Clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism: a multicenter study report.

BACKGROUND: Clinical characteristics of patients with pulmonary thromboembolism have been described in previous studies. Although very old patients with pulmonary thromboembolism are a special group based on comorbidities and age, they do not receive special attention. OBJECTIVE: This study aims to explore the clinical characteristics and mortality predictors among very old patients with pulmonary thromboembolism in a relatively large population. DESIGN AND PARTICIPANTS: The study included a total of 7438 patients from a national, multicenter, registry study, the China pUlmonary thromboembolism REgistry Study (CURES). Consecutive patients with acute pulmonary thromboembolism were enrolled and were divided into three groups. Comparisons were performed between these three groups in terms of clinical characteristics, comorbidities and in-hospital prognosis. Mortality predictors were analyzed in very old patients with pulmonary embolism. KEY RESULTS: In 7,438 patients with acute pulmonary thromboembolism, 609 patients aged equal to or greater than 80 years (male 354 (58.1%)). There were 2743 patients aged between 65 and 79 years (male 1313 (48%)) and 4095 patients aged younger than 65 years (male 2272 (55.5%)). Patients with advanced age had significantly more comorbidities and worse condition, however, some predisposing factors were more obvious in younger patients with pulmonary thromboembolism. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2, malignancy, anticoagulation as first therapy were mortality predictors for all-cause death in very old patients with pulmonary thromboembolism. The analysis found that younger patients were more likely to have chest pain, hemoptysis (the difference was statistically significant) and dyspnea triad. CONCLUSION: In very old population diagnosed with pulmonary thromboembolism, worse laboratory results, atypical symptoms and physical signs were common. Mortality was very high and comorbid conditions were their features compared to younger patients. PaO2 < 60 mmHg, eGFR < 60 mL/min/1.73m2 and malignancy were positive mortality predictors for all-cause death in very old patients with pulmonary thromboembolism while anticoagulation as first therapy was negative mortality predictors.

Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population: An integrated genomic and transcriptional analysis.

Objective: The clinical significance of homologous recombination deficiency (HRD) in breast cancer, ovarian cancer, and prostate cancer has been established, but the value of HRD in non-small cell lung cancer (NSCLC) has not been fully investigated. This study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical care. Methods: A total of 355 treatment-naïve NSCLC patients were retrospectively enrolled. HRD status was assessed using the AmoyDx Genomic Scar Score (GSS), with a score of ≥50 considered HRD-positive. Genomic, transcriptomic, tumor microenvironmental characteristics and prognosis between HRD-positive and HRD-negative patients were analyzed. Results: Of the patients, 25.1% (89/355) were HRD-positive. Compared to HRD-negative patients, HRD-positive patients had more somatic pathogenic homologous recombination repair (HRR) mutations, higher tumor mutation burden (TMB) (P<0.001), and fewer driver gene mutations (P<0.001). Furthermore, HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes, MET and MYC in epidermal growth factor receptor (EGFR)/anaplastic lymphoma kinase (ALK) mutant NSCLC, and more PIK3CA and AURKA in EGFR/ALK wild-type NSCLC. HRD-positive NSCLC displayed higher tumor proliferation and immunosuppression activity. HRD-negative NSCLC showed activated signatures of major histocompatibility complex (MHC)-II, interferon (IFN)-γ and effector memory CD8+ T cells. HRD-positive patients had a worse prognosis and shorter progression-free survival (PFS) to targeted therapy (first- and third-generation EGFR-TKIs) (P=0.042). Additionally, HRD-positive, EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy regimens. Conclusions: Unique genomic and transcriptional characteristics were found in HRD-positive NSCLC. Poor prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive NSCLC. This study highlights potential actionable alterations in HRD-positive NSCLC, suggesting possible combinational therapeutic strategies for these patients.

Genome-wide association analyses identified novel susceptibility loci for pulmonary embolism among Han Chinese population.

