Pamrevlumab for Idiopathic Pulmonary Fibrosis: The ZEPHYRUS-1 Randomized Clinical Trial.

Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.

Cushing's disease with pulmonary Cryptococcus neoformans infection in a single center in Beijing, China: A retrospective study and literature review.

BACKGROUND: Patients with Cushing's disease (CD) with hypercortisolism have an increased risk of opportunistic infection. However, most CD patients exposed to infections are diagnostic latency, leading to a poor prognosis. METHODS: Six patients in our hospital and an additional six patients in the literature were included in this study. Clinical information of CD patients with pulmonary Cryptococcus neoformans are reviewed. RESULTS: The average baseline total cortisol and ACTH in serum at 8 am of all the patients was 44.85 µg/dL (normal range 4.0-22.3 µg/dL) and 200.3 pg/mL (normal range 0-46 pg/mL), respectively. Lymphopenia was found in 2 out of 6 patients in our hospital. The pulmonary radiologic findings included nodules (4/12), masses with or without a cavity (5/12), infiltration (5/12), and consolidation (4/12). The diagnosis of C.neoformans was established by lung pathology results (7/12), microorganism culture (3/12), and serum cryptococcal polysaccharide antigen (4/12). Lung lobectomy was performed in two patients who had a nodule in one lung lobe. Antifungal drugs were administered, including amphotericin-B (7/12), fluconazole (4/12), flucytosine (2/12) and liposomal amphotericin (1/12). Additional therapies for CD included trans-sphenoidal pituitary adenoma surgery (9/12), adrenalectomy (1/12) and ketoconazole (2/12). Seven patients survived, and five patients died. CONCLUSION: Pulmonary C.neoformans is an uncommon but fatal opportunistic infection in CD patients. Pulmonary nodules or masses should be aggressively investigated to exclude the C.neoformans among CD patients. The infiltration lesions in chest CT scan and lymphopenia are associated with poor prognosis.

Impact of smoking on health-related quality of Life after percutaneous coronary intervention treated with drug-eluting stents: a longitudinal observational study.

BACKGROUND: Smoking has been shown to reduce health-related quality of life (HRQOL) in patients with coronary artery disease (CAD) undergoing percutanous coronary intervention (PCI) either by means of balloon angioplasty or with the use of bare-metal stents (BMS). Drug-eluting stents (DES) have now been widely used and are related to substantial reduction of restenosis and significantly improved HRQOL compared with BMS. This study aimed to evaluate the effects of smoking on HRQOL in patients after PCI in DES era. METHODS: A cohort of 649 patients admitted for CAD and treated with drug-eluting stents were included in this prospective, observational study. Patients were classified as non-smokers (n = 351, 54.1%), quitters (n = 126, 19,4%), or persistent smokers (n = 172, 26.5%) according to their smoking status at the time they first admitted to hospital and during the first year of follow-up. Each patient was prospectively interviewed at baseline, 6 months and 1 year following PCI. HRQOL was assessed with the use of Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). RESULTS: For the overall population, HRQOL scores at 1-year follow-up were significantly higher than baseline for all 8 domains. At 1-year follow-up, the HRQOL scores in persistent smokers were still lower than that in non-smokers in 6 domains except for bodily pain and mental health, and than that in quitters in 5 domains except for bodily pain, role emotional and mental health. There were no significant differences with regard to the scores between non-smokers and quitters except role emotional for which non-smokers had higher scores. After adjustment, persistent smokers demonstrated significantly less improvements in HRQOL than non-smokers in 6 domains except for bodily pain and social functioning and significantly less improvement than quitters for general health. Improvements of quitters were comparable to that of non-smokers in all domains. Multivariate linear regression analyses showed persistent smoking was an independent risk factor for PCS and MCS improvements. CONCLUSIONS: Persistent smoking substantially diminishes the potential quality-of-life benefits of DES. Efforts should be made to promote smoking cessation after DES implantation which could greatly improve the health quality outcomes.

Model design for screening effective Antihyperlipidemic drugs using zebrafish system.

