M. Varricchio

Prognostic importance of insulin-mediated glucose uptake in aged patients with congestive heart failure secondary to mitral and/or aortic valve disease

Previous studies have demonstrated that insulin resistance is a common feature of congestive heart failure (CHF), but the clinical significance of such insulin resistance is still debated. We tested the hypothesis that insulin-mediated glucose uptake (IMGU) is a prognostic factor in CHF in aged patients. For this purpose 174 aged patients with CHF participated in a cross-sectional and a longitudinal study of 24 months duration. In this latter study survival analysis was calculated comparing subjects at the first and second tertile of IMGU with those at third tertile. All subjects underwent anthropometric (body mass index, waist/hip ratio), cardiovascular (arterial blood pressure, 24-hour Holter monitoring, peak VO2, left ventricular ejection fraction, echocardiography), and metabolic (determination of fasting plasma glucose, insulin, catecholamine, free fatty acids, tumor necrosis factor-alpha concentrations, and assessment of IMGU by euglycemic hyperinsulinemic glucose clamp) investigations. In the cross-sectional study, IMGU correlated with age (r = -0.33, p <0.001), body mass index (r = -0.46 p <0.001), ventricular premature complexes (r = -0.78, p <0.001), left ventricular ejection fraction (r = -0.15, p <0.05), fasting plasma norepinephrine (r = -0.75, p <0.001), tumor necrosis factor-alpha (r = -0.45, p <0.001), free fatty acids (r = -0.54, p <0.001), and peak VO2 (r = 0.67, p <0.001). In the longitudinal study patients at the first and second tertile of IMGU had a lower probability of survival than patients at the third tertile (p <0.03). Cox regression analysis showed IMGU to be a prognostic factor independent of fasting plasma norepinephrine, tumor necrosis factor-alpha, free fatty acid concentration, New York Heart Association class, peak VO2, and left ventricle ejection fraction (relative risk 1.1, 95% confidence intervals 1.0 to 2.1). In conclusion, our study demonstrates that insulin resistance is a common feature of CHF most likely due to elevated plasma norepinephrine and tumor necrosis factor-alpha concentrations, and that IMGU is an independent prognostic factor in CHF.

Metabolic aspects of the extreme longevity

Starting from young to very old subjects, aging is associated with a progressive remodeling. Such an age-dependent remodeling process mainly affects anthropometrics, endocrine and thus, also metabolic factors. Interestingly, it occurs in some individuals successfully, while in others unsuccessfully. Centenarians in good health conditions are a very selected group of subjects representing an exceptional condition. Why the centenarians reach the extreme human life span is still unknown. Thus, in this article we will review the best known causes of age-related insulin resistance, outline the main metabolic differences between aged subjects and healthy centenarians, underline the clinical relevance of insulin resistance in the elderly and finally, we will try to propose a unifying hypothesis for explaining the development of insulin resistance with aging.

Neurotoxicity induced by Cefepime in a very old hemodialysis patient

Neurotoxicity is an unusual complication of cephalosporin therapy. Only few cases of neurotoxicity induced by Cefepime have been described and probably the frequency of Cefepime-induced status epilepticus is underestimated. We report a case of an 82 year-old male, ESRD patient on chronic hemodialysis program affected by pneumonia, who received a treatment with intravenous Cefepime (1 g/day) and developed a seizure 4 days after the starting antibiotic therapy. Cefepime-induced neurotoxicity was suspected and its administration was immediately discontinued. In order to increase Cefepime clearance a hemodialysis session was urgently started and an improvement of his conscious level was observed. On the following day, after a second hemodialysis session his clinical condition and the status of neurotoxicity were completely recovered. The patient was discharged from the hospital in stable clinical condition one week later. At variance with the cases previously reported, the daily dose of Cefepime administrated to our patient was 50% lower and respected drug prescription dosage. Thus, we speculate on the hypothesis that advanced age of our patient and metabolic encephalopathy induced by chronic uremia made him more sensitive to the neurotoxicity induced by the drug. In conclusion, our case suggests that, in very old patients on long-term hemodialysis, it should be considered, to avoid neurotoxicity, to monitor the clinical neurological status, to use Cefepime at lower dosage than that allowed in patients with severe renal impairment (1 g/day) and, when possible, to evaluate Cefepime plasma levels. However, in these patients, other agents of the same class should be considered such as Cefotaxime and Ceftriaxone which are characterized by both an hepatic and renal excretion. In alternative to cephalosporins, antibiotics with the same action spectrum in the absence of neurological toxicity (i.e. Meropenem) should be recommended.

