Association Between Prior Antiplatelet Therapy and Prognosis in Patients With Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis.

PURPOSE: Approximately 20% to 30% of intracerebral hemorrhage (ICH) patients were reported to be on antiplatelet therapy (APT), and association between prior APT and prognosis was unclear. We aimed to clarify the impact of APT on the prognosis of ICH through an updated systematic review and meta-analysis, and to further compare the risk of single APT (SAPT) or dual APT (DAPT) prior to ICH as well as the risk associated with various antiplatelet drugs. METHODS: EMBASE, MEDLINE via Ovid SP and Web of Science were searched from inception of each database to November 4, 2023. Included studies reported prognosis in both patients with prior APT and those without. FINDINGS: A total of 433,103 patients from 43 studies were included in the meta-analysis. Both univariate and multivariate analyses demonstrated a significant association between prior-APT and an increased mortality risk (odd ratio [OR] 1.43, 95% confidence interval [CI] 1.28-1.59; OR 1.20, 95%CI 1.10-1.30, respectively). The risk was higher in short term follow-up (Univariate OR 1.73, 95%CI 1.22-2.46; Multivariate OR 1.94, 95%CI 1.48-2.55). A notably increased risk of hematoma expansion was also observed in patients previously treated with APT (Univariate OR 1.47, 95%CI 1.12-1.94; Multivariate OR 1.88, 95%CI 1.30-2.71), which were mainly attributed to events within 24 hours. The impact of prior-APT on poor functional outcome was inconsistent between univariate and multivariate analyses. Both direct and indirect comparisons showed that SAPT significantly reduced the risk of mortality (OR 0.67, 95%CI 0.64-0.70; OR 0.84, 95%CI 0.71-0.99) and poor functional outcome (OR 0.84, 95%CI 0.72-0.98; OR 0.81, 95%CI 0.72-0.91) compared to DAPT. IMPLICATIONS: Prior-APT increased the risk of mortality and hematoma expansion in patients with ICH. The increased risk of mortality and hematoma expansion was more obvious in the short term follow-up and within 24 hours, respectively. The effect of APT on poor functional outcome exhibited inconsistency between univariate and multivariate analyses, suggesting that further investigation is warranted to clarify this relationship. In comparison with DAPT, SAPT could decrease the risk of mortality and poor functional outcome. Further studies focusing on antiplatelet drug response, racial differences, and specific APT regimens may help verify the influence.

Age-adjusted D-Dimer Thresholds Combined with the Modified Wells Score as a Predictor of Lower Extremity Deep Venous Thrombosis.

BACKGROUND: Neurosurgical patients are at an increased risk of deep venous thrombosis (DVT), which, if not properly managed, can lead to pulmonary embolism. This study aimed to investigate the accuracy of age-adjusted D-dimer thresholds combined with the modified Wells score as a predictor for lower extremity DVT diagnosis. METHODS: We conducted a study among patients aged >50 years with suspected lower extremity DVT in the neurosurgery intensive care unit between December 2019 and December 2020. Receiver operating characteristic curve analysis was performed to examine the diagnostic capacity of age-adjusted D-dimer combined with the modified Wells score. RESULTS: A total of 233 participants, with an average age of 71.81 ± 12.59 years, were enrolled in the study. The mean D-dimer levels were 0.73 ± 0.39 mg/L. Among the participants, 57 (57.9%, 33 males) were diagnosed with DVT. The age-adjusted D-dimer combined with the modified Wells score had the highest area under the curve for diagnosing lower extremity DVT compared to D-dimer and age-adjusted D-dimer alone, with an AUC of 0.858. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the age-adjusted D-dimer combined with the modified Wells score for DVT diagnosis were 78.95%, 80.68%, 57%, 92.2%, and 80.26%, respectively. When analyzing subgroups, the accuracy was 79.55% for participants with cerebral hemorrhage, 81.69% for those with craniocerebral injury, 74.99% for participants with intracranial infection, and 88.89% for those with craniocerebral tumor. CONCLUSION: The combination of the age-adjusted D-dimer thresholds with the modified Wells score might effectively predict lower extremity DVT.

Craniocervical Manual Lymphatic Drainage Increases the Efficiency of Atorvastatin-Based Treatment of Chronic Subdural Hematoma.