The purpose of this paper was to explore a new method for screening lipid-lowering drugs in zebrafish models. The suitable drug concentrations of atorvastatin (ATV), fenofibrate (FEF) and ezetimibe (EZE) were first determined. Then, the serum cholesterol and triglyceride levels were detected in high-fat diet (HFD)-fed zebrafish. The HFD zebrafish models were constructed and the effects of drugs on them were observed by Oil red O staining and fluorescence labeling. Statistical analyses among groups were conducted using SPSS software. The lowest drug concentration (LDC) and the highest (HDC) of ATV, FEF and EZE were 0.3 µM/37.0µM, 1.2µM/3.5µM, and 6.3 µM/26.4µM, respectively, while, the intermediate (IDC) was, in order, 18.5µM, 1.8µM, 13.2µM. The cholesterol and triglyceride levels in HFD-fed zebrafish were increased after 7 weeks fat feeding (p<0.05). Moreover, the levels of triglyceride were significantly decreased after LDC of ATV and FEF treated (p<0.05), but not that of EZE. While, the cholesterol levels were reduced in three groups (p<0.05). Moreover, the 5 dpf high-fat zebrafish model was established successfully and maintained stably for 24h. ATV produced effects in a concentration-dependent manner, while only IDC and HDC of FEF and EZE made effects on this model. Intravascular cholesterol levels were significantly increased after HCD treatment and decreased after drug treated. The high-fat zebrafish model induced by HFD-fed was available and successful, besides, the Oil red O staining may be an available and rapid method for screening lipid-lowering drugs.

Idiopathic pulmonary fibrosis in BRIC countries: the cases of Brazil, Russia, India, and China.

Idiopathic pulmonary fibrosis (IPF), the prototype of interstitial lung diseases, has the worst prognosis and is the only interstitial lung disease for which approved pharmacological treatments are available. Despite being considered a rare disease, IPF patients pose major challenges to both physicians and healthcare systems. It is estimated that a large number of IPF patients reside in BRIC countries (Brazil, Russia, India, and China) given their overall total population of approximately 3 billion inhabitants. Nevertheless, the limited availability of chest imaging in BRIC countries is considered a chief obstacle to diagnosis, since high-resolution computed tomography of the chest is the key diagnostic test for IPF. Further, obtaining reliable lung function tests and providing treatment access is difficult in the more rural areas of these countries. However, IPF might represent an opportunity for BRIC countries: the exponentially increasing demand for the enrollment of IPF patients in clinical trials of new drugs is predicted to face a shortage of patients - BRIC countries may thus play a crucial role in advancing towards a cure for IPF.

Clinical spectrum of intrathoracic Castleman disease: a retrospective analysis of 48 cases in a single Chinese hospital.

BACKGROUND: Thorax is the common place to develop Castleman disease (CD), but there is no systemic clinical analysis for intrathoracic CD. METHODS: We conducted a retrospective analysis of 48 intrathoracic CD patients with definite pathological diagnosis who were hospitalized between 1992 and 2012 in a Chinese tertiary referral hospital. RESULTS: The study included 16 cases with unicentric CD (UCD) and 32 cases with multicentric CD (MCD). UCD were younger than MCD (30.5y vs 41.6ys, P < 0.05). MCD were more symptomatic (50% vs 96.9%, P < 0.001) and sicker than UCD, including more fever, hepatomegaly and/or splenomegaly and hypoalbuminemia. All of UCD showed solitary mass in various sites and two of them were complicated by small pleural effusion. In the MCD group, their chest CT showed obvious lymphadenopathy in the hilum and/or mediastinum (100%), diffuse parenchymal lung shadows (43.75%), pleural effusion (40.6%), mass in the mediastinum (6.25%) or hilum (3.12%) and bronchiolitis obliterans (BO) (3.12%). Besides LIP-like images, multiple nodules of different size and sites, patchy, ground-glass opacities and consolidation were showed in their chest CT. Surgery were arranged for all UCD for diagnosis and treatment and all were alive. In MCD group, superficial lymph nodes biopsies (21 cases), surgery biopsy (9 cases) and CT-guided percutaneous lung biopsy (2 cases) were performed. Hyaline vascular (HV) variant were more common in the UCD group (75% vs 37.5%, P < 0.05). In MCD group, 28 cases were prescribed with chemotherapy, one refused to receive therapy and the rest three were arranged for regular follow-up. Among MCD, 18 cases was improved, 7 cases was stable, 4 cases lost follow-up and 3 cases died. CONCLUSIONS: Intrathoracic MCD was more common than UCD in our hospital. MCD was older, more symptomic and sicker than UCD. HV variant were more common in UCD. All of UCD showed mass in various intrathoracic locations and surgery resection was performed for all and all were alive. Mass, pleural effusion, BO and diffuse pulmonary shadows, including LIP-like images, multiple nodules of different size and sites, patchy, GGO and consolidations were showed in our MCD. Most of MCD cases were arranged with chemotherapy and their prognosis were worse than UCD's.

