Purpose: Plasminogen activator inhibitor-1 (PAI-1) participates in thrombotic, fibrinolytic, inflammatory and metabolic cascades. Since previous studies have focused on tissue and blood level concentrations, our goal was to investigate for the first time the independent relationship between plasma PAI-1 activity in resectable non small cell cell lung cancer (NSCLC) taking into consideration its several interfaces, and study its diagnostic and prognostic potential. Methods: In an adequately powered case-control study, plasma PAI-1 activity, metabolic parameters, classic adipokines, hemostatic, inflammatory and tumor biomarkers were measured in 110 consecutive patients with resectable NSCLC and 110 healthy subjects matched on age, sex and date of blood draw. Results: NSCLC patients exhibited significantly higher PAI-1 activity compared to controls (p<0.001). In NSCLC cases, PAI-1 activity correlated with somatometric variables, insulin, WBC, antithrombin III, protein C, plasminogen, IL-6 and tumor size (p<0.05). Plasma PAI-1 activity was independently associated with NSCLC beyond risk factors associated with NSCLC (OR: 6.9, 95% CI: 2.9-16.6, p<0.001). Plasminogen activity and body mass index emerged as independent predictors of PAI-1 activity in cases. Due to its high specificity, PAI-1 activity could represent a potentially useful parameter in ruling out NSCLC, alone or in combination with serum tumor markers associated with NSCLC. Conclusions: PAI-1 activity, reflecting PAI-1 functionality, may represent a potentially useful biomarker in NSCLC associated with thrombotic, tumor-promoting and metabolic networks. More clinical studies are needed to explore whether PAI-1 activity may be a practical biomarker in the risk assessment of NSCLC, at the crossroads of hemostasis and metabolism.

OBJECTIVES: Chemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. MATERIALS AND METHODS: In a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). RESULTS: NSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09-4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 μg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. CONCLUSION: Chemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.

Bisphenol-A (BPA), a prototype endocrine disrupting molecule, has been associated with many disease entities such as diabetes mellitus, obesity, polycystic ovarian disease, cardiovascular disease, reproductive and neurodevelopmental disorders. BPA has also been associated mainly with hormone sensitive cancers such as breast, prostate, endometrial, ovarian, testicular and thyroid cancers but also non-hormonal sensitive cancers such as cervical and lung cancers, osteosarcoma and meningioma. Recent research has investigated the sources of contamination which are responsible for higher BPA concentrations in the oral cavity and oropharyngeal space, representing the first site of BPA exposure after ingestion. Besides growing awareness and case registration, the incidence and prevalence of oral (OC) and oropharyngeal cancer (OPC) have increased during the last decades correlating with the increased production of BPA worldwide. So far, no study in the medical literature has explored the association of BPA with OC and OPC. BPA may be linked to the etiopathogenesis of OC and OPC through a multitude of mechanisms encompassing and interconnecting genetic, epigenetic, inflammatory, immune, metabolic, hormonal and oxidative stress alterations as well as modulation of oral microbiome. Hence, it is not possible to rule out a potential role of BPA exposure in oral and oropharyngeal tissue carcinogenesis, especially knowing its potential to participate in other non hormonal sensitive malignancies and to deregulate signaling pathways implicated in OC and OPC. This perspective aims at outlining evidence and proposing for the first time a potential link between BPA with OC and OPC, the most frequent subtypes of head and neck malignancies.

Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.

PURPOSE OF REVIEW: In this review, we investigate the role of classic and novel adipocytokines in cancer pathogenesis synopsizing the mechanisms underlying the association between adipocytokines and malignancy. Special emphasis is given on novel adipocytokines as new evidence is emerging regarding their entanglement in neoplastic development. RECENT FINDINGS: Recent data have emphasized the role of the triad of overweight/obesity, insulin resistance and adipocytokines in cancer. In the setting of obesity, classic and novel adipocytokines present independent and joint effects on activation of major intracellular signaling pathways implicated in cell proliferation, expansion, survival, adhesion, invasion, and metastasis. Until now, more than 15 adipocytokines have been associated with cancer, and this list continues to expand. While the plethora of circulating pro-inflammatory adipocytokines, such as leptin, resistin, extracellular nicotinamide phosphoribosyl transferase, and chemerin are elevated in malignancies, some adipocytokines such as adiponectin and omentin-1 are generally decreased in cancers and are considered protective against carcinogenesis. Elucidating the intertwining of inflammation, cellular bioenergetics, and adiposopathy is significant for the development of preventive, diagnostic, and therapeutic strategies against cancer. Novel more effective and safe adipocytokine-centered therapeutic interventions may pave the way for targeted oncotherapy.

Cloud computing is a reality in most business sectors. Hospitals have been more reluctant to adopt cloud technology due to strict data security regulations. Cloud could provide economies of scale reducing Information Technology spending in the Greek state-owned hospitals, while giving the opportunity to the hospitals to upgrade their profile offering web-based services. We propose a simple, robust and easy to apply approach for the Greek hospitals, focusing on clinical and laboratory data in order to move to the cloud environment. To the best of our knowledge, there is no other study regarding the adoption of cloud infrastructure in the Greek hospital sector. This innovative method could transform the business model of the hospitals.

Quality standards have been widely adopted in healthcare, while the Hospital Information Systems (HIS) support quality management in modern hospitals. However, staff compliance lags behind. In this study, we investigated the effect of a novel application, implemented in the HIS, on staff compliance in the Intensive Care Unit of a tertiary teaching hospital. This application integrates quality protocols to the HIS, which is routinely used by the nursing staff. Demographic data and self-reported compliance were recorded before and after the intervention. We found that the compliance rate was significantly increased and the application was well accepted by the majority of the staff. We also showed that previous ICU working experience is independently and positively associated with compliance (p=0.02, OR=2.86; 95% CI: 1.16 - 7.06), after adjustment for age and total nursing experience In conclusion, we developed an effective application for quality improvement aiming at facilitating educational processes and enhancing staff compliance.

PURPOSE: Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors. METHODS: In a large case-control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed. RESULTS: SH cases exhibited significantly higher circulating irisin than controls (p < 0.001). In all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk factors, including Framigham score and apolipoprotein B/apolipoprotein A-I. Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones. Serum irisin was independently associated with SH, above and beyond body mass index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09). CONCLUSIONS: Irisin may represent an adipo-myokine counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.

Nicotinamide phosphoribosyl-transferase (Nampt) or pre-B cell colony-enhancing factor or visfatin represents a pleiotropic molecule acting as an enzyme, a cytokine and a growth factor. Intracellular Nampt plays an important role in cellular bioenergetics and metabolism, particularly NAD biosynthesis. NAD biosynthesis is critical in DNA repair, oncogenic signal transduction, transcription, genomic integrity and apoptosis. Although its insulin-mimetic function remains a controversial issue, extracellular Nampt presents proliferative, anti-apoptotic, pro-inflammatory, pro-angiogenic and metastatic properties. Nampt is upregulated in many malignancies, including obesity-associated cancers, and is associated with worse prognosis. Serum Nampt may be a potential diagnostic and prognostic biomarker in cancer. Pharmacologic agents that neutralize Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer treatments. In particular, Nampt inhibitors as monotherapy or in combination therapy have displayed anti-cancer activity in vivo and in vitro. The aim of this review is to explore the role of Nampt in cancer pathophysiology as well as to synopsize the mechanisms underlying the association between extracellular and intracellular Nampt, and malignancy. Exploring the interplay of cellular bioenergetics, inflammation and adiposopathy is expected to be of importance in the development of preventive and therapeutic strategies against cancer.

PURPOSE: Fetuin-A and adiponectin, major hepatokine and adipokine respectively, have been implicated in systematic inflammation. Our aim was to jointly investigate whether kinetics of circulating fetuin-A, adiponectin and its isoform HMWA predict 28-day mortality in sepsis. MATERIALS AND METHODS: In a prospective study, serum fetuin-A, adiponectin and HMWA were determined in 102 ICU patients fulfilling the diagnostic criteria of SEPSIS-3, at enrollment and one week after, and in 102 healthy controls matched on age and gender. RESULTS: Serum fetuin-A was significantly lower in septic patients than controls (p<0.001). Among septic patients, those with septic shock and nonsurvivors presented lower fetuin-A, but higher adiponectin and HMWA compared to patients with sepsis and survivors respectively, both at baseline and day 7 (p<0.001). Fetuin-A exhibited negative correlations with APACHE II, CRP, procalcitonin, adiponectin and IL-6 but a positive one with albumin. Reduced fetuin-A as well as lower serum kinetics of fetuin-A (HR: 0.55, 95% C.I. 0.34-0.91, p=0.02), adiponectin but not HMWA were independently associated with 28-day mortality adjusting for age, gender, BMI, APACHE II, septic shock and laboratory biomarkers. CONCLUSIONS: Circulating fetuin-A kinetics may be a prognostic biomarker in septic patients. More research is essential to elucidate fetuin-A's ontological role in sepsis pathophysiology.

PURPOSE: Obstructive sleep apnea (OSA) represents a breathing disorder during sleep with significant health consequences. Few studies have examined the prevalence of OSA in psoriatic patients and whether OSA may be associated with psoriasis risk. We aimed to explore: (1) the inverse relationship, that is whether psoriasis might represent an independent predictor of OSA and its severity considering important predisposing factors and (2) the psoriatic phenotype related to severe OSA. METHODS: In a large hospital-based case-control study, we examined a total of 253 patients with OSA and a control group of 104 subjects without OSA, who underwent full nocturnal polysomnography and dermatologic examination. RESULTS: The prevalence of psoriasis was significantly greater in OSA patients than in controls (p = 0.03). Psoriasis was associated with OSA risk (p = 0.04) but not severity of OSA, sleepiness severity or sleep efficiency, independently from age, gender, anthropometric features, and significant comorbidities. The phenotype of a psoriatic patient suffering from severe OSA is not different from that of a patient with severe OSA and is not associated with psoriasis severity indexes. OSA psoriatic patients were not compliant with CPAP treatment in comparison with OSA patients without psoriasis. CONCLUSION: Psoriasis may represent an independent risk factor for OSA above and beyond significant comorbidities, anthropometric and metabolic parameters. Physicians should be aware of the bi-directional association of psoriasis and OSA. Managing psoriasis may be a potential target for preventing OSA as well as the potential cardiovascular mortality related to OSA and psoriasis.

CONTEXT: Resistin is associated with inflammation, atherosclerosis and cardiovascular (CV) disease. OBJECTIVE: To associate circulating resistin with all-cause and CV mortality in chronic kidney disease (CKD) patients. METHODS: Serum resistin was determined in a cohort of 80 elderly, non-diabetic patients with stable CKD at different stages in a follow-up period of 5 years. RESULTS: Circulating resistin was significantly elevated in deceased compared to alive patients. Resistin emerged as an independent biomarker of all-cause and CV mortality after a 5-year follow-up period. CONCLUSION: Elevated circulating resistin was a significant independent predictor of CV and all-cause mortality in elderly, non-diabetic CKD patients.

