The Effect of Tranexamic Acid on Neurosurgical Intervention in Spontaneous Intracerebral Hematoma: Data From 121 Surgically Treated Participants From the Tranexamic Acid in IntraCerebral Hemorrhage-2 Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: An important proportion of patients with spontaneous intracerebral hemorrhage (ICH) undergo neurosurgical intervention to reduce mass effect from large hematomas and control the complications of bleeding, including hematoma expansion and hydrocephalus. The Tranexamic acid (TXA) for hyperacute primary IntraCerebral Hemorrhage (TICH-2) trial demonstrated that tranexamic acid (TXA) reduces the risk of hematoma expansion. We hypothesized that TXA would reduce the frequency of surgery (primary outcome) and improve functional outcome at 90 days in surgically treated patients in the TICH-2 data set. METHODS: Participants enrolled in TICH-2 were randomized to placebo or TXA. Participants randomized to either TXA or placebo were analyzed for whether they received neurosurgery within 7 days and their characteristics, outcomes, hematoma volumes (HVs) were compared. Characteristics and outcomes of participants who received surgery were also compared with those who did not. RESULTS: Neurosurgery was performed in 5.2% of participants (121/2325), including craniotomy (57%), hematoma drainage (33%), and external ventricular drainage (21%). The number of patients receiving surgery who received TXA vs placebo were similar at 4.9% (57/1153) and 5.5% (64/1163), respectively (odds ratio [OR] 0.893; 95% CI 0.619-1.289; P-value = .545). TXA did not improve outcome compared with placebo in either surgically treated participants (OR 0.79; 95% CI 0.30-2.09; P = .64) or those undergoing hematoma evacuation by drainage or craniotomy (OR 1.19 95% 0.51-2.78; P-value = .69). Postoperative HV was not reduced by TXA (mean difference -8.97 95% CI -23.77, 5.82; P-value = .45). CONCLUSION: TXA was not associated with less neurosurgical intervention, reduced HV, or improved outcomes after surgery.

Prognosis Factors of Patients Undergoing Renal Replacement Therapy.

BACKGROUND: Survival in patients with end-stage kidney disease (ESKD) on renal replacement therapy (RRT) is less than that of the general population of the same age, and depends on patient factors, the medical care received, and the type of RRT used. The objective of this study is to analyze the factors associated with survival in patients undergoing RRT. METHODS: We conducted a retrospective observational study of adult patients with an incident of ESKD on RRT in Andalusia from 1 January 2008 to 31 December 2018. Patient characteristics, nephrological care received, and survival from the beginning of RRT were evaluated. A survival model for the patient was developed according to the variables studied. RESULTS: A total of 11,551 patients were included. Median survival was 6.8 years (95% CI (6.6; 7.0)). After starting RRT, survival at one year and five years was 88.7% (95% CI (88.1; 89.3)) and 59.4% (95% CI (58.4; 60.4)), respectively. Age, initial comorbidity, diabetic nephropathy, and a venous catheter were independent risk factors. However, non-urgent initiation of RRT and follow-up in consultations for more than six months had a protective effect. It was identified that renal transplantation (RT) was the most influential independent factor in patient survival, with a risk ratio of 0.13 (95% CI (0.11; 0.14)). CONCLUSIONS: The receiving of a kidney transplant was the most beneficial modifiable factor in the survival of incident patients on RRT. We consider that the mortality of the renal replacement treatment should be adjusted, taking into account both modifiable and nonmodifiable factors to achieve a more precise and comparable interpretation.

Deep Learning Applied to Intracranial Hemorrhage Detection.

Intracranial hemorrhage is a serious medical problem that requires rapid and often intensive medical care. Identifying the location and type of any hemorrhage present is a critical step in the treatment of the patient. Detection of, and diagnosis of, a hemorrhage that requires an urgent procedure is a difficult and time-consuming process for human experts. In this paper, we propose methods based on EfficientDet's deep-learning technology that can be applied to the diagnosis of hemorrhages at a patient level and which could, thus, become a decision-support system. Our proposal is two-fold. On the one hand, the proposed technique classifies slices of computed tomography scans for the presence of hemorrhage or its lack of, and evaluates whether the patient is positive in terms of hemorrhage, and achieving, in this regard, 92.7% accuracy and 0.978 ROC AUC. On the other hand, our methodology provides visual explanations of the chosen classification using the Grad-CAM methodology.

