Elena Ceccarelli

Evaluation of C-Reactive Protein Measurement for Assessing the Risk and Prognosis in Ischemic Stroke: A Statement for Health Care Professionals From the CRP Pooling Project Members

Background and Purpose— Several studies have shown, in different populations, that modest elevation of plasma C-reactive protein (CRP) in the range seen in apparently healthy individuals is a strong predictor of future vascular events. Elevated plasma CRP concentrations are also associated with an increased risk of cerebrovascular events and an increased risk of fatal and nonfatal cardiovascular events in ischemic stroke patients. These epidemiological and clinical observations suggest that determination of plasma CRP concentrations could be used as an adjunct for risk assessment in primary and secondary prevention of cerebrovascular disease and be of prognostic value. The aim of this review is to summarize the evidence for CRP as an independent predictor of cerebrovascular events in at-risk individuals and ischemic stroke patients and to consider its usefulness in evaluating prognosis after stroke. Summary of Review— CRP fulfils most of the requirements of a new risk and prognostic predictor, but several issues await further confirmation and clarification before this marker can be included in the routine evaluation of stroke patients and subjects at risk for cerebrovascular disease. Potentially important associations have been established between elevated plasma CRP concentrations and increased efficacy of established therapies, particularly lipid-lowering therapy with statins. Conclusion— At present, there is not sufficient evidence to recommend measurement of CRP in the routine evaluation of cerebrovascular disease risk in primary prevention, because there is insufficient evidence as to whether early detection, or intervention based on detection, improves health outcomes, although shared risk of cardiovascular disease indicates this may be of value. In secondary prevention of stroke, elevated CRP adds to existing prognostic markers, but it remains to be established whether specific therapeutic options can be derived from this.

Circulating Sclerostin Levels and Bone Turnover in Type 1 and Type 2 Diabetes

CONTEXT Previous observations showed a condition of low bone turnover and decreased osteoblast activity in both type 1 and 2 diabetes mellitus (DM1 and DM2). Sclerostin is a secreted Wnt antagonist produced by osteocytes that regulates osteoblast activity and thus bone turnover. Its levels increase with age and are regulated by PTH. OBJECTIVES The aim of the present study was to evaluate circulating sclerostin levels in patients with DM1 or DM2 with normal renal function and to analyze its relationship with PTH, 25-hydroxyvitamin D, and bone turnover markers. DESIGN, AND SETTING: This was a cross-sectional study conducted at a clinical research center. PARTICIPANTS Forty DM2 and 43 DM1 patients were studied and compared with a reference control group (n = 83). RESULTS In the overall cohort, sclerostin levels were higher in males than in females and significantly increased with age in both genders. The positive correlation between sclerostin and age was maintained in DM1 but not in DM2 patients. Moreover, sclerostin levels were higher in DM2 than in controls or DM1 patients, and this difference persisted when adjustments were made for age and body mass index. Consistent with previous clinical and experimental observations, sclerostin was negatively associated with PTH in nondiabetic patients (r = -0.30; P < 0.01), independently of age and gender. Conversely, an opposite but nonsignificant trend between PTH and sclerostin was observed in both DM1 (r = 0.26; P = 0.09) and DM2 (r = 0.32; P = 0.07) cohorts. CONCLUSIONS These findings suggest that sclerostin is increased in DM2. Moreover, the transcriptional suppression of sclerostin production by PTH might be impaired in both DM1 and DM2.

Characteristics and Familial Aggregation of Paget's Disease of Bone in Italy

This study examined the characteristics of 147 PDB cases from Italy. Our data showed a reduced clinical severity of PDB with respect to other populations and provided further support of the importance of environmental factors (rural area of residence and animal contact) in the pathogenesis of PDB. Familial aggregation was observed in 15% of cases.

