A New Lung Ultrasound Protocol Able to Predict Worsening in Patients Affected by Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can generate severe pneumonia associated with high mortality. A bedside lung ultrasound (LUS) examination has been shown to have a potential role in this setting. The purpose of this study was to evaluate the potential prognostic value of a new LUS protocol (evaluation of 14 anatomic landmarks, with graded scores of 0-3) in patients with SARS-CoV-2 pneumonia and the association of LUS patterns with clinical or laboratory findings. METHODS: A cohort of 52 consecutive patients with laboratory-confirmed SARS-CoV-2 underwent LUS examinations on admission in an internal medicine ward and before their discharge. A total LUS score as the sum of the scores at each explored area was computed. We investigated the association between the LUS score and clinical worsening, defined as a combination of high-flow oxygen support, intensive care unit admission, or 30-day mortality as the primary end point. RESULTS: Twenty (39%) patients showed a worse outcome during the observation period; the mean LUS scores ± SDs were 20.4 ± 8.5 and 29.2 ± 7.3 in patients without and with worsening, respectively (P < .001). In a multivariable analysis, adjusted for comorbidities (>2), age (>65 years), sex (male), and body mass index (≥25 kg/m2 ), the association between the LUS score and worsening (odds ratio, 1.17; 95% confidence interval, 1.05 to 1.29; P = .003) was confirmed, with good discrimination of the model (area under the receiver operating characteristic curve, 0.82). A median LUS score higher than 24 was associated with an almost 6-fold increase in the odds of worsening (odds ratio, 5.67; 95% confidence interval, 1.29 to 24.8; P = .021). CONCLUSIONS: Lung ultrasound can represent an effective tool for monitoring and stratifying the prognosis of patients with SARS-CoV-2 pulmonary involvement.

Acetonic Extract from the Feijoa sellowiana Berg. Fruit Exerts Antioxidant Properties and Modulates Disaccharidases Activities in Human Intestinal Epithelial Cells.

Feijoa sellowiana fruit has been shown to possess various biological activities, such as anti-bacterial and anti-cancer properties, in a variety of cellular models, but its activity on human intestinal epithelial cells has never been tested. The purpose of this study was to investigate the effects of the acetonic extract of F. sellowiana fruits on the viability, membrane peroxidation, disaccharidases activities and proliferation of in vitro models of human intestinal epithelial cells. To obtain this goal, Caco-2 and HT-29 cells were exposed to the acetonic extract for 24 h. Cell proliferation, viability, lactase and sucrase-isomaltase activity and H2 O2 -induced membrane lipid peroxidation were tested. We found that, compared to control conditions, the acetonic extract significantly increased lactase and sucrase-isomaltase activity in Caco-2, but not HT-29, cells, decreased proliferation, had no effects on viability and restored lipid peroxidation in both cell models. This study suggests that the acetonic extract improves lactase and sucrase-isomaltase activity, inhibits cell proliferation, have no cytotoxic effects and prevent lipid peroxidation of intestinal epithelial cells. These effects may be exploited in case of disaccharidases deficit and also as an adjuvant treatment of diseases related to oxidative stress. Copyright © 2016 John Wiley & Sons, Ltd.

WT1 regulates murine hematopoiesis via maintenance of VEGF isoform ratio.

Mutations in the Wilms tumor suppressor 1 (WT1) gene are as frequent in acute myeloid leukemia (AML) as in nephroblastma and predict poor prognosis. However, the role of WT1 in hematopoiesis remains unclear. We show that Wt1-deficient mouse embryonic stem cells exhibit reduced hematopoietic potential caused by vascular endothelial growth factor A (Vegf-a)-dependent apoptosis of hematopoietic progenitor cells associated with overproduction of the Vegf-a120 isoform. We demonstrate that Wt1 promotes exon inclusion using a Vegf-a minigene-based splicing assay. These data identify a critical role for Wt1 in hematopoiesis and Vegf-a as a cellular RNA whose splicing is potentially regulated by Wt1. The correction of Wt1 deficiency by treatment with exogenous Vegf-a protein indicates that the Wt1/Vegf-a axis is a molecular pathway that could be exploited for the management/treatment of poor prognosis AMLs.

