Risk factors associated with COVID-19 pneumonia in Chinese patients with pre-existing interstitial lung disease during the SARS-CoV-2 pandemic.

In China, the emergence of a nationally widespread epidemic infection of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has appeared within a month since December 7, 2022. To evaluate the risk factors for suffering from coronavirus disease 2019 (COVID-19) pneumonia due to infection with SARS-CoV-2 in different kinds of interstitial lung disease (ILD) patients with diverse immunizations, we conducted this retrospective study on 525 patients with ILDs who underwent regular follow-up in our ILD clinic. Among them, 128 ILD patients (24.4%) suffered from COVID-19 pneumonia after SARS-CoV-2 infection. Patients were older with a male predominance in the pneumonia group than in the nonpneumonia group (65.0 ± 10.0 years vs. 56.4 ± 11.7 years, p < 0.001, 55.5% vs. 39.5%, p = 0.002, respectively). Connective tissue disease-associated ILD (CTD-ILD) (25%), idiopathic pulmonary fibrosis (23.4%), and interstitial pneumonia with autoimmune features (21.1%) were the main pre-existing ILDs in the pneumonia group. In Cox multivariable analysis, only male sex and corticosteroid use were risk factors for COVID-19 pneumonia after infection. Two or three doses of vaccination were a protective factor for pre-existing ILD patients suffering from COVID-19 pneumonia. More than two doses of vaccination were strongly recommended for pre-existing ILD patients, particularly for males who were administered corticosteroids.

Uncommon manifestations of a rare disease: a case of autoimmune GFAP astrocytopathy.

BACKGROUND: Manifestations of intractable hyponatremia and hypokalemia in autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy have been rarely reported. CASE PRESENTATION: A 75-year-old male patient presented as the case of syndrome of inappropriate antidiuretic hormone secretion (SIADH) and intractable hypokalemia, showed fever, fatigue, and mental disorders. Signs and symptoms of meningoencephalitis, ataxia, and cognitive abnormalities. Magnetic resonance imaging (MRI) revealed multiple white matter lesions of the central nervous system. He had GFAP-IgG in the cerebrospinal fluid (CSF). After treatment with corticosteroids, his symptoms were alleviated gradually, and the level of electrolytes was normal. However, head contrast-enhanced MRI + susceptibility-weighted imaging (SWI) showed a wide afflicted region, and the serum GFAP-IgG turned positive. Considering the relapse of the disease, ha was treated with immunoglobulin and mycophenolate mofetil (MMF) to stabilize his condition. CONCLUSION: This case showed a rare disease with uncommon manifestations, suggesting that careful examination and timely diagnosis are essential for disease management and satisfactory prognosis.

Association Between Peripheral Eosinophilia and Clinical Characteristics of Adult-onset Still's Disease with Persistent Eruption: A Retrospective Study.

Persistent eruption occurs in a subset of patients with adult-onset Still's disease. In our experience, a considerable proportion of these patients present with peripheral eosinophilia. The aims of this study were to summarize the clinical and histological features of patients with adult-onset Still's disease with persistent eruption in the current study cohort, and to assess the association between peripheral eosinophil levels and disease characteristics. A total of 21 patients with adult-onset Still's disease with persistent eruption were included in this retrospective study. Koebner signs, an important diagnostic clue, were found in 85.7% of patients. The proportion of patients presenting with eosinophilia within the disease course was 57.1%. Skin histology revealed infiltration of eosinophils in 90.5% of patients. Peripheral eosinophil levels were positively associated with involved body surface area. Patients with normal peripheral eosinophil counts were more likely to achieve complete remission than those with abnormal peripheral eosinophil counts. Eosinophils may be involved in the pathogenesis of skin eruption. Abnormal peripheral eosinophil counts in these patients may indicate a more refractory disease course.

Clinical manifestations and long-term prognosis of Good syndrome: Results from a single-center cohort study from China.

