Erratum to: pegylated liposomal doxorubicin in combination with dexamethasone and bortezomib (VMD) or lenalidomide (RMD) in multiple myeloma pretreated patients

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PRDI-BF1 and PRDI-BF1P isoform expressions correlate with disease status in multiple myeloma patients

Human positive regulatory domain I binding factor 1 (PRDI-BF1 or BLIMP-1) is a transcription factor that acts as a master regulator and has crucial roles in the control of differentiation and in maintaining survival of plasma cells (PC). The PRDM1 gene, which codifies for PRDI-BF1, contains an alternative promoter capable of generating a PRDI-BF1 deleted protein (called PRDI-BF1β), which lacks 101 amino acids comprising most of the regulatory domain. PRDI-BF1β has been detected in relevant quantities especially in multiple myeloma cell lines (U266 and NCI- H929). The first aim of the study was to compare, using real time polymerase chain reaction (RT-PCR), the levels of PRDI-BF1 and PRDI-BF1β in myeloma patients and in normal human bone marrow. The second step was the examination of the expression of PRDI-BF1 and PRDI-BF1β isoform depending on disease status and treatment response. We demonstrate the correlation of PRDI-BF1 and the shorter PRDI-BF1β isoform protein levels with the clinical evolution and the management of myeloma patients

Bortezomib with Thalidomide plus Dexamethasone Compared with Thalidomide plus Doxorubicin and Dexamethasone as Induction Therapy in Previously Untreated Multiple Myeloma Patients

We conducted a retrospective study to compare thalidomide, bortezomib and dexamethasone (VTD) with thalidomide plus doxorubicin and dexamethasone (TAD). Until now, first-line treatment with these combinations has not been reported in any comparative study. The principal objective of this study was to determine whether VTD would improve the complete response (CR) and CR plus very good partial response rates compared with TAD. Second, using additional methods, such as flow cytometric assays and polymerase chain reaction technology, we evaluated the molecular residual disease in the subgroup of patients that obtained CR. Our study shows that VTD is a superior induction regimen compared with TAD, with a higher response rate after induction, translating into greater CR plus very good partial response

Adherence to therapeutic guidelines among patients treated with statins. Results from STAR study

INTRODUCTION: the objective of this study was to analyze adherence to therapeutic guidelines among patients treated with lipid lowering drugs (statins).MATERIAL AND METHODS: a retrospective observational study including 5 Local Health Units (LHUs) was conducted using administrative databases. Patients who received at least one prescription for statins between January 1st, 2007 and June 30th, 2008 were selected and followed for 12 months. Patients were classified according to their level of absolute cardiovascular risk (moderate, high, very high according to Nota 13 AIFA).RESULTS: a total of 71,855 patients were included (14,133 newly treated patients with statins, representing 19.4% of total sample), (age 68.8±10.7, male 51%). Level of absolute cardiovascular risk were: moderate risk (45.4%), high risk (33.4%), very high risk (16.3%), familial hypercholesterolemia (4.9%). Statins assumed by patients in analysis were stratified in two groups (first or second choice), accordingly to their efficacy (level of LDL cholesterol reduction) in relation to the patient’s cardiovascular risk (coherently with new Nota 13 AIFA, 2011). Among patients with a very high cardiovascular risk, only 52.8% used statins indicated by Nota13 as a first choice while 2.9% used a second choice statin and 44.3% used an inadequate statin and/or dosage; among familial hypercholesterolemia patients, those percentages were, respectively: 53.8%, 21.1% and 25.1%. When only patients naïve to statins treatment were analyzed, similar percentages were found. Only few patients in very high risk group used adequate dosages: among patients treated with rosuvastatin and atorvastatin, 11.2% used atorvastatin 40 mg, and 0.2% used atorvastatin 80 mg (this population was not analyzed for events because of low numerosity) while 4.1% used rosuvastatin 20 mg and 0.2% used rosuvastatin 40 mg; overall, 84.3% of patients in this group used inadequate dosages. Cardiovascular events at one year of follow up were 1.6% for patients treated with rosuvastatin 20 mg, 1.6% for rosuvastatin 40 mg and 6.1% for atorvastatin 40 mg; death rates (any cause) were 0.9%, 0.0%, 2.6% respectively. The analysis of the sub-population of patients treated with rosuvastatin 20 mg with previous CV event showed a percentage of patients with a CV event during the observational period of 3.4%, a percentage of patients with cerebrovascular event of 0.9% and a mortality percentage of 0.9%.Conclusions: in real practice setting, the percentage of patients prescribed for recommended statins and dosages is low

Donor-transmitted Triple-Hit Lymphoma in a Renal Allograft Recipient

simultaneous appearance of DLBCL in the donor and recipient after renal transplantatio

Piezoelectric Signals in Vascularized Bone Regeneration

The demand for bone substitutes is increasing in Western countries. Bone graft substitutes aim to provide reconstructive surgeons with off-the-shelf alternatives to the natural bone taken from humans or animal species. Under the tissue engineering paradigm, biomaterial scaffolds can be designed by incorporating bone stem cells to decrease the disadvantages of traditional tissue grafts. However, the effective clinical application of tissue-engineered bone is limited by insufficient neovascularization. As bone is a highly vascularized tissue, new strategies to promote both osteogenesis and vasculogenesis within the scaffolds need to be considered for a successful regeneration. It has been demonstrated that bone and blood vases are piezoelectric, namely, electric signals are locally produced upon mechanical stimulation of these tissues. The specific effects of electric charge generation on different cells are not fully understood, but a substantial amount of evidence has suggested their functional and physiological roles. This review summarizes the special contribution of piezoelectricity as a stimulatory signal for bone and vascular tissue regeneration, including osteogenesis, angiogenesis, vascular repair, and tissue engineering, by considering different stem cell sources entailed with osteogenic and angiogenic potential, aimed at collecting the key findings that may enable the development of successful vascularized bone replacements useful in orthopedic and otologic surgery

