251 Hellenic Air Force and VA General Hospital

Athens, Greece

251 Hellenic Air Force and VA General Hospital

Athens, Greece
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Girschikofsky M.,Elisabethinen Hospital | Arico M.,Azienda Ospedaliero Universitaria A. Meyer | Castillo D.,Hospital Of La Santa Creu I Sant Pau | Chu A.,Imperial College London | And 12 more authors.
Orphanet Journal of Rare Diseases | Year: 2013

Langerhans Cell Histiocytosis (LCH) is an orphan disease of clonal dendritic cells which may affect any organ of the body. Most of the knowledge about the diagnosis and therapy is based on pedriatic studies. Adult LCH patients are often evaluated by physicians who focus on only the most obviously affected organ without sufficient evaluation of other systems, resulting in patients being underdiagnosed and/or incompletely staged. Furthermore they may be treated with pediatric-based therapies which are less effective and sometimes more toxic for adults. The published literature on adult LCH cases lacks a comprehensive discussion on the differences between pediatric and adult patients and there are no recommendations for evaluation and comparative therapies. In order to fill this void, a number of experts in this field cooperated to develop the first recommendations for management of adult patients with LCH. Key questions were selected according to the clinical relevance focusing on diagnostic work up, therapy, and follow up. Based on the available literature up to December 2012, recommendations were established, drafts were commented by the entire group, and redrafted by the executive editor. The quality of evidence of the recommendations is predominantly attributed to the level of expert opinion. Final agreement was by consensus. © 2013 Girschikofsky et al.; licensee BioMed Central Ltd.

Makras P.,251 Hellenic Air Force and VA General Hospital | Terpos E.,National and Kapodistrian University of Athens | Kanakis G.,National and Kapodistrian University of Athens | Papatheodorou A.,251 Hellenic Air Force and VA General Hospital | And 3 more authors.
Pediatric Blood and Cancer | Year: 2012

This retrospective study evaluated bone mineral density (BMD) and bone turnover in adults with LCH. Twenty-five adult patients and 25 matched controls were evaluated with BMD measurement and indices of bone metabolism. A BMD value below the expected range for age (Z-score≤-2.0) was found in 20% of patients; in particular, all postmenopausal women and men over 50-years had either osteoporosis or osteopenia. Patients with active disease had significantly lower Z-scores compared to patients with inactive disease and controls. Reduced bone turnover was found in all 14 patients treated with chemotherapy. No fractures due to osteoporosis were identified during 305.15 patient-years of follow-up. © 2011 Wiley Periodicals, Inc.

Papalou O.,National and Kapodistrian University of Athens | Livadas S.,National and Kapodistrian University of Athens | Karachalios A.,National and Kapodistrian University of Athens | Tolia N.,National and Kapodistrian University of Athens | And 3 more authors.
Hormones | Year: 2015

OBJECTIVE: To study white blood cells count (WBC) in women suffering from PCOS and compare these results with age and BMI-matched healthy women. The specific aim of this study was to assess the possible correlations of WBC with the major components of PCOS, obesity, insulin resistance and hyperandrogenism. DESIGN: Anthropometrical, metabolic and hormonal data were analyzed from 203 women with PCOS (NIH criteria) and 76 agematched controls. RESULTS: In the total population studied (N=279), WBC was significantly higher (P=0.003) in the PCOS group compared with age-matched healthy women and was positively correlated with BMI (r=0.461, p<0.001), total testosterone (r= 0.210, p<0.001), insulin (r=0.271, p<0.001), triglycerides (r=0.285, p<0.001), HOMA score (r=0.206, p=0.001), FAI (r=0.329, p<0.001) and negatively correlated with SHBG (r=-0.300, p<0.001) and HDL (r= -0.222, p<0.001). Due to the fact that WHR was only available in the group of PCOS women, the role of central adiposity is assessed only in this group. Multiple regression analysis in the PCOS group, including WHR, revealed BMI, SHBG and TGL as the main predicting factors of WBC. Multinomial logistic regression analysis was also conducted and overweight/obesity was the sole independent risk factor for elevated WBC (higher tertile) (OR:0.907 CI:0.85-0.96, p=0.002). After dividing the sample based on BMI in the lean subgroups, WBC did not differ significantly between PCOS and controls, while multiple regression analysis indicated SHBG as the main predicting factor of WBC. Finally, we picked out the group of overweight/obese (BMI ≥25 kg/m2) women with PCOS and conducted another classification based on HOMA score (HOMA-IR≤2: insulin-sensitive women, HOMA-IR>2: insulin-resistant women) in the group of overweight and obese women with PCOS separately. In overweight women with PCOS, WBC, although higher in the group of insulin-resistant, did not differ significantly between the two groups, while in the subcategory of overweight women WBC was significantly (p=0.02) higher in the group of insulin-resistant women (HOMA-IR >2). CONCLUSIONS: Chronic low-grade inflammation and increased white cell count do occur in PCOS. Obesity and insulin resistance are the two leading parameters that act accumulatively in the development of leucocytosis, whereas hyperandrogenism does not seem to affect it. © 2015, Hellenic Endocrine Society. All rights reserved.

