Aortic Stiffness Is Independently Associated with Intracranial Carotid Artery Calcification in Patients with Ischemic Stroke.

INTRODUCTION: Intracranial carotid artery calcification (ICAC), as a strong contributor to the occurrence of ischemic stroke, might be present in the medial or intimal arterial layer. Traditional cardiovascular risk factors (CVRFs) are associated with ICAC; however, its association with new markers of vascular function is less understood. The paper aimed to evaluate the relationship between carotid-femoral pulse wave velocity (CF-PWV) and ICAC subtypes. METHODS: We enrolled 65 patients with ischemic stroke. CF-PWV, systolic, diastolic, mean blood pressure, and pulse pressure were measured within 6 ± 2 days after stroke onset, and CT was performed within 24 h. ICAC on the stroke site was classified by two methods: volume and score based. Tertiles of ICAC volume were determined, and low-grade ICAC (T1) was regarded as a reference. According to the score-based method, (dominant) medial and (dominant) intimal ICAC subtypes were determined. Data were analyzed with multivariate logistic regression. RESULTS: Medial and intimal ICAC subtypes were found in 34 (52%) and 24 (37%) patients, respectively. In 11% of patients, no ICAC calcifications were found. CF-PWV was higher in patients with high-grade ICAC (OR = 1.56, 95% CI = 1.03-2.35, p = 0.035). CF-PWV was higher in patients with the medial ICAC subtype (OR = 1.60, 95% CI = 1.00-2.55, p = 0.049) after adjustment for traditional CVRFs. CONCLUSION: Our study demonstrates that among patients with ischemic stroke, aortic stiffness is independently associated with ICAC and that medial ICAC, compared with intimal ICAC, is accompanied by more advanced aortic stiffness.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Comparative analysis of GOLPH3 expression in lymph node-positive prostate cancer: immunohistochemistry staining patterns and clinical significance.

Introduction: Prostate cancer (PCa) is the second most commonly diagnosed cancer in men worldwide. Lymph node metastasis is a poor prognostic factor for PCa. Previous studies have found that Golgi phosphoprotein 3 (GOLPH3) is overexpressed in various cancers, including PCa. We examined GOLPH3 expression in PCa cells from primary tumor and, as the first, also in metastatic lymph nodes to assess its potential as a new risk factor for PCa progression. Methods: The study included 78 patients diagnosed with lymph node-positive PCa confirmed in the postoperative material. All the patients underwent radical prostatectomy (RP) with extended lymphadenectomy. The clinical data of the patients were retrospectively analyzed, and their histopathological specimens were selected for further analysis. Immunohistochemistry (IHC) staining was performed and the expression of GOLPH3 was assessed by an experienced uropathologist using an immunoreactive scale (IRS). A correlational analysis of the obtained data with the clinicopathological data of patients was performed. Results: A positive IHC reaction for GOLPH3 was observed in all samples. IRS score for GOLPH3 expression was higher in the metastatic lymph nodes than in the prostate (not statistically significant; p=0.056). Several significant correlations were identified in connection with GOLPH3 expression levels in the prostate and metastatic lymph node tissues. No significant correlations were found between GOLPH3 expression and patient characteristics (e.g. BMI, EAU risk group, or preoperative PSA level), pathological features, or postoperative outcomes. However, we found that lymphovascular invasion (LVI) tended to be more common in patients with a higher percentage of GOLPH3-positive cells (p=0.02). We also found a positive association between the intensity of GOLPH3 staining in metastatic lymph nodes and the EAU classification. Finally, we found a significant negative correlation between the GOLPH3 expression and the efficacy of RP - the higher the expression of GOLPH3, the lower the efficacy of RP was (p<0.05). Conclusion: GOLPH3 is expressed in both prostate and metastatic lymph nodes, with higher expression in metastatic lymph nodes. High GOLPH3 expression was associated with the occurrence of LVI, higher-risk group in the EAU classification, and lower efficacy of the RP, but there was no significant correlation with other pathological features or postoperative outcomes.

Structural Health Monitoring of Chemical Storage Tanks with Application of PZT Sensors.