MicroRNA-124a is hyperexpressed in type 2 diabetic human pancreatic islets and negatively regulates insulin secretion

AbstractAimsMicroRNAs are a class of negative regulators of gene expression, which have been shown to be involved in the development of endocrine pancreas and in the regulation of insulin secretion. Since type 2 diabetes (T2D) is characterized by beta cell dysfunction, we aimed at evaluating expression levels of miR-124a and miR-375, both involved in the control of beta cell function, in human pancreatic islets obtained from T2D and from age-matched non-diabetic organ donors.MethodsWe analyzed miR-124a and miR-375 expression by real-time qRT-PCR in human pancreatic islets and evaluated the potential role of miR-124a by overexpressing or silencing such miRNA in MIN6 pseudoislets.ResultsWe identified a major miR-124a hyperexpression in T2D human pancreatic islets with no differential expression of miR-375. Of note, miR-124a overexpression in MIN6 pseudoislets resulted in an impaired glucose-induced insulin secretion. In addition, miR-124a silencing in MIN6 pseudoislets resulted in increased expression of predicted target genes (Mtpn, Foxa2, Flot2, Akt3, Sirt1 and NeuroD1) involved in beta cell function. For Mtpn and Foxa2, we further demonstrated the actual binding of miR-124a to their 3UTR sequences by luciferase assay.ConclusionsWe uncovered a major hyperexpression of miR-124a in T2D islets, whose silencing resulted in increased expression of target genes of major importance for beta cell function and whose overexpression impaired glucose-stimulated insulin secretion, leading to the hypothesis that an altered miR-124a expression may contribute to beta cell dysfunction in type 2 diabetes.

Prognostic role of C-reactive protein in very old patients with acute ischaemic stroke

Background and scope.  Recent literature has demonstrated that inflammation contributes to all phases of atherosclerosis and brain damage caused by stroke. In acute phase of cerebrovascular diseases biochemical markers of inflammation, such as C‐reactive protein (CRP), could represent an indicator of severity of stroke, but few studies have verified this hypothesis, especially in very old patients. The aim of this study was to evaluate the role of CRP on short‐ and long‐term prognosis in 75‐year old and over elderly patients with acute ischaemic stroke.

The relationship between plasma homocysteine levels and bone mineral density in post-menopausal women

BACKGROUND Whether or not mild hyperhomocysteinemia and low serum levels of folates or vitamin B12 are risk factors for osteoporosis in the elderly is controversial. AIMS AND METHODS To investigate whether or not plasma levels of total homocysteine (tHcy) and serum levels of folates and vitamin B12 are associated with bone mineral density (BMD), we carried out a cross-sectional study on 446 post-menopausal women (mean age: 65.1+/-9.4 years), consecutively seen at the Siena Unit (Tuscany region, Central Italy) for BMD evaluation over a two-year period. BMD of the total femur, femoral neck and lumbar spine was detected by dual-energy X-ray absorptiometry. RESULTS The age-adjusted geometric mean of plasma tHcy levels (micromol/L) was 9.96+/-1.29 in women with normal BMD, 11.06+/-1.32 in those with osteopenia and 11.88+/-1.35 in those with osteoporosis (p<0.0001). On multiple linear regression analysis, adjusting for age, body mass index, folates, vitamin B12, creatinine clearance, smoking habit and alcohol intake, tHcy was negatively related to BMD of the total femur [beta estimate for log-homocysteine: -0.050 (95% CI: -0.100 to -0.001, p=0.048; R(2)=0.02)], but not of femoral neck or lumbar spine. There was no significant association between BMD and serum levels of folates and vitamin B12. CONCLUSIONS tHcy is negatively associated with BMD of the total femur. The contribution of tHcy to explain the variance of BMD is small (2% of the total variance) but clinically relevant, considering the high prevalence of osteoporosis among post-menopausal women and the possibility to lower tHcy by vitamin supplementation.

Plasma D-Dimer Levels in Elderly Patients with Suspected Pulmonary Embolism

been shown to be a useful aid in the diagnosis of PE. DD, a degradation product of cross-linked fibrin, has high sensitivity (89‐98.8%) and high

Pulmonary embolism in the elderly: clinical, instrumental and laboratory aspects.

