Antimicrobial use and microbiological testing in district general hospital ICUs of the Veneto region of north-east Italy.

International - predominantly American - studies undertaken in the ICUs of teaching centres show that inadequate antibiotic therapy increases mortality and length of stay. We sought to ascertain whether this also pertains to smaller ICUs in the Veneto region of north-east Italy. To the best of our knowledge, this is the first such survey in the Veneto area or in Italy as a whole. A retrospective, observational study was performed across five general-hospital ICUs to examine appropriateness of microbiological sampling, empirical antibiotic adequacy, and outcomes. Among 911 patients (mean age, 65.8 years ± 16.2 SD; median ICU stay, 17.0 days [IQR, 8.0-29.0]), 757 (83.1 %) were given empirical antibiotics. Treatment adequacy could be fully assessed in only 212 patients (28.0 %), who received empirical treatment and who had a relevant clinical sample collected at the initiation of this antibiotic (T0). Many other patients only had delayed microbiological investigation of their infections between day 1 and day 10 of therapy. Mortality was significantly higher among the 34.9 % of patients receiving inadequate treatment (48.6 % vs 18.80 %; p < 0.001). Only 32.5 % of combination regimens comprised a broad-spectrum Gram-negative ß-lactam plus an anti-MRSA agent, and many combinations were irrational. Inadequate treatment was frequent and was strongly associated with mortality; moreover, there was delayed microbiological investigation of many infections, precluding appropriate treatment modification and de-escalation. Improvements in these aspects and in antibiotic stewardship are being sought.

III Italian Consensus Conference on Malignant Mesothelioma of the Pleura. Epidemiology, Public Health and Occupational Medicine related issues.

The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up-to-date methodology; 4) Necroscopy should be practiced for validation. Expert referral centres could contribute to the definition of uncertain cases. Health surveillance should aim to all asbestos effects. No diagnostic test is recommended for MM screening. Health surveillance should provide information on risks, medical perspective, and smoking cessation. The economic burden associated to MM was estimated in 250,000 Euro per case.

Twelve-month azathioprine as maintenance therapy in early diffuse systemic sclerosis patients treated for 1-year with low dose cyclophosphamide pulse therapy.

OBJECTIVE: To investigate the role of azathioprine in maintaining improvement after 1-year low-dose IV pulse CYC therapy in patients with early diffuse Systemic Sclerosis (dcSSc). METHODS: Thirteen patients with early dcSSc who had completed a year of treatment with low-dose IV pulse CYC underwent AZA treatment (100 mg/day) in a prospective 1-year study. Modified Rodnan skin score (mRss), Health Assessment Questionnaire-Disability Index (HAQ-DI), forced vital capacity (FVC), and diffusing lung capacity for CO (DLCO) were assessed as outcome measures. In addition, the nine organ/system Medsger et al. severity scores and the European Scleroderma Study Group (ESSG) activity index were evaluated. RESULTS: The improvement from a year of CYC therapy was maintained by AZA treatment. No outcome measures deteriorated (mRss 8.23 +/- 2.9 vs. 6.38 +/- 3.4; HAQ-DI 0.38 +/- 0.4 vs. 0.32 +/- 0.3; FVC 89.5 +/- 13.2 vs. 89.4 +/- 15.9; DLCO 73.6 +/- 14.4 vs. 75.0 +/- 19.5), nor were there any increases in any organ/system severity scores or ESSG activity index detected. CONCLUSION: This study suggests a role of AZA in maintaining the improvement induced by low dose pulse CYC in early dcSSc, making it possible a short duration of treatment at a low cumulative dose of the drug. These results, however, await confirmation in controlled studies.

[Activity of the Campania Register of Mesothelioma from July 2003 to October 2007]. / Attività del Registro Mesoteliomi della Campania dal luglio 2003 all'ottobre 2007.

Campania Mesothelioma Register was established in 2002; its purpose is to record every case of malignant mesothelioma that occurs in the registered population of Campania. Its aim is to identify new dangerous asbestos sources, by giving patients a questionnaire about their working and living habits. The questionnaire used is by National Mesothelioma Register (ReNaM). Analyzing carefully the answers to the questionnaire, it is possible to classify patients' exposure with a code given by ReNaM. By means of a recognition identification network, COR Campania identified 492 cases of malignant mesothelioma (pleura, pericardium, peritoneum and tunica vaginalis of the testis) diagnosed between 1996-2007. The analysis of the ReNaM questionnaire confirms a prevalence of professional exposures (71%), however unknown exposures (15%) also play an important role. The economic sector that determined the greatest number of professional exposures are Construction (17.5%), Industrial Metalwork (13.13%), Railway Car (9.3%), Vehicle production and maintenance (8.16%), Ship building (7.5%).

