Generation of Human-Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells of C9ORF72-Associated Amyotrophic Lateral Sclerosis Patients.

Disease modeling of neuromuscular disorders, such as amyotrophic lateral sclerosis (ALS), is hindered by limited accessibility of affected cells. This problem can be overcome by generation of human induced pluripotent stem cells (hiPSC), which can be then differentiated into required cells. Here, we describe the detailed protocol of hiPSC establishment from peripheral blood mononuclear cells (PBMC) of two ALS patients with detected expansion of G4C2 (GGGGCC) repeats in the first intron of C9ORF72 gene, known to be linked with the most common form of familial ALS.Successful PBMC reprogramming with non-integrating Sendai vectors was confirmed by expression of pluripotency markers: OCT4, NANOG, SSEA4, and TRA-1-60 in obtained hiPSC and their ability to differentiate into cells of three germ layers.The generated ALS-patient-specific hiPSC create a possibility for deciphering molecular basis of this devastating neuromuscular disease.

Evaluating the interaction between hemorrhagic transformation and cerebral edema on functional outcome after ischemic stroke.

BACKGROUND: Hemorrhagic transformation (HT) and cerebral edema (CED) are both major complications following ischemic stroke, but few studies have evaluated their overlap. We evaluated the frequency and predictors of CED/HT overlap and whether their co-occurrence impacts functional outcome more than each in isolation. METHODS: 892 stroke patients enrolled in a prospective study had follow-up CT imaging evaluated for HT and CED; the latter was quantified using the ratio of hemispheric CSF volumes (with hemispheric CSF ratio < 0.90 used as the CED threshold). The interaction between HT and CED on functional outcome (using modified Rankin Scale at 3 months) was compared to that for each condition separately. RESULTS: Among the 275 (31%) who developed HT, 233 (85%) manifested hemispheric CSF ratio < 0.9 (CED/HT), with this overlap group representing half of the 475 with measurable CED. Higher baseline NIHSS scores and larger infarct volumes were observed in the CED/HT group compared with those with CED or HT alone. Functional outcome was worse in those with CED/HT [median mRS 3 (IQR 2-5)] than those with CED [median 2 (IQR 1-4)] or HT alone [median 1 (IQR 0-2), p < 0.0001]. Overlap of CED/HT independently predicted worse outcome [OR 1.89 (95% CI: 1.12-3.18), p = 0.02] while HT did not; however, CED/HT was no longer associated with worse outcome after adjusting for severity of CED [adjusted OR 0.35 (95% CI: 0.23, 0.51) per 0.21 lower hemispheric CSF ratio, p < 0.001]. CONCLUSIONS: Most stroke patients with HT also have measurable CED. The co-occurrence of CED and HT occurs in larger and more severe strokes and is associated with worse functional outcome, although this is driven by greater severity of stroke-related edema in those with HT.

The benefit of optimizing recanalization during mechanical thrombectomy in patients with acute ischemic stroke depends on preprocedural tissue-level collateralization.

PURPOSE: Thrombolysis in Cerebral Infarction (TICI) 3 represents the optimal angiographic outcome following mechanical thrombectomy (MT) for acute ischemic stroke (AIS). Although it is known to yield better outcomes than TICI 2b, the influence of preprocedural cerebral hemodynamics on the clinical advantage of TICI 3 over TICI 2b remains unexplored. METHODS: This single-center retrospective analysis involved patients with anterior circulation AIS who underwent successful recanalization during MT at the Comprehensive Stroke Center, University Hospital, Krakow between January 2019 and July 2023. We assessed the benefit of achieving TICI 2c/3 over TICI 2b on the basis of preprocedural computed perfusion imaging results, primarily focusing on early infarct volume (EIV) and tissue-level collaterals indicated by hypoperfusion intensity ratio (HIR). Good functional outcome (GFO) was defined as a modified Rankin Score < 3 on day 90. RESULTS: The study comprised 612 patients, of whom 467 (76.3%) achieved TICI 2c/3. GFO was more frequent in the TICI 2c/3 group (54.5% vs 69.4%, p < 0.001). There was interaction between the recanalization status and both HIR (Pi = 0.042) and EIV (Pi = 0.012) in predicting GFO, with disproportionately higher impact of HIR and EIV in TICI 2b group. The benefit from TICI 2c/3 over TICI 2b was insignificant among patients with good collaterals, defined by HIR < 0.3 (odds ratio:1.36 [0.58-3.18], p = 0.483). CONCLUSION: TICI 2c/3 improves patient functional outcomes compared to TICI 2b regardless of EIV. However, such angiographic improvement may be clinically futile in patients with good tissue-level collateralization. Our findings suggest that preprocedural HIR should be considered when optimization of recanalization is considered during MT.

