ADAMTS-7 deficiency attenuates thoracic aortic aneurysm and dissection in mice.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening cardiovascular disease with severe extracellular matrix (ECM) remodeling that lacks efficient early stage diagnosis and nonsurgical therapy. A disintegrin and metalloproteinase with thrombospondin motif 7 (ADAMTS-7) is recognized as a novel locus for human coronary artery atherosclerosis. Previous work by us and others showed that ADAMTS-7 promoted atherosclerosis, postinjury neointima formation, and vascular calcification. However, whether ADAMTS-7 is involved in TAAD pathogenesis is unknown. We aimed to explore the alterations in ADAMTS-7 expression in human and mouse TAAD, and investigate the role of ADAMTS-7 in TAAD formation. A case-control study of TAAD patients (N = 86) and healthy participants (N = 88) was performed. The plasma ADAMTS-7 levels were markedly increased in TAAD patients within 24 h and peaked in 7 days. A TAAD mouse model was induced with 0.5% ß-aminopropionitrile (BAPN) in drinking water. ELISA analysis of mouse plasma, Western blotting, and immunohistochemical staining of aorta showed an increase in ADAMTS-7 in the early stage of TAAD. Moreover, ADAMTS-7-deficient mice exhibited significantly attenuated TAAD formation and TAAD rupture-related mortality in both male and female mice, which was accompanied by reduced artery dilation and inhibited elastin degradation. ADAMTS-7 deficiency caused repressed inflammatory response and complement system activation during TAAD formation. An increase in plasma ADAMTS-7 is a novel biomarker for human TAAD. ADAMTS-7 deficiency attenuates BAPN-induced murine TAAD. ADAMTS-7 is a potential novel target for TAAD diagnosis and therapy. KEY MESSAGES: A case-control study revealed increased plasma ADAMTS-7 is a risk factor for TAAD. ADAMTS-7 was elevated in plasma and aorta at early stage of mouse TAAD. ADAMTS-7 knockout attenuated mouse TAAD formation and mortality in both sexes.

Targeting endothelial tight junctions to predict and protect thoracic aortic aneurysm and dissection.

AIMS: Whether changes in endothelial tight junctions (TJs) lead to the formation of thoracic aortic aneurysm and dissection (TAAD) and serve as an early indicator and therapeutic target remains elusive. METHODS AND RESULTS: Single-cell RNA sequencing analysis showed aberrant endothelial TJ expressions in the thoracic aortas of patients with TAAD. In a ß-aminopropionitrile (BAPN)-induced TAAD mouse model, endothelial TJ function was disrupted in the thoracic aortas at an early stage (5 and 10 days) as observed by a vascular permeability assay, while the intercellular distribution of crucial TJ components was significantly decreased by en face staining. For the non-invasive detection of endothelial TJ function, two dextrans of molecular weights 4 and 70 kDa were conjugated with the magnetic resonance imaging (MRI) contrast agent Gd-DOTA to synthesize FITC-dextran-DOTA-Gd and rhodamine B-dextran-DOTA-Gd. MRI images showed that both probes accumulated in the thoracic aortas of the BAPN-fed mice. Particularly, the mice with increased accumulated signals from 5 to 10 days developed TAAD at 14 days, whereas the mice with similar signals between the two time points did not. Furthermore, the protease-activated receptor 2 inhibitor AT-1001, which seals TJs, alleviated the BAPN-induced impairment of endothelial TJ function and expression and subsequently reduced TAAD incidence. Notably, endothelial-targeted ZO-1 conditional knockout increased TAAD incidence. Mechanistically, vascular inflammation and edema were observed in the thoracic aortas of the BAPN-fed mice, whereas these phenomena were attenuated by AT-1001. CONCLUSION: The disruption of endothelial TJ function is an early event prior to TAAD formation, herein serving as a potential indicator and a promising target for TAAD.

Early Prediction Model of Acute Aortic Syndrome Mortality in Emergency Departments.