Whole lung lavage combined with Granulocyte-macrophage colony stimulating factor inhalation for an adult case of refractory pulmonary alveolar proteinosis.

BACKGROUND: Whole-lung lavage (WLL) is classically the first-line treatment for symptomatic pulmonary alveolar proteinosis (PAP). However, some patients require multiple WLLs because of refractory nature of their PAP. In this instance, these patients may benefit from new treatment regimens, and new therapies should be tried for these patients. CASE PRESENTATION: We describe a 47-year-old Chinese woman who was confidently diagnosed with pulmonary alveolar proteinosis (PAP) after bronchoalveolar lavage and transbronchial lung biopsy. The patient received four sessions of bilateral whole lung lavage (WLL) and one session of WLL in combination with plasmapheresis, each only producing short-term symptomatic relief. The patient was given a trial of combination therapy, which consisted of WLL and Granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation. The patient showed a gradual improvement in oxygenation and her daily activity, as well as a dramatic improvement in her pulmonary CT examination. CONCLUSION: Bilateral WLL, in combination with GM-CSF inhalation, may be an effective treatment option for severe refractory PAP.

A retrospective study of microscopic polyangiitis patients presenting with pulmonary fibrosis in China.

BACKGROUND: Pulmonary involvement is a common feature of MPA. Although alveolar hemorrhage is the most common pulmonary manifestation of MPA, a few recent studies have described instances of MPA patients with pulmonary fibrosis. Pulmonary fibrosis was seen to predate, be concomitant with, or occur after the diagnosis of MPA. The goal of this study was to describe the clinical features and prognosis of microscopic polyangiitis (MPA) patients whose initial respiratory presentation was pulmonary fibrosis. METHODS: We conducted a retrospective analysis of 19 MPA patients who presented with pulmonary fibrosis at Peking Union Medical College Hospital between 1990 and 2012. RESULTS: Of 67 total MPA cases, 19 patients presented with pulmonary fibrosis. There were 8 males and 11 females, with a median age of 63.6 years. Common clinical manifestations included fever (89.5%), cough (84.2%), dyspnea (78.9%) and velcro rales (84.2%). Eleven patients experienced weight loss, several had kidney involvement, and most had an increased erythrocyte sedimentation rate and C-reactive protein. All were positive for myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA), with 6 patients being positive at the time of their initial diagnosis of pulmonary fibrosis. Every patient had typical features of usual interstitial pneumonia on High-resolution CT. All were treated with corticosteroids and cyclophosphamide, which lead to an improvement in twelve cases. One of the remaining patients progressed slowly, whereas six died. CONCLUSIONS: Patients with MPA, who also presented with pulmonary fibrosis in our cohort, were more likely to be older, female, and have extrapulmonic involvement. Most patients had a delayed positive ANCA. Corticosteroids plus cyclophosphamide was the remission-induction treatment scheme for all cases. The current prognosis for MPA patients with pulmonary fibrosis appears to be poor, suggesting that they may be candidates for new therapies.

[Therapeutic effects and the underlying mechanism of umbilical cord-derived mesenchymal stem cells for bleomycin induced lung injury in rats].

