Effect of a Perioperative Nutritional Supplementation with Oral Impact® in Patients undergoing Hepatic Surgery for Liver Cancer: A Prospective,Placebo-Controlled,Randomized, Double-Blind Study

Perioperative nutrition with supplements containing l-arginine, ω3-polyunsaturated fatty acids, and nucleotides could boost liver function recovery, immune response, and resistance to infection after hepatic resection. We conducted a placebo-controlled, randomized, double-blind study to assess the effect of a perioperative nutritional supplementation with Oral Impact® in patients undergoing hepatic surgery for liver cancer. Treatment was given three times daily for 7 days before and 3 days after surgery. Primary outcome was factor V, 3 days after surgery. Thirty-five patients (placebo: 17; Oral Impact: 18) were included. Five patients (placebo: three; Oral Impact: two) were not operated and five (placebo: two; Oral Impact: three) did not undergo hepatic resection. Factor V (mean ± SD) was 70 ± 27% and 79 ± 25% (P = 0.409) 3 days after surgery and 90 ± 30% and 106 ± 16% (P = 0.066) 5 days after surgery, in placebo and Oral Impact groups, respectively. There were no significant differences between groups on other outcomes assessing liver function recovery (bile production, γ-glutamyl transferase, α-fetoprotein), immune response (CD3, CD4, CD8 cells, CD4/CD8 ratio, natural killer cells, B lymphocytes), number of infections, and tolerance. A 10-day perioperative nutritional supplementation with Oral Impact does not improve hepatic function, immune response, and resistance to infection in patients undergoing hepatic surgery for liver cancer.     

Cytoskeleton as an emerging target of anthrax toxins

Bacillus anthracis, the agent of anthrax, has gained virulence through its exotoxins produced by vegetative bacilli and is composed of three components forming lethal toxin (LT) and edema toxin (ET). So far, little is known about the effects of these toxins on the eukaryotic cytoskeleton. Here, we provide an overview on the general effects of toxin upon the cytoskeleton architecture. Thus, we shall discuss how anthrax toxins interact with their receptors and may disrupt the interface between extracellular matrix and the cytoskeleton. We then analyze what toxin molecular effects on cytoskeleton have been described, before discussing how the cytoskeleton may help the pathogen to corrupt general cell processes such as phagocytosis or vascular integrity.     

Human oligodendrocytes are susceptible to cytolysis by major histocompatibility complex class I-restricted lymphocytes

The majority of human oligodendrocytes in enriched glial cell cultures expresses class I major histocompatibility complex (MHC) antigens. We used a 51Cr release assay to study the susceptibility of oligodendrocyte-enriched glial cells to MHC-restricted and non-restricted immune-mediated cytolysis. Mitogen-activated mononuclear cells induced significant lysis in a lectin-dependent cytotoxicity assay. Mononuclear cells allo-activated in a one-way mixed lymphocyte culture with E- cells from the glial cell donor induced a significantly higher degree of oligodendrocyte cytolysis than mononuclear cells activated with E- cells bearing MHC-class I antigens discordant with the glia. Cytolysis by alloactivated unfractionated lymphocytes and by purified CD8+ lymphocytes was reduced by an anti-class I antibody (W6/32). Our findings suggest that human oligodendrocytes can be susceptible targets for MHC class I-restricted lysis.     

Evaluation of consumer satisfaction using the tetra-class model

BACKGROUND: A number of studies have shown the importance of consumers' satisfaction toward pharmacy services. The measurement of patient satisfaction through different elements of services provided is challenging within the context of a dynamic economic environment. Patient satisfaction is the result of long-term established habits and expectations to the pharmacy as an institution. Few studies to date have attempted to discern whether these changes have led to increased patient satisfaction and loyalty, particularly within developing nations. OBJECTIVES: The objective of this study was to evaluate the elements of the services provided in Bulgarian pharmacies and their contribution to consumer satisfaction using a tetra-class model. Three main hypotheses were tested in pharmacies to validate the model in the case of complex services. Additionally, the contribution of the different service elements to the clients' satisfaction was studied. METHODS: The analysis was based on a survey of customers in central and district pharmacies in Sofia, Bulgaria. The data were analyzed through a correspondence analysis which was applied to the results of the 752 distributed questionnaires. RESULTS: It was observed that different dimensions of the pharmacies contribute uniquely to customer satisfaction, with consumer gender contributing greatly toward satisfaction, with type/location of pharmacy, consumer age, and educational degree also playing a part. The duration of time over which the consumers have been clients at a given pharmacy influences the subsequent service categorization. CONCLUSIONS: This research demonstrated that the tetra-class model is suitable for application in the pharmaceutical sector. The model results could be beneficial for both researchers and pharmacy managers.     

Inflammation and aging: Can endocannabinoids help?

Aging often leads to cognitive decline due to neurodegenerative process in the brain. As people live longer, there exists a growing concern linked to long-term, slowly debilitating diseases, such as Alzheimer's disease for which a cure has not yet been found. Recently, the role of neuroinflammation has attracted attention due to its slow onset, chronic nature and its possible role in the development of many different neurodegenerative diseases. In the future, treatment of chronic neuroinflammation may help counteract aspects of neurodegenerative disease. Our recent studies have focused upon the endocannabinoid system for its unique effects on the expression of neuroinflammation. The basis for the manipulation of the endocannabinoid system in the brain in combination with existing treatments for Alzheimer's disease will be discussed in this review.     

