Identification of a geographic area characterized by extreme longevity in the Sardinia island: the AKEA study

High prevalence and low female/male ratio for validated centenarians are observed in Sardinia and these findings appear to be thus far unique to this island. Moreover a specific region on the island is characterized by exceptional male longevity. We calculated the extreme longevity index (ELI), defined as the percentage of persons born in Sardinia between 1880 and 1900, who became centenarians. A gaussian smoothing method was used in order to identify the so-called 'Blue Zone', where longevity is concentrated in the central-eastern part of the island and covers all the mountainous areas of central Sardinia. The estimated life expectancy in the 'Blue Zone' is longer than in the remaining territory of the island especially for men and the male to female ratio among centenarians born in this area is 1.35 compared to 2.43 in the rest of Sardinia. The specific mechanism by which persons living in this territory were more likely to reach extreme longevity remains unknown but it is interesting to note that most of the 'longevity hot spots' identified in various regions of the world over the years have been located in mountainous geographical areas even if none of these longevity regions have been fully validated. An alternative and interesting hypothesis is that the high rate of inbreeding determined by frequent marriages between consanguineous individuals and low immigration rates have progressively decreased the variability of the genetic pool and facilitated the emergence of genetic characteristics that protect individuals from diseases that are major causes of mortality particularly in older individuals. Given the exceptionally high prevalence of male centenarians in the 'Blue Zone', it is reasonable to assume that either the environmental characteristics or the genetic factors, or both, exert their favorable effect more strongly in men than in women. Thus, the mechanism involved may be modulated by the hormonal milieu, or may be associated with genes located in the sex chromosomes.     

Blood pressure components in clinical hypertension

This review offers a critical evaluation of the remarkable progress in antihypertensive therapy since its inception. Despite the introduction of newer, more sophisticated drugs, treatment results have remained stable. Problems impeding further improvement include limited patient compliance, clinical inertia, incomplete adherence to guidelines, and dependence on brachial artery cuff pressures for diagnosis, risk assessment, and treatment response. Brachial artery systolic and pulse pressures do not reliably represent aortic or carotid artery pressures, which are better risk predictors for the heart and brain. Mean pressure, which is the same throughout the arterial tree, is directly measurable by cuff oscillometry, and might become the best single risk predictor. Available drugs have limited ability to decrease the aortic stiffness that is responsible for the elevated systolic blood pressure of aging. Therefore, to improve risk assessment and therapeutic benefit, we might include mean blood pressure and pulse pressure into blood pressure measurements, pursue efforts to measure central blood pressure, and search for new drugs to reduce arterial stiffness.     

Imaging in Lymphoma: The Key Role of Fluorodeoxyglucose‐Positron Emission Tomography

This review focuses on the impact of new imaging guidelines for fluorodeoxyglucose-positron emission tomography (FDG-PET) on clinical practice and the future directions of lymphoma imaging.Fluorodeoxyglucose-positron emission tomography (FDG-PET) has progressively changed lymphoma management over the past decade, and new imaging guidelines integrating FDG-PET for staging and response evaluation in lymphoma have been recently published [1, 2]. The present review focuses on the impact of these guidelines on clinical practice and the future directions of lymphoma imaging. In lymphoma, we are now facing a therapeutic dilemma, which explains why FDG-PET has gained wide acceptance. New treatments have improved the outcomes in the most common types of lymphoma; however, the classic prognostic factors fail to select the small percentage of patients with a high risk of relapse and treatment failure [3, 4]. In contrast, patients are also at risk of serious treatment-related morbidity and mortality; thus, overtreatment should be avoided in those patients who respond well to therapy. For these reasons, we need new prognostic and predictive factors, a precise determination of the initial disease extent, and an accurate and early assessment of the responsiveness to therapy. The objective is now to personalize treatment to improve cure rates in patients with adverse risk factors and to reduce toxicity in other patients without risking undertreatment or disease, respectively. Imaging using FDG-PET can satisfy many of these requirements. A case report of a patient with diffuse large B-cell lymphoma illustrates a typical use and value of FDG-PET in lymphoma management (Fig. 1).Open in a separate windowFigure 1.Case report: 60-year-old woman with a bulky mediastinal tumor. Eastern Cooperative Oncology Group classification, 1; age-adjusted international prognostic index, 2; lactate dehydrogenase greater than normal. Induction: rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone, with a 14-day schedule (six cycles). Positron emission tomography (PET) performed at baseline (PET0, top); after 2 cycles (PET2, middle), and after 4 cycles (PET4, bottom). PET corrected by attenuation, computed tomography (CT), and PET-CT-fused images are displayed for PET0, PET2, and PET4. PET2 showed a partial metabolic response (score 4, residual uptake in the mediastinal mass moderately increased compared with that of the liver). PET4 showed a complete metabolic response (score 2, some foci of residual uptake slightly increased compared with the mediastinal uptake). Consolidation therapy was autologous stem cell transplantation based on PET2 positivity in the context of a trial [34]. The patient was free of progression after 4 years.     