Anastasilakis A.D.,424 General Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Makras P.,251 Hellenic Air Force and VA General Hospital | Savvides M.,424 General Military Hospital | And 4 more authors.
Hormone and Metabolic Research | Year: 2014

Periostin is a secreted extracellular matrix protein preferentially expressed in bone by osteocytes and periosteal osteoblasts. Reduced periostin expression may affect osteoblast differentiation and collagen type I synthesis and predispose to osteoporosis and increased fracture risk. We aimed to evaluate circulating periostin levels in postmenopausal women with low bone mass, their possible correlations with clinical and laboratory parameters, as well as the 3-month effect of zoledronic acid. Serum samples for periostin, 25-hydroxyvitamin D, parathyroid hormone (PTH), C-terminal telopeptide of type I collagen (CTx), and total alkaline phosphatase (tALP) were obtained from 46 postmenopausal women with low bone mass at baseline and 3 months after zoledronic acid infusion and from 30 age-matched, postmenopausal controls with normal bone mass at baseline. There was no difference in periostin levels between women with normal and low bone mass (250±15 vs. 272±14 ng/ml, respectively; p=0.279). Periostin remained essentially unchanged after zoledronic acid infusion (262±18 ng/ml; p=0.130). Serum periostin levels at baseline were not affected by previous bisphosphonate treatment, and were correlated only to tALP (rs=0.351; p=0.018). In multiple linear regression analysis, tALP (B=3.17; 95% CI=0.59-5.79; p=0.018) was associated with serum periostin levels at baseline, independently from previous anti-osteoporotic treatment, age, body mass index, and 25-hydroxyvitamin D. In conclusion, serum periostin levels do not differ between postmenopausal women with normal and low bone mass and are not affected by zoledronic acid treatment. Women with higher tALP have independently higher periostin levels. © Georg Thieme Verlag KG Stuttgart · New York.

PubMed | 251 Hellenic Air Force and VA General Hospital, Aristotle University of Thessaloniki, National and Kapodistrian University of Athens and 424 General Military Hospital
Type: Journal Article | Journal: Journal of bone and mineral metabolism | Year: 2016

There is increasing evidence for bone-liver interplay. The main aim of this study was to determine serum sclerostin and Dickkopf (DKK)-1 levels in patients with nonalcoholic fatty liver disease (NAFLD) and their association with the disease severity. Patients with biopsy-proven NAFLD, 13 with nonalcoholic simple steatosis (SS) and 14 with steatohepatitis (NASH), and 20 gender-, age-, body mass index- and waist circumference-matched controls were enrolled. Serum sclerostin, DKK-1, bone turnover markers, vitamin D, insulin and standard biochemical and hematologic parameters were measured; lumbar spinal dual-energy X-ray absorptiometry was performed. We observed that there was a progressive decline in serum sclerostin levels from the controls (76.16.8) to SS (53.56.4) and NASH (46.08.1pmol/l) patients (p=0.009); in adjusted pairwise comparisons, sclerostin was significantly higher in the controls than in NASH patients (p=0.012). Although serum DKK-1 did not differ between groups (p=0.135), there was a trend toward U-shaped distribution (controls 35.82.8; SS 27.32.9; NASH 36.84.4pmol/l). Higher DKK-1 levels were independently associated with NASH. Regarding specific histological lesions, DKK-1 levels were marginally lower in NAFLD patients with lower (33%) than higher (>33%) steatosis grade (27.73.1 and 38.84.7pmol/l, respectively; p=0.049). No other significant difference was observed within histological lesions. In conclusion, serum sclerostin levels were lower in NASH patients than in controls. DKK-1 levels were independently associated with NASH in NAFLD patients. The potential importance of these findings indicates a possible bone-liver interaction and warrants further investigation.

