BackgroundRadiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of heart disease is uncertain. We performed a meta‐analysis to investigate the link between radiotherapy and long‐term cardiovascular morbidity and mortality in patients with breast cancer.Methods and ResultsWe performed a literature search using MEDLINE (January 1966 to January 2015) and EMBASE (January 1980 to January 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95%CIs for the associations of interest were included. Pooled effect estimates were obtained by using random‐effects meta‐analysis. Thirty‐nine studies involving 1 191 371 participants were identified. Patients who received left‐sided radiotherapy, as compared with those receiving right‐sided radiotherapy, experienced increased risks of developing coronary heart disease (RR 1.29, 95%CI 1.13‐1.48), cardiac death (RR 1.22, 95%CI 1.08‐1.37) and death from any cause (RR 1.05, 95%CI 1.01‐1.10). In a comparison of patients with radiotherapy and without radiotherapy, the RRs were 1.30 (95%CI 1.13‐1.49) for coronary heart disease and 1.38 (95%CI 1.18‐1.62) for cardiac mortality. Radiotherapy for breast cancer was associated with an absolute risk increase of 76.4 (95%CI 36.8‐130.5) cases of coronary heart disease and 125.5 (95%CI 98.8‐157.9) cases of cardiac death per 100 000 person‐years. The risk started to increase within the first decade for coronary heart disease and from the second decade for cardiac mortality.ConclusionsExposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent risk of coronary heart disease and cardiac mortality.

BackgroundAn early repolarization pattern (ERP) has been hypothesized to be arrhythmogenic in experimental studies, but the prognostic significance of the ERP in the general population is controversial. We performed a meta‐analysis to examine the link between ERP and the risk of sudden cardiac arrest (SCA), cardiac death, and death from any cause.Methods and ResultsWe performed a literature search using MEDLINE (January 1, 1966 to July 31, 2015) and EMBASE (January 1, 1980 to July 31, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Sixteen studies involving 334 524 subjects were identified. Compared with those without ERP, subjects with ERP experienced significantly increased risk for developing SCA (RR 2.18; 95% CI 1.29–3.68), cardiac death (RR 1.48; 95% CI 1.06–2.07), and death from any cause (RR 1.21; 95% CI 1.02–1.42), respectively. The increased risk was present predominantly in Asians and whites but not in African Americans. ERP with J‐point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk. ERP was associated with an absolute risk increase of 139.6 (95% CI 130.3–149.3) additional SCAs per 100 000 person‐years and responsible for 7.3% (95% CI 1.9–15.2) of SCA in the general population.Conclusions ERP is associated with significant increased risk for SCA, cardiac death, and death from any cause. Future studies should focus on understanding the exact mechanisms for the arrhythmia risk and developing reliable tools for risk stratification.

Background: Although great progress has been made in the pathogenesis and treatment of acute kidney injury (AKI), it still has high incidence and poor prognosis. The present study was performed in order to further understand the metabolomic changes of ischemia/reperfusion (I/R)-induced AKI and the protective effect of L-carnitine on AKI. Methods: Kidney tissues and serum samples were collected at different time points from three groups of rats including control group, I/R group and L-carnitine-pretreated group. High-performance liquid chromatography coupled with mass spectrometry-based metabolomics approach was applied to investigate the characteristic of I/R-induced AKI and the protective effects of L-carnitine in rat kidney I/R model. Antioxidant enzymatic activity and phospholipase A₂ activity were determined to validate the metabolic outcomes. Results: Changes in the pattern of endogenous metabolites as a result of kidney I/R injury were readily detected as early as 2 h after reperfusion, and earlier than the increase in blood urea nitrogen and serum creatinine. Twenty-eight differential endogenous metabolites were discovered and structurally identified by MSⁿ analysis. After I/R injury, lysophospholipids, free fatty acids and nitrotyrosine significantly increased, while carnitine and acetyl-carnitine significantly decreased compared to control. Phospholipase A₂ activity and malondialdehyde level also increased, while superoxide dismutase activity decreased in kidney I/R injury rats. Treatment of L-carnitine 30 min prior to reperfusion significantly relieved I/R-induced metabolomic changes. Conclusion: I/R-induced AKI could be characterized by oxidative stress and changes in lipid metabolism through metabolomic investigation, and L-carnitine treatment 30 min before reperfusion had protective effects against I/R-induced AKI.

