneumomediastinum in anti-MDA5-positive dermatomyositis: Prevalence, risk factors, and prognosis.

OBJECTIVE: To depict the clinical panorama of spontaneous pneumomediastinum (SPM) in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5+ DM). METHODS: A total of 1352 patients with idiopathic inflammatory myopathy (IIM), including 384 anti-MDA5+ DM patients were retrospectively enrolled. The clinical profiles of anti-MDA5+ DM-associated SPM were analyzed. RESULTS: We identified that 9.4 % (36/384) of anti-MDA5+ DM patients were complicated with SPM, which was significantly higher than that of non-anti-MDA5+ DM and other IIM subtypes (P all <0.001). SPM developed at a median of 5.5 (3.0, 12.0) months after anti-MDA5+ DM onset. Anti-MDA5+ DM patients complicated with SPM showed a significantly higher frequency of fever, dyspnea, and pulmonary infection including viral and fungal infections compared to those without SPM (P all < 0.05). Cytomegalovirus (CMV) and fungal infections were identified to be independent risk factors for SPM development in the anti-MDA5+ DM. SPM and non-SPM patients in our anti-MDA5+ DM cohort showed comparable short-term and long-term survival (P = 0.236). Furthermore, in the SPM group, we found that the non-survivors had a lower peripheral lymphocyte count, higher LDH level, and higher frequency of intensification of immunosuppressive treatment (IST) than survivors. The elevated LDH level and intensification of IST were independent risk factors for increased mortality in anti-MDA5+ DM-associated SPM patients. CONCLUSIONS: Nearly one-tenth of patients with anti-MDA5+ DM develop SPM. Both CMV and fungal infections are risk factors for SPM occurrence. The development of SPM does not worsen the prognosis of anti-MDA5+ DM patients, and the intensification of IST does harm to the SPM prognosis.

CD8 T cell-derived perforin regulates macrophage-mediated inflammation in a murine model of gout.

OBJECTIVES: Gout is characterized by hyperuricemia and recurrent inflammatory episodes caused by intra-articular crystal deposition of monosodium urate (MSU). There is a clear relationship between gout and metabolic syndrome. Recent evidence indicates that perforin plays a role in regulating glucose homeostasis and provides protection in diet-induced non-alcoholic steatohepatitis models. However, the impact of perforin on immune inflammation in gout remains unclear. METHODS: We induced acute gout models in both wild-type (WT) mice and Prf1null mice by administering intra-articular injections of MSU crystals. We compared the ankle joint swelling and the histological score between the two groups. Furthermore, we investigated underlying mechanisms through in vitro co-culture experiments involving CD8 T cells and macrophages. RESULTS: In this study, Prf1null mice showed significantly more pronounced ankle swelling with increased inflammatory cell infiltrations compared with WT mice 24 h after local MSU injection. Moreover, MSU-induced Prf1null mice exhibited increased accumulation of CD8 T cells but not NK cells. Perforin-deficient CD8 T cells displayed reduced cytotoxicity towards bone marrow-derived M0 and M1 macrophages and promoted TNF-α secretion from macrophage. CONCLUSIONS: Perforin from CD8 T cells limits joint inflammation in mice with acute gout by downregulating macrophage-mediated inflammation. Key Points • Perforin deficiency increased swelling in the ankle joints of mice upon MSU injection. • Perforin deficiency is associated with increased immune cell recruitment and severe joint damage in gout. • Perforin regulated CD8 T cell accumulation in gout and promoted CD8 T cell cytotoxicity towards M0 and M1 macrophages. • CD8 T cell-derived perforin regulated pro-inflammatory cytokine secretion of macrophage.

Systematic analysis for clinical characteristics and outcomes of IgG4-related disease patients during the COVID-19 pandemic.