The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.

Possible mechanism and Atorvastatin-based treatment in cupping therapy-related subdural hematoma: A case report and literature review.

Subdural hematoma (SDH) is one of the most lethal types of traumatic brain injury. SDH caused by Intracranial Pressure Reduction (ICPR) is rare, and the mechanism remains unclear. Here, we report three cases of SDH that occurred after substandard cupping therapy and are conjected to be associated with ICPR. All of them had undergone cupping treatments. On the last cupping procedure, they experienced a severe headache after the cup placed on the occipital-neck junction (ONJ) was suddenly removed and were diagnosed with SDH the next day. In standard cupping therapy, the cups are not usually placed on the ONJ. We speculate that removing these cups on the soft tissue over the cisterna magna repeatedly created localized negative pressure, caused temporary but repeated ICPR, and eventually led to SDH development. The Monro-Kellie Doctrine can explain the mechanism behind this - it states that the intracranial pressure is regulated by a fixed system, with any change in one component causing a compensatory change in the other. The repeated ICPR promoted brain displacement, tearing of the bridging veins, and development of SDH. The literature was reviewed to illustrate the common etiologies and therapies of secondary ICPR-associated SDH. Despite the popularity of cupping therapy, its side effects are rarely mentioned. This case is reported to remind professional technicians to fully assess a patient's condition before cupping therapy and ensure that the cups are not placed at the ONJ.

Establishment and validation of a prediction model for self-absorption probability of chronic subdural hematoma.

Background: Chronic subdural hematoma (CSDH) is common in elderly people with a clear or occult traumatic brain injury history. Surgery is a traditional method to remove the hematomas, but it carries a significant risk of recurrence and poor outcomes. Non-surgical treatment has been recently considered effective and safe for some patients with CSDH. However, it is a challenge to speculate which part of patients could obtain benefits from non-surgical treatment. Objective: To establish and validate a new prediction model of self-absorption probability with chronic subdural hematoma. Method: The prediction model was established based on the data from a randomized clinical trial, which enrolled 196 patients with CSDH from February 2014 to November 2015. The following subjects were extracted: demographic characteristics, medical history, hematoma characters in imaging at admission, and clinical assessments. The outcome was self-absorption at the 8th week after admission. A least absolute shrinkage and selection operator (LASSO) regression model was implemented for data dimensionality reduction and feature selection. Multivariable logistic regression was adopted to establish the model, while the experimental results were presented by nomogram. Discrimination, calibration, and clinical usefulness were used to evaluate the performance of the nomogram. A total of 60 consecutive patients were involved in the external validation, which enrolled in a proof-of-concept clinical trial from July 2014 to December 2018. Results: Diabetes mellitus history, hematoma volume at admission, presence of basal ganglia suppression, presence of septate hematoma, and usage of atorvastatin were the strongest predictors of self-absorption. The model had good discrimination [area under the curve (AUC), 0.713 (95% CI, 0.637-0.788)] and good calibration (p = 0.986). The nomogram in the validation cohort still had good discrimination [AUC, 0.709 (95% CI, 0.574-0.844)] and good calibration (p = 0.441). A decision curve analysis proved that the nomogram was clinically effective. Conclusions: This prediction model can be used to obtain self-absorption probability in patients with CSDH, assisting in guiding the choice of therapy, whether they undergo non-surgical treatment or surgery.

MicroRNA alteration in cerebrospinal fluid from comatose patients with traumatic brain injury after right median nerve stimulation.

Electrical stimulation of the right median nerve can aid coma arousal after traumatic brain injury (TBI). This study aimed to confirm the efficacy further and explore possible mechanisms of right median nerve electrical stimulation (RMNS). Five comatose patients after severe TBI from May to September 2020 in the Tianjin Medical University General Hospital received RMNS for 2 weeks besides standard management. After the 2-week treatment, the mean Glasgow Coma Scale (GCS) and neurophysiological examination were used. We then investigated the alterations in microRNA (miRNA) expression in cerebrospinal fluid (CSF) by high-throughput whole transcriptome sequencing, analyzed the data by Gene Ontology (GO) and pathway analysis, and constructed the miRNA-target gene network. Patient awareness and brain function showed a more rapid increase after treatment. We also found 38 differently expressed miRNAs, 34 of which were upregulated and 4 downregulated. GO analysis showed a relation of these differentially expressed miRNAs with neuronal growth, repair, and neural signal transmission. The most highly correlated pathways were primarily associated with the tumor necrosis factor (TNF) signaling pathway and dopaminergic synapse. The application of RMNS effectively promoted early awakening in comatose patients with severe TBI. Moreover, differentially expressed miRNAs might reduce neuronal apoptosis and increase dopamine levels by regulating target gene expression, thus participating in the specific biological process after arousal therapy. Our study provided novel targets for further research on the molecular mechanisms of RMNS arousal treatment and a new way to treat neurotraumatic diseases.