Chemical pressure storage tanks are containers designed to store fluids at high pressures, i.e., their internal pressure is higher than the atmospheric pressure. They can come in various shapes and sizes, and may be fabricated from a variety of materials. As aggressive chemical agents stored under elevated pressures can cause significant damage to both people and the environment, it is essential to develop systems for the early damage detection and the monitoring of structural integrity of such vessels. The development of early damage detection and condition monitoring systems could also help to reduce the maintenance costs associated with periodic inspections of the structure and unforeseen operational breaks due to unmonitored damage development. It could also reduce the related environmental burden. In this paper, we consider a hybrid material composed of glass-fiber-reinforced polymers (GFRPs) and a polyethylene (PE) layer that is suitable for pressurized chemical storage tank manufacturing. GFRPs are used for the outer layer of the tank structure and provides the dominant part of the construction stiffness, while the PE layer is used for protection against the stored chemical medium. The considered damage scenarios include simulated cracks and an erosion of the inner PE layer, as these can be early signs of structural damage leading to the leakage of hazardous liquids, which could compromise safety and, possibly, harm the environment. For damage detection, PZT sensors were selected due to their widely recognized applicability for the purpose of structural health monitoring. For sensor installation, it was assumed that only the outer GFRP layer was available as otherwise sensors could be affected by the stored chemical agent. The main focus of this paper is to verify whether elastic waves excited by PZT sensors, which are installed on the outer GFRP layer, can penetrate the GFRP and PE interface and can be used to detect damage occurring in the inner PE layer. The efficiency of different signal characteristics used for structure evaluation is compared for various frequencies and durations of the excitation signal as well as feasibility of PZT sensor application for passive acquisition of acoustic emission signals is verified.

Role of IL-17A and IL-17RA in Prostate Cancer with Lymph Nodes Metastasis: Expression Patterns and Clinical Significance.

Prostate cancer (PCa) is the second most frequently diagnosed cancer among men. The use of IL-17A and its receptor IL-17RA as prognostic markers for PCa has shown promising results. We analyzed the clinical data of 77 patients with PCa after radical prostatectomy with lymphadenectomy and lymph node metastasis (LN+). We assessed the expression levels of IL-17A and IL-17RA in cancer cells in prostate and, for the first time, also in LN+. Prostate IL-17A expression positively correlated with BMI (p = 0.028). In LN+, the expression of IL-17A was positively correlated with the percentage of affected lymph nodes (p = 0.006) and EAU risk groups (p = 0.001). Additionally, in the group with high IL-17A expression in LN+, the extracapsular extension (ECE) of the prostate was significantly more frequent (p = 0.033). Also, significant correlations with the level of IL-17RA expression was found-expression was higher in prostate than in LN+ (p = 0.009); in LN+, expression positively correlated with the EAU risk group (p = 0.045), and in the group of high expression in LN+ ECE of lymph nodes was detected significantly more often (p = 0.009). Our findings support the potential role of IL-17A and IL-17RA as PCa markers; however, further studies are needed to determine their roles and potential clinical applications.

Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives.

Prostate cancer (PCa) is the second most frequently diagnosed cancer in men. Despite the significant progress in cancer diagnosis and treatment over the last few years, the approach to disease detection and therapy still does not include histopathological biomarkers. The dissemination of PCa is strictly related to the creation of a premetastatic niche, which can be detected by altered levels of specific biomarkers. To date, the risk factors for biochemical recurrence include lymph node status, prostate-specific antigen (PSA), PSA density (PSAD), body mass index (BMI), pathological Gleason score, seminal vesicle invasion, extraprostatic extension, and intraductal carcinoma. In the future, biomarkers might represent another prognostic factor, as discussed in many studies. In this review, we focus on histopathological biomarkers (particularly CD169 macrophages, neuropilin-1, cofilin-1, interleukin-17, signal transducer and activator of transcription protein 3 (STAT3), LIM domain kinase 1 (LIMK1), CD15, AMACR, prostate-specific membrane antigen (PSMA), Appl1, Sortilin, Syndecan-1, and p63) and their potential application in decision making regarding the prognosis and treatment of PCa patients. We refer to studies that found a correlation between the levels of biomarkers and tumor characteristics as well as clinical outcomes. We also hypothesize about the potential use of histopathological markers as a target for novel immunotherapeutic drugs or targeted radionuclide therapy, which may be used as adjuvant therapy in the future.

