Relationship between achieved personalized glycaemic targets and monitoring of clinical events in elderly diabetic patients.

AIM: Recent guidelines for the management of type 2 diabetes (T2DM) in the elderly recommend adjusting the therapeutic target (HbA1c) according to the patient's health. Our study aimed to explore the association between achieving the recommended personalized HbA1c target and the occurrence of major clinical events under real-life conditions. METHODS: The T2DM S.AGES cohort was a prospective multicentre study into which 213 general practitioners recruited 983 non-institutionalized T2DM patients aged>65 years. The recommended personalized HbA1c targets were<7%, <8% and <9% for healthy, ill and very ill patients, respectively. Major clinical events (death from any cause, major vascular events and/or hospitalization) were recorded during the 3-year follow-up. Mixed-effects logistic regression models were used for the analyses. RESULTS: Of the 747 patients analyzed at baseline, 551 (76.8%) were at their recommended personalized HbA1c target. During follow-up, 391 patients (52.3%) experienced a major clinical event. Of the patients who did not achieve their personalized HbA1c target (compared with those who did), the risk (OR) of a major clinical event was 0.95 (95% CI: 0.69-1.31; P=0.76). The risk of death, major vascular event and hospitalization were 0.88 (95% CI: 0.40-1.94; P=0.75), 1.14 (95% CI: 0.7-1.83; P=0.59) and 0.84 (95% CI: 0.60-1.18; P=0.32), respectively. CONCLUSION: Over a 3-year follow-up period, our results showed no difference in risk of a major clinical event among patients, regardless of whether or not they achieved their personalized recommended HbA1c target. These results need to be confirmed before implementing a more permissive strategy for treating T2DM in elderly patients.

[Update on endocrine hypertension]. / Données récentes sur l'hypertension endocrine.

Endocrine hypertension is the most common cause of secondary hypertension affecting ~3 % of the population, with primary hyperaldosteronism and pheochromocytoma being the principal conditions. Both diseases share an increased cardiovascular risk in comparison with essential hypertension patients (at the same blood pressure level). This augmented cardiovascular risk as well as the availability of specific treatment emphasize the importance of timely and correct diagnosis. Primary hyperaldosteronism, representing one tenth of hypertensive patients, is an under-diagnosed disease partly because of difficult diagnostic steps and absence of standard criteria. Recently, the description of somatic mutations in KCNJ5 gene in Conn adenomas had precipitated a resurgence of research activity to understand the pathophysiology of this common disease. Research had confirmed the role of these mutations in aldosterone hypersecretion; however, its role in adenoma formation is still to be elucidated. Elsewhere, much remains to be done in order to understand the pathogenesis of bilateral idiopathic hyperaldosteronism, the other common subtype of primary hyperaldosteronism. In pheochromocytoma, the revolution of genetics has led to major advances in the characterization of this rare disease. It is now clear that up to 50 % of patients with pheochromocytoma have a genetic abnormality and that different pheochromocytomas segregate into two clusters with distinct genotypes, signal transduction pathways and expression of biomarkers (phenotype). This continuing progress has huge effects on patient's management and follow-up. In this article we will shed light on the recent developments in both diseases with emphasis on their role in patient care.

p53 and P-glycoprotein expression do not correlate with survival in nonsmall cell lung cancer: a long-term study and literature review.

This long-term study includes up to 13 years of follow-up on 56 patients who underwent surgical resection of nonsmall cell lung cancers (NSCLC) at the University of Texas Medical Branch. The purpose of this study was to investigate whether p53 and P-glycoprotein expression in the tumor correlates with survival. The study included 35 men and 21 women with mean age at diagnosis of 63.6 years and 58.0 years, respectively. Follow-up ranged from four to 156 months (mean, 52 mo). Actual five-year survival was 50% and 10-year survival was 22%. There were 25 patients who survived more than 60 months. Commercially available antibodies, DO-7 monoclonal antibody to p53 protein, and NCL-PGLyp polyclonal antibody to P-glycoprotein were used. p53 expression was seen in 45%, and P-glycoprotein expression was seen in 61% of the tumors, using standard immunohistochemical techniques. Expression of p53 showed correlation with Caucasian race and a better, although nonsignificant, five-year survival. P-glycoprotein expression showed a highly significant association with squamous cell carcinoma. No association was found between P-glycoprotein expression and survival. A negative association was seen between p53 and P-glycoprotein expression. Using nonparametric analysis, significant correlations were found between female sex and younger age at diagnosis of lung cancer compared with males, adenocarcinoma, and Caucasian race. Using Kaplan-Meier survival tables, significantly better five-year survival was seen with stage I tumors, negative lymph nodes at surgery, Caucasian race, and well-differentiated tumors. Stage I and negative lymph nodes at surgery showed an independent significant association with long-term (>5-yr) survival. This study indicates that p53 and P-glycoprotein may not be useful as immunohistochemical markers for guiding therapy and predicting survival in NSCLC.

Oncogenicity of AKR mink cell focus-inducing murine leukemia virus correlates with induction of chronic phosphatidylinositol signal transduction.

Naturally occurring recombinant murine leukemia viruses (MuLVs), termed mink cell focus-inducing (MCF) viruses, are the proximal leukemogens in spontaneous thymic lymphomas of AKR mice. The mechanism by which these viruses transform lymphocytes is not clear. Previous studies have implicated either integrational activation of proto-oncogenes, chronic autocrine immune stimulation, and/or autocrine stimulation of growth factor receptors (e.g., interleukin 2 receptors) via binding of the viral env glycoprotein (gp70) to these receptors. Any one of these events could also involve activation of second messenger signaling pathways in the cell. We examined whether infection with oncogenic AKR-247 MCF MuLV induced transmembrane signaling cascades in thymocytes of AKR mice. Cyclic AMP levels were not changed, but there was enhanced turnover of phosphatidylinositol phosphates, with concomitant increases in diacyglycerol and inositol 1,4,5-triphosphate. Thus, phospholipase C activity was increased. Protein kinase C activity was also elevated in comparison to that in uninfected thymocytes. The above events occurred in parallel with MCF expression in the thymus and were chronically maintained thereafter. No changes in phospholipid turnover occurred in an organ which did not replicate the MCF virus (spleen) or in thymocytes of AKR mice infected with a thymotropic, nononcogenic MCF virus (AKV-1-C36). Therefore, only the oncogenic MCF virus induced phosphatidylinositol signal transduction. Flow cytometric comparison of cell surface gp70 revealed that AKR-247 MCF virus-infected thymocytes expressed more MCF virus gp70 than did thymocytes from AKV-1-C36 MCF virus-infected mice, suggesting that certain threshold quantities of MCF virus env glycoproteins may be involved in this signaling. This type of signal transduction is not induced by stimulation of the interleukin 2 receptor but is involved in certain oncogene systems (e.g., ras and fms). Its chronic induction by oncogenic MCF MuLV may thus initiate thymocyte transformation.