BACKGROUND: To systematically describe clinical characteristics and investigate factors associated with COVID-19-related infection, hospital admission, and IgG4-related disease relapse in IgG4-RD patients. METHODS: Physician-reported IgG4-RD patients were included in this retrospective study. Using multivariable logistic regression analysis to determine factors for primary outcome (COVID-19-related IgG4-RD relapse) and secondary outcome (COVID-19-related infection and hospital admission). Covariates included age, sex, body mass index, smoking status, comorbidities, IgG4-RD clinical features, and treatment strategies. RESULTS: Among 649 patients, 530 had a diagnosis of COVID-19, 25 had COVID-19-related hospital admission, and 69 had COVID-19-related IgG4-RD relapse. Independent factors associated with COVID-19 infection were age (OR, 0.98; 95% CI, 0.96-1.00), body mass index (1.10, 1.03-1.18), and tofacitinib (0.34, 0.14-0.79). Further analysis indicated that age (1.10, 1.03-1.16), coronary heart disease (24.38, 3.33-178.33), COVID-19-related dyspnea (7.11, 1.85-27.34), pulmonary infection (73.63, 16.22-4615.34), and methotrexate (17.15, 1.93-157.79) were associated with a higher risk of COVID-19-related hospital admission. Importantly, age (0.93, 0.89-0.98), male sex (0.16, 0.03-0.80), ever/current smoking (19.23, 3.78-97.80), COVID-19-related headache (2.98, 1.09-8.17) and psychiatric symptoms (3.12, 1.07-9.10), disease activity before COVID-19 (1.89, 1.02-3.51), number of involved organs (1.38, 1.08-1.76), glucocorticoid dosage (1.08, 1.03-1.13), and methotrexate (5.56, 1.40-22.08) were strong factors for COVID-19-related IgG4-RD relapse. CONCLUSIONS: Our data add to evidence that smoking and disease-specific factors (disease activity, number of involved organs, and specific medications) were risk factors of COVID-19-related IgG4-RD relapse. The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate and increasing glucocorticoid dosages in the COVID-19 era. Key Points • COVID-19-related infection or hospital admission were associated with known general factors (age, body mass index, specific comorbidities and methotrexate) among IgG4-RD patients. • Smoking and disease-specific factors (disease activity, number of involved organs and specific medications) were associated with higher odds of COVID-19-related IgG4-RD relapse. • The results highlight the importance of adequate disease control with b/tsDMARDs, preferably without using methotrexate or increasing glucocorticoid dosages.

Decrease in cell counts and alteration of phenotype characterize peripheral NK cells of patients with anti-MDA5-positive dermatomyositis.

OBJECTIVE: To investigate the levels and phenotypes of peripheral natural killer (NK) cells in anti-MDA5+ dermatomyositis (DM) patients, and their association with clinical features. METHODS: Peripheral NK cell counts (NKCCs) were retrospectively collected from 497 patients with idiopathic inflammatory myopathies and 60 healthy controls. Multi-color flow cytometry was used to determine the NK cell phenotypes in additional 48 DM patients and 26 healthy controls. The association of NKCC and NK cell phenotypes with the clinical features and prognosis were analyzed in anti-MDA5+ DM patients. RESULTS: NKCC was significantly lower in anti-MDA5+ DM patients than in those with other IIM subtypes and healthy controls. A significant decrease in NKCC was associated with disease activity. Furthermore, NKCC < 27 cells/µL was an independent risk factor for 6-month mortality in anti-MDA5+ DM patients. In addition, identification of the functional phenotype of NK cells revealed significantly increased expression of the inhibitory marker CD39 in CD56brightCD16dimNK cells of anti-MDA5+ DM patients. CD39+NK cells of anti-MDA5+ DM patients showed increased expression of NKG2A, NKG2D, Ki-67, decreased expression of Tim-3, LAG-3, CD25, CD107a, and reduced TNF-α production. CONCLUSION: Decreased cell counts and inhibitory phenotype are significant characteristics of peripheral NK cells in anti-MDA5+ DM patients.

Liquid Metal Microgels for Three-Dimensional Printing of Smart Electronic Clothes.

Gallium-based liquid metals (LMs), with the combination of liquid fluidity and metallic conductivity, are considered ideal conductive components for flexible electronics. However, huge surface tension and poor wettability seriously hinder the patterning of LMs and their wider applications. Herein, a recyclable liquid-metal-microgel (LMM) ink composed of LM droplets encapsulated into alginate microgel shells is proposed. During the mechanical stirring process, the released Ga3+ can cross-link with sodium alginate to form microgels covering the surface of LM droplets, which exhibits shear-thinning performance due to the formation and rupture of hydrogen bonds under different stress conditions, making the LMM ink possess excellent printability and superior adhesion to various substrates. Although patterns printed with the LMM ink are not initially conductive, they can be activated to recover conductivity by microstrain (<5%), pressing, and freezing. Additionally, the activated LMM circuit exhibits superior Joule heating behaviors and electrical performance in further investigation, including excellent conductivity, significant resistance response to strain with small hysteresis, great durability to nonplanar forces, and so forth. Furthermore, smart electronic clothes were fabricated and investigated by directly printing functional circuits on commercial clothes with the LMM ink, which integrate multiple functions, including tactile sensing, motion monitoring, human-computer interaction, and thermal management.