Palmitoylethanolamide improves colon inflammation through an enteric glia/toll like receptor 4-dependent PPAR-α activation.

OBJECTIVE: Enteric glia activation has been reported to amplify intestinal inflammation via the enteroglial-specific S100B protein. This neurotrophin promotes macrophage recruitment in the mucosa, amplify colonic inflammation and interacts with toll-like receptors (TLR). Molecules inhibiting S100B-driven enteric activation might mitigate the course of ulcerative colitis (UC). This study aims to investigate the effects of palmitoylethanolammide (PEA), a drug able to counteract astroglial activation in the central nervous system, on intestinal inflammation, in humans and mice. DESIGN: Mouse models of dextran sodium sulphate (DSS)-induced colitis, colonic biopsies deriving from UC patients and primary cultures of mouse and human enteric glial cells (EGC), have been used to assess the effects of PEA, alone or in the presence of specific PPARα or PPARγ antagonists, on: macroscopic signs of UC (DAI score, colon length, spleen weight, macrophages/neutrophils infiltration); the expression and release of proinflammatory markers typical of UC; TLR pathway in EGCs. RESULTS: PEA treatment improves all macroscopic signs of UC and decreases the expression and release of all the proinflammatory markers tested. PEA anti-inflammatory effects are mediated by the selective targeting of the S100B/TLR4 axis on ECG, causing a downstream inhibition of nuclear factor kappa B (NF-kB)-dependent inflammation. Antagonists at PPARα, but not PPARγ, abolished PEA effects, in mice and in humans. CONCLUSIONS: Because of its lack of toxicity, its ability in reducing inflammation and its selective PPARα action, PEA might be an innovative molecule to broaden pharmacological strategies against UC.

Enteroglial-derived S100B protein integrates bacteria-induced Toll-like receptor signalling in human enteric glial cells.

OBJECTIVE: Enteric glial cells (EGC) have been suggested to participate in host-bacteria cross-talk, playing a protective role within the gut. The way EGC interact with microorganisms is still poorly understood. We aimed to evaluate whether: EGC participate in host-bacteria interaction; S100B and Toll-like receptor (TLR) signalling converge in a common pathway leading to nitric oxide (NO) production. DESIGN: Primary cultures of human EGC were exposed to pathogenic (enteroinvasive Escherichia coli; EIEC) and probiotic (Lactobacillus paracasei F19) bacteria. Cell activation was assessed by evaluating the expression of cFos and major histocompatibility complex (MHC) class II molecules. TLR expression in EGC was evaluated at both baseline and after exposure to bacteria by real-time PCR, fluorescence microscopy and western blot analysis. S100B expression and NO release from EGC, following exposure to bacteria, were measured in the presence or absence of specific TLR and S100B pathway inhibitors. RESULTS: EIEC activated EGC by inducing the expression of cFos and MHC II. EGC expressed TLR at baseline. Pathogens and probiotics differentially modulated TLR expression in EGC. Pathogens, but not probiotics, significantly induced S100B protein overexpression and NO release from EGC. Pretreatment with specific inhibitors of TLR and S100B pathways abolished bacterial-induced NO release from EGC. CONCLUSIONS: Human EGC interact with bacteria and discriminate between pathogens and probiotics via a different TLR expression and NO production. In EGC, NO release is impaired in the presence of specific inhibitors of the TLR and S100B pathways, suggesting the presence of a novel common pathway involving both TLR stimulation and S100B protein upregulation.

Risk of venous thromboembolism and arterial events in patients with hypoalbuminemia: a comprehensive meta-analysis of more than 2 million of patients.

