Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study‡.

Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age ≤35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks trastuzumab (arm B, short). This study was designed as a non-inferiority trial with disease-free survival (DFS) as primary end point. A DFS hazard ratio (HR) <1.29 was chosen as the non-inferiority margin. Analyses according to the frequentist and Bayesian approach were planned. Secondary end points included 2-year failure rate and cardiac safety. Results: A total of 1254 patients from 82 centers were randomized (arm A, long: n = 627; arm B, short: n = 626). Five-year DFS is 88% in the long and 85% in the short arm. The HR is 1.13 (90% CI 0.89-1.42), with the upper limit of the CI crossing the non-inferiority margin. According to the Bayesian analysis, the probability that the short arm is non-inferior to the long one is 80%. The 5-year overall survival (OS) is 95.2% in the long and 95.0% in the short arm (HR 1.07, 90% CI 0.74-1.56). Cardiac events are significantly lower in the short arm (risk-ratio 0.33, 95% CI 0.22-0.50, P < 0.0001). Conclusions: This study failed to show the non-inferiority of a shorter trastuzumab administration. One-year trastuzumab remains the standard. However, a 9-week administration decreases the risk of severe cardiac toxicity and can be an option for patients with cardiac events during treatment and for those with a low risk of relapse. Trial Registration: EUDRACT number: 2007-004326-25; NCI ClinicalTrials.gov number: NCT00629278.

Hospital hygiene in Italy: the GISIO-SItI survey.

BACKGROUND: In Italy there are no rules concerning the establishment of a hospital hygiene structure in hospitals and other healthcare settings, and the hospital organization plans vary widely. The aim of the survey, carried out by the Italian Study Group of Hospital Hygiene of the Italian Society of Hygiene, Preventive medicine and Public health, was to evaluate the presence in the hospital organization plan of a structure referred to as Hospital hygiene, or including in its denomination the words "hygiene" or "hospital hygiene", the activities carried out, the relation to other areas, like patient safety, the type and quantity of professionals involved, the strengths and the critical aspects. METHODS: A semi-structured questionnaire was administered to Healthcare Trusts representing all Italian Regions through the members of the above Study Group. RESULTS: 35 Trusts, 13 in Northern, 8 in Central, 14 in Southern Italy (including Sicily and Sardinia), completed the questionnaire. In 19 Trusts (54.3%) a structure whose denomination included the words "hospital hygiene" or "hygiene" was present. The activities related to the management of infectious risk were most represented, carried out autonomously or in collaboration, but many other activities were covered. In all hospitals the activities of the Hospital Hygiene Unit inter-linked with those of the clinical risk, with different forms of collaboration. CONCLUSION: This survey, even though on a limited sample, provided a picture of hospital hygiene at a national level, showing a considerable heterogeneity and highlighting critical issues but also strengths. It is essential to share organizational and management models that enhance and promote hospital hygiene, to ensure the appropriateness of healthcare practices offered in a safe and comfortable environment to patients, operators, and visitors.

Thunderstorm-related asthma: what happens and why.

The fifth report issued by the Intergovernmental Panel on Climate Change forecasts that greenhouse gases will increase the global temperature as well as the frequency of extreme weather phenomena. An increasing body of evidence shows the occurrence of severe asthma epidemics during thunderstorms in the pollen season, in various geographical zones. The main hypotheses explaining association between thunderstorms and asthma claim that thunderstorms can concentrate pollen grains at ground level which may then release allergenic particles of respirable size in the atmosphere after their rupture by osmotic shock. During the first 20-30 min of a thunderstorm, patients suffering from pollen allergies may inhale a high concentration of the allergenic material that is dispersed into the atmosphere, which in turn can induce asthmatic reactions, often severe. Subjects without asthma symptoms, but affected by seasonal rhinitis can also experience an asthma attack. All subjects affected by pollen allergy should be alerted to the danger of being outdoors during a thunderstorm in the pollen season, as such events may be an important cause of severe exacerbations. In light of these observations, it is useful to predict thunderstorms and thus minimize thunderstorm-related events.

Near fatal asthma: treatment and prevention.