There are limited data on fetuin-A, soluble leptin receptor (sOB-R) and free leptin index (FLI) in patients with chronic lymphocytic leukemia (CLL). The aim of this study was to compare circulating fetuin-A, sOB-R levels and FLI between 95 patients with CLL and 95 matched controls, as well as among different stages of CLL. Circulating fetuin-A was significantly lower in cases than controls (241.9 ± 99.2 vs. 288.8 ± 127.7 μg/mL; p = 0.005). Although circulating sOB-R levels were similar between groups, FLI was lower in cases than controls (0.45 ± 0.42 vs. 0.67 ± 0.57; p = 0.003). Furthermore, lower fetuin-A or FLI, but not sOB-R, were independently associated with CLL (p < 0.05), particularly among overweight/obese individuals. Fetuin-A, s-OB-R and FLI were similar between different stages of CLL severity, or between symptomatic and asymptomatic disease. In conclusion, circulating fetuin-A and FLI, but not sOB-R, were lower in patients with CLL than controls, a finding warranting further investigation.

OBJECTIVES: To evaluate the prevalence and its clinical characteristics of psoriatic arthritis (PsA) in a specialized psoriasis clinic of a University Hospital. METHODS: In this retrospective study, 278 patients with psoriasis were evaluated between 2011 and 2013. RESULTS: The study included 278 patients with psoriasis: 144 (52%) were male and 134 (48%) female. Their median age was 51.41 with median psoriasis presenting age of 34.52 years. Referring to the type of psoriasis, 86% presented with plaque psoriasis, 5% guttate, 2% palms and soles, 2% inverse, 1% pustular and 4% with psoriasis of more than one type. Nail disease appeared in 121 patients (43.5%) and scalp disease in 175 (63%). Of these patients, 85 (30%) had PsA, whereas 51% of patients with PsA had psoriatic nail disease. With reference to the PsA type, 43 (51%) patients presented with polyarthritis, 10 (12%) with oligoarthritis, 7 (8%) with axial arthritis, whereas the rest 25 of them (31%) had PsA of more than one type. The subgroup of patients with PsA had significantly higher rates of comorbidities including arterial hypertension, diabetes and hypercholesterolaemia compared to non-PsA patients with 41% vs. 17% (P = 0.001), 20% vs. 8% (P = 0.021) and 41% vs. 19% (P = 0.004), respectively. CONCLUSION: The prevalence of PsA among patients with psoriasis was relatively higher in Greece compared to other ethnic-based studies. Comorbidities related to life expectancy were more frequent. As there is a high percentage of undiagnosed cases with active arthritis among patients with psoriasis, dermatologists should be aware of PsA clinical signs in order to recognize it earlier and provide successful treatment.

Lymphomatoid papulosis (LyP) refers to an indolent cutaneous lymphoma. The association of prognostic clinicopathological risk factors with a second hematologic malignancy has not yet been determined. We investigated the prognostic effect of clinicopathological characteristics on the occurrence of a second lymphoma, as well as the first-line treatment, in 24 patients diagnosed with LyP using logistic regression models. We showed that lymphoma occurrence was associated with a lower mean age at onset of LyP symptoms, histological types B and C, head-located LyP lesions and a higher frequency of LyP recurrences. In multivariate analyses, histologic type A was associated with a lower risk of second lymphoma (odds ratio [OR] = 0.12, 95% confidence interval [CI] 0.014-0.98; p = 0.045) adjusting for age of LyP first symptomatology, and an important increased lymphoma-free survival rate (long-rank test; p = 0.06). Clinicopathological characteristics are important in defining the clearance or persistence of LyP lesions and may predict the occurrence of a second lymphoma.

OBJECTIVE: Hypertensive patients with CKD present an increased risk for cardiovascular mortality. Among the proteins synthesized and released from adipose tissue, resistin is a cytokine whose physiologic role has been the subject of much research and controversy. We and others have demonstrated that serum resistin levels are higher in patients with CKD and correlate directly with inflammatory markers, including TNF-α and hsCRP. Since inflammation has been consistently linked to atherosclerosis, death, and cardiovascular (CV) events, our goal was to investigate the interaction between resistin levels and long term all-cause and CV mortality in elderly non-obese and non-diabetic with hypertension. DESIGN AND METHOD: We studied 80 patients (52 men/28 women) 70.9 ± 8.6 years of age with hypertension and CKD. Exclusion criteria was obesity and diabetes mellitus, active infection, acute illness, chronic inflammatory disease or cancer, and immunosuppresive, anti-inflammatory or anti-lipidemic drugs. Demographic data, clinical information and blood samples were collected prospectively. The patients were observed for 5 years. RESULTS: During the follow-up 28 of 80 (35%) patients died: 16 (57%) deaths due to CV events and 12 (43%) of other causes. Patients who died were older and had higher DBP, compared to survivors, but had no differences in BMI, smoking, SBP and HR. Deceased patients had higher WBC, hsCRP, BUN, creatinine, cystatin C, phosphate, magnesium and potassium levels and lower eGFR, Hct/Hg, T3, T4, total cholesterol, LDL-C, albumin and sodium levels compared to survivors. No significant differences in platelet count, TNF-α, fibrinogen, oxLDL, ADMA, HgA1C and HOMA-index were revealed between the groups. eceased patients had significantly higher resistin levels than survivors at baseline (p = 0.025), but adiponectin, visfatin and leptin did not differ between the two groups. Five variables, namely resistin, sodium, cholesterol, T3 and WBC remained significantly associated with survival and were used in the multivariate Cox regression analysis, which revealed that only resisitin, cholesterol and WBC maintained their discriminatory ability, as independent predictors of mortality both by forward and backward stepwise analysis. CONCLUSIONS: Elevated serum resistin was a significant independent biomarker of CV and all-cause mortality in elderly, non-diabetic CKD patients with hypertension.

Higher body mass index and adiposopathy have been associated with increased risk of hematologic malignancies such as leukemia, multiple myeloma, myeloproliferative disorders, Hodgkin's and non-Hodgkin's lymphoma, and myelodysplastic syndromes. Adiponectin is a multimeric protein of the white adipose tissue presenting anti-inflammatory, insulin-sensitizing, anti-atherogenic, cardioprotective, and anti-neoplastic properties. Its anti-neoplastic actions are manifested via two mechanisms: (i) direct action on tumor cells by enhancing receptor-mediated signaling pathways and (ii) indirect action by regulating inflammatory responses, influencing cancer angiogenesis, and modulating insulin sensitivity at the target tissue site. In the bone marrow milieu, adiponectin and its main receptors are expressed by the majority of bone marrow stromal cell populations influencing hematopoietic stem cells function. Adiponectin may represent a molecular mediator relating adiposopathy with leukemogenesis and myelomagenesis. Several epidemiological studies conducted to date relate hypoadiponectinemia to the risk of myeloid-derived hematopoietic cancer and multiple myeloma. Adiponectin may be a promising biomarker with potential diagnostic and prognostic utility in determining the likelihood of myeloma and leukemia progression in certain cohorts of monoclonal gammopathy of undetermined significance patients and in myeloid hematologic malignancies, respectively. This review summarizes experimental and epidemiologic data regarding the role of adiponectin in hematologic malignancies in the context of adiposopathy. Enhancement of endogenous adiponectin, adiponectin replacement, or manipulation of adiponectin receptor sensitivity may be an attractive goal for prevention and an effective therapeutic strategy against hematopoietic cancer, specifically in overweight/obese individuals. Further studies are required to elucidate the role of the bone marrow microenvironment adiponectin in complex interactions involved in preleukemic and leukemic states.

A growing body of evidence suggests that adiponectin presents anti-neoplastic effects via two mechanisms. First, adiponectin can act directly on tumor cells by enhancing receptor-mediated signaling pathways. Secondly, adiponectin may act indirectly by regulating inflammatory responses, influencing cancer angiogenesis and regulating insulin sensitivity at the target tissue site

BACKGROUND: Survivin is a novel antiapoptotic gene, which is a member of the inhibitor of apoptosis protein (IAP) family. Recently, 3 splice variants of this gene were cloned and characterized. This study aimed to validate a sensitive and specific method for the detection of survivin variants in breast cancer. METHODS: Real-time quantitative polymerase chain reaction (qPCR) was performed on the cDNA with a reverse primer specific for each splice variant and a pair of common hybridization probes. RESULTS: The expression of wild-type survivin was significantly correlated with survivin-2b, survivin-ΔEx3, and the ratio of survivin-ΔEx3 to wild-type survivin (P < .001). The ratio of survivin-2b to wild-type survivin was strongly associated with the ratio of survivin-ΔEx3 to wild-type survivin (P < .001). There was a strong positive association between the grade of the tumor and survivin-2b mRNA, survivin-ΔEx3 mRNA, and the ratio of survivin-ΔEx3 to wild-type survivin mRNA (P < .05). The ratio of survivin-2b to wild-type survivin was significantly associated with the presence of estrogen receptors (P = .05). CONCLUSION: Our validated data suggest that survivin isoforms may be related to clinicopathological features and could be used as molecular prognostic tools or as new therapy targets.

Excess body weight is associated with various types of malignancies. Resistin, originally described as an adipocyte-specific hormone modulating insulin resistance in rodents, may exhibit proliferative, antiapoptotic, proinflammatory, proangiogenic and metastatic properties. Accumulating evidence supports a role of resistin as a risk factor and potential diagnostic and prognostic biomarker in cancer. In this report, the current knowledge about resistin's properties and pathophysiological implications in cancer in the context of dysregulated adipose tissue in obesity is summarized; clinical translations, preventive and therapeutic considerations, and future perspectives in the field of resistin research are discussed. At the same time, several enigmatic issues involving resistin receptor and signaling pathways remain to be clarified in order to unmask its ontological role in cancer pathophysiology.

BACKGROUND: Scalp psoriasis, one of the most common sites of psoriasis involvement, is often difficult to control with topical agents. There is a lack of substantial evidence-based data for the efficacy and safety of systemic therapies. METHODS: Two patients from our university-based psoriasis clinic with chronic plaque psoriasis and severe recalcitrant scalp involvement were assessed by Psoriasis Area and Severity Index and Psoriasis Scalp Severity Index scores, respectively, and quality of life by the Dermatology Life Quality Index. RESULTS: We report 2 psoriasis patients with very severe scalp psoriasis who developed a fast clinical response of scalp psoriasis to ustekinumab in 8 weeks with excellent patient adherence up to 28 weeks of follow-up and positive impact on quality of life due to rapid and long-term clearing. CONCLUSION: Ustekinumab produces a fast clinical response of recalcitrant scalp psoriasis with excellent patient adherence and a positive impact on quality of life due to rapid and long-term clearing in patients with very severe scalp involvement who failed conventional topical and systemic treatment.

