Serum LDH predicts benefit from bevacizumab beyond progression in metastatic colorectal cancer.

BACKGROUND: Different antiangiogenics are currently indicated in the second-line treatment of metastatic colorectal cancer (mCRC), following a first-line bevacizumab-containing treatment. The magnitude of benefit is limited, but no predictors of benefit have been identified. METHODS: A total of 184 mCRC patients progressing to a first-line bevacizumab-containing treatment were randomised in the BEBYP study to continue or not the antiangiogenic in combination with a second-line chemotherapy. A subgroup analysis according to baseline serum lactate dehydrogenase (LDH) levels was carried out. RESULTS: A significant interaction effect between LDH levels and treatment was found in terms of progression-free survival (PFS; P=0.002). Although patients with low LDH levels achieved significant PFS benefit from the continuation of bevacizumab (HR: 0.39 (95% CI: 0.23-0.65)), patients with high levels did not (HR: 1.10 (95% CI: 0.74-1.64)). Consistent results were reported in overall survival (OS; P=0.075). CONCLUSIONS: As preclinical evidence suggests that serum LDH may be a marker of tumour angiogenesis activation, low levels may indicate that bevacizumab is still efficacious in inhibiting angiogenesis. Validation of present results in subgroup analyses of other randomised trials of second-line angiogenesis inhibitors is warranted.

ACE gene insertion/deletion polymorphism has a mild influence on the acute development of left ventricular dysfunction in patients with ST elevation myocardial infarction treated with primary PCI.

BACKGROUND: We evaluated the associations among angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism, ACE activity and post-myocardial infarction (MI) left ventricular dysfunction and acute heart failure (AHF) early after presentation with MI with ST-segment elevation (STEMI). METHODS: A total of 556 patients with STEMI treated by primary PCI (421 patients without AHF and 135 patients with AHF) were the study population. The activity of BNP, NT-ProBNP and ACE were measured at hospital admission and 24 h after MI onset. Left ventricular angiography was done before PCI; echocardiography was undertaken between the third and fifth day after MI. RESULTS: In comparison with the II genotypes group, the DD/ID group had a higher level of ACE activity upon hospital admission (p < 0.001). We found a significantly higher level of ACE activity in patients with moderate LV dysfunction (EF 40-54%) in comparison both with patients with preserved LV function (EF ≥ 55%) and with patients with severe LV dysfunction (p = 0.028). A non-significant trend towards a higher incidence of mild AHF (22.1% vs. 16.02%, p = 0,093), a significantly higher value of end-systolic volume (ESV/BSA) (30.0 ± 12.3 vs. 28.5 ± 13.0; p < 0.05) and lower EF (50.2 ± 11.1 vs. 52.7 ± 11.7; p < 0.05) in the DD/ID genotypes group was noted. Even after multiple adjustments according to multivariate models, the EF for the DD/ID group remained significantly lower (p = 0,033). The DD/ID genotypes were associated with a significantly higher risk of EF <45% (OR 2.04 [95% CI 1.28; 3.25]). CONCLUSIONS: These results suggest that the I/D polymorphism of ACE is associated with the development of LV dysfunction in the acute phase after STEMI. We demonstrated for the first time an association of the low ACE activity with the severe LV dysfunction, although patients with moderate LV dysfunction had higher level ACE activity than patients with preserved LV function.

Evaluation of the safety and efficacy of the organic acids lactic and acetic acids to reduce microbiological surface contamination on pork carcasses and pork cuts.

