Risk factors for postoperative myocardial injury-related cardiogenic shock in patients undergoing cardiac surgery.

BACKGROUND: Myocardial injury-related cardiogenic shock (MICS) is significantly associated with poor outcomes in patients after cardiac surgery. Herein, we aimed to investigate the risk factor for postoperative MICS. METHODS: We performed a case-control study on 792 patients undergoing cardiac surgery from 2016 to 2019, including 172 patients with postoperative MICS and 620 age- and sex-matched controls. MICS was defined as composite criteria: a cardiac index of < 2.2 L/m2/min, arterial lactate levels of > 5 mmol/L at the end of the surgery, a vasoactive-inotropic score of > 40 at the end of the surgery, and a cardiac troponin T (cTnT) level of > 0.8 µg/L on postoperative day 1 (POD1) with an increase of > 10% on POD 2. RESULTS: A total of 4671 patients who underwent cardiac surgery in our hospital between 2016 and 2019 were included; of these, 172 (3.68%) had MICS and the remaining 4499 did not. For investigating the risk factors, we selected 620 age- and sex-matched controls. In the univariate analysis, MICS was significantly associated with death (P < 0.05), extracorporeal membrane oxygenation (P < 0.05), continuous renal replacement therapy (P < 0.01), and ventricular arrhythmias (P < 0.05). Multivariable logistic regression analysis revealed that diabetes mellitus (OR:8.11, 95% CI: 3.52-18.66, P < 0.05) and a cardiopulmonary bypass (CPB) time of > 2 h (OR: 3.16, 95% CI: 1.94-5.15, P < 0.05) were associated with postoperative MICS. Moreover, long-time administration of preoperative calcium channel blocker (CCB) was associated with a less incidence of MICS (OR: 0.11, 95% CI: 0.05-0.27, P < 0.05). CONCLUSIONS: Postoperative MICS is significantly associated with poor outcomes. Diabetes mellitus and long CPB time are associated with MICS. Preoperative CCB administration is associated with less incidence of MICS.

Corrigendum: The neutrophil elastase inhibitor, Sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass.

[This corrects the article DOI: 10.3389/fimmu.2023.1082830.].

The low-dose colchicine in patients after non-CABG cardiac surgery: a randomized controlled trial.

BACKGROUND: Recent high-quality trials have shown that the anti-inflammatory effects of colchicine reduce the risk of cardiovascular events in patients suffering post-myocardial infarction and chronic coronary disease. The effect of colchicine in patients undergoing non-coronary artery bypass grafting (non-CABG) with cardiopulmonary bypass remains unclear. We aim to evaluate the effect of colchicine on myocardial protection in patients who underwent non-CABG cardiac surgery. METHOD: Patients were randomly assigned to colchicine or placebo groups starting 72 h before scheduled cardiac surgery and for 5 days thereafter (0.5 mg daily).The primary outcome was the level of cardiac troponin T (cTnT) at postoperative 48 h. The secondary outcomes included troponin I (cTnI) and creatine kinase-MB (CK-MB), inflammatory biomarkers (procalcitonin and interleukin-6, etc.), and adverse events (30-day mortality, stroke, ECMO and IABP use, etc.). RESULTS: A total of 132 patients underwent non-CAGB cardiac surgery, 11were excluded because of diarrhea (n = 6) and long aortic cross-clamp time > 2 h (n = 5), 59 were assigned to the colchicine group and 62 to the placebo group. Compared with the placebo group, cTnT (median: 0.3 µg/L, IQR 0.2-0.4 µg/L vs. median: 0.4 µg/L, IQR 0.3-0.6 µg/L, P < 0.01), cardiac troponin I (median: 0.9 ng/ml, IQR 0.4-1.7 ng/ml vs. median: 1.3 ng/ml, IQR 0.6-2.3 ng/ml, P = 0.02), CK-MB (median: 1.9 ng/ml, IQR 0.7-3.2 ng/ml vs. median: 4.4 ng/ml, IQR 1.5-8.2 ng/ml, P < 0.01), and interleukin-6 (median: 73.5 pg/ml, IQR 49.6-125.8 pg/ml vs. median: 101 pg/ml, IQR 57.5-164.7 pg/ml, P = 0.048) were significantly reduced in colchicine group at postoperative 48 h. For safety evaluation, the colchicine (n = 65) significantly decreased post-pericardiotomy syndrome (3.08% vs. 17.7%, P < 0.01) and increased the rate of diarrhea (9.23% vs. 0, P = 0.01) compared with the placebo group (n = 62). No significant difference was observed in other adverse events between the two groups. CONCLUSION: A short perioperative course of low-dose colchicine was effective to attenuate the postoperative biomarkers of myocardial injury and inflammation, and to decrease the postoperative syndrome compared with the placebo. Trial registration ChiCTR2000040129. Registered 22nd Nov. 2020. This trial was registered before the first participant was enrolled. http://www.chictr.org.cn/showproj.aspx?proj=64370 .

The neutrophil elastase inhibitor, sivelestat, attenuates acute lung injury in patients with cardiopulmonary bypass.

Background: The sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery. Methods: Firstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc. Results: In propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P<0.01), bilateral pulmonary infiltrates (P<0.01), oxygen index (P<0.01), interleukin-6(P=0.02), procalcitonin(P<0.01) and C-reactive protein(P<0.01). Conclusion: Administration of sivelestat might improve postoperative outcomes in patients with ALI after emergent cardiovascular surgery. Our results show that sivelestat may be considered to protect pulmonary function against inflammatory injury by CPB. Registration: http://www.chictr.org.cn/showproj.aspx?proj=166643, identifier ChiCTR2200059102.

Expression and purification of a recombinant ELRL-MAP30 with dual-targeting anti-tumor bioactivity.

MAP30 (Momordica antiviral protein 30kD) is a single-chain Ⅰ-type ribosome inactivating protein with a variety of biological activities, including anti-tumor ability. It was reported that MAP30 would serve as a novel and relatively safe agent for prophylaxis and treatment of liver cancer. To determine whether adding two tumor targeting peptides could improve the antitumor activities of MAP30, we genetically modified MAP30 with an RGD motif and a EGFRi motif, which is a ligand with high affinity for αvß3 integrins and with high affinity for EGFR. The recombinant protein ELRL-MAP30 (rELRL-MAP30) containing a GST-tag was expressed in E. coli. The rELRL-MAP30 was highly expressed in the soluble fraction after induction with 0.15 mM IPTG for 20 h at 16 °C. The purified rELRL-MAP30 appeared as a band on SDS-PAGE. It was identified by western blotting. Cytotoxicity of recombinant protein to HepG2, MDA-MB-231, HUVEC and MCF-7 cells was detected by MTT analysis. Half maximal inhibitory concentration (IC50) values were 54.64 µg/mL, 70.13 µg/mL, 146 µg/mL, 466.4 µg/mL, respectively. Proliferation inhibition assays indicated that rELRL-MAP30 could inhibit the growth of Human liver cancer cell HepG2 effectively. We found that rELRL-MAP30 significantly induced apoptosis in liver cancer cells, as evidenced by nuclear staining of DAPI. In addition, rELRL-MAP30 induced apoptosis in human liver cancer HepG2 cells by up-regulation of Bax as well as down-regulation of Bcl-2. Migration of cell line were markedly inhibited by rELRL-MAP30 in a dose-dependent manner compared to the recombinant MAP30 (rMAP30). In summary, the fusion protein displaying extremely potent cytotoxicity might be highly effective for tumor therapy.