Short- and long- term outcomes of mechanical thrombectomy in acute ischemic stroke patients with chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is a risk factor of acute ischemic stroke (AIS). Outcomes of treatment with mechanical thrombectomy (MT) in patients with CKD seem to be poorer than in the general population. Long­term follow­up studies are lacking. OBJECTIVES: Our aim was to asses short- and long­term outcomes (up to 365 days after stroke) in MT­treated AIS patients with concomitant CKD. PATIENTS AND METHODS: The study included all AIS patients treated with MT at the Comprehensive Stroke Center in Kraków, Poland, from 2019 to 2021. The patients were divided into the CKD group (best glomerular filtration rate [GFR] during hospitalization <60 ml/min/1.73 m2 or diagnosed CKD) and the controls. In­hospital, 90­day, and 365­day mortality and rate of good functional outcomes (defined as modified Rankin Scale ≤2) were compared between the CKD patients and controls as well as between patients with CKD stages 1-3 (GFR ≥30 ml/min/1.73 m2) and 4-5 (GFR <30 ml/min/1.73 m2). Factors associated with the abovementioned outcomes were identified using univariable logistic regression analyses and then added to multivariable analyses. RESULTS: The CKD patients had higher 90- and 365­day mortality and lower 90- and 365­day good functional outcome rates than the controls. The patients with CKD stage 4-5 had significantly higher in­hospital, 90­day, and 365­day mortality than the patients with CKD stage 1-3. Neither CKD nor its late stages (4-5) were independently associated with short- and long­term mortality and functional outcomes of MT. CONCLUSIONS: MT outcomes in CKD patients are worse, especially in advanced stages of the disease, but CKD is not independently associated with poor prognosis. CKD alone should not be a contraindication for MT in otherwise eligible patients, although patients with impaired kidney function require more careful postprocedural monitoring.

Mechanical thrombectomy in very elderly people: shortand long-term outcomes of endovascular stroke treatment in nonagenarians.

AIM OF STUDY: To assess outcomes of mechanical thrombectomy (MT) in nonagenarians suffering from acute ischaemic stroke (AIS) in a 1-year follow-up. CLINICAL RATIONALE FOR STUDY: Age is a factor associated with both the occurrence of AIS and a poorer prognosis. As the population ages, the prevalence of AIS among the very old (90 and older) is expected to rise. Data on long-term outcomes of MT, being the optimal treatment of AIS caused by large vessel occlusions, is scarce in the population of nonagenarians. MATERIAL AND METHODS: We analysed all AIS patients treated with MT in a single Comprehensive Stroke Centre. We compared two subgroups: nonagenarians (people aged 90-99) and controls ( < 90 years) in terms of cardiovascular risk factors profile, stroke severity, treatment course, presence of in-hospital complications, and outcomes (mortality and good functional outcome defined as modified Rankin Scale ≤ 2) at discharge and at 90- and 365-day follow-ups. RESULTS: Nonagenarians were more commonly female and suffering from atrial fibrillation. They more often developed urinary tract infection during hospitalisation. Stroke severity, treatment course and in-hospital outcomes were comparable between the groups. Nonagenarians had non-significantly higher 90-day and 365-day mortality, and a significantly lower rate of good functional outcomes after 90 days (25.0% vs 57.7%, p = 0.011) and 365 days (31.5% vs 61.0%, p = 0.020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Despite worse outcomes than in younger patients, 25% of nonagenarians were functionally independent three months after MT, and almost one in three of them were so a year after the procedure, thereby showing the benefits of the treatment in this group.

Associations between Microglia and Astrocytic Proteins and Tau Biomarkers across the Continuum of Alzheimer's Disease.

