Atorvastatin Plus Low-Dose Dexamethasone May Be Effective for Leukemia-Related Chronic Subdural Hematoma but Not for Leukemia Encephalopathy: A Report of Three Cases.
Ontology highlight
ABSTRACT:
SUBMITTER: Yuan J
PROVIDER: S-EPMC8320332 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Atorvastatin has been shown to be a safe and effective non-surgical treatment option for patients with chronic subdural hematoma. However, treatment with atorvastatin is not effective in some patients, who must undergo further surgical treatment. Dexamethasone has anti-inflammatory and immunomodulatory effects, and low dosages are safe and effective for the treatment of many diseases, such as ankylosing spondylitis and community-acquired pneumonia. However, the effects of atorvastatin and low-dose dexamethasone for the treatment of chronic subdural hematoma remain poorly understood. Hematoma samples of patients with chronic subdural hematoma admitted to the General Hospital of Tianjin Medical University of China were collected and diluted in endothelial cell medium at 1:1 as the hematoma group. Atorvastatin, dexamethasone, or their combination was added to the culture medium. The main results were as follows: hopping probe ion conductance microscopy and permeability detection revealed that the best dosages to improve endothelial cell permeability were 0.1 μM atorvastatin and 0.1 μM dexamethasone. Atorvastatin, dexamethasone, or their combination could markedly improve the recovery of injured endothelial cells. Mice subcutaneously injected with diluted hematoma solution and then treated with atorvastatin, dexamethasone, or their combination exhibited varying levels of rescue of endothelial cell function. Hopping probe ion conductance microscopy, western blot assay, and polymerase chain reaction to evaluate the status of human cerebral endothelial cell status and expression level of tight junction protein indicated that atorvastatin, dexamethasone, or their combination could reduce subcutaneous vascular leakage caused by hematoma fluid. Moreover, the curative effect of the combined treatment was significantly better than that of either single treatment. Expression of Krüppel-like factor 2 protein in human cerebral endothelial cells was significantly increased, as was expression of the tight junction protein and vascular permeability marker vascular endothelial cadherin in each treatment group compared with the hematoma stimulation group. Hematoma fluid in patients with chronic subdural hematoma may damage vascular endothelial cells. However, atorvastatin combined with low-dose dexamethasone could rescue endothelial cell dysfunction by increasing the expression of tight junction proteins after hematoma injury. The effect of combining atorvastatin with low-dose dexamethasone was better than that of atorvastatin alone. Increased expression of Krüppel-like factor 2 may play an important role in the treatment of chronic subdural hematoma. The animal protocols were approved by the Animal Care and Use Committee of Tianjin Medical University of China on July 31, 2016 (approval No. IRB2016-YX-036). The study regarding human hematoma samples was approved by the Ethics Committee of Tianjin Medical University of China on July 31, 2018 (approval No. IRB2018-088-01).
| S-EPMC7996011 | biostudies-literature
Project description:Importance:Chronic subdural hematoma (CSDH) is a trauma-associated condition commonly found in elderly patients. Surgery is currently the treatment of choice, but it carries a significant risk of recurrence and death. Nonsurgical treatments remain limited and ineffective. Our recent studies suggest that atorvastatin reduces hematomas and improves the clinical outcomes of patients with CSDH. Objective:To investigate the safety and therapeutic efficacy of atorvastatin to nonsurgically treat patients with CSDH. Design, Setting, and Participants:The Effect of Atorvastatin on Chronic Subdural Hematoma (ATOCH) randomized, placebo-controlled, double-blind phase II clinical trial was conducted in multiple centers in China from February 2014 to November 2015. For this trial, we approached 254 patients with CSDH who received a diagnosis via a computed tomography scan; of these, 200 (78.7%) were enrolled because 23 patients (9.1%) refused to participate and 31 (12.2%) were disqualified. Interventions:Patients were randomly assigned to receive either 20 mg of atorvastatin or placebo daily for 8 weeks and were followed up for an additional 16 weeks. Main Outcomes and Measures:The primary outcome was change in hematoma volume (HV) by computed tomography after 8 weeks of treatment. The secondary outcomes included HV measured at the 4th, 12th, and 24th weeks and neurological function that was evaluated using the Markwalder grading scale/Glasgow Coma Scale and the Barthel Index at the 8th week. Results:One hundred ninety-six patients received treatment (169 men [86.2%]; median [SD] age, 63.6 [14.2] years). The baseline HV and clinical presentations were similar between patients who were taking atorvastatin (98 [50%]) and the placebo (98 [50%]). After 8 weeks, the HV reduction in patients who were taking atorvastatin was 12.55 mL more than those taking the placebo (95% CI, 0.9-23.9 mL; P?=?.003). Forty-five patients (45.9%) who were taking atorvastatin significantly improved their neurological function, but only 28 (28.6%) who were taking the placebo did, resulting in an adjusted odds ratio of 1.957 for clinical improvements (95% CI, 1.07-3.58; P?=?.03). Eleven patients (11.2%) who were taking atorvastatin and 23 (23.5%) who were taking the placebo underwent surgery during the trial for an enlarging hematoma and/or a deteriorating clinical condition (hazard ratio, 0.47; 95% CI, 0.24-0.92; P?=?.03). No significant adverse events were reported. Conclusions and Relevance:Atorvastatin may be a safe and efficacious nonsurgical alternative for treating patients with CSDH. Trial Registration:ClinicalTrials.gov Identifier: NCT02024373.
