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Machine learning systems based on minimizing average error have been shown to perform inconsistently across notable subsets of the data, which is not exposed by a low average error for the entire dataset. In consequential social and economic applications, where data represent people, this can lead to discrimination of underrepresented gender and ethnic groups. Distributionally Robust Optimization (DRO) seemingly addresses this problem by minimizing the worst expected risk across subpopulations. We establish theoretical results that clarify the relation between DRO and the optimization of the same loss averaged on an adequately weighted training dataset. A practical implication of our results is that neither DRO nor curating the training set should be construed as a complete solution for bias mitigation.

The aim of our study was to analyse EEG findings in patients with COVID-19 not requiring respiratory support.We reviewed EEGs performed in patients with COVID-19 between April 2020 and May 2021 at the University Hospital in Kraków, Poland. Demographic and clinical data, including comorbid conditions, discharge disposition, survival, neuroimaging findings, laboratory results, and treatment was collected.The study included 44 EEGs performed in 35 patients (51.4% females), aged 65.5 ± 13.9 years. Almost all patients had at least one comorbidity, and one-third had one or more preexisting neurological conditions. Three quarters of EEGs were abnormal. The most frequent EEG finding was background slowing (16 patients; 45.7%). Frontal findings included frontally predominant rhythmic delta (FIRDA) in 10 (28.6%) patients and focal slowing in the left frontal lobe. Patients with abnormal EEG significantly more often required oxygen supplementation (p = 0.003) and were less likely to recover (p = 0.048).Patients with COVID-19 infection may frequently manifest with an abnormal EEG. FIRDA seems to be a frequent EEG pattern in less severe cases of COVID-19 infection. Future studies are needed to establish whether COVID-19 infection increases the risk for FIRDA, and to investigate its pathogenesis.

Patients with advanced ovarian cancer (OC) have a detrimental prognosis. The options for systemic treatment of advanced OC in later lines of treatment are limited by the availability of active therapies and their applicability to often fragile, exhausted patients with poor performance status. Metronomic chemotherapy (MC) is a concept of a continuous administration of cytotoxic drugs, which is characterized by multidirectional activity (anti-proliferative, anti-angiogenic, and anti-immunosuppressive) and low toxicity. We have performed a retrospective analysis of consecutive, advanced, chemo-refractory OC patients treated with MC based on single-agent topotecan (1 mg p.o. q2d) or on a topotecan (1 mg q2d) and cyclophosphamide (50 mg p.o. qd) combination (CyTo). Metronomic chemotherapy demonstrated promising activity, with 72% and 86% of patients achieving biochemical or objective disease control and 18% and 27% of patients achieving a biochemical or objective response, respectively. The median PFS in the whole population was 3.65 months, but the median PFS in patients with a biochemical response to MC (18.2% of patients) reached 10.7 months. The study also suggested that overweight or obese patients had significantly better outcomes on MC than patients with BMI

Synaptic loss and dysfunction are one of the earliest signs of neurodegeneration associated with cognitive decline in Alzheimer’s disease (AD) and other neurodegenerative diseases. This study aimed to assess the relationships between biological processes of the synaptic pathology underlying AD, molecular functions, and dynamics of the change concentrations of selected proteins reflecting synaptic and axonal pathology in dementia stages. Neurogranin (Ng), neuronal pentraxin receptor (NPTXR), and Visinin-like protein 1 (VILIP1) concentrations were measured in the cerebrospinal fluid (CSF) of MCI, AD, and non-demented controls (CTRL) using quantitative immunological methods. Gene ontology (GO) enrichment analysis was used for the functional analysis of tested proteins. The CSF Aβ42/Ng ratio was significantly different between all the compared groups. The CSF NPTXR/Ng ratio was significantly different between MCI compared to CTRL and AD compared to CTRL. The GO enrichment analysis revealed that two terms (the Biological Process (BP) and Cellular Component (CC) levels) are significantly enriched for NPTXR and Ng but not for VILIP1. Both Ng and NPTXR concentrations in CSF are promising synaptic dysfunction biomarkers for the early diagnosis of the disease. Moreover, both proteins are biochemically associated with classical biomarkers and VILIP-1. Mapping shared molecular and biological functions for the tested proteins by GO enrichment analysis may be beneficial in screening and setting new research targets.