Recent investigations implicate neuroinflammatory changes, including astrocyte and microglia activation, as crucial in the progression of Alzheimer's disease (AD) Thus, we compared selected proteins reflecting neuroinflammatory processes to establish their connection to AD pathologies. Our study, encompassing 80 subjects with (n = 42) AD, (n = 18) mild cognitive impairment (MCI) and (n = 20) non-demented controls compares the clinical potential of tested molecules. Using antibody-based methods, we assessed concentrations of NGAL, CXCL-11, sTREM1, and sTREM2 in cerebrospinal fluid (CSF). Proinflammatory proteins, NGAL, and CXCL-11 reached a peak in the early stage of the disease and allowed for the identification of patients with MCI. Furthermore, the concentration of the anti-inflammatory molecule sTREM2 was highest in the more advanced stage of the disease and permitted differentiation between AD and non-demented controls. Additionally, sTREM2 was biochemically linked to tau and pTau in the AD group. Notably, NGAL demonstrated superior diagnostic performance compared to classical AD biomarkers in discriminating MCI patients from controls. These findings suggest that proteins secreted mainly through microglia dysfunction might play not only a detrimental but also a protective role in the development of AD pathology.

Circulating Chemokines and Short- and Long-Term Outcomes After Ischemic Stroke.

Chemokines are vital in post-cerebral ischemia inflammatory reactions. We investigate the possible relationship between plasma chemokines and short-term and long-term outcomes after stroke. This study included 235 patients (median age, 72 years; 49.8% female) suffering from ischemic stroke, or transient ischemic attack admitted to the hospital within 24 h of onset. We evaluated chemokines CCL2, CCL5, CXCL8, CXCL9, and CXCL10 in plasma samples collected upon admission. Further, we assessed functional outcomes at 3- and 12-months, all-cause fatality over 5 years, and episodes of delirium within the first 7 days of admission. Multivariate analysis revealed an association between higher CXCL10 levels and an increased risk of poor functional outcomes at 3 months (OR: 3.02, 95%CI: 1.22-7.46, p = 0.016) and 12 months (OR: 2.32, 95%CI: 1.03-5.26, p = 0.043), as well as an increased death risk (HR: 1.79, 95%CI: 1.04-3.07, p = 0.036). High CXCL8 levels independently predicted poor functional outcomes at 12 months (OR: 2.69, 95%CI: 1.39-6.31, p = 0.005) and a higher 5-year case fatality rate (HR: 1.90, 95%CI: 1.23-2.93, p = 0.004). Elevated CXCL9 levels also predicted unfavourable functional outcomes at 12 months (OR: 2.45, 95%CI: 1.07-5.61, p = 0.034). In univariate analysis, increased levels of CXCL8, CXCL9, and CXCL10 showed an association with delirium, although this link was not evident in the multivariate analysis. Plasma CXCL8 and CXCL10 show potential as prognostic biomarkers for stroke outcomes and as therapeutic targets suitable for reverse translation.

Risk factors of acute kidney injury during hospitalization in acute ischaemic stroke patients undergoing mechanical thrombectomy.

Introduction: Acute kidney injury (AKI) seems to worsen the prognosis of acute ischaemic stroke (AIS) patients treated with mechanical thrombectomy (MT). At the same time, the procedure of MT increases AKI risk by iodinated contrast use. Identification of factors predisposing to AKI after MT is important for recognizing vulnerable patients and successful prevention. Aim: To identify factors associated with the occurrence of AKI during hospitalization in MT-treated AIS patients. Material and methods: The study included all AIS patients treated with MT in the University Hospital in Krakow from 2019 to 2021. The diagnosis of AKI during hospitalisation was based on serum creatinine concentration levels, according to the Kidney Disease Improving Global Outcomes guidelines. We compared patients with and without AKI in terms of age, sex, comorbidities, stroke course and laboratory test results at admission. We identified factors associated with the occurrence of AKI using univariate logistic regression analysis, with significant variables subsequently added to the multivariate analyses. Results: Among 593 MT-treated AIS patients the incidence of AKI during hospitalisation was 12.6%. AKI development was associated with diabetes, chronic kidney disease, total volume of iodinated contrast obtained during hospitalisation, posterior circulation stroke, lack of intravenous thrombolysis, and laboratory test results at admission: haemoglobin, glucose, urea, potassium, and creatinine. Total contrast volume and urea level were the most important independent risk factors associated with occurrence of AKI. Conclusions: AKI is common in MT-treated AIS patients. There is a need to establish a protocol for decreasing the risk of AKI in AIS patients undergoing MT and, in case it occurs, a procedure for its treatment.