Durability and Additional Properties of Anodized Aluminum-Based Coatings with Different Wettability under Natural Conditions.

The study aimed to test the durability of coatings under natural conditions. The present study focused on the changes in wettability and additional properties of the coatings under natural conditions. The specimens were subjected to outdoor exposure and additionally immersed in the pond. Impregnating porous anodized aluminum is a popular production method for hydrophobic and superhydrophobic surfaces. However, prolonged exposure of such coatings to natural conditions causes leaching of the impregnate and, thus, the loss of hydrophobic properties. After the loss of hydrophobic properties, all kinds of impurities and fouling adhere better to the porous structure. Additionally, deterioration of anti-icing and anti-corrosion properties was observed. Finally, the self-cleaning, anti-fouling, anti-icing and anti-corrosion properties were comparable or even worse to those of the hydrophilic coating. In the case of superhydrophobic specimens, during outdoor exposure there was no loss of superhydrophobicity, self-cleaning and anti-corrosion properties. Still, despite this, the icing delay time dropped. During outdoor exposure, the structure, which initially had anti-icing properties, may degrade. Nevertheless, the hierarchical structure responsible for the superhydrophobic effect can still be preserved. The superhydrophobic coating initially had the best anti-fouling properties. However, the coating was also gradually losing its superhydrophobic properties during water immersion.

Assessment of Accuracy in Unmanned Aerial Vehicle (UAV) Pose Estimation with the REAL-Time Kinematic (RTK) Method on the Example of DJI Matrice 300 RTK.

The growing possibilities offered by unmanned aerial vehicles (UAV) in many areas of life, in particular in automatic data acquisition, spur the search for new methods to improve the accuracy and effectiveness of the acquired information. This study was undertaken on the assumption that modern navigation receivers equipped with real-time kinematic positioning software and integrated with UAVs can considerably improve the accuracy of photogrammetric measurements. The research hypothesis was verified during field measurements with the use of a popular Enterprise series drone. The problems associated with accurate UAV pose estimation were identified. The main aim of the study was to perform a qualitative assessment of the pose estimation accuracy of a UAV equipped with a GNSS RTK receiver. A test procedure comprising three field experiments was designed to achieve the above research goal: an analysis of the stability of absolute pose estimation when the UAV is hovering over a point, and analyses of UAV pose estimation during flight along a predefined trajectory and during continuous flight without waypoints. The tests were conducted in a designated research area. The results were verified based on direct tachometric measurements. The qualitative assessment was performed with the use of statistical methods. The study demonstrated that in a state of apparent stability, horizontal deviations of around 0.02 m occurred at low altitudes and increased with a rise in altitude. Mission type significantly influences pose estimation accuracy over waypoints. The results were used to verify the accuracy of the UAV's pose estimation and to identify factors that affect the pose estimation accuracy of an UAV equipped with a GNSS RTK receiver. The present findings provide valuable input for developing a new method to improve the accuracy of measurements performed with the use of UAVs.

Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+).

The purpose of this review is to present the current knowledge about the diagnostic and treatment options for bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). This review shows compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines; recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. The curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach, with a combination of neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND). The role of adjuvant chemotherapy (AC) remains uncertain; however, emerging evidence indicates comparable outcomes to NAC. Therefore, in cN+ patients who have not received NAC, AC should be implemented. The response to ChT is a crucial prognostic factor for cN+ patients. Recent studies demonstrated the growing importance of immunotherapy, especially in ChT-ineligible patients. Moreover, immunotherapy can be suitable as adjuvant therapy in selected cases. In cN+ patients, the extended template of PLND should be utilized, with the total resected node count being less important than the template. This review is intended to draw special attention to cN+ BCa patients, as the oncological outcomes are significantly worse for this group.

Boosting the Immune Response-Combining Local and Immune Therapy for Prostate Cancer Treatment.