The increasing roles of epigenetics in breast cancer: Implications for pathogenicity,biomarkers, prevention and treatment

Nowadays, the mechanisms governing the occurrence of cancer are thought to be the consequence not only of genetic defects but also of epigenetic modifications. Therefore, epigenetic has become a very attractive and increasingly investigated field of research in order to find new ways of prevention and treatment of neoplasia, and this is particularly the case for breast cancer (BC). Thus, this review will first develop the main known epigenetic modifications that can occur in cancer and then expose the future role that control of epigenetic modifications might play in prevention, prognostication, follow‐up and treatment of BC. Indeed, epigenetic biomarkers found in peripheral blood might become new tools to detect BC, to define its prognostic and to predict its outcome, whereas epi‐drugs might have an increasing potential of development in the next future. However, if DNA methyltransferase inhibitors and histone desacetylase inhibitors have shown encouraging results in BC, their action remains nonspecific. Thus, additional clinical studies are needed to evaluate more precisely the effects of these molecules, even if they have provided encouraging results in cotreatment and combined therapies. This review will also deal with the potential of RNA interference (RNAi) as epi‐drugs. Finally, we will focus on the potential prevention of BC through epigenetic based on diet and we will particularly develop the possible place of isothiocyanates from cruciferous vegetables or of Genistein from soybean in a dietary program that might potentially reduce the risk of BC in large populations.     

Cause of death in older patients with anatomo-pathological evidence of chronic bronchitis or emphysema: a case-control study based on autopsy findings

OBJECTIVES: To determine the most frequent causes of death of hospitalized older patients based on anatomo-pathological evidence and to compare the relative frequency of fatal events between patients with and without evidence of either chronic bronchitis (CB) or emphysema (E). DESIGN: Retrospective, case-control study based on a computerized database including anatomo-pathological data of patients deceased and autopsied over a 25-year period. SETTING: Two geriatric hospitals in Geneva. PARTICIPANTS: Not applicable. MEASUREMENTS: Autopsy records for cause(s) of death in patients with CB or E. RESULTS: 3,685 patients deceased in our institution (1,540 men; 2,145 women) were autopsied between 1972 and 1996; mean age at death was 81.5 +/- 8.0 years. Anatomo-pathological evidence of CB or E was found in 983 patients (26.6% of total); 262 (7.2%) had predominantly CB, and 456 (12.3%) predominantly E. Pneumonia was the most frequent cause of death in all patients (21.8%). Myocardial infarction (MI) (17.6% vs 14%), and respiratory failure (5.1% vs 1.5%) occurred more frequently in subjects with CB and/or E than in controls. Fatal pulmonary embolism (PE) was more frequent in patients with E (18.4%) than in patients with CB (10.7%; odds ratio ( OR) = 1.89, P =.008), or in controls (12.7%; OR = 1.56, P =.0008). CONCLUSION: Anatomo-pathological evidence of CB or E is highly prevalent in older patients, suggesting that CB and E are clinically underdiagnosed in this age group. Fatal MI occurred significantly more frequently in older patients with E or CB than in controls. Furthermore, patients with E were at significantly higher risk of fatal PE than patients with CB or controls.     

Childhood acute lymphoblastic leukaemia and indicators of early immune stimulation: the Estelle study (SFCE)

Background:

Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL).

Methods:

The national registry-based case–control study, ESTELLE, was carried out in France in 2010–2011. Population controls were frequency matched with cases on age and gender. The participation rates were 93% for cases and 86% for controls. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, gender, and potential confounders.

Results:

In all, 617 ALL and 1225 controls aged ⩾1 year were included. Inverse associations between ALL and early common infections (OR=0.8, 95% confidence interval (CI): 0.6, 1.0), non-first born (⩾3 vs 1; OR=0.7, 95% CI: 0.5, 1.0), attendance of a day-care centre before age 1 year (OR=0.7, 95% CI: 0.5, 1.0), breastfeeding (OR=0.8, 95% CI: 0.7, 1.0), and regular contact with pets (OR=0.8, 95% CI: 0.7, 1.0) in infancy were observed.

Conclusions:

The results support the hypothesis that conditions promoting the maturation of the immune system in infancy have a protective role with respect to ALL.