Innate immunity serves as the rapid and first-line defense against invading pathogens, and this process can be regulated at various levels, including epigenetic mechanisms. The bromodomain and extraterminal domain (BET) family of proteins consists of four conserved mammalian members (BRD2, BRD3, BRD4, and BRDT) that regulate the expression of many immunity-associated genes and pathways. In particular, in response to infection and sterile inflammation, abnormally expressed or dysfunctional BETs are involved in the activation of pattern recognition receptor (e.g., TLR, NLR, and CGAS) pathways, thereby linking chromatin machinery to innate immunity under disease or pathological conditions. Mechanistically, the BET family controls the transcription of a wide range of proinflammatory and immunoregulatory genes by recognizing acetylated histones (mainly H3 and H4) and recruiting transcription factors (e.g., RELA) and transcription elongation complex (e.g., P-TEFb) to the chromatin, thereby promoting the phosphorylation of RNA polymerase II and subsequent transcription initiation and elongation. This review covers the accumulating data about the roles of the BET family in innate immunity, and discusses the attractive prospect of manipulating the BET family as a new treatment for disease.

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The BET family in immunity and disease

Background: Veno-arterial extracorporeal life support (VA-ECLS) is widely used to treat refractory cardiogenic shock. However, increased left ventricular (LV) afterload in VA-ECLS can worsen pulmon...

https://ahajournals.org/doi/pdf/10.1161/CIRCHEARTFAILURE.119.006486

Optimal Strategy and Timing of Left Ventricular Venting During Veno-Arterial Extracorporeal Life Support for Adults in Cardiogenic Shock: A Systematic Review and Meta-Analysis.

Strategies of left ventricular unloading during VA-ECMO support: a network meta-analysis

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a life-saving technology that provides transient respiratory and circulatory support for patients with profound cardiogenic shock or refractory cardiac arrest. Among its potential complications, VA-ECMO may adversely affect lung function through various pathophysiological mechanisms. The interaction of blood components with the biomaterials of the extracorporeal membrane elicits a systemic inflammatory response which may increase pulmonary vascular permeability and promote the sequestration of polymorphonuclear neutrophils within the lung parenchyma. Also, VA-ECMO increases the afterload of the left ventricle (LV) through reverse flow within the thoracic aorta, resulting in increased LV filling pressure and pulmonary congestion. Furthermore, VA-ECMO may result in long-standing pulmonary hypoxia, due to partial shunting of the pulmonary circulation and to reduced pulsatile blood flow within the bronchial circulation. Ultimately, these different abnormalities may result in a state of persisting lung inflammation and fibrotic changes with concomitant functional impairment, which may compromise weaning from VA-ECMO and could possibly result in long-term lung dysfunction. This review presents the mechanisms of lung damage and dysfunction under VA-ECMO and discusses potential strategies to prevent and treat such alterations.

/pdf/pulmonary-complications-associated-with-veno-arterial-extra-4do0casiol.pdf

Pulmonary complications associated with veno-arterial extra-corporeal membrane oxygenation: a comprehensive review

Acute kidney injury is a common complication in patients receiving extracorporeal membrane oxygenation (ECMO). The underlying mechanisms are multifactorial including the primary disease, effects of invasive mechanical ventilation, ECMO circuit-related factors and critical illness in general. Renal replacement therapy (RRT) is often required to control fluid balance and is associated with worse outcomes. No consensus exists for indication, timing, modality, and how to best to combine RRT and ECMO. This chapter provides an update of the epidemiology, outcomes and pathophysiology of acute kidney injury in patients receiving ECMO, highlights technical aspects when combining RRT with ECMO, and identifies future research questions.

/pdf/acute-kidney-injury-in-ecmo-patients-227foqgk7g.pdf

Acute kidney injury in ECMO patients.

An intra-aortic balloon pump (IABP) concomitant with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is frequently used to support patients with refractory cardiogenic shock (CS). Because of the lack of evidence of the adjunctive benefit, the goal of the study was to compare the effect of VA-ECMO plus IABP with that of VA-ECMO alone. Systematic searches were conducted to identify studies using PubMed, Embase, the Cochrane Library and the International Clinical Trials Registry Platform. Studies reporting on patients with adult CS treated with VA-ECMO plus IABP or VA-ECMO alone were identified and included. The primary outcome was in-hospital death. The secondary outcomes included neurological, gastrointestinal and limb-related complications. The study protocol was registered at PROSPERO (CRD42017069259). A total of 29 studies comprising 4576 patients were included. The pooled in-hospital deaths of patients on VA-ECMO were 1441/2285 (63.1%) compared with 1339/2291 (58.4%) for patients with adjunctive IABP. VA-ECMO plus IABP was associated with decreased in-hospital deaths [risk ratio (RR) 0.90; 95% confidence interval (CI) 0.85-0.95; P < 0.0001]. Moreover, IABP was related to decreased in-hospital deaths of patients with extracorporeal cardiopulmonary resuscitation, postcardiotomy CS and ischaemic heart disease (RR 0.78; 95% CI 0.64-0.95; P = 0.01; RR 0.91; 95% CI: 0.85-0.98; P = 0.008; RR 0.83; 95% CI 0.73-0.96, P = 0.009). Neurological, gastrointestinal and limb-related complications did not differ significantly between patients on ECMO with and without concurrent IABP. VA-ECMO plus IABP was associated with decreased in-hospital deaths in patients with CS.

Effect of an intra-aortic balloon pump with venoarterial extracorporeal membrane oxygenation on mortality of patients with cardiogenic shock: a systematic review and meta-analysis†.

A novel target to reduce microglial inflammation and neuronal damage after deep hypothermic circulatory arrest

https://www.jtcvs.org/article/S0022-5223(18)32495-4/pdf

Cold-inducible RNA-binding protein as a novel target to alleviate blood-brain barrier damage induced by cardiopulmonary bypass.

https://doi.org/10.1016/j.buildenv.2022.109184

Evaluating SARS‐CoV‐2 airborne quanta transmission and exposure risk in a mechanically ventilated multizone office building

Objective:The aim of this retrospective study was to review and report short-term and mid-term outcomes of pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension at our institut...

Shujie Yan

Papers

Effect of an intra-aortic balloon pump with venoarterial extracorporeal membrane oxygenation on mortality of patients with cardiogenic shock: a systematic review and meta-analysis†.

A novel target to reduce microglial inflammation and neuronal damage after deep hypothermic circulatory arrest

Cold-inducible RNA-binding protein as a novel target to alleviate blood-brain barrier damage induced by cardiopulmonary bypass.

Evaluating SARS‐CoV‐2 airborne quanta transmission and exposure risk in a mechanically ventilated multizone office building

Perfusion strategy and mid-term results of 58 consecutive pulmonary endarterectomy.