BACKGROUND: Albumin has antiplatelet and anticoagulant functions. Hypoalbuminemia, as defined by serum values <3.5 g/dl is associated with arterial thrombosis; its impact with venous thromboembolism (VTE) is unclear. The objective of this meta-analysis is to assess the VTE risk in patients with hypoalbuminemia. PATIENTS/METHODS: MEDLINE and EMBASE were searched up to January 2024 for observational studies and randomized trials reporting data of interest. Primary outcome was the risk of VTE while secondary outcome was myocardial infarction and stroke risk in patients with versus without hypoalbuminemia. The risk of bias was evaluated using Newcastle-Ottawa scale and Cochrane tool. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated in a random-effects model. RESULTS: 43 studies for a total of 2,531,091 patients (39,738 medical, 2,491,353 surgical) were included in primary analysis; 79.1% of the studies used 3.5 g/dl cut-off value for hypoalbuminemia definition. Follow-up duration was 30 days in 60.5% of studies. Patients with hypoalbuminemia had a higher risk of VTE (RR, 1.88; 95%CI, 1.66-2.13). RR were similar in both medical (RR, 1.87; 95%CI, 1.53-2.27) and surgical patients (RR, 1.87; 95%CI, 1.61-2.16) and in patients with (RR, 1.86; 95%CI, 1.66-2.10) and without cancer (RR, 1.89; 95%CI, 1.47-2.44). Risk of myocardial infarction (RR, 1.88; 95%CI, 1.54-2.31) and stroke (RR 1.77; 95%CI, 1.26-2.48) was higher in patients with hypoalbuminemia. CONCLUSIONS: Hypoalbuminemia is a risk factor for VTE in both medical and surgical patients irrespective of cancer coexistence. Serum albumin analysis may represent a simple and cheap tool to identify patients at VTE risk.

Impact of heat-not-burn cigarette passive smoking on children's oxidative stress, endothelial and platelet function.

Growing global use of heat-not-burn cigarettes (HNBC) prompts investigation. Prior studies assessed HNBC's effects on cardiovascular health, revealing heightened oxidative stress, platelet activation, and endothelial dysfunction. However, limited understanding exists regarding passive smoking's impact on children exposed to HNBC. This study aims to assess levels of oxidative stress, endothelial and platelet function among children exposed to passive smoke from HNBC, traditional tobacco (TT) cigarettes and unexposed subjects. Seventy-eight children (2-18 years) were divided into three groups: HNBC passive smokers (n = 26), TT cigarette exposed (n = 26), and control (CNT) group (n = 26, unexposed). Oxidative stress was evaluated by serum NADPH oxidase-2 (NOX2) activity, assessed by soluble Nox2-derived peptide (sNOX2-dp), isoprostanes, hydrogen peroxide (H2O2) production, hydrogen break-down activity (HBA) and NO bioavailability. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Platelet function was evaluated by soluble CD40 ligand (sCD40L), soluble P-selectin (sP-selectin) and thrombus formation by T-TAS analysis. Passive smoking-exposed children (both HNBC and TT) exhibited significantly increased serum sNOX2-dp, isoprostanes, H2O2, sCD40L sP-selectin and thrombus formation versus controls. Conversely, exposed children displayed reduced brachial FMD and serum NO bioavailability. No significant differences were found between children exposed to passive smoking of HNBC vs TT. Multivariable regression linked sNOX2 (standardized coefficient ß: 0.284; SE: 0.040; p = 0.01) and H2O2 (standardized coefficient ß: 0.243; SE: 0.0; p = 0.02) as independent predictors of FMD, and isoprostanes (standardized coefficient ß:0.388; SE: 0.022; p < 0.001) and serum cotinine (standardized coefficient ß:0.270; SE: 0.048; p = 0.01) with sNOX2-dp levels. Exposure to HNBC smoke heightened oxidative stress, endothelial dysfunction, platelet activation, and thrombus formation in children. Findings suggest avenues for interventions to curb childhood passive smoking exposure.

How to treat patients with splanchnic vein thrombosis: recent advances.

