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The objective of this study was to investigate the factors underlying the development of metabolic syndrome (MetS) in HIV-infected patients. Two hundred and sixty-six clinical cases were selected for a retrospective study. The sample was classified using the Adult Treatment Panel III guidelines and the identification of risk or protective factors associated with MetS evaluated via multivariate logistic or multinomial regressions. HIV-infected individuals diagnosed with MetS tend to be older, overweight, or obese (85% have a BMI ≥ 25), with a waist circumference > 90 cm (96.5 [88.8-105.5] cm, median [interquartile range]). Blood testing these individuals revealed high fasting levels of insulin (8.1 [5.8-21.6] pg/ml), glucose (98.0 [84.0-116.0] mg/dl), triglycerides (201.0 [142.0-267.3] mg/dl), and high-density lipoprotein cholesterol (36.5 [29.8-43.3] mg/dl) in addition with higher levels of inflammatory mediators such as high-sensitivity C-reactive protein (2.5 [1.0-4.9] mg/dl) and interleukin-6 (3.4 [2.8-3.8] pg/ml). The likelihood of HIV-infected individuals who are virally suppressed developing MetS is about 60% higher than those with acute infection. Treatment with nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) increases the chance of developing MetS by around 2.4 times. Individuals with a lower antioxidant capacity (total antioxidant status [TAS] <1.33) have a 2.6 times higher risk of developing MetS. HIV-related chronic inflammation, a low TAS, and treatment with NRTIs in association with PIs are additional MetS risk factors.

Background: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty., Patients and Methods: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL., Results: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens., Conclusion: Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit., Clinicaltrialsgov: NCT02409472., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To study dysglycaemia in human immunodeficiency virus (HIV)-infected patients we conducted a retrospective cohort study of the glucose profile in HIV-infected patients. The fasting blood glucose was analysed taking into consideration conventional risk factors as well as HIV infection and highly active antiretroviral therapy (HAART). One hundred seventy-three cases were selected for this study. Five risk factors had significant effects (p < 0.05) on glucose levels: age, body mass index (BMI), hepatitis C virus/hepatitis B virus (HCV/HBV) co-infection, viral load (VL), and CD4(+) T-lymphocyte count. Fasting blood glucose levels increased with age (0.59 mg/dL/year), decreased with the VL (-4.1 × 10(-6 )mg/dL/number of viral RNA copies) and the CD4(+) T-lymphocyte count (-0.016 mg/dL/cell count). Furthermore, obese patients and those co-infected with HCV/HBV were more prone to develop dysglycaemia having, on average, 15.4 mg/dL and 13.8 mg/dL higher levels, respectively, of fasting blood glucose. Despite an increase of 1.0% and 8.4% in the glucose levels noticed among HIV patients treated with non-nucleotide inhibitors of reverse transcriptase and protease inhibitors, respectively, HAART did not prove to be a significant predictor of fasting glucose levels as well as lipodystrophy and male gender. Age, BMI, HCV/HBV co-infection and HIV-related (VL and CD4(+) T-lymphocyte count) factors seem to be the most influential on fasting blood glucose levels in HIV-infected individuals., (© The Author(s) 2015.)

