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  • Pedersen Just posted an update 1 month ago

    Multiple sclerosis (MS) is a chronic inflammatory disease and the most common neurodegenerative status. MicroRNAs play an important role in macrophage response to inflammatory processes, and alterations in miRNA levels trigger the inactivation of specific T lymphocytes. As a result, these factors can lead to autoimmune diseases such as MS. Therefore, to determine the role of MicroRNA-146a and MicroRNA-155 in MS patients, their expression levels in serum of MS patients were compared with healthy controls. In this study, the expression levels of MicroRNA-146a and MicroRNA-155 in 30 serum samples of MS and healthy patients as a control group. MicroRNA extraction and cDNA synthesis was performed according manufacture protocols. The expression levels of MicroRNAs were evaluated by Real Time-PCR. MicroRNA-146a and MicroRNA-155 levels were increased in patients with MS compared to controls. The results demonstrated that EDSS score are increased with increasing level of MicroRNA-146a and MicroRNA-155. ROC curve analysis showed that the area under curve (AUC) was significant for MicroRNA-146a and MicroRNA-155. Increased expression levels of MicroRNA-146a and MicroRNA-155 may be associated with the pathogenesis of MS disease. If this study is conducted in a larger sample population and the above results can be used to identify patients or control patients who are under medical care. A carotid-cavernous fistula (CCF) is an abnormal connection between the carotid circulation and the cavernous sinus. Treatment of CCFs often consists of obliteration of the fistula by a transarterial or transvenous endovascular approach using embolic agents. However, fistula embolization is often halted due to the potential embolic complications that may arise from the retrograde flow of the embolic agents into the arterial circulation, which often leads to the development of fistula recurrence. Moreover, retreatment of a CCF recurrence is challenging and more complex approaches may be required. Selleck NVP-ADW742 In this technical note, we describe our experience with CCF embolization in 25 patients treated at a single center. We utilized a transvenous approach for CCF embolization with simultaneous balloon occlusion of the internal carotid artery during the infusion of the embolic material into the fistula. In our series, this simultaneous protection of the internal carotid artery showed to be a safe technique to prevent embolic complications and to achieve successful obliteration of the fistula. On follow-up, 2 cases presented a recurrence, one due to technical difficulties and the other related to an undetected vascular injury. In conclusion, this technique provides a safe approach in the treatment of CCFs by decreasing the risk of embolic complications and increasing the effectiveness of the embolic agents in accomplishing the obliteration of the CCF. Pseudarthrosis following spinal fusion is correlated with poorer patient outcomes and consequently is an area of continued interest within spinal research. Recently, bioactive glasses have been proposed as a means of augmenting fusion rates. Here, we present the first systematic review and meta-analysis of the existing preclinical and clinical literature on the effect of bioactive glasses on spinal fusion. Using the MEDLINE, Embase, and Web of Science databases, we queried all publications in the English-language literature examining the effect of bioactive glasses on spinal fusion. The primary endpoint was fusion rate at last follow-up and the secondary endpoint for clinical studies was the rate of deep wound infection. Random-effects meta-analyses were performed independently for the preclinical and clinical data. Twelve preclinical studies (267 animals) and 12 clinical studies (396 patients) evaluating a total of twelve unique bioactive glass formulations were included. Across clinical studies, fusion was seen in 84% treated with bioactive glass. On sub-analysis, fusion rates were similar for standalone autograft (91.6%) and bioactive glass-local autograft mixtures (89.6%). Standalone bioactive glass substrates produced inferior fusion rates relative to autograft alone (33.6% vs. 98.8%; OR 0.01, p  less then  0.02). Rates of deep wound infection did not differ between the bioactive glass and autograft groups (3.1%). The preclinical data similarly showed comparable rates of fusion between autograft and bioactive glass-treated animals. The available data suggest that bioactive glass-autograft mixtures confer similar rates of spinal fusion relative to standalone autograft without altering the risk of deep wound infection. Intracranial peripherally enhancing lesions in immunosuppressed solid organ transplant recipients represent a unique diagnostic and management dilemma due to the vast array of differentials that demand consideration. Diagnosis of the underlying pathology is often guided by the use of magnetic resonance imaging (MRI). We present the first published case series of three cardiac transplant recipients with significantly atypical neuroradiological findings contrary to the tenets of contemporary literature. Our rare case series consists of (1) A sterile Mycobacterium pyogenic abscess mimicking glioblastoma multiforme due to an immunosuppressed state (2) Epstein Barr Virus encephalitis masquerading as Central Nervous System Post-Transplant Lymphoproliferative Disorder (3) An unusual case of partially treated disseminated Nocardiosis warning of the need to consider the immunosuppressed state and partial treatment response obfuscating classical MRI appearances. We utilise these unprecedented cases as the basis of a literature review to understand the pathophysiology behind the peculiar imaging findings in this rarefied cohort of transplant recipients, and rationalise why the MRI findings in each instance contradicts the accepted imaging patterns. In the setting of potential unreliability of neuroradiology in this immunosuppressed unique subgroup, we hope to impart to clinicians that definitive