Splanchnic vein thrombosis (SVT) is an unusual-site venous thromboembolism that includes portal, mesenteric, and splenic vein thrombosis as well as the Budd-Chiari syndrome. SVT is a relatively rare disease (portal vein thrombosis and Budd-Chiari syndrome are, respectively, the most and the least common presentations); roughly one­third of the cases are detected incidentally, and liver cirrhosis and solid cancer represent the main risk factors. Once SVT is diagnosed, careful patient evaluation should be performed to assess the stage, grade, and extension of the thrombosis, as well as the risks and benefits of the anticoagulation regimen. Anticoagulant therapy is effective in SVT treatment and is associated with high rates of vein recanalization, low rates of thrombosis progression or recurrence, and an acceptable rate of bleeding complications. Most available data come from observational studies in patients with liver cirrhosis-related SVT receiving low­molecular­weight heparin or vitamin K antagonists. Data on the use of direct oral anticoagulants are increasing and promising. In selected patients and in specialized centers, interventional procedures may be considered in adjunction to anticoagulation in the cases of mesenteric or extensive SVT, intestinal ischemia, or in the patients whose condition deteriorates despite adequate anticoagulant therapy. In this narrative review, we summarize the available data regarding anticoagulation in patients with SVT, identify specific subgroups of patients who may achieve the greatest benefits from anticoagulant therapy, and provide practical advice for clinicians caring for these patients.

Low Grade Endotoxemia and Oxidative Stress in Offspring of Patients with Early Myocardial Infarction.

Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H2O2) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H2O2, TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H2O2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population.

ECHOPAEDIA: Echography in Paediatric Patients in the Age of Coronavirus Disease 2019: Utility of Lung Ultrasound and Chest X-Ray in Diagnosis of Community-Acquired Pneumonia and Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

Background: In recent years, lung ultrasound (LUS) has spread to emergency departments and clinical practise gaining great support, especially in time of pandemic, but only a few studies have been done on children. The aim of the present study is to compare the diagnostic accuracy of LUS (using Soldati LUS score) and that of chest X-ray (CXR) in CAP and COVID-19 pneumonia in paediatric patients. Secondary objective of the study is to examine the association between LUS score and disease severity. Finally, we describe the local epidemiology of paediatric CAP during the study period in the era of COVID-19 by comparing it with the previous 2 years. Methods: This is an observational retrospective single-centre study carried out on patients aged 18 or younger and over the month of age admitted to the Paediatric Unit of our Foundation for suspected community-acquired pneumonia or SARS-CoV-2 pneumonia during the third pandemic wave of COVID-19. Quantitative variables were elaborated with Shapiro-Wilks test or median and interquartile range (IQR). Student's t-test was used for independent data. Association between quantitative data was evaluated with Pearson correlation. ROC curve analysis was used to calculate best cut-off of LUS score in paediatric patients. Area under the ROC curve (AUC), sensibility, and specificity are also reported with 95% confidence interval (CI). Results: The diagnostic accuracy of the LUS score in pneumonia, the area underlying the ROC curve (AUC) was 0.67 (95% CI: 0.27-1) thus showing a discrete discriminatory power, with a sensitivity of 89.66% and specificity 50% setting a LUS score greater than or equal to 1 as the best cut-off. Nine patients required oxygen support and a significant statistical correlation (p = 0.0033) emerged between LUS score and oxygen therapy. The mean LUS score in patients requiring oxygen therapy was 12. RCP was positively correlated to the patient's LUS score (p = 0.0024). Conclusions: Our study has shown that LUS is a valid alternative to CXR. Our results show how LUS score can be applied effectively for the diagnosis and stratification of paediatric pneumonia.

Modification of vascular and inflammation biomarkers after OGTT in overweight healthy and diabetic subjects.

We evaluated the effect of an oral glucose tolerance test (OGTT) on the level of biomarkers of vascular remodelling. We enrolled 256 Caucasian overweight healthy subjects (H) and 274 overweight type 2 diabetic patients (D). All patients underwent basal measurements of blood glucose (BG), nitrites/nitrates, adiponectin (ADP), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) before and after OGTT. Nitrites/nitrates decrease was present after 60, 90, 120, and 180 min in both groups. Nitrite/nitrate levels were decreased at baseline, after 30 and 60 min in D group compared to H group. ADP decrease was present after 90, 120, and 180 min, in both groups. ADP levels were lower in D group than in H group during OGTT. MMP-2 increase was present after 60, 90, and 120 min in H group, while MMP-2 increase was observed after 90, 120, and 180 min in D group. MMP-2 levels were higher in D group than in H group during OGTT. MMP-9 increase was present in H group after 60, 90, 120, and 180 min, while MMP-9 increase was observed after 90, 120, and 180 min in D group. MMP-9 levels were higher in D group than in H group during OGTT. Postprandial glycemia induces an acute increase in biomarkers of vascular remodelling.