Adrenomedullin Expression Is Associated With the Severity and Poor Prognosis of Interstitial Lung Disease in Dermatomyositis Patients.

Objective: To evaluate adrenomedullin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of patients with dermatomyositis (DM) as well as their correlation with the severity of interstitial lung disease (ILD). Methods: A total of 41 DM patients and seven immune-mediated necrotizing myopathy (IMNM) patients were recruited, in addition to 21 healthy controls (HCs). The adrenomedullin mRNA levels in PBMCs were measured via quantitative reverse-transcription real-time polymerase chain reaction (qRT-PCR). The associations between adrenomedullin expression levels and major clinical, laboratory, pulmonary function parameters and the prognosis of patients with DM-related ILD (DM-ILD) were analyzed. Immunohistochemical analysis was performed on lung tissues of DM-ILD patients to determine adrenomedullin expression. Results: Adrenomedullin mRNA levels in PBMCs were significantly higher in DM patients than in IMNM patients and HCs (p = 0.022 and p<0.001, respectively). Among DM patients, the levels were significantly higher in those with rapidly progressive ILD (RP-ILD) than in those with chronic ILD (p = 0.002) or without ILD (p < 0.001). The adrenomedullin mRNA levels in DM-ILD were positively correlated with serum ferritin (r =0.507, p =0.002), lactate dehydrogenase (LDH) (r =0.350, p =0.045), and lung visual analog scale (VAS) (r=0.392, p=0.021) and were negatively correlated with pulmonary function test parameters, including predicted forced vital capacity (FVC)% (r = -0.523, p = 0.025), forced expiratory volume in 1 s (FEV1)% (r = -0.539, p = 0.020), and diffusing capacity of carbon monoxide (DLco)% (r = -0.495, p = 0.036). Immunohistochemical analysis of adrenomedullin confirmed higher expression in the alveolar epithelial cells and macrophages of DM patients with RP-ILD. Among the DM patients with ILD, the six decedents exhibited higher adrenomedullin levels than the 28 survivors (p = 0.042). The cumulative survival rate was significantly lower (62.5% vs. 100%, P = 0.005) in patients with an adrenomedullin level > 0.053 than in those with a level <0.053. Conclusions: Adrenomedullin levels are upregulated in DM patients with RP-ILD and are associated with ILD severity and poor prognosis. Adrenomedullin may be a potential prognostic biomarker in DM patients with ILD, although need further investigation.

Resistin Expression Is Associated With Interstitial Lung Disease in Dermatomyositis.

Objective: In the current study, we aimed to assess resistin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of dermatomyositis patients with interstitial lung disease (DM-ILD) and their correlation with disease activity. Methods: We detected resistin mRNA levels in the PBMCs of 37 DM-ILD, 8 DM patients without ILD, and 19 healthy control (HC) subjects by performing quantitative reverse transcription real-time polymerase chain reaction analysis. Associations between resistin expression levels and major clinical manifestations, laboratory examinations, and disease activity were also analyzed. In addition, resistin expression in lung specimens from patients with DM-ILD was examined via immunohistochemistry and immunofluorescence. Results: Resistin mRNA levels in PBMCs were significantly higher in DM-ILD than that in DM patients without ILD and HCs (p = 0.043, 0.014, respectively). Among these DM-ILD patients, the resistin levels were significantly elevated in those with rapidly progressive ILD than in those with chronic ILD (p = 0.012). The resistin mRNA levels in DM-ILD positively correlated with serum alanine aminotransferase (r = 0.476, p = 0.003), aspartate aminotransferase (r = 0.488, p = 0.002), lactate dehydrogenase (r = 0.397, p = 0.014), C-reactive protein (r = 0.423, p = 0.008), ferritin (r = 0.468, p = 0.003), carcinoembryonic antigen (r = 0.416, p = 0.011), carbohydrate antigen 125 (r = 0.332, p = 0.047), interleukin-18 (r = 0.600, p < 0.001), and lung visual analog scale values (r = 0.326, p = 0.048), but negatively correlated with the diffusing capacity of carbon monoxide (DLco)% (r = -0.447, p = 0.041). Immunohistochemical analysis of resistin showed its elevated expression in the macrophages, alveolar epithelial cells, and weak fibrotic lesions from patients with DM-ILD. Immunofluorescence staining confirmed CD68+ macrophages co-express resistin. Conclusions: Resistin levels were increased in patients with DM-ILD and associated with disease activity and ILD severity. Therefore, resistin may participate in the pathogenesis of DM-ILD and may act as a useful biomarker.

