Objective: Coronavirus disease 2019 (COVID‐19) outbreak is a major challenge all over the world, without acknowledged treatment. Intravenous immunoglobulin (IVIG) has been recommended to treat critical coronavirus disease 2019 (COVID‐19) patients in a few reviews, but the clinical study evidence on its efficacy in COVID‐19 patients was lacking.Methods: 325 patients with laboratory‐confirmed critical COVID‐19 were enrolled from 4 government‐designated COVID‐19 treatment centres in southern China from December 2019 to March 2020. The primary outcomes were 28‐ and 60‐day mortality, and the secondary outcomes were the total length of in‐hospital and the total duration of the disease. Subgroup analysis was carried out according to clinical classification of COVID‐19, IVIG dosage and timing.Results: In the enrolled 325 patients, 174 cases used IVIG and 151 cases did not. The 28‐day mortality was improved with IVIG after adjusting confounding in overall cohort (P = 0.0014), and the in‐hospital and the total duration of disease were longer in the IVIG group (P < 0.001). Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28‐day mortality, decrease the inflammatory response and improve some organ functions (all P < 0.05); the application of IVIG in the early stage (admission ≤ 7 days) with a high dose (> 15 g per day) exhibited significant reduction in 60‐day mortality in the critical‐type patients.Conclusion: Early administration of IVIG with high dose improves the prognosis of critical‐type patients with COVID‐19. This study provides important information on clinical application of IVIG in the treatment of SARS‐CoV‐2 infection, including patient selection and administration dosage and timing.

Parthanatos is a new form of programmed cell death. It has been recognized to be critical in cerebral ischemia–reperfusion injury, and reactive oxygen species (ROS) can induce parthanatos. Recent studies found that propofol, a widely used intravenous anesthetic agent, has an inhibitory effect on ROS and has neuroprotective in many neurological diseases. However, the functional roles and mechanisms of propofol in parthanatos remain unclear. Here, we discovered that the ROS–ER–calcium–mitochondria signal pathway mediated parthanatos and the significance of propofol in parthanatos. Next, we found that ROS overproduction would cause endoplasmic reticulum (ER) calcium release, leading to mitochondria depolarization with the loss of mitochondrial membrane potential. Mitochondria depolarization caused mitochondria to release more ROS, which, in turn, contributed to parthanatos. Also, we found that propofol inhibited parthanatos through impeding ROS overproduction, calcium release from ER, and mitochondrial depolarization in parthanatos. Importantly, our results indicated that propofol protected cerebral ischemia–reperfusion via parthanatos suppression, amelioration of mitochondria, and ER swelling. Our findings provide new insights into the mechanisms of how ER and mitochondria contribute to parthanatos. Furthermore, our studies elucidated that propofol has a vital role in parthanatos prevention in vivo and in vitro, and propofol can be a promising therapeutic approach for nerve injury patients.

EGFR phosphorylation is required for TLR4-mediated macrophage activation during sepsis. However, whether and how intracellular EGFR is transported during endotoxemia have largely been unknown. Here, we show that LPS promotes high levels cell surface expression of EGFR in macrophages through two different transport mechanisms. On one hand, Rab10 is required for EEA1-mediated the membrane translocation of EGFR from the Golgi. On the other hand, EGFR phosphorylation prevents its endocytosis in a kinase activity-dependent manner. Erlotinib, an EGFR tyrosine kinase inhibitor, significantly reduced membrane EGFR expression in LPS-activated macrophage. Mechanistically, upon LPS induced TLR4/EGFR phosphorylation, MAPK14 phosphorylated Rab7a at S72 impaired membrane receptor late endocytosis, which maintains EGFR membrane localization though blocking its lysosomal degradation. Meanwhile, Rab5a is also involved in the early endocytosis of EGFR. Subsequently, inhibition of EGFR phosphorylation switches M1 phenotype to M2 phenotype and alleviates sepsis-induced acute lung injury. Mechanistic study demonstrated that Erlotinib suppressed glycolysis-dependent M1 polarization via PKM2/HIF-1ɑ pathway and promoted M2 polarization through up-regulating PPARγ induced glutamine metabolism. Collectively, our data elucidated a more in-depth mechanism of macrophages activation, and provided stronger evidence supporting EGFR as a potential therapeutic target for the treatment of sepsis.

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis. To provide clinical practice recommendations on the immune function in sepsis, an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed. Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed, Web of Science, and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire. Then, the Delphi method was used to form consensus opinions, and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions. This consensus achieved satisfactory results through two rounds of questionnaire survey, with 2 statements rated as perfect consistency, 13 as very good consistency, and 9 as good consistency. After summarizing the results, a total of 14 strong recommended opinions, 8 weak recommended opinions and 2 non-recommended opinions were produced. Finally, a face-to-face discussion of the consensus opinions was performed through an online meeting, and all judges unanimously agreed on the content of this consensus. In summary, this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Calpains are a family of cysteine proteases, implicated in a wide range of cellular calcium‑regulated functions. Evidence from previous studies using an inhibitor of calpain indicates that calpain activation is involved in the process of numerous inflammation‑associated diseases. As a result of in‑depth studies, calpains have been proposed to influence the process of inflammation via a variety of mechanisms. The aim of the present study is to provide an overview of recent reports regarding the role of calpain in the process of inflammation, including regulation of immune cell migration, modulation of the activation of inflammatory mediators, degradation of certain associated proteins and induction of cell apoptosis. Understanding these mechanisms may contribute to the investigation of novel therapeutic targets for inflammation‑associated diseases.

Introduction Catheter management strategies for suspected catheter-related bloodstream infection (CRBSI) remain a major challenge in intensive care units (ICUs). The objective of this study was to determine the incidence, risk factors, and mortality attributable to CRBSIs in those patients. Methods A population-based surveillance on suspected CRBSI was conducted from 2009 to 2018 in a tertiary care hospital in China. We used the results of catheter tip culture to identify patients with suspected CRBSIs. Demographics, systemic inflammatory response syndrome (SIRS) criteria, interventions, and microorganism culture results were analysed and compared between patients with and without confirmed CRBSIs. Univariate and multivariate analyses identified the risk factors for CRBSIs, and attributable mortality was evaluated with a time-varying Cox proportional hazard model. Results In total, 686 patients with 795 episodes of suspected CRBSIs were included; 19.2% (153/795) episodes were confirmed as CRBSIs, and 17.4% (119/686) patients died within 30 days. The multifactor model shows that CRBSIs were associated with fever, hypotension, acute respiratory distress syndrome, hyperglycaemia and the use of continuous renal replacement therapy. The AUC was 77.0% (95% CI 73.3%–80.7%). The population attributable mortality fraction of CRBSI in patients was 18.2%, and mortality rate did not differ significantly between patients with and without CRBSIs (95% CI 0.464–1.279, P = 0.312). Conclusions This initial model based on the SIRS criteria is relatively better at identifying patients with CRBSI but only in domains of the sensitivity. There were no significant differences in attributable mortality due to CRBSI and other causes in patients with suspected CRBSI, which prompt catheter removal and re-insertion of new catheter may not benefit patients with suspected CRBSIs. Trial Registration China Clinical Trials Registration number; ChiCTR1900022175.