Postoperative neutrophil-to-lymphocyte ratio variation is associated with chronic subdural hematoma recurrence.

INTRODUCTION: Chronic subdural haematoma (CSDH) is one of the most common neurosurgical pathologies. The recurrence of chronic subdural haematomas is an important concern, considering that elderly patients are the most affected and reoperations in these patients may represent a risk of neurological and clinical complications. In accordance with the inflammatory theory regarding CSDH and its recurrence, we aimed to evaluate the role of an inflammatory marker, neutrophil-to-lymphocyte ratio (NLR), as a risk factor and prognostic variable for CSDH recurrence. METHODS: We performed a cohort study of adult patients operated for post-traumatic CSDH traumatic CSDH between January 2015 and December 2019 in our neurotrauma unit, whose data was retrospectively retrieved. We excluded patients with previous inflammatory or infectious diseases as well as use of anticoagulant/antiplatelet medications. Neutrophil and lymphocyte counts were obtained 24 h preoperatively and 48-72 h postoperatively. The primary endpoint was symptomatic recurrence of CSDH up to 1 year after the surgery. An independent sample was used to validate the findings. RESULTS: The testing sample comprised 160 patients (59.4% male, mean age 69.3 ± 14.3 years, recurrence rate 22.5%). Postoperative neutrophil count and NLR were higher in those who recurred, as well as the neutrophils (median 1.15 vs 0.96, p = 0.022) and NLR (median 1.29 vs 0.79, p = 0.001) postoperative-to-preoperative ratios. Preoperative laboratory parameters or other baseline variables were not associated with recurrence. Postoperative NLR ratio (each additional unit, OR 2.53, 95% CI 1.37-4.67, p = 0.003) was independently associated with recurrence. The best cut-off for the postoperative NLR ratio was 0.995 (AUC-ROC 0.67, sensitivity 63.9%, specificity 76.6%). Postoperative NLR ratio ≥ 1 (i.e. a post-operative NLR that does not decrease compared to the preoperative value) was associated with recurrence (OR 4.59, 95% CI 2.00-10.53, p < 0.001). The validation sample analysis (66 patients) yielded similar results (AUC-ROC 0.728, 95% CI 0.594-0.862, p = 0.002) and similar cut-off (≥ 1.05, sensitivity 77.8%, specificity 66.7%). CONCLUSION: NLR ratio can be a useful parameter for the prediction of post-traumatic CSDH recurrence. This hypothesis was validated in an independent sample and the accuracy was moderate.

The Brazilian octocoral Phyllogorgia dilatata as a source of cytotoxic compounds.

The extensive marine biodiversity has proved to be a promising source of substances with biomedical potential. In this study, the cytotoxicity of the Brazilian octocoral Phyllogorgia dilatata (Gorgoniidae) was evaluated against two tumor cell lines and three bacterial strains. The methanol/dichloromethane crude extract presented no antibacterial activity up to the highest concentration tested (512 µg/mL), however it revealed a noteworthy antiproliferative effect against HCT-116 (80%) and MCF-7 (54%) cell lines at 50 µg/mL. Therefore, guided by the cytotoxic activity, a multistep chemical fractionation of the extract provided the subfraction 5 (PDPH2-5) with IC50 values of 3.18 and 17.80 µg/mL against HCT-116 and MCF-7, respectively. The LC-HRMS/MS analysis of PDPH2-5 showed ions of m/z 219.1742 and 219.1743, characterized as (E,E) and (Z,E) germacrone, after a LC-DAD-SPE/NMR analysis of the hexanic fraction and comparisons of NMR data with the literature. Previously reported assessments to the cytotoxic activity of the (E,E)-diastereoisomer disclosed higher IC50 values than that obtained for the PDPH2-5 fraction, suggesting, herein, a potentiated effect of the diastereoisomeric mixture. Such remark encourage further bioactivity studies with stereoisomer mixtures and reduce the urge for compound isolation.

Integrated analytical workflow for chromatographic profiling and metabolite annotation of a cytotoxic Phorbas amaranthus extract.

Phorbas is a widely studied genus of marine sponge and produce structurally rich cytotoxic metabolites. Still, only few studies have assessed metabolites present in Brazilian species. To circumvent redundancy, in this work, we applied and herein report the use of a scouting liquid chromatographic system associate to the design of experiment produced by the DryLab® software to obtain a fast and efficient chromatographic separation of the active hexane fraction, further enabling untargeted high-resolution mass spectrometry (HRMS) data. To this end, a crude hydroalcoholic extract of the sponge Phorbas amaranthus collected in Brazilian coast was prepared and partitioned. The cytotoxicity of the crude extract and the fractions was evaluated using tumor cell culture models. Fragmentation pathways assembled from HRMS data allowed the annotation of 18 known Phorbas metabolites, while 17 metabolites were inferred based on Global Natural Product Social Molecular Networking (GNPS), matching with a further 29 metabolites annotated through molecular subnetwork. The workflow employed demonstrates that chromatographic method development can be accelerated by the use of automated scouting systems and DryLab®, which is useful for profiling natural product libraries, as well as data curation by molecular clusters and should be incorporated to the tools of natural product chemists.