The effectiveness of radiotherapy in patients with basal cell carcinoma (BCC) has been already reported in the literature. However, there is little information about the irradiation of BCC in elderly patients, especially due to the low conformity of them to daily irradiation. Thirty-eight retrospectively selected elderly patients (78 years as median age) diagnosed with skin BCC of the head and neck area were treated with five weekly fractions of 600 cGy by three-dimensional conformal radiotherapy (3DCRT) as an adjuvant treatment. The primary endpoint was the relapse free survival. Acute toxicity, as secondary endpoint, was assessed according to EORTC/RTOG criteria. Among our patients, there were only three local recurrences at 15, 32 and 38 months post-3DCRT. There was no severe toxicity, while only 10 out of 38 patients presented grade II/III skin toxicity. Our proposed irradiation schedule seems effective in terms of local control and acute toxicity and could be an alternative scheme for elderly patients unfit for daily irradiation.

Breast cancer (BC) is the most frequent type of non skin cancer among women and a major leading cause of cancer-related deaths in Western countries. It is substantial to discover novel biomarkers with diagnostic, prognostic or predictive usefulness as well as therapeutic value for BC. Micro-RNAs (miRNAs) belong to a novel class of endogenous interfering RNAs that play a crucial role in post transcriptional gene silencing through mRNA targeting and, thus, are involved in many biological processes encompassing apoptosis, cell-cycle control, cell proliferation, DNA repair, immunity, metabolism, stress, aging, etc. MiRNAs exert their action mainly in a tumor suppressive or oncogenic manner. The specific aberrant expression patterns of miRNAs in BC that are detected with the use of high-throughput technologies reflect their key role in cancer initiation, progression, migration, invasion and metastasis. The detection of circulating extracellular miRNAs in plasma of BC patients may provide novel, non-invasive biomarkers in favor of BC diagnosis and prognosis and, at the same time, accumulating evidence has underscored the possible contribution of miRNAs as valuable biomarkers to predict response to chemotherapy or radiotherapy. Data from in vitro and in vivo studies on BC have revealed promising therapeutic approaches via miRNA delivery and miRNA inhibition. The purpose of this review is to explore the ontological role of miRNAs in BC etiopathogenesis as well as to highlight their potential, not only as non-invasive circulating biomarkers with diagnostic and prognostic significance, but also as treatment response predictors and therapeutic targets aiding BC management.

CONTEXT: A proteomic analysis has proposed fetuin-A (alpha-2-HS-glycoprotein) as a new potential marker for pancreatic cancer (PC). OBJECTIVE: Circulating fetuin-A levels in patients with PC. METHODS: Serum fetuin-A was measured in 81 cases with PC and 81 matched controls before the initiation of any treatment. RESULTS: Serum fetuin-A was not independently associated with the presence of PC. Although there was a trend with higher fetuin-A levels across PC stages, comparisons of fetuin-A in patients within different PC prognostic stages revealed no differences. CONCLUSIONS: Circulating fetuin-A was similar between patients and controls and was not associated with the disease severity.

Psoriasis has been lately seen as a potential systemic inflammatory disease associated with a range of co-morbidities exhibiting an overlapping pathology and presenting a great social health impact such as cardiovascular disease and metabolic diseases, including obesity. Adipose tissue is considered a genuine endocrine organ producing a variety of bioactive adipocytokines, such as leptin, adiponectin, resistin and visfatin, participating in physiological and pathological processes, such as energy balance, insulin sensitivity and resistance, immunity, inflammation, hematopoiesis and angiogenesis. Adipocytokines could serve as a missing link in the association between psoriasis, obesity and metabolic co-morbidities. In chronic inflammatory disease states such as psoriasis, adipocytokines may be implicated in psoriasis onset, progression, severity as well as in the pathogenesis of co-morbidities. Measuring serum adipocytokine levels in the future may be useful in predicting psoriasis severity, progression, treatment outcome and risk of any co-morbidities. Interventions to decrease pro-inflammatory adipocytokine levels could offer preventive and therapeutic options for improving psoriasis severity and protecting against its co-morbidities. Candidate strategic interventions incorporate increased physical activity, weight control and pharmacologic approaches such as metformin. However, the mechanisms underlying the actions of adipocytokines in psoriasis as well as their potential diagnostic, prognostic and/or therapeutic utility require further investigation with larger prospective, longitudinal and mechanistic studies.

Accumulating evidence supports that psoriasis may be a potential multisystem inflammatory disease associated with a range of co-morbidities showing an overlapping pathology and an important health impact such as metabolic diseases.   Psoriasis is associated with an increased risk of obesity, metabolic syndrome (Mets) and diabetes mellitus type 2 (t2DM), following a “dose-response” relationship from mild to severe psoriasis. Conversely, recent evidence from large prospective studies suggests that obesity constitutes a risk factor for psoriasis and psoriatic arthritis. Also, a dyslipidemic profile may precede psoriasis onset. Both obesity, Mets and psoriasis, characterized as chronic inflammatory states, stem from a shared underlying pathophysiology exhibiting common genetic predisposition and risk factors such as high caloric intake, physical inactivity and psychological stress. Excess weight may potentiate the inflammation of psoriasis through the deregulation of adipocytokines while, at the same time, it may help the development of Mets. Interestingly, recent translational data has shown that psoriasis, through increased T-helper inflammatory cytokines in skin and sera, may exert a plethora of effects on insulin regulation and lipid metabolism. Larger population-based prospective cohort and longitudinal studies are needed to unravel the association between psoriasis and metabolic co-morbidities. The recognition of the intricate complex interplay between psoriasis and metabolic co-morbidities may help dermatologists to be aware of associated metabolic co-morbidities in order to screen for metabolic diseases and manage holistically and effectively the psoriatic patient.

AIM: To determine the prevalence and frequency of non classical congenital adrenal hyperplasia (NC-CAH) due to 21-OHD at the time of clinical presentation and at the peripubertal period in a substantial sample of Greek women with acne and to investigate the correlation of serum T, 17-OHP and DHEA-S with acne appearance at the time of clinical presentation. METHODS: One hundred and twenty-three unselected women with hyperandrogenemic symptoms were examined. After the ACTH stimulation test, 6 (4.9%) women were diagnosed with NC-CAH due to 21-OHD. RESULTS: There was not any statistical significant difference in the frequency of peripubertal acne between NC-CAH group of patients (6.4%) and patients with hyperandrogenemia of other aetiology (93%), mainly ovarian (P = 0.41). However, there was a statistical significant difference in the prevalence of acne at the time of clinical examination between the two groups (P = 0.04). Acne was present in 83.3% of women with NC-CAH vs. 41.02% of women in the hyperandrogenic group without NC-CAH. A statistically significant decrease of acne from the peripubertal time to the time of clinical examination in the group of women with hyperandrogenemia of other aetiology (-21.37%) was observed compared to women with NC-CAH (P < 0.001). CONCLUSION: We have shown that acne persists from peripubertal period to adult life in NC-CAH women whereas it tends to diminish in women with hyperandrogenemia of other aetiology. Acne is a prominent finding in women with NC-CAH. Serum concentrations of 17-OHP after ACTH stimulation (17-OHP6O ) should be investigated in women with persistent acne in adult life.

BACKGROUND: Psoriasis is associated with a variety of comorbidities such as obesity and cardiovascular disease. OBJECTIVE: In a cross-sectional study, we explored whether obstructive sleep apnea and hypopnea syndrome (OSAHS) is associated with psoriasis characteristics and metabolic parameters. METHODS: Thirty-five patients with chronic plaque psoriasis underwent a nocturnal polysomnography study and were analysed for Apnoea-Hypopnoea Index to assess OSAHS severity and Framigham score to predict the absolute risk of coronary artery disease at 10 years. The association of OSAHS with psoriasis was examined according to psoriasis characteristics (PASI and DLQI scores, disease duration and previous use of systemic treatments), metabolic parameters (Body Mass Index - BMI, waist to hip ratio - WHR, lipid profile) and other comorbidities (obesity, hypertension, arthritis and cardiovascular disease). RESULTS: There was no correlation between psoriasis characteristics and OSAHS. Psoriasis patients with OSAHS presented more frequent snoring and lower sleep quality compared with those without OSAHS. In univariate analyses, OSAHS was associated with increased BMI and hypertension in psoriasis patients. In multivariable logistic regression models, there was statistically significant evidence that only BMI and hypertension were associated with increased risk of OSAHS, adjusting for psoriasis characteristics, age and gender. Presence of metabolic syndrome, WHR, and smoking were not significant risk factors for OSAHS. In subgroup analyses, OSAHS correlated with duration of psoriasis (>8 years) in women (P = 0.021) and with Framigham score in men (P = 0.035). CONCLUSION: OSAHS may be a comorbidity in obese psoriasis patients with hypertension. Treatment with continuous positive airway pressure and weight loss interventions should be initiated.

OBJECTIVE: Previous few studies have shown that resistin is significantly elevated in breast cancer (BC) patients. Therefore, we investigated whether serum resistin could be used as a potential diagnostic and prognostic tool for postmenopausal BC (PBC), taking into account clinicopathological features, serum tumor markers, anthropometric, metabolic, and, for the first time, inflammatory parameters. METHODS: Serum resistin, tumor markers (CA 15-3 and CEA), metabolic, anthropometric and inflammatory parameters (TNF-α, IL-6, hsCRP) were determined in 103 postmenopausal women with incident, pathologically confirmed, invasive BC, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL). RESULTS: Mean serum resistin was significantly higher in cases than in controls and patients with BBL (p<0.001). In patients, resistin was significantly associated with tumor and inflammatory markers, cancer stage, tumor size, grade and lymph node invasion but not with anthropometric, metabolic parameters and hormone receptor status. Multivariable regression analysis revealed that serum IL-6 (p=0.02) and cancer stage (p=0.048) were the strongest determinants of serum resistin in cases adjusting for demographic, metabolic and clinicopathological features. Although resistin's diagnostic performance was low based on ROC curve analysis [0.72, 95% CI: 0.64-0.79], it could, however, represent a BC biomarker reflecting advanced disease stage and inflammatory state. CONCLUSION: Further prospective and longitudinal studies are needed to evaluate whether serum resistin could be used as a prognostic tool in BC monitoring and management. More research is essential to elucidate resistin's ontological role in the association between obesity, representing a chronic low-grade subclinical inflammation, and PBC.