Effects of a standardized oral fat load on vascular remodelling markers in healthy subjects.

The most adequate way to experimentally reproduce the post-prandial lipemia condition appears to be the administration of a standardized oral fat load (OFL) to fasting patients. We studied the effects of a standardized OFL on markers of vascular remodelling in healthy subjects. We enrolled 286 Caucasians aged >or= 18 of either sex. The OFL was given after a 12-h fast. Blood samples were drawn before and 3, 6, 9 and 12h after the fat load. The following parameters were evaluated: body mass index (BMI), blood glucose (BG), systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid profile, nitrites and nitrates, adiponectin (ADP), metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9). High density lipoprotein-cholesterol (HDL-C) decrease was present in subjects after 6h. Triglycerides (Tg) change was observed after 6h. Nitrites/nitrates variation was observed after 6 and 9h during OFL. Adiponectin level was decreased after 6 and 9h during OFL. Both MMP-2 and MMP-9 levels were higher after 6h during OFL. We observed that nitrites/nitrates and ADP significantly decreased and MMP-2 and MMP-9 significantly increased after a standardized OFL. Other studies need to confirm the direct acute effects of post-prandial lipemia on vascular damage.

Effects of one year treatment of sibutramine on insulin resistance parameters in type 2 diabetic patients.

PURPOSE: Comparison of the effects of one year treatment with sibutramine compared to placebo on insulin resistance parameters, body weight, glycemic control, and lipid profile, in type 2 diabetic patients. METHODS: Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: homeostasis model assessment insulin resistance index (HOMA-IR), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP), body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and triglycerides (T(g)). RESULTS: A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups, and a faster improvement of HbA(1c), FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. CONCLUSIONS: Sibutramine gave a faster improvement of insulin resistance parameters and glycemic control compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight.

Orlistat and L-carnitine compared to orlistat alone on insulin resistance in obese diabetic patients.

Our study wants to evaluate the effects of one year treatment with orlistat plus L-carnitine compared to orlistat alone on body weight, glycemic and lipid control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-eight patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) > 8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take orlistat 120 mg three times a day plus L-carnitine 2 g one time a day or orlistat 120 mg three times a day. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). We observed a faster, and better decrease of body weight, HbA(1c), FPG, PPG, LDL-C, HOMA-IR with orlistat plus L-carnitine compared to orlistat. A faster improvement of TC, Tg, FPI, resistin, RBP-4, visfatin, and Hs-CRP was reached with orlistat plus L-carnitine compared to orlistat. We can safely conclude that the association of orlistat plus L-carnitine was better than orlistat in improving body weight, glycemic and lipid profile, insulin resistance, and inflammatory parameters and no significant adverse events were recorded.

Is There an Association Between Atherosclerotic Burden, Oxidative Stress, and Gut-Derived Lipopolysaccharides?

Aims: Recent studies hypothesized a role of gut microbiota favoring atherosclerosis via an increased oxidative stress, but data in peripheral artery disease (PAD) have not been provided yet. The aim of this study was to assess serum lipopolysaccharide (LPS) as well as oxidative stress in PAD patients and controls (CT). Furthermore, we wanted to analyze the relationship between LPS and the severity of atherosclerosis in the lower limb arteries. Results: Eighty consecutive subjects, including 40 PAD patients and 40 CT were recruited. A cross-sectional study was performed to compare serum LPS, soluble Nox2-derived peptide (sNox2-dp), hydrogen peroxide (H2O2), H2O2 breakdown activity (HBA) and ankle brachial index (ABI) in these two groups. Serum zonulin was used to assess gut permeability. Compared with CT, PAD patients had significant higher values of LPS, zonulin, sNox2-dp, and H2O2; conversely ABI and HBA were significantly lower in PAD patients. LPS serum levels were associated with atherosclerotic burden as depicted by the inverse correlation with ABI. LPS was also associated with oxidative stress as shown by its direct correlation with markers of oxidative stress such as sNox2-dp, serum H2O2, and HBA. Finally, we found a significant correlation between LPS and zonulin. A multiple linear regression analysis showed that LPS was significantly associated only with ABI. Innovation and Conclusion: These findings suggest that LPS is elevated in PAD patients with a close association with the atherosclerotic burden and oxidative stress. The correlation between LPS and zonulin suggests that changes in gut permeability could be a potential trigger of LPS translocation in the peripheral circulation.

