Background: In newly diagnosed myeloma patients the combination of bortezomib with melphalan-prednisone (VMP) was superior to MP. In relapsed-refractory patients the 4 drug combination of ...bortezomib-melphalan-prednisone-thalidomide (VMPT) induced a high proportion of complete responses (CR).
Methods: Newly diagnosed myeloma patients (N=393) older than 65 years, from 58 centers in Italy, were randomly assigned to receive VMPT (N=193) or VMP (N=200). Initially, patients were treated with nine 6-week cycles of VMPT (bortezomib 1.3 mg/m2 days 1,4,8,11,22,25,29,32 in cycles 1–4 and days 1,8,22,29 in cycles 5–9; melphalan 9 mg/m2 days 1–4; prednisone 60 mg/m2 days 1–4 and thalidomide 50 mg days 1–42, followed by bortezomib 1.3 mg/m2 every 15 days and thalidomide 50 mg/day as maintenance) or VMP (bortezomib, melphalan and prednisone at the same doses and schedules previously described without maintenance). In March 2007, the protocol was amended: both VMPT and VMP schedules were changed to nine 5-week cycles and bortezomib schedule was modified to weekly administration (bortezomib 1.3 mg/m2 days 1,8,15,22 in cycles 1–9). Primary end-point was progression-free survival (PFS).
Results: Patient characteristics were similar in both groups: median age was 71 years, 23% of patients were aged > 75 years. Patients who received at least 1 cycle were evaluated: 152 patients for VMPT (62 received bortezomib bi-weekly infusion and 90 weekly infusion) and 152 patients for VMP (62 received bortezomib bi-weekly infusion and 90 weekly infusion). Data were analyzed in intention-to-treat. The very good partial response (VGPR) rate was higher in the VMPT group (55% versus 42%, p=0.02), including a CR rate of 31% in the VMPT group and 16% in the VMP group (p=0.003). In the subgroup treated with weekly infusion of bortezomib, VGPR was 59% for VMPT and 37% for VMP (p=0.004), including 28% CR for VMPT and 10% for VMP (p=0.004). Subgroup analyses did not show any statistical difference between responses and either age, B2-microglobulin or chromosomal abnormalities, such as del13, t(4;14), t(14;16) and del17. After a median follow-up of 13.6 months, the 2-year PFS was 83.9% in the VMPT group and 75.7% in the VMP group (HR=0.73, 95% CI 0.38–1.42, p=0.35). In patients who received weekly infusion of bortezomib, the 2-year PFS was 86.8% in the VMPT group and 78.1% in the VMP group (HR=0.65, 95% CI 0.24–1.8, p=0.41). In patients who achieved CR after induction, the 2-year PFS was 100% for VMPT and 79% for VMP (p=0.02). The 3-year overall survival (OS) was 89.5% in the VMPT group and 88.7% in the VMP group (HR=1.02, 95% CI 0.43–2.46, p=0.96). The incidence of grade 3–4 adverse events (AEs) was similar in both groups. In the VMPT patients and in the VMP patients, the more frequent AEs were neutropenia (36% vs 31%), thrombocytopenia (20% vs 19%), peripheral neuropathy (18% vs 12%), infections (14% vs 10%), and gastrointestinal complications (7% vs 8%), respectively. The weekly infusion of bortezomib significantly decreased the incidence of grade 3–4 peripheral neuropathy (9% for VMPT and 3% for VMP).
Conclusion: VMPT is superior to VMP in terms of response rates. Longer follow-up is needed to assess their effects on PFS and OS. The weekly infusion of bortezomib significantly reduced the incidence of grade 3–4 peripheral neuropathy without influencing outcome.
Table. Complete responses, progression-free survival and peripheral neuropathy in all patients and in those who received weekly infusion of bortezomib
VMPT group (n=152)VMP group (n=152)All patients (n=152)Subgroup with bortezomib weekly infusion (n=90)All patients (n=152)Subgroup with bortezomib weekly infusion (n=90)CR rate (%)312816102-year PFS (%)84877678Grade 3–4 peripheral neuropathy (%)189123
Chemically decorated microalgae for environmental application Flemma, Annarita; Vicente-Garcia, Cesar; Rizzo, Giorgio ...
2022 IEEE International Workshop on Metrology for the Sea; Learning to Measure Sea Health Parameters (MetroSea),
2022-Oct.-3
Conference Proceeding
The presence of polychlorinated biphenyls (PCBs) in different natural matrices and consequent toxic effects represent a public health issue. Due to their bioaccumulation, they have negative effects ...on different living organisms, including humans. Here we report a preliminary investigation of suitability of a microalgae-based technique for the bioremediation of marine sediment and water column. Phaeodactylum tricornutum, a model benthic diatom is tested for removal of different biphenyl molecules from sea water solutions. Moreover, cells are individually modified with a polydopamine coating, to enhance both their resistance in harsh environmental conditions and the capability of remediation to hydrophobic pollutants.
