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Dimopoulos M.A.,National and Kapodistrian University of Athens | Garcia-Sanz R.,Hospital Universitario Of Salamanca | Gavriatopoulou M.,National and Kapodistrian University of Athens | Morel P.,Hopital Schaffner | And 10 more authors.
Blood | Year: 2013

In this phase 2 multicenter trial, we evaluated the activity of bortezomib, dexamethasone, and rituximab (BDR) combination in previously untreated symptomatic patients with Waldenström macroglobulinemia (WM). To prevent immunoglobulin M (IgM) "flare," single agent bortezomib (1.3 mg/m 2 IV days 1, 4, 8, and 11;21-day cycle), was followed by weekly IV bortezomib (1.6 mg/m2 days 1, 8, 15, and 22) every 35 days for 4 additional cycles, followed by IV dexamethasone (40 mg) and IV rituximab (375 mg/m2) in cycles 2 and 5. Fifty-nine patients were treated; 45.5% and 40% were high and intermediate risk per the International Prognostic Scoring System for WM. On intent to treat, 85% responded (3% complete response, 7% very good partial response, 58% partial response [PR]).In 11% of patients, an increase of IgM ≥25% was observed after rituximab; no patient required plasmapheresis. After a minimum follow-up of 32 months, median progression-free survival was42months, 3-year durationof response for patients with≥PR was 70%, and 3-year survival was 81%. Peripheral neuropathy occurred in 46% (grade ≥3 in 7%); only 8% discontinued bortezomib due to neuropathy. BDR is rapidly acting, well tolerated, and nonmyelotoxic, inducing durable responses in previously untreated WM. © 2013 by The American Society of Hematology.


Kastritis E.,National and Kapodistrian University of Athens | Zagouri F.,National and Kapodistrian University of Athens | Symeonidis A.,University of Patras | Roussou M.,National and Kapodistrian University of Athens | And 19 more authors.
Leukemia | Year: 2014

Suppression of uninvolved immunoglobulins is common in multiple myeloma (MM) but the prognostic significance of this phenomenon has not been assessed. We evaluated the prognostic significance of the preservation of uninvolved immunoglobulins in 1755 consecutive, unselected, patients with newly diagnosed, symptomatic MM with pre-therapy immunoglobulin levels measured by nephelometry. Suppression of at least one uninvolved immunoglobulin was observed in 87% of patients and was more common in patients with immunoglobulin A myeloma, those aged over 65 years, in patients with advanced-International Staging System (ISS) stage, extensive-bone marrow infiltration, anemia, low platelet counts, high levels of serum M-monoclonal protein or renal dysfunction. Patients with preserved immunoglobulins had a better survival than patients with suppressed immunoglobulins (median survival 55 vs 41.5 months, P<0.001). In multivariate analysis, preservation of uninvolved immunoglobulins was independently associated with better survival (hazard ratio: 0.781, 95% confidence interval: 0.618-0.987, P=0.039); irrespective of the treatment. In a subset of 500 patients, which were strictly followed for disease progression, preservation of uninvolved immunoglobulins was associated with a significantly longer progression-free survival (60 vs 25 months, P<0.001), independently of other common prognostic factors. In conclusion, preservation of uninvolved immunoglobulins in newly diagnosed patients with symptomatic MM was independently associated with long term disease control and improved survival.Leukemia advance online publication, 11 April 2014; doi:10.1038/leu.2014.110.


Terpos E.,National and Kapodistrian University of Athens | Anargyrou K.,251 General Air Force Hospital | Katodritou E.,Theagenion Cancer Center | Kastritis E.,National and Kapodistrian University of Athens | And 14 more authors.
International Journal of Cancer | Year: 2012

