The Implementation of Preconditioned Epidermal Neural Crest Stem Cells to Combat Ischemic Stroke. Comment on Othman, F.A.; Tan, S.C. Preconditioning Strategies to Enhance Neural Stem Cell-Based Therapy for Ischemic Stroke. Brain Sci. 2020, 10, 893.

From MDPI via Jisc Publications RouterHistory: accepted 2021-05-13, pub-electronic 2021-05-17Publication status: PublishedIn the recent review published in Brain Sciences, Othman and Tan suggested several preconditioning strategies to improve stem cell therapy after ischemic brain injury [...

Comparison of the cost-effectiveness of transesophgeal and transthoracic echocardiographies to detect cardioembolic causes of stroke in non-selected patients

Background: Both Transthoracic Echocardiography (TTE) and Transesophgeal Echocardiography (TEE) are effective investigation tools to detect cardioaortic sources of embolism in ischemic stroke. Nevertheless, there are still uncertainties about the cost-effectiveness of these methods in non-selected patients with acute stroke. Objectives: This study aimed to investigate the cost-effectiveness of TTE and TEE using a decision analytic model in non-selected patients with acute ischemic stroke with or without clinical and radiological signs of embolic pattern. Patients and Methods: This cross-sectional cost-effectiveness study was performed in Nemazee hospital affiliated to Shiraz University of Medical Sciences from January 2014 to April 2014. TTE and TEE were performed for all 65 consecutive patients with ischemic stroke (51.3 male, mean age of 69.7 ± 17.9 years). The required data were direct costs related to performance of TTE and TEE, which were obtained from the patients� bills in their charts. A decision analytic model was implemented to assess the cost-effectiveness of these two methods, which demonstrated an Incremental Cost-Ef-fectiveness Ratio (ICER). Effectiveness was determined based on the number of disorders diagnosed using each of the two echoes confirmed by two cardiologists. All analyses were done using Tree Age Pro 2011. Results: The results showed that TEE was more expensive than TTE in non-selected patients. Performing TEE increased the cost by 1494 USD and the effectiveness by 7. As per ICER equation, for each increment unit in the effectiveness, performing TEE would increase the cost by 213.4 USD compared to TTE. TEE was cost-effective in comparison to TTE regardless of age factor considering the cutoff of Gross Domestic Product (GDP) by three for ICER. Moreover, TTE was cost-effective in 41-60-and 61-80-year-old age groups, while TEE was cost-effective in the 41-60-year-old age group. However, none of the techniques was cost-effective in patients above 81 years old. Conclusions: The results of this study can help reduce the unnecessary use of echocardiography by considering the age group and their corresponding risk factors for developing ischemic stroke. © 2018, Iranian Cardiovascular Research Journal. All rights reserved

Comparison of the cost-effectiveness of transesophgeal and transthoracic echocardiographies to detect cardioembolic causes of stroke in non-selected patients

Background: Both Transthoracic Echocardiography (TTE) and Transesophgeal Echocardiography (TEE) are effective investigation tools to detect cardioaortic sources of embolism in ischemic stroke. Nevertheless, there are still uncertainties about the cost-effectiveness of these methods in non-selected patients with acute stroke. Objectives: This study aimed to investigate the cost-effectiveness of TTE and TEE using a decision analytic model in non-selected patients with acute ischemic stroke with or without clinical and radiological signs of embolic pattern. Patients and Methods: This cross-sectional cost-effectiveness study was performed in Nemazee hospital affiliated to Shiraz University of Medical Sciences from January 2014 to April 2014. TTE and TEE were performed for all 65 consecutive patients with ischemic stroke (51.3 male, mean age of 69.7 ± 17.9 years). The required data were direct costs related to performance of TTE and TEE, which were obtained from the patients� bills in their charts. A decision analytic model was implemented to assess the cost-effectiveness of these two methods, which demonstrated an Incremental Cost-Ef-fectiveness Ratio (ICER). Effectiveness was determined based on the number of disorders diagnosed using each of the two echoes confirmed by two cardiologists. All analyses were done using Tree Age Pro 2011. Results: The results showed that TEE was more expensive than TTE in non-selected patients. Performing TEE increased the cost by 1494 USD and the effectiveness by 7. As per ICER equation, for each increment unit in the effectiveness, performing TEE would increase the cost by 213.4 USD compared to TTE. TEE was cost-effective in comparison to TTE regardless of age factor considering the cutoff of Gross Domestic Product (GDP) by three for ICER. Moreover, TTE was cost-effective in 41-60-and 61-80-year-old age groups, while TEE was cost-effective in the 41-60-year-old age group. However, none of the techniques was cost-effective in patients above 81 years old. Conclusions: The results of this study can help reduce the unnecessary use of echocardiography by considering the age group and their corresponding risk factors for developing ischemic stroke. © 2018, Iranian Cardiovascular Research Journal. All rights reserved