BACKGROUND: A large proportion of pulmonary embolism (PE) heritability remains unexplained, particularly among the East Asian (EAS) population. Our study aims to expand the genetic architecture of PE and reveal more genetic determinants in Han Chinese. METHODS: We conducted the first genome-wide association study (GWAS) of PE in Han Chinese, then performed the GWAS meta-analysis based on the discovery and replication stages. To validate the effect of the risk allele, qPCR and Western blotting experiments were used to investigate possible changes in gene expression. Mendelian randomization (MR) analysis was employed to implicate pathogenic mechanisms, and a polygenic risk score (PRS) for PE risk prediction was generated. RESULTS: After meta-analysis of the discovery dataset (622 cases, 8853 controls) and replication dataset (646 cases, 8810 controls), GWAS identified 3 independent loci associated with PE, including the reported loci FGG rs2066865 (p-value = 3.81 × 10-14), ABO rs582094 (p-value = 1.16 × 10-10) and newly reported locus FABP2 rs1799883 (p-value = 7.59 × 10-17). Previously reported 10 variants were successfully replicated in our cohort. Functional experiments confirmed that FABP2-A163G(rs1799883) promoted the transcription and protein expression of FABP2. Meanwhile, MR analysis revealed that high LDL-C and TC levels were associated with an increased risk of PE. Individuals with the top 10% of PRS had over a fivefold increased risk for PE compared to the general population. CONCLUSIONS: We identified FABP2, related to the transport of long-chain fatty acids, contributing to the risk of PE and provided more evidence for the essential role of metabolic pathways in PE development.

LMWHs dosage and outcomes in acute pulmonary embolism with renal insufficiency, an analysis from a large real-world study.

BACKGROUND: Renal function is associated with prognoses for acute pulmonary embolism (PE). OBJECTIVE: To investigate the application of anticoagulants and dosage of LMWH among patients with renal insufficiency (RI), and the association between LWMH dosage and the patients' in-hospital outcomes. METHODS: Adult patients diagnosed with non-high risk acute PE from 2009 to 2015, with available data of creatinine clearance (CCr) were enrolled from a multicenter registry in China. Renal insufficiency (RI) was defined as CCr < 60 ml/min. LMWH dosage was converted into IU/kg daily dose and presented as adjusted dose (≤ 100 IU/kg/day) and conventional dose (> 100 IU/kg/day). All-cause death, PE-related death and bleeding events during hospitalization were analyzed as endpoints. RESULTS: Among the enrolled 5870 patients, RI occurred in 1311 (22.3%). 30 ≤ CCr < 60 ml/min was associated with higher rate of bleeding events and CCr < 30 ml/min was associated with all-cause death, PE-related death and major bleeding. Adjusted-dose LMWH was applied in 26.1% of patients with 30 ≤ CCr < 60 ml/min and in 26.2% of CCr < 30 ml/min patients. Among patients with RI, in-hospital bleeding occurred more frequently in those who were administered conventional dose of LMWH, compared with adjusted dose (9.2% vs 5.0%, p = 0.047). Adjusted dose of LMWH presented as protective factor for in-hospital bleeding (OR 0.62, 95%CI 0.27-1.00, p = 0.0496) and the risk of bleeding increased as length of hospital stay prolonged (OR 1.03, 95%CI 1.01-1.06, p = 0.0014). CONCLUSIONS: The proportion of adjusted usage of LMWH was low. The application of adjusted-dose LMWH was associated with lower risk of in-hospital bleeding for RI patients, in real-world setting of PE treatment. Anticoagulation strategy for RI patients should be paid more attention and requires evidence of high quality. TRIAL REGISTRATION: The CURES was registered in ClinicalTrias.gov, identifier number: NCT02943343 .

Trends in risk stratification, in-hospital management and mortality of patients with acute pulmonary embolism: an analysis from the China pUlmonary thromboembolism REgistry Study (CURES).