This paper reports the strategy implemented by the Palermo University (Italy) aimed at fostering the energy performance of its campus, particularly towards financing energy saving measures. The basic ...idea is that the money saved through the energy efficiency actions, constitute the main flywheel to fund further savings and energy efficiency interventions. Results of this paper might bring a useful contribution to the energy planning of cities, since campuses may be regarded as emblematic case study of what can be done in cities because they reproduce, at a little scale, the functioning of wider urban contexts.
Current policies addressing the energy efficiency of buildings aimed at the control of their overall primary energy demand, require not only that the edifice envelope has to be properly designed to ...optimize its thermal performances, but also that the eco-friendly properties of the involved building materials have to be properly taken into account, in order of assessing all the associated environmental costs. In fact, the design of envelope structures that are able to realize proper levels of thermal insulation and, in the same time, to employ materials characterized by low environmental impacts, are believed as the most effective strategies to be adopted in the aim of addressing the above-mentioned issues. In this regard natural materials, such as vegetal fibres or materials derived from the recycling of industrial/ agricultural waste, reveal very attractive characteristics. Indeed, recent studies on the use of natural materials in buildings concentrate on raw materials deriving from either agriculture, waste, or recycling processes. Such topics are the focuses of the present analysis. Specifically, this paper intends to provide a contribution in the field by identifying new types of environment-friendly composites, containing vegetal matters and ecological waste resulting from recycling activities. Outcomes of a series of performed laboratory analyses concerning the thermal conductivity of four different samples of assemblies, are quite promising and candidate these new composites - albeit further analyses are certainly recommended - as a practicable alternative to the mostly used traditional insulating materials.
The ability of trimetazidine (2,3,4, trimethoxybenzylpiperazine dihydrochloride, TMZ) to protect the myocardium against anthracycline (ANT)-induced cardiotoxicity during chemotherapy has been ...evaluated in female patients with breast cancer. A clinical trial was conducted in 61 patients subdivided into three groups: group 1 (n = 15, G1) treated with standard ANT protocol and cardioprotection by dexrazoxane (DEX) plus TMZ (60 mg, daily dose); group 2 (n = 22, G2) treated with ANT and cardioprotection by TMZ only; and group 3 (n = 24, G3) scheduled to receive ANT therapy and DEX. All the patients submitted to an echocardiographic evaluation of diastolic function (E wave velocity, A wave velocity, isovolumetric relaxation time IVRT, deceleration time DT) at enrollment (TO), at T1 time, at T2 time, and at T3 time. After a 12- month follow-up period, the patients showed a good conservation of diastolic function both in G1 and G2 groups. No statistically significant difference was observed in E wave and A wave velocity and E/A ratio after ANT treatment. TMZ produced a cardioprotective effect, compa rable to DEX protection, against subacute and chronic subclinical cardiotoxicity with no signif icant changes in diastolic function after 1 year of follow-up.
Background: A wide pulse pressure (PP) can provide important risk assessment information about myocardial infarction, carotid artery atherosclerosis, and global cardiovascular risk. Ambulatory pulse ...pressure (APP) does not have a well‐known prognostic value in hypertensive patients. Methods: To evaluate the relationship among high APP, atrial volumes, and cardiac function, an observational study was performed on 108 untreated nonelderly hypertensive patients (mean age 54.23 ± 7.12). Twenty‐four‐hour ambulatory blood pressure monitoring, Doppler and echocardiographic measurements of systolic, diastolic function, left and right atrial volumes, left ventricular mass index and dimensions, were performed in subjects with both clinic and APP > 60 mmHg (APP1 Group). A control group of hypertensive selected subjects with both clinic and APP < 60 mmHg was chosen (APP 2 Group). Results: The APP1 group showed left atrial volume enlargement, high left ventricular mass index, and impaired diastolic function. A positive correlation was found in the APP1 group results among left ventricular end diastolic diameter (r = 0.39, P < 0.01), left atrial volume (0.38, P < 0.05), and left ventricular mass index (r = 0.33, P < 0.05); clinic PP showed a statistically significant correlation with left atrial volume, left ventricular end diastolic diameter, and left ventricular mass index only in the APP1 group. Conclusions: These results suggest that elevated APP can be considered an effective predictor of cardiovascular risk in hypertensive subjects. In these patients echocardiographic evaluation of left ventricular function and morphology can increase the prognostic value of PP. (ECHOCARDIOGRAPHY, Volume 21, January 2004)
Despite the increasing concern of institutions and technical organizations toward the improvement of the building energy (and, therefore, environmental) efficiency, the main goal of technicians ...should be also devoted toward the levels of internal thermal comfort that buildings are able to realize. As that, the relationships between energy performances and comfort conditions provided by the enclosures are of paramount importance in guiding designers in their work. In this paper, the influence of diverse roof construction typologies on energy and indoor performance of buildings has been investigated, in different Italian sites during heating and cooling seasons. In addition, it must be properly considered that buildings operate in given climate and weather contexts that deeply affect their performances. Hence, for taking into account the different weather conditions of each site, a new parameter has been used, that is the "Climatic Severity Index" corresponding to a value of magnitude of a climatic vector less a constant value, recently released by an Italian technical standard. The actions for improving the energy efficiency sometimes lead to a reduction of indoor comfort, therefore, not always easily applicable.
