Red blood cell transfusion in neurocritical patients: a systematic review and meta-analysis.

BACKGROUND: Anemia can lead to secondary brain damage by reducing arterial oxygen content and brain oxygen supply. Patients with acute brain injury have impaired self-regulation. Brain hypoxia may also occur even in mild anemia. Red blood cell (RBC) transfusion is associated with increased postoperative complications, poor neurological recovery, and mortality in critically ill neurologic patients. Balancing the risks of anemia and red blood cell transfusion-associated adverse effects is challenging in neurocritical settings. METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and MEDLINE (PubMed) from inception to January 31, 2024. We included all randomized controlled trials (RCTs) assessing liberal versus restrictive RBC transfusion strategies in neurocritical patients. We included all relevant studies published in English. The primary outcome was mortality at intensive care unit (ICU), discharge, and six months. RESULTS: Of 5195 records retrieved, 84 full-text articles were reviewed, and five eligible studies were included. There was no significant difference between the restrictive and liberal transfusion groups in ICU mortality (RR: 2.53, 95% CI: 0.53 to 12.13), in-hospital mortality (RR: 2.34, 95% CI: 0.50 to 11.00), mortality at six months (RR: 1.42, 95% CI: 0.42 to 4.78) and long-term mortality (RR: 1.22, 95% CI: 0.64 to 2.33). The occurrence of neurological adverse events and most major non-neurological complications was similar in the two groups. The incidence of deep venous thrombosis was lower in the restrictive strategy group (RR: 0.41, 95% CI: 0.18 to 0.91). CONCLUSIONS: Due to the small sample size of current studies, the evidence is insufficiently robust to confirm definitive conclusions for neurocritical patients. Therefore, further investigation is encouraged to define appropriate RBC transfusion thresholds in the neurocritical setting.

The upregulation of NLRP3 inflammasome in dorsal root ganglion by ten-eleven translocation methylcytosine dioxygenase 2 (TET2) contributed to diabetic neuropathic pain in mice.

BACKGROUND: The nucleotide oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) in dorsal root ganglion (DRG) contributes to pain hypersensitivity in multiple neuropathic pain models, but the function of the NLRP3 in diabetic neuropathic pain (DNP) and the regulation mechanism are still largely unknown. Epigenetic regulation plays a vital role in the controlling of gene expression. Ten-eleven translocation methylcytosine dioxygenase 2 (TET2) is a DNA demethylase that contributes to transcriptional activation. TET2 is also involved in high glucose (HG)-induced pathology. METHODS: DNP was induced in mice via the intraperitoneal injection of streptozotocin (STZ) for five consecutive days and the mechanical threshold was evaluated in STZ-diabetic mice by using von Frey hairs. The expression level of the NLRP3 pathway and TET2 in DRG were determined through molecular biology experiments. The regulation of the NLRP3 pathway by TET2 was examined in in vitro and in vivo conditions. RESULTS: In the present research, we first established the DNP model and found that NLRP3 pathway was activated in DRG. The treatment of NLRP3 inhibitor MCC950 alleviated the mechanical allodynia of DNP mice. Then we revealed that in STZ-diabetic mice DRG, the genomic DNA was demethylated, and the expression of DNA demethylase TET2 was increased evidently. Using RNA-sequencing analysis, we found that the expression of Txnip, a gene that encodes a thioredoxin-interacting protein (TXNIP) which mediates NLRP3 activation, was elevated in the DRG after STZ treatment. In addition, knocking down of TET2 expression in DRG using TET2-siRNA suppressed the mRNA expression of Txnip and subsequently inhibited the expression/activation of NLRP3 inflammasome in vitro and in vivo as well as relieved the pain sensitivity of DNP animals. CONCLUSION: The results suggested that the upregulation of the TXNIP/NLRP3 pathway by TET2 in DRG was involved in the pain hypersensitivity of the DNP model.

Effects of Lidocaine on Motor-Evoked Potentials and Somatosensory-Evoked Potentials in Patients Undergoing Intraspinal Tumour Resection: Study Protocol for a Prospective Randomized Controlled Trial.