Similar trends of management and in-hospital mortality of acute pulmonary embolism (PE) have been reported in European and American populations. However, these tendencies are not clear in Asian countries. We retrospectively analysed the trends of risk stratification, management and in-hospital mortality for patients with acute PE through a multicentre registry in China (CURES).Adult patients with acute symptomatic PE were included between 2009 and 2015. Trends in disease diagnosis, treatment and death in hospital were fully analysed. Risk stratification was retrospectively classified by haemodynamic status and the simplified Pulmonary Embolism Severity Index (sPESI) score according to the 2014 European Society of Cardiology/European Respiratory Society guidelines.Among 7438 patients, the proportions with high (haemodynamic instability), intermediate (sPESI≥1) and low (sPESI=0) risk were 4.2%, 67.1% and 28.7%, respectively. Computed tomographic pulmonary angiography was the most widely used diagnostic approach (87.6%) and anticoagulation was the most frequently adopted initial therapy (83.7%). Between 2009 and 2015, a significant decline was observed for all-cause mortality (from 3.1% to 1.3%, adjusted pfor trend=0.0003), with a concomitant reduction in the use of initial systemic thrombolysis (from 14.8% to 5.0%, pfor trend<0.0001). The common predictors for all-cause mortality shared by haemodynamically stable and unstable patients were co-existing cancer, older age and impaired renal function.The considerable reduction of mortality over the years was accompanied by changes in initial treatment. These findings highlight the importance of risk stratification-guided management throughout the nation.

The dynamic changes of serum IgM and IgG against SARS-CoV-2 in patients with COVID-19.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic since it emerged in December 2019. Previous studies have reported rapid antibody response to SARS-CoV-2 in the first 2 to 3 weeks after symptom onset. Here, we retrospectively described the dynamic changes of serum immunoglobulin M (IgM) and IgG specifically against SARS-CoV-2 in later weeks (mainly 4-10 weeks) in 97 hospitalized patients with COVID-19. We observed that serum IgM and IgG, especially in patients with moderate-to-high levels, declined significantly between week 4 to 10 after illness onset. Notably, IgG levels in high percentage of patients (77.5%, 31 of 40) rapidly declined by half, from 212.5 (range, 163.7-420.3) to 96.3 (range, 75.0-133.4) AU/mL, within 1 to 2 weeks in the second month and then sustained at around 100 AU/mL until discharge from hospital. Significant reduction of IgM was also observed as SARS-CoV-2 nucleic acid turned negative (P = .002). In the recovery stage, serum IgG declined significantly (early vs late recovery stage, n = 16, P = .003) with a median reduction of 50.0% (range, 3.7%-77.0%). Our results suggested that the decline of IgM may be an indicator of virus clearance and recovered patients may have a robust immunity against reinfection within at least 3 months after illness onset. Yet, the rapid reduction of IgG by half rises serious concerns on the robustness and sustainability of the humoral immune response in the period after discharge, which is crucial for immunity strategy and developing a vaccine.

Characteristics of peripheral white blood cells in COVID-19 patients revealed by a retrospective cohort study.

BACKGROUND: Peripheral hematological changes in severe COVID-19 patients may reflect the immune response during SARS-CoV-2 infection. Characteristics of peripheral white blood cells as early signals were needed to be investigated for clarifying its associations with the fatal outcomes in COVID-19 patients. METHODS: A retrospective cohort study was performed and the hospitalized COVID-19 patients were recruited in wards of Sino-French New City Branch of Tongji Hospital in Wuhan, Hubei province, China. Characteristics of peripheral white blood cells in survivors and non-survivors were analyzed. Comparison among patients with different level of eosinophils was performed. RESULTS: Of 198 patients included in this study, 185 were discharged and 13 died. Levels of eosinophils, lymphocytes and basophils in non-survivors were significantly lower than those in survivors. Death rate in low eosinophils group was higher and no patient died in normal eosinophils group (16.7% vs 0, P < 0.001). The proportion of patients in low eosinophils group who used glucocorticoids was higher than in normal eosinophils group, but glucocorticoids usage was not an indicator for death in subgroup analysis in low eosinophils patients. Moreover, positive correlation was found between the counts of lymphocytes and eosinophils in patients with glucocorticoids use but not in patients without the treatment. CONCLUSIONS: Hematological changes differed between survivors and non-survivors with COVID-19. Lymphopenia and eosinopenia could be predictors for poor prognosis of COVID-19 patients. Initial counts of eosinophils may guide us in usage of glucocorticoids for COVID-19 treatment.