Mouse nerve growth factor promotes neurological recovery in patients with acute intracerebral hemorrhage: A proof-of-concept study.

BACKGROUND: ew drugs were confirmed to be effective in the treatments of neurological dysfunction caused by acute intracerebral hemorrhage (ICH). The present prospective clinical trial aims to evaluate the effect of mouse nerve growth factor (mNGF) on neurological function in patients with acute ICH. METHODS: 60 patients with acute spontaneous ICH were randomized to receive mNGF (mNGF group) and citicoline (control group) for 4 weeks within 24-72 h after onset, respectively. The primary outcome was difference in the neurological functional outcome at 3 months by the modified Rankin Scale score (mRS). The secondary outcomes were the changes in hematoma volume at 4 weeks and 3 months. RESULTS: There were 55 patients receiving treatment (29 patients in the mNGF group, 26 patients in the control group). Among the patients, 46 patients finished the trial at 3 months; the odds of a shift towards death or dependence (mRS > 3) at 3 months in the mNGF group were lower than that in the control group with adjustment for age, sex, NIHSS at admission, and hematoma volume at admission (adjusted OR, 0.185; 95%CI, 0.059-0.582; P = 0.0039). The hematoma was gradually reduced in all 46 patients and absorbed after non-surgical treatment at 3 months. There was no significant difference in hematoma volume between the two groups. No serious adverse event was found. CONCLUSIONS: The administration of mNGF and citicoline was well-tolerated in patients with acute ICH. mNGF was associated with improved neurological function and less disability in patients with ICH. Therefore, the quality of life of patients with ICH may be improved by mNGF. TRIAL REGISTRATION: The trial is registered with the Chinese Clinical Trial Registry, number ChiCTR1800020258.

Analysis of the association of fluid balance and short-term outcome in traumatic brain injury.

INTRODUCTION: A balance of fluid intake and output (fluid balance) influences outcomes of critical illness, but the level of such influence remains poorly understood for traumatic brain injury (TBI) and was quantitatively examined in this study. METHODS: We conducted a retrospective cohort study of 351 moderate and severe TBI patients to associate the degree of fluid balance with clinical outcomes of TBI. Fluid balance and intracranial pressure (ICP) were continuously recorded for 7days on patients admitted to neurocritical care unit (NCCU). The short-term outcome was dichotomized into improvement and deterioration groups based on changes in Glasgow Coma Scale (GCS) measured between admission and 30days after admission. Fluid balance was calculated as: Fluid intake (mL) - fluid outputs (mL)/day×5 and used to group patients in tertiles to study its effect on TBI outcome. RESULTS: Patients at the low (<637mL) and upper (>3673mL) tertiles of fluid balance were associated with poor outcomes. Those in the upper tertile also had a higher incidence of acute kidney injury (AKI) and refractory intracranial hypertension (RIH). There was a negative correlation between the cumulative fluid balance and the short-term outcome for patients in the low tertile and a positive correlation between the cumulative fluid balance and the short-term outcome in the upper fluid balance group. Levels of fluid balance were also associated with serum creatinine (Cr, r=0.451, P<0.0001) and days in NCCU (r=0.188, P=0.001). More patients in the upper tertile had ICP higher than 20mmHg (P=0.009). A fluid balance in the upper tertile is an independent predictor of poor 30-day clinical outcomes after the adjustment for confounding variables in a multivariable logistic regression model. CONCLUSION: We found that fluid balance in low and upper tertiles were associated with poor short-term outcomes and ICP variations. Fluid balance in the upper tertile may be an independent predictor for poor 30-day outcome, primarily due to high AKI and RIH.