Oral fat load effects on inflammation and endothelial stress markers in healthy subjects.

The aim was to study the effect of a standardized oral fat load (OFL) on different inflammatory parameters in a large sample of adult healthy subjects (n = 286) of both sexes. The fat load was given between 08:00 and 09:00 h after a 12-h fast. Blood samples were drawn before and 3, 6, 9, and 12 h after the OFL. All patients underwent a measurement of body mass index (BMI), blood glucose (BG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (Tg), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha). Fasting plasma glucose (FPG) increase was +3.26% at 3 h, +4.35% at 6 h, +1.09% at 9 h while FPG decrease was -1.09% at 12 h. High-density lipoprotein cholesterol increase was +2.08% at 3 h, and at 12 h during OFL study; a significant HDL-C decrease was present in subjects after 6 h (-4.17%; P < 0.05 vs 0). A significant Tg change was observed after 6 h (+70.37%; P < 0.01 vs 0) and 9 h (+58.33%; P < 0.05 vs 0) respectively, and the increase was +22.22% at 3 h and +18.52% at 12 h. Total cholesterol increase was +0.52% after 3 h, +1.04% after 6 h, while after 12 h the decrease was -0.52%. Low-density lipoprotein cholesterol increase was +1.64% after 6 h with a decrease of -0.82% at 9 and 12 h. A significant sICAM-1, hsCRP, and sE-selectin variation was observed after 6 and 9 h, while a significant sVCAM-1 change occurred after 3, 6, and 9 h. Soluble ICAM-1 increase was +20.58% at 3 h, +34.10% at 6 h (P < 0.05 vs 0) +25.94% at 9 h (P < 0.01 vs 0), and +19.14% at 12 h; sVCAM-1 increase was +13.97% (P < 0.05 vs 0) at 3 h, +18.55% at 6 h (P < 0.01 vs 0), +12.02% at 9 h (P < 0.05 vs 0), and +8.70% at 12 h. High-sensitivity CRP increase was +36.36% at 3 h, +90.91% at 6 h (P < 0.01 vs 0), +63.64% at 9 h (P < 0.05 vs 0), and +36.36% at 12 h. Soluble E-selectin increase was +27.11% at 3 h, +51.90% at 6 h (P < 0.05 vs 0), +45.19% at 9 h (P < 0.01 vs 0), and +20.12% at 12 h. Interleukin-6 increase was +61.11% at 3 h (P < 0.05 vs 0), +83.33% at 6 h (P < 0.001 vs 0), +55.56% at 9 h (P < 0.01 vs 0), and +22.22% at 12 h. Tumor necrosis factor-alpha increase was +42.86% at 3 h (P < 0.05 vs 0), +71.43% at 6 h (P < 0.01 vs 0), (+50.00% at 9 h (P < 0.05 vs 0), and +28.57% at 12 h. We observed that the OFL induces a complex and massive systemic inflammatory response that includes IL-6, TNF-alpha, hsCRP, and cell adhesion molecules, even before Tg significantly rises.

Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in combined dyslipidemia.

PURPOSE: To evaluate the distribution of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and their specific inhibitors in a sample of patients affected by mild dyslipidemia but not yet treated with antihyperlipidemic drugs. METHODS: One hundred and sixty-eight Caucasian patients aged >or=18 yr of either sex with combined dyslipidemia and who had never previously taken lipid-lowering medications were evaluated. As a control population, we enrolled 179 Caucasian healthy subjects, aged >or=18 yr of either sex. We evaluated body mass index (BMI), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) Lp(a), plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct), fibrinogen (Fg), high sensitivity C-reactive protein (Hs-CRP), adiponectin (ADP), MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1 (TIMP-1), and tissue inhibitors of metalloproteinase-2 (TIMP-2). RESULTS: TC, Tg, and LDL-C were higher (P < < 0.05, P < < 0.01 and P < < 0.05, respectively) in the dyslipidemic group, while HDL-C levels were lower (P < < 0.01) compared with the control group. Increases of PAI-1, Hct, Fg, and Hs-CRP (P < < 0.01, P < < 0.05, P < < 0.05, and P < < 0.05, respectively) were present in the dyslipidemic group, while ADP level was lower (P < < 0.01) in the dyslipidemic patients compared with controls. MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were higher (P < < 0.0001) in the dyslipidemic group. CONCLUSIONS: Combined hyperlipidemic patients have increased levels of prothrombotic and microinflammatory parameters and higher levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 than control subjects. The prognostic importance of this observation has to be evaluated in adequately designed prospective studies.