Clinical characteristics and outcome of influenza virus infection among adults hospitalized with severe COVID-19: a retrospective cohort study from Wuhan, China.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that rapidly spreads worldwide and co-infection of COVID-19 and influenza may occur in some cases. We aimed to describe clinical features and outcomes of severe COVID-19 patients with co-infection of influenza virus. METHODS: Retrospective cohort study was performed and a total of 140 patients with severe COVID-19 were enrolled in designated wards of Sino-French New City Branch of Tongji Hospital between Feb 8th and March 15th in Wuhan city, Hubei province, China. The demographic, clinical features, laboratory indices, treatment and outcomes of these patients were collected. RESULTS: Of 140 severe COVID-19 hospitalized patients, including 73 patients (52.14%) with median age 62 years were influenza virus IgM-positive and 67 patients (47.86%) with median age 66 years were influenza virus IgM-negative. 76 (54.4%) of severe COVID-19 patients were males. Chronic comorbidities consisting mainly of hypertension (45.3%), diabetes (15.8%), chronic respiratory disease (7.2%), cardiovascular disease (5.8%), malignancy (4.3%) and chronic kidney disease (2.2%). Clinical features, including fever (≥38 °C), chill, cough, chest pain, dyspnea, diarrhea and fatigue or myalgia were collected. Fatigue or myalgia was less found in COVID-19 patients with IgM-positive (33.3% vs 50/7%, P = 0.0375). Higher proportion of prolonged activated partial thromboplastin time (APTT) > 42 s was observed in COVID-19 patients with influenza virus IgM-negative (43.8% vs 23.6%, P = 0.0127). Severe COVID-19 Patients with influenza virus IgM positive have a higher cumulative survivor rate than that of patients with influenza virus IgM negative (Log-rank P = 0.0308). Considering age is a potential confounding variable, difference in age was adjusted between different influenza virus IgM status groups, the HR was 0.29 (95% CI, 0.081-1.100). Similarly, difference in gender was adjusted as above, the HR was 0.262 (95% CI, 0.072-0.952) in the COX regression model. CONCLUSIONS: Influenza virus IgM positive may be associated with decreasing in-hospital death.

Hydroxychloroquine/chloroquine in patients with COVID-19 in Wuhan, China: a retrospective cohort study.

BACKGROUND: Since the COVID-19 pandemic, several therapeutic agents have been used in COVID-19 management. However, the results were controversial. Here, we aimed to evaluate the efficacy and safety of hydroxychloroquine (HCQ)/chloroquine (CQ) in COVID-19. METHODS: We retrospectively reviewed the medical charts of patients with COVID-19 admitted to an inpatient ward in Wuhan from 2020/Feb/08 to 2020/Mar/05. Patients with HCQ/CQ and age, gender, disease severity matched ones without HCQ/CQ were selected at a 1:2 ratio. The clinical, laboratory and imaging findings were compared between these two groups. The multivariate linear regression analysis was performed to identify the factors that might influence patients' virus shedding periods (VSPs). RESULTS: A total of 14 patients with HCQ/CQ and 21 matched ones were analyzed. The HCQ/CQ treatment lasted for an average of 10.36 ± 3.12 days. The mean VSPs were longer in the HCQ/CQ treatment group (26.57 ± 10.35 days vs. 19.10 ± 7.80 days, P = 0.020). There were 3 patients deceased during inpatient period, two patients were with HCQ/CQ treatment (P = 0.551). In the multivariate linear regression analysis, disease durations at admission (t = 3.643, P = 0.001) and HCQ/CQ treatment (t = 2.637, P = 0.013) were independent parameters for patients' VSPs. One patient with CQ had recurrent first-degree atrioventricular block (AVB) and obvious QTc elongation, another one complained about dizziness and blurred vision which disappeared after CQ discontinuation. One patient with HCQ had transient AVB. CONCLUSIONS: In summary, we identify that the HCQ/CQ administration is not related to less mortality cases at later phase of COVID-19. More studies are needed to explore whether HCQ/CQ treatment would lead to SARS-Cov-2 RNA clearance delay or not.

Development of a nomogram for predicting the presence of combined pulmonary fibrosis and emphysema.