OBJECTIVE: To study the efficacy of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for bleomycin-induced pulmonary fibrosis in mice. METHODS: UC-MSCs were isolated from the umbilical cord after parental consent. One hundred C57BL/6 mice were randomly divided into 4 groups (12 of these for preliminary experiment). Mice in the control group (n = 20) were instilled with PBS via trachea and NS was injected via the tail vein after 3 days. Mice in the stem cell group (n = 20) were instilled with PBS via trachea and were injected with MSC via the tail vein after 3 days. Mice in the bleomycin group (n = 24) were instilled with bleomycin via trachea and NS was injected via the tail vein after 3 days. Mice in the bleomycin plus stem cell group (n = 24) were instilled with bleomycin via trachea and were injected with MSCs via the tail vein after 3 days. All of the mice were sacrificed at the 21(th) day, and the lungs were immediately fixed with 4% paraformaldehyde for 48 h, embedded in paraffin and sectioned at 5 µmol/L thickness. The sections were stained with hematoxylin and eosin (H&E) and Masson-trichrome. Histopathological scoring of pulmonary fibrosis was performed according to Ashcroft's method. The concentrations of matrix metalloproteinases-2 and tissue inhibitor of metalloproteinase-1were determined using immunohistochemistry. RESULTS: Compared with the bleomycin group, MSC transplantation significantly reduced pulmonary inflammation, fibrosis and deposition of collagen in the bleomycin plus stem cell group [(1.55 ± 0.51) vs (2.16 ± 0.77), and (1.45 ± 0.60) vs (2.32 ± 0.82), respectively, P < 0.05]. There was no difference between the control group and the stem cell group [(0.35 ± 0.49) vs (0.37 ± 0.50), P > 0.05]. The expression of MMP-2 in the bleomycin plus stem cell group was lower than the bleomycin group [(1.59 ± 0.59) vs (2.37 ± 0.68), P < 0.05], but there was no difference between the control group and the stem cell group [(0.80 ± 0.69) vs (0.84 ± 0.77), P > 0.05]. The expression of TIMP-1 in the bleomycin plus stem cell group was higher than the bleomycin group [(1.95 ± 0.58) vs (0.79 ± 0.71), P < 0.05], but there was no difference between the control group and the stem cell group [(1.10 ± 0.72) vs (1.32 ± 0.58), P > 0.05]. CONCLUSION: UC-MSC transplantation could relieve bleomycin-induced fibrosing alveolitis in mice. The mechanism might be related to the expression of MMP-2 and TIMP-1. UC-MSC had no effect on normal lungs.

[The phenotype of Th17 cells in sarcoidosis and its correlation with glucocorticoid therapy].

OBJECTIVE: To describe the characteristic of Th17 cells in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) from patients with sarcoidosis, and to investigate the effect of glucocorticoid therapy on the expression of RORγt mRNA, and therefore to explore the role of Th17 cells in the immunopathogenesis of pulmonary sarcoidosis. METHODS: Ten patients with active pulmonary sarcoidosis who were prescribed with prednisone according to the guidelines were defined as the study group. All of them had positive pathological results and had definite response to corticosteroids. Ten healthy controls were recruited from volunteers with similar sex distribution and age. The proportion of CD(4)(+)IL-17A(+)T cells in peripheral blood mononuclear cells (PBMC) and BALF were calculated by flow cytometry. The mRNA expression of RORc in PBMC was measured by Real-time PCR. RESULTS: The mean age was (52 ± 8) years in both the study group and the controls, and there were 9 females and 1 male in both groups. The proportion of CD(4)(+)IL-17A(+)T cells was higher in the PB of sarcoidosis patients compared to that of the controls [(1.61 ± 1.09)% vs (0.51 ± 0.43)%, t = 3.02, P = 0.014]. For the same patients, the proportion of CD(4)(+)IL-17A(+)T cells was higher in the BALF compared to that in the PB [(3.05 ± 1.87)% vs (1.61 ± 1.09)%, t = 2.94, P = 0.001]. After 4 to 6 week therapy with glucocorticoids, all the 10 patients showed definite response. The level of RORc mRNA in the PB did not decrease significantly after treatment [(0.952 ± 0.367) vs (0.168 ± 0.272), t = 1.76, P = 0.057], although a trend was noted. CONCLUSIONS: Th17 cells was probably involved in the immunopathogenesis of sarcoidosis, and glucocorticoids might modulate the disturbance of Th17 cells in pulmonary sarcoidosis.