Use of spiral computed tomography contrast angiography and ultrasonography to exclude the diagnosis of pulmonary embolism in the emergency department

Spiral computed tomography (CT) contrast angiography is a promising imaging modality for the diagnosis of pulmonary embolism but the negative predictive value of this test remains controversial. We performed a multi-center prospective cohort study to determine the safety of relying on a negative spiral CT contrast angiography scan to exclude pulmonary embolism. Patients presenting to the Emergency Departments of three tertiary care institutions with clinically suspected pulmonary embolism were potentially eligible for the study. Patients underwent a clinical evaluation to categorize pretest probability into low, moderate, and high categories, and had D-dimer testing performed. Patients at low pretest probability with normal D-dimer were considered to have pulmonary embolism excluded. The remaining patients underwent spiral CT contrast angiography scan of the pulmonary arterial circulation and bilateral venous ultrasound of the proximal leg veins. Patients who were confirmed to have pulmonary embolism or deep vein thrombosis were treated with anticoagulant therapy. Patients in whom the diagnosis of pulmonary embolism was excluded did not receive anticoagulant therapy and were followed for a 3-month period for the development of venous thromboembolic complications. Eight hundred fifty-eight (858) patients were enrolled in this study. Three-hundred sixty-nine (369) patients had low pretest probability and negative D-dimer results and no further diagnostic tests were performed. None of these patients subsequently developed venous thromboembolic complications (0%, 95% confidence interval [CI] 0% to 1.0%). The remaining 489 were referred for spiral CT contrast angiography scan and ultrasound. Sixty-seven patients were confirmed to have pulmonary embolism and an additional 15 patients with negative CT scans had proximal deep vein thrombosis (DVT) on ultrasound for a total prevalence of venous thromboembolism of 82/489 (16.8%). Two of 409 patients who had pulmonary embolism excluded in the initial evaluation phase developed proximal venous thromboembolism (0.5%; 95% CI 0% to 1.8%) in the 3-month follow-up period. These findings suggest that the combination of a negative spiral CT contrast angiography scan and normal venous ultrasound imaging safely excludes the diagnosis of pulmonary embolism in the Emergency Department setting.     

Histopathological growth patterns of resected non-colorectal,non-neuroendocrine liver metastases: a retrospective multicenter study

Background

Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.

Methods

A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan–Meier and multivariable Cox regression analysis.

Results

In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36–78%) versus 40% (30–53%), and 33% (19–61%) versus 15% (9–27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p?=?0.031 & p?=?0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25–0.86]) and RFS (0.38 [0.21–0.69]).

Conclusions

This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.

     

Usefulness of B-type natriuretic peptide in elderly patients with acute dyspnea

Objective Differentiating cardiogenic pulmonary edema (CPE) from respiratory causes of dyspnea is particularly difficult in elderly patients. The aim of our study was to evaluate B-type natriuretic peptide (BNP) in patients older than 65 years presenting with acute dyspnea.Design Prospective study.Setting Medical emergency department of a 2000-bed urban teaching hospital.Patients Patients aged over 65 years presenting with acute dyspnea and a respiratory rate more than 25/min or a PaO₂ below 70 mmHg, SpO₂ less than 92%, PaCO₂ higher than 45 mmHg with pH less than 7.35, were included. BNP levels, measured blind at admission were compared with the final diagnosis (CPE or no CPE) as defined by experts.Intervention None.Measurements and results Three hundred eight patients (mean age of 80 years) were enrolled in the study. The median BNP was 575 pg/ml [95% confidence interval (CI): 410–898] in the CPE group (n=141) versus 75 pg/ml (95% CI: 59–98) in the no CPE group (n=167) (p<0.001). The best threshold value of BNP was 250 pg/ml, with a sensitivity and specificity for CPE of 0.78 (95% CI: 0.71–0.84) and 0.90 (95% CI: 0.84–0.93), respectively. The area under the ROC curve was 0.874±0.081 (p<0.001). The accuracy of BNP-assisted diagnosis was higher than that of the emergency physician (0.84 versus 0.77, p<0.05).Conclusion Analysis of BNP is useful in elderly patients with acute dyspnea, but the threshold value is higher than that previously determined.Presented, in part, at the 30^th annual congress of the Société de Réanimation de Langue Française, Paris, January 2002 (abstract no. SP 94).     

Combined measurements of N-terminal pro-brain natriuretic peptide and cardiac troponins in potential organ donors

Objective Brain death may induce cardiac dysfunction. In potential organ donors measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP) and circulating cardiac troponins T and I (cTnT and cTnI), alone or in combination, are performed to investigate the accuracy of these biomarkers for early diagnosis of left ventricular systolic dysfunction. Design and setting Prospective study in a multidisciplinary intensive care unit of an university hospital. Patients 63 brain-dead patients scheduled for multiple organ harvesting. Measurements and results We measured NT-proBNP, cTnT, and cTnI and determined fractional area change (FAC) using transesophageal echocardiography. Forty-five patients had normal FAC, 9 a moderate decrease in FAC (30–50), and 9 a severe decrease in FAC (≤ 30%). NT-proBNP and cTnT concentrations were significantly higher in patients with a severe decrease in FAC than in those with a moderate decrease. Combining measurements of these two biomarkers, the sensitivity of the test to predict severe decrease in FAC increased significantly to reach 1.00 compared with the sensitivities of individual measurements. The ROC curve area of combined measurements of NT-proBNP and cTnT was significantly higher than single measurements: 0.87 vs. 0.82 for NT-proBNP, 0.78 for cTnT, and 0.72 for cTnI. Conclusions In potential organ donors the combined measurement of NT-proBNP and cTnT concentrations is more accurate than individual measurement of NT-proBNP, cTnT, and cTnI in the early diagnosis of severe left ventricular systolic dysfunction. These findings may lead to improve the quality of cardiac care of the potential organ donors.