Immunomodulation of Oxidative Stress during Organ Donation Process: Preliminary Results.

The objective was to quantify oxidative stress resulting from ischemia during the donation process, using malondialdehyde (MDA) measurement, and its modulation by the administration of melatonin. We designed a triple-blind clinical trial with donors randomized to melatonin or placebo. We collected donors by donation after brain death (DBD) and controlled donation after circulatory death (DCD), the latter maintained by normothermic regional perfusion (NRP). Melatonin or placebo was administered prior to donation or following limitation of therapeutic effort (LTE). Demographic variables and medical history were collected. We also collected serial measurements of MDA, at 60 and 90 min after melatonin or placebo administration. A total of 53 donors were included (32 from DBD and 21 from DCD). In the DBD group, 17 donors received melatonin, and 15 placebo. Eight DCD donors were randomized to melatonin and 13 to placebo. Medical history and cause for LTE were similar between groups. Although MDA values did not differ in the DBD group, statistical differences were observed in DCD donors during the 0-60 min interval: -4.296 (-6.752; -2.336) in the melatonin group and -1.612 (-2.886; -0.7445) in controls. Given the antioxidant effect of melatonin, its use could reduce the production of oxidative stress in controlled DCD.

Effectiveness Factors of Organ Donation in Andalusia.

OBJECTIVES: Donation effectiveness is one of the most important factors for the sustainability of the donation transplant process. The aim of this study was to characterize and identify hypothetical factors associated with effective donation (at least one organ transplanted) in the Andalusian population. METHOD: Cross-sectional descriptive observational study of a sample of 4144 potential organ donors registered in the Andalusian Information System of Transplant from January 2006 to December 2018. Donors were categorized according to the result of the donation and analyzed depending their effectiveness. RESULTS: The Andalusian donors were mainly men (60%) and were between 55 and 75 years of age (47.6%). The majority died of brain death (87.45%) caused by a cerebrovascular accident (63.5%). They had cardiovascular risk factors such as hypertension (38.3%), diabetes mellitus (14.8%), dyslipidemia (11.1%), smoking (20.4%), and overweight with a median body mass index of 27.1 kg/m2 (IQR, 24.6-29.4). Effective donor rate was 84.5%. Increasing age, diabetes mellitus, increasing body mass index, and the presence of antibodies against hepatitis C virus were hypothetical predictors of an ineffective donation. CONCLUSIONS: In view of our results, we can say that the Andalusian donor population has a high effectiveness rate, presenting hypothetical factors that could allow one to predict the outcome of an effective donation.

Brief Consent Methods Enable Rapid Enrollment in Acute Stroke Trial: Results From the TICH-2 Randomized Controlled Trial.

BACKGROUND: Seeking consent rapidly in acute stroke trials is crucial as interventions are time sensitive. We explored the association between consent pathways and time to enrollment in the TICH-2 (Tranexamic Acid in Intracerebral Haemorrhage-2) randomized controlled trial. METHODS: Consent was provided by patients or by a relative or an independent doctor in incapacitated patients, using a 1-stage (full written consent) or 2-stage (initial brief consent followed by full written consent post-randomization) approach. The computed tomography-to-randomization time according to consent pathways was compared using the Kruskal-Wallis test. Multivariable logistic regression was performed to identify variables associated with onset-to-randomization time of ≤3 hours. RESULTS: Of 2325 patients, 817 (35%) gave self-consent using 1-stage (557; 68%) or 2-stage consent (260; 32%). For 1507 (65%), consent was provided by a relative (1 stage, 996 [66%]; 2 stage, 323 [21%]) or a doctor (all 2-stage, 188 [12%]). One patient did not record prerandomization consent, with written consent obtained subsequently. The median (interquartile range) computed tomography-to-randomization time was 55 (38-93) minutes for doctor consent, 55 (37-95) minutes for 2-stage patient, 69 (43-110) minutes for 2-stage relative, 75 (48-124) minutes for 1-stage patient, and 90 (56-155) minutes for 1-stage relative consents (P<0.001). Two-stage consent was associated with onset-to-randomization time of ≤3 hours compared with 1-stage consent (adjusted odds ratio, 1.9 [95% CI, 1.5-2.4]). Doctor consent increased the odds (adjusted odds ratio, 2.3 [1.5-3.5]) while relative consent reduced the odds of randomization ≤3 hours (adjusted odds ratio, 0.10 [0.03-0.34]) compared with patient consent. Only 2 of 771 patients (0.3%) in the 2-stage pathways withdrew consent when full consent was sought later. Two-stage consent process did not result in higher withdrawal rates or loss to follow-up. CONCLUSIONS: The use of initial brief consent was associated with shorter times to enrollment, while maintaining good participant retention. Seeking written consent from relatives was associated with significant delays. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.