Background: Paraneoplastic neurological syndromes (PNS) affecting the CNS (central nervous system) are rare, presenting in less than 1% of all those with cancer. The pathogenesis of paraneoplastic neurological syndromes is not fully understood, but it is presumed to result from an immune attack on the underlying malignancy. The presence of different types of onconeural antibodies may occur in different tumors and can lead to different clinical manifestations, making the early detection of cancers challenging. Aim: An evaluation of [18F]FDG PET/CT in neoplastic tumor detection in patients with paraneoplastic neurological syndromes having negative or unremarkable results of conventional radiological imaging. Methods: Among all patients diagnosed with paraneoplastic neurological syndromes in the Neurology Department in 2016–2020, 15 patients with unremarkable conventional radiological findings who underwent [18F]FDG PET/CT were included in the study. Results: [18F]FDG PET/CT enabled localization of suspected malignancy in 53% (8 of 15) of PNS cases with previous unremarkable conventional radiological findings. Conclusion: [18F]FDG PET/CT may be considered as a useful tool for neoplastic tumor detection in patients with paraneoplastic neurological syndromes, accelerating the diagnostic process and enabling faster initiation of appropriate treatment.

The aim of this study was to assess the clinical profiles and outcomes of patients with confirmed COVID-19 infection and acute ischaemic stroke (AIS) treated with mechanical thrombectomy (MT) at the Comprehensive Stroke Centre (CSC) of the University Hospital in Krakow.COVID-19 is a risk factor for AIS and worsens prognosis in patients with large artery occlusions. During the pandemic, the global number of MT has dropped. At the same time, studies assessing outcomes of this treatment in COVID-19-associated AIS have produced divergent results.In this single-centre study, we retrospectively analysed and compared the clinical profiles (age, sex, presence of cardiovascular risk factors, neurological deficit at admission), stroke size (measured using postprocessing analysis of perfusion CT with RAPID software), time from stroke onset to arrival at the CSC, time from arrival at the CSC to groin puncture, treatment with intravenous thrombolysis, length of hospitalisation, laboratory test results, and short-term outcomes (measured with Thrombolysis in Cerebral Infarction scale, modified Rankin Scale and National Health Institute Stroke Scale) in patients with AIS treated with MT during the pandemic. A comparison between patients with and without concomitant SARS-CoV2 infection was then performed.There were no statistically significant differences between 15 COVID (+) and 167 COVID (-) AIS patients treated with AIS with respect to clinical profiles (p0.05), stroke size (p0.05) or outcomes (NIHSS at discharge, 8.1 (SD = 7.1) vs. 8.8 (SD = 9.6), p = 0.778, mRS at discharge 2.9 (SD = 2) vs. 3.1 (SD = 2.1), p = 0.817, death rate 6.7% vs. 12.6%, p = 0.699). There was a significant difference between patients with and without COVID-19 concerning time from arrival at the CSC to groin puncture [104.27 (SD = 51.47) vs. 97.63 (SD = 156.94) min., p = 0.044] and the length of hospitalisation [23.7 (SD = 11.9) vs. 10.5 (SD = 6.9) days, p0.001].In AIS patients treated with MT, concomitant SARS-CoV2 infection did not affect the outcome. Our observations need to be confirmed in larger, and preferably multicentre, studies.

Prior ischemic cerebrovascular event and younger age have been shown to increase bleeding acceptance among anticoagulated outpatients with atrial fibrillation (AF). We sought to determine factors affecting bleeding acceptance in acute ischemic stroke (AIS) survivors on various types of antithrombotic therapy.We enrolled 173 consecutive patients hospitalized for AIS (aged 68.2±11.7 years, 54.9% male), including 54 (31.2%) with AF, who had favorable functional outcome. On discharge, the Bleeding ratio, defined as the declared maximum number of major bleedings that a patient is willing to accept to prevent one major stroke, was evaluated. We assessed the predicted bleeding risk in non-cardioembolic and cardioembolic stroke survivors using SPatients with the low Bleeding ratio, defined as 5 (median) or less accepted bleeds (n=92; 53.2%), were older and more likely to receive thrombolysis and/or thrombectomy, with no impact of previous stroke. Prior major bleed (odds ratio [OR] 4.67; 95% confidence interval [CI] 0.92-23.72), AF with use of oral anticoagulants (OR 2.35, 95% CI 1.12-4.93), reperfusion treatment (OR 1.95, 95% CI 1.02-3.76), and hospitalization ≤10 days (OR 4.56; 95% CI 1.50-13.87) were associated with the low Bleeding Ratio. Prior use of anticoagulants or aspirin as well as HAS-BLED and SLower bleeding acceptance declared on discharge by AIS survivors is determined by prior bleeding, anticoagulation in AF, reperfusion treatment, and duration of hospitalization, which might affect medication adherence. The results might help optimize post-discharge management and educational efforts in patients on antithrombotic therapy.

Background: Breast cancer, with 2.3 million new cases and 0.7 million deaths every year, represents a great medical challenge worldwide. These numbers confirm that approx. 30% of BC patients will develop an incurable disease requiring life-long, palliative systemic treatment. Endocrine treatment and chemotherapy administered in a sequential fashion are the basic treatment options in advanced ER+/HER2- BC, which is the most common BC type. The palliative, long-term treatment of advanced BC should not only be highly active but also minimally toxic to allow long-term survival with the optimal quality of life. A combination of metronomic chemotherapy (MC) with endocrine treatment (ET) in patients who failed earlier lines of ET represents an interesting and promising option. Methods: The methodology includes retrospective data analyses of pretreated, metastatic ER+/HER2- BC (mBC) patients who were treated with the FulVEC regimen combining fulvestrant and MC (cyclophosphamide, vinorelbine, and capecitabine). Results: Thirty-nine previously treated (median 2 lines 1–9) mBC patients received FulVEC. The median PFS and OS were 8.4 and 21.5 months, respectively. Biochemical responses (CA-15.3 serum marker decline ≥50%) were observed in 48.7%, and any increase in CA-15.3 was observed in 23.1% of patients. The activity of FulVEC was independent of previous treatments with fulvestrant of cytotoxic components of the FulVEC regimen. The treatment was safe and well tolerated. Conclusions: Metronomic chemo-endocrine therapy with FulVEC regimen represents an interesting option and compares favorably with other approaches in patients’ refractory to endocrine treatments. A phase II randomized trial is warranted.

Background and Purpose— Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods— In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results— Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64–79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9–15), and time from last known well median 18.6 hours (interquartile range, 14.5–22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89–2.47); P =0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P =0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08–6.73); P =0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions— SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.

Multiple sclerosis (MS) is most often diagnosed in women of childbearing age. Therefore, it is important to examine the impact of pregnancy on the course of MS and to enable patients to make decisions about motherhood based on reliable data. The main objective of this study was to assess the impact of pregnancy on the course of MS by comparing the frequency of MS-related hospitalizations during pregnancy and 40 weeks postpartum versus 40 weeks before pregnancy. We used administrative health claims to identify female patients with MS, their deliveries, and their MS-related hospital admissions and calculated the frequency of MS-related hospital admissions before, during, and after pregnancy. We observed that MS is diagnosed approximately three times less often during pregnancy than before or after pregnancy. The number of MS-related hospital admissions decreased during pregnancy, especially in the third trimester. In contrast with other studies, we did not observe an increased level of MS-related admissions postpartum. The number of hospitalizations reported with steroid injections and emergency department visits also decreased during pregnancy. Our results show that pregnancy has a protective effect on the course of MS.

To assess cardiovascular responses to cold face test (CFT) in patients with classic-onset ALS (bulbar or limb onset, ALS-C) and in patients with flail arm and flail leg phenotypes (FA/FL).In 18 ALS-C, eight FA/FL patients and 10 age-matched controls we continuously monitored heart rate (HR), systolic (SBP), diastolic (DBP) and mean blood pressure (MBP) during two-minute baseline and one-minute cold stimulus application. HR and BP responses to CFT were calculated as differences between the peak responses and baseline values (dHR, dSBP, dDBP, dMBP), as percent changes from baseline (dHR%, dSBP%, dDBP%, dMBP%), and also latencies and durations of HR and BP responses were assessed (LatThere were no differences in baseline values of HR, SBP, DBP and MBP among ALS-C, FA/FL and controls (p 0.05). A decrease in HR and increases in SBP, DBP and MBP were observed in all subjects (p 0.05). However, in FA/FL, the magnitude of BP responses, i.e. dSBP, dSBP%, dDBP, dMBP, and dMBP% were significantly higher than in controls. Moreover, these BP responses occurred with a significantly shorter latency in FA/FL than in controls and ALS-C. Furthermore, duration of the BP changes was significantly longer in FA/FL than in ALS-C. In contrast, ALS-C patients had a significantly longer LatSympathetic vascular response to facial cooling is increased in flail phenotypes of ALS.

Sphenopalatine ganglion stimulation increased cerebral collateral blood flow, stabilised the blood-brain barrier, and reduced infarct size, in preclinical models of acute ischaemic stroke, and showed potential benefit in a pilot randomised trial in humans. The pivotal ImpACT-24B trial aimed to determine whether sphenopalatine ganglion stimulation 8-24 h after acute ischaemic stroke improved functional outcome.ImpACT-24B is a randomised, double-blind, sham-controlled, pivotal trial done at 73 centres in 18 countries. It included patients (men aged 40-80 years and women aged 40-85 years) with anterior-circulation acute ischaemic stroke, not undergoing reperfusion therapy. Enrolled patients were randomly assigned via web-based randomisation to receive active sphenopalatine ganglion stimulation (intervention group) or sham stimulation (sham-control group) 8-24 h after stroke onset. Patients, clinical care providers, and all outcome assessors were masked to treatment allocation. The primary efficacy endpoint was the difference between active and sham groups in the proportion of patients whose 3-month level of disability improved above expectations. This endpoint was evaluated in the modified intention-to-treat (mITT) population (defined as all patients who received one active or sham treatment session) and the population with confirmed cortical involvement (CCI) and was analysed using the Hochberg multi-step procedure (significance in both populations if p0·05 in both, and in one population if p0·025 in that one). Safety endpoints at 3 months were all serious adverse events (SAEs), SAEs related to implant placement or removal, SAEs related to stimulation, neurological deterioration, and mortality. All patients who underwent an attempted sphenopalatine ganglion stimulator or sham stimulator placement procedure were included in the safety analysis. This trial is registered with ClinicalTrials.gov, number NCT00826059.Between June 10, 2011, and March 7, 2018, 1078 patients were enrolled and randomly assigned to either the intervention or the sham-control group. 1000 patients received at least one session of sphenopalatine ganglion stimulation or sham stimulation and entered the mITT population (481 [48%] received sphenopalatine ganglion stimulation, 519 [52%] were sham controls), among whom 520 (52%) patients had CCI on imaging. The proportion of patients in the mITT population whose 3-month disability level was better than expected was 49% (234/481) in the intervention group versus 45% (236/519) in the sham-control group (odds ratio 1·14, 95% CI 0·89-1·46; p=0·31). In the CCI population, the proportion was 50% (121/244) in the intervention group versus 40% (110/276) in the sham-control group (1·48, 1·05-2·10; p=0·0258). There was an inverse U-shaped dose-response relationship between attained sphenopalatine ganglion stimulation intensity and the primary outcome in the CCI population: the proportion with favourable outcome increased from 40% to 70% at low-midrange intensity and decreased back to 40% at high intensity stimulation (p=0·0034). There were no differences in mortality or SAEs between the intervention group (n=536) and the sham-control group (n=519) in the safety population.Sphenopalatine ganglion stimulation is safe for patients with acute ischaemic stroke 8-24 h after onset, who are ineligible for thrombolytic therapy. Although not reaching significance, the trial's results support that, among patients with imaging evidence of cortical involvement at presentation, sphenopalatine ganglion stimulation is likely to improve functional outcome.BrainsGate Ltd.

Direct oral anticoagulants (DOACs) such as apixaban, dabigatran, edoxaban, and rivaroxaban are mainly used in the prevention of thromboembolic complications in patients with atrial fibrillation (AF) and in the treatment of venous thromboembolism. As compared with vitamin K antagonists (VKAs), they are characterized by at least similar efficacy and better safety profiles, especially with respect to intracranial hemorrhages. Moreover, they are more convenient therapeutic agents. The 2016 European Society of Cardiology guidelines clearly favor DOACs over VKAs in patients with AF. However, DOAC therapy is also associated with the risk of bleeding complications. The aim of this review was to provide recommendations for the management of bleeding complications during DOAC therapy in the Polish setting. The recommendations were based on the most important documents concerning this issue and were developed by representatives of different medical specialties. Experience in managing cases of bleeding on DOAC therapy is still limited. Therefore, we hope that this publication will be helpful in everyday clinical practice and that it will be useful for developing in‑hospital recommendations for the management of patients with DOAC‑related bleeding.

Objectives Mechanical thrombectomy (MT) is not reimbursed by the Polish public health system. We present a description of 5 years of experience with MT in acute stroke in Comprehensive Stroke Centers (CSCs) in Poland. Methods and results We retrospectively analyzed the results of a structured questionnaire from 23 out of 25 identified CSCs and 22 data sets that include 61 clinical, radiological and outcome measures. Results Most of the CSCs (74%) were founded at University Hospitals and most (65.2%) work round the clock. In 78.3% of them, the working teams are composed of neurologists and neuro-radiologists. All CSCs perform CT and angio-CT before MT. In total 586 patients were subjected to MT and data from 531 of them were analyzed. Mean time laps from stroke onset to groin puncture was 250 ± 99 min. 90.3% of the studied patients had MT within 6 h from stroke onset; 59.3% of them were treated with IV rt-PA prior to MT; 15.1% had IA rt-PA during MT and 4.7% – emergent stenting of a large vessel. M1 of MCA was occluded in 47.8% of cases. The Solitaire device was used in 53% of cases. Successful recanalization (TICI2b–TICI3) was achieved in 64.6% of cases and 53.4% of patients did not experience hemorrhagic transformation. Clinical improvement on discharge was noticed in 53.7% of cases, futile recanalization – in 30.7%, mRS of 0–2 – in 31.4% and mRS of 6 in 22% of cases. Conclusion Our results can help harmonize standards for MT in Poland according to international guidelines.

Objective: Genome-wide association studies (GWAS) have been successful at identifying associations with stroke and stroke subtypes, but have not yet identified any associations solely with small vessel stroke (SVS). SVS comprises one quarter of all ischemic stroke and is a major manifestation of cerebral small vessel disease, the primary cause of vascular cognitive impairment. Studies across neurological traits have shown that younger-onset cases have an increased genetic burden. We leveraged this increased genetic burden by performing an age-at-onset informed GWAS meta-analysis, including a large younger-onset SVS population, to identify novel associations with stroke. Methods: We used a three-stage age-at-onset informed GWAS to identify novel genetic variants associated with stroke. On identifying a novel locus associated with SVS, we assessed its influence on other small vessel disease phenotypes, as well as on messenger RNA (mRNA) expression of nearby genes, and on DNA methylation of nearby CpG sites in whole blood and in the fetal brain. Results: We identified an association with SVS in 4,203 cases and 50,728 controls on chromosome 16q24.2 (odds ratio [OR; 95% confidence interval {CI}] = 1.16 [1.10–1.22]; p = 3.2 × 10−9). The lead single-nucleotide polymorphism (rs12445022) was also associated with cerebral white matter hyperintensities (OR [95% CI] = 1.10 [1.05–1.16]; p = 5.3 × 10−5; N = 3,670), but not intracerebral hemorrhage (OR [95% CI] = 0.97 [0.84–1.12]; p = 0.71; 1,545 cases, 1,481 controls). rs12445022 is associated with mRNA expression of ZCCHC14 in arterial tissues (p = 9.4 × 10−7) and DNA methylation at probe cg16596957 in whole blood (p = 5.3 × 10−6). Interpretation: 16q24.2 is associated with SVS. Associations of the locus with expression of ZCCHC14 and DNA methylation suggest the locus acts through changes to regulatory elements. Ann Neurol 2017;81:383–394.

Introduction: Although recently a matter of epidemiologic controversy, sodium overload and its interaction with genetic factors predispose to hypertension and related target organ complications. Methods: In 131 (66 male) treated hypertensives, we measured peripheral and central arterial pressures and pulse wave augmentation indexes (AIx P , AIx C1 , AIx C2 ), pulse wave velocity (PWV), daily urinary sodium excretion and did genetic studies of AGTR1 A1166C and AGTR2 G1675A polymorphisms. Proximal (FE Li ) and distal (FDR Na ) sodium reabsorption measurements were performed using endogenous lithium clearance. Results: In men, we found interaction between FDR Na and AGTR2 G1675A polymorphism with respect to AIx C1 ( p INT =0.01), AIx C2 ( p INT =0.05) and AIx P ( p INT =0.006). Arterial stiffness increased with higher sodium reabsorption in the distal tubule, in the presence of AGTR2 G allele with the opposite tendency in A allele carriers. In the subgroup with FDR Na below median, as compared to those with FDR Na above median, the AIx C1 (139.6±3.8 vs 159.1±5.7%; p =0.009), AIx C2 (26.3±1.8 vs 33.3±1.7%; p =0.016) and AIx P (83.4±2.5 vs 96.5±2.6%; p

Cardiotoxicity of chemotherapy is a serious complication of oncological treatment. Assessment of cardiac function before, during and after cardiotoxic chemotherapy course should be a standard procedure in oncology. There are several methods for evaluation of the changes in myocardium such as: electrocardiography, radiology techniques (RTG, CT, MRI, PET-CT, PET-MRI), echocardiography, radioisotope imaging techniques (scyntygraphy, MUGA, PET), and ultra-structure evaluation in biopsy samples. Nevertheless, there is a continuous need for new diagnostic methods of cardiac dysfunction of great predictive and prognostic importance. Unfortunately advanced imaging techniques are still not available in many oncological centers in Poland. Nowadays to evaluate potential cardiotoxicity of drugs in oncology it is postulated to perform serial echocardiographic examinations as a basal imaging method. Thus constant cooperation between cardiologist and oncologist plays crucial role during chemotherapy.

The treatment based on athracyclines and trastuzumab may lead to heart failure in oncological setting. Assessment of the heart function is conducted using radiological examinations, especially echocardiography. Biochemical diagnostics enables to depict clinically silent cardiac dysfunction at an earlier stage. Biomarkers that showed to be the most promising in predicting the development of deterioration of systolic and/or diastolic function in course of chemotherapy are troponins and NT-pro-BNP. However, no cut-off point had been yet determined, especially in terms of cardiotoxicity induced by oncological therapy. Biomarkers serum level may be dependent on many conditions, mostly comorbidities, what makes the interpretation of the results difficult. Trials involving mikro RNA particles, which depict the molecular level of the pathological changes, also those involved in the development of cardiomyopathy, are underway.

To lower the number of complications of acute cerebral ischemic stroke and to reduce the time of rehabilitation in these patients it is necessary to induce treatment within the first 3 hours of the onset of the stroke. Early intervention however, is possible only in cases with the confirm localized ischemic focus visualized in one of the diagnostic imaging methods. The most widespread is CT, hovewer the first symptoms of ischemic stroke can be seen not beforel2 hours of the onset. The study evaluated the effectiveness of early diagnostics of ischemic stroke using perfusion CT (pCT) with subsequent intravenous or intra-arterial thrombolysis. The patients with ischemic stroke confirmed by pCT and qualified to thrombolysis in the first 3 hours of the onset of the stroke were randomly selected to intravenous or intra-arterial thrmobolysis. Those, who were 3 to 6 hours of the onset of the stroke were qualified to intra-arterial thrombolysis. A study group consisted of 377 patients hospitalized due to ischemic stroke. Of these pCT was performed in 76 cases, intravenous thrombolysis in 4 and intra-arterial thrombolysis in 2. Clinical condition substantially improved in 3 patients. Obtained results indicate the necessity to introduce pCT to the routine diagnostics of the acute ischemic stroke. A small number of patients eligible for thrombolysis does not allow to compare the effectiveness of intra-arterial and intravenous thrombolysis, however the project allowed to work out the efficient system of diagnostics and treatment of the acute ischemic stroke in the area of Krakow based on the standards used in the European countries.

Subclinical hepatic encephalopathy (SHE) is a serious clinical problem in patiens with liver damage and precise pathophisiological mechanisms resonsible for encephalopathy are not fully understood. Is definied as a spectrum of neuropsychiatric abnormalities in patients with liver dysfunction after exclusion of other known brain disease. Recent date have shown that increased CNS (central nervous system) ammonia concentration and presence of mild diffuse brain oedema plays a key role in the pathogenesis of SHE. Diagnosis of manifest HE (hepatic encephalopathy) is made on the basis of clinical symptoms, whereas psychometric or neurophisiological tests are required for detection of SHE. PET, MRI, H-MRS allow the rapid and noninvasive evaluation of structural, phisiologic and biochemical features of the brain.

A growing body of evidence suggests that semiquantitative assessment of perfusion computed tomography (PCT) may improve evaluation of acute ischaemic stroke patients and provide some prognostic values. The Alberta Stroke Program Early CT Score (ASPECTS) is one of the tools quantifying ischaemic changes on CT scans. While introducing PCT for routine evaluation of patients with clinical suspicion of acute stroke in our Neurology Department, we aimed to investigate the agreement in analysis of non-contrast CT (NCCT) and PCT using ASPECTS between neuroradiologists and stroke neurologists.We analyzed the data of 34 patients with hemispheric ischaemic stroke, in whom NCCT and PCT were performed within 12 hours after stroke onset. Two pairs of reviewers independently assessed NCCT and PCT [colour-coded maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and time-to-peak (TTP)] using ASPECTS. Based on the literature data, we dichotomized the score. The chosen cut-off points were: 6 vs.6, 7 vs.7, and 8 vs.8. The agreement was determined using kappa statistics.A better agreement was achieved for PCT maps compared with NCCT scans and when the cut-off point was 7 vs.7. The results were as follows: for NCCT fair agreement (k=0.27), for CBF and for CBV moderate agreement (k=0.46 and k=0.57, respectively), for TTP substantial agreement (k=0.77).A good agreement in semiquantitative assessment of PCT using ASPECTS indicates that it is a reliable tool to analyze acute ischaemic stroke patients and superior to NCCT.

There is increasing availability of perfusion computed tomography (PCT) for assessment of acute ischaemic stroke patients. A semiquantitative evaluation of CT scans can be easily and quickly performed by the examining physician. In the current study, we investigated the correlation between the Alberta Stroke Program Early CT Score (ASPECTS) quantifying acute ischaemic changes on CT scans and clinical status of ischaemic stroke patients.We analyzed the data of 34 patients with hemispheric ischaemic stroke, in whom both non-contrast CT (NCCT) and PCT were performed within 12 hours after stroke onset. NCCT and PCT [colour-coded maps of cerebral blood flow (CBF), cerebral blood volume (CBV), and time-to-peak (TTP)] were evaluated using ASPECTS. The correlations between ASPECTS and severity of neurological deficit, and prognostic value of ASPECTS for long-term clinical outcome were studied.We found a significant correlation between the baseline clinical status and ASPECTS for all CT techniques as well as between CBV and neurological deficit at discharge. ASPECTS ł7 in all CT techniques had a high sensitivity and positive predictive value for prognosis of 3-month functional independency.ASPECTS used for PCT and NCCT shows a good correlation with clinical status and prognosis of ischaemic stroke patients.

Hyperthermia worsens prognosis in ischaemic, but probably not in haemorrhagic stroke. The reason for this discrepancy is unknown; therefore we designed this study to compare factors related to the occurrence of hyperthermia in patients with ischaemic and haemorrhagic stroke.We studied 100 consecutive patients with hemispheric intracerebral haemorrhage and 100 patients with hemispheric ischaemic stroke, who were strictly matched regarding sex (53% were men), age (mean: 67+/-10 years) and severity of neurological deficit on admission according to the Scandinavian Stroke Scale [median: 22 (8-34)]. Body temperature was measured on admission and every 4 hours within the first 48 hours after admission. We recorded neurological deficit, disorders of consciousness, major infectious complications, and a range of routine biochemical markers. Outcome was assessed by 30-day mortality and by the functional status of survivors 30 and 90 days after stroke.The percentages of patients with hyperthermia (37.5 degrees C) were similar in ischaemic and haemorrhagic stroke (26% vs. 33% on day 1 and 19% vs. 23% on day 2, respectively). Patients with hyperthermia on day 1 in both groups had higher 30-day mortality, worse functional status after 90 days and more often had decreased consciousness on admission. Markers of inflammation were slightly higher in hyperthermic patients with ischaemic, but not with haemorrhagic stroke.Hyperthermia in acute stroke, whether ischaemic or haemorrhagic, is associated with worse prognosis. Ischaemic stroke patients with hyperthermia have slightly increased levels of inflammatory markers when compared to patients without hyperthermia, but the same difference was not found in patients with haemorrhagic stroke.

Late-onset Alzheimer's disease (LOAD) is the most common neurodegenerative disorder, and has a complex etiology. Recently an intronic polymorphism in the ubiquilin 1 gene (UBQLN1) and a particular haplotype was reported to be associated with LOAD. We investigated whether variants in UBQLN1 confer a risk for the disease in 407 Polish LOAD patients and 407 controls. We observed a weak association with the rs2781002 polymorphism, however, contrary to the initial reports, in our group the association was with the A allele. Risk estimation for AA versus GG genotypes showed that the AA genotype is a weak risk factor for AD (OR = 1.8, 95% CI = 1.1-3.1, p = 0.025). This effect was stronger in a group of LOAD patients without APOE4 allele. Haplotype analyses indicate that there is an increase of haplotypes with an A allele in the case group. Also, the specific haplotypes with the A allele that increase AD risk differ between the APOE4-positive and APOE4-negative pools. However, the association observed seems to be driven mostly by rare (5%) haplotypes. Results suggest a need for additional association studies and in silico analysis of the UBQLN1 locus.

Previous epidemiological studies of stroke in Poland completed more than 10 years ago reported moderate incidence rates but very high case fatality rates due to stroke. We used the data of the Krakow Stroke Registry to calculate the attack rates as well as short- and long-term case fatality rates from stroke in hospitalized inhabitants of Krakow, Poland.We prospectively recorded all cases of stroke (defined according to the ICD-10) in adult permanent residents of Krakow, who were admitted to hospitals in that city. The registration took one year (between 1 July 1999 and 30 June 2000). The vital status of participants was established on days 30, 90 and 180 and at one year after their stroke.1096 strokes occurred in a population of 589,820. Attack rate standardized for the European population was 180.0 per 100,000 (218.3 in men and 151.9 in women). Ischaemic stroke was diagnosed in 532 (48.6%), stroke not specified as haemorrhagic or ischaemic in 406 subjects (37.0%), intracerebral haemorrhage in 86 (7.8%), and subarachnoid haemorrhage in 72 (6.6%). The 30-day, 90-day, 180-day and one-year case fatality rates for all strokes were 17.8%, 28.1%, 30.8% and 39.7%, respectively. Case fatality rates for ischaemic stroke were 9.8%, 19.0%, 21.6% and 31.2%, respectively and for intracerebral haemorrhage 44.2%, 55.8%, 55.8% and 60.5%, respectively.The attack rates of stroke in urban areas of Poland are similar to the average European rates. Short- and long-term case fatality rates are much lower than previously reported.

