Rising Cardiac Troponin: A Prognostic Biomarker for Mortality After Acute Ischemic Stroke.

BACKGROUND: Elevated cardiac troponin (cTn) is detected in 10% to 30% of patients with acute ischemic stroke (AIS) and correlates with poor functional outcomes. Serial cTn measurements differentiate a dynamic cTn pattern (rise/fall >20%), specific for acute myocardial injury, from elevated but stable cTn levels (nondynamic), typically attributed to chronic cardiac/noncardiac conditions. We investigated if the direction of the cTn change (rising versus falling) affects mortality and outcome. METHODS AND RESULTS: We retrospectively screened consecutive patients with AIS admitted to 5 stroke centers for elevated cTn at admission and at least 1 additional cTn measurement within 48 hours. The pattern of cTn was defined as rising if >20% increase from baseline, falling if >20% decrease, or nondynamic if ≤20% change in either direction. Logistic regression analyses were performed to assess the association of cTn patterns and 7-day mortality and unfavorable discharge disposition. Of 3789 patients with AIS screened, 300 were included. Seventy-two had a rising pattern, 66 falling, and 162 nondynamic. In patients with AIS with rising cTn, acute ischemic myocardial infarction was present in 54%, compared with 33% in those with falling cTn (P<0.01). Twenty-two percent of patients with a rising pattern had an isolated dynamic cTn in the absence of any ECG or echocardiogram changes, compared with 53% with falling cTn. A rising pattern was associated with higher risk of 7-day mortality (adjusted odds ratio [OR]=32 [95% CI, 2.5-415.0] rising versus aOR=1.3 [95% CI, 0.1-38.0] falling versus nondynamic as reference) and unfavorable discharge disposition (aOR=2.5 [95% CI, 1.2-5.2] rising versus aOR=0.6 [95% CI, 0.2-1.5] versus falling). CONCLUSIONS: Rising cTn is independently associated with increased mortality and unfavorable discharge disposition in patients with AIS.

Stroke-Heart Syndrome: Does Sex Matter?

Background Cardiovascular complications after acute ischemic stroke (AIS) can be related to chronic/comorbid cardiac conditions or acute disruption of the brain-heart autonomic axis (stroke-heart syndrome). Women are known to be more vulnerable to certain stress-induced cardiac complications, such as Takotsubo cardiomyopathy. We investigated sex differences in cardiac troponin (cTn) elevation, cardiac events, and outcomes after AIS. Methods and Results We retrospectively analyzed consecutive patients with AIS from 5 stroke centers. Patients with AIS with elevated baseline cTn and at least 2 cTn measurements were included, while patients with acute comorbid conditions that could impact cTn levels were excluded. Poststroke acute myocardial injury was defined as the presence of a dynamic cTn pattern (rise/fall >20% in serial measurements) in the absence of acute atherosclerotic coronary disease (type 1 myocardial infarction) or cardiac death (type 3 myocardial infarction). From a total cohort of 3789 patients with AIS, 300 patients were included in the study: 160 were women (53%). Women were older, had a lower burden of cardiovascular risk factors, and more frequently had cardioembolic stroke and right insula involvement (P values all <0.05). In multivariate analysis, women were more likely to have a dynamic cTn pattern (adjusted odds ratio, 2.1 [95% CI, 1.2-3.6]) and develop poststroke acute myocardial injury (adjusted odds ratio, 2.1 [95% CI, 1.1-3.8]). Patients with poststroke acute myocardial injury had higher 7-day mortality (adjusted odds ratio, 5.5 [95% CI, 1.2-24.4]). Conclusions In patients with AIS with elevated cTn at baseline, women are twice as likely to develop poststroke acute myocardial injury, and this is associated with higher risk of short-term mortality. Translational studies are needed to clarify mechanisms underlying sex differences in cardiac events and mortality in AIS.

The need for a central brain tumor registry in Africa: A review of central nervous system tumors in Africa from 1960 to 2017.