[The clinicopathological analysis of 4 cases of IgG4-related nonspecific interstitial pneumonia].

OBJECTIVES: To observe the immunohistochemical staining of IgG4 in nonspecific interstitial pneumonia (NSIP) and to study the clinicopathological features of IgG4-related NSIP. METHODS: Retrospective analysis was carried out for 32 patients with NSIP who had been admitted into Peking Union Medical College Hospital from November 2002 to October 2010. The diagnosis of NSIP was established by surgical lung biopsy and all specimens were fixed in neutral formalin and embedded in paraffin. Sections were cut for HE and immunohistochemical stain. According to the diagnostic criteria for IgG4-related disease, 4 cases were confirmed to be IgG4-related NSIP. The clinicopathological features including clinical history, laboratory examination, and pathologic evaluation were studied. RESULTS: The 4 patients with IgG4-related NSIP included 1 man and 3 women, with a median age of 48 years (range, 44 - 56 years). The presenting symptoms were dry cough or shortness of breath. One patient (1/4, 25.0%) was found to have a positive autoantibody but no cases showed positive RF in serum. The histological finding of the 4 cases was characterized by inflammatory cell infiltration in interstitium with fibrosis, and 1 case showed obliterative arteritis. The numbers of IgG4-positive plasma cells in the 4 cases were 42/hpf, 22/hpf, 11/hpf, and 33/hpf respectively, while the percentages of IgG4-positive to IgG-positive plasma cells were 70%, 71%, 57%, 43% respectively. CONCLUSIONS: IgG4-related interstitial pulmonary disease can be characterized as the NSIP pattern. The pathological features of IgG4-related NSIP include infiltration of lympho-plasmacytes and eosinophils in interstitium with fibrosis, and lymphoid follicles are frequently identified in the area of lymphocyte aggregation, but obliterative arteritis is infrequently identified in the lesion. Immunohistochemical staining of IgG and IgG4 is very helpful for a definite diagnosis of IgG4-related disease.

Diagnostic value of elevated serum carbohydrate antigen 125 level in sarcoidosis.

BACKGROUND: Sarcoidosis is a multisystem disorder with unknown etiology, and it predominantly affects the lungs and intrathoracic lymph nodes. For patients with atypical clinical manifestations, the diagnosis of sarcoidosis is difficult and specific biomarkers may play an important role in assisting diagnosis. Previous research has demonstrated a correlation between sarcoidosis and increased carbohydrate antigen 125 (CA125), but remains a lack of large cohort studies to validate this observation. AIM: To compare serum CA125 levels in sarcoidosis patients and healthy controls, and explore whether CA125 can be used as a biomarker for the diagnosis of sarcoidosis. METHODS: In this study, the serum CA125 levels were measured by enzyme-linked immunosorbent assay in 108 consecutive sarcoidosis patients between June 2016 and December 2020 (31 males, 77 females; age at diagnosis 49.69 ± 9.10 years) and 112 healthy subjects. Data on the C-reactive protein, erythrocyte sedimentation rate, and angiotensin-converting enzyme were also collected. The association of serum CA125 levels with clinical, radiological, and respiratory functional characteristics was analyzed between patient groups with CA125 ≤ 35 U/mL or CA125 > 35 U/mL. RESULTS: We found that serum CA125 levels were higher in sarcoidosis patients compared to healthy controls (median: 44.78 vs 19.11 U/mL, P < 0.001). The area under the receiver operator characteristic was 0.9833 (95%CI: 0.9717-0.9949), and the best cutoff point was 32.33 U/mL. The elevated serum CA125 was notably associated with the percentage of predicted forced vital capacity (FVC%) and neutrophil-to-lymphocyte ratio (P = 0.043 and P = 0.038, respectively) in sarcoidosis patients. Multivariate analysis revealed that FVC% was a statistically notable predictor of elevated serum CA125 (P = 0.029). Also, our research revealed that compared to patients with Stage I of radiology classification, patients with Stage II and III showed a higher concentration of serum CA125 (46.16 ± 8.32 vs 41.00 ± 6.04 U/mL, P = 0.005, and 47.92 ± 10.10 vs 41.00 ± 6.04 U/mL, P = 0.002, respectively). CONCLUSION: Serum CA125 was highly increased in sarcoidosis patients and showed high efficiency for noninvasive diagnosis of the disease. In addition, abnormally elevated serum CA125 was correlated with pulmonary function and radiological Scadding's classification of sarcoidosis.