Purpose: Acute aortic syndrome is a constellation of life-threatening medical conditions for which rapid assessment and targeted intervention are important for the prognosis of patients who are at high risk of in-hospital death. The current study aims to develop and externally validate an early prediction mortality model that can be used to identify high-risk patients with acute aortic syndrome in the emergency department. Patients and Methods: This retrospective multi-center observational study enrolled 1088 patients with acute aortic syndrome admitted to the emergency departments of two hospitals in China between January 2017 and March 2021 for model development. A total of 210 patients with acute aortic syndrome admitted to the emergency departments of Peking University Third Hospital between January 2007 and December 2021 was enrolled for model validation. Demographics and clinical factors were collected at the time of emergency department admission. The predictive variables were determined by referring to the results of previous studies and the baseline analysis of this study. The study's endpoint was in-hospital death. To assess internal validity, we used a fivefold cross-validation method. Model performance was validated internally and externally by evaluating model discrimination using the area under the receiver-operating characteristic curve (AUC). A nomogram was developed based on the binary regression results. Results: In the development cohort, 1088 patients with acute aortic syndromes were included, and 88 (8.1%) patients died during hospitalization. In the validation cohort, 210 patients were included, and 20 (9.5%) patients died during hospitalization. The final model included the following variables: digestive system symptoms (OR=2.25; P=0.024), any pulse deficit (OR=7.78; P<0.001), creatinine (µmol/L)(OR=1.00; P=0.018), lesion extension to iliac vessels (OR=4.49; P<0.001), pericardial effusion (OR=2.67; P=0.008), and Stanford type A (OR=10.46; P<0.001). The model's AUC was 0.838 (95% CI 0.784-0.892) in the development cohort and 0.821 (95% CI 0.750-0.891) in the validation cohort, and the Hosmer-Lemeshow test showed p=0.597. The fivefold cross-validation demonstrated a mean accuracy of 0.94, a mean precision of 0.67, and a mean recall of 0.13. Conclusion: This risk prediction tool uses simple variables to provide robust prediction of the risk of in-hospital death from acute aortic syndrome and validated well in an independent cohort. The tool can help emergency clinicians quickly identify high-risk acute aortic syndrome patients, although further studies are needed for verifying the prospective data and the results of our study.

Factors related to improved American Spinal Injury Association grade of acute traumatic spinal cord injury.

BACKGROUND: Acute traumatic spinal cord injury (ATSCI) usually results in disability, yet data on contemporary national trends of ATSCI incidence are limited. AIM: To provide a systematic and basic theoretical basis for improving the treatment of acute spinal cord injury. METHODS: Data from the Peking University Third Hospital Inpatient Sample databases were analyzed. A total of 304 patients with ATSCI were included from 2012 to 2017. The epidemiological data, treatment, complications and clinical outcomes of these patients were reviewed. RESULTS: Of the 304 patients, 257 (84.5%) were male, and 75% of the patients were 55 years old or younger. 135 patients had improved follow-up American Spinal Injury Association (ASIA) grades (44.4%). Only 14 patients with ASIA grade A improved. A statistically significant difference in prognosis between patients who underwent surgery within 72 h and those who underwent surgery after 72 h was observed (P < 0.05). Surgery within 72 h resulted in better prognosis. The Steroid group and the Non-Steroid group showed a significant difference in outcome among patients with ASIA grades A and B (P < 0.05). Patients with pneumonia had a poorer prognosis than patients without pneumonia (P < 0.05). Surgery within 72 h resulted in better prognosis. CONCLUSION: This study found that there was no significant difference in hospitalization time and prognosis between the Steroid group and the Non-Steroid group, but the patients with severe spinal cord injury (ASIA grades A and B) who underwent surgery combined with steroid therapy had a better prognosis than those who underwent surgery alone. The disastrous consequences of ATSCI and lack of consensus on the management strategy are obvious. Further improvements in treatment planns are needed in order to obtain more reliable functional outcomes.

Serial disseminated intravascular coagulation score with neuron specific enolase predicts the mortality of cardiac arrest-a pilot study.

BACKGROUND: Prognosis in cardiac arrest (CA) patients has been challenging. We sought to investigate prognostic value combining serial disseminated intravascular coagulation (DIC) score and neuron-specific enolase (NSE) in out-of-hospital cardiac arrest (OHCA) patients. METHODS: Sixty-one consecutive patients successfully resuscitated after CA were included in the analysis. DIC score and NSE levels were serially analyzed after return of spontaneous circulation (ROSC). The outcome measure was death before hospital discharge. Prognostication performance was assessed as the area under the receiver-operating characteristics curve (AUC). Hosmer-Lemeshow test was used for internal validation of predictive models. Calibration curves were drawn to visualize the results of tests. RESULTS: The NSE levels continued to increase in the first 72 h in non-survivors. In survivors, the NSE levels decreased after 48 h. Both DIC score at 48 h and NSE level at 48 h were good predictors of outcome. The AUC for predictive mortality in OHCA patients was 0.869 (95% CI, 0.781-0.956) for DIC score at 48 h combining NSE at 24 h, 0.878 (95% CI, 0.791-0.965) for DIC score at 48 h combining NSE at 48 h and 0.882 (95% CI, 0.792-0.972) for DIC score at 48 h combining NSE at 72 h, respectively. Significance of Hosmer-Lemeshow test was 0.488, 0.324, 0.011 for each combination. CONCLUSIONS: Serial DIC score combined with measurement of NSE levels is a useful and accessible tool for prognostication following OHCA.