The effects of statin use on inflammatory markers among patients with metabolic syndrome and related disorders: A systematic review and meta-analysis of randomized controlled trials

Current evidence suggests that statin use decreases the incidence of cardiovascular diseases (CVD) through reducing LDL cholesterol and decreasing inflammation. Metabolic syndrome (MetS) is usually associated with increased inflammatory markers and increased risk of CVD. We conducted a systematic review and meta-analysis to determine the effect of statin use on inflammatory markers including C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1 (IL-1) among patients with MetS and related disorders. PubMed, EMBASE, Web of Science databases, and Cochrane Library were searched for randomized controlled trials (RCTs) through April 2018. Three independent investigators evaluated study eligibilities, extracted data, and assessed study quality using the Cochrane Collaboration risk of bias tool and Jadad's quality scales. Heterogeneity was determined using Cochran's Q statistic and I-square (I 2 ) test. Based on the heterogeneity results, we pooled data using random-effect or fixed effect models presented as standardized mean differences (SMD) and corresponding 95 confidence intervals (CI). One hundred thirteen RCTs (19,644 patients) were included in our meta-analysis. The pooled results using random effects model showed that statin use statistically significantly decreased CRP level (SMD= -0.97; 95 CI, -1.10, -0.85; P < 0.001; I 2 : 95.1), TNF-α (SMD= -1.88; 95 CI, -2.40, -1.38; P < 0.001; I 2 : 97.2), IL-6 (SMD= -1.67; 95 CI, -1.98, -1.34; P < 0.001; I 2 : 96.5), and IL-1 concentrations (SMD= -8.35; 95 CI, -10.49, -6.22; P < 0.001; I 2 : 98.4) among patients with MetS and related disorders. Our meta-analysis showed beneficial effects of statin use on reducing inflammatory markers in patients with MetS and related disorders. © 2018 Elsevier Lt

Diagnosis and management of Neuro-Behçet's disease: international consensus recommendations.

Neuro-Behçet's disease (NBD) is one of the more serious manifestations of Behçet's disease (BD), which is a relapsing inflammatory multisystem disease with an interesting epidemiology. Though NBD is relatively uncommon, being potentially treatable, neurologists need to consider it in the differential diagnosis of inflammatory, infective, or demyelinating CNS disorders. Evidence-based information on key issues of NBD diagnosis and management is scarce, and planning for such studies is challenging. We therefore initiated this project to develop expert consensus recommendations that might be helpful to neurologists and other clinicians, created through an extensive literature review and wide consultations with an international advisory panel, followed by a Delphi exercise. We agreed on consensus criteria for the diagnosis of NBD with two levels of certainty in addition to recommendations on when to consider NBD in a neurological patient, and on the use of various paraclinical tests. The management recommendations included treatment of the parenchymal NBD and cerebral venous thrombosis, the use of disease modifying therapies, prognostic factors, outcome measures, and headache in BD. Future studies are needed to validate the proposed criteria and provide evidence-based treatments

The beneficial effects of chick embryo extract preconditioning on hair follicle stem cells: A promising strategy to generate Schwann cells

The beneficial effects of hair follicle stem cells in different animal models of nervous system conditions have been extensively studied. While chick embryo extract (CEE) has been used as a growth medium supplement for these stem cells, this is the first study to show the effect of CEE on them. The rat hair follicle stem cells were isolated and supplemented with 10% fetal bovine serum plus 10% CEE. The migration rate, proliferative capacity and multipotency were evaluated along with morphometric alteration and differentiation direction. The proteome analysis of CEE content identified effective factors of CEE that probably regulate fate and function of stem cells. The CEE enhances the migration rate of stem cells from explanted bulges as well as their proliferation, likely due to activation of AP-1 and translationally controlled tumour protein (TCTP) by thioredoxin found in CEE. The increased length of outgrowth may be the result of cyclic AMP response element binding protein (CREB) phosphorylation triggered by active CamKII contained in CEE. Further, CEE supplementation upregulates the expression of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor. The elevated expression of target genes and proteins may be due to CREB, AP-1 and c-Myc activation in these stem cells. Given the increased transcript levels of neurotrophins, VEGF, and the expression of PDGFR-α, S100B, MBP and SOX-10 protein, it is possible that CEE promotes the fate of these stem cells towards Schwann cells

Sex Differences in Cerebral Venous Sinus Thrombosis after Adenoviral Vaccination against COVID-19

INTRODUCTION Cerebral venous sinus thrombosis associated with vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is a severe disease with high mortality. There are few data on sex differences in CVST-VITT. The aim of our study was to investigate the differences in presentation, treatment, clinical course, complications, and outcome of CVST-VITT between women and men. PATIENTS AND METHODS We used data from an ongoing international registry on CVST-VITT. VITT was diagnosed according to the Pavord criteria. We compared the characteristics of CVST-VITT in women and men. RESULTS Of 133 patients with possible, probable, or definite CVST-VITT, 102 (77%) were women. Women were slightly younger [median age 42 (IQR 28-54) vs 45 (28-56)], presented more often with coma (26% vs 10%) and had a lower platelet count at presentation [median (IQR) 50x109/L (28-79) vs 68 (30-125)] than men. The nadir platelet count was lower in women [median (IQR) 34 (19-62) vs 53 (20-92)]. More women received endovascular treatment than men (15% vs 6%). Rates of treatment with intravenous immunoglobulins were similar (63% vs 66%), as were new venous thromboembolic events (14% vs 14%) and major bleeding complications (30% vs 20%). Rates of good functional outcome (modified Rankin Scale 0-2, 42% vs 45%) and in-hospital death (39% vs 41%) did not differ. DISCUSSION AND CONCLUSIONS Three quarters of CVST-VITT patients in this study were women. Women were more severely affected at presentation, but clinical course and outcome did not differ between women and men. VITT-specific treatments were overall similar, but more women received endovascular treatment

Cancer treatment-related neuropathic pain:proof of concept study with menthol—a TRPM8 agonist

PURPOSE: Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol. PATIENTS AND METHODS: Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation. RESULTS: Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59), P < 0.001). Improvements in mood (P = 0.0004), catastrophising (P = 0.001), walking ability (P = 0.008) and sensation (P < 0.01) were also observed. CONCLUSION: This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia

Background and purpose: Cerebral venous sinus thrombosis due to vaccine-induced im-mune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in- hospital mortality in these patients are explored.Methods: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV- 2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680–1689), were included. Results: Decompressive surgery was performed in 34/128 (27%) patients with CVST- VITT. In- hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non- surgical group (p< 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p< 0.001) and bilaterally absent pupillary re-flexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bi-laterally reactive pupils; p= 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) pa-tients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived ad-mission were functionally independent.Conclusions: Almost two-thirds of surgical CVST-VITT patients died during hospital ad-mission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.Peer reviewe