Crohn's disease (CD) has been correlated with altered macrophage response to microorganisms. Considering the efficacy of infliximab treatment on CD remission, we investigated infliximab effects on circulating monocyte subsets and on macrophage cytokine response to bacteria. Human peripheral blood monocyte-derived macrophages were obtained from CD patients, treated or not with infliximab. Macrophages were infected with Escherichia coli, Enterococcus faecalis, Mycobacterium avium subsp. paratuberculosis (MAP) or M. avium subsp avium, and cytokine levels [tumour necrosis factor (TNF) and interleukin (IL)-10] were evaluated at different time-points. To evaluate infliximab-dependent effects on monocyte subsets, we studied CD14 and CD16 expression by peripheral blood monocytes before and after different infliximab administrations. We also investigated TNF secretion by macrophages obtained from CD16(+) and CD16(-) monocytes and the frequency of TNF(+) cells among CD16(+) and CD16(-) monocyte-derived macrophages from CD patients. Infliximab treatment resulted in elevated TNF and IL-10 macrophage response to bacteria. An infliximab-dependent increase in the frequency of circulating CD16(+) monocytes (particularly the CD14(++) CD16(+) subset) was also observed (before infliximab: 4·65 ± 0·58%; after three administrations: 10·68 ± 2·23%). In response to MAP infection, macrophages obtained from CD16(+) monocytes were higher TNF producers and CD16(+) macrophages from infliximab-treated CD patients showed increased frequency of TNF(+) cells. In conclusion, infliximab treatment increased the TNF production of CD macrophages in response to bacteria, which seemed to depend upon enrichment of CD16(+) circulating monocytes, particularly of the CD14(++) CD16(+) subset. Infliximab treatment of CD patients also resulted in increased macrophage IL-10 production in response to bacteria, suggesting an infliximab-induced shift to M2 macrophages., (© 2014 British Society for Immunology.)

Objective: Study of the lipid profile in patients infected with HIV treated with different combinations of high activity anti-retroviral therapy (HAART)., Design and Methods: A retrospective cohort study of the lipid profile in patients undergoing HAART. The study analyzes the evolution of concentrations of triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDLc) and HDL-cholesterol (HDLc) in a period of at least 3 years of treatment. From a total of 750 clinical cases analyzed in Hospital Joaquim Urbano (Oporto, Portugal) 124 patients were selected for this study., Results: After 3 years of treatment, we observed the development of dyslipidaemia by increases in TG (17%), TC (29%) and LDLc (9%), particularly in patients treated with a combination of drugs which included protease inhibitors (PI). Moreover, the non-nucleoside reverse transcriptase inhibitors (NNRTI) were associated with better lipid profile. The increase of 46% in HDLc was the most surprising finding., Conclusions: The results indicate that patients with HAART have a more atherogenic lipidic profile with increased TC, LDLc and TG levels. Since the effectiveness of NNRTI is similar to that of PI, but with a smaller atherogenic profile, it should be the first choice drug to be selected in the HIV treatment., (Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Recent guidelines do not recommend antithrombotic prophylaxis (AP) to prevent catheter-related thrombosis in cancer patients with a central line., Patients and Methods: This study assessed the management of central lines in cancer patients, current attitude towards AP, catheter-related and systemic venous thromboses, and survival., Results: Of 1410 patients enrolled, 1390 were seen at least once in the 6-month median follow-up. Continuous AP, mainly low-dose warfarin, was given to 451 (32.4%); they were older, with a more frequent history of venous thromboembolism (VTE), and more advanced cancer. There was no difference in catheter-related thrombosis in patients given AP or not (2.8% and 2.2%, odds ratio 1.29, 95% confidence interval 0.64-2.6). The median time to first catheter-related complication was 120 days. Systemic VTE including deep and superficial thromboses and pulmonary embolism, were less frequent with AP (4% versus 8.2%, P = 0.005). Mortality was also lower (25% versus 44%, P = 0.0001). Multiple logistic regression analysis found only advanced cancer and no AP significantly associated with mortality. No major bleeding was recorded with AP., Conclusions: Current AP schedules do not appear to prevent catheter-related thrombosis. Systemic VTE and mortality, however, appeared lower after prophylaxis.