OBJECTIVE: To describe clinical features and long-term prognosis in patients with Good syndrome (GS). METHODS: We retrospectively reviewed medical records of GS patients at Peking Union Medical College Hospital from January 2001 to May 2019. Data regarding clinical manifestations and treatments were collected. Patients were routinely followed-up via clinical and telephone interviews, and survival analysis was performed with Kaplan-Meier analysis. RESULTS: Twenty-four patients were identified, including eight males and 16 females, with a median age at diagnosis of 58 years (interquartile range [IQR], 52-62 years). Twelve patients (50%) had autoimmune manifestations. Multi-organ involvements included musculoskeletal (37.5%), respiratory (33.3%), gastrointestinal (29.2%), hematologic (29.2%) systems, et.al. Infections were detected in 23 (95.8%) patients, mostly located in lung (69.6%), blood (26.1%), and gastrointestinal tract (21.7%). Thymectomy was performed in 23 patients, with the most common histology of type AB (10, 47.6%). Twenty-one patients were consecutively followed-up with a median follow-up of 84 (IQR, 48-116) months and 11 (52.4%) died, mainly due to infection (8/11, 72.7%). The 5- and 10-year survival rates were 90% (95% confidence interval [CI], 77.8-100%) and 38.5% (95% CI, 19.6-75.5%), respectively. CONCLUSION: GS patients tended to present with various infections and autoimmune manifestations. The 10-year survival rate from the Chinese population was poor, mainly due to infections.

[Chest High-resolution Computed Tomography Imaging Features of Lung Involvement in Rheumatoid Arthritis].

Objective To explore the chest high-resolution computed tomography (HRCT) features in patients with rheumatoid arthritis (RA) complicated with pulmonary involvement. Methods Totally 161 patients with RA with lung involvement were collected from June 2014 to May 2018. The chest HRCT findings were retrospectively analyzed. According to the imaging features as well as the results of history taking,pulmonary function test,pathology,and bronchoalveolar lavage fluid test,RA-related lung diseases (RA-LD) were classified and their clinical characteristics were compared. Results These 161 RA-LD patients (56 males and 105 females) whose mean age at diagnosis was (60.7±12.8) years (14-85 years) included 87 cases of usual interstitial pneumonia (UIP) (including 16 cases of possible UIP),44 cases of non-specific interstitial pneumonia (NSIP),10 cases of organizing pneumonia,7 cases of lymphocytic interstitial pneumonia,9 cases of small airway disease (SAD) (including 8 cases of bronchiolitis obliterans and 1 case of follicular bronchiolitis),and 4 other lung manifestations (including 3 cases of diffuse alveolar hemorrhage and 1 case of rheumatoid nodules). The UIP group had the oldest average age [(63.3±12.1) years old] and the highest smoking rate (41.4%). The SAD group had the youngest average age [(54.7±15.1) years old] and there was no smoking history. There were significant differences between these two groups (P=0.020,P<0.001). Seventy patients (43.5%) with RA-LD were complicated with pleural lesions. Conclusions RA involving the lung is common and has varied imaging manifestations,with interstitial lung diseases (mainly UIP and NSIP) being the most important manifestations. RA patients should undergo lung HRCT as early as possible to identify the lung involvement and related types.

Multiple food-borne trematodiases with profound systemic involvement: a case report and literature review.

BACKGROUND: Food-borne trematodiases are an important group of neglected global diseases. Affected patients in regions with low prevalence usually experience delayed diagnosis, especially when presenting with atypical clinical symptoms. Here, we presented a rare case of a Chinese patient infected with three food-borne trematodiases. CASE PRESENTATION: A 42-year-old man presented with diarrhea, lower extremity edema, and symptoms of cardiac dysfunction. He had a history of intermittent consumption of raw freshwater fishes for 6-7 years. Upon evaluation, he had eosinophilia, anemia, intrahepatic bile duct dilatation and a growing space-occupying lesion in the left atrium. The patient underwent a cardiac surgery which revealed an endocardial hematoma due to mechanical injuries. Imaging investigations also revealed intracranial and pulmonary lesions. A total of three trematodiases were diagnosed based upon microscopic stool examination, from which eggs of Clonorchis sinensis, Heterophyidae and Echinostomatidae were identified. Deposition of Clonorchis sinensis eggs was also observed from ileocecal squash slides. The patient was successfully treated with three cycles of praziquantel. CONCLUSIONS: Food-borne trematodiases may present with systemic involvement. Patients with dietary history of high risk or atypical ingestions should be evaluated for parasitic infection, even in non-endemic areas.

