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Hepatocellular carcinoma (HCC) still lacks valuable diagnostic and prognostic tools. This study aimed to investigate the potential diagnostic and prognostic value of baseline interleukin (IL)-10, fatty acid-binding protein 2 (FABP2) and lipopolysaccharide (LPS) levels in patients with HCC. Serum levels of IL-10, FABP2 and LPS in 47 newly diagnosed HCC patients and 50 healthy individuals were estimated and compared. The best cut-off points for baseline IL-10, FABP2 and LPS levels predicting overall survival (OS) were evaluated. Both levels of FABP2 and IL-10 were significantly higher in HCC patients vs. control group (median 2095 vs. 1772 pg/mL, p = 0.026; 9.94 vs. 4.89 pg/mL, p < 0.001) and may serve as potential biomarkers in complex HCC diagnostic tools. The cut-off value of 2479 pg/mL for FABP2 was determined to have the highest sensitivity (66.7%) and specificity (55.6%) to distinguish patients with a median OS longer than 17 months. However, the median OS of patients with high and low levels of FABP2 were not significantly different (p = 0.896). The prognostic value of LPS as well as FABP2 and IL-10 for HCC patients appears to be limited. [ABSTRACT FROM AUTHOR]

Author(s): Andrius Pranskunas [sup.1], Matty Koopmans [sup.2], Peter M. Koetsier [sup.2], Vidas Pilvinis [sup.1], E. Christiaan Boerma [sup.2] [sup.3] Author Affiliations: (1) grid.45083.3a, 0000000404326841, Department of Intensive Care Medicine, Hospital [...], Purpose The aim of this study is to assess the incidence of sublingual microcirculatory flow alterations, according to a predefined arbitrary cutoff value, in patients with 'clinical signs of impaired organ perfusion'. Secondary endpoints were the changes in microvascular flow index (MFI), 'clinical signs of impaired organ perfusion', and stroke volume (SV) after fluid administration, and the differences between groups. Methods Prospective, single-center, observational study in a 22-bed mixed intensive care unit (ICU). Patients [greater than or equal to]18 years with invasive hemodynamic monitoring and 'clinical signs of impaired organ perfusion' as the principal reason for fluid administration were included. Before and after fluid challenge, systemic hemodynamics and direct in vivo observation of the sublingual microcirculation with sidestream dark-field imaging were obtained. Microvascular flow index (MFI) Results N = 50. At baseline, MFI Conclusions These data add to the understanding that noninvasive assessment of microvascular blood flow may help to identify patients eligible for fluid therapy, and to evaluate its effect.

Abstract Background Microcirculatory alterations play a pivotal role in sepsis and persist despite correction of systemic hemodynamic parameters. Therefore it seems tempting to test specific pro-microcirculatory strategies, including vasodilators, to attenuate impaired organ perfusion. As opposed to nitric oxide donors, magnesium has both endothelium-dependent and non-endothelium-dependent vasodilatory pathways. Methods In a single-center open label study we evaluated the effects of magnesium sulphate (MgS) infusion on the sublingual microcirculation perfusion in fluid resuscitated patients with severe sepsis and septic shock within the first 48 hours after ICU admission. Directly prior to and after 1 hour of magnesium sulphate (MgS) infusion (2 gram) systemic hemodynamic variables, sublingual SDF images and standard laboratory tests, were obtained. Results Fourteen patients (12 septic shock, 2 severe sepsis) with a median APACHE II score of 20 were enrolled. No significant difference of the systemic hemodynamic variables was found between baseline and after MgS infusion. We did not observe any significant difference pre and post MgS infusion in the primary endpoint microvascular flow index (MFI) of small vessels: 2.25(1.98-2.69) vs. 2.33(1.96-2.62), p = 0.65. Other variables of microcirculatory perfusion were also unaltered. In the overall unchanged microvascular perfusion there was a non-significant trend to an inverse linear relationship between the changes of MFI and its baseline value (y = -0.7260 × + 1.629, r2 = 0.270, p = 0.057). The correlation between baseline Mg concentrations and the change in MFI pre- and post MgS infusion was non-significant (rs = -0.165, p = 0.67). Conclusions In the setting of severe sepsis and septic shock sublingual microcirculatory alterations were observed despite fulfillment of sepsis resuscitation guidelines. After infusion of a limited and fixed dose of MgS, microcirculatory perfusion did not improve over time. Trial registration ClinicalTrials.gov NTC01332734.