PURPOSE: At present, it is believed that intravenous (IV) infusion of lidocaine can inhibit hyperalgesia, relieve postoperative acute and chronic pain, and accelerate the rehabilitation of patients. However, studies of its effects on necessary electrophysiological monitoring during neurosurgery are few, and the results are controversial. This study assumes that the propofol-remifentanil based anaesthesia combined with lidocaine in patients undergoing intraspinal tumour resection will not have adverse effects on motor-evoked potentials (MEPs) or somatosensory-evoked potentials (SEPs). STUDY DESIGN AND METHODS: This is a prospective, randomized, placebo-controlled double-blind trial. A total of 96 patients undergoing intraspinal tumour resection will be randomly allocated to lidocaine and placebo group. The lidocaine group will receive IV lidocaine during anaesthesia, while the placebo group will receive the same dose of normal saline with the same infusion rate and infusion time, and the anaesthesia procedures of the two groups will be the same. All patients will be monitored the MEPs and SEPs of all four limbs during operation. The primary outcome will be the MEP amplitudes of both upper limbs at the end of operation. The secondary outcome measures will be the other electrophysiological parameters at the end of operation, the incidence of alert events for all four limbs, and the incidence of false positive events. DISCUSSION: The purpose of this study is to evaluate the effects of IV infusion of lidocaine on SEPs and MEPs during intraspinal tumour resection to determine whether electrophysiological monitoring can accurately reflect the integrity of nerve functions while infusing lidocaine and to explore the possibility of lidocaine use during intraspinal tumour resection as an anaesthesia option.

Effect of tranexamic acid on the prognosis of patients with traumatic brain injury undergoing craniotomy: study protocol for a randomised controlled trial.

INTRODUCTION: Abnormal coagulation function aggravates the prognosis of patients with traumatic brain injury (TBI). It was reported that the antifibrinolytic drug tranexamic acid (TXA) could reduce intracranial haemorrhage and mortality in non-operative patients with TBI. However, there is a lack of evaluation of TXA in patients with TBI undergoing craniotomy. METHODS AND ANALYSIS: This is a single-centre randomised controlled, double-blind, parallel study aiming to investigate the effectiveness and safety of TXA in patients with TBI during the perioperative period. Blood loss and transfusion, neurological function, adverse events, mortality and serum immune-inflammatory cytokines will be collected and analysed. ETHICS AND DISSEMINATION: Ethical approval has been granted by the Medical Ethics Committee of Beijing Tian Tan Hospital, Capital Medical University (reference number KY 2020-136-03). The results of this study will be disseminated through presentations at scientific conferences and publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2100041911.

Whole Genomic DNA Methylation Profiling of CpG Sites in Promoter Regions of Dorsal Root Ganglion in Diabetic Neuropathic Pain Mice.

DNA methylation and demethylation play an important role in neuropathic pain. In general, DNA methylation of CpG sites in the promoter region impedes gene expression, whereas DNA demethylation contributes to gene expression. Here, we evaluated the methylation status of CpG sites in genomic DNA promoter regions in dorsal root ganglions (DRGs) of diabetic neuropathic pain (DNP) mice. In our research, streptozotocin (STZ) was intraperitoneally injected into mice to construct DNP models. The DNP mice showed higher fasting blood glucose (above 11.1 mmol/L), lower body weight, and mechanical allodynia than control mice. Whole-genome bisulfite sequencing (WGBS) revealed an altered methylation pattern in CpG sites in the DNA promoter regions in DRGs of DNP mice. The results showed 376 promoter regions with hypermethylated CpG sites and 336 promoter regions with hypomethylated CpG sites. In addition, our data indicated that altered DNA methylation occurs primarily on CpG sites in DNA promoter regions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially methylated CpG sites annotated genes were involved in activities of the nervous and sensory systems. Enrichment analysis indicated that genes in these pathways contributed to diabetes or pain. In conclusion, our study enriched the role of DNA methylation in DNP.