Exploring the molecular mechanism of sepsis-associated encephalopathy by integrated analysis of multiple datasets.

BACKGROUND: We aim to deal with the Hub-genes and signalling pathways connected with Sepsis-associated encephalopathy (SAE). METHODS: The raw datasets were acquired from the Gene Expression Omnibus (GEO) database (GSE198861 and GSE167610). R software filtered the differentially expressed genes (DEGs) for hub genes exploited for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Hub genes were identified from the intersection of DEGs via protein-protein interaction (PPI) network. And the single-cell dataset (GSE101901) was used to authenticate where the hub genes express in hippocampus cells. Cell-cell interaction analysis and Gene Set Variation Analysis (GSVA) analysis of the whole transcriptome validated the interactions between hippocampal cells. RESULTS: A total of 161 DEGs were revealed in GSE198861 and GSE167610 datasets. Biological function analysis showed that the DEGs were primarily involved in the phagosome pathway and significantly enriched. The PPI network extracted 10 Hub genes. The M2 Macrophage cell decreased significantly during the acute period, and the hub gene may play a role in this biological process. The hippocampal variation pathway was associated with the MAPK signaling pathway. CONCLUSION: Hub genes (Pecam1, Cdh5, Fcgr, C1qa, Vwf, Vegfa, C1qb, C1qc, Fcgr4 and Fcgr2b) may paticipate in the biological process of SAE.

Application background and mechanism of short-chain fatty acids in sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) is a frequent brain dysfunction found in sepsis patients, manifesting as delirium, cognitive impairment, and abnormal behaviors. The gut microbiome and short-chain fatty acids (SCFAs) are particularly associated with neuroinflammation in patients with SAE, thus noticeably attracting scholars' attention. The association of brain function with the gut-microbiota-brain axis was frequently reported. Although the occurrence, development, and therapeutic strategies of SAE have been extensively studied, SAE remains a critical factor in determining the long-term prognosis of sepsis and is typically associated with high mortality. This review concentrated on the interaction of SCFAs with microglia in the central nervous system and discussed the anti-inflammatory and immunomodulatory effects of SCFAs by binding to free fatty acid receptors or acting as histone deacetylase inhibitors. Finally, the prospects of dietary intervention using SCFAs as dietary nutrients in improving the prognosis of SAE were reviewed.

Review of Neurofilaments as Biomarkers in Sepsis-Associated Encephalopathy.

Sepsis is a common and fatal disease, especially in critically ill patients. Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction with acute altered consciousness, permanent cognitive impairment, and even coma, accompanied by sepsis, without direct central nervous system infection. When managing SAE, early identification and quantification of axonal damage facilitate faster and more accurate diagnosis and prognosis. Although no specific markers for SAE have been identified, several biomarkers have been proposed. Neurofilament light chain (NFL) is a highly expressed cytoskeletal component of neurofilament (NF) proteins that can be found in blood and cerebrospinal fluid (CSF) after exposure to axonal injury. NFs can be used as diagnostic and prognostic biomarkers for sepsis-related brain injury. Phosphorylation of NFs contributes to the maturation and stabilization of cytoskeletal structures, especially axons, and facilitates axonal transport, including mitochondrial transport and energy transport. The stability of NF proteins can be assessed by monitoring the expression of NF genes. Furthermore, phosphorylation levels of NFs can be monitored to determine mitochondrial axonal transport associated with cellular energy metabolism at distal axons to assess progression during SAE treatment. This paper provides new insights into the biological characteristics, detection techniques, and scientific achievements of NFs, and discusses the underlying mechanisms and future research directions of NFs in SAE.

Bronchial blocker versus double-lumen endobronchial tube in minimally invasive cardiac surgery.