Objective: To focus on diagnostic and therapeutic problems of pulmonary embolism in the elderly. Methods: Retrospective analysis of 5 years of clinical, instrumental, and laboratory data (collected at the time of hospital admission) for patients 65 years and older with pulmonary embolism proven by a high-probability scintigraphic lung scan or necropsy. Sixty-eight patients, 46 females and 22 males, 78.61 ± (SD) 7.71 years old, were enrolled in the study. Results: Dyspnea, chest pain, tachycardia, and tachypnea were the most common symptoms and signs; they were present alone or in combination in all patients. Bed rest over 4 days was found in 65% of the patients and deep vein thrombosis in the leg in 35%. Only 7 patients were on anticoagulant therapy which was likely to reduce the incidence of pulmonary embolism. The mortality was 29.5%. Major bleeding due to anticoagulant therapy was observed in 4.4% of the patients; 1 case was fatal. Sinus tachycardia, ST segment and T wave abnormalities in anterior leads, and incomplete bundle branch block were the most frequent electrocardiographic findings. Chest X-ray was normal in 19.5% of the patients and compatible with pulmonary embolism in 10%. A transthoracic two-dimensional echocardiogram was abnormal in 74% of the cases, with involvement of the right ventricle in the majority of them. Many patients had laboratory parameters within the normal range. The value of the latex agglutination D-dimer assay was less than the cutoff value of 500 µg/l in 16% of the patients. Hypoxemia and a high alveolar-arterial oxygen gradient were the most frequent aspects of the arterial blood gas analysis. Respiratory alkalosis was observed in only one third of the patients. Conclusions: Pulmonary embolism is often underdiagnosed in the elderly. Clinical, instrumental, and laboratory findings are nonspecific. Only acute suspicion can increase the number of diagnoses, reduce the time to diagnosis, and improve the prognosis.

Beyond glycemic control in diabetes mellitus: effects of incretin-based therapies on bone metabolism.

Diabetes mellitus (DM) and osteoporosis (OP) are common disorders with a significant health burden, and an increase in fracture risk has been described both in type 1 (T1DM) and in type 2 (T2DM) diabetes. The pathogenic mechanisms of impaired skeletal strength in diabetes remain to be clarified in details and they are only in part reflected by a variation in bone mineral density. In T2DM, the occurrence of low bone turnover together with a decreased osteoblast activity and compromised bone quality has been shown. Of note, some antidiabetic drugs (e.g., thiazolidinediones, insulin) may deeply affect bone metabolism. In addition, the recently introduced class of incretin-based drugs (i.e., GLP-1 receptor agonists and DPP-4 inhibitors) is expected to exert potentially beneficial effects on bone health, possibly due to a bone anabolic activity of GLP-1, that can be either direct or indirect through the involvement of thyroid C cells. Here we will review the established as well as the putative effects of incretin hormones and of incretin-based drugs on bone metabolism, both in preclinical models and in man, taking into account that such therapeutic strategy may be effective not only to achieve a good glycemic control, but also to improve bone health in diabetic patients.

Length of hospitalization in elderly patients with community-acquired pneumonia

Community-acquired pneumonia (CAP) is a serious social and medical problem in the elderly. Mortality, hospitalization and length of stay increase with age. The aim of this study was to determine the risk factors associated with prolonged hospital stay in elderly patients with CAP. Clinical and laboratory data were collected for 115 community-living patients, 65 years old and over, admitted to the geriatric ward of a University Hospital from 1995 to 1998 because of symptoms and signs of pneumonia confirmed by a pulmonary infiltrate on chest x-ray. We divided the patients into two groups, with length of stay more than 13 days (70 patients, cases), and length of stay less than 13 days (45 patients, controls) according to Diagnosis Related Groups criteria for complicated and uncomplicated pneumonia, respectively. A prolonged hospital stay was associated with a higher fever peak and a higher number of days with fever (p<0.005), greater comorbidity (p<0.001), urinary catheterization and secondary urinary infections (p<0.001), higher erythrocyte sedimentation rate (p<0.001), dehydration (p<0.005), and caloric-proteic malnutrition (p=0.01). In conclusion, knowledge of the risk factors for prolonged hospital stay in elderly patients with CAP may be used to identify high-risk patients, prevent the risks with prophylactic measures, and contain the costs of hospitalization.