scholarly journals High CSF thrombin concentration and activity is associated with an unfavorable outcome in patients with intracerebral hemorrhage

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0241565
Author(s):  
Harald Krenzlin ◽  
Christina Frenz ◽  
Jan Schmitt ◽  
Julia Masomi-Bornwasser ◽  
Dominik Wesp ◽  
...  

Background The cerebral thrombin system is activated in the early stage after intracerebral hemorrhage (ICH). Expression of thrombin leads to concentration dependent secondary neuronal damage and detrimental neurological outcome. In this study we aimed to investigate the impact of thrombin concentration and activity in the cerebrospinal fluid (CSF) of patients with ICH on clinical outcome. Methods Patients presenting with space-occupying lobar supratentorial hemorrhage requiring extra-ventricular drainage (EVD) were included in our study. The CSF levels of thrombin, its precursor prothrombin and the Thrombin-Antithrombin complex (TAT) were measured using enzyme linked immune sorbent assays (ELISA). The oxidative stress marker Superoxide dismutase (SOD) was assessed in CSF. Initial clot size and intraventricular hemorrhage (IVH) volume was calculated based on by computerized tomography (CT) upon admission to our hospital. Demographic data, clinical status at admission and neurological outcome were assessed using the modified Rankin Scale (mRS) at 6-weeks and 6-month after ICH. Results Twenty-two consecutive patients (9 females, 11 males) with supratentorial hemorrhage were included in this study. CSF concentrations of prothrombin (p < 0.005), thrombin (p = 0.005) and TAT (p = 0.046) were statistical significantly different in patients with ICH compared to non-hemorrhagic CSF samples. CSF concentrations of thrombin 24h after ICH correlated with the mRS index after 6 weeks (r2 = 0.73; < 0.005) and 6 months (r2 = 0.63; < 0.005) after discharge from hospital. Thrombin activity, measured via TAT as surrogate parameter of coagulation, likewise correlated with the mRS at 6 weeks (r2 = 0.54; < 0.01) and 6 months (r2 = 0.66; < 0.04). High thrombin concentrations coincide with higher SOD levels 24h after ICH (p = 0.01). Conclusion In this study we found that initial thrombin concentration and activity in CSF of ICH patients did not correlate with ICH and IVH volume but are associated with a poorer functional neurological outcome. These findings support mounting evidence of the role of thrombin as a contributor to secondary injury formation after ICH.

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Chelsea S Kidwell ◽  
Laura German ◽  
Ravi S Menon ◽  
Nawar Shara ◽  
M. Christopher Gibbons ◽  
...  

Background: Previous studies have reported racial differences in the incidence, location and risk factors for primary intracerebral hemorrhage (ICH). We now report differences in imaging characteristics and risk factors for ICH from the DiffErenCes in the Imaging of Primary Hemorrhage based on Ethnicity or Race (DECIPHER) study. Methods: DECIPHER is a longitudinal, multicenter, MRI-based, natural history study of racial differences in primary ICH. Inclusion criteria were: primary ICH, age ≥ 18, baseline and 1 year MRI scan obtained. Clinical and demographic data were collected on all subjects. Results: A total of 193 subjects of black or white race were enrolled. Subject characteristics overall and by race are provided in the table. Black subjects were younger, had a higher rate of hypertension, cocaine use, and were more frequently smokers. White subjects had a higher rate of hyperlipidemia. A lobar ICH location was more frequent in the white subjects, while infratentorial hemorrhages were more common in blacks. 60% of blacks had 1 or more microbleeds compared to 52% of whites (NS), and blacks tended to have more severe white matter disease. Conclusions: In the DECIPHER study, there were significant racial differences both in the risk factors for primary ICH and in the imaging characteristics. Compared to whites, blacks have a greater rate of hypertension, as well as cocaine and tobacco use. Imaging findings are indicative of a more severe underlying small vessel vasculopathy in the black cohort. The risk factor information may be used to enhance prevention programs tailored for black communities at risk of ICH, while imaging data may provide a useful biomarker to assess the impact of these interventions.


2015 ◽  
Vol 122 (2) ◽  
pp. 408-413 ◽  
Author(s):  
Christian Fung ◽  
Mathias Balmer ◽  
Michael Murek ◽  
Werner J. Z'Graggen ◽  
Janine Abu-Isa ◽  
...  