Background: Hemodialysis (HD) with ultrafiltration (UF) in chronic renal replacement therapy is associated with hemodynamic instability, morbidity and mortality. Sublingual Sidestream Dark Field (SDF) imaging during HD revealed reductions in microcirculatory blood flow (MFI). This study aims to determine underlying mechanisms.Methods: The study was performed in the Medical Centre Leeuwarden and the Lithuanian University of Health Sciences. Patients underwent 4-h HD session with linear UF. Nine patients were subject to combinations of HD and UF: 4 h of HD followed by 1 h isolated UF and 4 h HD with blood-volume-monitoring based UF. Primary endpoint: difference in MFI before and after intervention. During all sessions monitoring included blood pressure, heartrate and SDF-imaging.Trial Registration Number: NCT01396980.Results: Baseline characteristics were not different between the two centres as within the HD/UF modalities. MFI was not different before and after HD with UF. Total UF did not differ between modalities. Median MFI decreased significantly during isolated UF [2.8 (2.5-2.9) to 2.5 (2.2-2.8), p = 0.03]. Baseline MFI of each UF session was correlated with MFI after the intervention (r s = 0.52, p = 0.006).Conclusion: During HD with UF or isolated HD we observed no changes in MFI. This indicates that non-flow mediated mechanisms are of unimportance. During isolated UF we observed a reduction in MFI in conjunction with a negative intravascular fluid balance. The correlation between MFI before and after intervention suggests that volume status at baseline is a factor in microvascular alterations. In conclusion we observed a significant decrease of sublingual MFI, related to UF rate during chronic renal replacement therapy. [ABSTRACT FROM AUTHOR]

