MicroRNAs as biomarkers in spontaneous intracerebral hemorrhage: A systematic review of recent clinical evidence.

OBJECTIVES: Spontaneous intracerebral hemorrhage (SICH) is a subtype of stroke associated with high mortality and devastating disabilities. Therefore, identifying non-invasive biomarkers for SICH would have a tremendous clinical impact. MicroRNAs (miRNAs) are non-coding single-stranded RNAs containing 21-23 nucleotides that control the activity of various protein-coding genes through post-transcriptional repression. In this systematic review, we report the recent clinical evidence on the role of miRNAs as biomarkers for the prediction, prognosis, early detection, and risk stratification of SICH. METHODS: We conducted a systematic search of PubMed, PubMed Central, MEDLINE, and Embase databases and included only full-text peer-reviewed articles published in English. RESULTS: We included 10 studies comprising seven case-control studies, two cohort studies, and one cross-sectional study, among which we found 27 altered miRNAs, suggesting their role as biomarkers for the early detection of ICH. Additionally, the expression of 34 miRNAs was associated with poor prognosis of ICH; miR-126 and miR-23a-3p expression correlated with relative perihematomal edema (PHE) volume, and using a subset of 10 miRNA signatures had an accuracy of 100% in predicting hematoma in patients with ICH. Moreover, miR-4317 and miR-4325 profiling predicted the development of late seizures. Thirty-nine miRNAs were associated with the incidence of all types of strokes, while 10 miRNAs correlated with the predicted risk of stroke but were not specific to a stroke subtype. The altered miRNA signatures contributed to endothelial dysfunction, hematoma, and PHE through leukocyte activation, oxidative stress response, programmed cell death, smooth muscle cell proliferation, and apoptosis of cerebrovascular endothelial cells. The current data had limitations and gaps, especially the human studies, and there may have been selection bias in the prospective studies. There were also some limitations regarding the methods for obtaining miRNAs and identifying target RNAs specific to SICH pathology. Additionally, there may have been correlations between the outcomes and other factors, such as therapeutic interventions and ICH severity, the circulating miRNA profiles and gene expression profiles, and other pathological conditions and patients' age. Finally, the prediction and risk stratification of SICH could not be calculated separately from ischemic stroke. CONCLUSIONS: Following our literature retrieval, we noted alterations in various miRNA signatures, suggesting their potential role as biomarkers for the early detection and differentiation of SICH. Indeed, miRNA expression was associated with a poor prognosis of SICH and correlated with the predicted risk of stroke but was not specific to a stroke subtype. Further studies are needed, especially on the therapeutic potential of miRNAs and their target RNAs in SICH.

Control of Hemodynamic Responses and Perioperative Outcomes in Transsphenoidal Pituitary Surgery: A Qualitative Systematic Review of the Available Evidence.

Transnasal transsphenoidal (TNTS) pituitary surgery is associated with short-lived but intense nociceptive stimuli which cause substantial hemodynamic perturbations that may increase blood loss and impair visualization of the surgical field. This systematic review aimed to critically appraise the clinical evidence for the efficacy and safety of various anesthetic techniques, other pharmacological modalities, and supplementary interventions by assessing intraoperative systemic hemodynamics, use of adjunct medications, quality of the surgical field, intraoperative blood loss, and recovery profiles in patients undergoing TNTS pituitary surgery. Relevant randomized clinical trials and observational studies were identified in a systematic literature search; 16 studies (13 randomized clinical trials, 3 observational studies) enrolling a total of 907 patients were identified for inclusion in this review. Propofol provided more potent hemodynamic control compared with volatile anesthetics with a sparing effect on the need for additional drugs to blunt hemodynamic responses. Recovery profiles between propofol and sevoflurane were either equivalent or favored sevoflurane, but both agents were superior to isoflurane. Regarding intraoperative analgesia, remifentanil was associated with superior hemodynamic control and recovery profiles than fentanyl. Dexmedetomidine had beneficial effects on hemodynamics, surgical field quality, recovery characteristics, and nociceptive properties compared with placebo. Although there was no clear-cut superiority of other adjunct pharmacological modalities on hemodynamic responses during surgery, regional blocks were associated with beneficial impacts on both primary and secondary outcomes. In summary, short-acting anesthetics, analgesics and dexmedetomidine seem to improve intraoperative hemodynamics, blood loss, and recovery qualities during TNTS pituitary surgery. However, definitive conclusions cannot be drawn because of methodological heterogeneity in the identified studies.

Cerebral Perfusion and Brain Oxygen Saturation Monitoring with: Jugular Venous Oxygen Saturation, Cerebral Oximetry, and Transcranial Doppler Ultrasonography.

Accumulating evidence indicates that cerebral desaturation in the perioperative period occurs more frequently than recognized. Combining monitoring modalities that reflect different aspects of cerebral perfusion status, such as near-infrared spectroscopy, jugular bulb saturation, and transcranial Doppler ultrasonography, may provide an extended window for prevention, early detection, and prompt intervention in ongoing hypoxic/ischemic neuronal injury and, thereby, improve neurologic outcome. Such an approach would minimize the impact of limitations of each monitoring modality, while individual components complement each other, enhancing the accuracy of acquired information. Current literature has failed to demonstrate any clear-cut clinical benefit of these modalities on outcome prognosis.