BACKGROUND: In the clinical management of patients with combined pulmonary fibrosis and emphysema (CPFE), early recognition and appropriate treatment is essential. This study was designed to develop an accurate prognostic nomogram model to predict the presence of CPFE. METHODS: We retrospectively enrolled 85 patients with CPFE and 128 patients with idiopathic pulmonary fibrosis (IPF) between January 2015 and January 2020. Clinical characteristics were compared between groups. A multivariable logistic regression analysis was performed to identify risk factors for CPFE. Then, and a nomogram to predict the presence of CPFE was constructed for clinical use. Concordance index (C-index), area under the receiver operating characteristic curve (AUC), and calibration plot was used to evaluate the efficiency of the nomogram. RESULTS: Compared to the IPF group, the proportion of patients with male, smoking and allergies were significantly higher in the CPFE group. In terms of pulmonary function tests, patients with CPFE had lower FEV1/FVC%, DLCO/VA% pred, and higher RV, RV%pred, VC, VC%pred, TLC%pred, VA, TLC, TLC%pred, FVC, FVC%pred and FEV1 with significant difference than the other group. Positive correlation was found between DLCO and VA%, RV%, TLC% in patients with IPF but not in patients with CPFE. By multivariate analysis, male, smoking, allergies, FEV1/FVC% and DLCO/VA%pred were identified as independent predictors of the presence of CPFE. The nomogram was then developed using these five variables. After 1000 internal validations of bootstrap resampling, the C-index of the nomogram was 0.863 (95% CI 0.795-0.931) and the AUC was 0.839 (95% CI 0.764-0.913). Moreover, the calibration plot showed good concordance of incidence of CPFE between nomogram prediction and actual observation (Hosmer-Lemeshow test: P = 0.307). CONCLUSIONS: Patients of CPFE have a characteristic lung function profile including relatively preserved lung volumes and ventilating function, contrasting with a disproportionate reduction of carbon monoxide transfer. By incorporating clinical risk factors, we created a nomogram to predict the presence of CPFE, which may serve as a potential tool to guide personalized treatment.

The predictive value of PaO2/FIO2 and additional parameters for in-hospital mortality in patients with acute pulmonary embolism: an 8-year prospective observational single-center cohort study.

BACKGROUND: Rapid stratification and appropriate treatment on admission are critical to saving lives of patients with acute pulmonary embolism (PE). None of the clinical prediction tools perform well when applied to all patients with acute PE. It may be important to integrate respiratory features into the 2014 European Society of Cardiology model. First, we aimed to assess the relationship between the arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FIO2) ratio and in-hospital mortality, determine the optimal cutoff value of PaO2/FIO2, and determine if this value, which is quick and easy to obtain on admission, is a predictor of in-hospital mortality in this population. Second, we aimed to evaluate the potential additional determinants including laboratory parameters that may affect the in-hospital mortality. We hypothesized that the PaO2/FiO2 ratio would be a clinical prediction tool for in-hospital mortality in patients with acute PE. METHODS: A prospective single-center observational cohort study was conducted in Beijing Hospital from January 2010 to November 2017. Arterial blood gas analysis data captured on admission, clinical characteristics, risk factors, laboratory data, imaging findings, and in-hospital mortality were compared between survivors and non-survivors. The area under the receiver operating characteristic curve (AUC) for in-hospital mortality based on the PaO2/FiO2 value was determined, and the association between the parameters and in-hospital mortality was analyzed by using logistic regression analysis. RESULTS: Body mass index, history of cancer, PaO2/FiO2 value, pulse rate, cardiac troponin I level, lactate dehydrogenase level, white blood cell count, D-dimer level, and risk stratification measurements differed between survivors and non-survivors. The optimal cutoff value of PaO2/FiO2 for predicting mortality was 265 (AUC = 0.765, P < 0.001). Only a PaO2/FiO2 ratio < 265 (95% confidence interval [CI] 1.823-21.483, P = 0.004), history of cancer (95% CI 1.161-15.927, P = 0.029), and risk stratification (95% CI 1.047-16.957, P = 0.043) continued to be associated with an increased risk of in-hospital mortality of acute PE. CONCLUSION: A simple determination of the PaO2/FiO2 ratio at <265 may provide important information on admission about patients' in-hospital prognosis, and PaO2/FiO2 ratio < 265, history of cancer, and risk stratification are predictors of in-hospital mortality of acute PE.

cGMP interacts with tropomyosin and downregulates actin-tropomyosin-myosin complex interaction.