Background: The conjunctival microcirculation has potential as a window to cerebral perfusion due to related blood supply, close anatomical proximity and easy accessibility for microcirculatory imaging technique, such as sidestream dark field (SDF) imaging. Our study aims to evaluate conjunctival and sublingual microcirculation in brain dead patients and to compare it with healthy volunteers in two diametrically opposed conditions: full stop versus normal arterial blood supply to the brain.Methods: In a prospective observational study we analyzed conjunctival and sublingual microcirculation using SDF imaging in brain dead patients after reaching systemic hemodynamic targets to optimize perfusion of donor organs, and in healthy volunteers. All brain death diagnoses were confirmed by cerebral angiography. Microcirculatory images were obtained and analyzed using standardized published recommendations. Study registered at ClinicalTrials.gov, number NCT02483273.Results: Eleven brain dead patients and eleven apparently healthy controls were enrolled in the study. Microvascular flow index (MFI) of small vessels was significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (2.7 [2.4-2.9] vs. 3.0 [2.9-3.0], p = 0.01) and in sublingual mucosa (2.8 [2.6-2.9] vs. 3.0 [2.9-3.0], p = 0.02). Total vessel density (TVD) and perfused vessel density (PVD) of small vessels were significantly lower in brain dead patients in comparison to healthy controls in ocular conjunctiva (10.2 [6.6-14.8] vs. 18.0 [18.0-25.4] mm/mm(2), p = 0.001 and 5.0 [3.5-7.3] vs. 10.9 [10.9-13.5] 1/mm, p = 0.001), but not in sublingual mucosa.Conclusion: In comparison to healthy controls brain dead patients had a significant reduction in conjunctival microvascular blood flow and density. However, the presence of conjunctival flow in case general cerebral flow is completely absent makes it impossible to use the conjunctival microcirculation as a substitute for brain flow, and further research should focus on the link between the ocular microcirculation, intracranial pressure and alternative ocular circulation. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to evaluate and compare the microcirculatory perfusion during experimental sepsis in different potentially available parts of the body, such as sublingual mucosa, conjunctiva of the eye, and mucosa of jejunum and rectum. Methods: Pigs were randomly assigned to sepsis (n = 9) and sham (n = 4) groups. The sepsis group received a fixed dose of live Escherichia coli infusion over a 1-hour period (1.8 × 109/kg colony-forming units). Animals were observed 5 hours after the start of E. coli infusion. In addition to systemic hemodynamic assessment, we performed conjunctival, sublingual, jejunal, and rectal evaluation of microcirculation by using Sidestream Dark Field (SDF) videomicroscopy at the same time points: at baseline, and at 3 and 5 hours after the start of live E. coli infusion. Assessment of microcirculatory parameters of convective oxygen transport (microvascular flow index (MFI) and proportion of perfused vessels (PPV)), and diffusion distance (perfused vessel density (PVD) and total vessel density (TVD)) was done by using a semiquantitative method. Results: Infusion of E. coli resulted in a hypodynamic state of sepsis associated with low cardiac output and increased systemic vascular resistance despite fluid administration. Significant decreases in MFI and PPV of small vessels were observed in sublingual, conjunctival, jejunal, and rectal locations 3 and 5 hours after the start of E. coli infusion in comparison with baseline variables. Correlation between sublingual and conjunctival (r = 0.80; P = 0.036), sublingual and jejunal (r = 0.80; P = 0.044), and sublingual and rectal (r = 0.79; P = 0.03) MFI was observed 3 hours after onset of sepsis. However, this strong correlation between the sublingual and other regions disappeared 5 hours after the start of E. coli infusion. Overall, the sublingual mucosa exhibited the most-pronounced alterations of microcirculatory flow in comparison with conjunctival, jejunal, and rectal microvasculature (P < 0.05). Conclusions: In this pig model, a time-dependent correlation exists between sublingual and microvascular beds during the course of a hypodynamic state of sepsis. [ABSTRACT FROM AUTHOR]

Background: Microcirculatory alterations play a pivotal role in sepsis and persist despite correction of systemic hemodynamic parameters. Therefore it seems tempting to test specific pro-microcirculatory strategies, including vasodilators, to attenuate impaired organ perfusion. As opposed to nitric oxide donors, magnesium has both endothelium-dependent and non-endothelium-dependent vasodilatory pathways. Methods: In a single-center open label study we evaluated the effects of magnesium sulphate (MgS) infusion on the sublingual microcirculation perfusion in fluid resuscitated patients with severe sepsis and septic shock within the first 48 hours after ICU admission. Directly prior to and after 1 hour of magnesium sulphate (MgS) infusion (2 gram) systemic hemodynamic variables, sublingual SDF images and standard laboratory tests, were obtained. Results: Fourteen patients (12 septic shock, 2 severe sepsis) with a median APACHE II score of 20 were enrolled. No significant difference of the systemic hemodynamic variables was found between baseline and after MgS infusion. We did not observe any significant difference pre and post MgS infusion in the primary endpoint microvascular flow index (MFI) of small vessels: 2.25(1.98-2.69) vs. 2.33(1.96-2.62), p = 0.65. Other variables of microcirculatory perfusion were also unaltered. In the overall unchanged microvascular perfusion there was a nonsignificant trend to an inverse linear relationship between the changes of MFI and its baseline value (y = -0.7260 x + 1.629, r² = 0.270, p = 0.057). The correlation between baseline Mg concentrations and the change in MFI preand post MgS infusion was non-significant (rs = -0.165, p = 0.67). Conclusions: In the setting of severe sepsis and septic shock sublingual microcirculatory alterations were observed despite fulfillment of sepsis resuscitation guidelines. After infusion of a limited and fixed dose of MgS, microcirculatory perfusion did not improve over time. [ABSTRACT FROM AUTHOR]