Leptin is an adipocyte-secreted hormone that has been proposed to regulate energy homeostasis as well as metabolic, reproductive, neuroendocrine, and immune functions. In the context of open-label uncontrolled studies, leptin administration has demonstrated insulin-sensitizing effects in patients with congenital lipodystrophy associated with relative leptin deficiency. Leptin administration has also been shown to decrease central fat mass and improve insulin sensitivity and fasting insulin and glucose levels in HIV-infected patients with highly active antiretroviral therapy (HAART)-induced lipodystrophy, insulin resistance, and leptin deficiency. On the contrary, the effects of leptin treatment in leptin-replete or hyperleptinemic obese individuals with glucose intolerance and diabetes mellitus have been minimal or null, presumably due to leptin tolerance or resistance that impairs leptin action. Similarly, experimental evidence suggests a null or a possibly adverse role of leptin treatment in nonlipodystrophic patients with nonalcoholic fatty liver disease. In this review, we present a description of leptin biology and signaling; we summarize leptin's contribution to glucose metabolism in animals and humans in vitro, ex vivo, and in vivo; and we provide insights into the emerging clinical applications and therapeutic uses of leptin in humans with lipodystrophy and/or diabetes.

Since its discovery as an adipocyte-secreted hormone, leptin has been found to impact food intake, energy homeostasis, and metabolism through its effects on the central nervous system and peripheral organs. Recent research indicates that leptin may also be involved in cognition, immune function, and bone metabolism. These findings place leptin at the intersection of neuroendocrinology and metabolism, and possibly immune function, and render it an appealing therapeutic target for several niche areas of unmet clinical need. Current evidence regarding classic and emerging roles of leptin as well as the pros and cons of its potential clinical use are summarized herein.

BACKGROUND: SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. OBJECTIVE: In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. METHODS: In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. RESULTS: SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. LIMITATION: There was no performance of skin biopsies. CONCLUSION: The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities.

OBJECTIVE: The constellation of obesity, insulin resistance, and serum adipocytokine levels is associated with the risk and prognosis of postmenopausal breast cancer (PBC). Altered secretion of resistin may underlie the association between overweight/obesity and PBC. We thus explored the association of serum resistin with PBC, taking into account established risk factors, including adipokines and anthropometric, metabolic, and inflammatory markers. METHODS: In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control participants matched on age and time of diagnosis between 2003 and 2010 at the Veterans' Administration General Hospital of Athens (NIMTS Hospital). Serum resistin, adiponectin, leptin, metabolic (homeostasis model assessment score of insulin resistance) and inflammatory (tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein) parameters, and tumor markers (carcinoembryonic antigen and CA 15-3) were determined. RESULTS: The mean serum resistin level was significantly higher in case participants than in control participants (P < 0.001) in both univariate and multivariable analyses, adjusting for age, date of diagnosis, education, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, physical activity, reproductive markers, metabolic markers, anthropometric (body mass index and weight circumference) markers, inflammatory markers, and adipokines (odds ratio, 1.17; 95% CI, 1.03-1.34; P = 0.02). In case participants, resistin level correlated significantly with tumor markers and inflammatory parameters, but not with metabolic and anthropometric variables. CONCLUSIONS: Further prospective, longitudinal, and mechanistic studies are needed to determine whether hyperresistinemia is involved in the development of PBC or reflects changes during PBC progression and therefore could be used as a biomarker for PBC. Targeting resistin inhibition could be an effective therapeutic strategy in breast cancer by down-regulating the inflammatory microenvironment in breast tissue.

OBJECTIVE: Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. MATERIALS & METHODS: In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. RESULTS: Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. CONCLUSION: Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications.

Excess body weight constitutes a worldwide health problem with epidemic proportions impacting on the risk and prognosis of several disease states including malignancies. It is believed that the metabolic changes associated with weight gain, particularly visceral obesity, and physical inactivity could lead to dysfunctional adipose and muscle tissues causing insulin resistance, low-grade chronic inflammation and abnormal secretion of adipokines and myokines. The complex paracrine and endocrine interconnection between adipokines and myokines reflects a yin-yang balance with important implications in processes such as lipolysis control, insulin sensitivity and prevention from obesity-driven chronic low-grade inflammation and cancer promotion through anti-inflammatory adipokines and myokines. Furthermore, the complex pathophysiology of cancer cachexia is based on the interplay between muscle and adipose tissue mediated by free fatty acids, various adipokines and myokines. The purpose of this editorial is to explore the role of the adipose and muscle tissue interplay in carcinogenesis, cancer progression and cachexia, and to examine the mechanisms underpinning their association with malignancy. Understanding of the mechanisms connecting the interplay of adipokines and myokines with cancer pathophysiology is expected to be of importance in the development of therapeutic strategies against cancer cachexia. Advances in the field of translational investigation may lead to tangible benefits to obese and inactive persons who are at increased risk of cancer as well as to cancer patients with cachexia.

Worldwide, breast cancer (BC) represents the most common type of non-skin human malignancy and the second leading cause of cancer-related deaths amid women in Western countries. Obesity and its metabolic complications have rapidly become major global health issues and are associated with increased risk for cancer, especially BC in postmenopausal women. Adipose tissue is considered as a genuine endocrine organ secreting a variety of bioactive adipokines, such as leptin, adiponectin, resistin and nicotinamide phosphoribosyl-transferase/visfatin. Recent evidence has indicated that the constellation of obesity, insulin resistance and adipokines is associated with the risk and prognosis of postmenopausal BC. Direct evidence is growing rapidly supporting the stimulating and/or inhibiting role of adipokines in the process of development and progression of BC. Adipokines could exert their effects on the normal and neoplastic mammary tissue by endocrine, paracrine and autocrine mechanisms. Recent studies support a role of adipokines as novel risk factors and potential diagnostic and prognostic biomarkers in BC. This editorial aims at providing important insights into the potential pathophysiological mechanisms linking adipokines to the etiopathogenesis of BC in the context of a dysfunctional adipose tissue and insulin resistance in obesity. A better understanding of these mechanisms may be important for the development of attractive preventive and therapeutic strategies against obesity-related breast malignancy.

BACKGROUND: Renal function may be a major determinant of resistin levels, since most studies revealed association between elevated resistin levels and decreased glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD). The aim of the present study was to test the hypothesis whether serum resistin is associated with markers of malnutrition and inflammation in elderly non-diabetic adults in different stages of CKD including hemodialysis. METHODS: This was a cross-sectional study of 80 elderly patients divided in four groups of 20 patients each according to eGFR and matched for age (+/- 5 years) and gender. Patients with eGFR more than 1.5 mL/second served as controls. Multivariate regression was used to evaluate the association of resistin with eGFR, demographic, metabolic and inflammatory markers, and insulin resistance. Hematological, biochemical, and immunochemical analyses were performed using commercially available enzyme immunoassays. RESULTS: Our results showed that: 1) serum resistin levels were two times higher in patients with advanced CKD especially those undergoing hemodialysis compared to controls, 2) in univariate analysis, resistin levels correlated directly with Tumor Necrosis Factor-alpha (TNF-alpha), high sensitive C-Reactive Protein (hsCRP), and serum phosphate and inversely correlated with albumin, eGFR, and hematocrit levels. We failed to reveal any relationship between resistin levels and Homeostasis Model Assessment Score of Insulin Resistance (HOMA-IR), body mass index (BMI), cholesterol and leptin levels, 3) in multivariate analysis, only TNF-alpha (p < 0.001) and hsCRP (p = 0.032) were the most important independent determinants of serum resistin levels. CONCLUSIONS: These results indicate that resistin increases as GFR declines and may be involved in the malnutrition-inflammation state and the reverse epidemiology phenomenon present in elderly, non-diabetic patients with CKD.

In the early 80s, the word automation was used in the clinical laboratory setting referring only to analyzers. But in late 80s and afterwards, automation found its way into all aspects of the diagnostic process, embracing not only the analytical but also the pre- and post-analytical phase. While laboratories in the eastern world, mainly Japan, paved the way for laboratory automation, US and European laboratories soon realized the benefits and were quick to follow. Clearly, automation and robotics will be a key survival tool in a very competitive and cost-concious healthcare market. What sets automation technology apart from so many other efficiency solutions are the dramatic savings that it brings to the clinical laboratory. Further standardization will assure the success of this revolutionary new technology. One of the main difficulties laboratory managers and personnel must deal with when studying solutions to reengineer a laboratory is familiarizing themselves with the multidisciplinary and technical terminology of this new and exciting field. The present review/glossary aims at giving an overview of the most frequently used terms within the scope of laboratory automation and to put laboratory automation on a sounder linguistic basis.

Because of its pivotal role in the recycling pathway allowing NAD generation from nicotinamide, NAMPT occupies a central position in controlling the activity of several NAD-dependent enzymes. NAD, a universal energy-and signal-carrying molecule and its phosphorylated form, NADP, are required in several intracellular processes such as redox reactions, DNA repair, G-protein coupled receptor signaling, intra-cellular calcium-mobilizing molecules, transcriptional regulation, mono-adenosine diphosphate (ADP)-ribosylation in immune response, and activity of poly-ADP ribosyltransferases and deacetylases (sirtuins) with roles in regulating cell survival and cytokine responses. Under the influence of NAMPT, adequate levels of NAD control SIRT-6 (sirtuin) activity, which in turn positively regulates TNF-α mRNA translation favoring cell survival. NAMPT activity enhances cellular proliferation, tips the balance toward cellular survival following a genotoxic insult and controls the circadian clock machinery of some key transcriptions factors.

OBJECTIVE: Previous studies have shown that visfatin is significantly elevated in patients with gastric carcinoma and postmenopausal breast cancer (PBC). We thus explored whether serum visfatin could be used as a potential diagnostic and prognostic tool for PBC, taking into account clinicopathological features, serum tumor markers, anthropometric and metabolic parameters. METHODS: Serum visfatin, tumor marker CA 15-3, carcinoembryonic antigen, metabolic and anthropometric parameters were determined in 103 postmenopausal women with pathologically confirmed, incident invasive breast cancer, 103 controls matched on age and time of diagnosis, and 51 patients with benign breast lesions (BBL). RESULTS: Mean serum visfatin was significantly higher in cases than in controls and patients with BBL (p<0.001). In cases, visfatin was significantly associated with CA 15-3 (p=0.03), hormone-receptor status (p<0.001), lymph node invasion (p=0.06) but not with metabolic and anthropometric variables (p>0.05). Multivariable regression analysis revealed that absence of estrogen and progesterone receptors (ER-PR-) was the strongest significant determinant of serum visfatin (p<0.001) in cases adjusting for demographic, metabolic and clinicopathological features. Based upon receiver operator characteristic analysis, serum visfatin outperformed CA 15-3 only in discriminating between PBC cases with early cancer stage than those with late stage, and in differentiating particularly patients with ER-PR- breast tumors. CONCLUSION: Further prospective and longitudinal studies are needed to determine whether serum visfatin could be used as a prognostic tool in the armamentarium of PBC monitoring and management in conjunction with other biomarkers.

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies.