[A clinical analysis of 9 cases of pulmonary alveolar proteinosis with secondary infection].

OBJECTIVE: To describe the clinical characteristics of 9 cases of idiopathic pulmonary alveolar proteinosis (iPAP) with secondary infections. METHOD: The clinical and radiological data of 9 patients with iPAP and secondary infections admitted into Peking Union Medical College Hospital from 1st January 1990 to 1st January 2010 were retrospectively analyzed. RESULTS: In that period, there were 97 patients of iPAP were admitted in our hospital. There were 9 patients of iPAP with secondary infections, aged (46.4 ± 14.6) y. There were 5 males and 4 females. Among them, 6 patients were misdiagnosed as interstitial pneumonia and corticosteroids were given to them. When the infection appeared, corticosteroids were still given to 3 patients, and the other 3 patients had stopped corticosteroids for 3 to 15 and a half months. Five patients had accepted mono-lung or whole lung lavage before 1, 2, 9, 14, 24 months. The clinical manifestations were fever (8 cases), cough (9 cases), expectoration (8 cases), hemoptysis (2 cases), chest pain (1 case) and moist rales (1 case). Glass-ground opacities (9 cases) and cavitations (4 case) were the main manifestations of chest radiology. Pleural effusions (1 case) was not common. The locations of infection was limited in chest: 9 cases had pulmonary infection and one case was associated with pleurisy. The infectious pathogens were the acid-fast tubercle bacillus (4 cases), fungus (3 cases, candida albicans, penicillium and aspergillus fumigatus for each one) and nocardia (2 cases, one case was associated with cytomegalovirus infection). FOLLOW-UP: 6 patients were cured, 1 patient was improved and 2 patients were died. CONCLUSIONS: For patients with iPAP, especially when they had been receiving corticosteroids, if they had fever and/or recently exaggerated dyspnea, especially whose chest radiology showed nodules and cavitations, the clinicians should be aware of infections diseases for them. Further specific microbiological studies and sufficient therapy should be obtained as quickly as possible.

[Retrospective analysis of the prognosis factors in patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the prognostic implications of clinical and physiological variables, and the cellular classification of bronchoalveolar lavage fluid (BALF) in patients with idiopathic pulmonary fibrosis (IPF). The effect of treatment with glucocorticoids with or without cytotoxic drugs was also evaluated. METHODS: The significances of clinical, arterial blood gas analysis, pulmonary function test, lung high-resolution computed tomography, echocardiography and BALF in the prognosis of patients with IPF were assessed in 65 patients with IPF at diagnosis. Univariate Cox proportional-hazards regression analysis was used to evaluate the various parameters associated with hazard ratio. The survival rates of all groups were compared using the Kaplan-Meier method. RESULTS: In 38 months of average follow-up time, the survival rate of the patients was 43.1%, and the median survival time was 39 months after diagnosis. Univariate Cox proportional-hazards regression analysis showed that body mass index, clubbing fingers, ESR, PaO(2)/FiO(2), SaO(2), TLC%, D(L)CO%, pulmonary arterial pressure and the percent of neutrophil in BALF were factors that affected the prognosis of the patients with IPF (HR 0.842 - 1.945, Wald 3.782 - 12.963, P < 0.05). In the meanwhile, the patients were divided into 2 groups by the median of significant variables in univariate Cox proportional-hazards regression analysis (the cut off point value), and the survival rate group comparison showed statistically significant difference in body mass index, clubbing fingers, ESR, TLC% as well as D(L)CO% (Log-rank 3.907 - 10.452, P < 0.05), while glucocorticoids with or without cytotoxic drugs for patients with IPF did not change the prognosis (Log-rank 2.405, P > 0.05). CONCLUSIONS: Body mass index, clubbing fingers, ESR, PaO(2)/FiO(2), TLC%, and D(L)CO% maybe the factors affecting the prognosis of patients with IPF, while glucocorticoids with or without cytotoxic drugs did not change the course of IPF.