LightGBM: accelerated genomically designed crop breeding through ensemble learning.

LightGBM is an ensemble model of decision trees for classification and regression prediction. We demonstrate its utility in genomic selection-assisted breeding with a large dataset of inbred and hybrid maize lines. LightGBM exhibits superior performance in terms of prediction precision, model stability, and computing efficiency through a series of benchmark tests. We also assess the factors that are essential to ensure the best performance of genomic selection prediction by taking complex scenarios in crop hybrid breeding into account. LightGBM has been implemented as a toolbox, CropGBM, encompassing multiple novel functions and analytical modules to facilitate genomically designed breeding in crops.

Butane-2,3-dione bis-[(4-bromo-benzyl-idene)hydrazone].

The title compound, C(18)H(16)Br(2)N(4), is a linear double Schiff base compound having two parallel 4-bromo-phenyl groups connected across a crystallographic inversion centre by flexible C-C and C=N-N=C bonds and stabilized in the solid state by weak inter-molecular Br⋯Br inter-actions [3.7992 (11) Å], generating an infinite two-dimensional network structure.

Risk factors for progression and prognosis of primary Sjögren's syndrome-associated interstitial lung disease in a Chinese population.

OBJECTIVE: This study explored differences between primary Sjögren's syndrome-associated interstitial lung disease (pSS-ILD) patients with and without ILD progression, and analyzed the factors affecting the progression and prognosis of pSS-ILD. METHODS: This study is a retrospective cohort study which enrolled 113 pSS-ILD patients hospitalized between 2011 and 2017. RESULTS: The 3-year survival rate of the pSS-ILD patients was 91.15%, and the 5-year survival rate was 84.07%. Univariate analysis showed that Raynaud's syndrome, hypoproteinemia, extensive lung involvement, possible usual interstitial pneumonia pattern were risk factors for the progression of ILD in patients with pSS-ILD, and cyclophosphamide was a protective factor for the progression of ILD in patients with pSS-ILD. Multiple logistic regression analysis showed that extensive lung involvement (odds ratio 4.143, 95% CI: 1.203-14.267, P < .05) was an independent risk factor for the progression of pSS-ILD. Cox hazard analysis showed that pSS-ILD with hypoproteinemia (hazard ratio [HR] 17.758, 95% CI: 4.753-66.340, P <- .05) and extensive lung involvement (HR 3.450, 95% CI: 1.419-8.390, P < .05) were associated with worse survival of patients. CONCLUSION: Extensive lung involvement is an independent risk factor for the progression of ILD in patients with pSS-ILD. Hypoproteinemia and extensive lung involvement are independent risk factors for mortality in patients with pSS-ILD, after controlling for potentially influential variables.

A retrospective study on the predictive implications of clinical characteristics and therapeutic management in patients with rheumatoid arthritis-associated interstitial lung disease.