Granulocyte colony-stimulating factor (GM-CSF), produced by CD4 + T cells, has recently been implicated in the pathogenesis of inflammatory diseases, such as multiple sclerosis and juvenile arthritis. However, the role of GM-CSF-producing CD4 + T cells in sepsis remains unknown. This study reports peripheral changes in GM-CSF-producing CD4 + T cells in septic patients and the possible underlying mechanism by which GM-CSF influences the outcome of sepsis. Forty-three septic patients, 20 SIRS patients, and 20 healthy controls were enrolled in this study and followed for 28 days to assess mortality. We measured the peripheral frequency of GM-CSF + CD4 + T cells and recorded their associated relationship with disease progression. Our data demonstrated that peripheral GM-CSF-producing CD4 + T cells were significantly higher in septic patients than in both SIRS patients and healthy controls. These cells exhibit a memory phenotype and impaired IFN-γ-secreting capacity in sepsis patients. Using a receiver operating curve analysis with 8.01% as a cutoff point, the percentage of GM-CSF + CD4 + T cells could predict the outcome of septic patients. Combined with the increase in GM-CSF-producing CD4 + T cells, inflammatory cytokines IL-1β and IL-6 were also upregulated. Using an in vitro neutrophil model, we found that GM-CSF inhibited C3aR expression, while inducing IL-8 production. Furthermore, this effect was transferrable in plasma from sepsis patients and was attenuated by inhibition of GM-CSF using an anti-GM-CSF antibody. These results indicate that GM-CSF-producing CD4 + T cells may serve as a marker of sepsis severity. Thus, targeting GM-CSF overproduction may benefit sepsis patients.

To describe the epidemiological and clinical characteristics of patients with Corona Virus Disease 2019 (COVID-19) in Beijing. To analyze the application of corticosteroids in patients with severe pneumonia. We collected information on demographic characteristics, exposure history, clinical characteristics, corticosteroids use, and outcomes of the 65 confirmed cases of COVID-19 at Fifth Medical Center of PLA General Hospital from Jan 20 to Feb 23, 2020. The final follow-up date observed was April 15th, 2020. The number of patients with mild, general, severe, and critical type were 10 (15.38%), 32 (49.23%), 8 (12.31%), and 15 (23.08%), respectively. The median incubation period was 6 days. Notable outliers were 1 patient at 16 days and 1 patient at 21 days. In lymphocyte subgroup analysis, decreases in total, T, CD4, and CD8 lymphocytes were more common as the disease worsened (All P < 0.05). Methylprednisolone (mPSL) was applied to 31 (47.69%) patients with pneumonia, including 10 (31.25%) general, 8 (100%) severe, and 13 (86.67%) critical patients, respectively. Corticosteroids inhibited Interleukin-6(IL-6) production (P = 0.0215) but did not affect T lymphocyte (P = 0.0796). There was no significant difference between patients using lower dose (≤ 2 mg/kg day) and higher dose (> 2 mg/kg day) mPSL in inhibiting IL-6 production (P = 0.5856). Thirty of 31 patients (96.77%) had stopped mPSL due to improvement of pneumonia. Virus RNA clearance time lengthened with disease progression (P = 0.0001). In general type, there was no significant difference in virus clearance time between patients with (15, 12-19 days) and without (14.5, 11-18 days) (P = 0.7372) mPSL use. Lymphocyte, especially T lymphocyte, in severe and critical patients showed a dramatic decrease. Application of lower dose corticosteroids (≤ 2 mg/kg day) could inhibit IL-6 production (a representative of cytokines) as effectively as a higher dose. Proper use corticosteroids in general type patients did not delay virus clearance. In December 2019, cases of acute respiratory disease (ARD), now known as a Corona Virus Disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China 1-3. Presently, the laboratory-confirmed cases and recorded deaths in the world are still increasing at an alarming rate 4-10. COVID-19 clinical types were defined according to the Diagnosis and Treatment of Pneumonia caused by Novel Coronavirus (Version 6 Trial) published on the website of the Central Government of the People's Republic of China 11. There are four distinct clinical types based on the severity of the disease. However, the differences in clinical characteristics, corticosteroids application, and outcomes among different clinical types have not been reported.