BACKGROUND: Lobomycosis, also known as Jorge Lobo's disease, represents a rare chronic subcutaneous mycosis caused by the fungus Lacazia loboi, an organism that is found within lesions but has not been cultured to date. The natural reservoir of L. loboi is unknown but it is believed to be aquatic, or associated with soil and vegetation. More than 550 human cases have been reported, especially in patients with a history of travel or residence in endemic areas (Central and South America, particularly Brazil) or in communities along rivers. MAIN OBSERVATIONS: We describe a 64-year-old Greek female farmer living in a coastal region, who presented with an erythematous plaque on her left inner thigh resembling a keloid. The diagnosis was based on the triad: 1) absence of fungal growth in cultures, 2) positive direct microscopic examination of the lesion and 3) histopathology, all consistent with lobomycosis. Particularly, skin biopsy showed deep cutaneous fungal infection with granulomatous reaction. Fungal cells were found inside giant cells. The fungi were thick-walled with some budding, isolated or in short chains. Dermal fibrosis was present. Our patient had a medical history of common variable immunodeficiency but no history of travel to South or Central America. She probably acquired this rare infection by injury during her agricultural works. CONCLUSION: Our case represents probably the first documented case of human lobomycosis in Southeastern Europe. This case is unusual due to the rarity of lobomycosis in Mediterranean countries, particularly in Southeastern Europe.

Worldwide breast cancer (BC) constitutes a significant public health concern. Excess body weight is associated with postmenopausal BC (PBC) risk. Recent studies have shown that the constellation of obesity, insulin resistance and serum adipokine levels are associated with the risk and prognosis of PBC. Nicotinamide phosphoribosyl-transferase (Nampt), also known as visfatin and pre-B-cell-colony-enhancing factor, found in the visceral fat, represents a novel pleiotropic adipokine acting as a cytokine, a growth factor and an enzyme. It plays an important role in a variety of metabolic and stress responses as well as in the cellular energy metabolism, particularly NAD biosynthesis. Nampt exhibits proliferative, anti-apoptotic, pro-inflammatory and pro-angiogenic properties. Nampt's insulin-mimetic function remains a controversial issue. Circulating Nampt levels are increased in obese women. Also, Nampt levels are significantly elevated in women suffering from PBC than in healthy controls independently from known risk factors of BC, anthropometric and metabolic parameters as well as serum concentrations of well known adipokines. High expression of Nampt in BC tissues was reported to be associated with more malignant cancer behavior as well as adverse prognosis. Taking into account the mitogenicity of Nampt as well as its proliferative, anti-apoptotic and pro-angiogenic properties, a novel hypothesis is proposed whereas Nampt may be involved in the etiopathogenesis of PBC and may represent a missing link between overweight/obesity and PBC. Nampt could exert its effects on the normal and neoplastic mammary tissue by endocrine and paracrine mechanisms; Nampt could also be secreted by tumor epithelial cells in an autocrine manner. It could stimulate mammary epithelial cell proliferation, invasion, metastasis, and angiogenesis, which is essential for BC development and progression. Serum Nampt might be a novel risk factor as well as a potential diagnostic and prognostic biomarker in PBC. In addition, pharmacologic agents that neutralize biochemically Nampt or medications that decrease Nampt levels or downregulate signaling pathways downstream of Nampt may prove to be useful anti-cancer agents. The potential harmful effect on PBC risk due to vitamin B3 (nicotinic acid, a natural NAD precursor in the biosynthetic route leading to NAD) intake is speculated for the first time. In this hypothesis, the role of Nampt in BC carcinogenesis and progression is explored as well as the pathophysiological mechanisms that underlie the association between Nampt and PBC in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against PBC.

OBJECTIVE: Menopause is associated with weight gain and an increase of cardiovascular risk. The aim of the present study was to estimate serum ischemia-modified albumin (IMA) levels in postmenopausal women and evaluate their association with body mass index (BMI) and coronary artery disease (CAD). METHODS: The study included 130 non-smoker postmenopausal women aged 43-80: 40 with BMI 26-32 kg/m(2) (Group A), 60 with BMI 21-25 kg/m(2) (Group B), and 30 with documented CAD and BMI 23-29 kg/m(2) (Group C). Serum IMA, albumin, hsCRP and NT-proBNP, glucose and insulin were measured. Homeostasis assessment model score (HOMA) and Quantitative insulin sensitivity index (QUICKI) were co-estimated. RESULTS: Serum IMA and IMA to albumin ratio were significantly elevated in Group A as compared to Group B (p<0.001) and similar to those of Group C. hsCRP and NT-proBNP did not differ between Groups A and B while they were lower in comparison to Group C (p<0.001). Glucose, insulin and HOMA were elevated in Group A compared to Group B (p<0.001) while QUICKI was lower (p<0.001). In Group A, IMA was positively correlated with BMI, hsCRP, insulin, HOMA and negatively with QUICKI. In postmenopausal women, multivariable regression analysis revealed that obesity was the strongest significant determinant of circulating IMA levels (p<0.001) contributing, therefore, to the elevated serum IMA concentration. CONCLUSIONS: Postmenopausal obesity is associated with elevated serum IMA possibly due to obesity associated oxidative stress. IMA measurement could provide an assessment of atherosclerotic burden in postmenopausal women. Further clinical evaluation is under investigation.

OBJECTIVE: Obesity has been implicated in the etiology of postmenopausal breast cancer (PBC). We hypothesized that altered secretion of visfatin may underlie this association. We thus investigated the association of serum visfatin with PBC risk, taking into account known risk factors including adipokines and anthropometric and metabolic parameters. METHODS: In a case-control study, we studied 102 postmenopausal women with pathologically confirmed, incident invasive breast cancer and 102 control women matched on age and time of diagnosis between 2003 and 2010 at Army Share Fund Hospital, Veterans' Hospital (NIMTS). Levels of serum visfatin, adiponectin, leptin, metabolic parameters, carcinoembryonic antigen, and CA 15-3 were determined. RESULTS: The mean serum visfatin level was significantly higher in case than in control participants (P < 0.001). Women in the highest quartile of visfatin concentration presented significantly higher odds for PBC, adjusting for age, date of diagnosis, education, body mass index, waist circumference, years with menstruation, parity/age at first full-term pregnancy, breast-feeding, family history of cancer, use of exogenous hormones, alcohol consumption, smoking status, homeostasis model assessment score, and serum leptin and adiponectin concentrations (odds ratio, 7.93; 95% CI, 2.52-24.9). In case participants, the visfatin level correlated significantly with the tumor marker CA 15-3 (P = 0.03) but not with metabolic and anthropometric variables (P > 0.05). CONCLUSIONS: Further prospective studies are needed to determine whether an elevated serum visfatin level is implicated in the etiopathogenesis of PBC or reflects changes during PBC progression and could therefore be used as a biomarker for PBC.

Conditions resulting in insulin resistance, as well as metabolic, immune, and angiogenic perturbations, have been associated with an increased risk of preeclampsia (PE). Our purpose was to assess whether the adipose tissue-secreted hormones adiponectin, which has immune-modulating, metabolic, and angiogenic properties, and leptin, which reflects overall fat mass, are associated with PE risk. We performed a case-control design study within a hospital-based cohort of 368 pregnant women (106 with PE and 262 controls; mean age, 26.6 ± 6.8 years; mean gestational age at admission, 38.2 ± 2.8 weeks) between March 2005 and August 2007 at the Hospital of Pennsylvania University. Serum adiponectin and leptin were measured by radioimmunoassay. Statistical analysis of data was performed using simple and multiple regression analyses. No significant differences in adiponectin or leptin levels between preeclamptic and control pregnant women emerged in univariate analyses (P = .57 and P = .15, respectively). Among preeclamptic women, there were also no differences in adipokines between those with mild and severe disease. Serum adiponectin and leptin were not associated with higher risk of PE before and after adjustment for maternal age, race, primigravida, smoking status, body mass index at screening, gestational age at admission, history of PE, chronic hypertension, and gestational diabetes (odds ratio, 0.93; 95% confidence interval, 0.83-1.04 and odds ratio, 1; 95% confidence interval, 0.97-1.03, respectively). Maternal serum adiponectin and leptin levels, drawn at the time of PE diagnosis, were not associated with PE.

AIM: To investigate three isoforms of survivin in colorectal adenocarcinomas. METHODS: We used the LightCycler Technology (Roche), along with a common forward primer and reverse primers specific for the splice variants and two common hybridization probes labeled with fluorescein and LightCycler-Red fluorophore (LC-Red 640). Real time quantitative polymerase chain reaction (PCR) was performed on cDNAs from 52 tumor specimens from colorectal cancer patients and 10 unrelated normal colorectal tissues. In the patients group, carcinoembryonic antigen (CEA) and CA19-9 tumor markers were also measured immunochemically. RESULTS: Wild type survivin mRNA isoform was expressed in 48% of the 52 tumor samples, survivin-2b in 38% and survivin-ΔΕx3 in 29%, while no expression was found in normal tissues. The mRNA expression of wild type survivin presented a significant correlation with the expression of the ratio of survivin-2b, survivin-ΔΕx3, survivin-2b/wild type survivin and survivin-ΔΕx3/wild type survivin (P < 0.001). The mRNA expression of wild-survivin and survivin-ΔΕx3 was related with tumor size and invasion (P = 0.006 and P < 0.005, respectively). A significant difference was found between survivin-2b and morphologic cancer type. Also, the ratio of survivin-ΔEx3/wild-survivin was significantly associated with prognosis. No association was observed between the three isoforms and grade, metastasis, Dukes stage and gender. The three isoforms were not correlated with CEA and CA19-9. CONCLUSION: Survivin isoforms may play a role in cell apoptosis and their quantification could provide information about clinical management of patients suffering from colorectal cancer.

OBJECTIVE: In obese postmenopausal women we assessed leptin and adiponectin, high-sensitive C-reactive protein (hsCRP), serum lipids and lipoxidative stress products: oxidized LDL (oxLDL) and malondialdehyde (MDA), in relation to impaired glucose tolerance (IGT). METHODS: Thirty-eight overweight/obese postmenopausal women were included in the study. Eighteen with normal glucose metabolism (NGT) and twenty with IGT, as it is diagnosed by OGTT. Serum leptin, adiponectin, hsCRP and MDA were measured at time 0 and 120 min of OGTT while total-cholesterol, LDL, HDL, triglycerides, oxLDL and anti-oxLDL autoantibodies at time 0. Insulin resistance (HOMA)/sensitivity (QUICKI) indexes were estimated. RESULTS: In subjects with NGT, hsCRP was positively correlated with fasting leptin and HOMA, while in subjects with IGT negatively with QUICKI. In both groups, hsCRP was positively correlated with fasting insulin, body mass index and waist circumference. Fasting adiponectin was positively associated with HDL in both groups and negatively with triglycerides in subjects with NGT as well as with serum glucose levels at time 120 min of OGTT in subjects with IGT. No association was observed between oxLDL and adipokines. A significant positive association was found between oxLDL and HOMA in subjects with IGT. During OGTT there was a significant increase of leptin and MDA levels in both groups. CONCLUSIONS: A relationship exists between obesity, insulin and sub-clinical inflammation. Leptin and lipid peroxidation are linked to hyperglycaemic state while oxLDL might be considered as a predictor of insulin resistance. Adiponectin could exert its antiatherogenic effect through HDL independently of the presence of IGT.