OBJECT After subarachnoid hemorrhage (SAH), seizure occurs in up to 26% of patients. The impact of seizure on outcome has been studied, yet its impact on grading is unknown. The authors evaluated the impact of early-onset seizures (EOS) on grading of spontaneous SAH and on outcome. METHODS This retrospective analysis included consecutive patients with SAH who were treated at the NeuroCenter, Inselspital, University Hospital Bern, Switzerland, between January 2005 and December 2010. Demographic data, clinical data, and reports of EOS were recorded. The EOS were defined as seizures occurring within 24 hours after ictus. Patients were graded according to the World Federation of Neurosurgical Societies (WFNS) scale pre- and postresuscitation and dichotomized into good (WFNS I–III) and poor (WFNS IV–V) grades. Outcome was assessed at 6 months by using the modified Rankin Scale (mRS); an mRS score of 0–3 was considered a good outcome and an mRS score of 4–6 was considered a poor outcome. RESULTS Forty-one of 425 patients with SAH had EOS. Twenty-seven of those 41 patients (65.9%) had a poor WFNS grade. Twenty-eight (68.3%) achieved a good outcome, 11 (26.8%) had a poor outcome, and 2 (4.9%) were lost to followup. Early-onset seizures were proven in 9 of 16 electroencephalograms. The EOS were associated with poor WFNS grade (OR 2.81, 97.5% CI 1.14–7.46; p = 0.03) and good outcome (OR 4.01, 97.5% CI 1.63–10.53; p = 0.03). Increasing age, hydrocephalus, intracerebral hemorrhage, and intraventricular hemorrhage were associated with poor WFNS grade, whereas only age, intracerebral hemorrhage (p < 0.001), and poor WFNS grade (p < 0.001) were associated with poor outcome. CONCLUSIONS Patients with EOS were classified significantly more often in a poor grade initially, but then they significantly more often achieved a good outcome. The authors conclude that EOS can negatively influence grading. This might influence decision making for the care of patients with SAH, so grading of patients with EOS should be interpreted with caution.


2019 ◽  
Vol 18 (3) ◽  
pp. 205-211 ◽  
Author(s):  
Lingzhi Li ◽  
Pingping Wang ◽  
Haiping Zhao ◽  
Yumin Luo

Background & Objective:Intracerebral hemorrhage (ICH) is the most devastating subtype of stroke, for which there are few effective interventions. Computed tomography is accepted as the gold standard for diagnosis, whereas surgical evacuation is the main treatment for ICH. However, in emergency rooms, time is limited and information regarding a patient’s clinical status or tolerance is typically not available. Many studies over the last decade have investigated the fundamental mechanisms of ICH and especially hematoma, which not only cause physical damage but also release toxins that have detrimental effects. However, there remain many gaps in our understanding of ICH. Compared to ischemic stroke, there is little known about the ICH pathogenesis and treatment options, and few specific biomarkers are available for monitoring disease progression, which include hematoma enlargement and perihematoma edema. Noncoding RNAs (ncRNAs) are involved in various biological processes and are potential biomarkers and therapeutic tools in central nervous system diseases. Recent studies have examined the role of ncRNAs including microRNAs, long noncoding RNAs, and circular RNAs—the three main subgroups associated with stroke—in ICH models. A deeper understanding of the functions of ncRNAs in different biological processes can provide a basis for developing more effective therapeutic strategies to prevent neuronal damage following ICH. In clinical settings, ncRNAs can serve as biomarkers for predicting the degree of injury resulting from ICH.Conclusion:In this review, we discuss the current state of knowledge of the role of ncRNAs in ICH.


2017 ◽  
Vol 15 (2) ◽  
pp. 78
Author(s):  
M. Zainuddin

This research to analyze the impact of closure policy Teleju brothel by Pekanbaru govermentin 2010. Guidelines for works are Pekanbaru Local Regulations No. 12 of 2008 on Social Order-liness. Closure this brothel inflicts positive and negative impact for society.The research wasconducted to obtain early stage formula for the government to take action against the prostitu-tion activities. This research uses policy research approach with a qualitative method, becausein prostitution activities and prohibition by goverment is an assessment that needs to be done byanalyzing documents and unstructured interview.The results showed that after the closing of the Teleju brothel have an impact on the deploy-ment of a prostitution and affect the economy of the surrounding residents. Government seeksto tackle prostitution in Pekanbaru by moving the brothel, conduct regular raids and providetraining. The effort is considered to be less than the maximum because the handling is not basedon the root of the problem and not programmed properly. There are several causes of failure ofgovernment to overcome the prostitution problem in Pekanbaru, including: policy content isless focus on the prostitution problem, the government did not proceeds with data, lack of finan-cial support, contra productive programs between local government with the police and TNI,and the policy object is difficult to be given understanding.