Outcomes in Antiplatelet-Associated Intracerebral Hemorrhage in the TICH-2 Randomized Controlled Trial.

Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH-2 (Tranexamic Acid in Intracerebral Hemorrhage-2) double-blind, randomized, placebo-controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre-ICH antiplatelet therapy, and 24-hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre-ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no-antiplatelet group. Pre-ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01-1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32-1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25-2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62-0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41-0.91) with no significant interaction between pre-ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN93732214.

Continuing Training Accreditation in the Organ Donation Process in Andalusia: Results From the Education and Training Unit of the Regional Transplant Organization of Andalusia.

OBJECTIVE: The objective of this study is to evaluate the results obtained by the Training Unit of the Regional Transplant Organization of Andalusia from 2015 to 2017. METHODS: The following indicators were analyzed: number of activities carried out, number of students trained per year, students who do not complete the course, student and teacher satisfaction, learning assessment via postformation test, and transfer of training to the workplace. RESULTS: Between the years 2015 to 2017, 86 courses were carried out, and 2600 students were trained (1325 doctors, 1064 nurses, and 211 students with other degrees). A total of 83 students (3.2%) withdrew from training after its initiation. The overall assessments from teachers and students were 95/100 and 92/100, respectively. Student scores from the postformation test to assess learning averaged 77 points. CONCLUSION: It is worth noting the elevated number of courses offered and students trained over this 3-year period. We believe this has had a strong impact on the donation rate in Andalusia, which rose from 37.5 donors per million inhabitants in 2014 to 52.5 donors in 2018. Although student and teacher satisfaction was very high, it is clear that the transfer of new skills to the workplace could benefit from improvements in teamwork, communication with the transplant coordinator, the overall work environment, and the resources at their disposal.

Geographic Information System Analysis: Promoting the Organ Donation Process in Andalusia.

OBJECTIVE: The objective is to study the geographic distribution of public awareness and acceptance of organ donation in Andalusian municipalities and determine its relationship with each population and the rate of aging. METHODS: Data on organ donors from the Information System for Autonomous Regional Transplant Coordination in Andalusia were analyzed from 2006 to 2017. The geographic analysis was performed using free software from the Generalitat Valenciana Geographic Information System (gvGIS, Valencia, Spain). Data from the Spanish National Statistics Institute for the year 2017 were used as a reference for population estimates and calculating the rate of aging. RESULTS: From 2006 to 2017, a total of 3698 donors were registered in Andalusia, 28 of whom were residing in another autonomous community and 120 who were not censored as residents of their municipality, leaving a final total of 3550 donors. The rate of aging in 2017 was 1.02. Choropleth mapping was used to identify donors in each municipality. Population and aging rate in 2017 for these areas were also analyzed. CONCLUSION: Georeferenced data on organ donation not only reveals spatial differences in the distribution of public acceptance; it also provides insight into the relationship between this distribution and the sociodemographic characteristics of each community. In this study, areas with the least number of donors seem to coincide with difficult accessibility, higher aging index, and low population rates. These maps can assist transplant coordinators in targeting areas for public education and information campaigns to heighten awareness of the positive results of organ donation and potentiate its acceptance.

False-Positive Tumor During Organ Retrieval: All Cats Are Gray in the Dark.

OBJECTIVE: Efforts to expand the organ donor pool to meet growing transplant demands remains a top priority, as does maintaining the quality and safety standards of potential recipients. There is a short window of time from organ retrieval to decision making on organ acceptance, based on the available data. Furthermore, the limitations of intraoperative biopsy can often lead to donor or organ refusal due to a suspected tumor, which, if not confirmed in the final biopsy, results in the loss of a transplant opportunity. METHODS: Donor characteristics and organs discarded on suspicion of neoplastic disease at the time of extraction were analyzed in Andalusia between January 2014 and July 2018. The variable analysis included sociodemographic data, type of donor, location of the potential malignancy, histopathologic examination, and discarded organs. RESULTS: A total of 43 cases were identified. The organs of 33 donors (76.7%) were discarded. Kidneys were the most frequent location for a suspected tumor (44%), followed by the liver (21%). In 18 of the 43 cases (42%), the suspected malignancy was not confirmed, and of these, only 3 livers and 1 kidney were implanted. Sixty potentially transplantable organs were discarded, including those that would have been extracted and/or implanted in the absence of a suspected tumor. CONCLUSIONS: These results highlight the need not only to improve the accuracy of intraoperative biopsies but to seek new decision-making strategies for the short interval after organ retrieval. This involves avoiding both extremes of donation contraindications, while maintaining quality and safety standards.

