Rosalba Rosato

Nonopioid placebo analgesia is mediated by CB1 cannabinoid receptors

Placebo analgesia is mediated by both opioid and nonopioid mechanisms, but so far nothing is known about the nonopioid component. Here we show that the specific CB1 cannabinoid receptor antagonist 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (rimonabant or SR141716) blocks nonopioid placebo analgesic responses but has no effect on opioid placebo responses. These findings suggest that the endocannabinoid system has a pivotal role in placebo analgesia in some circumstances when the opioid system is not involved.

Survival of peritoneal malignant mesothelioma in Italy: a population-based study.

In some population‐based studies, a shorter median survival was observed in peritoneal as compared with pleural, malignant mesothelioma, but in others, longer median survival times or higher proportions of long‐term survivors were reported. Statistical instability could have caused these differences. We analyzed survival in peritoneal mesothelioma in a large and unselected population‐based case series. Cases (338) registered from 1990 to 2001 by 9 Italian regional mesothelioma registries contributing to the network of the National Mesothelioma Registry were followed until December 31, 2005. Univariate (Kaplan‐Meier) and multivariate (Cox proportional hazards regression) analyses of survival were performed according to selected individual characteristics, including limited treatment information in a subset of 194 cases. The results were compared with those obtained in a parallel study on pleural mesothelioma cases. Epithelioid histotype, younger age at diagnosis and, to a lesser degree, gender (women), and being diagnosed in a hospital with a thoracic surgery unit positively and significantly affected survival. The effect of treatment was positive but not statistically significant. No trend in the risk of death according to calendar period of diagnosis was present. Peritoneal mesothelioma cases had shorter median survival time than pleural cases, but a larger proportion of long‐term survivors. Survival patterns after peritoneal and pleural mesothelioma differed markedly. Treatment was not associated with a statistically significant improvement in survival, but our study included cases first diagnosed before the introduction of the most recent therapeutic approaches. This provides a large historical comparison for future studies on survival trends at the population level.

High-dose sequential chemotherapy and peripheral blood progenitor cell autografting in patients with refractory and/or recurrent Hodgkin lymphoma: a multicenter study of the intergruppo Italiano Linfomi showing prolonged disease free survival in patients treated at first recurrence.

The objective of the current study was to evaluate in a multicenter setting the feasibility and efficacy of a high‐dose sequential (HDS) chemotherapy regimen that combined intensive debulking and high‐dose therapy (HDT) with peripheral blood progenitor cell (PBPC) autografting in patients with refractory or recurrent Hodgkin lymphoma (HL).

Cancer mortality reduction and metformin: a retrospective cohort study in type 2 diabetic patients.

Aims: Few studies suggest that metformin decreases cancer mortality in type‐2 diabetic patients (T2DP). We explored the association between the type and duration of antidiabetic therapies and cancer and other‐than‐cancer mortality in a T2DP cohort, taking into account the competing risks between different causes of death and multiple potential confounding effects. The mortality rates were compared with the general population from the same area.

Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi)

A prospective multicenter program was performed to evaluate the combination of rituximab and high-dose (hd) sequential chemotherapy delivered with multiple autologous peripheral blood progenitor cell (PBPC) support (R-HDS-maps regimen) in previously untreated patients with diffuse large B-cell lymphoma (DLB-CL) and age-adjusted International Prognostic Score (aaIPI) score 2-3. R-HDS-maps includes: (i) three APO courses; (ii) sequential administration of hd-cyclophosphamide (CY), hd-Ara-C, both supplemented with rituximab, hd-etoposide/cisplatin, PBPC harvests, following hd-CY and hd-Ara-C; (iii) hd-mitoxantrone (hd-Mito)/L-Pam + 2 further rituximab doses; (iv) involved-field radiotherapy. PBPC rescue was scheduled following Ara-C, etoposide/cisplatin and Mito/L-Pam. Between 1999 and 2004, 112 consecutive patients aged <65 years (74 score 2, 38 score 3) entered the study protocol. There were five early and two late toxic deaths. Overall 90 patients (80%) reached clinical remission (CR); at a median 48 months follow-up, 87 (78%) patients are alive, 82 (73%) in continuous CR, with 4 year overall survival (OS) and event-free survival (EFS) projections of 76% (CI 68–85%) and 73% (CI 64–81%), respectively. There were no significant differences in OS and EFS between subgroups with Germinal-Center and Activated B-cell phenotype. Thus, life expectancy of younger patients with aaIPI 2-3 DLB-CL is improved with the early administration of rituximab-supplemented intensive chemotherapy compared with the poor outcome following conventional chemotherapy.

Fear of Crime in Italy Spread and Determinants

The aim of this study is to examine the spread and determinants of fear of crime in Italy. A secondary analysis was performed on the 1995 Italian National Statistics Institute data (Italian representative sample: 19,785 participants). In addition, data from official judicial statistics were analyzed. Main results are as follows: (a) fear of crime correlates with crime spread; (b) fear of crime is more widespread than crime itself; (c) the best predictors of fear of crime are urbanization, degradation of residential areas, and residence in Northeastern Italy; (d) criminal victimization exerts a minor influence on fear of crime; and (e) sociodemographic variables under investigation exert little influence on fear of crime. These results are discussed in reference to international literature, and possible subsequent lines of research are suggested.

