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Baitar A.,ZNA Middelheim | Kenis C.,University Hospitals Leuven | Moor R.,Cliniques universitaires Saint Luc | Decoster L.,Vrije Universiteit Brussel | And 12 more authors.
Journal of Geriatric Oncology | Year: 2015

Purpose: The main objective of this study was to describe geriatric recommendations based on a geriatric assessment (GA) and to evaluate the implementation of these recommendations. Patients and Methods: A two-step approach of screening followed by a GA was implemented in nine hospitals in Belgium. Patients ≥. 70. years were included at diagnosis or at disease progression/relapse. Concrete geriatric recommendations were systematically documented and reported to the treating physicians and consisted of referrals to professional health care workers. Patient charts were reviewed after one month to verify which geriatric recommendations have been performed. Results: From August 2011 to July 2012, 1550 patients were included for analysis. The median age was 77 (range: 70-97) and 57.0% were female. A solid tumour was diagnosed in 91.4% and a haematological malignancy in 8.6%. Geriatric screening with the G8 identified 63.6% of the patients for GA (n. = 986). A median of two geriatric recommendations (range: 1-6) were given for 76.2% (95%CI: 73.4-78.8) of the evaluable patients (n. = 710). A median of one geriatric recommendation (range: 1-5) was performed in 52.1% (95%CI: 48.4-55.8) of the evaluable patients (n. = 689). In general, 460 or 35.3% (95%CI: 32.8-38.0) of all the geriatric recommendations were performed. Geriatric recommendations most frequently consisted of referrals to the dietician (60.4%), social worker (40.3%), and psychologist (28.9%). Conclusion: This implementation study provides insight into GA-based recommendations/interventions in daily oncology practice. Geriatric recommendations were given in about three-fourths of patients. About one-third of all geriatric recommendations were performed in approximately half of these patients. © 2015 Elsevier Inc.


Mesenchymal stromal cells (MSCs) can be isolated not only from bone marrow (BM) but also from other tissues, including adipose tissue (AT) and umbilical cord Wharton's Jelly (WJ). Thanks to their ability to differentiate into various cell types, MSC are considered attractive candidates for cell-based regenerative therapy. In degenerative clinical settings, inflammation or infection is often involved. In the present work, we hypothesized that an inflammatory environment and/or Toll-like receptor (TLR) ligation could affect the MSC differentiation potential. MSC were isolated from BM, AT, and WJ. Inflammation was mimicked by a cytokine cocktail, and TLR activation was induced through TLR3 and TLR4 ligation. Osteogenesis was chosen as a model for differentiation. Osteogenic parameters were evaluated by measuring Ca2+ deposits and alkaline phosphatase (ALP) activity at day 7, 14, and 21 of the culture in an osteogenic medium. Our results show that WJ-MSC exhibit a much lower osteogenic potential than the other two MSC types. However, inflammation was able to strongly increase the osteogenic differentiation of WJ-MSC as calcification, and ALP activity appeared as early as day 7. However, this latter enzymatic activity remained much lower than that disclosed by BM-MSC. TLR3 or TLR4 triggering increased the osteogenesis in AT- and, to lesser extent, in BM-MSC. In conclusion, WJ-MSC constitutively disclose a lower osteogenic potential as compared with BM and AT-MSC, which is not affected by TLR triggering but is strongly increased by inflammation, then reaching the level of BM-MSC. These observations suggest that WJ-MSC could constitute an alternative of BM-MSC for bone regenerative applications, as WJ is an easy access source of large amounts of MSC that can effectively differentiate into osteoblasts in an inflammatory setting.


