scholarly journals Association between vasoactive peptide urotensin II in plasma and cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a potential therapeutic target

2019 ◽  
Vol 131 (4) ◽  
pp. 1278-1288
Author(s):  
Thomas Clavier ◽  
Alexandre Mutel ◽  
Laurence Desrues ◽  
Antoine Lefevre-Scelles ◽  
Gioia Gastaldi ◽  
...  
Keyword(s):  
Clinical Study ◽  
Mouse Model ◽  
Healthy Volunteers ◽  
Neurological Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Urotensin Ii ◽  
Potential Therapeutic Target ◽  
Significant Difference ◽  
Median Plasma ◽  
Vasoactive Peptide

OBJECTIVECerebral vasospasm (VS) is a severe complication of aneurysmal subarachnoid hemorrhage (SAH). Urotensin II (UII) is a potent vasoactive peptide activating the urotensin (UT) receptor, potentially involved in brain vascular pathologies. The authors hypothesized that UII/UT system antagonism with the UT receptor antagonist/biased ligand urantide may be associated with post-SAH VS. The objectives of this study were 2-fold: 1) to leverage an experimental mouse model of SAH with VS in order to study the effect of urotensinergic system antagonism on neurological outcome, and 2) to investigate the association between plasma UII level and symptomatic VS after SAH in human patients.METHODSA mouse model of SAH was used to study the impacts of UII and the UT receptor antagonist/biased ligand urantide on VS and neurological outcome. Then a clinical study was conducted in the setting of a neurosurgical intensive care unit. Plasma UII levels were measured in SAH patients daily for 9 days, starting on the 1st day of hospitalization, and were compared with plasma UII levels in healthy volunteers.RESULTSIn the mouse model, urantide prevented VS as well as SAH-related fine motor coordination impairment. Seventeen patients with SAH and external ventricular drainage were included in the clinical study. The median plasma UII level was 43 pg/ml (IQR 14–80 pg/ml). There was no significant variation in the daily median plasma UII level (median value for the 17 patients) from day 0 to day 8. The median level of plasma UII during the 9 first days post-SAH was higher in patients with symptomatic VS than in patients without VS (77 pg/ml [IQR 33.5–111.5 pg/ml] vs 37 pg/ml [IQR 21–46 pg/ml], p < 0.05). Concerning daily measures of plasma UII levels in VS, non-VS patients, and healthy volunteers, we found a significant difference between SAH patients with VS (median 66 pg/ml [IQR 30–110 pg/ml]) and SAH patients without VS (27 pg/ml [IQR 15–46 pg/ml], p < 0.001) but no significant difference between VS patients and healthy volunteers (44 pg/ml [IQR 27–51 pg/ml]) or between non-VS patients and healthy volunteers.CONCLUSIONSThe results of this study suggest that UT receptor antagonism with urantide prevents VS and improves neurological outcome after SAH in mice and that an increase in plasma UII is associated with cerebral VS subsequent to SAH in humans. The causality link between circulating UII and VS after SAH remains to be established, but according to our data the UT receptor is a potential therapeutic target in SAH.

scholarly journals Sphingosine 1-phosphate levels in cerebrospinal fluid after subarachnoid hemorrhage

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Anika Männer ◽  
Dominique Thomas ◽  
Marlies Wagner ◽  
Jürgen Konczalla ◽  
Helmuth Steinmetz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Subarachnoid Hemorrhage ◽  
Neurological Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
High Sensitivity ◽  
Control Subjects ◽  
Symptomatic Vasospasm ◽  
Significant Difference ◽  
Hemorrhage Volume

Abstract Background and purpose Sphingosin-1-phosphate (S1P) plays a crucial role as a signaling molecule in the immune system and the vasculature. Previous studies suggested a role as a vasoconstrictor of cerebral arteries via the S1P3-Receptor. Cerebral vasospasm (VS) following aneurysmal subarachnoid hemorrhage (SAH) is a major cause of disability and poor neurological outcome. Early detection of vasospasm could facilitate the prevention of cerebral ischemia in SAH patients. The aim of this prospective case-control study was to characterize the dynamics of S1P in the cerebrospinal fluid (CSF) of patients with SAH in relation to hemorrhage volume, the occurrence of VS, and neurological outcome. Methods S1P levels in CSF of 18 control subjects and 18 SAH patients with placement of an external ventricular drainage (EVD) were determined by high sensitivity mass spectrometry from day 1 through 14 after SAH onset. Hemorrhage volume, development of asymptomatic vasospasm (aVS) and symptomatic vasospasm (sVS), and neurological outcome were correlated to day 1 S1P levels. Results The intrathecal S1P levels of SAH patients were higher than those of the control subjects, and correlated with hemorrhage volume. There was no significant difference in S1P levels between patients with aVS and those with sVS. S1P levels significantly correlated with neurological outcome on a sliding modified Rankin scale. Conclusion S1P levels were highest directly after placement of the EVD and correlated strongly with hemorrhage volume, which may be caused by the intrathecal clot and subsequent lysis of red blood cells, an important source of S1P. We did not detect a second peak of S1P release over the course of the intensive care period.

Introduction of intraoperative neuromonitoring does not necessarily improve overall long-term outcome in elective aneurysm clipping

2020 ◽  
Vol 132 (4) ◽  
pp. 1188-1196 ◽  
Author(s):  
Tobias Greve ◽  
Veit M. Stoecklein ◽  
Franziska Dorn ◽  
Sophia Laskowski ◽  
Niklas Thon ◽  
...  
Keyword(s):  
Evoked Potentials ◽  
Predictive Value ◽  
Neurological Outcome ◽  
Positive Impact ◽  
Case Series ◽  
Intraoperative Neuromonitoring ◽  
Neurosurgical Procedures ◽  
Long Term Outcome ◽  
Unruptured Intracranial Aneurysms ◽  
Significant Difference

OBJECTIVEIntraoperative neuromonitoring (IOM), particularly of somatosensory-evoked potentials (SSEPs) and motor-evoked potentials (MEPs), evolved as standard of care in a variety of neurosurgical procedures. Case series report a positive impact of IOM for elective microsurgical clipping of unruptured intracranial aneurysms (ECUIA), whereas systematic evaluation of its predictive value is lacking. Therefore, the authors analyzed the neurological outcome of patients undergoing ECUIA before and after IOM introduction to this procedure.METHODSThe dates of inclusion in the study were 2007–2014. In this period, ECUIA procedures before (n = 136, NIOM-group; 2007–2010) and after introduction of IOM (n = 138, IOM-group; 2011–2014) were included. The cutoff value for SSEP/MEP abnormality was chosen as an amplitude reduction ≥ 50%. SSEP/MEP changes were correlated with neurological outcome. IOM-undetectable deficits (bulbar, vision, ataxia) were not included in risk stratification.RESULTSThere was no significant difference in sex distribution, follow-up period, subarachnoid hemorrhage risk factors, aneurysm diameter, complexity, and location. Age was higher in the IOM-group (57 vs 54 years, p = 0.012). In the IOM group, there were 18 new postoperative deficits (13.0%, 5.8% permanent), 9 hemisyndromes, 2 comas, 4 bulbar symptoms, and 3 visual deficits. In the NIOM group there were 18 new deficits (13.2%; 7.3% permanent, including 7 hemisyndromes). The groups did not significantly differ in the number or nature of postoperative deficits, nor in their recovery rate. In the IOM group, SSEPs and MEPs were available in 99% of cases. Significant changes were noted in 18 cases, 4 of which exhibited postoperative hemisyndrome, and 1 suffered from prolonged comatose state (5 true-positive cases). Twelve patients showed no new detectable deficits (false positives), however 2 of these cases showed asymptomatic infarction. Five patients with new hemisyndrome and 1 comatose patient did not show significant SSEP/MEP alterations (false negatives). Overall sensitivity of SSEP/MEP monitoring was 45.5%, specificity 89.8%, positive predictive value 27.8%, and negative predictive value 95.0%.CONCLUSIONSThe assumed positive impact of introducing SSEP/MEP monitoring on overall neurological outcome in ECUIA did not reach significance. This study suggests that from a medicolegal point of view, IOM is not stringently required in all neurovascular procedures. However, future studies should carefully address high-risk patients with complex procedures who might benefit more clearly from IOM than others.

Comparative Clinical study of Jatyadi Taila and Jatyadi Ghrita in the management of Dushta Vrana

2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Rajendra Joshi ◽  
N. B. Mashetti ◽  
Rakesh Kumar Gujar
Keyword(s):  
Clinical Study ◽  
Burning Sensation ◽  
Normal Process ◽  
Surgical Practice ◽  
Local Factors ◽  
Significant Difference ◽  
Comparative Clinical Study ◽  
Group A ◽  
Contaminated Wound ◽  
Group B

Dushta Vrana is a common and frequently encountered problem faced in surgical practice. The presence of Dushta Vrana worsens the condition of the patient with different complications and may become fatal. Local factors on wound like slough, infection and foreign body, affect the normal process of healing. A healthy wound in a normal body heals earlier with a minimum scar as compared to a contaminated wound. Therefore in this study all the efforts are made to make a Dushta Vrana into a Shuddha Vrana. Once the Vrana becomes Shuddha, Ropana of the Vrana will start. The objective of the study was to evaluate the clinical efficacy of Jatyadi Taila and Jatyadi Ghrita in Dushta Vrana. Clinically diagnosed 60 Patients of Dushta Vrana were randomly divided into two groups, each consisting of 30 Patients. Group A were treated with the Jatyadi Taila and Group B was treated by Jatyadi Ghrita. The results observed was based on the relief obtained on the subjective and objective parameters taken for consideration for this study viz, size of ulcer, discharge, smell, pain, burning sensation, itching and granulation were found significant (P Lass Than 0.05). On the basis of assessment criteria and overall result of treatment, the patients of Jatyadi Taila group showed better results when compared to Jatyadi Ghrita group. Even though statistically there is no much significant difference between the two groups, but by seeing the effect on individual parameters (subjective and objective) and over all response, Jatyadi Taila seems to be effective when compared to Jatyadi Ghrita. It is having more Ropana qualities when compared to Shodhana.

scholarly journals Impact of Face Masks on 6-Minute Walk Test in Healthy Volunteers

2021 ◽  
Vol 11 (1) ◽  
pp. 204589402098843
Author(s):  
Kevin M. Swiatek ◽  
Charnetta Lester ◽  
Nicole Ng ◽  
Saahil Golia ◽  
Janet Pinson ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Face Mask ◽  
Walk Test ◽  
Six Minute Walk Test ◽  
Significant Difference ◽  
6 Minute Walk Test ◽  
The Impact ◽  
Minute Walk

Our objective was to establish the impact of wearing a face mask on the outcome of six-minute walk test in healthy volunteers. In a study of 20 healthy volunteers who each completed two 6MWTs, one with a mask and one without, there was no difference in distance walked. However, there was a significant difference in perception of dyspnea between the two groups.

Safety evaluation of an antimalarial herbal product from Andrographis paniculata (AS201-01) in healthy volunteers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Aty Widyawaruyanti ◽  
Arijanto Jonosewojo ◽  
Hilkatul Ilmi ◽  
Lidya Tumewu ◽  
Ario Imandiri ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Healthy Volunteers ◽  
Day Treatment ◽  
Phase 1 ◽  
Andrographis Paniculata ◽  
Control Group ◽  
Healthy Human ◽  
Double Blind ◽  
Random Blood Glucose ◽  
Significant Difference

Abstract Objectives Andrographis paniculata tablets (AS201-01) have previously been shown to have potent bioactivity as an antimalarial and to produce no unwanted side effects in animal models. Here, we present the phase 1 clinical trial conducted to evaluate the safety of AS201-01 tablets in healthy volunteers. Methods The study was a randomized, double-blind controlled cross-over, a placebo-controlled design consisting of a 4-day treatment of AS201-01 tablets. A total of 30 healthy human volunteers (16 males and 14 females) were divided into two groups, and each group was given 4 tablets, twice daily for 4 days. Group 1 received AS201-01, while group 2 received placebo tablets. Volunteers were given a physical examination before the treatment. The effects of AS201-01 on random blood glucose, biochemical, and hematological as well as urine profiles were investigated. Results There were no changes in observed parameters as a result of AS201-01 being administered. Statistical analysis showed no significant difference (p>0.05) between the test and control group regarding hematology profile, biochemical profile, and random blood glucose. Increased appetite and better sleep, which categorized as grade 1 adverse event was reported after treatment with AS201-01 tablet Conclusions The outcome supports our previous observation that the AS201-01 tablet, given twice a day for 4 days, is safe and nontoxic.

scholarly journals Mortality after cardiopulmonary resuscitation on a medical ICU

2021 ◽  
Author(s):  
Richard Rezar ◽  
Bernhard Wernly ◽  
Michael Haslinger ◽  
Clemens Seelmaier ◽  
Philipp Schwaiger ◽  
...  
Keyword(s):  
Cardiopulmonary Resuscitation ◽  
Neurological Outcome ◽  
Cox Regression ◽  
Cerebral Performance Category ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Study Endpoint ◽  
Primary Study ◽  
Postresuscitation Care ◽  
Significant Difference

Summary Background Performing cardiopulmonary resuscitation (CPR) and postresuscitation care in the intensive care unit (ICU) are standardized procedures; however, there is evidence suggesting sex-dependent differences in clinical management and outcome variables after cardiac arrest (CA). Methods A prospective analysis of patients who were hospitalized at a medical ICU after CPR between December 2018 and March 2020 was conducted. Exclusion criteria were age < 18 years, hospital length of stay < 24 h and traumatic CA. The primary study endpoint was mortality after 6 months and the secondary endpoint neurological outcome assessed by cerebral performance category (CPC). Differences between groups were calculated by using U‑tests and χ2-tests, for survival analysis both univariate and multivariable Cox regression were fitted. Results A total of 106 patients were included and the majority were male (71.7%). No statistically significant difference regarding 6‑month mortality between sexes could be shown (hazard risk, HR 0.68, 95% confidence interval, CI 0.35–1.34; p = 0.27). Neurological outcome was also similar between both groups (CPC 1 88% in both sexes after 6 months; p = 1.000). There were no statistically significant differences regarding general characteristics, pre-existing diseases, as well as the majority of clinical and laboratory parameters or measures performed on the ICU. Conclusion In a single center CPR database no statistically significant sex-specific differences regarding post-resuscitation care, survival and neurological outcome after 6 months were observed.

scholarly journals Stereotactic cisternal lavage in patients with aneurysmal subarachnoid hemorrhage with urokinase and nimodipine for the prevention of secondary brain injury (SPLASH): study protocol for a randomized controlled trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Roland Roelz ◽  
Fabian Schubach ◽  
Volker A. Coenen ◽  
Carolin Jenkner ◽  
Christian Scheiwe ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Neurological Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Standard Of Care ◽  
Secondary Brain Injury ◽  
Ringer’S Solution ◽  
Randomized Controlled ◽  
Therapy Protocol

Abstract Background Delayed cerebral infarction (DCI) is a major cause of death and poor neurological outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). Direct intrathecal therapies with fibrinolytic and spasmolytic drugs have appeared promising in clinical trials. However, access to the subarachnoid space for intrathecal drug administration is an unsolved problem so far, especially in patients with endovascular aneurysm securing. We investigate a therapy protocol based on stereotactic catheter ventriculocisternostomy (STX-VCS), a new approach to overcome this problem. The primary objective of this study is to assess whether cisternal lavage with urokinase, nimodipine, and Ringer’s solution administered via a stereotactically implanted catheter into the basal cisterns (= investigational treatment (IT)) is safe and improves neurological outcome in patients with aSAH. Methods This is a randomized, controlled, parallel-group, open-label phase II trial. Fifty-four patients with severe aSAH (WFNS grade ≥ 3) will be enrolled at one academic tertiary care center in Southern Germany. Patients will be randomized at a ratio of 1:1 to receive either standard of care only or standard of care plus the IT. The primary endpoint is the proportion of subjects with a favorable outcome on the Modified Rankin Scale (defined as mRS 0–3) at 6 months after aSAH. Further clinical and surrogate outcome parameters are defined as secondary endpoints. Discussion New approaches for the prevention and therapy of secondary brain injury in patients with aSAH are urgently needed. We propose this RCT to assess the clinical safety and efficacy of a novel therapy protocol for intrathecal administration of urokinase, nimodipine, and Ringer’s solution. Trial registration Deutsches Register Klinischer Studien (German Clinical Trials Register), DRKS00015645. Registered on 8 May 2019

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