2020 ◽  
Vol 17 (1) ◽  
pp. 93-103 ◽  
Author(s):  
Jing Ma ◽  
Yuan Gao ◽  
Wei Tang ◽  
Wei Huang ◽  
Yong Tang

Background: Studies have suggested that cognitive impairment in Alzheimer’s disease (AD) is associated with dendritic spine loss, especially in the hippocampus. Fluoxetine (FLX) has been shown to improve cognition in the early stage of AD and to be associated with diminishing synapse degeneration in the hippocampus. However, little is known about whether FLX affects the pathogenesis of AD in the middle-tolate stage and whether its effects are correlated with the amelioration of hippocampal dendritic dysfunction. Previously, it has been observed that FLX improves the spatial learning ability of middleaged APP/PS1 mice. Objective: In the present study, we further characterized the impact of FLX on dendritic spines in the hippocampus of middle-aged APP/PS1 mice. Results: It has been found that the numbers of dendritic spines in dentate gyrus (DG), CA1 and CA2/3 of hippocampus were significantly increased by FLX. Meanwhile, FLX effectively attenuated hyperphosphorylation of tau at Ser396 and elevated protein levels of postsynaptic density 95 (PSD-95) and synapsin-1 (SYN-1) in the hippocampus. Conclusion: These results indicated that the enhanced learning ability observed in FLX-treated middle-aged APP/PS1 mice might be associated with remarkable mitigation of hippocampal dendritic spine pathology by FLX and suggested that FLX might be explored as a new strategy for therapy of AD in the middle-to-late stage.


2020 ◽  
Vol 21 (15) ◽  
pp. 5475 ◽  
Author(s):  
Manuela Pennisi ◽  
Giuseppe Lanza ◽  
Luca Falzone ◽  
Francesco Fisicaro ◽  
Raffaele Ferri ◽  
...  

Increasing evidence suggests that Severe Acute Respiratory Syndrome-coronavirus-2 (SARS-CoV-2) can also invade the central nervous system (CNS). However, findings available on its neurological manifestations and their pathogenic mechanisms have not yet been systematically addressed. A literature search on neurological complications reported in patients with COVID-19 until June 2020 produced a total of 23 studies. Overall, these papers report that patients may exhibit a wide range of neurological manifestations, including encephalopathy, encephalitis, seizures, cerebrovascular events, acute polyneuropathy, headache, hypogeusia, and hyposmia, as well as some non-specific symptoms. Whether these features can be an indirect and unspecific consequence of the pulmonary disease or a generalized inflammatory state on the CNS remains to be determined; also, they may rather reflect direct SARS-CoV-2-related neuronal damage. Hematogenous versus transsynaptic propagation, the role of the angiotensin II converting enzyme receptor-2, the spread across the blood-brain barrier, the impact of the hyperimmune response (the so-called “cytokine storm”), and the possibility of virus persistence within some CNS resident cells are still debated. The different levels and severity of neurotropism and neurovirulence in patients with COVID-19 might be explained by a combination of viral and host factors and by their interaction.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rahinatou N. Ghapoutsa ◽  
Maurice Boda ◽  
Rashi Gautam ◽  
Valantine Ngum Ndze ◽  
Akongnwi E. Mugyia ◽  
...  