Long-term outcomes of mechanical thrombectomy in acute ischaemic stroke patients with concomitant malignancy.

Introduction: Patients with cancer (CP) need a different approach to acute ischaemic stroke (AIS) treatment as intravenous thrombolysis (IVT) may be contraindicated. Mechanical thrombectomy (MT) is a treatment of choice for otherwise eligible patients, although the literature on its long-term outcomes in CP is limited. Aim: Assessing outcomes of MT-treated AIS patients with concomitant malignancy in a year-long follow-up. Material and methods: The study included 593 MT-treated AIS patients admitted in 2019-2021. The group was divided into CP (defined as a diagnosis of malignancy and undergoing/qualified for cancer treatment within previous 5 years) and a control group. The profile of cardiovascular risk factors, stroke severity and discharge, 90-day and 365-day outcomes were compared between the groups. Results: CP and controls had a similar profile of cardiovascular risk factors and comparable stroke severity. CP were less frequently treated with IVT (25.7% vs. 59.1%, p < 0.001). There were no differences between the groups in the successful reperfusion rate and occurrence of haemorrhagic complications. Discharge and 90-day outcomes were similar. CP had higher 365-day mortality (48.6% vs. 29.9%, p = 0.024) but the percentage of patients achieving good functional outcome in a year-long observation was comparable. Conclusions: Treatment with MT seems beneficial for AIS patients with concomitant malignancy both in short- and long-term observation.

Sex Alters the Effect of Perfusion Deficits on Functional Outcome in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy.

INTRODUCTION: The discourse surrounding differences in cerebral hemodynamics and clinical outcomes among male and female patients treated with mechanical thrombectomy (MT) for acute ischemic stroke (AIS) remains unresolved. We aimed to elucidate these differences by employing computed tomography perfusion (CTP) imaging before MT and examining the influence of perfusion deficits on the 90-day functional outcome. METHODS: This single-center retrospective analysis involved patients with anterior circulation AIS treated with MT at the Comprehensive Stroke Center, University Hospital, Krakow, from January 2019 to July 2023. We compared male and female patients in terms of baseline characteristics, CTP deficits, hypoperfusion intensity ratio (HIR, defined as T10max/T6max), and complications. The endpoints included the 90-day excellent functional outcome, defined as modified Rankin Score <2, and the 90-day mortality rate. RESULTS: We included 794 patients, of whom 408 were female (51.4%). Female patients had a smaller early infarct volume (median [interquartile range]: 7 mL [0-24.8] vs. 10 mL [0-33], p = 0.004), smaller penumbra volume (77.5 mL [46-117] vs. 99.5 mL [59.8-140], p < 0.001), lower HIR (0.34 [0.16-0.5] vs. 0.37 [0.2-9.53], p = 0.043) and were less likely to achieve an excellent functional outcome (55.6% vs. 66.1%, p = 0.003). For every 10 mL increase in early infarct volume, the odds for achieving an excellent outcome were lower in females (odds ratio [OR]: 0.82 [95% confidence interval: 0.73-0.92]) compared to males (OR: 0.96 [0.88-1.04]), whereas the risk of death was higher for females (OR: 1.25 [1.13-1.39] than for males (OR: 1.05 [0.98-1.14]). DISCUSSION: Despite more favorable cerebral hemodynamic profile, female AIS patients have worse outcomes than their male counterparts. This effect seems to be independently mediated by the more pronounced impact of early infarct volume on the prognosis in female patients. These findings underscore the possible explanatory power arising from sex-specific interpretation of early infarct volume in clinical practice.

Association of Imaging-based Predictors with Outcome in Different Treatment Options for Intracerebral Hemorrhage.

PURPOSE: Intracerebral hemorrhage is the deadliest form of stroke. This study aimed to enhance the prediction of 30-day mortality in intracerebral hemorrhage patients by integrating computational parameters. METHODS: This study retrospectively analyzed 435 patients with spontaneous intracerebral hemorrhage (ICH). Utilizing the acquired computed tomography (CT) images, we extracted the contour and visual representation of ICH. For the extracted contour, the analysis encompassed factors including compactness, fractal dimension, Fourier factor, and circle factor. For the images depicting ICH, we calculated various factors related to density distribution including mean, coefficient of variance, skewness and kurtosis, as well as texture parameters, such as energy, entropy, contrast and homogeneity. To assess the impact of surgical treatment on 30-day mortality, logistic regression analysis was used. RESULTS: A total of 126 patients (29.09%) died within 30 days. A total of 62 (14.25%) patients underwent surgical treatment. Multivariate logistic regression analysis revealed that surgical treatment was independently associated with a lower risk of 30-day mortality (odds ratio, OR 0.226, 95% confidence interval, CI 0.049-0.85; p = 0.039). Based on the moderated analysis, we found that the volume of ICH (OR 0.905, 95% CI 0.902-0.908; p < 0.001) and ICH energy (OR 1.389, 95%CI 0.884-0.988; p = 0.010) had positive moderating effect on such associations while the presence of intraventricular blood had negative moderating effect (OR 1.154, 95% CI 1.034-1.628; p = 0.010). CONCLUSION: Patients exhibiting a higher volume and energy of ICH might benefit from surgical treatment; however, this efficacy was found to be diminished in cases involving the presence of intraventricular blood.

Diffusion tensor imaging metrics as natural markers of multiple sclerosis-induced brain disorders with a low Expanded Disability Status Scale score.

Non-invasive and effective differentiation along with determining the degree of deviations compared to the healthy cohort is important in the case of various brain disorders, including multiple sclerosis (MS). Evaluation of the effectiveness of diffusion tensor metrics (DTM) in 3T DTI for recording MS-related deviations was performed using a time-acceptable MRI protocol with unique comprehensive detection of systematic errors related to spatial heterogeneity of magnetic field gradients. In a clinical study, DTMs were acquired in segmented regions of interest (ROIs) for 50 randomly selected healthy controls (HC) and 50 multiple sclerosis patients. Identical phantom imaging was performed for each clinical measurement to estimate and remove the influence of systematic errors using the b-matrix spatial distribution in the DTI (BSD-DTI) technique. In the absence of statistically significant differences due to age in healthy volunteers and patients with multiple sclerosis, the existence of significant differences between groups was proven using DTM. Moreover, a statistically significant impact of spatial systematic errors occurs for all ROIs and DTMs in the phantom and for approximately 90 % in the HC and MS groups. In the case of a single patient measurement, this appears for all the examined ROIs and DTMs. The obtained DTMs effectively discriminate healthy volunteers from multiple sclerosis patients with a low mean score on the Expanded Disability Status Scale. The magnitude of the group differences is typically significant, with an effect size of approximately 0.5, and similar in both the standard approach and after elimination of systematic errors. Differences were also observed between metrics obtained using these two approaches. Despite a small alterations in mean DTMs values for groups and ROIs (1-3 %), these differences were characterized by a huge effect (effect size ∼0.8 or more). These findings indicate the importance of determining the spatial distribution of systematic errors specific to each MR scanner and DTI acquisition protocol in order to assess their impact on DTM in the ROIs examined. This is crucial to establish accurate DTM values for both individual patients and mean values for a healthy population as a reference. This approach allows for an initial reliable diagnosis based on DTI metrics.

Association between brain fog, cardiac injury, and quality of life at work after hospitalization due to COVID-19.

