Naoxueshu Oral Liquid Accelerates Post-Craniotomy Hematoma Absorption in Patients: An Open-Label, Multicenter, and Randomized Controlled Trial.

OBJECTIVE: To investigate whether Naoxueshu Oral Liquid (NXS) could promote hematoma absorption in post-craniotomy hematoma (PCH) patients. METHODS: This is an open-label, multicenter, and randomized controlled trial conducted at 9 hospitals in China. Patients aged 18-80 years with post-craniotomy supratentorial hematoma volume ranging from 10 to 30 mL or post-craniotomy infratentorial hematoma volume less than 10 mL, or intraventricular hemorrhage following cranial surgery were enrolled. They were randomly assigned at a 1:1 ratio to the NXS (10 mL thrice daily for 15 days) or control groups using a randomization code table. Standard medical care was administered in both groups. The primary outcome was the percentage reduction in hematoma volume from day 1 to day 15. The secondary outcomes included the percentage reduction in hematoma volume from day 1 to day 7, the absolute reduction in hematoma volume from day 1 to day 7 and 15, and the change in neurological function from day 1 to day 7 and 15. The safety was closely monitored throughout the study. Moreover, subgroup analysis was performed based on age, gender, history of diabetes, and etiology of intracerebral hemorrhage (ICH). RESULTS: A total of 120 patients were enrolled and randomly assigned between March 30, 2018 and April 15, 2020. One patient was lost to follow-up in the control group. Finally, there were 119 patients (60 in the NXS group and 59 in the control group) included in the analysis. In the full analysis set (FAS) analysis, the NXS group had a greater percentage reduction in hematoma volume from day 1 to day 15 than the control group [median (Q1, Q3): 85% (71%, 97%) vs. 76% (53%, 93%), P<0.05]. The secondary outcomes showed no statistical significance between two groups, either in FAS or per-protocol set (P>0.05). Furthermore, no adverse events were reported during the study. In the FAS analysis, the NXS group exhibited a higher percentage reduction in hematoma volume on day 15 in the following subgroups: male patients, patients younger than 65 years, patients without diabetes, or those with initial cranial surgery due to ICH (all P<0.05). CONCLUSIONS: The administration of NXS demonstrated the potential to promote the percentage reduction in hematoma volume from day 1 to day 15. This intervention was found to be safe and feasible. The response to NXS may be influenced by patient characteristics. (Registration No. ChiCTR1800017981).

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.

Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages.

BACKGROUND: We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. METHODS: Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. RESULTS: ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. CONCLUSIONS: We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

Low-temperature laminar flow ward for the treatment of multidrug resistance Acinetobacter baumannii pneumonia.

This study was designed to investigate the effect of low-temperature laminar flow ward (LTLFW) on the Acinetobacter baumannii pneumonia (MDR-ABP) in neurosurgical intensive care unit (NICU) patients. We evaluated whether patients in a LTLFW had significantly improved clinical outcomes as compared to those in nonconstant-temperature NICU (room temperature). The association of temperature with the prevalence of ABP and A. baumannii isolates (ABI) found in NICU patients was specifically investigated. In vitro microbiological experiments were conducted to measure the proliferation, antibiotic sensitivity, and genomic profiles of A. baumannii (AB) that grew in variable temperatures. MDR-ABP patients in LTLFW had significantly improved outcomes than those in the room temperature NICU. In addition, the numbers of ABI were positively associated with mean ambient outdoor temperatures (P = 0.002), with the incidence of ABP and average numbers of ABI among NICU patients being substantially lower in the winter as compared to other seasons. However, there were no significant seasonal variations in the other strains of the top five bacteria. Consistent with these clinical observations, AB growing at 20°C and 25°C had significantly reduced viability and antibiotic resistance compared to those growing at 35°C. The expression of genes related to AB survival ability, drug resistance, and virulence also differed between AB growing at 20°C and those at 35°C. LTLFW is effective in promoting the recovery of MDR-ABP patients because low temperatures reduced the density and virulence of AB and enhanced the efficacy of antibiotics, likely at the genetic level.

Drug treatment of chronic subdural hematoma.

Introduction: Chronic subdural hematoma (CSDH) is a common neurosurgical disease, whose incidence has been steadily increasing with our aging population. While not common, CSDH can also occur in children. CSDH is often associated with traumatic head injury, but its underlying mechanism remains poorly understood. The first line treatment for CSDH is surgery. However, surgery is contraindicated in some patients and has a high rate of recurrence. Effective non-surgical treatment is therefore highly desirable.Areas covered: This review discusses the pathogenesis of CSDH and drugs that have been used to treat CSDH either as monotherapy or an adjuvant to surgery, including controlled clinical trials.Expert opinion: The pathophysiology of CSDH remains poorly understood. Developing effective drug treatments is therefore challenging. Most drugs discussed in this review are evaluated in small clinical studies without sufficient sample size and controls for confounding variables. More controlled clinical trials are therefore needed to carefully evaluate drugs for the non-surgical treatment of CSDH, especially for drugs targeting specific pathogenic pathways of CSDH.

Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model.

BACKGROUND AND PURPOSE: Statins are active in reducing plasma lipids, suppressing inflammation and promoting angiogenesis. Because angiogenesis is critical for the absorbance of subdural hematoma (SDH), we hypothesize that atorvastatin promotes angiogenesis to enhance hematoma absorption. METHODS: SDH was induced in adult Wistar rats and treated with 3mg/kg, 8mg/kg of atorvastatin, or vehicle saline daily for 7days. The treated rats were examined for the level of CD34+/CD133+ endothelial progenitor cells (EPCs) in the circulation by flow cytometry, hematoma volumes by magnetic resonance imaging (MRI), and changes in cognitive functions. We also examined angiogenesis in the hematoma wall by transmission electronic microscopy and immunohistochemistry for the expression of vascular endothelial growth factor (VEGF), matrix metalloprotease 9 (MMP 9) and angiopoietin. RESULTS: SDH volume was significantly reduced and neurological deficits improved in rats receiving the low dose atorvastatin compared to those receiving either the high dose of atorvastatin or saline. Consistent with these outcome measures, the low dose atorvastatin increased the expression of angiopoient-1 and VEGF and reduced MMP9 expression in the connective tissue of the SDH wall, resulting in an increased vascular density and enhanced vascular maturation. CONCLUSIONS: The low-dose atorvastatin is effective in reducing SDH and improving neurological deficits in a rat model, primarily by promoting angiogenesis and vascular maturation.

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats.

INTRODUCTION: The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. METHODS: Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. RESULTS: We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood-brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. CONCLUSIONS: Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus.