The Importance of Increased Serum GFAP and UCH-L1 Levels in Distinguishing Large Vessel from Small Vessel Occlusion in Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is one of the leading causes of morbidity worldwide, thus, early recognition is essential to accelerate treatment. The only definite way to diagnose AIS is radiological imaging, which is limited to hospitals. However, two serum neuromarkers, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1), have been proven as indicators of brain trauma and AIS. We aimed to investigate the potential utility of these markers in distinguishing between large vessel occlusion (LVO) and small vessel occlusion (SVO), considering differences in treatment. Sixty-nine AIS patients were included in our study and divided into LVO and SVO groups based on radiological imaging. Control group consisted of 22 participants without history of neurological disorders. Results showed differences in serum levels of both GFAP and UHC-L1 between all groups; control vs. SVO vs. LVO (GFAP: 30.19 pg/mL vs. 58.6 pg/mL vs. 321.3 pg/mL; UCH-L1: 117.7 pg/mL vs. 251.8 pg/mL vs. 573.1 pg/mL; p < 0.0001), with LVO having the highest values. Other prognostic factors of stroke severity were analyzed and did not correlate with serum biomarkers. In conclusion, a combination of GFAP and UCH-L1 could potentially be a valuable diagnostic tool for differentiating LVO and SVO in AIS patients.

Chronic Endothelial Dysfunction after COVID-19 Infection Shown by Transcranial Color-Coded Doppler: A Cross-Sectional Study.

In addition to respiratory symptoms, COVID-19 often causes damage to many other organs, especially in severe forms of the disease. Long-term consequences after COVID-19 are common and often have neurological symptoms. Cerebral vasoreactivity may be impaired after acute COVID-19 and in our study, we wanted to show how constant and reversible are the changes in brain vasoreactivity after infection. This cross-sectional observational study included 49 patients diagnosed with COVID-19 and mild neurological symptoms 300 days after the onset of the disease. We used a transcranial color-coded Doppler (TCCD) and a breath-holding test (BHT) to examine cerebral vasoreactivity and brain endothelial function. We analyzed the parameters of the flow rate through the middle cerebral artery (MCA): peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), resistance index (RI) and pulsatility index (PI), and we calculated the breath-holding index (BHI). Subjects after COVID-19 infection had lower measured velocity parameters through MCA at rest period and after BHT, lower relative increases of flow velocities after BHT, and lower BHI. We showed that subjects, 300 days after COVID-19, still have impaired cerebral vasoreactivity measured by TCCD and they have chronic endothelial dysfunction.

Experiences and attitudes of medical professionals on treatment of end-of-life patients in intensive care units in the Republic of Croatia: a cross-sectional study.

BACKGROUND: Decisions about limitations of life sustaining treatments (LST) are made for end-of-life patients in intensive care units (ICUs). The aim of this research was to explore the professional and ethical attitudes and experiences of medical professionals on treatment of end-of-life patients in ICUs in the Republic of Croatia. METHODS: A cross-sectional study was conducted among physicians and nurses working in surgical, medical, neurological, and multidisciplinary ICUs in the total of 9 hospitals throughout Croatia using a questionnaire with closed and open type questions. Exploratory factor analysis was conducted to reduce data to a smaller set of summary variables. Mann-Whitney U test was used to analyse the differences between two groups and Kruskal-Wallis tests were used to analyse the differences between more than two groups. RESULTS: Less than third of participants (29.2%) stated they were included in the decision-making process, and physicians are much more included than nurses (p < 0.001). Sixty two percent of participants stated that the decision-making process took place between physicians. Eighteen percent of participants stated that 'do-not-attempt cardiopulmonary resuscitations' orders were frequently made in their ICUs. A decision to withdraw inotropes and antibiotics was frequently made as stated by 22.4% and 19.9% of participants, respectively. Withholding/withdrawing of LST were ethically acceptable to 64.2% of participants. Thirty seven percent of participants thought there was a significant difference between withholding and withdrawing LST from an ethical standpoint. Seventy-nine percent of participants stated that a verbal or written decision made by a capable patient should be respected. Physicians were more inclined to respect patient's wishes then nurses with high school education (p = 0.038). Nurses were more included in the decision-making process in neurological than in surgical, medical, or multidisciplinary ICUs (p < 0.001, p = 0.005, p = 0.023 respectively). Male participants in comparison to female (p = 0.002), and physicians in comparison to nurses with high school and college education (p < 0.001) displayed more liberal attitudes about LST limitation. CONCLUSIONS: DNACPR orders are not commonly made in Croatian ICUs, even though limitations of LST were found ethically acceptable by most of the participants. Attitudes of paternalistic and conservative nature were expected considering Croatia's geographical location in Southern Europe.

Differential influence of vitamin C on the peripheral and cerebral circulation after diving and exposure to hyperoxia.

We examined if the diving-induced vascular changes in the peripheral and cerebral circulation could be prevented by oral antioxidant supplementation. Fourteen divers performed a single scuba dive to eighteen meter sea water for 47 min. Twelve of the divers participated in a follow-up study involving breathing 60% of oxygen at ambient pressure for 47 min. Before both studies, participants ingested vitamin C (2 g/day) or a placebo capsule for 6 days. After a 2-wk washout, the study was repeated with the different condition. Endothelium-dependent vasodilator function of the brachial artery was assessed pre- and postintervention using the flow-mediated dilation (FMD) technique. Transcranial Doppler ultrasound was used to measure intracranial blood velocities pre- and 90 min postintervention. FMD was reduced by ∼32.8% and ∼21.2% postdive in the placebo and vitamin C trial and posthyperoxic condition in the placebo trial by ∼28.2% ( P < 0.05). This reduction in FMD was attenuated by ∼10% following vitamin C supplementation in the hyperoxic study ( P > 0.05). Elevations in intracranial blood velocities 30 min after surfacing from diving were reduced in the vitamin C study compared with the placebo trial ( P < 0.05). O2 breathing had no postintervention effects on intracranial velocities ( P > 0.05). Prophylactic ingestion of vitamin C effectively abrogated peripheral vascular dysfunction following exposure to 60% O2 but did not abolish the postdive decrease in FMD. Transient elevations of intracranial velocities postdive were reduced by vitamin C. These findings highlight the differential influence of vitamin C on peripheral and cerebral circulations following scuba diving, which are only partly mediated via hyperoxia.

Characterization of blood flow through intrapulmonary arteriovenous anastomoses and patent foramen ovale at rest and during exercise in stroke and transient ischemic attack patients.

OBJECTIVES: We determined whether stroke and/or TIA subjects have exercise-induced blood flow through intrapulmonary arteriovenous anastomoses (QIPAVA ) and/or patent foramen ovale (QPFO ) and a genetic predisposition for ischemic stroke. METHODS: Twenty-eight stroke and/or TIA subjects (33-63 years old) underwent transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect QIPAVA and QPFO at rest and during supine exercise with and without breathing 100% O2 . We also examined genetic polymorphisms in FV Leiden (G1691A; rs6025), factor II (FII) prothrombin (G20210A; rs1799963), methylene tetrahydfropholate reductase (C677T, rs1801133), and plasminogen-activator inhibitor-1 (PAI-1) (4G/5G; rs1799889) and angiotensin-converting enzyme (ACE; I/D, rs4646994) in 24/28 subjects. RESULTS: No subject without PFO had QIPAVA at rest (n=17), but 12/17 did with exercise. All PFO subjects had QPFO at rest (n=11) and 7/11 had either QIPAVA or QPFO with exercise. Breathing 100% O2 during exercise reduced or eliminated left heart contrast in all subjects. Gene analyses revealed that 15/24 patients were either heterozygous or homozygous for methylenetetrahydrofolate reductase gene polymorphism; 4G/4G and 4G/5G genotypes of plasminogen-activator inhibitor-1 were present in 7/24 and 13/24 patients, respectively; polymorphisms of ACE D/D genotype were present in 6/24 and I/D in 14/24 patients. Having both I/D and 4G/4G genotypes was more prevalent in PFO+ subjects (P=.03), and there was a trend (P=.06) for PFO- subjects to have a greater D/D genotype prevalence. CONCLUSIONS: Novel genetic predispositions reported here in PFO subjects should be investigated further in larger stroke and/or TIA patient datasets.

Resting arterial hypoxaemia in subjects with chronic heart failure, pulmonary hypertension and patent foramen ovale.