diagnosis obtained by emergent neurosurgical intervention may be necessary to accurately and expediently guide further medical management. Hospital-acquired conditions (HACs) have been the focus of recent initiatives by the Centers for Medicare and Medicaid Services in an effort to improve patient safety and outcomes. Spine surgery can be complex and may carry significant comorbidity burden, including so called “never events.” The objective was to determine the rates of common HACs that occur within 30-days post-operatively for elective spine surgeries and compare them to other common surgical procedures. Patients >18 y/o undergoing elective spine surgery were identified in the American College of Surgeons’ NSQIP database from 2005 to 2013. Patients were stratified by whether they experienced >1 HAC, then compared to those undergoing other procedures including bariatric surgery, THA and TKA. Of the 90,551 spine surgery patients, 3021 (3.3%) developed at least one HAC. SSI was the most common (1.4%), followed by UTI (1.3%), and VTE (0.8%). Rates of HACs in spine surgery were significantly higher than other elective procedures including bariatric surgery (2.8%) and THA (2.8%) (both p  less then  0.001). Spine surgery and TKA patients had similar rates of HACs(3.3% vs 3.4%, p = 0.287), though spine patients experienced higher rates of SSI (1.4%vs0.8%, p  less then  0.001) and UTI (1.3%vs1.1%, p  less then  0.001) but lower rates of VTE (0.8%vs1.6%, p  less then  0.001). Spine surgery patients had lower rates of HACs overall (3.3%vs5.9%) when compared to cardiothoracic surgery patients (p  less then  0.001). When compared to other surgery types, spine procedures were associated with higher HACs than bariatric surgery patients and knee and hip arthroplasties overall but lower HAC rates than patients undergoing cardiothoracic surgery. INTRODUCTION Parkinson’s disease (PD) patients are reported to score significantly lower on the Judgement of Line Orientation (JLO) test compared with controls. The traditional method of scoring JLO ignores potentially interesting information on the mechanism of errors made. AIM The aim of the current study was to analyse the performance of PD patients on the JLO while monitoring eye movements. Employing eye tracking methods while PD participants attempt JLO items may prove valuable in further characterising error-patterns. METHODS We recruited three groups, each comprising 16 participants PD participants with normal cognition (PD-N), PD participants with mild cognitive impairment (PD-MCI) and matched controls. RESULTS The mean correct response rates were high 93% (±6) for controls, 88% (±12) for PD-N and 87% (±11) for PD-MCI; the difference did not reach statistical significance (p = 0.21). Participants made more errors as they progressed from easy to harder item (r = 0.7; p = 0.02). Using the Ska classification, error types QO1 and QO3 were by far and away the most common. The mean amplitudes of saccadic eye movements were 5.9° (±0.9) for controls, 5.7° (±1.1) for PD-N, and 5.5° (±1.0) for PD-MCI. The differences among the three groups did not reach statistical significance (p = 0.64). As a whole, participant fixation patterns were similar throughout the JLO task. For the reference lines, most fixations were made on the distal ends. Fixations on the test lines, on the other hand, appeared to vary among trials, dependent on whether the response was correct or incorrect. CONCLUSIONS There were few differences among the study groups in test performance-eye movement associations. However, we gained important insights into oculomotor behaviour during JLO test completion in both healthy controls and PD patients which could reflect the underlying disease state as we hypothesised. PURPOSE To determine the diagnostic and prognostic value of glial fibrillary acidic protein (GFAP) and S100B after traumatic brain injury (TBI) in an Erythropoietin (EPO) clinical trial and examine whether EPO therapy reduces biomarker concentrations. MATERIALS AND METHODS Forty-four patients with moderate-to-severe TBI were enrolled to a sub-study of the EPO-TBI trial. Patients were randomized to either Epoetin alfa 40,000 IU or 1 ml sodium chloride 0.9 as subcutaneous injection within 24 h of TBI. RESULTS GFAP and S100B were measured in serum by ELISA from D0 (within 24 h of injury, prior to EPO/vehicle administration) to D5. Biomarker concentrations were compared between injury severities, diffuse vs. focal TBI, 6-month outcome scores (GOS-E) and EPO or placebo treatments. At D0 GFAP was significantly higher than S100B (951 pg/mL vs. 476 pg/mL, p = 0.018). ROC analysis of S100B at 1D post-injury distinguished favorable vs. unfavorable outcomes (area under the curve = 0.73; p = 0.01). EPO did not reduce concentration of either biomarker. CONCLUSIONS Elevated serum concentrations of GFAP and S100B after TBI reflect a robust, acute glial response to injury. Consistent with lack of improved outcome in TBI patients treated with EPO and prior findings on neuronal and axonal markers, glial biomarker concentrations and acute profiles were not affected by EPO. BACKGROUND Heterozygous familial hypercholesterolemia (HeFH) is a genetic disorder characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C). OBJECTIVE This phase 2 dose-finding study (NCT02890992) evaluated the efficacy, safety, and dose selection of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab in pediatric HeFH patients. METHODS HeFH patients (n = 42) who were aged 8-17 years, had body weight (BW) ≥25 kg, and had LDL-C ≥130 mg/dL despite optimal statin/other lipid-modifying therapies were enrolled in 4 cohorts according to BW cohort #1 30 mg ( less then 50 kg) or 50 mg (≥50 kg) every 2 weeks (Q2W), #2 40 mg ( less then 50 kg) or 75 mg (≥50 kg) Q2W, #3 75 mg ( less then 50 kg) or 150 mg (≥50 kg) every 4 weeks (Q4W), #4 150 mg ( less then 50 kg) or 300 mg (≥50 kg) Q4W. Primary endpoint was LDL-C % change from baseline to week 8. RESULTS Mean age was 12.4 years and 95% of patients were on a statin. Baseline LDL-C levels were 160.0-188.9 mg/dL and free PCSK9 was 186.