Effects of insulin therapy with continuous subcutaneous insulin infusion (CSII) in diabetic patients: comparison with multi-daily insulin injections therapy (MDI).

We compared the effects of continuous subcutaneous insulin infusion (CSII) and multi-daily insulin injections therapy (MDI) on glicemic control and on lipid profile in type 1 and type 2 diabetic patients. We divided the patients in two groups: in the first one (n=32) CSII was administered, in the second one (n=32) MDI was administered. HbA(1C) value was lower after 3, 6, 9, and 12 months with CSII compared to MDI. Fasting plasma glucose (FPG) value was lower with CSII after 3, 6, and 12 months compared to MDI. Post-prandial glucose (PPG) value was lower in the group with CSII after 3, 6, 9, and 12 months compared to MDI. A significant TC decrease was observed in the group treated with CSII at 9, and 12 months while a significant TC increase was observed with MDI at 6, and 12 months. A significant LDL-C decrease was obtained with CSII after 9, and 12 months while no significant changes were observed with MDI. A significant HDL-C increase was observed with CSII after 12 months. A significant Tg decrease was observed with CSII after 12 months while a significant Tg increase was observed with MDI at 6, and at 12 months. CSII therapy allows a faster and better achievement of the therapeutic target and also gives an improvement of the lipid profile.

Oxaliplatin-eluting microspheres for the treatment of intrahepatic cholangiocarcinoma: a case report.

Intrahepatic cholangiocarcinoma account for 13% of annual cancer-related deaths worldwide and for 3% in the USA. Patient with unresectable disease can benefit from palliative therapies such as systemic chemotherapy. However, the only curative treatment for intrahepatic cholangiocarcinoma is complete surgical resection with histologically negative resection margins.

Transhepatic arterial chemoembolization with oxaliplatin-eluting microspheres (OEM-TACE) for unresectable hepatic tumors.

BACKGROUND: While conventional transhepatic arterial chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC), its use in other hepatic tumors is not supported by randomized studies. Preliminary results have shown that new drug-eluting microspheres (DEM) seem to optimize TACE procedures. The aim of this study was to evaluate the capability of HepaSphere to load oxaliplatin and their pharmacokinetic outcome. The feasibility and safety of treatment with oxaliplatin-eluting microspheres (OEM-TACE) was also evaluated in patients with unresectable liver metastasis of colorectal cancer and unresectable intrahepatic cholangiocarcinoma. PATIENTS AND METHODS: An inductively coupled plasma mass spectrometer (ICP-MS) was used to quantify the oxaliplatin bound to microspheres and the oxaliplatin in liver biopsies. Fifteen patients (8 with colorectal carcinoma liver metastases, 7 with intrahepatic cholangiocarcinoma) were treated with 27 sessions of OEM-TACE. RESULTS: The data suggested that the microspheres can bind oxaliplatin entirely. The pharmacokinetic parameters were significantly different between the OEM-TACE patients and a control group of patients treated with oxaliplatin chemotherapy. The mean oxaliplatin concentration within the tumor was twenty-times higher than the extratumoral liver concentration in the OEM-TACE patients. According to response evaluating criteria in solid tumors (RECIST), stable disease was observed in 8 out of the 15 patients (53.3%), a partial response in 2 (13.3%) and intrahepatic or extrahepatic tumor progression in 5 out of the 15 patients (33.3%). No major adverse event (AE G3/4) occurred. CONCLUSION: TACE with oxaliplatin-loaded microspheres is a safe and feasible treatment without major adverse events and with a favorable pharmacokinetic profile.