Ioannis Ntanasis-Stathopoulos

Obesity and Risk for Brain/CNS Tumors, Gliomas and Meningiomas: A Meta-Analysis

Objective This meta-analysis aims to examine the association between being overweight/obese and risk of meningiomas and gliomas as well as overall brain/central nervous system (CNS) tumors. Study Design Potentially eligible publications were sought in PubMed up to June 30, 2014. Random-effects meta-analysis and dose-response meta-regression analysis was conducted. Cochran Q statistic, I-squared and tau-squared were used for the assessment of between-study heterogeneity. The analysis was performed using Stata/SE version 13 statistical software. Results A total of 22 studies were eligible, namely 14 cohort studies (10,219 incident brain/CNS tumor cases, 1,319 meningioma and 2,418 glioma cases in a total cohort size of 10,143,803 subjects) and eight case-control studies (1,009 brain/CNS cases, 1,977 meningioma cases, 1,265 glioma cases and 8,316 controls). In females, overweight status/obesity was associated with increased risk for overall brain/CNS tumors (pooled RR = 1.12, 95%CI: 1.03–1.21, 10 study arms), meningiomas (pooled RR = 1.27, 95%CI: 1.13–1.43, 16 study arms) and gliomas (pooled RR = 1.17, 95%CI: 1.03–1.32, six arms). Obese (BMI>30 kg/m2) females seemed particularly aggravated in terms of brain/CNS tumor (pooled RR = 1.19, 95%CI: 1.05–1.36, six study arms) and meningioma risk (pooled RR = 1.48, 95%CI: 1.28–1.71, seven arms). In males, overweight/obesity status correlated with increased meningioma risk (pooled RR = 1.58, 95%CI: 1.22–2.04, nine study arms), whereas the respective association with overall brain/CNS tumor or glioma risk was not statistically significant. Dose-response meta-regression analysis further validated the findings. Conclusion Our findings highlight obesity as a risk factor for overall brain/CNS tumors, meningiomas and gliomas among females, as well as for meningiomas among males.

Pathogenesis of bone disease in multiple myeloma: from bench to bedside

Osteolytic bone disease is the hallmark of multiple myeloma, which deteriorates the quality of life of myeloma patients, and it affects dramatically their morbidity and mortality. The basis of the pathogenesis of myeloma-related bone disease is the uncoupling of the bone-remodeling process. The interaction between myeloma cells and the bone microenvironment ultimately leads to the activation of osteoclasts and suppression of osteoblasts, resulting in bone loss. Several intracellular and intercellular signaling cascades, including RANK/RANKL/OPG, Notch, Wnt, and numerous chemokines and interleukins are implicated in this complex process. During the last years, osteocytes have emerged as key regulators of bone loss in myeloma through direct interactions with the myeloma cells. The myeloma-induced crosstalk among the molecular pathways establishes a positive feedback that sustains myeloma cell survival and continuous bone destruction, even when a plateau phase of the disease has been achieved. Targeted therapies, based on the better knowledge of the biology, constitute a promising approach in the management of myeloma-related bone disease and several novel agents are currently under investigation. Herein, we provide an insight into the underlying pathogenesis of bone disease and discuss possible directions for future studies.

Association between problematic internet use, socio-demographic variables and obesity among European adolescents