Background: Although leucovorin (LV) + 5-fluorouracil (5-FU) is considered the treatment of choice for advanced colorectal cancer in most countries, the optimal schedule of this combination has not yet been established. Low-dose LV appears to be as active as high-dose LV in the daily-times-five regimen, but no randomized study of the levorotatory stereoisomer (6S-LV) given at two different dose levels has been published., Patients and Methods: Between November 1991 and June 1994, 422 patients (all with measurable disease previously untreated with chemotherapy) were randomized to 6S-LV (100 mg/sqm/i.v.) + 5-FU (370 mg sqm/15 min i.v. infusion), both administered for 5 days every 28 days (arm A), or to 6S-LV (10 mg/sqm/i.v./5-FU (doses as above), also given for 5 days every 28 days (arm B). The primary endpoint of the study was the comparison of response rates (WHO criteria): the secondary endpoint was the assessment of survival and tolerability. No evaluation of the quality of life or the symptomatic effect of treatment was planned., Results: The response rate was 9.3% in arm A (95% CI: 5.4-13.1), with 2 CR and 18 PR, and 10.7% in arm B (95% CI: 6.5-14.9), with 3 CR + 19 PR, without any significant difference (P = 0.78). The median time to progression was eight months in both groups and overall survival was 11 months, with no difference between treatments. Toxicity mainly consisted of gastrointestinal side effects (mucositis and diarrhoea), which were rarely severe (grade 3-4: 5%-10% of patients) and similar in the two groups., Conclusions: In this large-scale multicentre trial, the low and high doses of 6S-LV appeared to be equivalent in terms of the biochemical modulation of 5-FU in advanced colorectal cancer although, for several reasons (including the timing and the strict criteria of response evaluation, the high number of patients with unfavourable prognostic factors, the multi-institutional nature of the study, the dose and modality of 5-FU administration), the response rate was lower than that reported in some of the other published studies. Given the considerable difference in economic cost between the two dosages, the use of high-dose 6S-LV in the daily-times-five regimen is not recommended in clinical practice.

In advanced colorectal cancer the addition of folinic acid (FA) has been shown to lead to increased activity, at least in terms of response rate, in comparison with 5-fluorouracil (5FU) alone. Similarly, interferon-alpha (IFN) is able to potentiate 5FU, although high doses cause heavy toxicity. Given the different mechanisms of action of the two agents, the double modulation of 5FU deserves clinical evaluation. In a multicenter study (involving both primary care and referral institutions) 63 patients with advanced colorectal cancer, previously untreated with chemotherapy, received, in an outpatient setting, FA (200 mg/m2 i.v. bolus) + 5FU (400 mg/m2 i.v. in 15 min) for 5 consecutive days every 4 weeks + IFN 3 x 10(6) U on alternate days, starting 1 week before chemotherapy. During the 5 days of 5FU + FA, IFN was administered daily. The antitumour activity, the impact on response duration and survival and toxicity of the combination were evaluated according to WHO criteria. Of the 63 enrolled patients, 56 were evaluable: there were 2 complete responses (3%) and 13 partial responses (21%), giving an objective response rate of 24% (95% confidence interval 13-35%); no change was observed in 17 cases and progressive disease in 24. Median duration of response was 9 months and median survival (all patients) 13 months. Toxicity was acceptable, even though 4 patients presented reversible grade 4 side-effects (2 mucositis and 2 diarrhoea). With this schedule and these doses, addition of IFN did not lead to any increase in the activity of 5FU + FA. In colorectal cancer, further clinical studies with these drugs should be based on a deeper experimental knowledge of their mechanisms of interaction.

To verify that variations caused by total parenteral nutrition (TPN) in O2 intake (VO2) and CO2 output (VCO2) can affect respiratory function of non-hypercatabolic patients, we studied 18 patients in two groups; group I (control): eight patients receiving 75-100 g glucose/24 h, and group II: ten patients fed intravenously on 13.6 g N2 and approximately 2,800 kcal/24 h given as a) 62% glucose + 38% fats (TPN-G + F) and b) 100% glucose (TPN-G). VO2, VCO2, respiratory quotient (RQ) and minute ventilation (VE) were measured in all patients. We found that VCO2 was 27% higher in intravenously fed patients (p less than 0.01 and p less than 0.02). Similarly, VE was 26% higher in intravenously fed patients (p less than 0.001 and p less than 0.02). Comparison of TPN-G + F and TPN-G results showed no differences in VCO2; by contrast, VO2 was 21% less during TPN-G (p less than 0.01).