The renal manifestations of type 4 familial partial lipodystrophy: a case report and review of literature.

BACKGROUND: Lipodystrophy syndromes are rare disorders of variable body fat loss associated with potentially serious metabolic complications. Familial partial lipodystrophy (FPLD) is mostly inherited as an autosomal dominant disorder. Renal involvement has only been reported in a limited number of cases of FPLD. Herein, we present a rare case of proteinuria associated with type 4 FPLD, which is characterized by a heterozygous mutation in PLIN1 and has not been reported with renal involvement until now. CASE PRESENTATION: A 15-year-old girl presented with insulin resistance, hypertriglyceridaemia, hepatic steatosis and proteinuria. Her glucose and glycated haemoglobin levels were within normal laboratory reference ranges. A novel heterozygous frameshift mutation in PLIN1 was identified in the patient and her mother. The kidney biopsy showed glomerular enlargement and focal segmental glomerulosclerosis under light microscopy; the electron microscopy results fit with segmental thickening of the glomerular basement membrane. Treatment with an angiotensin-converting enzyme inhibitor (ACEI) decreased 24-h protein excretion. CONCLUSIONS: We report the first case of proteinuria and renal biopsy in a patient with FPLD4. Gene analysis demonstrated a novel heterozygous frameshift mutation in PLIN1 in this patient and her mother. Treatment with ACEI proved to be beneficial.

Overexpression of synuclein-γ predicts lack of benefit from radiotherapy for breast cancer patients.

BACKGROUND: Although radiotherapy following mastectomy was demonstrated to reduce the recurring risk and improve the prognosis of patients with breast cancer, it is also notorious for comprehensive side effects, hence only a selected group of patients can benefit. Therefore, the screening of molecular markers capable of predicting the efficacy of radiotherapy is essential. METHODS: We have established a cohort of 454 breast cancer cases and selected 238 patients with indications for postoperative radiotherapy. Synuclein-γ (SNCG) protein levels were assessed by immunohistochemistry, and SNCG status was retrospectively correlated with clinical features and survival in patients treated or not treated with radiotherapy. Gene Set Enrichment Analysis (GSEA) and survival analysis for online datasets were also performed for further validation. RESULTS: Among patients that received radiotherapy (82/238), those demonstrating positive SNCG expression had a 55.0 month shorter median overall survival (OS) in comparison to those demonstrating negative SNCG expression (78.4 vs. 133.4 months, log rank χ (2) = 16.13; p < 0.001). Among the patients that received no radiotherapy (156/238), SNCG status was not correlated with OS (log rank χ (2) = 2.40; p = 0.121). A COX proportional hazard analysis confirmed SNCG as an independent predictor of OS, only for patients who have received radiotherapy. Similar results were also obtained for distant metastasis-free survival (DMFS). A GSEA analysis indicated that SNCG was strongly associated with genes related to a radiation stress response. A survival analysis was performed with online databases consisting of breast cancer, lung cancer, and glioblastoma and further confirmed SNCG's significance in predicting the survival of patients that have received radiotherapy. CONCLUSION: A positive SNCG may serve as a potential marker to identify breast cancer patients who are less likely to benefit from radiotherapy and may also be extended to other types of cancer. However, the role of SNCG in radiotherapy response still needs to be further validated in randomized controlled trials prior to being exploited in clinical practice.

Smoking contribution to the global burden of metabolic disorder: A cluster analysis.