Near-fatal asthma (NFA) is described as acute asthma associated with a respiratory arrest or arterial carbon dioxide tension greater than 50 mmHg, with or without altered consciousness, requiring mechanical ventilation. Risk factors for near fatal asthma have not been fully elucidated. In 80-85% of all fatal events, a phenotype, characterized by eosinophilic inflammation associated with gradual deterioration occurring in patients with severe and poorly controlled asthma, has been identified. Regarding to the management, acute severe asthma remains a significant clinical problem, which needs to be identified to facilitate early and appropriate therapeutic interventions. The assessment relies on clinical signs, but additional information might be obtained from chest radiography or blood gas analysis. No investigation should delay the initiation of appropriate therapy. The goals of therapy are the maintenance of oxygenation, relief of airflow obstruction, reduction of airways edema and mucus plugging (with Increased use of medications such as beta-agonists via metered dose inhalers and nebulizers, oral and/or intravenous (other than by inhalation) corticosteroids and oral or intravenous theophylline) whereas supporting ventilation as clinically indicated. Of course, the emergency physician needs to consider the wide range of potential complications, as attention to these problems when managing severe acute asthma might significantly improve outcome. An understanding of the available agents and potential pitfalls in the management of NFA is mandatory for the emergency physician.

Observational study on adjuvant trastuzumab in HER2-positive early breast cancer patients.

AIM: This observational study investigates the use of adjuvant trastuzumab (AT) in HER2-positive breast cancer patients in a real-life setting, focusing on relapse and discontinuation rates. PATIENTS & METHODS: Data on a group of HER2-positive patients collected from 13 oncology centers of northeast Italy were analyzed. RESULTS: In total, 1245 patients were analyzed. 13.1% of patients were excluded from AT because of comorbidities, age, tumor stage, refusal or other reasons; 8.2% of patients who received AT interrupted the therapy, mainly for toxicity. Overall the relapse rate was 10.9% in the AT-treated population versus 22.6% in nontreated patients (follow-up: 37.4 and 62.1 months, respectively). Disease-free survival (DFS) was lower in AT-relapsed patients than in not-relapsed. Statistical analysis showed a correlation between DFS and estrogen receptor status in AT-treated patients. CONCLUSION: Relapse rates are lower in clinical setting compared to clinical trials. Overall, AT is effective in HER2-positive early-stage breast cancer patients.

Photostimulation of Japanese quail.

To adapt commercial poultry production to a new scenario of energy savings and to develop specific practices for quail production aimed at reducing costs while maintaining or improving productivity, four experiments were conducted. In the first experiment, birds were allocated to four treatments (photoperiod duration): T1: 14 L:10 D; T2: 15 L:9 D; T3: 16 L:8 D; and T4: 17 L:7 D. In the second experiment, birds were subjected to four levels of brightness: T1: 5 lux; T2: 10 lux; T3:15 lux; and T4: 22 lux (control). In the third experiment, four types of lamps were evaluated: T1: compact fluorescent lamp (color temperature: 6,500 K); T2: compact fluorescent lamp (color temperature: 2,700 K); T3: incandescent lamp; and T4: yellow LED. In the last experiment, four lighting programs were compared: T1: continuous program (control), in which there was a single photoperiod of 15 h; the other treatments consisted of intermittent lighting programs, as follows: T2: 1 h of light provided 1 h after dusk; T3: 1 h of light provided 2 h before dawn; T4: half an hour of light provided 1 h after dusk and half an hour of light provided 1.5 h before dawn. In each experiment, 1,296 Japanese quail were evaluated for four 28-d cycles, totaling 112 experimental days. A completely randomized experimental design of 4 treatments with 12 replicates of 27 birds each was applied in all trials. Performance and egg quality were evaluated in each experiment. Higher egg production and adequate egg quality, as well as energy savings, can be obtained with Japanese quail using compact fluorescent lamps or LEDs and a photoperiod of 15 h/d supplied using an intermittent lighting program, with 1 h of artificial light 2 h before dawn at a brightness of 5 lux.

Coupling of photocatalysis and catalysis using an optical fiber textile for room temperature depollution.

Herein, we investigate the interplay between a photocatalyst (TiO2) and a catalyst (Pt/TiO2 and Pt/CeO2) for the oxidation of formaldehyde and toluene at room temperature. A luminous textile is used as support and as light source for the photocatalyst. Our results indicate that the presence of the catalyst and the photocatalyst increases the catalytic performance for the oxidation of formaldehyde, while the photocatalytic performance for toluene oxidation decreases. The overall performance (toluene and formaldehyde degradation) of the system can be optimized with respect to the choice of support for the catalyst (e.g. TiO2 or CeO2), the quantity of Pt used, and the ratio between the catalyst and photocatalyst. In addition, different configurations of the photocatalyst and the catalyst on the textile are studied: under leaching and flow-through gas streams, catalyst and photocatalyst deposition on the same and opposite site of the textile are tested. The performance of the system can be optimized by adapting a configuration where the gas stream goes through the textile, while the deposition side of the catalyst and/or photocatalyst with respect to the gas stream is of minor importance.

Graded contrast echocardiography in pulmonary arteriovenous malformations.