Transplant of Tissue-Engineered Artificial Autologous Human Skin in Andalusia: An Example of Coordination and Institutional Collaboration.

A new model of tissue-engineered artificial autologous human skin developed in Andalusia is currently being transplanted into patients suffering from large burns within the Andalusian Public Healthcare System. This product is considered an advanced therapy medicinal product (ATMP) in Europe, and its clinical use implies meeting transplant and medicinal product legal requirements, being the Guidelines of Good Manufacturing Practice for ATMPs of particular importance. The preclinical research and clinical translation of the product have represented a technical, regulatory, and organizational challenge, which has taken 10 years since the first preclinical experiments were designed. Twelve patients with large burns, including 3 pediatric patients, have hitherto received artificial autologous skin grafts with an overall survival rate of 75% and positive clinical, homeostatic, and histologic results. Achieving such a milestone within our Healthcare System was possible through a multidisciplinary approach and the joint efforts of multiple publicly funded institutions and units under the coordination of the Andalusian Initiative for Advanced Therapies. In this article, we present the organizational model set up to facilitate collaboration and logistics among the professionals involved, totaling more than 80 people. The similarities between the tissue-engineered artificial autologous human skin transplant and other organ and tissue transplants, in terms of logistic requirements, reveal how regional and hospital transplant coordination have played a crucial role.

Normothermic Regional Perfusion and Donation After Circulatory Death (Controlled and Uncontrolled): Metabolic Differences and Kidney Transplantation Evolution.

OBJECTIVE: To analyze metabolic differences during normothermic regional perfusion (NRP) between the dissimilar types of donation after circulatory death, uncontrolled (uDCD) and controlled (cDCD), and the evolution of the transplanted kidneys. METHODS: Observational, prospective, cohort study. We included patients from uDCD and cDCD maintained with NRP in 2017. Six consecutive blood gases were collected with determination of pH and lactic acid. Creatinine levels were monitored at 24 hours, 3 months, and 6 months after transplant and the need for renal replacement therapy was evaluated. Descriptive statistical analysis was performed, presenting the qualitative variables as frequencies and percentages, and quantitative as mean ± SD or median (interquartile range [IQR]). We used χ2 testing for bivariate analysis of qualitative variables. RESULTS: We collected 18 donors. Fifteen out of 18 (83.3%) were men with a median of 51 years (IQR, 46-60). Eleven out of 18 (61.1%) were cDCD and 7 out of 18 (38.9%) were uDCD. The blood gas results are illustrated in Table 1. A total of 28 renal transplants were obtained with a median age of 47 years (IQR, 45-57); 83% were male. Ten out of 28 (35.7%) came from uDCD and 18 out of 28 (64.7%) from cDCD. Table 2 shows the monitoring of the creatinine values of the recipients after the transplantation. CONCLUSIONS: There are more metabolic disorders in our series in uDCD organ donation compared with cDCD. The recovery of the renal function of organs from uDCD is slower than that of cDCD, however; the tendency is toward normality.

Brain Injury Biomarker Behavior in Spontaneous Intracerebral Hemorrhage.