BACKGROUND: Central nervous system (CNS) tumors pose a substantial health problem. Although data on specific time periods and regions of Africa have been previously reported, no study has yet to provide a systematic review of CNS tumors for the entire continent of Africa. This study aims to analyze the frequency of CNS tumors in Africa from 1960 to 2017. METHODS: A comprehensive literature search on CNS tumors in Africa was performed using multiple online scientific databases. The following keywords were queried in combination with the phrase "CNS tumors in Africa": incidence, frequency, epidemiology, prevalence, brain, and cancer. A total of 26 articles met the inclusion criteria. Each selected article reported incidence and mortality rates from different regions of Africa in a time period between 1960 and 2017. SPSS21 statistical software was used to analyze the data. RESULTS: Nigeria, Egypt, and Uganda were found to have the most of the cases of CNS tumors in Africa. Males made up 54% of the 5902 cases per 100 000 population. The most common CNS tumors found were astrocytoma (24.70%), meningioma (22.22%), pituitary adenoma (8.4%), medulloblastoma (4.26%), craniopharyngioma (4.07%), and other not specified (25.17%). CONCLUSIONS: Given the large population of Africa, the total reported cases may be underestimated when compared with other continents due to the lack of a central brain tumor registry in Africa. A comprehensive knowledge of CNS tumors in Africa is critical to population-based research and improving the current healthcare system.

An Exploratory Study of the Frequency of Central Nervous System Tumors by Type in the Central Texas Military and Civilian Populations.

BACKGROUND:  The types of central nervous system (CNS) tumors in a patient population with a history of military service were compared to the types of CNS tumors in a similar patient population without a military service history to determine if a relationship exists between military service and CNS tumor type. METHODS:  This study analyzed data for adult patients diagnosed with an intra- or extra-axial CNS tumor from January 2016 to July 2019. One cohort was constructed of patients who had a history of military service (MIL), and the other cohort was made of patients who did not have a history of military service (NMIL). Appropriate parametric and non-parametric analyses were used to compare frequencies of tumor types between cohorts adjusting for potential confounders. RESULTS:  We identified 2001 patients (MIL, n = 190; NMIL, n = 1811). In the MIL cohort, most patients were males, younger, and more racially diverse. In the primary analysis, the MIL cohort showed higher diagnoses of metastatic tumors compared with the NMIL cohort (X2(1)= 3.71, p=.05). The MIL cohort also showed lower diagnoses of meningioma compared to the NMIL cohort. There was no statically significant difference between cohorts or tumors after adjusting for primary source by gender. CONCLUSIONS:  MIL experience was associated with lower diagnoses of meningioma but higher diagnoses of metastatic cancer, providing support that there may be potential differences in tumor types between patients with a history of military service and those without military history regarding primary CNS tumor frequency.

Elevated circulating TGFß1 during acute liver failure activates TGFßR2 on cortical neurons and exacerbates neuroinflammation and hepatic encephalopathy in mice.

BACKGROUND: Acute liver failure resulting from drug-induced liver injury can lead to the development of neurological complications called hepatic encephalopathy (HE). Hepatic transforming growth factor beta 1 (TGFß1) is upregulated due to liver failure in mice and inhibiting circulating TGFß reduced HE progression. However, the specific contributions of TGFß1 on brain cell populations and neuroinflammation during HE are not known. Therefore, the aim of this study was to characterize hepatic and brain TGFß1 signaling during acute liver failure and its contribution to HE progression using a combination of pharmacological and genetic approaches. METHODS: C57Bl/6 or neuron-specific transforming growth factor beta receptor 2 (TGFßR2) null mice (TGFßR2ΔNeu) were treated with azoxymethane (AOM) to induce acute liver failure and HE. The activity of circulating TGFß1 was inhibited in C57Bl/6 mice via injection of a neutralizing antibody against TGFß1 (anti-TGFß1) prior to AOM injection. In all mouse treatment groups, liver damage, neuroinflammation, and neurological deficits were assessed. Inflammatory signaling between neurons and microglia were investigated in in vitro studies through the use of pharmacological inhibitors of TGFß1 signaling in HT-22 and EOC-20 cells. RESULTS: TGFß1 was expressed and upregulated in the liver following AOM injection. Pharmacological inhibition of TGFß1 after AOM injection attenuated neurological decline, microglia activation, and neuroinflammation with no significant changes in liver damage. TGFßR2ΔNeu mice administered AOM showed no effect on liver pathology but significantly reduced neurological decline compared to control mice. Microglia activation and neuroinflammation were attenuated in mice with pharmacological inhibition of TGFß1 or in TGFßR2ΔNeu mice. TGFß1 increased chemokine ligand 2 (CCL2) and decreased C-X3-C motif ligand 1 (CX3CL1) expression in HT-22 cells and reduced interleukin-1 beta (IL-1ß) expression, tumor necrosis factor alpha (TNFα) expression, and phagocytosis activity in EOC-20 cells. CONCLUSION: Increased circulating TGFß1 following acute liver failure results in activation of neuronal TGFßR2 signaling, driving neuroinflammation and neurological decline during AOM-induced HE.