NEW FINDINGS: What is the central question of this study? Does a patent foramen ovale contribute to resting arterial hypoxaemia, defined as arterial oxygen saturation <95%, in subjects with chronic heart failure with or without pulmonary arterial hypertension? What is the main finding and its importance? The presence of a patent foramen ovale contributed to resting arterial hypoxaemia only in subjects with chronic heart failure with pulmonary arterial hypertension. These data suggest that the presence of a patent foramen ovale should be considered in chronic heart failure patients with arterial hypoxaemia and pulmonary hypertension. The roles of intrapulmonary and intracardiac shunt in contributing to arterial hypoxaemia at rest in subjects with chronic heart failure (CHF) have not been well investigated. We hypothesized that blood flow through intrapulmonary arteriovenous anastomoses (Q̇ IPAVA ) and/or patent foramen ovale (Q̇ PFO ) could potentially contribute to arterial hypoxaemia and, with pulmonary hypertension (PH) secondary to CHF, this contribution may be exacerbated. Fifty-six subjects with CHF (New York Heart Association Classes I-III), with (+) or without (-) PH [defined as peak tricuspid regurgitation velocity ≥2.9 m s(-1) (CHF PH+, n = 32) and peak tricuspid regurgitation velocity ≤2.8 m s(-1) (CHF PH-, n = 24)], underwent arterial blood gas analysis and transthoracic saline contrast echocardiography concomitant with transcranial Doppler to detect Q̇ IPAVA and Q̇ PFO . Seventeen of 56 subjects with CHF (30%) had Q̇ PFO , but only four of 56 subjects with CHF had Q̇ IPAVA (7%), both similar to age- and sex-matched control subjects. Mean arterial oxygen saturation (SaO2) was lower in subjects with Q̇ PFO . Only CHF PH+ subjects with Q̇ PFO had arterial hypoxaemia (mean SaO2 <95%). Bubble scores assessed using transthoracic saline contrast echocardiography were correlated with microembolic signals detected with transcranial Doppler in subjects with Q̇ PFO . Significant Q̇ IPAVA was not present in either CHF PH+ or PH- subjects, suggesting that Q̇ IPAVA is not dependent on increased pulmonary pressure and does not contribute significantly to arterial hypoxaemia in older subjects with CHF. Given that SaO2 was lower in all subjects with CHF who had Q̇ PFO compared with those without Q̇ PFO , a patent foramen ovale should be considered when determining potential causes of arterial hypoxaemia, because Q̇ PFO was present in 30% of these subjects.

Two Cases of Rare Basilar Hypoplasia.

In this article, we report two cases of basilar artery hypoplasia; the first case was a primitive trigeminal artery, and the second was an isolated basilar artery hypoplasia. Both patients had general neurologic disturbances, including periodic intention tremor of the left hand. Our data underscore the utility of complementary time of flight (TOF) magnetic resonance and multidetector computed tomography (MDCT) angiography as reliable first detection methods for steno-occlusive diseases and in cases of suspected congenital vascular anomalies.

[Anticoagulant therapy in patients with permanent atrial fibrillation - evidence based medicine and clinical practice]. / Antikoagulantno lijecenje u bolesnika s trajnom fibrilacijom atrija - medicina utemeljena na dokazima i klinicka praksa.

Objective of study was to assess the concordance of the tromboprophylactic treatment in patients with permanent atrial fibrillation (pAF) with guidelines of the European Society of Cardiology. Prospective cross-sectional study consecutivelly included 674 patients (400 S59%C male) discharged from cardiology department with the diagnosis pAF. The thromboembolic risk (TE) has been established according to CHA2DS2-VASc score, whereas the bleeding risk has been assessed according to HAS-BLED score. 578 (86%) belonged to the group of high, 57 (8%) to the group of moderate, and 39 (6%) patients to the group of low TE risk. 601 (89%) patients received thromboprophylaxis: 310 (46%) warfarin, 258 (38%) acetylsalicylic acid, and 33 (5%) patients clopidogrel. Warfarin has been prescribed to 47% of patients with high, 49% of patients with moderate and to 26% of patients with low TE risk (P=0.03). Acetylsalicylic acid (ASA) has equally been prescribed to patients of all TE risk groups: low, moderate and high (39% vs. 39% vs.38%/o; P=0.998). ASA (P<0.001) and warfarin (P=0.007) have been used more frequently in the group of patients with high bleeding risk, in which the same incidence of warfarin and ASA administration has been registered (53% vs. 47%; P=0.416). Age > or =75 has been an independent predictor of non-administration (OR 1.7; 95% CI 1.2-2.4; P=0.003), whereas the history of stroke was for warfarin administration (OR 0.47; 95% CI 0.29-0.76; P-0.002). In prescribing thromboprophylaxis to patients with pAF, cardiologists do not observe the recommended clinical guidelines. Despite nonexistence of contraindications, a significant number of patients with high TE risk has not been administered warfarin. At the same time, warfarin has been administered to the patients with low TE risk, exposing them unnecessarily to the undesired effect of anticoagulant treatment.

[Thromboembolic and bleeding risk assessment in patients with non-rheumatic atrial fibrillation using CHA2DS2-VASc and HAS-BLED scoring systems]. / Procjena tromboembolijskog rizika i rizika od krvarenja u bolesnika s nereumatskom atrijskom fibrilacijom primjenom bodovnih sustava CHA2DS2-VASC i HASBLED.