Toulis K.A.,424 General Military Hospital | Anastasilakis A.D.,424 General Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Makras P.,251 Hellenic Air Force and VA General Hospital
Hormones | Year: 2011

Targeting osteoblast may be the means of effectively improving both bone quality and mass, thus offering an intriguing alternative in the treatment of osteoporosis. Aside from injectable parathyroid hormone (PTH) and its novel preparations, PTH-related peptide (PTHrP), calcilytics, beta-adrenergic receptors, enhancement of Wnt signaling (mainly via sclerostin and Dickkopf-1 neutralization), regulation of low-density lipoprotein receptor-related protein (LPR) 5/osteoblast axis, activin, IGF-1, and bone morphogenic proteins (BMPs) are reviewed for their basic rationale and evidence of bone anabolic potential. Sclerostin neutralizing antibody, teriparatide transdermal patch, and PTHrP (1-36) are currently at an advanced stage of research. Safety and tissue specificity are the prerequisites in the development of a novel treatment, especially when addressing a chronic condition such as osteoporosis.

Anastasilakis A.D.,424 General Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Gkiomisi A.,424 General Military Hospital | Bisbinas I.,424 General Military Hospital | And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Decreased bone formation due to a coupling effect limits bone mass increases after antiresorptive treatment. Objective: The purpose of this study was to compare the effects of 2 potent antiresorptive agents with different mechanism of action on serum levels of Wnt antagonists, sclerostin and dickkopf-1 (Dkk-1). Design: This was an interventional, parallel assignment, open-label, randomized clinical trial. Setting: The study was conducted at the outpatient clinics for metabolic bone diseases of 424 General Military Hospital, Thessaloniki, Greece. Patients and Interventions: Naive postmenopausal women with low bone mass were assigned to zoledronic acid infusion (n = 46) or denosumab injection (n = 46). One woman in the zoledronic acid group was lost to follow-up. Main Outcome Measures: Serum sclerostin and Dkk-1 levels were the main outcomes. Secondary measurements were serum osteoprotegerin, receptor activator of nuclear factor κB ligand, procollagen type 1 N-terminal propeptide, and C-terminal cross-linking telopeptide of type 1 collagen. Results: Serum sclerostin levels significantly decreased in the zoledronic acid (P < .001) but increased in the denosumab group (P = .003). Dkk-1 levels significantly decreased in the zoledronic acid group (P = .006) but did not change in the denosumab group (P = .402). Serum osteoprotegerin remained essentially unchanged in either group, where as receptor activator of nuclear factorκBliganddecreased in the zoledronic acid group (P=.004) but increased in the denosumab group (P=.037). Bone markers (procollagentype1N- terminal propeptide, C-terminal cross-linking telopeptide oftype1collagen,and total serum alkaline phosphatase) decreased in both groups (all P < .001). Conclusions: Although they both decrease bone resorption, zoledronic acid and denosumab exert opposite effects on Wnt signaling: the former decreases serum levels of both sclerostin and Dkk-1, whereas the latter increases sclerostin and does not affect Dkk-1. Copyright © 2013 by The Endocrine Society.