Screening of depressive symptoms in young-old hemodialysis patients: Relationship between beck depression inventory and 15-item geriatric depression scale

Aims: We studied the relationship between the Beck Depression Inventory (BDI) and the 15-item Geriatric Depression Scale (GDS-15) in young–old hemodialysis and hospitalized patients in order to evaluate the possible usefulness of GDS-15 in hemodialysis patients. Methods: Thirty-one hospitalized and 31 young–old hemodialysis patients aged 65–74 (young–old) were enrolled in the study. Comprehensive geriatric assessment (Mini Mental State Examination (MMSE), BDI, GDS-15, Cumulative Illness Rating Scale (CIRS) and Activities of Daily Living (ADL)) was made for all patients. The internal consistency between BDI and GDS-15 was evaluated with Cronbach’s α coefficient. Sensitivity, specificity and receiver operating characteristic (ROC) curves for GDS-15 were determined using BDI as the standard. Results: In the hospitalized group, the prevalence of depressive symptoms, as evaluated by BDI (≧14) and GDS-15 (≧6), were 29 and 32%, respectively. In the hemodialysis group, the prevalence of depressive symptoms, as evaluated by BDI and GDS-15, were 61 and 58%, respectively. A significantly positive correlation between the BDI and GDS-15 was found in hospitalized (r = 0.808; p < 0.001), hemodialysis (r = 0.692; p < 0.001) and both patient groups together (r = 0.777; p < 0.001). The area under the ROC curve was 0.99 in the hospitalized and 0.95 in the hemodialysis groups. The ROC curves indicate a best effectiveness cutoff point (balancing sensitivity and specificity) of ≧6 for GDS-15 compared to BDI. Conclusions: The GDS-15 could be a useful instrument for evaluating depressive symptoms in young–old hemodialysis patients.

The oncological therapy in the elderly.

The rising incidence of cancer in old subjects yields great scientific interest. Cancer itself has different features in the elderly. Thus the choice of therapy must follow a wide investigation on the performance status through acknowledgements on psychological and social factors, too. The therapeutic strategy is not usually different from the one used in other sections of life, but it is important to remember that an aged patient with cancer has to be submitted to a multidimensional evaluation using specific tools, that consider not only the neoplastic pathology but also the functional consequences. Always respecting quality of life and the eventual side effects, the choice of less aggressive strategies is especially important in those patients presenting a reduced expectancy of life. The improvement of surgery and anesthesiological techniques, the use of high-energy radiotherapy, the use of hemopoietic growing factors, antiemetics of last generation and a suitable support therapy give the medical specialist the chance to choose the adequate therapeutic strategy. This is a short review of the main guide-lines to be taken into consideration in the assessment and management of elderly patients with cancer.

The therapy of aged diabetic hypertensives

The great prevalence and incidence of non-insulin dependent diabetes mellitus (NIDDM) and hypertension in the elderly represent several therapeutic problems. Due to aged-related changes in glucose handling and cardiovascular functions which occur with advancing age, it is necessary to treat aged diabetic hypertensive patients with drugs lowering arterial blood pressure but without side effects on glucose metabolism. Non-pharmacological and pharmacological protocols can be taken into account. With regard to the non-pharmacological therapy, a decline in body fatness, an increase in body fitness and an appropriate dietary assumption of sodium, potassium, calcium and magnesium are the most important approach. As far as the therapeutic approach, calcium channel blockers and angiotensin converting enzyme (ACE)-inhibitors seem to be particularly useful in the treatment of aged diabetic hypertensive patients. Calcium channel blockers have no effects on glucose tolerance while they are very effective on heart beating and arterial blood pressure. ACE-inhibitors lowers arterial blood pressure, delay the progression of diabetic nephropathy to the renal failure and, have null or beneficial effects on glucose handling. In conclusion, in aged diabetic hypertensive patients non-pharmacological therapy should be combined to administration of calcium channel blockers and ACE-inhibitors.