INTRODUCTION AND OBJECTIVES: Smoking is associated with various health risks, including cancer, cardiovascular disease, and chronic obstructive pulmonary disease. In this retrospective cohort study, we aimed to determine whether smoking is harmful to the whole metabolic system. METHODS: We collected data from 340 randomly selected participants who were divided into three groups: smokers (n=137), non-smokers (n=134), and ex-smokers (n=69). We obtained information on participants' body mass index, waist circumference, indicators of glucose metabolism, lipid metabolism, bone metabolism, and uric acid from health screen data during the past three years. A cluster analysis was used to synthesize each participant's overall metabolic characteristics. RESULTS: According to the cluster analysis, the 340 participants were divided into three groups: excellent metabolizers (137, 40.3%), adverse metabolizers (32, 9.4%), and intermediate metabolizers (171, 50.3%). The Chi-squared test analysis shows that people with different smoking statuses have different metabolic patterns. Non-smokers had the highest proportion of excellent metabolizers (56%), and current smokers had the highest proportion of adverse metabolizers (15.3%). The proportion of adverse metabolizers (5.8%) in the ex-smoker group was clinically relevantly lower than that of current smokers. CONCLUSION: The statistically significant differences in the distribution of smokers into different metabolic clusters indicate that smoking has adverse effects on the whole metabolic system of the human body, which further increases the existing global burden of metabolic disorders.

The Clinical Analysis of Checkpoint Inhibitor Pneumonitis with Different Severities in Lung Cancer Patients: A Retrospective Study.

Immune-related adverse events (irAEs) of immunotherapy would lead to the temporary or permanent discontinuation of immune checkpoint inhibitors (ICIs). Among them, checkpoint inhibitor pneumonitis (CIP) is a potentially life-threatening irAE. This study aimed to identify the differences between patients with low-grade CIPs (grades 1-2) and high-grade CIPs (grades 3-5) and to explore the prognostic factors. We retrospectively reviewed the medical records of 916 lung cancer patients who were treated with ICIs. Patients with CIPs were identified after multidisciplinary discussion, and their clinical, laboratory, radiological, and follow-up data were analyzed. Among the 74 enrolled CIP patients, there were 31 low-grade CIPs and 43 high-grade CIPs. Compared with low-grade CIP patients, patients with high-grade CIPs were older (65.8 years vs. 61.5 years) and had lower serum albumin (35.2 g/L vs. 37.9 g/L), higher D-dimer (5.1 mg/L vs. 1.7 mg/L), and more pulmonary infectious diseases (32.6% vs. 6.5%) during follow-up. In addition, complication with pulmonary infectious diseases, management with intravenous immunoglobulin, tocilizumab, and longer duration of large dosage corticosteroids might be associated with worse outcomes for patients with CIPs. This study highlights potential risk factors for high-grade CIP and poor prognosis among lung cancer patients who were treated with anti-cancer ICIs.

Tacrolimus alleviates pulmonary fibrosis progression through inhibiting the activation and interaction of ILC2 and monocytes.

Idiopathic pulmonary fibrosis (IPF) is a heterogeneous group of lung diseases with different etiologies and characterized by progressive fibrosis. This disease usually causes pulmonary structural remodeling and decreased pulmonary function. The median survival of IPF patients is 2-5 years. Predominantly accumulation of type II innate immune cells accelerates fibrosis progression by secreting multiple pro-fibrotic cytokines. Group 2 innate lymphoid cells (ILC2) and monocytes/macrophages play key roles in innate immunity and aggravate the formation of pro-fibrotic environment. As a potent immunosuppressant, tacrolimus has shown efficacy in alleviating the progression of pulmonary fibrosis. In this study, we found that tacrolimus is capable of suppressing ILC2 activation, monocyte differentiation and the interaction of these two cells. This effect further reduced activation of monocyte-derived macrophages (Mo-M), thus resulting in a decline of myofibroblast activation and collagen deposition. The combination of tacrolimus and nintedanib was more effective than either drug alone. This study will reveal the specific process of tacrolimus alleviating pulmonary fibrosis by regulating type II immunity, and explore the potential feasibility of tacrolimus combined with nintedanib in the treatment of pulmonary fibrosis. This project will provide new ideas for clinical optimization of anti-pulmonary fibrosis drug strategies.

Diffuse lung involvement in rheumatoid arthritis: a respiratory physician's perspective.

ABSTRACT: The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.

Microscopic polyangiitis initially presenting with idiopathic pulmonary fibrosis: a case report.

Usual interstitial pneumonia is the most common type of microscopic polyangiitis (MPA)-associated interstitial lung disease, and patients may initially present with isolated pulmonary fibrosis, which often leads to a misdiagnosis of idiopathic pulmonary fibrosis (IPF). Here, we describe a patient who developed fever of unknown origin, microscopic hematuria and renal insufficiency, who then tested positive for antineutrophil cytoplasmic antibody (ANCA) and was diagnosed with MPA after receiving antifibrotic medication for IPF (original diagnosis) for almost 10 years. The patient's symptoms were ameliorated after administration of additional glucocorticoids and immunosuppressants.