Incident Heart Failure in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention.

Background: The contemporary incidence of heart failure (HF) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This prospective cohort study was designed to study the incidence and predictors of new-onset HF in CAD patients after PCI (ChiCTR1900023033). Methods: From January 2014 to December 2018, 3,910 CAD patients without HF history undergoing PCI were prospectively enrolled. Demographics, medical history, cardiovascular risk factors, cardiac parameters, and medication data were collected at baseline. Multivariable adjusted competing-risk regression analysis was performed to examine the predictors of incident HF. Results: After a median follow-up of 63 months, 497 patients (12.7%) reached the primary endpoint of new-onset HF, of which 179, 110, and 208 patients (36.0, 22.1, and 41.9%) were diagnosed as having HF with reduced ejection fraction (EF) (HFrEF), HF with mid-range EF (HFmrEF), and HF with preserved EF (HFpEF), respectively. Higher B-type natriuretic peptide (BNP) or E/e' level, lower estimated glomerular filtration rate (eGFR) level, and atrial fibrillation were the independent risk factors of new-onset HF. Gender (male) and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (ACEI/ARB) prescription were the negative predictors of new-onset HF. Moreover, it was indicated that long-term ACEI/ARB therapy, instead of beta-blocker use, was linked to lower risks of development of all three HF subtypes (HFrEF, HFmrEF and HFpEF). Conclusions: This prospective longitudinal cohort study shows that the predominant subtype of HF after PCI is HFpEF and ACEI/ARB therapy is accompanied with reduced risks of incident HF across three subtypes.

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.

[Clinical analysis of 26 cases of nocardiosis].

OBJECTIVE: To describe the clinical characteristics of nocardiosis. METHOD: The clinical and radiological data of 26 patients with nocardiosis admitted into Peking Union Medical College Hospital from 1st January 1990 to 1st January 2010 were retrospectively analyzed. All of the patients had our microbiology laboratory identified nocardia species in one or more clinical specimens. RESULTS: Nocardiosis was diagnosed in 10 men, aged from 29 to 80 years, mean (52 ± 14) years, and in 16 women, aged from 15 to 71 years, mean (42 ± 17) years. No cases were identified in children. Six patients had no significant underlying conditions, while the other patients had at least one underlying condition, including autoimmune diseases (n = 6), chronic lung disease (n = 6), neoplastic disease (n = 2), chronic renal disease (n = 3), diabetes mellitus (n = 1), chest crush injuries (n = 1) and Cushing's syndrome (n = 1). Eleven cases had been receiving corticosteroids. The most common manifestations were moderate to high fever (n = 25), cough (n = 22), expectoration (n = 19), pleuritic chest pain (n = 10), hemoptysis (n = 8) and moist rales (n = 10). Some of them had subcutaneous (n = 5) and brain abscess (n = 4). Blood tests showed elevated ESR in 14 cases and decreased albumin levels in 14 cases. Patchy infiltrates or consolidation (n = 21) and cavitations (n = 10) were the main manifestations of chest radiology. Pleural effusions (n = 13) were common complicated manifestations. Thoracic lesions were always bilateral (n = 15). Only 4 patients were diagnosed by sputum culture. The other patients were diagnosed by culture of specimens obtained invasively: 8 positive pleural effusions, 2 positive bronchioalveolar lavage culture, 1 positive bronchial washings, 4 positive abscesses, 7 positive lung tissues, and 1 positive brain abscess. Nocardia brasiliensis (n = 9) and Nocardia asteroids (n = 6) were the main species. There was one case with Nocardia otitisdiscaviarium infection and the other cases with Nocardia undifferentiated. Result of antimicrobial susceptibility was unavailable in 10 cases. Among the other 16 results, 7 strains of nocardia were resistant to trimethoprim sulfamethoxazole (TMP(CO)). Six cases were treated with a single drug, 5 cases with trimethoprim-sulfamethoxazole and 1 with minocycline. The other patients were given combination treatment, including trimethoprim-sulfamethoxazole, amikacin, cefuroxime, ceftriaxone, amoxicillin-clavulanic acid, streptomycin, evofloxacin, ciprofloxacin, minocycline and imipenem. Four patients died, 2 patients relapsed and the other 20 cases cured. CONCLUSIONS: For immunosuppressed patients, nocardia infections should be considered when they had moderate to high fever and respiratory manifestations, especially accompanied with subcutaneous and/or brain abscess, and the chest radiology showed patchy infiltrates and/or consolidations. Further specific microbiological studies and sufficient therapy should be obtained as quickly as possible.