BACKGROUND: Rheumatoid arthritis (RA)-associated interstitial lung disease (ILD) is associated with significant morbidity and is a critical cause of mortality in patients with RA. OBJECTIVE: Our aim was to evaluate predictive and prognostic factors for RA-ILD and to describe the therapeutic management of the condition from a large China cohort. METHODS: This was a retrospective cohort study. We collected data of 1121 RA patients who underwent chest HRCT from 2008 to 2017. Patients without ILD at RA diagnosis were included in the analysis. The development and evolution of ILD in RA patients were followed up. Determinants of ILD development and progression were identified through multivariable logistic analysis. Cox hazards analysis was used to determine significant variables associated with survival. RESULTS: A total of 923 patients without ILD at RA diagnosis were identified and enrolled. Among them, 278 cases (30.12%) were diagnosed as ILD during follow-up. Logistic regression analysis showed that advanced age (> 60 years old) at RA onset (OR: 1.485), male (OR: 1.882), short duration of RA (0~5 years) (OR: 2.099), RF positive (OR: 1.728), elevated lactate dehydrogenase (LDH) (OR: 3.032), and no medication (OR: 1.833) were closely correlated to the development of RA-ILD. No correlation was found between ILD development and traditional DMARDs such as methotrexate and leflunomide. According to the follow-up data, 83 RA-ILD patients were identified as interstitial lung disease (ILD) progression, and 102 participants were stable. Logistic regression modeling demonstrated that DLCO% < 45% (OR: 3.025) and UIP possible pattern on HRCT (OR: 3.476) were independent risk factors for the ILD progression. No correlation was found between ILD progression and traditional DMARDs such as methotrexate and leflunomide. A total of 53 RA-ILD deaths occurred during follow-up. Cox hazards analysis revealed that advanced age (> 60 years old) at RA-ILD diagnosis (HR: 3.181) and extensive lung involvement on HRCT (HR: 2.401) were associated with worse survival. Treatment with cyclophosphamide (HR: 0.210) was associated with better survival. CONCLUSIONS: Advanced age, male, short duration of RA, RF positive, elevated LDH, and no medication are closely correlated with RA-ILD. No correlation was found between traditional DMARDs and ILD development. DLCO% < 45% and UIP possible pattern are predictive factors for ILD progression. No correlation was found between traditional DMARDs and ILD progression. Advanced age and extensive lung involvement on HRCT independently predict mortality; cyclophosphamide treatment helps to improve the prognosis of RA-ILD.Key Points• We designed this study to investigate the predictive and prognostic factors for RA-ILD and to explore the potential role of DMARDs in the evolution of RA-ILD from the development to progression and death.• Patients without ILD at RA diagnosis were enrolled and followed up retrospectively.• Our results showed that no correlation was found between traditional DMARDs and the development and progression of ILD, and regular treatment may improve the development of RA-ILD.• Our results revealed that clinical variables appeared predictive implications for the diagnosis of ILD and physiological and radiological variables appeared predictive implications for the prognosis of ILD, which can provide reference to rheumatologists and help to improve poor prognosis of RA-ILD.

A retrospective analysis of distinguishing features of chest HRCT and clinical manifestation in primary Sjögren's syndrome-related interstitial lung disease in a Chinese population.

To characterize the distinctive chest high-resolution computerized tomography (HRCT) features and clinical manifestations of primary Sjögren syndrome (pSS)-related interstitial lung disease (ILD). The demographic data, clinical manifestations, and laboratory and radiological findings of 527 pSS patients were retrospectively analyzed. ILD was defined based on the presences of pulmonary signs in HRCT. Two hundred six of 527 patients were diagnosed as pSS-ILD, and the prevalence was 39.1%. The three most frequent abnormalities in HRCT were reticular pattern (92.7%), ground-glass attenuation (87.4%), and bronchovascular bundle thickening (82%). One hundred twenty-four cases (60.2%) of the pSS-ILD patients had only a single HRCT pattern, which involved 86 non-specific interstitial pneumonitis (NSIP) cases (41.7%), 22 usual interstitial pneumonia (UIP) cases (10.68%), 8 organizing pneumonia (OP) cases (3.9%), and 8 lymphocytic interstitial pneumonia (LIP) cases (3.9%), respectively. Besides, the more important observation was that 82 cases had no less than two HRCT patterns, and NSIP admixed with OP (43.9%), NSIP admixed with UIP (35.4%), and NSIP admixed with LIP (19.5%) were the most frequent. HRCT of pSS-ILD patients demonstrated bilateral infiltrates (99%), with abnormalities predominantly in the lower lobes (89.3%) and subpleural areas (81.1%), and a few lesions were characterized by hilum distributed (8.7%). Pulmonary function tests (PFTs) revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and the rate of small airway lesions in the pSS-ILD patients was 3.5 times higher in patients of pSS. Logistic regression analysis showed that dry cough (OR 59.05), clubbing (OR 6.26), elevated lactate dehydrogenase (OR 21.38) and positive anti-Ro (OR 7.86) were relevant factors of pSS-ILD. ILD is the common pulmonary involvement of pSS and the prevalence of pSS-ILD is 39.1%. The single pattern of NSIP and UIP in HRCT are the commonest, and about 40% of the pSS-ILD patients possess multiple patterns in HRCT. The classification of idiopathic pulmonary fibrosis cannot completely include the pulmonary imaging features of pSS-ILD.