A high positive predictive value algorithm using hospital administrative data identified incident cancer cases

OBJECTIVE We have developed and validated an algorithm based on Piedmont hospital discharge abstracts for ascertainment of incident cases of breast, colorectal, and lung cancer. STUDY DESIGN AND SETTING The algorithm training and validation sets were based on data from 2000 and 2001, respectively. The validation was carried out at an individual level by linkage of cases identified by the algorithm with cases in the Piedmont Cancer Registry diagnosed in 2001. RESULTS The sensitivity of the algorithm was higher for lung cancer (80.8%) than for breast (76.7%) and colorectal (72.4%) cancers. The positive predictive values were 78.7%, 87.9%, and 92.6% for lung, colorectal, and breast cancer, respectively. The high values for colorectal and breast cancers were due to the models ability to distinguish prevalent from incident cases and to the accuracy of surgery claims for case identification. CONCLUSIONS Given its moderate sensitivity, this algorithm is not intended to replace cancer registration, but it is a valuable tool to investigate other aspects of cancer surveillance. This method provides a valid study base for timely monitoring cancer practice and related outcomes, geographic and temporal variations, and costs.

Telomere length identifies two different prognostic subgroups among VH-unmutated B-cell chronic lymphocytic leukemia patients

Some evidences suggest that telomere restriction fragment length (TRF-L) is an effective indicator of histopathogenesis in B-cell tumors. As histopathogenesis is relevant for B-cell chronic lymphocytic leukemia (B-CLL) prognosis, TRF-L was assessed by Southern blot in 201 patients and compared to variable immunoglobulin heave chain gene mutational status (VH-MS) and to other known prognostic features. Overall survival (OS), time to first treatment (TTFT) and progression-free survival (PFS) were evaluated. Our results indicate the following: (1) TRF-L is heterogeneous among B-CLL patients (median 6014 bp, range 1465–16 762); (2) TRF-L correlates to VH-MS (r2=0.1994, P<0.0001) with VH-mutated patients showing long and VH-unmutated short telomeres; however, 41% of VH-unmutated and 5% of VH-mutated patients did not show this correlation and were thus defined as ‘discordant’; (3) TRF-L effectively predicts outcome in terms of TTFT, PFS and OS; (4) VH-unmutated discordant patients have a better clinical outcome than VH-unmutated concordant patients (OS P<0.01, PFS P<0.05) and similar to that of VH-mutated patients (OS, PFS P=NS). Compared to VH-unmutated concordant patients, VH-unmutated discordant patients showed no peculiarity in their immunoglobulin rearrangement nor in their flow cytometry or fluorescence in situ hybridization profile. In conclusion, TRF-L can be helpful to refine prognostication of B-CLL patients, particularly those with a VH-unmutated immunoglobulin sequence.

Renal damage in patients with Type 2 diabetes: a strong predictor of mortality.

Aims  (i) To compare mortality rates in a cohort of Type 2 diabetic patients with those of the general population; (ii) to assess the prognostic role of pre‐existing chronic conditions; (iii) to evaluate the impact of different severity of renal damage on mortality.

High-normal blood pressure is associated with a cluster of cardiovascular and metabolic risk factors: a population-based study.

Objective A Few population-based studies have shown that high-normal blood pressure clusters with other cardiovascular risk factors. Increased inflammation, endothelial dysfunction, oxidative stress, and reduced adiponectin values have sporadically been reported in these patients. Methods We cross-sectionally compared blood pressure categories with cardiovascular risk factors in an adult population-based cohort (n = 1658) and evaluated the relationships between C-reactive-protein, nitrotyrosine, total antioxidant status, E-selectin, vascular adhesion molecule-1, intercellular adhesion molecule-1, resistin, adiponectin values and blood pressure categories in a subgroup of healthy lean individuals from this cohort (n = 107) in order to exclude the impact of obesity/insulin resistance on these variables. Results Glucose, triglyceride, low-density lipoprotein-cholesterol, alanine aminotranferase, γ-glutamyl transferase values, and diabetes and metabolic syndrome prevalence were significantly higher in high-normal compared with the optimal blood pressure category. In the healthy subgroup, adiponectin (β = −4315.3; 95% confidence interval −5916.4 −2654.2), total antioxidant status (−0.15; −0.3 −0.04) were significantly lower, and nitrotyrosine (1.2; 0.3 2.1), E-selectin (11.7; 1.8 21.6), vascular adhesion molecule-1 (0.3; 0.1 0.5), and intercellular adhesion molecule-1 (0.3; 0.1 0.5) were higher in high-normal compared with the optimal blood pressure category, at multiple regression analyses. Conclusions Individuals with high-normal blood pressure had a higher prevalence of cardiovascular and metabolic risk factors than those with optimal, and, even if healthy, they showed reduced adiponectin values, early signs of endothelial dysfunction, and oxidative stress. Further research is needed to determine whether they will benefit from blood pressure reduction.