The glycocalyx is an endothelial surface layer that is essential for maintaining microvascular homeostasis. Impaired integrity of the endothelial glycocalyx may be directly related to the development of microvascular dysfunction. To explore this hypothesis, we conducted a prospective observational study on adult patients diagnosed with sepsis. The study aimed to evaluate the degree of damage to the glycocalyx and to identify correlations between microcirculatory parameters and glycocalyx thickness based on capillary diameter. Sublingual microcirculation was examined using a handheld Cytocam-incident dark field video microscope. A sidestream dark field video microscope attached to a GlycoCheck monitor was used to determine the perfused boundary regions (PBRs) of sublingual blood vessels grouped by diameter (5–9 μm, 10–19 μm, and 20–25 μm). We identified significant damage to the glycocalyx in sublingual blood vessels of all the aforementioned diameters in septic patients compared to healthy age-matched controls. Furthermore, we found that the PBRs of the smallest capillaries (diameter class 5–9µm) correlated moderately and inversely with both total and perfused blood vessel densities. Collectively, our data suggest that there may be a functional relationship between damage to the endothelial glycocalyx of the smallest capillaries and alterations in the microcirculation observed in response to sepsis. [ABSTRACT FROM AUTHOR]

Unlabelled: Recently improved microcirculatory imaging techniques, such as orthogonal polarization spectral (OPS) and its technical successor sidestream dark field (SDF) imaging, in handheld devices have allowed a direct observation of the microcirculation at the bedside. Usually a cut-off of 20 µm in diameter is used to differentiate small vessels (mainly capillaries) from large vessels (mainly venules) during this technique. We hypothesized that it was possible to measure the small vessels with a considerably smaller inner diameter., Material and Methods: Images of the sublingual, conjunctival, jejunal, and rectal mucosa microcirculation were obtained with SDF videomicroscopy (Microscan®, Microvision Medical, Amsterdam, the Netherlands). Using the validated software, the length and diameter of microvessels were manually traced with a computer-generated line. All vessels were divided into the groups according to the inner diameter., Results: A total of 156 SDF images of the sublingual, ocular conjunctival, jejunal, and rectal mucosa were taken in 13 pigs. The length of microscopic vessels progressively increased with a decrease in the vessel diameter less than 8 mm in all the lodges, such as sublingual (80.6% of total vessel length), ocular conjunctival (76.5% of total vessel length), jejunal (99.8% of total vessel length), and rectal (97.8% of total vessel length), due to capillary network formation. There was no significant difference in the distribution of vessels from 0 to 10 µm in diameter comparing sublingual and eye conjunctival as well as jejunal and rectal mucosa., Conclusion: In pigs, small-diameter microscopic vessels (<10 µm) dominated in all the studied lodges (sublingual, ocular conjunctival, jejunal, and rectal mucosa), and this is evidence to establish a new cut-off for capillaries in microcirculatory analysis of SDF imaging in experimental and clinical studies.

Unlabelled: The objective of this study was to identify case characteristics and clinical course of the disease in patients hospitalized with 2009 pandemic influenza A (H1N1) infection during the first wave of the pandemic and to identify risk factors associated with the complicated course of illness., Material and Methods: A retrospective study of adult cases of the laboratory-confirmed 2009 pandemic influenza A (H1N1) virus admitted to three hospitals in Kaunas between November 1, 2009, and March 15, 2010, was carried out. The main outcome measures were clinical characteristics, risk factors for complicated disease, treatment, and clinical course of the disease., Results: The study enrolled 121 of the 125 patients hospitalized due to 2009 pandemic influenza A (H1N1) virus infection. The median age was 31 years (range, 18-83); 5% of the patients were aged more than 65 years. Pregnant and postpartum women comprised 26% of all hospitalized cases. Nearly half (49.5%) of those who underwent chest radiography had findings consistent with pneumonia, which was bilateral in one-third of cases. The risk to have pandemic influenza complicated by pneumonia increased significantly with one-day delay from symptom onset to antiviral treatment (OR, 2.241; 95% CI, 1.354-3.710). More than half (57%) of the patients received antiviral treatment. In 45% of the treated patients, antiviral drugs were administered within 48 hours from symptom onset. Intensive care was required in 7.4% of the cases. The overall mortality was 5% (6/121). The median age of the patients who died was 43.5 years (range, 23-62); 4 patients had been previously healthy, 1 patient suffered from chronic lympholeukemia, and 1 patient was a pregnant woman., Conclusion: The 2009 pandemic influenza A (H1N1) caused considerable morbidity in a significant proportion of hospitalized adults. The main risk factor associated with the complicated course of illness was delayed antiviral treatment.