Due to its slow progression and susceptibility to radical forms of treatment, low-grade PC is associated with high overall survival (OS). With the clinical progression of PC, the therapy is becoming more complex. The immunosuppressive tumor microenvironment (TME) makes PC a difficult target for most immunotherapeutics. Its general immune resistance is established by e.g., immune evasion through Treg cells, synthesis of immunosuppressive mediators, and the defective expression of surface neoantigens. The success of sipuleucel-T in clinical trials initiated several other clinical studies that specifically target the immune escape of tumors and eliminate the immunosuppressive properties of the TME. In the settings of PC treatment, this can be commonly achieved with radiation therapy (RT). In addition, focal therapies usually applied for localized PC, such as high-intensity focused ultrasound (HIFU) therapy, cryotherapy, photodynamic therapy (PDT), and irreversible electroporation (IRE) were shown to boost the anti-cancer response. Nevertheless, the present guidelines restrict their application to the context of a clinical trial or a prospective cohort study. This review explains how RT and focal therapies enhance the immune response. We also provide data supporting the combination of RT and focal treatments with immune therapies.

Alternatives for MRI in Prostate Cancer Diagnostics-Review of Current Ultrasound-Based Techniques.

The purpose of this review is to present the current role of ultrasound-based techniques in the diagnostic pathway of prostate cancer (PCa). With overdiagnosis and overtreatment of a clinically insignificant PCa over the past years, multiparametric magnetic resonance imaging (mpMRI) started to be recommended for every patient suspected of PCa before performing a biopsy. It enabled targeted sampling of the suspicious prostate regions, improving the accuracy of the traditional systematic biopsy. However, mpMRI is associated with high costs, relatively low availability, long and separate procedure, or exposure to the contrast agent. The novel ultrasound modalities, such as shear wave elastography (SWE), contrast-enhanced ultrasound (CEUS), or high frequency micro-ultrasound (MicroUS), may be capable of maintaining the performance of mpMRI without its limitations. Moreover, the real-time lesion visualization during biopsy would significantly simplify the diagnostic process. Another value of these new techniques is the ability to enhance the performance of mpMRI by creating the image fusion of multiple modalities. Such models might be further analyzed by artificial intelligence to mark the regions of interest for investigators and help to decide about the biopsy indications. The dynamic development and promising results of new ultrasound-based techniques should encourage researchers to thoroughly study their utilization in prostate imaging.

Supine blood pressure normalised by daytime series values is independently associated with ischaemic wake-up stroke.

PURPOSE: Wake-up stroke constitutes up to 1/4 of all ischaemic strokes; however, its pathomechanisms remain largely unknown. Although low nocturnal blood flow may be the underlying cause, little is known about blood pressure (BP) characteristic of wake-up stroke patients. The aim of our study was to look for differences in BP variables between wake-up stroke and known-onset stroke patients and to seek BP indices which could distinguish wake-up stroke patients from other stroke patients. MATERIALS AND METHODS: In the study, we included ischaemic stroke patients in whom office BP measurement and Ambulatory BP monitoring (ABPM) were recorded at day 7, after acute hypertensive response. The daytime period was defined as the interval from 6 a.m. to 10 p.m. From ABPM, we obtained parameters of BP variability. Additionally, we calculated the BP percentage differences defined as (supine office BP-average daytime BP)/average daytime BP for systolic, diastolic, and mean blood pressure. We calculated analogous indices for night-time. The univariate and multivariate relationships between BP variables and wake-up stroke were analysed. RESULTS: Among the recruited 120 patients (aged 61.6 ± 12.3; 88 [73%] males; the baseline National Institutes of Health stroke scale score 4 [3-8]), 36 (30%) had wake-up stroke. In a univariate analysis, the systolic and mean daytime and night-time BP differences were significantly lower in patients with wake-up stroke [(-1.92 (-11.55 to 3.95) vs 4.12 (-2.48 to 11.31), p = 0.006 and -6.20 (-12.32 to 7.42) vs 2.00 (-6.86 to 11.65), p = 0.029 for daytime, respectively; 0.00 (-9.79 to 11.82) vs 9.84 (0.00 to 18.25), p = 0.003 and 0.51 (-8.49 to 12.08) vs 7.82 (-2.47 to 20.39), p = 0.026, for night-time, respectively]. After adjustment for possible confounders, the systolic BP difference remained significantly associated with wake-up stroke (odds ratio = 0.96, 95% confidence interval = 0.92-1.00, p = 0.039). CONCLUSION: The subacute office-ambulatory BP difference including the dynamic (systolic BP), but not static BP component was independently associated with wake-up stroke.

