Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features in lung metastases

Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be activated by the same biochemical stimulus; hypoxia. A correlation between these two parameters has been postulated. The objective of this study was to evaluate the relationship between Fluoro-desoxi-glucose uptake at positron emission tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose activity, expressed as a standard uptake value, and microvessel intratumoural density, were retrospectively calculated in a series of 43 lung metastasis resected in 19 patients. Primary sites were colorectal cancer in 16 metastases, sarcoma in eight, gynaecological in four and other sites in 15. The correlation between the two parameters was tested by logistic regression and multivariate analysis. Positron emission tomography scan was positive in 17 patients (sensitivity 89%). No correlation was observed between standard uptake value and microvessel intratumoural density in this series of lung metastasis. Positron emission tomography negative and positive nodules presented comparable value of microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was significantly correlated with nodules size and was higher in colon cancer metastasis than in sarcoma ones. Microvessel intratumoural density was independent from nodule size but significantly higher in sarcoma than in colon cancer metastasis. The lack of correlation was confirmed by multivariate analysis after adjustment for tumour type and nodules size. The present study demonstrated that positron emission tomography scan is positive in a high proportion of patients regardless of microvessel density. Glucose uptake and angiogenesis appear to be independent biological features in lung metastasis. This observation may have implications for future antiangiogenic therapies

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Avaliação otoneurológica em crianças com queixa de dificuldades escolares: pesquisa da função vestibular Otoneurologic evaluation in children with school difficulties: vestibular function investigation

Segundo a literatura, a disfunção vestibular infantil pode afetar consideravelmente a habilidade de comunicação e o desempenho escolar. OBJETIVO: Estudar a função vestibular em crianças com dificuldades escolares e suas queixas vestibulares. ESTUDO DE CASO: Estudo Clínico com coorte transversal. MATERIAL E MÉTODOS: Foram estudadas 50 crianças entre 7 e 12 anos, que freqüentavam escolas públicas de Piracicaba durante os anos de 2004 e 2005. Os procedimentos foram: anamnese; exame otorrinolaringológico; exame audiológico e avaliação vestibular. RESULTADOS: Das crianças avaliadas, 62,0% não relataram dificuldades escolares e 38,0% referiram ter dificuldades. A queixa geral mais comum foi de tontura (36,0%), e o sintoma mais comum no ambiente escolar foi de cefaléia (50,0%). Encontramos 74,2% de exame vestibular normal nas crianças sem dificuldades escolares e 31,6% de normalidade nas crianças com dificuldades. Encontramos alterações vestibulares de origem periférica irritativa tanto unilateral como bilateral, num total de 68,4% para as crianças com dificuldades escolares e um total de 25,8% para crianças sem dificuldades escolares. CONCLUSÃO: A queixa de atordoamento, o sintoma de náuseas e as dificuldades em ler e copiar apresentaram uma relação estatisticamente significante. Todas as alterações vestibulares encontradas foram de origem periférica irritativa. Os dados revelaram uma relação estatisticamente significante.<br>According to the literature, child vestibular dysfunctions can considerably affect their ability of communication and school performance. AIM: to study the vestibular function in children with school difficulties and associated symptoms. CASE STUDY: Clinical study with transversal cohort. METHOD: Research subjects were 50 school children between 7 and 12 years old, from a public school of Piracicaba city, during the years 2004 and 2005. The procedure was based on: anamnesis; otorrinolaryngologic evaluation; audiologic evaluation and vestibular evaluation. RESULTS: All children assessed, 62.0% did not have school difficulties and 38.0% had school difficulties. Dizziness was the most common general complaint (36.0%). Migraine was the most common symptom regarding the school environment (50.0%). We found a high rate of normal vestibular condition (74.2%) in children without school difficulties and low normality rate in those with school difficulties (31.6%). All found vestibular alterations, both unilateral and bilateral, had been of peripheral irritative origin, accounting for 68.4% of cases for children with school difficulties and 25.8% for children without school difficulties. CONCLUSION: Dizziness, nausea, reading and copying difficulties presented a statistically significant relationship between the studied variables. All found vestibular alterations had been of peripheral irritative origin. Data showed a statistically significant relationship among variables