[Case studies on the malignant mesothelioma in Pellezzano (SA)]. / Casistica di mesotelioma maligno nel comune di Pellezzano (SA).

41 malignant mesothelioma cases were reported between January 2000 and April 2007 in the province of Salerno. The small town of Pellezzano, near Salerno, has more cases than any other urban centre in the province; five mesothelioma cases (three male and two female) in Pellezzano (population 9,171 in 1991) means a standardized incidence rate of 32.7 males and 21.8 females per 100.000 inhabitants. That's very alarming, considering that in Italy mesothelioma standardized incidence rate per 100.000 inhabitants is 2,98 for males and 0,98 for females. Campania Mesothelioma Register aims to investigate which kind of exposure caused this abnormal incidence rate. All five patients answered the questionnaire and a team of doctors performed an on-the-spot investigation. The studies verified the existence of two kind of asbestos exposure, professional (Cotton Manufacture, Construction, Foundry) and environmental (cement-asbestos pre-fabricated since 1980 earthquake), that have to be analyzed further.

[Biaggi law, transformation of the labor market, protection of health at the workplace]. / Legge Biagi, trasformazione del mercato del lavoro, tutela della salute nei luoghi di lavoro.

The new legislation on the labor market (Biagi Law, Ministerial Decree approved by the Council of Ministers on 06.06.2003) introduces new contractual profiles imprinted to the criterion of maximum mobility and flexibility. This new legislation does not appear equipped from a parallel legislation that guarantees occupational safety and the protection of the new professional figures.

[Distribution of the incidence of pleural malignant tumors in Campania in the period 1988-1999 and 1995-1997]. / Distribuzione della incidenza dei tumori maligni della pleura in campania nei periodi 1988-1994 e 1995-1997.

From the comparative appraisal, an area is identified for the period 1995-1997, corresponding to the so-called inner zones, in which the "ex novo" emersion of consisting cluster of mesotheliomas is recorded. Such data are analyzed for a possible correlation with professional and/or extra professional causes.

[Respiratory function in a group of railway car repair workers]. / Funzionalità ventilatoria in un gruppo di addetti alla riparazione di carrozze ferroviarie.

A study was performed on respiratory function in 875 railways workers employed in an Italian Railways repair workshop, formerly exposed to asbestos. Workers were interviewed on personal and occupational histories and personal habits. They underwent physical examination and spirometry. Analysis of covariance was performed for FVC, FEV1/FVC, and FEF25-75%. FEV1/FVC and FEF25-75% were reduced in the most heavily exposed group. No reduction in the FVC corrected mean value was found in the exposed workers but an interaction between age and smoking was observed in the most exposed group.

[Mortality due to causes correlatable to asbestos in a cohort of workers in railway car construction]. / La mortalità per cause correlabili all'amianto in una coorte di addetti alla costruzione di carrozze ferroviarie.

A study was made of the mortality experience of a cohort of railway carriage construction workers with the aim of detecting asbestos-induced disease. The cohort included 1534 men who were active as at 01.01.1970 and/or hired up to 30.06.89. Vital status was ascertained for 97.7% of the cohort. The mortality experience of the cohort was compared with that of the population of the Campania Region. Altogether, 194 deaths were observed (SMR: 0.88). Significant mortality deficits were associated with circulatory causes (SMR: 0.64, 58 observed), non-malignant respiratory causes (SMR: 0.59, 12 observed), and accidents (SMR: 0.39, 5 observed). A significant increase in mortality from all neoplasms was detected (SMR: 1.25, 69 observed), mainly due to an excess of lung cancer (SMR: 1.45, 28 observed), pleural cancer (SMR: 4.72, 3 observed), and peritoneal cancer (SMR: 7.47, 2 observed). The excess of mortality from respiratory neoplasms mainly affected subjects who had started employment more than 20 years previously.