Studies evaluating the safety and efficacy of lactic and acetic acids to reduce microbiological surface contamination on pork carcasses pre-chill and pork meat cuts post-chill were assessed. Lactic acid treatments consisted of 2-5% solutions at temperatures of up to 80°C applied to carcasses by spraying or up to 55°C applied on cuts by spraying or dipping. Acetic acid treatments consisted of 2-4% solutions at temperatures of up to 40°C applied on carcasses by spraying or on cuts by spraying or dipping. The maximum treatment duration was 30 s. The Panel concluded that: [1] the treatments are of no safety concern, provided that the substances comply with the European Union specifications for food additives; [2] spraying of pork carcasses pre-chill with lactic acid was efficacious compared to untreated control, but based on the available data, the Panel could not conclude whether lactic acid was more efficacious than water treatment when spraying of pork carcasses pre-chill or pork meat cuts post-chill. The Panel concluded that dipping of pork meat cuts post-chill in lactic acid was more efficacious than water treatment. However, it could not conclude on the efficacy of acetic acid treatment of pork carcasses pre-chill and/or pork meat cuts post-chill; [3] the potential selection and emergence of bacteria with reduced susceptibility to biocides and/or resistance to therapeutic antimicrobials linked to the use of the substances is unlikely as long as Good Hygienic Practices are implemented; and [4] the release of both organic acids is not of concern for the environment, assuming that wastewaters released by the slaughterhouses are treated, if necessary, to counter the potentially low pH caused by lactic or acetic acid, in compliance with local rules.

Update of the tolerable upper intake level for vitamin D for infants.

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to revise the tolerable upper intake level (UL) for vitamin D for infants (≤ 1 year) set in 2012. From its literature review, the Panel concluded that the available evidence on daily vitamin D intake and the risk of adverse health outcomes (hypercalciuria, hypercalcaemia, nephrocalcinosis and abnormal growth patterns) cannot be used alone for deriving the UL for infants. The Panel conducted a meta-regression analysis of collected data, to derive a dose-response relationship between daily supplemental intake of vitamin D and mean achieved serum 25(OH)D concentrations. Considering that a serum 25(OH)D concentration of 200 nmol/L or below is unlikely to pose a risk of adverse health outcomes in infants, the Panel estimated the percentage of infants reaching a concentration above this value at different intakes of vitamin D. Based on the overall evidence, the Panel kept the UL of 25 µg/day for infants aged up to 6 months and set a UL of 35 µg/day for infants 6-12 months. The Panel was also asked to advise on the safety of the consumption of infant formulae with an increased maximum vitamin D content of 3 µg/100 kcal (Commission Delegated Regulation (EU) 2016/127 repealing Directive 2006/141/EC in 2020). For infants aged up to 4 months, the intake assessment showed that the use of infant formulae containing vitamin D at 3 µg/100 kcal may lead some infants to receive an intake above the UL of 25 µg/day from formulae alone without considering vitamin D supplemental intake. For infants aged 4-12 months, the 95th percentile of vitamin D intake (high consumers) estimated from formulae and foods fortified or not with vitamin D does not exceed the ULs, without considering vitamin D supplemental intake.

Predictors of survival in patients with established cirrhosis and hepatocellular carcinoma treated with sorafenib.

AIM: To investigate in greater detail the efficacy and safety of sorafenib for the treatment of hepatocellular carcinoma (HCC) in patients with established cirrhosis. METHODS: From October 2009 to July 2012 patients with an established diagnosis of cirrhosis and HCC treated with sorafenib were consecutively enrolled. According to the Barcelona Clinic Liver Cancer (BCLC) classification, patients were in the advanced stage (BCLC-C) or in the intermediate stage (BCLC-B) but unfit or unresponsive to other therapeutic strategies. Treatment was evaluated performing a 4-phase computed tomography or magnetic resonance imaging scan every 2-3 mo, and analyzed according to the modified Response Evaluation Criteria in Solid Tumors. Sorafenib was administered at 800 mg/d, until radiological progression or occurrence of unacceptable adverse events (AEs). Univariate and multivariate analyses identified predictors of 16-wk clinical benefit and overall survival. RESULTS: Forty-four patients were enrolled, 15 had intermediate HCC and 14 a Child-Pugh score of B7. AEs caused treatment interruption in 19 patients (43%), and median treatment duration was shorter in this subset (5 wk vs 19 wk, P < 0.001) and in the BCLC-C subgroup (13 wk vs 40 wk, P = 0.015). No significant differences in the reason for treatment interruption or in treatment duration were found comparing patients in Child-Pugh class A vs B or in patients older or younger than 70 years. After 16 wk of treatment, 18 patients (41%) had stable disease or partial response. Patients with viral infection or BCLC-C were at higher risk of disease progression. ECOG, extrahepatic spread, macrovascular invasion, alpha-fetoprotein or alkaline phosphatase levels at admission were independent predictors of overall survival. CONCLUSION: In patients with cirrhosis and HCC treated with sorafenib, AEs are a common cause of early treatment withdrawal. Vascular invasion and extrahepatic spread condition early response to treatment and survival. Baseline biochemical parameters may be helpful to identify patients at higher risk of shorter overall survival.