Migratory Pulmonary Infiltrates in a B-Cell-Depleted COVID-19 Patient.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still rampant around the world. Immunocompromised patients are prone to have long-term infection with coronavirus disease 2019 (COVID-19). However, it is difficult to decide on an appropriate treatment for persistent SARS-CoV-2 infection. Case Presentation: We present a case of prolonged SARS-CoV-2 infection in a patient who had undergone B-cell depletion therapy. Chest computed tomography (CT) revealed notable migratory pulmonary infiltrates, and bronchoalveolar lavage fluid was positive for SARS-CoV-2 (day-120). The patient responded well to the combination treatment of antiviral medication, convalescent plasma, and corticosteroid. Conclusion: When chest CT shows migratory pulmonary infiltrates in patients with recent COVID-19, it is necessary to be alert to the possibility of persistent SARS-CoV-2 infection, especially in B-cell-depleted immunocompromised patients. Once the diagnosis is confirmed, repeated antiviral therapy and intravenous convalescent plasma should be considered.

Clinical spectrum of Chinese hospitalized lung cancer patients with concomitant interstitial lung disease: before and after the new era of LC treatment.

This study aimed to explore the general characteristics and spectrum of hospitalized Chinese patients suffering from lung cancer with concomitant interstitial lung disease (LC-ILD). Furthermore, we compared their features before and after the period of immunotherapy for lung cancer. A retrospective analysis of the clinical characteristics of hospitalized LC patients with definite pathological diagnoses was performed from 2014 to 2021. ILD was defined after the review of chest CT imaging. There were 13,085 hospitalized LC patients. Among them, 509 patients (3.89%) had 551 cases of ILD. There were variable underlying causes of ILD, including idiopathic interstitial pneumonia (360 patients), LC treatment-associated ILD (134 cases), and connective tissue disease-associated ILD (55 patients). Although most LC-ILD patients were suffering from adenocarcinoma (204/40.1%), SCLC patients were prone to concomitant ILD (10.8% of all SCLC cases), followed by SCC (9.6% of all SCC cases). All but 10 LC-ILD patients received anti-LC treatment; however, only 39 (10.8%) LC-IIP patients received anti-ILD treatment. There were more LC-ILD patients in the 2018-2021 group than in the 2014-2017 group (5.16% vs. 2.03%, p < 0.001). The underlying causes of ILD were significantly different between the 2018-2021 group and the 2014-2017 group (p < 0.001). After adjusting for the number of hospitalized patients having the same LC pathological pattern, SCLC was determined to be the most likely to be concomitant with ILD, followed by SCC. Most LC-ILD patients were scheduled for anti-LC therapy; however, treatments for concomitant IIP were usually ignored. LC treatment-associated ILD should receive more attention than before.

Current medical education improves OSA-related knowledge but not confidence in residents: An underappreciated public health risk.

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder and induces a growing health care burden. However, a large proportion of patients with OSA do not receive appropriate treatment and are underdiagnosed or misdiagnosed in primary care. A contributing factor to the phenomenon is the lack of education, which reflects the current inadequacies in medical education. Therefore, assessing the level of knowledge and attitudes toward OSA and associated factors among resident physicians is highly warranted. Methods: A validated questionnaire, the OSA Knowledge and Attitudes (OSAKA) questionnaire was distributed to residents who had already completed undergraduate education and were attending an internal medicine residency training program. The questionnaire consists of 2 parts: including an assessment of (1) OSA-related knowledge involving epidemiology, pathophysiology, clinical manifestations, diagnosis, and treatment; (2) the importance of OSA and confidence in diagnosing and treating OSA patients. Other information including demographics, training experience, and questions exploring the future form of the sleep breathing disorder course was collected together. Results: Of the 160 residents who participated in the survey, 153 (95.6%) completed the survey and the mean total knowledge score was 12.6/18 (70% correct). Although all respondents believed that OSA was an important clinical disorder, only a minority of the residents felt confident in identifying patients at risk for OSA (38%), managing OSA patients (27.5%), or continuous positive airway pressure therapy (CPAP) (26.2%). We found that OSA training experience significantly increased knowledge scores (p = 0.002) but not confidence scores (p = 0.248). As for the specific form of medical education, "Small classes during residency training" was the most popular form of sleep-breathing disorder educational training in the future of the resident training program. Conclusion: Despite adequate knowledge of OSA, there was still a generalized lack of confidence in the management of OSA patients among residents. Current medical education can not build enough confidence for physicians, which may in turn affect patients' trust and reduce long-term compliance. Untreated OSA places a significant health threat and economic burden on not only the patients but also their families and society, causing an underappreciated public health risk. In the future, merely increasing OSA courses is not sufficient, a more specific focus on the course format and training effect is required.