BACKGROUND: To evaluate incidence and search for possible predictors of brain fog and quality of life at work (QoL-W) among low-to-moderate risk subjects previously hospitalized due to COVID-19. MATERIAL AND METHODS: Participants aged ≥18 retrospectively reported 8 brain fog symptoms pre-COVID-19, at 0-4, 4-12 and >12 weeks post-infection via validated clinical questionnaire. The QoL-W was assessed with a 4-point Likert scale where 0, 1, 2, and 3 meant no, mild, moderate, and severe impairment in performing activities at work, respectively. Data on age, sex, comorbidities, and laboratory results (including first in-hospital high-sensitivity cardiac troponin I [hs-cTnI] measurement) were gathered. RESULTS: The study included 181 hospitalized subjects (age Me = 57 years), 37.02% women. Most had low disease severity (Modified Early Warning Score = 1, 77.90%) and low comorbidity (Charlson Comorbidity Index 0: 28.72%, 1-2: 34.09%), with no intensive care unit treatment needed. COVID-19 led to almost 3-fold increased brain fog symptoms, with incidence of 58.56%, 53.59%, and 49.17% within 4, 4-12, and >12 weeks, respectively (p < 0.001). First in-hospital hs-cTnI levels were 47.3% higher in participants who later presented with brain fog at median follow-up of 26.7 weeks since the diagnosis of the SARS-CoV-2 infection. Individuals who experienced at least one brain fog symptom at follow-up, had elevated hs-cTnI, less often presented with atrial fibrillation, and used anticoagulants during initial hospitalization due to COVID-19. The Hs-cTnI >11.90 ng/l predicted brain fog symptoms in multivariable model. COVID-19 was associated with 3.6­fold, 3.0­fold, and 2.4-fold QoL-W deterioration within 4, 4-12, and >12 weeks post-infection (p < 0.05). Subjects with QoL-W decline >12 weeks were younger, mostly women, had more brain fog symptoms, and higher platelet counts. Multivariable models with self-reported brain fog symptoms (responding coherently and recalling recent information), age, and sex exhibited good discriminatory power for QoL-W impairment (area under the receiver operating characteristic curve 0.846, 95% CI: 0.780-0.912). CONCLUSIONS: This study highlighted that in non-high-risk subjects hospitalized during the first 2 pandemic's waves: 1) brain fog was common, affecting nearly half of individuals, and impacting QoL-W >12 weeks after initial infection, 2) after 3 months of COVID-19 onset, the decline in QoL-W was primarily attributed to brain fog symptoms rather than demographic factors, health conditions, admission status, and laboratory findings, 3) components of brain fog, such as answering in an understandable way or recalling new information increased the likelihood of significantly lower QoL-W up to tenfold, 4) biochemical indicators, such as the first hs-cTnI level, might predict the risk of experiencing brain fog symptoms and indirectly decreased QoL-W >12 weeks after COVID-19 onset. Occupational medicine practitioners should pay particular attention to younger and female subjects after COVID-19 complaining of problems with answering questions in understandable way or recalling new information as they have an increased risk of QoL-W impairment. Med Pr Work Health Saf. 2024;75(1):3-17.

Expert opinion of the Heart Rhythm Association of the Polish Cardiac Society and the Polish Neurological Society on evidence-driven implementation of implantable loop recorders in Poland.

Implantable loop recorders (ILR) are considered increasingly helpful in diagnosing cardio-neurological conditions, especially if arrhythmic events are of high clinical importance but are unlikely to be captured by standard methods of electrocardiogram recording due to the low frequency of events and short duration of a single event. The compelling evidence from randomized trials and observational studies strongly supports ILR utilization in patients after cryptogenic stroke or transient ischemic attack and in patients with recurrent transient loss of consciousness of unknown origin. These two groups of patients are expected to gain the most from initiating ILR-driven clinically effective management strategies. Stroke or transient ischemic attack survivors with detected subclinical atrial fibrillation can be switched from antiplatelets to anticoagulants, whilst patients with recurrent syncope may avoid severe injuries and/or substantial impairment of their quality of life. This joint opinion of the Heart Rhythm Association of the Polish Cardiac Society and experts from the Polish Neurological Society summarizes the up-to-date rationale for using ILR in everyday clinical practice and describes the road map for implementing this technology in Poland. Special emphasis is placed on the most recent guidelines issued by both cardiological and neurological scientific societies.

Predictors of good functional outcome in ischaemic stroke patients without delayed neurological improvement after mechanical thrombectomy.