BACKGROUND: To compare the therapeutic value of a bronchial blocker (BB) with a double-lumen tube (DLT) in minimally invasive cardiac surgery (MICS). METHODS: Sixty patients who underwent MICS were randomized to use either a DLT (Group D, n = 30) or a BB (Group B, n = 29; one failed was omitted). The following data were collected: time of intubation and tube localization; incidence of tube displacement; postoperative sore throat and hoarseness; time of cardiopulmonary bypass; maintenance time for SpO2 < 90% (PaCO2 < 60 mmHg); mean arterial pressure and heart rate; SpO2, PaO2, PaCO2, EtCO2, mean airway pressure, and airway peak pressure; surgeons' satisfaction with anesthesia; and short-term complications. RESULTS: The times of intubation and tube localization were significantly longer in Group B than in Group D (P < 0.05). Patients in Group B exhibited significantly lower incidence of tube displacement, postoperative sore throat, and hoarseness when compared with patients in Group D (P < 0.05). Mean arterial pressure and heart rate were significantly lower in Group B than in Group D after tracheal intubation (P < 0.05). The mean airway pressure and airway peak pressure were significantly lower in Group B than in Group D after one-lung ventilation (P < 0.05). SpO2 and PaO2 in Group B were significantly higher than in group D after cardiopulmonary bypass (P < 0.05). No short-term postoperative complications were observed in patients of Groups B and D during 3 month follow-up. CONCLUSION: BB can be a potential alternative to the conventional DLT for lung isolation in MICS. TRIAL REGISTRATION: ChiCTR1900024250, July 2, 2019.

Current understanding and future directions in the application of TIMP-2 and IGFBP7 in AKI clinical practice.

NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

International Survey on the Management of Acute Kidney Injury and Continuous Renal Replacement Therapies: Year 2018.

INTRODUCTION: Definition, prevention, and management of acute kidney injury (AKI) and the optimal prescription and delivery of renal replacement therapy (RRT) are currently matters of ongoing discussion. Due to the lack of definitive published literature, a wide gap might exist between routine clinical practice and available recommendations. The aim of this survey was to explore the clinical approach to AKI and RRT in a broad population of nephrologists and intensivists participating in the 36th International course on AKI and Continuous RRT (CRRT), held in Vicenza in June 2018. The responses of the 369 participants to a questionnaire on several aspects of critical care nephrology were analyzed and detailed. RESULTS: Approximately 450 participants attended the course; of these, 369 (82%) correctly filled the survey forms. According to the reported answers, the average incidence of AKI in respondents' intensive care units (ICU) was 26.8% (SD ±15.99) and AKI requiring dialysis was 13% (SD ±29.7). Sixty-four percent of participants defined AKI as an increase in serum creatinine (SCr) up to 0.99 mg/dL (SD ±0.88 mg/dL); 2.4% defined AKI as an increase in urea nitrogen up to 83.6 mg/dL (SD ±36.6 mg/dL); 33.6% defined AKI as decreased urine output to less than 1 mL/kg/h (SD ±0.6 mL/kg/h). The most common answer to classify AKI was Kidney Disease: Improving Global Outcomes (KDIGO; 41%) criteria. Most of the participants (25%) think novel biomarkers should replace SCr on daily routine laboratory screening, and Cystatin C was the most commonly used biomarker (19%). The use of diuretics in AKI patients was high (62%). Continuous RRT (59%) and heparin anticoagulation (42%) appeared to be the most common approaches in ICU. CONCLUSIONS: KDIGO appeared to be widely applied. The use of novel biomarkers has also emerged in recent years even if some consistent cost-benefit evidence is still lacking. There is a trend of increased awareness about AKI and extracorporeal treatments seem to be increasingly applied, when compared to previous surveys. Educational efforts and AKI management standardization still appear to be a fundamental aspect to harmonize therapeutic approaches and improve patients' outcomes.

A New Series of Sorbent Devices for Multiple Clinical Purposes: Current Evidence and Future Directions.

Adsorption is an extracorporeal technique utilized for blood purification. It complements convection and diffusion (the main modalities of solute removal). It involves the passage of blood (or plasma) through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Over the years, new adsorption cartridges, with improved characteristics have been developed. Furthermore, the therapeutic applications of adsorption have expanded. These now involve the treatment of inflammatory conditions, chronic uremic symptoms, and autoimmune disease, in addition to intoxication, which was once considered the classical indication for adsorption therapy. HA130, HA230, and HA330 (Jafron, Zhuhai City, China) are among the widely used adsorption cartridges in China. There has been sufficient body of evidence to support their effectiveness and safety. In this review, we aim to highlight their main clinical applications.