Resilience represents a new important feature that the anthropic systems, and cities among them, are called to cope with. In fact, the increasing negative stresses to which urban contexts are ...exposed, and mainly the climatic pressures, call for the capability of adapting to these modifications and, possibly, to restore the ex-ante situations. The role of the buildings and their envelope components is of crucial importance to this aim. This paper analyses the features of resilience of the roofs of buildings by means of proper quantitative indexes. On purpose, the performances of green and cool roofs are compared. The possibility of adopting nonstructural solutions, like the windows shading devices, is also considered.
Background
Several studies have shown that the main circulating biomarkers of liver and colorectal cancer can be detected in the bloodstream and are also associated with immunoglobulin M to form ...stable complexes. These immune complexes show increased capacity of discrimination between cancer patients and healthy controls if combined with the free biomarker form. Within the context of the Project FIRB 2003 - Nanosized Cancer Polymarker Biochip - we wanted to investigate if IgM complexes have importance also in breast cancer. We focused our study on the immune complexes between IgM and CA 15.3 because free CA 15.3 is the most commonly used breast cancer biomarker in clinical practice. However, this biomarker alone lacks satisfactory sensitivity especially in early cancer detection.
Aim
The aim of our study was to assess the occurrence of immune complexes between CA 15.3 and IgM in sera from patients with primary breast cancer and in sera from healthy controls to evaluate its putative diagnostic value compared with the diagnostic value of free CA 15.3.
Methods
A total of 130 serum samples were obtained from 56 healthy women (mean age±SD, 45±8.23 years) and 74 women with stage l and II breast cancer (mean age±SD, 59±13.6 years) before any treatment, either surgical or chemo-therapeutic. Serum samples were collected, aliquoted and stored at-80°C in the centralized biobank of the project according to very stringent standard operating procedures (SOPs) distributed by the coordinating unit. To evaluate the presence of CA 15.3-lgM immune complexes, we developed and validated a novel enzyme-linked immunosorbent assay (ELISA) with a polyclonal rabbit anti-human CA 15.3 antibody (Abcam) as the catcher antibody. CA 15.3-lgM was detected with peroxidase-conjugated anti-human IgM and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and hydrogen peroxide as substrate (Sigma Aldrich, Italy). The levels of CA 15.3-lgM were expressed in arbitrary units per mL (AU/mL) by interpolation on a calibration curve obtained by serial dilution of a reference calibrator purified by gel filtration chromatography from a pool of serum samples with high levels of CA 15.3-lgM. Serum levels of free CA 15.3 were assessed in parallel on each sample using an automated immunoassay system (ADVIA Centaur-Siemens Diagnostics) and expressed in U/mL.
Results
To discriminate between cancer patients and healthy controls, we used as cutoff values 31.5 U/mL for free CA 15.3 (corresponding to the cutoff used in the clinical routine) and 794 AU/mL for CA 15.3-lgM (representing the 95th percentile of the distribution of serum levels of CA 15.3-lgM in healthy controls). By using these cutoff values, we obtained a sensitivity of 1 0% (7/74 cases) and a specificity of 95% (53/56 controls) for CA 15.3-lgM. The sensitivity and specificity of free CA15.3 were 7% (5/74 cases) and 1 00% (56/56 controls), respectively. Interestingly, the serum levels of the two biomarkers did not overlap, so their combination at 95% specificity identified 12/74 cases (16.2%). When we took a cutoff of 22 U/ mL for free CA15.3 (the 95th percentile of its distribution in healthy controls), we calculated a sensitivity of 26% (1 9/74 cases) and a specificity of 95% (53/56 controls); its combination with CA 15.3-lgM had a sensitivity of 34% (25/74 cases) and a specificity of 90% (50/56 controls).
Conclusions
These results demonstrate for the first time the presence of CA 15.3-lgM in the bloodstream of patients with breast cancer. In addition, our data suggest that CA 15.3-lgM is a complementary serological marker to free CA 15.3 and the combination of these biomarkers could improve the diagnosis of breast cancer.
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