BACKGROUND: The nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway, plays a critical role in the pathogenesis of pulmonary arterial hypertension (PAH); however, its exact molecular mechanism remains undefined. METHODS: Biotin-cGMP pull-down assay was performed to search for proteins regulated by cGMP. The interaction between cGMP and tropomyosin was analyzed with antibody dependent pull-down in vivo. Tropomyosin fragments were constructed to explore the tropomyosin-cGMP binding sites. The expression level and subcellular localization of tropomyosin were detected with Real-time PCR, Western blot and immunofluorescence assay after the 8-Br-cGMP treatment. Finally, isothermal titration calorimetry (ITC) was utilized to detect the binding affinity of actin-tropomyosin-myosin in the existence of cGMP-tropomyosin interaction. RESULTS: cGMP interacted with tropomyosin. Isoform 4 of TPM1 gene was identified as the only isoform expressed in the human pulmonary artery smooth muscle cells (HPASMCs). The region of 68-208aa of tropomyosin was necessary for the interaction between tropomyosin and cGMP. The expression level and subcellular localization of tropomyosin showed no change after the stimulation of NO-sGC-cGMP pathway. However, cGMP-tropomyosin interaction decreased the affinity of tropomyosin to actin. CONCLUSIONS: We elucidate the downstream signal pathway of NO-sGC-cGMP. This work will contribute to the detection of innovative targeted agents and provide novel insights into the development of new therapies for PAH.

[A preliminary study of the distribution and the characteristics of nonspecific pulmonary function].

OBJECTIVE: To investigate the manifestations, pulmonary function test (PFT) characteristics and imaging features of patients with nonspecific pulmonary function (NSPF). METHODS: All the data from the same PFT apparatus in Beijing Hospital were collected from January 2003 to December 2012. NSPF was defined as normal FEV1/FVC and TLC, but decreased FEV1 or FVC or both. Patients with complete clinical data from January 2012 to June 2012 were enrolled into this analysis. The NSPF group was compared with the normal group, the obstructive group, the restrictive group and the mixed group. RESULTS: There were totally 14 771 cases of PFT on this apparatus during 10 year period, and those with NSPF were 2759 (18.68%). From January 2012 to June 2012, 341 patients were enrolled into this study with a sex ratio of 1.37:1, and an average age of 66±12 years. Compared with the normal group, the NSPF group had a significantly higher rate of small airway abnormalities and elevated RV/TLC. Multiple logistic regression analysis showed that statistical differences were found in TLC%pred (OR=0.668, P<0.01, 95%CI 0.563-0.791), FEF25-75%pred (OR=0.963, P<0.01, 95%CI 0.939-0.988), RV%pred (OR=1.144, P<0.01, 95%CI 1.075-1.217), and RV/TLC (OR=1.31, P<0.01, 95%CI 1.15-1.492). Compared with the obstructive group, the NSPF group had a significantly lower rate of small airway abnormalities. Multiple logistic regression analysis showed that female gender(OR=15.283, P<0.001, 95%CI 3.526-66.248), TLC%pred (OR=0.961, P=0.02, 95%CI 0.928-0.994), and FEF50%%pred (OR=1.189, P<0.001, 95%CI 1.103-1.281) were significantly different between the 2 groups. Respiratory symptoms were more common in the NSPF group. Airway diseases were diagnosed in more cases of the NSPF group when compared to the normal group, but in fewer cases when compared to the obstructive group. Clinical manifestations and imaging features of the NSPF cases were not specific. CONCLUSIONS: NSPF is a common clinical condition which mainly affects the small airway function with some degree of restrictive dysfunction. NSPF has limited predictive value for diagnosis because the manifestations and imaging features are not specific.

Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study.