| S-EPMC6248109 | biostudies-literature
Project description:Chronic subdural hematoma (CSDH) is a common form of intracranial hemorrhage in the aging population. We aimed to investigate the predictive factors for atorvastatin efficacy as a monotherapy for moderate CSDH. We retrospectively reviewed the medical records of patients who were diagnosed with moderate CSDH and received atorvastatin monotherapy between February 5, 2014, and November 7, 2015, in multiple neurosurgical departments. Univariate, multivariate and receiver operating characteristic curve analyses were performed to identify the potential significant factors indicative of the good therapeutic efficacy or poor therapeutic efficacy of atorvastatin for mild CSDH, such as age, sex, history of injury, Markwalder grading scale-Glasgow Coma Scale (MGS-GCS), Activities of Daily Life-the Barthel Index scale (ADL-BI), American Society of Anesthesiologists Physical Status classification system (ASA-PS), blood cell counts, serum levels and computed tomography findings. A total of 89 patients (75 men and 14 women) aged 24-88 years (mean age 61.95 ± 15.30 years) were followed-up for 24 weeks. Computed tomography findings at admission showed mixed-density hematoma in 22 patients, isodense hematoma in 13 patients, high-density hematoma in 26 patients, and low-density hematoma in 28 patients. In total, 3, 80, and 6 patients had MGS-GCS grades of 0, 1, and 2, respectively. The efficacy rate at 6 months was 87.6% (78/89). Eleven patients were switched to surgery due to a worsened neurological condition, of whom 8, 1, 1, and 1 had high-density, low-density, isodense and mixed-density hematomas, respectively. These patients were switched to surgery over a range of 2-27 days, with a median interval of 12 days after the medication treatment. Univariate and multivariate analyses, confirmed by ROC curves, revealed that high-density hematoma, basal cistern compression, and hematoma volume to be independent risk factors for the efficacy of atorvastatin monotherapy in patients with moderate CSDH. Atorvastatin is an effective monotherapy for the treatment of mild CSDH. High-density hematoma, basal cistern compression, and hematoma volume are independent predictors of the efficacy of atorvastatin as a non-surgical treatment. The results suggested that ADL-BI was more sensitive than the MGS-GCS and ASA-PS for determining patient outcomes in our moderate CSDH cohort.
| S-EPMC8440973 | biostudies-literature
Project description:Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH.We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight.Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH.ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013.
| S-EPMC4652431 | biostudies-literature
Project description:Some studies have revealed that treating chronic subdural hematoma (CSDH) with drugs is effective; however, the specific mechanism of this process has been seldom discussed. Herein, we sought to identify the potential underlying mechanism of atorvastatin and low-dose dexamethasone for CSDH treatment. We sequenced the hCMEC/D3 cell lines treated with single statin, dexamethasone and low dose dexamethasone after hematoma injuried and statin to find out the key point.
2019-10-22 | GSE139133 | GEO
Project description:A subdural hematoma (SDH) is a type of bleeding in which a collection of blood gathers between the inner layer of the dura mater and the arachnoid mater of the meninges surrounding the brain. Although most cases reported of subdural hematoma are due to traumatic brain injury, to the best of our knowledge this is a rare case of nontraumatic subdural hematoma. A 31 year-old-Male presented to the emergency department with a severe headache for 3 weeks, with the presence of oculomotor disorders. There is no history of major trauma, minor trauma or fights. Also, no history of hypertension, or Haematological diseases. Magnetic resonance imaging (MRI) showed bilateral subdural hematoma. The right-sided hematoma was treated conservatively and the Left-sided was treated by surgery. Follow-up for three months revealed no recurrence. Nontraumatic subdural hematoma is one of the challenging cases that neurosurgeons face. We presented a patient with idiopathic spontaneous subdural hematoma. Computed tomography (CT) is the first step for diagnosis and Magnetic resonance imaging (MRI) is considered an excellent imaging investigation to evaluate such patients. Symptomatic subdural hematomas require an emergent treatment by identifying and controlling sites of bleeding conservatively or by surgery. Subdural hematoma with no history of trauma should be treated emergently and evaluated strictly. Follow-up is essential in patients with neural symptoms. Massive symptomatic subdural hematoma (SDH) should be treated with surgery to control the bleeding.
| S-EPMC8528674 | biostudies-literature
Project description:Exosomes are small (30-150 nm diameter) lipid bilayer-enclosed vesicles found in all bodily fluids. We investigated whether exosomes play a role in chronic subdural hematoma (CSDH). Exosomes were identified and characterized using transmission electron microscopy and NanoSight particle tracking. The functions of hematoma-derived exosomes were evaluated in a rat model of acute subdural hematoma (SDH). The hematoma-derived exosomes inhibited hematoma absorption and exacerbated neurological deficits in SDH rats. We examined the effects of the exosomes on angiogenesis and cell permeability in human umbilical vein endothelial cells (HUVECs). Co-culture of exosomes with HUVECs revealed that the hematoma-derived exosomes were taken-in by the HUVECs, resulting in enhanced tube formation and vascular permeability. Additionally, there was a concomitant increase in ANG-2 expression and decrease in ANG-1 expression. Exosomes were enriched with microRNAs including miR-144-5p, which they could deliver to HUVECs to promote angiogenesis and increase membrane permeability. Overexpression of miR-144-5p in HUVECs and in SDH rats promoted abnormal angiogenesis and reduced hematoma absorption, which mimicked the effects of the hematoma-derived exosomes both in vitro and in vivo. Thus, hematoma-derived exosomes promote abnormal angiogenesis with high permeability and inhibit hematoma absorption through miR-144-5p in CSDH.
| S-EPMC6949077 | biostudies-literature
Project description:High-dose dexamethasone is a mainstay of therapy for multiple myeloma. We studied whether low-dose dexamethasone in combination with lenalidomide is non-inferior to and has lower toxicity than high-dose dexamethasone plus lenalidomide.Patients with untreated symptomatic myeloma were randomly assigned in this open-label non-inferiority trial to lenalidomide 25 mg on days 1-21 plus dexamethasone 40 mg on days 1-4, 9-12, and 17-20 of a 28-day cycle (high dose), or lenalidomide given on the same schedule with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle (low dose). After four cycles, patients could discontinue therapy to pursue stem-cell transplantation or continue treatment until disease progression. The primary endpoint was response rate after four cycles assessed with European Group for Blood and Bone Marrow Transplant criteria. The non-inferiority margin was an absolute difference of 15% in response rate. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00098475.445 patients were randomly assigned: 223 to high-dose and 222 to low-dose regimens. 169 (79%) of 214 patients receiving high-dose therapy and 142 (68%) of 205 patients on low-dose therapy had complete or partial response within four cycles (odds ratio 1.75, 80% CI 1.30-2.32; p=0.008). However, at the second interim analysis at 1 year, overall survival was 96% (95% CI 94-99) in the low-dose dexamethasone group compared with 87% (82-92) in the high-dose group (p=0.0002). As a result, the trial was stopped and patients on high-dose therapy were crossed over to low-dose therapy. 117 patients (52%) on the high-dose regimen had grade three or worse toxic effects in the first 4 months, compared with 76 (35%) of the 220 on the low-dose regimen for whom toxicity data were available (p=0.0001), 12 of 222 on high dose and one of 220 on low-dose dexamethasone died in the first 4 months (p=0.003). The three most common grade three or higher toxicities were deep-vein thrombosis, 57 (26%) of 223 versus 27 (12%) of 220 (p=0.0003); infections including pneumonia, 35 (16%) of 223 versus 20 (9%) of 220 (p=0.04), and fatigue 33 (15%) of 223 versus 20 (9%) of 220 (p=0.08), respectively.Lenalidomide plus low-dose dexamethasone is associated with better short-term overall survival and with lower toxicity than lenalidomide plus high-dose dexamethasone in patients with newly diagnosed myeloma.National Cancer Institute, Rockville, MD, USA.