The circulating levels of several angiogenic cytokines [angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), angiogenin and basic fibroblast growth factor (bFGF)] were evaluated in 174 consecutive patients with newly diagnosed, symptomatic, multiple myeloma (MM). Circulating levels of Ang-1/Ang-2 were reduced in myeloma patients compared to controls, whereas VEGF and angiogenin levels were increased. Reduced angiopoietin-1/angiopoietin-2 ratio correlated with advanced disease features including international staging system (ISS)-3 stage, renal impairment and extensive bone disease. Based on immunohistochemical results in 20 patients (10 with the higher and 10 with the lower values of circulating angiopoietin-2) we found that angiopoietin-2 is expressed by myeloma cells and correlates with increased microvessel density in subsets of patients. Furthermore, Ang-1/Ang-2 ratio correlated with survival. Patients with circulating Ang-1/Ang-2 below or equal to the median value (6.03) had a median survival of 26.3 months compared to 53 months of all others (p = 0.002). Interestingly, this was mainly observed in patients who received first-line therapy with novel agent-based regimens (65% of our patients). Furthermore, a subset of ISS-3 patients with serum Ang-1/Ang-2 above the median value had favourable prognosis (median survival: 45 months versus 17 months of all others; p = 0.0001). The multivariate analysis revealed that low Ang-1/Ang-2 ratio could independently predict for inferior survival in our cohort of patients (relative risk (RR) 2.07, 95% CI 1.50-2.42; p < 0.001). These results highlight the role of angiopoietins pathway in the biology of MM and reveal novel targets for the development of antimyeloma agents. Copyright © 2011 UICC.


Komninaka V.,Laikon General Hospital | Kolomodi D.,Laikon General Hospital | Christoulas D.,251 General Air Force Hospital | Marinakis T.,Georgios Gennimatas General Hospital | And 5 more authors.
European Journal of Haematology | Year: 2015

Objective: The aim of this study was to evaluate bone involvement in patients with Gaucher disease (GD) and to propose a novel semi-quantitative magnetic resonance imaging (MRI) staging. Methods: MRI of the lumbar spine, femur, and tibia was performed in 24 patients with GD and 24 healthy controls. We also measured circulating levels of C-C motif ligand-3 (CCL-3) chemokine, C-telopeptide of collagen type-1 (CTX), and tartrate-resistant acid phosphatase isoform type-b (TRACP-5b). Results: We used the following staging based on MRI data: stage I: region of interest (ROI) 1/2 of normal values and bone infiltration up to 30%; stage II: ROI 1/3 of normal values and bone infiltration from 30 to 60%; stage III: ROI 1/4 of normal values and bone infiltration from 60% to 80%; and stage IV: detection of epiphyseal infiltration, osteonecrosis and deformity regardless of the ROI's values. All but two patients had abnormal MRI findings: 9 (37.5%), 6 (25%), 3 (12.5%), and 4 (16.7%) had stages I-IV, respectively. Patients with GD had elevated chitotriosidase, serum TRACP-5b, and CCL-3 levels (P < 0.001). Conclusions: We propose an easily reproducible semi-quantitative scoring system and confirm that patients with GD have abnormal MRI bone findings and enhanced osteoclast activity possibly due to elevated CCL-3. © 2015 John Wiley & Sons A/S.


PubMed | Georgios Gennimatas General Hospital, Laikon General Hospital, National and Kapodistrian University of Athens and 251 General Air Force Hospital
Type: Journal Article | Journal: European journal of haematology | Year: 2015

The aim of this study was to evaluate bone involvement in patients with Gaucher disease (GD) and to propose a novel semi-quantitative magnetic resonance imaging (MRI) staging.MRI of the lumbar spine, femur, and tibia was performed in 24 patients with GD and 24 healthy controls. We also measured circulating levels of C-C motif ligand-3 (CCL-3) chemokine, C-telopeptide of collagen type-1 (CTX), and tartrate-resistant acid phosphatase isoform type-b (TRACP-5b).We used the following staging based on MRI data: stage I: region of interest (ROI) 1/2 of normal values and bone infiltration up to 30%; stage II: ROI 1/3 of normal values and bone infiltration from 30 to 60%; stage III: ROI 1/4 of normal values and bone infiltration from 60% to 80%; and stage IV: detection of epiphyseal infiltration, osteonecrosis and deformity regardless of the ROIs values. All but two patients had abnormal MRI findings: 9 (37.5%), 6 (25%), 3 (12.5%), and 4 (16.7%) had stages I-IV, respectively. Patients with GD had elevated chitotriosidase, serum TRACP-5b, and CCL-3 levels (P<0.001).We propose an easily reproducible semi-quantitative scoring system and confirm that patients with GD have abnormal MRI bone findings and enhanced osteoclast activity possibly due to elevated CCL-3.