Prognostic Analysis of Pneumocystis Jirovecii Pneumonia in Interstitial Lung Disease Patients: A Retrospective Clinical Study.

(1) Background: The clinical characteristics and the prognostic factors of HIV-negative Pneumocystis jirovecii pneumonia (PJP) patients (non-HIV-PJP) with interstitial lung disease (ILD) remain unclear. Our objectives were to describe the clinical characteristics and to explore the prognostic factors of non-HIV-ILD-PJP patients. (2) Methods: The enrolled patients in this retrospective study were stratified based on the presence or absence of ILD and fibrotic ILD (FILD). The log-rank test and Cox regression models were used to analyze the prognostic factors. (3) Results: Among 378 non-HIV-PJP patients, there were 133 patients with ILD-PJP, and 70 patients were classified as having FILD-PJP. The all-cause mortality rate for the ILD-PJP group is higher than that of the ILD-PJP group (57.9% vs. 38.4%, p < 0.001). However, the all-cause mortality is similar between the FILD-PJP group and non-FILD-PJP group. Preexisting ILD (HR: 2.156, p = 0.003) and honeycomb appearance on the chest HRCT (HR = 16.3, p < 0.001) are independent survival risk factors for ILD-PJP. Non-invasive ventilation is an independent survival risk factor for ILD-PJP patients (HR = 928.56, p < 0.01) and FILD-PJP patients (HR = 33.86, p < 0.001). (4) Conclusions: Pre-existing ILD and honeycomb appearance on the chest HRCT are independent survival risk factors for PJP patients. Non-invasive ventilation is associated with poor survival for both ILD-PJP and FILD-PJP patients.

Tacrolimus ameliorates bleomycin-induced pulmonary fibrosis by inhibiting M2 macrophage polarization via JAK2/STAT3 signaling.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease of unknown cause and characterized by excessive proliferation of fibroblasts and the irregular remodeling of extracellular matrix (ECM), which ultimately cause the severe distortion of the alveolar architecture. The median survival of IPF patients is 2-5 years. IPF patients are predominantly infiltrated by M2 macrophages during the course of disease development and progression. Predominantly accumulation of M2 macrophages accelerates fibrosis progression by secreting multiple cytokines that promote fibroblast to myofibroblast transition. In the process of M2 macrophage polarization, JAK2/STAT3 signaling plays a key role, thus, targeting activated macrophages to inhibit the pro-fibrotic phenotype is considered as an approach to the potential treatment of IPF. Tacrolimus is a macrolide antibiotic that as a specific inhibitor of T-lymphocyte function and has been used widely as an immunosuppressant in human organ transplantation. In this study we explored the potential effect and mechanism of tacrolimus on pulmonary fibrosis in vivo and vitro. Here, we found that tacrolimus is capable of suppressing M2 macrophages polarization by inhibiting pro-fibrotic factors secreted by M2 macrophages. This effect further alleviates M2-induced myofibroblast activation, thus resulting in a decline of collagen deposition, pro-fibrotic cytokines secretion, recovering of lung function, ultimately relieving the progression of fibrosis in vivo. Mechanistically, we found that tacrolimus can inhibit the activation of JAK2/STAT3 signaling by targeting JAK2. Our findings indicate a potential anti-fibrotic effect of tacrolimus by regulating macrophage polarization and might be meaningful in clinical settings.