Abstract Background Despite the global roll-out of rotavirus vaccines (RotaTeq/Rotarix / ROTAVAC/Rotasiil), mortality and morbidity due to group A rotavirus (RVA) remains high in sub-Saharan Africa, causing 104,000 deaths and 600,000 hospitalizations yearly. In Cameroon, Rotarix™ was introduced in March 2014, but, routine laboratory diagnosis of rotavirus infection is not yet a common practice, and vaccine effectiveness studies to determine the impact of vaccine introduction have not been done. Thus, studies examining RVA prevalence post vaccine introduction are needed. The study aim was to determine RVA prevalence in severe diarrhoea cases in Littoral region, Cameroon and investigate the role of other diarrheagenic pathogens in RVA-positive cases. Methods We carried out a study among hospitalized children < 5 years of age, presenting with acute gastroenteritis in selected hospitals of the Littoral region of Cameroon, from May 2015 to April 2016. Diarrheic stool samples and socio-demographic data including immunization and breastfeeding status were collected from these participating children. Samples were screened by ELISA (ProSpecT™ Rotavirus) for detection of RVA antigen and by gel-based RT-PCR for detection of the VP6 gene. Co-infection was assessed by multiplexed molecular detection of diarrheal pathogens using the Luminex xTAG GPP assay. Results The ELISA assay detected RVA antigen in 54.6% (71/130) of specimens, with 45, positive by VP6 RT-PCR and 54, positive using Luminex xTAG GPP. Luminex GPP was able to detect all 45 VP6 RT-PCR positive samples. Co-infections were found in 63.0% (34/54) of Luminex positive RVA infections, with Shigella (35.3%; 12/34) and ETEC (29.4%; 10/34) detected frequently. Of the 71 ELISA positive RVA cases, 57.8% (41/71) were fully vaccinated, receiving two doses of Rotarix. Conclusion This study provides insight on RVA prevalence in Cameroon, which could be useful for post-vaccine epidemiological studies, highlights higher than expected RVA prevalence in vaccinated children hospitalized for diarrhoea and provides the trend of RVA co-infection with other enteric pathogens. RVA genotyping is needed to determine circulating rotavirus genotypes in Cameroon, including those causing disease in vaccinated children.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2897
Author(s):  
Néstor Martínez-Hernández ◽  
Usue Caballero Silva ◽  
Alberto Cabañero Sánchez ◽  
José Luis Campo-Cañaveral de la Cruz ◽  
Andrés Obeso Carillo ◽  
...  

After the first wave of COVID-19, the Spanish Society of Thoracic Surgeons (SECT) surveyed its members to assess the impact of the pandemic on thoracic oncology surgery in Spain. In May 2020, all SECT members were invited to complete an online, 40-item, multiple choice questionnaire. The questionnaire was developed by the SECT Scientific Committee and sent via email. The overall response rate was 19.2%. The respondents answered at least 91.5% of the items, with only one exception (a question about residents). Most respondents (89.3%) worked in public hospitals. The reported impact of the pandemic on routine clinical activity was considered extreme or severe by 75.5% of respondents (25.5% and 50%, respectively). Multidisciplinary tumour boards were held either with fewer members attending or through electronic platforms (44.6% and 35.9%, respectively). Surgical activity decreased by 95.7%, with 41.5% of centers performing surgery only on oncological patients and 11.7% only in emergencies. Nearly 60% of respondents reported modifying standard protocols for early-stage cancer and in the preoperative workup. Most centers (≈80%) reported using full personal protective equipment when operating on COVID-19 positive patients. The COVID-19 pandemic severely affected thoracic oncology surgery in Spain. The lack of common protocols led to a variable care delivery to lung cancer patients.


2021 ◽  
pp. 089719002110282
Author(s):  
Karan Raja ◽  
Nicole Daniel ◽  
Susan Morrison ◽  
Ruben Patel ◽  
Jessica Gerges ◽  
...  

Background: Tocilizumab is an interleukin-6 receptor antagonist hypothesized to blunt the uncontrolled immune response, cytokine release syndrome, in severe COVID-19 and prevent attributable morbidity and mortality. Objective: The objective of this study was to assess the impact of tocilizumab on clinical outcomes in COVID-19-associated cytokine release syndrome. Methods: Single-center, retrospective cohort study assessing sixty-nine adult patients receiving tocilizumab for suspected COVID-19 cytokine release syndrome. The primary outcome was change in WHO clinical status scale on day seven post-dose analyzed using the Wilcoxon signed rank test. Secondary outcomes assessed impact of timing of administration on clinical outcome. Safety analyses included development of neutropenia, thrombocytopenia, transaminitis, and sepsis within 7 days post-dose. Statistical analyses were conducted using Microsoft Excel. Results: No aggregate clinical change was found between day 0 and day 7. Eleven patients improved, twenty-seven worsened, and thirty-one showed no change. Clinical outcomes were weakly correlated with time from symptom onset (rs = 0.21; p = 0.08) or hospital admission (rs = -0.08; p = 0.49) to dose. In-hospital mortality was 63%. Sepsis was diagnosed in 21 patients, five of which were post-dose. Transaminitis, neutropenia, and thrombocytopenia occurred in seven, one, and six patients, respectively. Conclusion: Tocilizumab did not appear to influence clinical outcomes in our study population, irrespective of timing of administration. Adverse events were not considered drug-related.


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