It is estimated that approximately 1-2% of the world population are affected with non-rheumatic atrial fibrillation (nAF). The most frequent complications of this arrhythmia are thromboembolic events, primarly ischemic stroke. In comparison with patients in sinus rhythm, stroke affected nAF patients have more severe clinical course and significantly higher mortality rate, and the survivors have significantly lower recovery rate and more serious permanent mental and physical impairments. The administration of anticoagulants to patients with nAF significantly reduces the incidence of stroke, while those who were stroke affected during the anticoagulant therapy show better treatment outcomes. Therefore, professional associations guidelines recommend the anticoagulant treatment for the majority of patients with nAF. The fear of bleeding caused by anticoagulants results in their frequently unjustified omission from the therapy in patients with high thromboembolic risk. This paper presents CHA2DS2-VASc- and HAS-BLED systems recommended for thromboembolic and bleeding risk assessment when deciding on thromboprophylactic therapy in patients with nAF.

Correlation analysis of visual analogue scale and measures of walking ability in multiple sclerosis patients.

Walking limitation assessment in multiple sclerosis patients (MSPs) is a demanding task, especially in the clinical setting. The aim of this study is to correlate the visual analogue scale (VAS), a simple method for measuring subjective experience, with measures of walking ability used in clinical research of MS. The study included 82 ambulatory MSPs who have resided in the local community. The applied measures of walking ability were the following: the single-item and patient-rated Walking Ability Visual Analogue Scale (WA-VAS), the Expanded Disability Status Scale (EDSS), the 25-foot walk test (25FWT), the Six Spot Step Test (SSST), the 2 min timed walk (2 min TW), the Multiple Sclerosis Walking Scale-12 (MSWS-12), and step activity monitor accelerometer (SAM) during 7 day period. The SAM analysis included the average daily step count, the average steps/min of the highest 1 min of a day, and the average steps/min of the highest continuous 60 min of a day. The WA-VAS scores significantly and strongly correlated with EDSS (ρ = 0.679, P < 0.001), 25FWT (ρ = 0.606, P < 0.001), SSST (ρ = 0.729, P < 0.001), 2 min TW (ρ = -0.643, P < 0.001), MSWS-12 (ρ = 0.746, P < 0.001), average daily step count (ρ = -0.507, P < 0.001), average steps/min of the highest 1 min of a day (ρ = -0.544, P < 0.001), and average steps/min of the highest continuous 60 min of a day (ρ = -0.473, P < 0.001). Correlations between WA-VAS and measures of walking ability used in clinical research of MS were satisfactory. The results obtained in this research indicate that the WA-VAS could be an instrument for simple measurement of walking limitations in MSPs in the clinical setting.

CT perfusion and noncontrast CT in acute ischemic stroke diagnosing--is there influence on early thrombolytic therapy outcome?

The objective of this study was to compare noncontrast computed tomography (NCCT) and computed tomography perfusion (CTP) in early diagnosis of acute ischemic stroke and to define influence of these diagnostic procedures on early outcome of thrombolytic therapy (TLTH). The study included 45 patients, 35 patients submitted to NCCT and CTP and 10 patients who underwent only NCCT, before CTP was introduced. Based on the National Institute of Health Stroke Scale (NIHSS) score we compared early outcome of patients who received TLTH after NCCT only (group 1) with the early outcome of patients who received TLTH following NCCT and CTP (group 2). Statistically significant difference was found in acute stroke diagnosing between CTP and NCCT (p = 0.002). There were no statistically significant differences in TLTH early outcome between group 1 and group 2. In conclusion, CTP should be done regulary in patients presenting with acute ischemic stroke symptoms. More research needs to be done in defining exact influence of CTP implementation on the TLTH outcome.

Risk factors and outcome differences between ischemic and hemorrhagic stroke.

The aim of the study was to justify the hypothesis that risk factors do not differ between ischemic and hemorrhagic stroke. This retrospective study included 1066 stroke patients. The prevalence of risk factors and hospital-based survival were compared between patients with ischemic and hemorrhagic stroke. Data were retrieved from patient records. Statistical analysis was done by use of chi2-test and t-test for dependent samples. The group of hemorrhagic stroke consisted of 70 (47.9%) female and 76 (52.1%) male patients. The group of ischemic stroke included 450 (48.9%) female and 470 (51.1%) male patients. Ischemic stroke patients had a higher prevalence of hypertension (79% vs. 72%), atherosclerotic diseases (50% vs. 34%) and atrial fibrillation (15.5% vs. 4.2%), and were statistically significantly older (72.5 +/-10.4 vs. 65.7 +/- 12.8) than those with hemorrhagic stroke, however, fatal outcome was more common in the latter (26% vs. 17%). In conclusion, data analysis pointed to differences between hemorrhagic and ischemic stroke according to both risk factors and stroke outcome.