INTRODUCTION: This study aimed to identify predictors of 90-day good functional outcome (GFO) in patients with acute ischaemic stroke (AIS) who were treated with mechanical thrombectomy but did not achieve a delayed neurological improvement (DNI). CLINICAL RATIONALE FOR THE STUDY: In-hospital neurological improvement in patients with AIS is consistently associated with long- -term GFO. Patients who experience neither early nor delayed neurological improvement can still achieve long-term GFO, but predictors of such an outcome have not been studied. MATERIAL AND METHODS: This single-centre retrospective study involved 307 patients with anterior circulation AIS treated with mechanical thrombectomy. Multiple clinical, biochemical, radiological, and treatment-related variables were collected and analysed. DNI on day 7 was defined as at least a 10-point reduction in the National Institutes of Health Stroke Scale (NIHSS) score or NIHSS score < 2. GFO on day 90 was defined as a modified Rankin Scale (mRS) score ≤ 2. We compared the characteristics of patients with and without DNI, with special attention paid to patients who achieved 90-GFO despite a lack of DNI. Multivariate analyses were then performed to establish independent predictors of 90-day GFO among patients without DNI. RESULTS: DNI occurred in 150 out of 307 patients (48.7%) and significantly increased the odds for 90-day GFO (odds ratio [OR]: 13.99; p < 0.001). Among patients without DNI, 41.4% achieved 90-day GFO. Younger age (OR: 0.96; 95% confidence interval [CI]: 0.93-0.99; p = 0.008), lower baseline NIHSS score (OR: 0.80; 95% CI: 0.73-0.89; p < 0.001), treatment with intravenous thrombolysis (OR: 3.06; 95% CI: 1.25-7.49; p = 0.014), lack of an undetermined aetiology (OR: 0.40; 95% CI: 0.16-0.998; p = 0.050), lack of pneumonia (OR: 0.08; 95% CI: 0.02-0.31; p < 0.001), and higher haemoglobin concentration on admission (OR: 1.31; 95% CI: 1.04-1.69; p = 0.024) were identified as predictors of 90-day GFO in this subgroup. CONCLUSION: Almost half of patients with AIS in anterior circulation treated with mechanical thrombectomy experience DNI, which is a good predictor of 90-day GFO. Furthermore, 40% of patients without DNI achieve 90-day GFO which can be independently predicted by younger age, lower baseline NIHSS score, treatment with intravenous thrombolysis, higher haemoglobin concentration on admission, lack of undetermined ischaemic stroke aetiology, and lack of pneumonia.

Acute Ischaemic Stroke in Patients Treated with Direct Oral Anticoagulants: Potential Causes, Clinical Characteristics, and Short-Term Outcomes.

Introduction: Direct oral anticoagulants (DOAC) are the first-line treatment for primary and secondary acute ischaemic stroke (AIS) prevention in patients with nonvalvular atrial fibrillation (NVAF), but a significant percentage of patients develop AIS despite being treated with DOAC. As the number of DOAC-treated patients is growing, so is the number of patients with AIS on DOAC. The aim of the study was to assess the incidence of AIS with prestroke DOAC treatment among patients hospitalised in the University Hospital in Kraków, to analyse the clinical characteristics of AIS occurring in patients on DOAC, and to identify potential causes of treatment ineffectiveness in this group. Materials and Methods: In the study, we included all patients hospitalised in the Department of Neurology of the University Hospital in Kraków within one year (July 2022 to June 2023) with the diagnosis of AIS. The group was divided into two subgroups of patients with and without prestroke DOAC treatment. Based on medical files, we retrospectively analysed the profile of cardiovascular risk factors, stroke severity (assessed with National Institutes of Health Stroke Scale, NIHSS), use of causative stroke treatment and short-term outcomes (defined as NIHSS score, modified Rankin scale (mRS) score at discharge, in-hospital mortality, and secondary intracerebral haemorrhage among patients treated with mechanical thrombectomy, MT). Within the DOAC-treated subgroup, we looked for potential causes of AIS occurring despite DOAC treatment (valvular AF, poor adherence to treatment, underdosing, other prothrombotic conditions, aetiology of stroke other than thromboembolic, and drug-drug interactions). Results: In the study, we included 768 AIS patients. 109 (14.2%) had a history of prestroke DOAC treatment. A potential cause of DOAC treatment failure was identified in the majority of them (n = 63, 57.8%). Patients with prestroke DOAC treatment had worse functional condition before stroke and higher stroke severity on admission but similar short-term outcomes and similar short-term effects of treatment with MT. DOAC (+) and DOAC (-) patients had different profiles of cardiovascular risk factors and different factors associated with short-term outcome. Conclusions and Clinical Implications. A potential cause of AIS occurring in DOAC-treated patients can be identified in most cases and in many of them prevented.

Outcomes following exposure to lacosamide monotherapy during pregnancy and breastfeeding - a prospective case series.