| S-EPMC3042271 | biostudies-literature
Project description:Background: Several pharmacological treatments have been used to treat patients with chronic subdural hematoma (CSDH), although little is known about the comparative effectiveness of different classes of medication. We performed a Bayesian network meta-analysis to compare and rank the efficacy and safety of five drug regimens to determine the best treatment for this group of patients. Methods: We systematically searched PubMed, Medline, clinicaltrials.gov, the Cochrane database, and Embase to identify relevant randomized clinical trials (RCTs) comparing drug treatments in adult patients with CSDH. A network meta-analysis was conducted using a Bayesian framework. Random- and fixed-effects models were used to pool the network results, and the preferred model was selected by comparing the deviance information criteria (DIC). Efficacy outcomes included recurrence requiring surgery, changes in hematoma volume, and a good recovery. The safety outcomes were treatment-related adverse events and all-cause mortality. Results: In this Bayesian network meta-analysis, available data were obtained from 12 eligible trials, including 2,098 patients and 5 techniques. Compared to placebo, atorvastatin (RR: 0.45, 95% CrI: 0.24-0.81) and dexamethasone (RR: 0.38, 95% CrI: 0.22-0.63) were similarly effective in reducing recurrence requiring surgery by 55% and 62%, respectively. Dexamethasone (RR: 0.46, 95% CrI: 0.23-0.91) was more effective in reducing recurrence requiring surgery than goreisan. Additionally, atorvastatin reduced the hematoma volume to a greater extent than placebo (MD: -7.44, 95% CrI: -9.49 to -5.43) or goreisan (MD: -14.09, 95% CrI: -23.35 to -4.82). Moreover, tranexamic acid (MD: -12.07, 95% CrI: -21.68 to -2.29) reduced the hematoma volume to a greater extent than goreisan. No significant differences were detected between drugs and placebo with regard to a good recovery. In terms of safety, dexamethasone (RR: 1.96, 95% CrI: 1.20-3.28) increased the risk of mortality compared to placebo. Conclusion: These findings suggest that dexamethasone is the best treatment to reduce recurrence and atorvastatin is the best treatment to reduce hematoma volume in patients with CSDH. However, clinicians should pay close attention to the elevated risk of all-cause mortality and potential adverse events caused by dexamethasone. Future well-designed RCTs with more participants are needed to verify these findings. Clinical Trial Registration: http://osf.io/u9hqp.
| S-EPMC8280518 | biostudies-literature
Project description:BACKGROUND:Low-dose acetylsalicylic acid (ASA) in patients with chronic subdural hematoma (cSDH) represents a significant neurosurgical challenge. While continuation of ASA during the perioperative phase might increase recurrence and bleeding rates, discontinuation increases the risk of thromboembolic events. The aim of this study is to compare the postoperative recurrence and cardiovascular complication rates of patients undergoing burr-hole trepanation for cSDH with and without discontinuation of ASA. METHODS:In this prospective randomized, placebo-controlled, double-blinded study we include all patients undergoing burr-hole drainage of cSDH who are under ASA treatment. The patients are randomized into two groups, one receiving ASA and the other placebo perioperatively. The study primarily seeks to compare the rate of recurrent events under ASA to that under placebo treatment. Secondary objectives are thromboembolic event rate, perioperative blood loss, postoperative anemia, intra- and postoperative blood transfusion rate, and clinical outcome. DISCUSSION:To date, there is no evidence-based consensus on how to manage patients undergoing burr-hole drainage for cSDH who are under ASA treatment. Therefore, the decision to maintain or interrupt ASA treatment is based mostly on the surgeons' preference. A randomized placebo-controlled study for this frequent question is urgently needed in order to provide class I evidence for the best possible treatment of this large group of patients. TRIAL REGISTRATION:ClinicalTrials.gov: NCT03120182 . Initial Release: 19.04.2017. STUDY PROTOCOL:V2_23.02.2017.
| S-EPMC6341728 | biostudies-literature