Organ Stiffness in the Work-Up of Myelofibrosis and Philadelphia-Negative Chronic Myeloproliferative Neoplasms

To define the role of spleen stiffness (SS) and liver stiffness (LS) in myelofibrosis and other Philadelphia (Ph)-negative myeloproliferative neoplasms (MPNs), we studied, by ultrasonography (US) and elastography (ES), 70 consecutive patients with myelofibrosis (MF) (no.43), essential thrombocythemia (ET) (no.10), and polycythemia vera (PV) (no.17). Overall, the median SS was not different between patients with MF and PV (p = 0.9); however, both MF and PV groups had significantly higher SS than the ET group (p = 0.011 and p = 0.035, respectively) and healthy controls (p < 0.0001 and p = 0.002, respectively). In patients with MF, SS values above 40 kPa were significantly associated with worse progression-free survival (PFS) (p = 0.012; HR = 3.2). SS also correlated with the extension of bone marrow fibrosis (BMF) (p < 0.0001). SS was higher in advanced fibrotic stages MF-2, MF-3 (W.H.O. criteria) than in pre-fibrotic/early fibrotic stages (MF-0, MF-1) (p < 0.0001) and PFS was significantly different in the two cohorts, with values of 63% and 85%, respectively (p = 0.038; HR = 2.61). LS significantly differed between the patient cohort with MF and healthy controls (p = 0.001), but not between the patient cohorts with ET and PV and healthy controls (p = 0.999 and p = 0.101, respectively). We can conclude that organ stiffness adds valuable information to the clinical work-up of MPNs and could be employed to define patients at a higher risk of progression

The first wave of pandemic influenza (H1N1) 2009 in Germany: From initiation to acceleration

<p>Abstract</p> <p>Background</p> <p>The first imported case of pandemic influenza (H1N1) 2009 in Germany was confirmed in April 2009. However, the first wave with measurable burden of disease started only in October 2009. The basic epidemiological and clinical characteristics of the pandemic were analysed in order to understand the course of the pandemic in Germany.</p> <p>Methods</p> <p>The analysis was based on data from the case-based, mandatory German surveillance system for infectious diseases. Cases notified between 27 April and 11 November 2009 and fulfilling the case definition were included in the study.</p> <p>Results</p> <p>Two time periods with distinct epidemiologic characteristics could be determined: 23,789 cases (44.1%) occurred during the initiation period (IP, week 18 to 41), and 30,179 (55.9%) during the acceleration period (AP, week 42 to 45). During IP, coinciding with school summer holidays, 61.1% of cases were travel-related and one death occurred. Strict containment efforts were performed until week 32. During AP the majority of cases (94.3%) was autochthonous, 12 deaths were reported. The main affected age group shifted from 15 to 19 years in IP to 10 to 14 years in AP (median age 19 versus 15 years; p < 0.001). The proportion of cases with underlying medical conditions increased from 4.7% to 6.9% (p < 0.001). Irrespective of the period, these cases were more likely to be hospitalised (OR = 3.6 [95% CI: 3.1; 4.3]) and to develop pneumonia (OR = 8.1 [95% CI: 6.1; 10.7]). Furthermore, young children (0 to 2 years) (OR = 2.8 [95% CI: 1.5; 5.2]) and persons with influenza-like illness (ILI, OR = 1.4 [95% CI: 1.0; 2.1]) had a higher risk to develop pneumonia compared to other age groups and individuals without ILI.</p> <p>Conclusion</p> <p>The epidemiological differences we could show between summer and autumn 2009 might have been influenced by the school summer holidays and containment efforts. The spread of disease did not result in change of risk groups or severity. Our results show that analyses of case-based information can advise future public health measures.</p

Genetics and molecular epidemiology of multiple myeloma : the rationale for the IMMEnSE consortium (review)

There is strong evidence suggesting the presence of a genetic component in the aetiology of multiple myeloma (MM). However no genetic risk factors have been unequivocally established so far. To further our understanding of the genetic determinants of MM risk, a promising strategy is to collect a large set of patients in a consortium, as successfully done for other cancers. In this article, we review the main findings in the genetic susceptibility and pharmacogenetics of MM and present the strategy of the IMMEnSE (International Multiple Myeloma rESEarch) consortium in contributing to determine the role of genetic variation in pharmacogenetics and in MM risk.We acknowledge support by the recruiting hospitals and physicians of the study regions as well as their collaborating nurses and technicians. Collection of blood samples from Spain, patients from Granada area and DNA extraction was partially supported by grants P08-CVI-4116 from Consejeria de Salud de la Junta de Andalucia (Sevilla, Spain) and PI081051 from Fondo de Investigaciones Sanitarias (Madrid, Spain). Collection of blood samples from Polish patients and controls from Lodz area and DNA extraction was supported by a grant from Polish Ministry of Science and Higher Education (No. N N402178334)