AIM: Leptin and adiponectin are two well-studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL. METHODS: Ninety-five patients with incident B-CLL and 95 hospital controls matched on age and gender were studied between 2001 and 2007, and blood samples were collected. Leptin, total and high molecular weight adiponectin, and prognostic markers of B-CLL were determined. RESULTS: Cases had a higher body mass index (BMI) than controls (p = 0.01) and lower levels of leptin (p < 0.01). Significantly more cases than controls presented a family history of lymphohematopoietic cancer (LHC) (p = 0.01). Higher serum leptin levels were associated with lower risk of B-CLL adjusting for age, gender, family history of LHC, BMI and serum adiponectin; the multivariate odds ratio comparing highest to lowest tertile was 0.05 (95% CI 0.01-0.29, p trend < 0.001); Adiponectin was not significantly different between cases and controls. CONCLUSION: Leptin was found to be inversely associated with risk of CLL but in contrast to prior studies of CLL and hematologic malignancies, this study found no significant association between CLL and adiponectin.

INTRODUCTION: the FcγRIIa receptor is responsible for the clearance of large immune complexes and recently has been proved to be a C-reactive protein (CRP) receptor as well. A polymorphism in the corresponding FCG2RA gene resulting in an amino acid change (R131H) has been implicated, with conflicting results in the pathogenesis of various autoimmune or inflammatory disorders (e.g., atherosclerosis and coronary artery disease [CAD]). METHODS: we recently developed a real-time polymerase chain reaction and melting curve analysis method for the genotyping of the above polymorphism. We further looked at its validity with bioinformatics study and DNA sequencing. Then we genotyped 134 CAD patients and 45 angiographically normal controls and determined serum high-sensitivity CRP by nephelometry (Dade-Behring). Also, we used apparently healthy platelet donors (n = 206) as a larger control group. RESULTS: our method is accurate and devoid of problems with homologs and copy number variants. The need for reference materials is stressed. There were statistically significant differences (p < 0.05) between the CAD patients and each of the two other control groups, with the percentage of RR genotype rising from 6.5% and 11% in the control groups to an average of 19% in all CAD patients (17%, 24%, and 18.5% in stable angina, unstable angina, and myocardial infarction, respectively). In a logistic regression model that included known risk factors for CAD including CRP, the RR genotype remained a significant predictor for CAD (odds ratio: 6.3 [1.1-36.3]). Also after linear regression analysis, CRP levels were reduced in the RR carriers (vs. HH + HR), controlling for age, sex, and disease (marginal p = 0.07). CONCLUSIONS: with our accurate genotyping method, the RR genotype was correlated with atherothrombotic CAD events. The inverse correlation found between CRP levels and genotype supports the in vitro data of RR cells binding CRP stronger than HH.

BACKGROUND: Altered thrombocyte morphology and function have been reported in patients with diabetes mellitus (DM) type 2. The aim of the present study was to determine the associations between platelet morphology markers and hemoglobin A1C (HbA(1c)), fasting glucose (FG), hypertension and coronary heart disease (CHD) in patients with myelodysplastic syndromes (MDS) and DM, in patients with DM and in controls. METHODS: This cross-sectional study included 30 cases with primary MDS with normal platelet count and non-insulin dependent diabetes, 30 non-insulin dependent diabetic patients and 30 non-diabetic, non-MDS controls matched on age and gender. RESULTS: After adjusting for body mass index, platelet number, CHD and hypertension, HbA(1c) and FG were significant predictors of mean platelet volume (MPV) and platelet distribution width (PDW) in diabetic patients. There was no correlation between platelet parameters and HbA(1c) or FG in diabetic MDS patients. In controls, FG and hypertension predicted significant differences in platelet morphology. Platelet count correlated with platelet morphology in diabetic MDS and control groups, but not in diabetics. CONCLUSIONS: MPV and PDW are associated with glycemic indices in diabetic patients but not in diabetic MDS patients with normal platelet counts. Non-diabetic controls also exhibit FG related changes in platelet morphology. This suggests other factors inherent to bone marrow dysplasia, platelet turnover and biochemistry, or vascular environment affect platelet morphology in diabetic MDS patients even with normal platelet count. Platelet morphology in this population may be an early marker for myelodysplasia. These findings also support platelet morphology change as a marker for elevated macrovascular disease risk.

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive non-Hodgkin's nodal peripheral T-cell lymphoma characterized by general lymphadenopathy, night sweats, fever, hepatosplenomegaly, polyclonal hypergammaglobulinemia, and cutaneous involvement. We present a rare case of AITL cutaneous involvement mimicking toxic erythema recurring with AITL relapse and suggesting a precursor of disease progression.

Accumulating evidence supports a role for obesity in the etiology of multiple myeloma (MM). The distinct possibility exists that obesity may be linked to MM through altered adipokine secretion and circulating levels, one of which, adiponectin, has a protective role in several malignancies, including leukemia. In this case-control study, we investigated the role of serum adiponectin, resistin, and leptin levels in the etiopathogenesis of MM and we explored their association with several established prognostic factors. Seventy three patients with incident, histologically confirmed MM and 73 controls matched on gender and age were studied between 2001 and 2007, and blood samples were collected. Serum adiponectin, leptin, resistin, as well as MM prognostic parameters were determined. Statistical analysis of the data was performed using univariate and multivariate analyses. Lower serum adiponectin and resistin levels were associated with higher risk of MM by bivariate analysis and after adjusting for age, gender, BMI, and serum levels of leptin (p < 0.0001). Adiponectin may have a protective role in MM, whereas leptin was not associated with risk for MM at a comparable level of significance and resistin levels may be decreased via a compensatory mechanism. Further studies are needed to confirm these associations and to explore the mechanisms underlying adiponectin's role in MM and plasma cell dyscrasias.

BACKGROUND: Ischemia modified albumin (IMA), is a new biomarker of oxidative processes involved with coronary artery disease (CAD). We determined serum IMA, high-sensitivity C-reactive protein (hsCRP), and natriuretic peptide (NT-proBNP), and evaluated their correlation with severity of coronary atherosclerosis in patients undergoing coronary angiography (CA). Cardiac troponin T (cTnT), CK-MB mass, albumin and Total Antioxidant Status (TAS) were also evaluated. METHODS: The study included 114 patients (88 men and 30 women) aged 43-80 years with documented CAD without evidence of acute coronary syndrome undergoing CA and 163 controls (131 men and 32 women) similarly aged. RESULTS: IMA, hsCRP and NT-proBNP were higher (p<0.001 and p=0.008 for NT-proBNP) while TAS was lower (p<0.001) in patients than in controls. IMA and TAS were negatively correlated in all subjects (p<0.01). Among patients, there was no correlation between IMA and the number of diseased vessels. For CAD diagnosis the best cut-off point for IMA was 101.5 KU/L with a sensitivity and a specificity of 87.7% and a negative predictive value of 83.3%. IMA was associated with an increased risk for CAD (OR=1.23, 95% CI: 1.16-1.31; p<0.001). CONCLUSIONS: IMA determination may provide earlier information of CAD presence before hsCRP or NT-proBNP elevation, contributing to early assessment of overall patient risk.

OBJECTIVE: The aim of the present study was to estimate circulating oxidized low-density lipoprotein (oxLDL) levels in postmenopausal women and evaluate their association with obesity and smoking status. DESIGN AND METHODS: The study included 135 postmenopausal women aged 52-75 years. Forty of them were overweight (BMI 32.4+/-6.4) and non-smokers (Group A), 40 non-overweight (BMI 22.6+/-1.8) and smokers (Group B) and 55 non-overweight (BMI 23.5+/-1.4) and non-smokers (Group C). oxLDL and antibodies against them (anti-oxLDL) were measured using ELISA. Serum total cholesterol, LDL, HDL and triglycerides were measured in an automated analyzer. RESULTS: Total cholesterol, LDL, HDL and oxLDL serum levels were significantly elevated in Group A as compared to Group B or C, as well as oxLDL in Group B in comparison to Group C (p<0.001). Triglycerides and anti-oxLDL were increased in Group A in comparison to Group C (p=0.043 and 0.023). Total cholesterol, LDL, triglycerides and anti-oxLDL did not differ between Groups B and C, while HDL was decreased in Group B as compared to Group C (p<0.001). A significant positive correlation was found between oxLDL and LDL in Group A (r=0.53, p<0.001) as well as in Group C (r=0.955, p

Obesity and insulin resistance have been implicated in the etiology of pancreatic cancer (PC). Whether adiponectin and/or leptin, two adipocyte-secreted hormones important in metabolic regulation, are associated with PC pathogenesis and whether adiponectin receptors are expressed in PC remains unknown. In a hospital-based case-control study, we studied 81 cases with incident, histologically confirmed PC and 81 controls matched on gender and age between 2000 and 2007 to investigate the role of adiponectin and leptin adjusting for risk factors linked to PC. In a separate study, we also studied for the first time whether adiponectin receptors 1 and 2 are expressed in PC by studying 16 PC tumor tissue samples which were analyzed using immunohistochemistry. When subjects were divided into control-defined quartiles of adiponectin and leptin, lower leptin but higher adiponectin levels were associated with PC (p = 0.001 and p = 0.05 respectively) before and after controlling for age, gender, BMI, smoking status, alcohol consumption, history of diabetes, and family history of pancreatic cancer. Of the PC tumor tissue samples analyzed, 87.5% had positive or strong positive expression of AdipoR1 and 93.7% had positive or strong positive expression of AdipoR2. Further prospective studies are needed to determine whether the elevated adiponectin and low leptin levels reported in this study reflect compensatory changes during PC progression and thus can be used as markers for PC or whether they are causally implicated in PC.

BACKGROUND: Cutaneous lesions in myelodysplastic syndrome (MDS) may be specific or not and may reveal bone marrow transformation. Our purpose was to investigate in a cohort of 84 MDS patients the correlation of cutaneous findings with immunologic parameters and prognostic features of MDS in order to clarify their potential clinical significance. MATERIALS AND METHODS: We studied a cohort of 84 newly diagnosed MDS patients in order to assess the cutaneous findings present at the time of diagnosis and during 1 to 3 years of follow-up. We described the clinical variety of cutaneous findings ascertained by histology. We also looked for any association between the group of MDS patients with skin manifestations and MDS subtype, immunologic and prognostic features highlighting transformation to acute leukaemia. RESULTS: Twenty-one patients presented cutaneous manifestations: 1 patient developed leukaemia cutis, 6 patients photosensitivity not associated with autoimmune disease, 3 prurigo nodularis, 2 Sweet's syndrome, 6 leucocytoclastic vasculitis, 2 ecchymoses and purpura associated with preexisting relapsing polychondritis, 1 patient subcutaneous nodules associated with Wegener's granulomatosis and 1 patient with malar rash and oral ulcers associated with preexisting systemic lupus erythematosus. Adjusted for age and gender, the presence of skin findings constitutes a significant predictor of the high-risk MDS subgroup (odds ratio, 3.59; 95% confidence interval, 1.18-10.92). Hypergammaglobulinemia was significantly higher in the MDS subgroup with skin manifestations (P = 0.03). CONCLUSION: Most MDS patients with cutaneous manifestations belong to the high-risk MDS subgroup and present hypergammaglobulinemia. Early biopsy of skin lesions in myelodysplasia is indicated.