BACKGROUND: S100B and neuron-specific enolase (NSE) have been widely studied in diverse neurocritical pathologies, being recognized as the most promising biomarkers for brain injury assessment. However, their role in intracerebral hemorrhage (ICH) has not been widely analyzed. METHODS: This was an observational prospective cohort study of patients with ICH admitted to a neurocritical care unit. Blood samples were collected on admission and at 24 hours, 48 hours, and 72 hours. Patient outcomes were assessed at 6 months after the event. RESULTS: Thirty-six patients with ICH were included in the study. The mortality rate was 36%. Nonsurvivors had higher S100B values than survivors at admission, 24 hours, and 48 hours (P < 0.05). Likewise, S100B levels were higher in patients with poor outcomes (modified Rankin Scale [mRS] score >4) compared with those with good outcome (mRS score ≤3) in the 24-hour, 48-hour, and 72-hour samples. Receiver operating characteristic (ROC) curve analysis showed that S100B at admission, 24 hours, and 48 hours can discriminate between patients who survive and those who die as a consequence of ICH. The 48-hour sample (area under the ROC curve, 0.817; P = 0.003) reached the best values for sensitivity (75%) and specificity (80%); cutoff, 0.250 µg/L. For 6-month functional outcome, S100B protein could differentiate between groups at 24, 48, and 72 hours. The S100B 24-hour sample had the best values for sensitivity (82.6%) and specificity (72.7%), with a cutoff of 0.202 µg/L. We found no clear relationship between NSE values and clinical characteristics. CONCLUSIONS: S100B protein acts as early predictor of mortality and functional outcome in patients with ICH. This biomarker measurement can provide additional information beyond clinical and radiologic findings to guide physicians in the management of these patients.

Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: the TICH-2 RCT.

BACKGROUND: Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage. OBJECTIVE: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH). DESIGN: The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial. SETTING: Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK). PARTICIPANTS: Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset. EXCLUSION CRITERIA: Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy < 3 months; and a Glasgow Coma Scale score of < 5. INTERVENTIONS: Participants, allocated by randomisation, received 1 g of an intravenous tranexamic acid bolus followed by an 8-hour 1-g infusion or matching placebo (i.e. 0.9% saline). MAIN OUTCOME MEASURE: The primary outcome was functional status (death or dependency) at day 90, which was measured by the shift in the mRS score, using ordinal logistic regression, with adjustment for stratification and minimisation criteria. RESULTS: A total of 2325 participants (tranexamic acid, n = 1161; placebo, n = 1164) were recruited from 124 hospitals in 12 countries between 2013 and 2017. Treatment groups were well balanced at baseline. The primary outcome was determined for 2307 participants (tranexamic acid, n = 1152; placebo, n = 1155). There was no statistically significant difference between the treatment groups for the primary outcome of functional status at day 90 [adjusted odds ratio (aOR) 0.88, 95% confidence interval (CI) 0.76 to 1.03; p = 0.11]. Although there were fewer deaths by day 7 in the tranexamic acid group (aOR 0.73, 95% CI 0.53 to 0.99; p = 0.041), there was no difference in case fatality at 90 days (adjusted hazard ratio 0.92, 95% CI 0.77 to 1.10; p = 0.37). Fewer patients experienced serious adverse events (SAEs) after treatment with tranexamic acid than with placebo by days 2 (p = 0.027), 7 (p = 0.020) and 90 (p = 0.039). There was no increase in thromboembolic events or seizures. LIMITATIONS: Despite attempts to enrol patients rapidly, the majority of participants were enrolled and treated > 4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK. CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events. FUTURE WORK: Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN93732214. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland.

BACKGROUND: Stroke caused by bleeding in the brain [i.e. an intracerebral haemorrhage (ICH)] is a medical emergency. Around one-third of such strokes are complicated by continuing bleeding, which usually occurs within the first few hours after trauma and childbirth, and is associated with death or severe disability. Tranexamic acid is a drug that is seen to reduce death from bleeding after trauma and childbirth. METHODS: The study enrolled adults within 8 hours of an ICH into this large randomised trial. Half of the participants were given an injection of tranexamic acid and the other half placebo (in the form of salt water). The main aim of the trial was to measure changes in recovery by a telephone questionnaire on how much the person was able to do or needed help with 90 days after the stroke (i.e. functional status). Other measures included amount of brain bleeding, complications after stroke (serious adverse events), drug side effects and death within 7 days of stroke. RESULTS: A total of 2325 participants from 124 hospitals in 12 countries were enrolled between 2013 and 2017. Participants treated with tranexamic acid had no significant difference in functional status 90 days after stroke. There were small but significant reductions in brain bleeding, death in the first 7 days and complications after stroke, and tranexamic acid was safe with no increased side effects. CONCLUSION: Treatment with tranexamic acid did not result in a significant improvement in recovery at 90 days (i.e. functional status), despite small reductions in the number of early deaths, amount of brain bleeding and the number of complications. Larger trials are needed to confirm if these small benefits observed after treatment with tranexamic acid can significantly improve functional status after stroke due to bleeding in the brain (ICH).