Superhydrophobic Coating Based on Porous Aluminum Oxide Modified by Polydimethylsiloxane (PDMS).

The aim of this study was to obtain a superhydrophobic coating by modifying anodized aluminum using polydimethylsiloxane (PDMS). In order to obtain a superhydrophobic coating on an aluminum substrate, a multistage treatment was implemented. Specimens of aluminum were treated by abrasive blasting, anodization in sulfuric acid, impregnation by PDMS, rinsing in toluene to remove excess of PDMS, and curing. A rough surface with an additional low free energy layer on it resulted in a superhydrophobic effect. The coating obtained has an average contact angle of 159°. The specimens were tested in terms of durability in natural conditions. Additionally, anti-icing and anti-fouling properties were evaluated. The coating was compared with anodized aluminum obtained by a basic process.

A Method of Damage Detection Efficiency Enhancement of PZT Sensor Networks under Influence of Environmental and Operational Conditions.

Two performance parameters are particularly important for the assessment of structural health monitoring (SHM) systems, i.e., their damage detection capabilities and risk of false positive indications due to varying environmental and operational conditions (EOCs). A reduced ratio of false-positive indications can be of significant importance for particular applications, for example, in aerospace, where the costs of unplanned maintenance procedures can be very high. In such cases, the reduction of the false calls ratio can be critical for the possibility of the practical application of the system, apart from damage detection efficiency and system costs. Among various sensor technologies, PZT networks are proven to be one of the most universal approaches to SHM, and they were successfully applied in different scenarios. Moreover, many EOCs which may have an impact on the risk of false positive indications have been identified. Over the years, different approaches to the influence of EOCs compensation have been proposed. Compensation methods can be tailored to the particular way in which a given measurement condition, for example, ambient temperature, alters signals acquired by the PZT network or can be formulated to be also applied in the more general case. In the paper, a method for enhancement of damage detection efficiency under influence of EOCs of general nature is proposed. The particular measurement condition affecting signals acquired by PZT sensors neither needs to be measured, which could be hard in some cases, but also nor even have to be identified. The efficiency of the proposed compensation algorithms is verified based on the example of experimental results obtained under varying temperatures.

The Experimental Verification of Direct-Write Silver Conductive Grid and ARIMA Time Series Analysis for Crack Propagation.

The paper presents experimental verification of customized resistive crack propagation sensors as an alternative method for other common structural health monitoring (SHM) techniques. Most of these are sensitive to changes in the sensor network configuration and a baseline dataset must be collected for the analysis of the structure condition. Sensors investigated within the paper are manufactured by the direct-write process with electrically conductive, silver-microparticle-filled paint to prepare a tailored measuring grid on an epoxy or polyurethane coating as a driving/insulating layer. This method is designed to enhance the functionality and usability compared to commercially available crack gauges. By using paint with conductive metal particles, the shape of the sensor measuring grid can be more easily adapted to the structure, while, in the previous approach, only a few grid-fixed sensors are available. A fatigue test on the compact tension (CT) specimen is presented and discussed to evaluate the ability of the developed sensors to detect and monitor fatigue cracks. Additionally, the ARIMA time series algorithm is developed both for monitoring and predicting crack growth, based on the acquired data. The proposed sensors' verification reveal their good performance to detect and monitor fatigue fractures with a relatively low measurement error and ARIMA estimated crack length compared with the crack opening displacement (COD) gauge.

A comprehensive use of ultrasound examination in infertility workup.