AIM OF THE STUDY: To evaluate the safety of lacosamide (LCM) monotherapy during pregnancy and breastfeeding. MATERIAL AND METHODS: Patients taking LCM monotherapy treated at the university epilepsy clinic were prospectively followed up during pregnancy, delivery, and breastfeeding. Data on seizure frequency, LCM dosage, pregnancy course, delivery and breastfeeding, birth outcome, congenital malformation, and development of newborns was collected. RESULTS: Four pregnancies in three patients with refractory focal epilepsy treated with LCM monotherapy were reported. One of these pregnancies ended in a miscarriage during the seventh week of gestation. The average daily LCM dose at the time of conception was 300 mg. Treatment with LCM was continued throughout pregnancy and breastfeeding. The dose of LCM was increased in two pregnancies: in one case following a seizure relapse, and in the other case as a preventive measure to avoid an increase in seizure frequency. Seizure frequency remained stable during pregnancy in two cases. All deliveries were carried out via caesarean section, with an average gestational age at birth of 37.6 weeks. The Apgar score was 10 in all newborns, and no congenital malformations were detected. At the age of 12 months, normal developmental milestones were reached. Infants were breastfed without any complications. CONCLUSIONS AND CLINICAL IMPLICATIONS: This case series adds to a growing body of evidence suggesting the relative safety of LCM monotherapy throughout pregnancy and breastfeeding.

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society.

Andexanet alfa (AA) is a recombinant inactive analog of human activated factor X (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was approved for clinical use registration after the publication of the results of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXa Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in patients receiving using the aforementioned anticoagulants was demonstrated. Hence, AA is now recommended for patients on apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows us to rule out the presence of clinically relevant plasma concentrations of any FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of coagulation tests, as it depends solely on the time that elapsed since the last dose of FXa inhibitor and oon the dose and type of FXa inhibitor. AA is administered as an intravenous (i.v.) bolus, followed by an i.v. infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be re-administered. In Poland AA is starting to become available and its urgent need to administer it to patients with severe bleeding on apixaban or rivaroxaban.

Treatment patterns in women of childbearing age and pregnant women with epilepsy in Poland between the years 2019 and 2022-A nationwide population-based cohort study.

AIM: To describe the antiseizure medications (ASMs) prescription pattern in women of childbearing age (WOCA) and pregnant women with epilepsy in the 2019-2022 period in Poland MATERIALS AND METHODS: The National Health Fund (NHF) databases were analyzed. Women aged 15-49 years were considered as being of childbearing age, while exposure during pregnancy was estimated taking into account 15 months before delivery. ASMs belonging to the N03A subgroup of the Anatomical Therapeutic Chemical Classification System, reimbursed by NHF were analyzed. RESULTS: During 2019, 36 784 WOCA and 921 pregnant women filled at least 1 ASM prescription. In 2022, these numbers were 32 304 and 594, respectively. Valproate was the most widely used ASM in WOCA (38.4 %) in 2019, followed by levetiracetam (35.6 %), lamotrigine (30.1 %), and carbamazepine (20.0 %). The percentage of ASM users decreased in 2022 for valproate (32.1 %; p < 0.001) and carbamazepine (17 %; p < 0.001) and increased for levetiracetam (40.8 %; p < 0.001) and lamotrigine (32.7 %; p < 0.001). In 2019 lamotrigine (42.1 %) and levetiracetam (41.5 %) were the most frequently prescribed ASMs to pregnant women. During the study period, a significant increase in prescriptions for levetiracetam was observed (49.5 %; p = 0.003). The proportion of ASMs exposed pregnancies declined for valproate (from 24.7 to 16 %; p < 0.001) and topiramate (from 6.6 to 3.2 %; p = 0.005). The percentage of polytherapy regimens remained stable over the years, both for WOCA (39 %) and pregnant women (32 %). CONCLUSION: Despite the decline in valproate usage, the drug was still among the most commonly prescribed ASMs in women of childbearing age and pregnant women with epilepsy. The awareness of teratogenic risks and new treatment guidelines should be improved in Poland.

CSF-Based Volumetric Imaging Biomarkers Highlight Incidence and Risk Factors for Cerebral Edema After Ischemic Stroke.

BACKGROUND: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. METHODS: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). RESULTS: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF). CONCLUSIONS: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.