OBJECTIVE: Thyroid disease has been associated with leukemia and lymphoma. No previous study using clinical and laboratory data has explored whether thyroid disease and especially autoimmune thyroid disease (ATD) is associated with myelodysplastic syndrome (MDS) risk. In this case-control study, we investigated the association of ATD with MDS. METHODS: Our study included 101 cases with incident primary MDS confirmed by histology and cytogenetics, and 101 controls matched on gender and age, admitted for non-neoplastic and non-infectious diseases. All subjects were submitted to clinical, ultrasound thyroid evaluation and serum free T3, free T4, TSH, thyroglobulin, and thyroperoxidase antibodies determination. RESULTS: Adjusting for age, gender, and body mass index, there was statistically significant evidence that ATD is associated with increased risk of MDS (OR = 2.58, 95% CI 1.29-5.16). Interestingly, ATD starting from the remote past (more than 10 years from MDS onset) was positively associated with MDS risk (OR = 5.73. 95% CI 2.03-16.16). Mean serum levels of fT3, fT4, and thyroid antibodies were significantly higher in MDS patients and mean TSH serum levels were significantly lower in MDS patients than in controls (p < 0.05). CONCLUSION: Biological plausibility and empirical evidence highlights the importance of ATD in MDS etiopathogenesis. Further studies are needed to explore underlying mechanisms associating thyroid autoimmunity with leukemogenesis.

Dermal exposure to hydrofluoric acid could potentially result in severe serum calcium and magnesium depletion induced by binding with fluoride anion. This report describes the case of a 48-year-old man who developed hypocalcemia and hypomagnesemia accompanied by hypokalemia-an interesting finding-following a chemical injury with exposure to 70% hydrofluoric acid. Successful treatment included administration of calcium gluconate and magnesium both intravenously and topically.

AIM: Obesity has been implicated in the aetiology of myelogenous leukaemia and myelodysplasia (MDS). We hypothesised that altered secretion of adiponectin and resistin may underlie this association. We thus investigated the role of both total and high molecular weight (HMW) adiponectin and resistin in MDS. METHODS: In a case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender and age between 2004 and 2007. Total and HMW adiponectin, resistin, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein (IGFBP-3) were determined. RESULTS: Lower serum total or HMW adiponectin and/or resistin levels were independently associated with higher risk of MDS controlling for age, gender, BMI and serum levels of leptin, IGF-I and IGFBP-3 (p<0.002). Although total and HMW adiponectin were both significantly inversely associated with MDS when modelled either in quartiles or continuously, HMW did not offer any substantial additional predictive value over total adiponectin (Odds ratio (OR)=0.91 versus 0.93 for a 1 microg/ml change, respectively). IGF-I was positively associated with MDS by bivariate analysis and both IGF-I and IGFBP-3 were higher in advanced MDS and higher risk stages, but were not significantly and independently associated with MDS. CONCLUSION: Total and HMW adiponectin may have a protective role in MDS, whereas resistin levels may be decreased via a compensatory mechanism.

Thyroid disease has been associated with lymphohematopoietic cancer (LHC). No previous study using clinical, sonographic and laboratory data has explored whether thyroid disease and specifically autoimmune thyroid disease (ATD) is associated with multiple myeloma (MM) risk. 73 patients with incident primary MM and 73 hospital controls admitted for non-neoplastic and non-infectious conditions, matched on gender and age were studied between 2001 and 2007. Blood samples were collected. All subjects were submitted to clinical, ultrasound and laboratory thyroid evaluation. The prevalence of clinical thyroid disease in MM patients was significantly higher than in controls (p = 0.002). ATD was associated with increased risk of MM, adjusting for age, gender, body mass index and familial history of LHC [OR = 5.68, 95% confidence interval (CI): 1.69-19.13]. Controlling for the above variables, an individual suffering from any thyroid disease more than 10 years has about 2.41 times more likely the risk to develop MM than an individual without any thyroid disease (OR = 2.41, 95% CI: 1.35-4.29). Also, adjusting for age, gender, BMI and family history of LHC, a familial history of thyroid disease is associated with increased risk of MM (OR = 3.23, 95% CI: 1.25-8.31). Further studies are needed to explore underlying mechanisms associating thyroid autoimmunity with plasma cell transformation.

OBJECTIVE: In obese postmenopausal women with normal glucose metabolism (NGT) and impaired glucose tolerance (IGT) we assessed serum leptin, adiponectin, resistin, soluble leptin receptor (sOB-R) during oral glucose tolerance test (OGTT) in order to investigate their response to acute changes in glucose and insulin in the abnormal glucose metabolism, as it is early detected by IGT. METHODS: Thirty in total, overweight/obese postmenopausal women, were included in the study: 15 with NGT and 15 with IGT as it was diagnosed by OGTT. Serum glucose and insulin levels were measured at 30 min intervals, leptin, sOB-R, adiponectin and resistin at 60 min intervals during the 120 min OGTT. RESULTS: In fasting state, leptin, adiponectin, resistin and sOB-R levels did not differ between the two groups. In women with NGT, leptin was positively correlated with BMI, insulin and HOMA, and negatively correlated with QUICKI and with sOB-R; adiponectin was negatively correlated with insulin and HOMA and positively correlated with QUICKI. In women with IGT, resistin was positively correlated with BMI and waist circumference. In both groups, sOB-R was negatively correlated with insulin. During OGTT, in both groups, leptin concentration increased significantly and fasting glucose predicts significantly serum leptin change; there was no change in adiponectin, resistin and sOB-R concentrations. CONCLUSION: In overweight/obese postmenopausal women fat distribution does not affect leptin and adiponectin production. Abnormal glucose metabolism is not accompanied by disturbance in adipokines production. Leptin secretion is acutely regulated by glucose levels in insulin presence.

Sarcoidosis is a multisystem disease encountered by general physicians as well as medical specialists. Subcutaneous sarcoidosis is not an uncommon clinical presentation of sarcoidosis and is challenging for physicians because it can mimic cellulitis or several chronic infections. Our patient presented with a swollen forearm and hand which were initially treated as acute cellulitis with antibiotics by general physicians but without any improvement. A skin biopsy showed granulomatous panniculitis but confirmation of the diagnosis of systemic sarcoidosis was based on the characteristic chest roentgenogram, the high CD4/CD8 ratio of T lymphocytes in bronchoalveolar lavage, and the typical 'panda' and 'lambda' signs on the (67)Ga scan. Such cases with atypical clinical presentation cause some difficulty in reaching the diagnosis but a skin biopsy as well as typical imaging and laboratory signs are usually important to establish the diagnosis of sarcoidosis, when invasive procedures cannot be performed to get confirmation from a second target organ.

OBJECTIVE: Adiponectin plays a protective role in several malignancies, including myeloblastic leukemia, whereas leptin may increase the proliferation of progenitor cells and may stimulate leukemic cell growth in vitro. We investigated the role of adiponectin and leptin levels in the etiopathogenesis of myelodysplastic syndromes (MDS), a preleukemic condition with increasing incidence which has recently been associated with obesity. METHODS: In a case-control study, 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender and age were studied between 2004 and 2007, and blood samples were collected. RESULTS: Higher serum adiponectin levels were associated with lower risk of MDS by bivariate analysis and after adjusting for age, gender, body mass index and serum levels of leptin (p < 0.001). Subjects in the third quartile for leptin levels had a lower risk of MDS than controls, and low leptin concentrations were observed in low-risk MDS patients with normal or good prognostic karyotype after adjusting for age, gender and body mass index. CONCLUSIONS: Circulating adiponectin and leptin may play an important role in MDS etiopathogenesis. Future studies are needed to confirm these associations and to explore underlying mechanisms.

The present study aimed to determine the serum carcinoembryonic antigen (CEA), CA 19-9, CA 50 and alpha-fetoprotein (alpha-FP) levels between patients with myelodysplastic syndromes (MDS) at diagnosis and controls to clarify their potential clinical significance. A case-control investigation was conducted over a three year period, covering 95 MDS cases and 95 age- and gender-matched controls. Mean serum CEA levels were significantly higher (P = 0.0002) in MDS patients at diagnosis than in hospital controls. Adjusting for age, gender, tobacco consumption, serum CA 19-9, CA 50 and alpha-FP levels, there is statistically significant evidence that serum CEA values are associated with increased risk of MDS (odds ratio = 2.33, 95% confidence interval = 1.56 - 3.49). Six patients with MDS developed malignancies 4-9 months after the diagnosis of myelodysplasia. Serum CEA could be used as marker together with other important diagnostic tools for evaluating an underlying or developing malignancy in patients suffering from MDS.

A case of spontaneous peritonitis caused by Leminorella grimontii in a 63-year-old man with cirrhosis is reported. To our knowledge, L. grimontii has never been reported as a cause of spontaneous bacterial peritonitis. The patient responded to antimicrobial therapy. Clinical and therapeutic implications are discussed.

AIM: To assess the relative occurrence of non motor-vehicle knee injuries and identify important clusters that can be targeted for preventive interventions. METHODS: The study subjects covered 2167 children (0-14 years) who suffered non motor-vehicle knee injuries out of 66870 registered during a three-year period in an established Emergency Department Injury Surveillance System (EDISS). A more serious joint injury was identified in 263 (12%) children, whereas the remaining 1904 children had only soft tissue knee injuries. RESULTS: The incidence of non motor-vehicle knee injuries was estimated at 6.5 per 1000 children-years. Both the incidence of knee injuries and the male-to-female ratio increase with increasing age, reflecting the gender and age pattern of physical activity. Three clusters were identified: The first consisted of more serious knee injuries among older children, frequently resulting after a fall from stairs or a collision in school during winter months; the second cluster consisted of rather minor knee injuries occurring mostly among younger girls at home or in playgrounds, following a fall after stumbling or hit by an object while playing, especially during the summer; the third cluster comprised injuries among older boys, sustained mainly subsequent to overexertion in a sports area. CONCLUSION: Knee injuries tend to be more common among boys but more serious among girls. More and less serious knee injuries tend to fall into distinct clusters that could facilitate prioritization of preventive measures.