Considering the growing availability of ultrasound diagnostic methods in gynecology, its role in the infertility setting is increasing.In this review, we present an up-to-date ultrasound based diagnostic scheme in infertility workup comprising the evaluation of ovarian anatomy and function, uterine exploration, as well as tubal patency. The possibility of performing the vast majority of infertility diagnostics by ultrasound in the ambulatory settings is not only attractive and beneficial to patients, but also to health care system.Thus, it is vital for gynecologists to implement modern non-invasive ultrasound modalities in their everyday practice.

Administration of CD4+CD25highCD127-FoxP3+ Regulatory T Cells for Relapsing-Remitting Multiple Sclerosis: A Phase 1 Study.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease in which autoimmune T conventional (Tconv) cells break the blood-brain barrier and destroy neurons of the central nervous system. It is hypothesized that CD4+CD25highCD127-FoxP3+ T regulatory (Treg) cells may inhibit this destruction through suppressive activity exerted on Tconv cells. METHODS: We present the results of a phase 1b/2a, open-label, two-arm clinical trial in 14 patients treated with autologous Treg cells for relapsing-remitting MS. The patients received either expanded ex vivo Treg cells intravenously (intravenous [IV] group, n = 11; dose 40 × 106 Treg cells/kg of body weight) or freshly isolated Treg cells intrathecally (intrathecal [IT] group, n = 3; dose 1.0 × 106 Treg cells). Importantly, patients were not treated with any other disease-modifying drugs for at least 6 months before the recruitment and during the follow-up. RESULTS: No severe adverse events were observed. Self-assessed quality of life (EuroQol-5 Dimensions [EQ-5D] form) did not change and did not differ significantly between the groups. A total of 12 relapses were noted in five intravenously treated patients, who had from one to three attacks per year. Three out of ten participants who completed the trial in the IV group deteriorated more than 1 point on the Expanded Disability Status Scale (EDSS) during the follow-up. At the same time, no patients in the IT group experienced a relapse or such a deterioration in the EDSS. No significant differences were found in the Multiple Sclerosis Functional Composite (MSFC) scale in both the IV and IT groups. Magnetic resonance imaging (MRI) scans revealed a significantly lower change in the T2 lesion volume in the IT group compared to the IV group. The increase in the number of new T2 lesions during the follow-up was significant for the IV group only. There were no significant changes in the level of Treg cells or Tconv cells in the peripheral blood throughout the follow-up or between the groups. Interestingly, Treg cells in all patients consisted of two different phenotypes: peripheral Treg cells Helios(-) (≈ 20%) and thymic Treg cells Helios(+) (≈ 80%). The analysis of the cytokine pattern revealed higher levels of transforming growth factor-α and proinflammatory factors MCP3, CXCL8, and IL-1RA in the IT group compared with the IV group. CONCLUSIONS: No serious adverse events were reported in the 14 patients with MS treated with Treg cells in this study. The results suggest that IT administration is more promising than IV administration. Because of the low number of patients recruited, the statistical results may be underpowered and further studies are necessary to reach conclusions on efficacy and safety. TRIAL REGISTRATION: EudraCT: 2014-004320-22; registered 18 November 2014.

Blood Pressure Management in Acute Ischemic Stroke.

PURPOSE OF REVIEW: Abrupt blood pressure (BP) rise is the most common clinical symptom of acute ischemic stroke (AIS). However, BP alterations during AIS reflect many diverse mechanisms, both stroke-related and nonspecific epiphenomena, which change over time and across patients. While extremes of BP as well as high BP variability have been related with worse outcomes in observational studies, optimal BP management after AIS remains challenging. RECENT FINDINGS: This review discusses the complexity of the factors linking BP changes to the clinical outcomes of patients with AIS, depending on the treatment strategy and local vessel status and, in particular, the degree of reperfusion achieved. The evidence for possible additional clinical markers, including the presence of arterial hypertension, and comorbid organ dysfunction in individuals with AIS, as informative and helpful factors in therapeutic decision-making concerning BP will be reviewed, as well as recent data on neurovascular monitoring targeting person-specific local cerebral perfusion and metabolic demand, instead of the global traditional parameters (BP among others) alone. The individualization of BP management protocols based on a complex evaluation of the homeostatic response to focal cerebral ischemia, including but not limited to BP changes, may be a valuable novel goal proposed in AIS, but further trials are warranted.