To compare the results of transthoracic contrast echocardiography (TTCE) adding a grading scale with the results of thoracic computed tomography (CT) in order to optimise the use of both techniques. 95 patients with hereditary haemorrhagic telangiectasia (HHT) were examined with TTCE and thoracic CT to detect pulmonary arteriovenous malformations (PAVMs). According to previous studies, TTCE was divided into a four grade scale depending on the degree of opacification of the left ventricle after the administration of a contrast agent. Of the 95 patients (50.5% female; mean age 46 yrs), none with normal or grade 1 TTCE had detectable PAVMs on thoracic CT. Shunts of grades 2, 3 and 4 were associated with PAVMs according to thoracic CT in 25, 80, and 100% of the cases. There was a statistically significant association between the TTCE grade and the detection of a PAVM by thoracic CT. There were also statistically significant associations between TTCE grade and the cardiac cycle when the contrast was first visible in the left atrium, and size of the feeding artery. Graded TTCE and timing of left atrium opacification may be useful techniques in selecting HHT patients for PAVM screening with thoracic CT scans.

Effects of a structured educational intervention in moderate-to-severe elderly asthmatic subjects.

BACKGROUND: Adherence to inhaled drugs is linked to patients' satisfaction with their device, and an incorrect use can negatively affect the outcomes of asthma treatment. We speculated that this is particularly true in elderly asthmatic subjects. AIM: We performed a national pre-post interventional multicentre study, enrolling moderate-to-severe asthmatic subjects aged ≥65 â€‹years treated with fixed inhaled combination drugs by dry powder inhaler (DPI) or pressurized metered dose inhaler (pMDI). Adherence and critical errors were evaluated by means of validated questionnaires at first visit (V1) and after 3-6 months (V2). At V1, subjects underwent intensive training on the correct use of their device by physical demonstration. RESULTS: A total of 411 asthmatics (F/M: 238/173, mean age±SD: 72 â€‹± â€‹5 â€‹years) participated to the study. At V1, 50% of the study subjects showed an Asthma Control Test (ACT) score ≤19 despite GINA step 3 and 4 treatment, and 40% had experienced at least one severe asthma exacerbation in the previous year. Poor adherence to treatment was recorded in 43% of subjects, and at least one error in using the device was registered in 56% of subjects. At V2, available for 318 patients, both the percentage of individuals with poor adherence and with at least one critical error significantly decreased (from 46% to 25%, and from 49% to 25%, respectively; p â€‹< â€‹0.001 for both comparisons) with a significant increase of the ACT score (from 19 â€‹± â€‹4.9 to 20 â€‹± â€‹4.0, p â€‹< â€‹0.001). CONCLUSIONS: Asthma in the elderly is characterized by low levels of symptom control. Educational interventions are strongly advocated in this age group in order to increase adherence to treatment and inhaler techniques.

[Monoclonal gammopathy of renal significance and membranoproliferative glomerulonephritis: a complex relationship with promising therapeutic opportunities].

In the last few years, the increasing awareness of the complex interaction between monoclonal component and renal damage has determined not only a new classification of the associated disorders, called Monoclonal Gammopathy of Renal Significance (MGRS), but has also contributed to emphasize the importance of an early diagnosis of the renal involvement, which is often hard to detect but can evolve towards terminal uraemia; it has also pointed at the need to treat these disorders with aggressive regimens, even if they are not strictly neoplastic. The case described here presented urinary abnormalities and renal failure secondary to a membranoproliferative glomerulonephritis (MPGN), with intensively positive immunofluorescence (IF) for monoclonal k light chain and C3, and in the absence of a neoplastic lympho-proliferative disorder documented on bone marrow biopsy. After the final diagnosis of MGRS, the patient was treated with several cycles of a therapy including dexamethasone, cyclophosphamide and bortezomib, showing a good functional and clinical response.

Biology, prognosis and response to therapy of breast carcinomas according to HER2 score.

BACKGROUND: The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. PATIENTS AND METHODS: A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. RESULTS: Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. CONCLUSIONS: The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

A late complication of transobturator tape: abscess and myositis.

The aim of the present study was to investigate a late complication of transobturator tape (TOT) implant: abscess and myositis. The case report included a 53 years-old vaginal multipara, subject to transobturator tape procedure in 2004, who came to the observation of the Department of Obstetrics and Gynecology (University of Catania, Italy) with a late vaginal polypropylene mesh erosion. She reported growing pain at her left leg, walking difficulty, fever and persistent stress urinary incontinence (SUI). She also described a shooting pain originating from the left inguinal ligament radiating down her left leg. Obturator internus and adducent muscles of the left thigh were involved. Ultrasounds and magnetic resonance imaging (MRI) clearly revealed the course of the mesh tape through the obturator muscles with myositis and abscess. The patient was treated by removing the polypropylene tape through the vaginal erosion. Her symptomatology improved within 3 weeks after the tape removal. Although developed to minimize surgical morbidity, the TOT procedure is not risk-free. Like for all the synthetic sling materials, the risk of erosion and resulting ascending infection from contamination exists. Because of the rarity of this complication, the Authors performed an assessment of this condition. Erosion may predispose the patient to secondary complications: abscess and myositis with great difficulty in deambulation. Imaging diagnosis is very effective. Ultrasound imaging is a useful method to investigate the whole pelvic floor condition. Moreover, MRI is a precise diagnostic procedure. This case not only proved the failure of the TOT for the treatment of stress incontinence, but also all the associated concerns. The study emphasizes the observation that abscess and symptomatic myositis may result into late disabling complications, although starting from a mini-invasive procedure.