Despite advances in cardiac arrest care, the overall survival to hospital discharge remains poor. The objective of this paper was to review the innovations in cardiopulmonary resuscitation that could influence survival or change our understanding about cardiopulmonary resuscitation. We have performed a search in the MEDLINE and the Cochrane databases for randomized controlled trials, meta-analyses, expert reviews from December 2005 to March 2010 using the terms cardiac arrest, basic life support, and advanced life support. The lack of randomized trials during the last 5 years remains the main problem for crucial decisions in cardiopulmonary resuscitation. Current trends in cardiopulmonary resuscitation are toward minimizing the interruptions of chest compressions and improving the quality of cardiopulmonary resuscitation. In addition, attention should be paid to all the parts of chain of survival, which remains essential in improving survival rates.

Objective: To determine the influence of electrocardiographically documented cardiac rhythm during sudden cardiac arrest on successful resuscitation among out-of-hospital deaths in Kaunas city., Material and Methods: An observational prospective study was conducted between 1 January, 2005, and 30 December, 2005, in Kaunas city with a population of 360,627 inhabitants. In this period, all cases of cardiac arrest were analyzed according to the guidelines of the Utstein consensus conference. Cardiac arrest (both of cardiac and noncardiac etiology) was confirmed in 72 patients during one year. Effective cardiopulmonary resuscitation was performed in 18 patients., Results: The total number of deaths from all causes in Kaunas during 1-year study period was 6691. Sixty-two patients due to sudden death of cardiac etiology were resuscitated by emergency medical services personnel. Return of spontaneous circulation was achieved in 11 patients. Ventricular fibrillation was observed in 33 (53.2%) patients. Asystole was present in 11 (17.7%) and other rhythms in 18 (29.1%) cases. Patients with ventricular fibrillation as an initial rhythm were more likely to be successfully resuscitated than patients with asystole., Conclusions: Ventricular fibrillation was the most common electrocardiographically documented cardiac rhythm registered during cardiac arrest in out-of-hospital settings. Ventricular fibrillation as a mechanism of cardiac arrest was associated with major cases of successful resuscitation.

Objective: To show differences in the changes of electrocardiographic and echocardiographic data after early and late mechanical recanalization of infarct related artery with and without stent implantation and to assess the value of QRS score in the follow-up period., Material and Methods: A total of 248 consecutive patients were divided into these groups: early angioplasty (24 hours) angioplasty without stents (n=114) or with stents (n=14). The changes in QRS score and echocardiographic left ventricular ejection fraction during the hospital and 3-month follow-up periods were compared between the groups., Results: QRS score did not increase in a hospital in early or late angioplasty with stents groups, while in the groups without stents especially of early angioplasty increased (2.6+/-2.5 vs. 3.6+/-2.4, P=0.001). Left ventricular ejection fraction increased after 3 months only in early angioplasty groups especially with stents (30.0+/-3.5 vs. 38.4+/-5.2, P=0.008), but there were no significant differences between the QRS score at discharge and after 3 months (5.4+/-4.3 vs. 5.0+/-1.9)., Conclusions: Myocardial injury did not increase in a hospital in the cases of early or late angioplasty with stents, while in the cases without stents increased. Left ventricular ejection fraction increased after 3 months only in the cases of early angioplasty especially with the stent implantation, but the QRS score showed no differences, so the QRS score may be not predictive of improvement in ejection fraction at follow-up.