PubMed | Euroclinic Hospital, Hoffmann-La Roche, St Paul Hospital, University of Thessaly and 12 more.
Type: Journal Article | Journal: Clinical and experimental rheumatology | Year: 2016

To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in daily clinical practice.This was a multicentre (17 Greek Rheumatology sites), prospective, long-term, pharmacovigilance study of patients with moderate to severe RA and an inadequate response or intolerance to 1 anti-tumour necrosis factor (TNF) agents. Adverse events (AEs) were recorded and collected prospectively every 2-6 months.234 patients (mean age: 5912.5, 79.5% women, mean DAS28: 5.351.32) were included and followed for 27.7 months (median). The overall AEs, serious AE (SAEs) and serious infection (SIEs) rate were 48.36, 6.68 and 2.53/100 patient-years, respectively. Three cases of hepatitis B virus (HBV) reactivation were recorded (two in chronic and one in past HBV infection). Withdrawals due to AEs (5.6%) occurred more frequently during the first cycles of RTX therapy while repeated RTX cycles were not associated with an increased risk of AEs. There were 3 deaths with an incidence rate of 0.69/100 patient-years. Age 65 years was associated with a higher incidence rate ratio of AEs and SAEs as compared to <65 years (1.53, p=0.002 and 2.88, p=0.005, respectively). Drug retention rate during 434.28 patient-years of follow-up was 57.3%. Factors associated with drug discontinuation by multivariate analysis included age, baseline swollen joint count and no use of concomitant methotrexate therapy.Long-term RTX therapy in a real-life RA cohort, did not reveal any new safety issues. Advanced age was associated with increased risk of AEs and premature drug discontinuation.


Lakis S.,Georgios Gennimatas General Hospital | Papamitsou T.,Aristotle University of Thessaloniki | Panagiotopoulou C.,Georgios Gennimatas General Hospital | Kotakidou R.,Georgios Gennimatas General Hospital | Kotoula V.,Aristotle University of Thessaloniki
World Journal of Gastroenterology | Year: 2010

AIM: To analyze α-methylacyl CoA racemase (AMACR) expression in relation to various dysplasia phenotypes and clinicopathological parameters of sporadic colorec-tal adenomas. METHODS: Fifty-five cases of sporadic colorectal adenomas were categorized according to the Vienna classification for Gastrointestinal Neoplasia. These corresponded to a total of 98 different intra-lesion microscopic fields that were further independently assigned a histological grade based on the old nomenclature (mild, moderate, severe dyplasia and carcinoma in situ). AMACR expression was evaluated by immunohistochemistry and statistical analysis was performed to investigate possible associations with various clinicopathologic parameters of adenomas i.e. gender, age, localization, grade of dysplasia, size and configuration. RESULTS: Patient age ranged from 41 to 84 years (mean 65 ± 13.2 years); 37 patients were males and 18 were females. Adenomas ranged in size between 0.5 and 30 cm (mean 2 ± 1.3 cm), including 18 tubular, 16 vil-lous, 20 mixed or tubulovillous, and 1 giant sessile vil-lous adenoma. AMACR expression was observed in 3 out of 16 (18.8%) of low-grade vs 23 out of 35 (62.8%) of high-grade lesions (P= 0.002). Most adenomas exhibiting high grade dysplasia with in situcarcinoma-like areas stained positive for AMACR (15/17 or 88.2%) as compared to adenomas with high grade dysplasia which contained severe dysplasia-like foci (6/15 or 40%), (P = 0.005). In AMACR positive adenomas featuring severe dysplasia-like or in situcarcinoma-like areas, AMACR staining was not necessarily observed in the nn sttu component. Positivity in intra-lesion of mild, moderate or severe dysplasia-like foci was more often encountered in adenomas harboring nn sttu, intramucosal or infiltrative carcinoma [21/33 (63.6%) vs 9/40 (22.5%), P < 0.001]. Strong AMACR expression was found in 11 out of 17 vil-lous adenomas, but in only 1 out of 18 tubular lesions (P = 0.005). Larger lesions, i.e. > 1 cm stained more frequently for AMACR than smaller ones [27/45 (60%) vs 2/10 (20%), P = 0.02]. Overall, AMACR expression was associated with the grade of dysplasia, as well as with the size and configuration of adenomas, i.e. the consensus risk factors applied to colorectal adenoma patient surveillance. CONCLUSION: It may be worthy to further evaluate the possible use of AMACR as an additional risk factor for the assessment of colorectal adenoma patients.