Impact of Dispatcher-Assisted Bystander Cardiopulmonary Resuscitation with Out-of-Hospital Cardiac Arrest: A Systemic Review and Meta-Analysis.

OBJECTIVE: This systemic review and meta-analysis was conducted to explore the impact of dispatcher-assisted bystander cardiopulmonary resuscitation (DA-BCPR) on bystander cardiopulmonary resuscitation (BCPR) probability, survival, and neurological outcomes with out-of-hospital cardiac arrest (OHCA). METHODS: Electronically searching of PubMed, Embase, and Cochrane Library, along with manual retrieval, were done for clinical trials about the impact of DA-BCPR which were published from the date of inception to December 2018. The literature was screened according to inclusion and exclusion criteria, the baseline information, and interested outcomes were extracted. Two reviewers assessed the methodological quality of the included studies. Pooled odds ratio (OR) and 95% confidence interval (CI) were calculated by STATA version 13.1. RESULTS: In 13 studies, 235,550 patients were enrolled. Compared with no dispatcher instruction, DA-BCPR tended to be effective in improving BCPR rate (I2 = 98.2%; OR = 5.84; 95% CI, 4.58-7.46; P <.01), return of spontaneous circulation (ROSC) before admission (I2 = 36.0%; OR = 1.17; 95% CI, 1.06-1.29; P <.01), discharge or 30-day survival rate (I2 = 47.7%; OR = 1.25; 95% CI, 1.06-1.46; P <.01), and good neurological outcome (I2 = 30.9%; OR = 1.24; 95% CI, 1.04-1.48; P = .01). However, no significant difference in hospital admission was found (I2 = 29.0%; OR = 1.09; 95% CI, 0.91-1.30; P = .36). CONCLUSION: This review shows DA-BPCR plays a positive role for OHCA as a critical section in the life chain. It is effective in improving the probability of BCPR, survival, ROSC before admission, and neurological outcome.

Association of emergency room visits for respiratory diseases with sources of ambient PM2.5.

Previous studies have reported associations of short-term exposure to different sources of ambient fine particulate matter (PM2.5) and increased mortality or hospitalizations for respiratory diseases. Few studies, however, have focused on the short-term effects of source-specific PM2.5 on emergency room visits (ERVs) of respiratory diseases. Source apportionment for PM2.5 was performed with Positive Matrix Factorization (PMF) and generalized additive model was applied to estimate associations between source-specific PM2.5 and respiratory disease ERVs. The association of PM2.5 and total respiratory ERVs was found on lag4 (RR = 1.011, 95%CI: 1.002, 1.020) per interquartile range (76 µg/m3) increase. We found PM2.5 to be significantly associated with asthma, bronchitis and chronic obstructive pulmonary disease (COPD) ERVs, with the strongest effects on lag5 (RR = 1.072, 95%CI: 1.024, 1.119), lag4 (RR = 1.104, 95%CI: 1.032, 1.176) and lag3 (RR = 1.091, 95%CI: 1.047, 1.135), respectively. The estimated effects of PM2.5 changed little after adjusting for different air pollutants. Six primary PM2.5 sources were identified using PMF analysis, including dust/soil (6.7%), industry emission (4.5%), secondary aerosols (30.3%), metal processing (3.2%), coal combustion (37.5%) and traffic-related source (17.8%). Some of the sources were identified to have effects on ERVs of total respiratory diseases (dust/soil, secondary aerosols, metal processing, coal combustion and traffic-related source), bronchitis ERVs (dust/soil) and COPD ERVs (traffic-related source, industry emission and secondary aerosols). Different sources of PM2.5 contribute to increased risk of respiratory ERVs to different extents, which may provide potential implications for the decision making of air quality related policies, rational emission control and public health welfare.