Anastasilakis A.D.,424 General Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Makras P.,251 Hellenic Air Force and VA General Hospital | Sakellariou G.T.,424 General Military Hospital | And 7 more authors.
Bone | Year: 2012

An acute phase response (APR) is frequently observed in patients treated with intravenous (i.v.) zoledronate (ZOL). We aimed to define clinical and laboratory parameters that may predict ZOL-induced APR in women with low bone mass. Fifty-one postmenopausal women with low bone mass were given a single i.v. infusion of ZOL 5. mg. APR was clinically defined by the visual analog pain scale (VAS) for the musculoskeletal symptoms and body temperature. White blood cell count (WBC), leucocyte subpopulations, C-reactive protein (CRP), parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], interleukins (IL)-1b and -6, tumor necrosis factor (TNF)α and interferon (IFN)γ were measured before and 48 h following the infusion. Subsequently, patients were divided into those experiencing APR (APR+) or not (APR-). WBC, granulocytes, CRP, IL-1b and IL-6 were significantly increased, whereas lymphocytes, eosinophils, calcium, phosphate and 25(OH)D decreased 48. h after ZOL infusion. Twenty-eight of the 51 patients (54.9%) experienced an APR. APR+ patients were younger and had higher baseline lymphocytes compared to APR- patients. There was no difference (p= 0.405) in the development of APR between treatment-naive patients (19/32, 59.4%) and patients previously treated with another oral nitrogen-containing bisphosphonate (9/19, 47.4%). In conclusion, our data suggest that pre-treatment higher lymphocyte number increases the risk of APR while previous treatment with another nitrogen-containing bisphosphonate does not significantly reduce the risk. Serum 25(OH)D concentrations decrease significantly after the infusion, possibly as part of the inflammatory response to ZOL. © 2012 Elsevier Inc.

Anastasilakis A.D.,424 General Military Hospital | Toulis K.A.,424 General Military Hospital | Polyzos S.A.,Aristotle University of Thessaloniki | Anastasilakis C.D.,424 General Military Hospital | Makras P.,251 Hellenic Air Force and VA General Hospital
Therapeutics and Clinical Risk Management | Year: 2012

Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL), a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. Denosumab treatment is associated with a rapid, sustained, and reversible reduction in bone turnover markers, a continuous marked increase in bone mineral density at all sites, and a marked decrease in the risk of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis. Therefore, it could be considered as an effective alternative to previous bisphosphonate treatment as well as first-line treatment of severe osteoporosis. Cost-effectiveness studies support this suggestion. In addition, denosumab seems to be the safest treatment option in patients with impaired renal function. Denosumab is characterized by reversibility of its effect after treatment discontinuation, in contrast with bisphosphonates. Large-scale clinical trials, including the extension of FREEDOM trial for up to 5 years, are reassuring for its safety. However, given its brief post-market period, vigilance regarding adverse events related to putative RANKL inhibition in tissues other than bone, as well as those related to bone turnover oversuppression, is advised. © 2012 Anastasilakis et al, publisher and licensee Dove Medical Press Ltd.

Makras P.,251 Hellenic Air Force and VA General Hospital | Delaroudis S.,424 General Military Hospital | Anastasilakis A.D.,424 General Military Hospital
Metabolism: Clinical and Experimental | Year: 2015

Since the identification of osteoporosis as a major health issue in aging populations and the subsequent development of the first treatment modalities for its management, considerable progress has been made in our understanding of the mechanisms controlling bone turnover and disease pathophysiology, thus enabling the pinpointing of new targets for intervention. This progress, along with advances in biotechnology, has rendered possible the development of ever more sophisticated treatments employing novel mechanisms of action. Denosumab, a monoclonal antibody against RANKL, approved for the treatment of postmenopausal and male osteoporosis, significantly and continuously increases bone mineral density (BMD) and maintains a low risk of vertebral, non-vertebral, and hip fractures for up to 8 years. Currently available combinations of estrogens with selective estrogen receptor modulators moderately increase BMD without causing the extra-skeletal adverse effects of each compound alone. The cathepsin K inhibitor odanacatib has recently been shown to decrease vertebral, non-vertebral, and hip fracture rates and is nearing approval. Romosozumab, an anti-sclerosin antibody, and abaloparatide, a PTH-related peptide analog, are at present in advanced stages of clinical evaluation, so far demonstrating efficaciousness together with a favorable safety profile. Several other agents are currently in earlier clinical and preclinical phases of development, including dickkopf-1 antagonists, activin A antagonists, β-arrestin analogs, calcilytics, and Src tyrosine kinase inhibitors. © 2015 Elsevier Inc. All rights reserved.

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