Removal of chromium ions from [corrected] aqueous solutions by adsorption on activated carbon and char.

Adsorption isotherms of chromium ions in aqueous solution have been experimentally measured on a granular activated carbon (GAC) and on a char of South African coal (CSAC). Experimental results show that the adsorption capacity for the GAC strongly depends on solution pH and salinity, with maximum values around 7mg/g at neutral pH and low salinity levels. On the contrary, the CSAC shows a smaller adsorption capacity, near 0.3mg/g, which slightly decreases by increasing pH and salinity levels. Chromium adsorption mainly depends on the availability of chromium ions in solution and on the occurrence of redox reactions between the surface groups and the Cr(VI) which lead to the formation of Cr(III). The reduction of Cr(VI) and the following sorption of Cr(III) cations appears as the leading mechanism for chromium uptake on the CSAC. A similar behaviour can be observed for the GAC at pH below 3. On the contrary, at pH>7, the multicomponent competitive adsorption of Cr(VI), OH(-) and Cl(-) has to be considered.

Conversion of methanol to hydrocarbons over zeolite ZSM-23 (MTT): exceptional effects of particle size on catalyst lifetime.

A variety of synthetic procedures have been used to obtain zeolite ZSM-23 (MTT) catalysts with crystallite sizes ranging from the micrometer to nanometer scale. When the acidic zeolite is used as a catalyst for the methanol to hydrocarbon (MTH) reaction, the catalytic lifetime is dramatically influenced by the crystallite shape and size.

Capture of mercury ions by natural and industrial materials.

In this paper the technical feasibility of various adsorbents for mercury removal from contaminated waters has been studied. Adsorption isotherms of mercury ions in aqueous solution have been experimentally measured on a granular activated carbon (Aquacarb 207EA), a char, a pozzolana and a yellow tuff. The experimental evidences show that the mercury capture capacity of yellow tuff and char is of few tenths of milligrams per gram of sorbent while for the pozzolana and the activated carbon this value is of the order of 1mg/g of sorbent. Moreover, for a mercury concentration as high as 3000 microg/l the pozzolana shows the highest adsorption capacity. This result seems to be quite interesting, especially in consideration of the extremely low cost of this natural sorbent.

[Function recovery in patients with knee arthroplasty: role of proprioceptive rehabilitation]. / Il recupero funzionale del ginocchio artroprotesizzato: ruolo dell'allenamento propriocettivo.

This study evaluates the outcome of proprioceptive rehabilitation in 18 patients who underwent knee joint prosthetic replacement using the dynamic electronic plate Pro-kin_machine. The proprioceptive performance was determined by having the patients trace a set of three outlines (horizontal, vertical and circular) using the foot of the operated limb. The measures of outcome parameters were: 1) time taken to do the test; 2) score of accuracy of the test measured in percentage. Tests were performed on admission, half way through rehabilitation and on discharge. Each patient had 15 sittings of physiotherapy. Our results demonstrate a significant improvement of both parameters at the end of the treatment. After prosthetic knee joint replacement, not only is it important to re-establish mechanical stability but also dynamic stability. The latter can be achieved through active virtual taping by the stabilizer muscles. Prompt management of instability of the joint in the rehabilitation phase is extremely important in the re-activating of the control mechanisms that are compromised by the surgical operation.

Exogenous lipoid pneumonia (ELP): when radiologist makes the difference.

Lipoid pneumonia is an uncommon disorder characterized by accumulation of lipid components into the interstitial and alveolar compartment. The usual classification distinguishes endogenous and exogenous and acute or chronic forms, related to the type of fats, the amount of damage and the time of exposure. We describe a case of exogenous lipoid pneumonia by inhalation of vaseline used for cleaning of the tracheostoma in a 63-year-old female, presenting as cough, worsening dyspnea in few weeks. The diagnosis was finally established with a re-evaluation of BAL with specific staining for lipids, revealing the presence of foamy macrophages lipids rich, according to HRCT findings.