We present a case of systemic sarcoidosis with ovarian and peritoneal involvement. The atypical clinical presentation of the disease has lead to a problem of the differential diagnosis with ovarian cancer. A 72-year-old female was admitted because of low grade fever, fatigue and dilatation of the abdomen. Clinical and laboratory evaluation of the patient revealed moderate right pleural effusion, ascites, diffuse ovarian infiltration, presence of enlarged intraabdominal lymph nodes and a substantially high value of serum CA 125. Histological examination after laparotomy was indicative of ovarian sarcoidosis.

UNLABELLED: Interferon (IFN) and especially IFN-alpha exhibit clinical anti-tumor activity against various types of malignant diseases. Natural inhibitors to various cytokines and IFNs have been documented in vitro as well as in vivo. IFN inhibitors have been implicated for the ineffectiveness of IFN treatment in malignant neoplasias. The aim of this study was to investigate the incidence of the IFN inhibiting activity in serum from patients with haematological malignancies versus patients with solid tumours, as an effort to explain, just in part, the different response of these patients to IFN treatment. PATIENTS AND METHODS: Ninety patients with a clinically evident solid tumour and forty-six patients with haematological malignancies were included in the study. Serum samples from all patients were collected before any treatment and stored at -70 degrees until use. Controls sera were selected from 50 apparently healthy blood donors. Interferon-inhibiting activity as well as endogenous IFN-like activity were determined in all serum samples in a cell line highly sensitive to IFN. RESULTS: There was no endogenous IFN-like activity in any of the patients' group or controls' group. Sera from patients with haematological malignancies exhibited IFN-blocking activity at a lower percentage (21.7%) in comparison to sera from patients with solid tumours (56.6%, P<0.001), but at a significantly higher percentage in comparison to sera from controls (P<0.01). CONCLUSIONS: The fact that IFN inhibitors were detected at a significantly lower percentage in sera from patients with haematological malignancies versus patients with solid tumours, could explain in part the better response of the haematological malignancies to IFN treatment.

Adiponectin, an adipocyte-secreted hormone, is closely and inversely associated with insulin resistance and was recently found to be inversely and independently associated with endometrial cancer. Because insulin resistance in the setting of obesity has also been associated with the development of breast cancer, we have hypothesized that decreased adiponectin levels might underlie the association between breast cancer and obesity/insulin resistance. We evaluated the association of adiponectin with the occurrence of breast cancer in a case-control study comprising 174 women with newly diagnosed, histologically confirmed breast cancer and 167 controls. We found an inverse, fairly strong, and statistically significant association of serum adiponectin with breast cancer (odds ratio, 0.84; 95% confidence interval, 0.71-0.99). Importantly, despite a fairly robust inverse association of adiponectin with breast cancer risk among postmenopausal women (odds ratio, 0.82; 95% confidence interval, 0.67-1.00), no such significant association between adiponectin and breast cancer was found among premenopausal women. The observed associations were independent of possible effects of major components of the IGF system, leptin, body mass index, sociodemographic variables, and known risk factors for breast cancer. Future studies are needed to prove causality and provide further insights into both the mechanisms underlying the actions of this hormone and its potential role in breast cancer.

BACKGROUND: While routine immunizations are very safe, their administration to healthy children requires minimization of immunization programmatic errors. In order to estimate the incidence and ascertain the nature of reported immunization errors in the Greek childhood population, we have undertaken a study using data from the National Poison Information Center in Greece, which also has the responsibility to address medication-induced errors. METHODS: All immunization errors concerning children and reported to the National Poison Information Center during the 2-yr period 1999-2000 were retrieved and the conditions of their occurrence were examined. The incidence of reported errors was calculated under the assumption that during each year 100,000 children are born in Greece, and during their childhood they receive a total of about 20 immunization doses of all childhood immunizations. RESULTS: There were 40 immunization errors reported, corresponding to a reported incidence of about 11 per million immunization doses. Of these errors, 20 concerned OPV, 13 DTP, 5 MMR, 1 Haemophilus influenza and 1 Hepatitis B immunizations. In 12 instances an erroneous route was used (out of which 11 concerned OPV), whereas overdose was documented in 13 instances (out of which 8 concerned OPV). The third most common error was administration of DTP instead of the recommended Td vaccine. No adverse patient outcomes were reported. CONCLUSIONS: In Greece, reported errors in immunization practice are relatively rare. Packaging modifications (about one in three errors in this study) of the OPV and DTP could further reduce their incidence.

Pseudomonas luteola is uncommonly implicated in clinical infections, but it constitutes a significant nosocomial pathogen causing mainly infections associated with foreign material. This report describes an unusual case of a Pseudomonas luteola strain that infected and caused cutaneous abscess and bacteraemia in a previously healthy man.

We report a rare case of a 21-year-old man with leptospirosis mimicking acute pancreatitis and cholecystitis. This case report aims at pointing out the need of taking into consideration the possibility of leptospirosis in patients with an influenza-like syndrome, headache accompanied by acute abdominal pain and a suspicious exposure in order to prevent unnecessary surgical interventions.

Stenotrophomonas maltophilia is rarely implicated in clinical infections but it constitutes a significant nosocomial pathogen, especially in immunocompromised patients. This report describes the first case of a generalised infection caused by S. maltophilia that included bacteremia, wound and respiratory tract infection in a patient suffering from burns. Given the emergence of S. maltophilia nosocomial infections, especially in patients with burns, isolation of the bacterium from blood cultures should prompt the commencement of adequate antibiotic treatment.

BACKGROUND: Knee injuries represent an important category of road traffic injuries among children, and they are heterogeneous in their aetiology. The aims of this study were to estimate the incidence of road traffic childhood knee injuries in Greece by age and gender, point out their time, place and person co-ordinates and identify clusters with distinct characteristics with a view to potential preventive interventions. METHODS: During a 3-year period, 305 children with knee injuries resulting from a road traffic accident were identified among the 66,870 children with injuries recorded in the Emergency Department Injury Surveillance System (EDISS) of Greece. Using previously derived sampling ratios and national data on childhood population, incidence data by age and gender were estimated. Hierarchical analysis was undertaken for cluster identification. RESULTS: The incidence of road traffic knee injuries was 97.5 per 100,000 children-years. The incidence increased with age and was higher among boys than among girls. Most childhood knee injuries (50.2%) occur among pedestrians, and the majority (90.9%) of the children or their guardians admitted responsibility in crossing the road. Of the 31 children injured as car passengers, the vast majority (87.1%) were unrestrained, and a large fraction (38.7%) were front seat passengers. Two clusters were identified: the first consisted of younger children who resided mostly in the Athens area and suffered less serious knee injuries as pedestrians or car passengers during the colder months; the second consisted of older children, frequently tourists, who suffered more serious injuries as cyclists while vacationing. CONCLUSIONS: Many of the children who suffered road traffic knee injuries as pedestrians admitted responsibility in road crossing, whereas a large proportion of children who were injured as car passengers were injured while improperly seated in the front and without seatbelt protection. Older children, frequently tourists, were at high risk of knee injuries while using motorcycles and bicycles.

We report herein a case of a 20-year-old previously healthy man who presented, 25 days after the onset of clinically and serologically confirmed Epstein-Barr virus (EBV) infectious mononucleosis, Fusobacterium necrophorum septicemia. The diagnosis of postanginal septicemia was confirmed by repeated demonstration of fusiform, obligate anaerobic, Gram-negative bacilli in anaerobic blood cultures, identified as F. necrophorum 15 days after admission. This case report aims at underlining the need of taking into consideration the possibility of severe Fusobacterium septicemia in previously healthy patients following EBV infectious mononucleosis in order to prevent increased mortality and morbidity.

The case is described of a 36 year-old man who presented with progressive proximal muscle weakness and weight loss. His serum creatine phosphokinase (CPK) levels were markedly elevated. The muscle biopsy showed lipid storage myopathy. The muscle carnitine concentration was extremely low (5.6% of normal levels), establishing the diagnosis of myopathic carnitine deficiency. The disorder was considered as primary because there were no indications of any other identifiable condition which could result in a secondary carnitine deficiency. The patient was treated with oral L-carnitine (2 g per day) and showed rapid improvement. Primary myopathic carnitine deficiency is a curable disorder and therefore it should always be considered as a potential diagnosis in cases of myopathy in young adults.

OBJECTIVE: The etiology of most cases of myelodysplastic syndromes (MDS) has not been elucidated. We have undertaken an investigation in Greece to determine the risk profile of adult de-novo MDS. METHODS: A case-control investigation was conducted in a large Veterans' hospital over a five-year period, covering 84 MDS cases and 84 age- and gender-matched controls with minor non-neoplastic non-infectious conditions from the same study base. Cases and controls reported to the medically trained principal investigator lifestyle characteristics and medical histories, with emphasis on autoimmune disorders and allergic conditions. RESULTS: Alcohol intake and tobacco smoking jointly increased significantly the risk of MDS (odd ratio contrasting ever smokers and regular drinkers of at least one glass per day to never smokers and drinkers of less than one glass per day: 9.54. 95% CI 3.52-25.82) whereas each of these factors alone had limited effect. There was also evidence that autoimmune conditions, but not allergic disorders, were positively associated with MDS risk, irrespective of their occurrence during the recent (less than ten years) or the remote (more than ten years) past (OR 3.34, 95% CI 1.15-9.74; OR 3.50, 95% CI 1.19-10.26, respectively). CONCLUSION: We found evidence that both exogenous and endogenous factors may play a role in the etiology of the so-called "de novo" myelodysplastic syndromes, but these findings need further confirmation.

OBJECTIVE: Acute lymphoblastic leukemia (ALL) among children may be a rare outcome of a delayed non-specific infection in situations of overall low herd immunity. We evaluated the hypothesis as to whether newly diagnosed ALL cases, compared to their controls, are characterized by lower herd immunity, as reflected in a more seronegative spectrum to several agents, with the exception of a strongly positive response to a single infectious agent, assumed to trigger ALL. METHODS: The study included 94 incident cases of ALL, from all pediatric hematology-oncology units of Greece, and 94, matched for age and gender, controls hospitalized with minor non-infectious conditions. The past exposure to common infections was assessed using 10 serological markers. RESULTS: There was little evidence for an association of ALL with the serology of any of the studied infectious agents among the very young children. In contrast, among children aged 5 years or older, leukemia was inversely associated with seropositivity to Epstein-Barr virus, human herpes virus-6, Mycoplasma pneumoniae and parvovirus B19. CONCLUSIONS: Among children aged 5 years or older the risk of leukemia may be higher when the low herd immunity for several agents is challenged by late infection from an agent that, as a rule, would attack children at a younger age.

Five hundred and fifty-nine human sera were examined using the Rose Bengal test (RBT), the Wright test and the immunofluorescence technique. Analysis of the collected data is indicative of the high sensitivity of the RBT, which is proved to be a very useful screening test. The inadequacy of the Wright test for an accurate diagnosis of chronic brucellosis is obvious and the need to be replaced or supplemented by another technique is suggested and discussed.