BACKGROUND: Oxidative stress (OS) and reduced nitric oxide (NO) bioavailability contribute to the pathogenesis of pulmonary hypertension (PH). Whether there are associations between OS and NO signaling biomarkers and whether these biomarkers are associated with the severity of PH remain unclear. METHODS: Blood samples were collected from 35 healthy controls and 35 patients with pulmonary arterial hypertension (PAH, n = 12) or chronic thromboembolic pulmonary hypertension (CTEPH, n = 23). The mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance index (PVRI) were measured by right heart catheterization. We measured the derivative of reactive oxygen molecules (d-ROMs), biological antioxidant potential (BAP) and superoxide dismutase (SOD) by automatic biochemical analyzer, malondialdehyde (MDA) and asymmetric dimethylarginine (ADMA) by enzyme-linked immunosorbent assay. The relationship between oxidative-antioxidative biomarkers and ADMA, as well as their association with pulmonary hemodynamics, were analyzed. RESULTS: Compared with age- and gender-matched controls, there was no significant difference of d-ROMs in PAH and CTEPH patients; MDA was increased in CTEPH patients (P = 0.034); BAP and SOD were decreased in PAH (P = 0.014, P < 0.001) and CTEPH patients (P = 0.015, P < 0.001); ADMA level was significantly higher in PAH (P = 0.007) and CTEPH patients (P < 0.001). No association between oxidative-antioxidative biomarkers and ADMA was found. Serum ADMA concentration was correlated with mPAP (r = 0.762, P = 0.006) and PVRI (r = 0.603, P = 0.038) in PAH patients. CONCLUSIONS: The antioxidative potential and NO signaling are impaired in PAH and CTEPH. Increased serum ADMA level is associated with unfavorable pulmonary hemodynamics in PAH patients. Thus, ADMA may be useful in the severity evaluation and risk stratification of PAH.

[Correlation of three common variation loci in von Willebrand factor gene and pulmonary thromboembolism disease].

OBJECTIVE: To elucidate the relationship between three common variation loci of von Willebrand factor (VWF) gene (rs216321, rs216325 and rs1800378) and pulmonary thromboembolism. METHODS: A total of 95 patients with definite pulmonary thromboembolism (PTE) at Beijing Chaoyang Hospital and Beijing Hospital during November 2008 to March 2012 served as PTE group while 90 healthy subjects at Beijing Hospital during the same period as control group. Fasting venous blood samples were collected for extracting genomic DNA. Three common variation loci with single nucleotide polymorphism were rs216321 (T/C), rs216325 (G/A) and rs1800378 (T/C) and their minor allele frequency was over 0.05 in VWF gene. The method of polymerase chain reaction (PCR)-Sanger was employed for sequencing. The differences of alleleic and genotypic frequencies between PTE and control groups were compared for each locus. And the correlations of their haplotypes with PTE were analyzed. RESULTS: The distributions of rs216325 (G/A) and rs1800378 (T/C) in VWF gene had significant difference between PTE and control groups (P=0.039, 0.006). And rs216325 with genotype AA was positively correlated with PTE occurrence (r=1.914, P=0.047). And rs1800378 with genotype TT was also positively correlated with PTE occurrence (r=0.282, P=0.008). The distributions of haplotype TGT had significant differences between PTE and control groups. This haplotype was positively correlated with PTE occurrence (r=0.239, P<0.001). CONCLUSIONS: The rs216325 and rs1800378 loci variations in VWF gene are associated with PTE, rs216325 with genotype AA and rs1800378 with genotype TT. And haplotype TGT indicates a high risk of PTE onset.

Association between KLKB1 Polymorphisms and Pulmonary Thromboembolism.

OBJECTIVE: To investigate the potential correlation between the single nucleotide polymorphisms (SNPs) in the KLKB1 region and pulmonary thromboembolism(PTE) in a Chinese Han population. METHODS: In this case-control study, 95 patients with confirmed PTE were enrolled as the PTE group and 90 healthy subjects as the control group. The genotypes, alleles, and haplotypes of the SNPs were analyzed with PLINK 1.07 and Haploview 4.2 software using chi-square test and Logistic regression analysis. SNPs were further analyzed under three genetic models (additive, dominant, and recessive). RESULTS: The distribution of rs3733402 in KLKB1 gene showed significant difference between PTE group and control group (P=0.041). The distributions of GTG haplotypes consisted of rs2292423, rs4253325,and rs3733402 in KLKB1 gene were also significantly different between PTE group and control group(P=0.040). CONCLUSION: The rs3733402 locus variation in KLKB1 gene is associated with PTE in Chinese Han people.