Risk of in-hospital mortality identified according to the typology of patients with acute heart failure: classification tree analysis on data from the Acute Heart Failure Database-Main registry.

PURPOSE: The purposes of this study are to identify the strongest clinical parameters in relation to in-hospital mortality, which are available in the earliest phase of the hospitalization of patients, and to create an easy tool for the early identification of patients at risk. MATERIALS AND METHODS: The classification and regression tree analysis was applied to data from the Acute Heart Failure Database-Main registry comprising patients admitted to specialized cardiology centers with all syndromes of acute heart failure. The classification model was built on derivation cohort (n = 2543) and evaluated on validation cohort (n = 1387). RESULTS: The classification tree stratifies patients according to the presence of cardiogenic shock (CS), the level of creatinine, and the systolic blood pressure (SBP) at admission into the 5 risk groups with in-hospital mortality ranging from 2.8% to 66.2%. Patients without CS and creatinine level of 155 µmol/L or less were classified into very-low-risk group; patients without CS, creatinine level greater than 155 µmol/L, and SBP greater than 103 mm Hg, into low-risk group, whereas patients without CS, creatinine level greater than 155 µmol/L, and SBP of 103 mm Hg or lower, into intermediate-risk group. The high-risk group patients had CS and creatinine of 140 µmol/L or less; patients with CS and creatinine level greater than 140 µmol/L belong to very-high-risk group. The area under receiver operating characteristic curve was 0.823 and 0.832, and the value of Brier's score was estimated on level 0.091 and 0.084, for the derivation and the validation cohort, respectively. CONCLUSIONS: The presented classification model effectively stratified patients with all syndromes of acute heart failure into in-hospital mortality risk groups and might be of advantage for clinical practice.

Association between laboratory markers and presence of coronary artery disease.

UNLABELLED: The aim of this paper is to elucidate the relation between laboratory markers and coronary artery disease (CAD). METHODS: The study involved 1254 consecutive patients with suspected or known CAD referred for coronary angiography. The blood samples including blood cell count, C-reactive protein, fibrinogen, uric acid, creatinine, and lipid spectrum were obtained after overnight fasting. One hundred and thirty-three patients were excluded due to incomplete records or inacceptable laboratory values. Differences among groups were tested with one-way ANOVA and Bonferroni post-hoc test for continuous variables and with chi-square test for categorical variables. Univariate and multivariate logistic regression was adopted for the analysis of risk factors and development of models for classification of patients into clinical categories. RESULTS: The linear logistic regression showed association of patient's biochemical markers with the presence of disease. Both acute and chronic CAD were associated with leukocyte count (Odds ratios 1.45 and 1.26), CRP (1.13; 1.05), fibrinogen (4.23; 1.95), uric acid (1.27; 1.38), creatinine (1.04; 1.04), HDL cholesterol (0.07; 0.12), triglycerides (1.4; 1.52) and glucose (1.56; 1.39). Presence of insignificant atherosclerosis was influenced only by fibrinogen (OR 1.73), creatinine (1.02), HDL cholesterol (0.5) and glucose level (1.23). There was no difference between one- and multivessel disease in laboratory values. CONCLUSION: Leukocyte count, CRP level, triglycerides and uric acid are associated with the presence of both acute and chronic ischaemic heart disease, but not with number of stenosed vessels. In addition, glycemia, HDL cholesterol and namely fibrinogen and creatinine have relation to occurence of insignificant atherosclerosis.