Risk factors for mortality of diffuse alveolar hemorrhage in systemic lupus erythematosus: a systematic review and meta-analysis.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). The current knowledge of the prognostic factors for SLE-associated DAH is controversial. This meta-analysis was undertaken to investigate the relevant risk factors for mortality in SLE-associated DAH. METHODS: Studies were searched from PubMed, EMBASE, and Web of Science databases published up to May 27, 2020, and were selected or removed according to the inclusion and exclusion criteria. Two reviewers extracted data independently from the enrolled studies, and the odds ratios (OR) or the standardized mean difference (SMD) was utilized to identify and describe the prognostic factors for mortality. RESULTS: Eight studies encompassing 251 patients with SLE-associated DAH were included in the meta-analysis. No significant publication bias was shown. Age at the diagnosis of DAH (SMD = 0.35, 95% confidence interval (CI) (0.08, 0.61), P = 0.01, I2 = 0.0%) was found to be an independent risk factor of mortality. Longer lupus disease duration (SMD = 0.28, 95% CI (0.01, 0.55), P = 0.042, I2 = 0.0%), concurrent infection (OR = 2.77, 95% CI (1.55, 4.95), P = 0.001, I2 = 37.5%), plasmapheresis treatment (OR = 1.96, 95% CI (1.04, 3.70), P = 0.038, I2 = 14.6%), and mechanical ventilation (OR = 6.11, 95% CI (3.27, 11.39), P < 0.0001, I2 = 23.3%) were also related to poor survival, whereas no noticeable relationships were revealed between survival and concurrent lupus nephritis (OR = 5.45, 95% CI (0.52, 56.95), P = 0.16, I2 = 58.4%) or treatment of cyclophosphamide (CTX) (OR = 0.74, 95% CI (0.16, 3.41), P = 0.70, I2 = 75.5%). CONCLUSIONS: Older age at the diagnosis of DAH, longer disease duration of SLE, concurrent infection, plasmapheresis treatment, and mechanical ventilation were found related to increased mortality in patients with SLE-associated DAH according to our meta-analysis. However, due to limited studies with heterogeneity, these results should be interpreted cautiously. Notably, severe diseases rendered the requirement of plasmapheresis treatment and mechanical ventilation are themselves associated with poor outcome. Randomized trials of therapeutics are needed to determine the most efficacious strategies for SLE-associated DAH for better management of this life-threatening complication.

Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACPA-Positive ILD: a Longitudinal Cohort of 282 Cases.

The aim of this study is to investigate the clinical features and outcome of interstitial lung disease (ILD)-onset rheumatoid arthritis (RA) and anti-citrullinated protein antibody (ACPA)-positive ILD-only patients. Arthritis-onset and ILD-onset RA-ILD and ACPA-positive ILD-only patients consecutively admitted to Peking Union Medical College Hospital from January 2008 to December 2017 were enrolled and followed-up. Their demographic, clinical, and laboratory features as well as outcome were collected and analyzed. Compared with arthritis-onset RA-ILD (n = 166, median arthritis-to-ILD interval: 60 months), the ILD-onset RA-ILD (n = 75, median ILD-to-arthritis interval: 2 months) had less rheumatoid nodules and higher titer of ACPA, and manifested more stable ILD (median estimated progression-free survival: 120 vs. 100 months, p = 0.019). Elder age (≥ 65 years) at ILD diagnosis and UIP pattern were associated with ILD progression by both univariate and Cox hazards modeling analysis (p < 0.05). In ACPA-positive ILD-only patients (n = 41), arthritis developed in 7 (17.1%) female patients after a median interval of 24 months. ACPA-positive ILD who subsequently developed arthritis exhibited higher frequency of rheumatoid factor (RF), higher titer of ACPA, and higher levels of ESR and CRP (p < 0.05). Multivariate regression analysis showed that positive RF (OR 12.55, 95% CI 1.31 to 120.48) was the independent risk factor for arthritis development in ACPA-positive ILD-only patients. ILD-onset RA-ILD had more stable ILD compared with arthritis-onset RA-ILD. ACPA-positive ILD patients with positive RF are at increased risk of developing RA.