[Clinical characteristic and outcomes of lung cancer patients with venous thromboembolism].

OBJECTIVE: To explore the clinical characteristics and outcomes of lung cancer patients with venous thromboembolism (VTE). METHODS: The clinical data of 80 lung cancer patients with VTE hospitalized from January 2003 to April 2013 at our hospital were reviewed. The clinical factors of age, gender, clinical manifestations, pathological type, clinical stage, performance status and therapeutic regimen were recorded and analyzed. And the pulmonary thromboembolism (PTE) patients with deep venous thrombosis (DVT) were enrolled into PTE group. The occurrences, clinical manifestations and prognosis of VTE were evaluated. RESULTS: A total of 80 patients were enrolled. There were 40 males and 40 females with a mean age of (65.8 ± 11.3) years. Adenocarcimoma was identified in 58 (72.5%) patients and advanced lung cancer in 71 (88.8%) patients. Among 37 (46.3%) patients with histodifferentiation results, 89.2% (33/37) of them were moderately and/or poorly differentiated. In 32 (40.0%) patients on chemotherapy, 71.9% (23/32) of them received a platinum-based regimen. There were 35 (43.8%) pulmonary thromboembolism embolism (PTE) and 45 (56.2%) DVT patients. Among PTE patents, 14 (40.0%) were identified incidentally. Dyspnea and swollen of limb were the most common symptoms. Only 20.0% (16/80) patients received VTE prophylaxis. After a definite diagnosis of cancer, 73.8%, 77.5%, 82.5% and 85.0% of patients experienced an event within 3, 6, 9 and 12 months respectively. Up to April 2014, among 53 deceased patients, 77.4% (41/53) died from lung cancer, 9.3% (5/53) PTE while 13.2% (7/53) due to other causes. The cumulative mortality rates within 3, 6, 9 and 12 months after VTE event were 49.1%, 67.9%, 77.4% and 79.2% respectively. CONCLUSIONS: Adenocarcimoma, advanced lung cancer, poor histodifferentiation and platinum-based chemotherapy regimen are the risk factors of VTE in lung cancer patients. Most events of VTE occur within 3-6 months after a diagnosis of lung cancer while most mortality cases within 1 year after VTE events.

[A retrospective clinicopathological study of aspiration pneumonia in the elderly].

OBJECTIVE: To explore the clinicopathological characteristics of aspiration pneumonia in the elderly. METHODS: The clinical data of 30 cases of autopsy-proven aspiration pneumonia in Beijing Hospital from 1973 to 2002 were reviewed. The patients consisted of 28 males and 2 females, aged from 63 to 103 [mean (83 ± 9)] years. RESULTS: Only 15 cases were clinically diagnosed as aspiration pneumonia before death. Concomitant diseases were severe and complex, mostly coronary disease, cerebrovascular disease, hypertension, COPD, and diabetes mellitus. All the patients suffered from at least 3 concomitant diseases. Long-term bedridden and nasogastric feeding was seen in 11 and 17 patients respectively. The clinical presentation and chest X-ray of aspiration pneumonia in the elderly were nonspecific and variable. Mixed infections were common . The main bacteria isolated were Gram-negative bacilli, in particular Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Escherichia coli and Candida albicans. By pathology, macrophages with foreign bodies were found in all the 30 cases and multiple small abscesses were found in 14 cases. The lesions were adjacent to the bronchioles and in the lung tissue around the bronchioles, mostly multi-lobar and bilateral. Unilateral or bilateral pleural effusion developed in 20 patients. The accordance between radiological and pathological diagnosis of aspiration pneumonia was very poor. The foci of infection detected by X-ray were proven by autopsy in 13 patients, while pleural effusions in X-ray were proven by autopsy in 15 patients. CONCLUSIONS: Multi-concomitant diseases, mixed infection and extra-pulmonary presentations were common in elderly patients with aspiration pneumonia. Multiple small abscesses were the pathological characteristics of aspiration pneumonia in the aged. A definite clinical diagnosis of aspiration pneumonia was difficult. Recurrent silent microaspiration was a feature of aspiration in the elderly. The assessment of risk factor of aspiration played an important role in the clinical diagnosis of aspiration pneumonia.