Balloon Deflation Strategy during Primary Percutaneous Coronary Intervention in Acute ST-Segment Elevation Myocardial Infarction: A Randomized Controlled Clinical Trial and Numerical Simulation-Based Analysis.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the best available reperfusion strategy in patients with acute ST-segment elevation myocardial infarction (STEMI). However, PCI is associated with a serious problem known as no-reflow phenomenon, resulting in poor clinical and functional outcomes. This study aimed to compare the influences of different balloon deflation velocity on coronary flow and cardiovascular events during primary PCI in STEM as well as transient hemodynamic changes in in vitro experiments. Method and Results. 211 STEMI patients were randomly assigned to either a rapid or a slow balloon deflation group during stent deployment. The primary end point was coronary flow at the end of PCI procedure, and secondary end points included myocardial infarct size. Transient hemodynamic changes were evaluated through an in vitro experimental apparatus and a computer model. In clinical practice, the level of corrected TIMI frame count (cTFC) in slow balloon deflation after primary PCI was significantly lower than that of rapid balloon deflation, which was associated with smaller infarct size. Numerical simulations revealed that the rapid deflation led to a sharp acceleration of flow in the balloon-vessel gap and a concomitant abnormal rise in wall shear stress (WSS). CONCLUSION: This randomized study demonstrated that the slow balloon deflation during stent implantation improved coronary flow and reduced infarct size in reperfused STEMI. The change of flow in the balloon-vessel gap and WSS resulted from different balloon deflation velocity might be partly accounted for this results.

Clinical features and prognosis in 21 patients with extrinsic allergic alveolitis.

OBJECTIVE: To assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis (EAA). METHODS: Patients with EAA diagnosed at Peking Union Medical College Hospital from August 1983 to May 2007 were analyzed retrospectively. Their medical records were examined to gather clinical, laboratorial, radiological, and histopathological data. Patients were divided to three phases (acute, subacute, and chronic) according to clinical presentations. Follow-up data regarding treatment response, subsequent radiological and pulmonary function studies, and clinical outcomes were collected. RESULTS: A total of 21 cases were enrolled. Among them, 11 were subacute, 10 were chronic. The most common exposure was pet birds (6 cases, 28.6%). The primary abnormality of pulmonary function was restriction and/or reduction in diffusing capacity (12 cases, 63.2%). The most common findings on high-resolution computed tomography (HRCT) were ground-glass opacities (13 cases, 68.4%) and centrilobular nodules (8 cases, 42.1%). Airway obstruction in pulmonary function test, emphysema, lung cysts, and fibrosis on HRCT were more frequently seen in chronic than in subacute patients, though the differences were not statistically significant. Bronchoalveolar lavage fluid (BALF) showed lymphocytosis. The total cell count and the percentage of neutrophils were significantly higher in subacute than in chronic patients (P<0.05). Nonnecrotizing granulomas were seen in 8 (47.1%) cases. Improvement or normalization in symptoms, radiography, and pulmonary function test after treatment were seen in all 18 patients with available follow-up data. Five patients recurred. CONCLUSIONS: The characteristic abnormalities of pulmonary function, findings on HRCT, and pathology are essential for all phases of EAA, and the atypical manifestations such as obstruction and fibrosis can also be present frequently, particularly in chronic cases. Differential cell counts of BALF are related to the phase of the disease. The treatment response and prognosis of EAA are good.