Czuczman M.S.,Roswell Park Cancer Institute | Kahanic S.,Siouxland Hematology Oncology Associates | Forero A.,University of Alabama at Birmingham | Davis G.,Teva Branded Pharmaceutical Products R & D Inc | And 6 more authors.
Annals of Hematology | Year: 2015

The efficacy/tolerability of bendamustine, a unique alkylator, plus ofatumumab, a human anti-CD20 monoclonal antibody, was evaluated for previously untreated indolent B cell non-Hodgkin’s lymphoma (NHL). The study investigated whether the overall response rate (ORR) for bendamustine-ofatumumab was similar to historical bendamustine-rituximab ORRs (≥90 %). In this multicenter, open-label, single-arm, phase II study, patients received six planned 28-day cycles of bendamustine (90 mg/m2 on days 1 and 2 of each cycle) and ofatumumab (300 mg on day 1, 1000 mg on day 8 of cycle 1, and on day 1 of subsequent cycles). The primary outcome was ORR. Secondary objectives included safety and tolerability. Exploratory evaluations included percentage of patients with positive baseline [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans who converted to negative postbaseline and quality of life (QOL) scores. The treated/safety analysis population received ≥1 dose of either therapy. The bendamustine-ofatumumab ORR was 90 % (95 % confidence interval, 77.8–96.6) in 49 treated patients (67 % complete response, 22 % partial response). No patients had progressive disease. Bendamustine-ofatumumab was acceptably tolerated. All 49 patients had ≥1 adverse event, the most common being nausea (61 %), fatigue (55 %), and infusion-related reactions (45 %, all but 1 occurring during cycle 1). The proportion of patients whose FDG-PET scans converted to negative postbaseline was 88 %. Changes in QOL scores were minor. In patients with treatment-naive, indolent B cell NHL, bendamustine-ofatumumab exhibited a high degree of activity (90 % ORR), comparable with historical bendamustine-rituximab ORRs (≥90 %), and was adequately tolerated (ClinicalTrials.gov identifier: NCT01108341). © 2015, Springer-Verlag Berlin Heidelberg.


Raicevic G.,Institute Jules Bordet ULB | Najar M.,Institute Jules Bordet ULB | Pieters K.,Institute Jules Bordet ULB | De Bruyn C.,Institute Jules Bordet ULB | And 5 more authors.
Tissue Engineering - Part A | Year: 2012

Mesenchymal stromal cells (MSCs) can be isolated not only from bone marrow (BM) but also from other tissues, including adipose tissue (AT) and umbilical cord Wharton's Jelly (WJ). Thanks to their ability to differentiate into various cell types, MSC are considered attractive candidates for cell-based regenerative therapy. In degenerative clinical settings, inflammation or infection is often involved. In the present work, we hypothesized that an inflammatory environment and/or Toll-like receptor (TLR) ligation could affect the MSC differentiation potential. MSC were isolated from BM, AT, and WJ. Inflammation was mimicked by a cytokine cocktail, and TLR activation was induced through TLR3 and TLR4 ligation. Osteogenesis was chosen as a model for differentiation. Osteogenic parameters were evaluated by measuring Ca2+ deposits and alkaline phosphatase (ALP) activity at day 7, 14, and 21 of the culture in an osteogenic medium. Our results show that WJ-MSC exhibit a much lower osteogenic potential than the other two MSC types. However, inflammation was able to strongly increase the osteogenic differentiation of WJ-MSC as calcification, and ALP activity appeared as early as day 7. However, this latter enzymatic activity remained much lower than that disclosed by BM-MSC. TLR3 or TLR4 triggering increased the osteogenesis in AT-and, to lesser extent, in BM-MSC. In conclusion, WJ-MSC constitutively disclose a lower osteogenic potential as compared with BM and AT-MSC, which is not affected by TLR triggering but is strongly increased by inflammation, then reaching the level of BM-MSC. These observations suggest that WJ-MSC could constitute an alternative of BM-MSC for bone regenerative applications, as WJ is an easy access source of large amounts of MSC that can effectively differentiate into osteoblasts in an inflammatory setting. © 2012 Mary Ann Liebert, Inc.


Lonnroth K.,World Health Organization | Migliori G.B.,Collaborating Center for Tuberculosis and Lung Diseases | Abubakar I.,Public Health England | D'Ambrosio L.,Collaborating Center for Tuberculosis and Lung Diseases | And 70 more authors.
European Respiratory Journal | Year: 2015

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions. ©ERS 2015.

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