To prevent the recurrence of primary intracerebral hemorrhage (PIH) it is important to identify patients with underlying structural vascular abnormalities (VA). According to previous study data-- the site of hemorrhage, the patient's age and pre-existing hypertension affect the likelihood of finding VA. However, the indications for angiography, the gold standard for the diagnosis of VA, still remain controversial.To assess the frequency of VA and to determine features that might increase the probability of finding VA in patients with PIH.100 patients with PIH, without a history of trauma, coagulopathy, or known pre-existing brain abnormality, who were admitted to the Stroke Unit of the Department of Neurology, Jagiellonian University, between January 1999 and November 2000 entered this prospectively designed study. In the group of 96 patients, 53 persons underwent conventional angiography within 14 days of stroke onset (in 4 cases we found bleeding into the tumor and these patients were not included in further analysis).Vascular abnormalities were found in 14 of 53 patients (26.4%); ruptured aneurysms in 9 patients (17.0%), arteriovenous malformations (AVM) in 3 patients (5.7%), venous angioma in 1 patient (1.8%) and cavernous angioma in 1 patient (1.9%). Vascular malformations were found in 12 of 25 patients with lobar hemorrhage, in 1 of 8 patients with hemorrhage originating in the thalamus and in 1 of 2 patients with hemorrhage originating in the pons. Angiographic findings were negative in 8 patients with hemorrhage in the periventricular white matter, in 8 with hemorrhage originating in the basal ganglia and in 2 patients with hemorrhage in the cerebellum. Patients with VA were significantly younger than patients without VA (49.9 +/- 11.7 years and 58.7 +/- 13.3 years respectively, p = 0.03) and they had a history of hypertension significantly less often (50.0% and 89.7%, p = 0.001). Intraventricular hemorrhage and subarachnoid bleeding occurred in a similar percentage of patients with ICH, independent of whether or not they had VA (28.6% and 38.5%; 21.4% and 10.3% respectively, p = n.s.).(1) A vascular abnormality is the cause of about 26% of ICH, with a higher likelihood in younger patients and with lobar hemorrhage. (2) A history of hypertension does not exclude the presence of VA. (3) Intraventricular hemorrhage or subarachnoid bleeding does not predict the presence of VA.

of the study was to compare hemostatic markers of endothelial injury in patients with ischaemic stroke caused by large vessel disease (LVD) or small vessel disease (SVD).We studied 30 patients with LVD and 41 patients with SVD (recruited out of 585 patients with ischaemic stroke) as well as 30 control subjects. Etiology of ischaemic stroke was established according to the TOAST criteria. In patients being 3-12 months after stroke we registered age, sex and the presence of common risk factors for stroke. We measured serum concentration of fibrinogen and plasminogen activator inhibitor 1 (PAI-1), activity of von Willebrand factor (vWF) and the level of beta-thromboglobulin (beta-TG).The concentration of fibrinogen was greater in patients with LVD (3.56 +/-0.88 g/L) when compared to patients with SVD (2.78 +/-0.69 g/L, pO.0005). Activity of vWF was higher in all stroke survivors (155.8+/-53.9%) when compared to controls (124.8+/-43.3%; p0.01). It was also higher in patients with LVD (179.9+/-53.6%) than in patients with SVD (139.3+/-48. 1%; pO.01). The level of /-TG in patients with LVD [192.0 (69.7-222.1) UI/mL] was higher than in patients with SVD [90.6 (56.6-165.8) UI/mL; p0.05] and higher than in controls [108.7 (49.0-166.5) Ul/mL, p0.05]. The concentration of PAl-1 was similar among all studied groups.Stroke patients with LVD are characterized by higher concentration of fibrinogen, higher activity of vWF and higher levels of (Beta-TG) than patients with SVD. PAI-1 concentration is similar in both groups. Our results confirm the need for reanalysis of risk factors and pathomechanism of each cause of stroke separately.