Giagtzidis I.,Hippokrateio General Hospital | Karkos C.,Hippokrateio General Hospital | Pitoulias G.,Georgios Gennimatas General Hospital | Papazoglou K.,Hippokrateio General Hospital
International Angiology | Year: 2015

It has been postulated that atherosclerosis should be considered as a chronic inflammatory process and peripheral arterial disease (PAD) is a manifestation of such an atherosclerotic vascular disease. Matrix metalloproteinases (MMPs) are significant circulating biomarkers which play a pivotal role in the initiation, progression and clinical manifestations of PAD. This review summarizes the current body of evidence with regard to the association between MMPs and PAD.


Skoura E.,Evangelismos Hospital | Rondogianni P.,Evangelismos Hospital | Alevizaki M.,Alexandra Hospital | Tzanela M.,Evangelismos Hospital | And 4 more authors.
Nuclear Medicine Communications | Year: 2010

PURPOSE: Many patients with medullary thyroid carcinoma (MTC) have persistently elevated calcitonin levels after initial treatment, indicating disease recurrence. Conventional imaging is often negative or shows equivocal findings. In this study we report our experience with 2-deoxy-2-[F]fluoro-D- glucose positron emission tomography/computed tomography ([F]FDG-PET/CT) in the evaluation of this specific group. Methods: Between February 2007 and May 2009, 38 [F]FDG-PET/CT scans were performed on 32 patients with MTC and elevated calcitonin levels for localization of recurrent disease. Six of these patients had a second [F]FDG-PET/CT scan. Results: Among the 38 [F]FDG-PET/CT scans there were 18 positive and 20 negative scans. Out of the 18 positive scans, 17 were true positive and one false positive. These findings suggest that [F]FDG-PET/CT provides additional information in almost half of all cases (overall per patient sensitivity of 47.4%) but using a serum calcitonin cut-off of 1000pg/ml this rate is increased to 80%. An interesting finding of the study was that none of the six patients with multiple endocrine neoplasia type IIA syndrome had a positive [F]FDG-PET/CT scan for MTC. When these patients were excluded, the overall per patient sensitivity rose to 60% and in patients with calcitonin levels >1000pg/ml this rate increased to 100%. The mean SUVmax of all lesions showing [F]FDG uptake was 3.96±1.61 (range, 2-7). Conclusion: [F]FDG-PET/CT seems to be valuable for the detection of recurrence in patients with highly elevated calcitonin levels and negative conventional imaging findings. In addition, it seems that the sensitivity of [F]FDG-PET/CT may be higher in patients with sporadic or familial MTC than in patients with MTC as part of multiple endocrine neoplasia type IIA syndrome. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


PubMed | Georgios Gennimatas General Hospital
Type: Journal Article | Journal: International angiology : a journal of the International Union of Angiology | Year: 2011

The aim of this study was to assess the effects of buflomedil on the peripheral microcirculation in patients with type 2 diabetes mellitus (T2DM) without overt micro- or macroangiopathy.Twenty-three patients with T2DM were randomly assigned to receive buflomedil 600 mg/day for six months (N.=12) or no medication (N.=11). Skin blood flow in the lower limbs was assessed at baseline and after 3 and 6 months using Laser Doppler. We measured the following laser Doppler parameters: volume, flow and velocity.In patients treated with buflomedil, there was a significant increase in volume (P=0.039) and a trend for an increase in both flow and velocity (P=0.097 for both parameters). In contrast, significant decreases in volume and flow were observed in the control group (P=0.045 and P=0.027, respectively) whereas velocity did not change (P=0.150).In conclusion, buflomedil appears to have a beneficial effect on the peripheral microcirculation in patients with T2DM.

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