3-O-Methylfunicone, a metabolite produced by Penicillium pinophilum, modulates ERK1/2 activity, affecting cell motility of human mesothelioma cells.

OBJECTIVES: 3-O-methylfunicone (OMF), a secondary metabolite produced by Penicillium pinophilum, affects cell proliferation and motility in a variety of human solid tumours. The aim of this study was to demonstrate whether OMF has the ability to arrest cell division and motility, in a human mesothelioma cell line. Malignant mesothelioma is an aggressive cancer that does not respond to standard therapies the cells of which are considered to be highly resistant to apoptosis. MATERIAL AND METHODS: Cell motility and invasion were measured using a modified Boyden chamber. Gene expression was examined by RT-PCR, while ERK1/2 was investigated by Western blot analysis. All experiments were also performed on primary cultures of mesothelial cells. RESULTS: The present study shows that OMF inhibited motility of the NCI mesothelioma cell line by modulating ERK signalling activity, and affected alphaVbeta5 integrin and MMP-2 expression, inducing marked downregulation at both mRNA and protein levels. Substantial downregulation of VEGF gene expression was also demonstrated. These effects were not observed in normal mesothelial cell cultures. CONCLUSION: OMF may have potential as a naturally derived anti-tumour drug for treatment of mesothelioma.

Low-dose intravenous cyclophosphamide in systemic sclerosis: an open prospective efficacy study in patients with early diffuse disease.

OBJECTIVE: To investigate the efficacy of a treatment with low-dose intravenous cyclophosphamide (CYC) and low-dose prednisone in early diffuse cutaneous systemic sclerosis (dcSSc). METHODS: Patients with dcSSc and a disease duration <24 months consecutively admitted to a tertiary centre underwent a prospective 1-year study. They were treated with i.v. CYC 500 mg/pulses, 10 mg prednisone equivalent, and supportive therapy. Modified Rodnan skin score (mRss), Health Assessment Questionnaire-Disability Index (HAQ-DI), forced vital capacity (FVC), and diffusing lung capacity for CO (DLCO) were assessed as outcome measures. In addition, the nine Medsger severity scale scores were evaluated. RESULTS: mRss and DLCO significantly improved at both 6 (p = 0.002 and 0.012, respectively) and 12 months (p = 0.002 and 0.003, respectively). HAQ-DI showed a nearly significant reduction at 12 months (p = 0.06). Medsger's severity scores also improved for general condition (p = 0.001), peripheral vascular (p = 0.05), skin (p = 0.02), joint/tendon (p = 0.001), muscle (p = 0.05), and lung (p = 0.02). No treatment interruption was needed. CONCLUSIONS: This preliminary study suggests a role for low-dose i.v. CYC in the treatment of early dcSSc. Controlled studies are warranted.

Quantitative analysis of an idiotypic determinant of light chains of normal human IgG and IgM.

Normal light chains of human IgG and IgM were analyzed for the presence of the idiotypic determinant of light chains identified by anti-"a". A quantitative evaluation indicated that this marker of the variable region was present in light chains obtained from IgG and IgM; however, light chains reacting with anti-"a" were preferentially associated with IgG molecules.

A one-generation cluster of malignant mesothelioma within a family reveals exposure to asbestos-contaminated jute bags in Naples, Italy.

Substantial evidence supports the role of asbestos in malignant mesothelioma. Clustering for this malignancy among relatives not only suggests genetic susceptibility as a relevant component but also provides a clue to investigate non-occupational sources of exposure. We identified five cases of malignant mesothelioma within one family with exposure to asbestos experienced during childhood, as 'next door' residents of a workshop recycling asbestos-contaminated jute sacks in Naples, Italy. This cluster discloses the health risk in the reuse of bags that previously had contained asbestos. Furthermore, it emphasizes the role of asbestos in the genetic-environmental interaction issue of malignant mesothelioma.

[The home risk added to industrial work]. / Rischio domestico aggiunto al lavoro industriale.

The research carried on 50 women and 50 men working in an electronic industry gives following results: a) housekeeping work represents a significant risk area in addition to industrial extra domestic work; b) domestic work load affects more women (100%) than men (58%); c) this condition gets worse by poor family cooperation and by almost complete absence of public welfare centres; d) household risk, as mentioned above, is an important element of women social disparity to approach and to make industrial work.