BACKGROUND Overweight of children and adolescents continues to be an important and alarming global public health problem. As the adolescents time spent online has increased, problematic internet use (PIU) potentially leads to negative health consequences. This study aimed to examine the relation between PIU and overweight/obesity among adolescents in seven European countries and assess the effect of demographic and lifestyle factors recorded in the European Network for Adolescent Addictive Behaviour (EU NET ADB) survey (www.eunetadb.eu). METHODS A cross-sectional school-based survey of 14- to 17-year-old adolescents was conducted in seven European countries: Germany, Greece, Iceland, the Netherlands, Poland, Romania and Spain. Anonymous self-completed questionnaires included sociodemographic data, internet usage characteristics, school achievement, parental control and the Internet Addiction Test. Associations between overweight/obesity and potential risk factors were investigated by logistic regression analysis, allowing for the complex sample design. RESULTS The study sample consisted of 10 287 adolescents aged 14-17 years. 12.4% were overweight/obese, and 14.1% presented with dysfunctional internet behavior. Greece had the highest percentage of overweight/obese adolescents (19.8%) and the Netherlands the lowest (6.8%). Male sex [odds ratio (OR) = 2.89, 95%CI: 2.46-3.38], heavier use of social networking sites (OR = 1.26, 95%CI: 1.09-1.46) and residence in Greece (OR = 2.32, 95%CI: 1.79-2.99) or Germany (OR = 1.48, 95%CI: 1.12-1.96) were independently associated with higher risk of overweight/obesity. A greater number of siblings (OR = 0.79, 95%CI: 0.64-0.97), higher school grades (OR = 0.74, 95%CI: 0.63-0.88), higher parental education (OR = 0.89, 95%CI: 0.82-0.97) and residence in the Netherlands (OR = 0.49, 95%CI: 0.31-0.77) independently predicted lower risk of overweight/obesity. CONCLUSIONS The results indicate an association of overweight/obesity with PIU and suggest the importance of formulating preventive public health policies that target physical health, education and sedentary online lifestyle early in adolescence with special attention to boys.

Management and Outcomes in Metaplastic Breast Cancer

Metaplastic breast cancer (MBC) constitutes a rare clinical entity with special clinicopathologic, immunohistochemical, and molecular features. Resistance to systemic therapies, whether chemotherapy or hormonal therapy, is among its main characteristics, which in turn explains the poor prognosis and renders its management a challenge. Thus, the scope of the present review is to discuss the current therapeutic strategies for MBC in clinical practice and the corresponding outcomes and to suggest possible directions for future research. Potential novel targeted therapies could provide a hope for better outcomes but limited data are available owing to the rarity of MBC. As knowledge accumulates on the pathogenesis and genetic characteristics of MBC, emphasis should be given to the implementation of more targeted treatments, which will allow more efficient and individualized management of the disease.

Liver transplantation in patients with liver metastases from neuroendocrine tumors: A systematic review

Background: Liver transplantation to treat neuroendocrine tumors, especially in the setting of diffuse liver involvement not amenable to operative resection remains controversial. We sought to perform a systematic review of the current literature to summarize data on patients undergoing liver transplantation with neuroendocrine tumors liver metastases as the indication. Methods: A systematic review was conducted in accordance to the Preferred Reporting Items for Systematic reviews and Meta‐Analysis guidelines. Eligible studies were identified using 3 distinct databases through March 2017: Medline (PubMed), ClinicalTrials.gov, and Cochrane library, Cochrane Central Register of Controlled Trials using a search algorithm: “(neuroendocrine or NET) and transplantation and liver.” Results: From the 1,216 records retrieved, 64 studies were eligible. Overall, 4 studies presented data from registries, namely the European Liver Transplant Registry and the United Network for Organ Transplantation/Organ Procurement and Transplantation Network databases, 3 were multicenter studies. The largest cohort of data on patients undergoing liver transplantation for neuroendocrine tumors liver metastasis indication were from single center studies comprising a total of 279 patients. Pancreas was the primary tumor site for most patients followed by the ileum. Several studies reported that more than half of patients presented with synchronous disease (55.9% and 57.7%); in contrast, metachronous neuroendocrine tumors liver metastasis ranged from 17.7% to 38.7%. Overall, recurrence after liver transplantation ranged from 31.3% to 56.8%. Reported 1‐, 3‐, and 5‐year overall survival was 89%, 69%, and 63%, respectively. Several prognostic factors associated with worse long‐term survival including transplantation >50% liver tumor involvement, high Ki67, as well as a pancreatic neuroendocrine tumors versus gastrointestinal neuroendocrine tumors tumor location. Conclusion: Liver transplantation may provide a survival benefit among patients with diffuse neuroendocrine tumors metastases to the liver. However, due to high recurrence rates, strict selection of patients is critical. Due to the scarcity of available grafts and the lack of level 1 evidence, the recommendations to endorse liver transplantation for extensive liver neuroendocrine tumors metastases warrants ongoing deliberations.

Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach

Abstract Background: This study aims to globally assess the network of insulin resistance (IR)-related factors in a sample of overweight and obese Greek youths. Methods: A total of 185 subjects were examined, and IR was quantified by homeostasis model assessment (HOMA-IR). Multivariate hierarchical approach was performed, and five distinct levels were recognized, namely, immutable demographic features and early life parameters, current anthropometric measures, IR, unfavorable clinical conditions, and social parameters. Two analyses were performed based on HOMA-IR cut-off values (3.16 and, as an alternative, 3.99). Results: Obesity was associated with IR (adjusted OR=3.19, 95% CI: 1.12–9.09). IR steadily predicted low HDL (adjusted OR=5.75, 95% CI: 1.58–20.87), hypertriglyceridemia (adjusted OR=10.28, 95% CI: 1.18–89.55), and systolic hypertension. At the alternative analysis, IR was also associated with older age, older age at menarche, hyperuricemia, and low school grades. Conclusion: Emerging on the grounds of obesity, IR confers risks for dyslipidemia and hypertension at a relatively early age. Along with weight loss, interventions targeted at IR are required to prevent cardiometabolic risk in adolescence.

The addition of IMiDs on daratumumab refractory multiple myeloma patients can overcome refractoriness in both agents

TO THE EDITOR: The survival of myeloma patients has doubled in the past decade, but patients refractory to both proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) still have poor prognosis.[1][1] Immunotherapy with monoclonal antibodies targeting cell-surface antigens is a promising new

Physical Activity and Gastric Cancer Risk: A Systematic Review and Meta-Analysis.

Objective:Physical activity represents a well-established way to prolong the life span; yet, it remains an unfulfilled goal for a great part of the population. In parallel, the burden of gastric cancer is considerable throughout the globe. In that context, the present meta-analysis aims to shed light on the association between physical activity and gastric cancer risk. Data Sources:Eligible observational studies were sought in PubMed up to June 01, 2015. In addition, a snowball procedure was conducted and contact with authors was implemented. Separate analyses were performed by type of physical activity (total; occupational; recreational), study design, published/provided data, anatomical site, and study location, along with stratification by gender. Main Results:Ten cohort studies (7551 incident cases in a total cohort size of 1 541 208 subjects) and 12 case–control studies (5803 cases and 73 629 controls) were eligible. “Any” type of physical activity was associated with lower risk of gastric cancer [pooled relative risk (RR) = 0.81; 95% CI: 0.73 to 0.89], which was reproducible in men (pooled RR = 0.87; 95% CI: 0.77-0.99). The protective effect was significant in the subgroup analyses of published data, noncardia cancer (pooled RR = 0.62; 95% CI: 0.52-0.75), and studies stemming from Asia (pooled RR = 0.82; 95% CI: 0.74-0.90). Conclusions:This meta-analysis suggests a protective effect of physical activity regarding gastric cancer risk, especially in Asian populations.

The Emerging Role of Tyrosine Kinase Inhibitors in Ovarian Cancer Treatment: A Systematic Review

ABSTRACT The present systematic review summarizes current evidence regarding the mechanisms of action, the efficacy, and the adverse effects of tyrosine kinase inhibitors (TKIs) in ovarian cancer patients. Phase II and III clinical trials were sought in the PubMed database and in the Clinical Trials.gov registry through September 30, 2015. Seventy-five clinical trials regarding TKIs targeting mainly vascular endothelial growth factor receptor, epidermal growth factor receptor, platelet-derived growth factor receptor, and sarcoma tyrosine kinase (Src) were yielded. The most promising results were noted with cediranib, nintedanib, and pazopanib. However, drawing universal conclusions about the potential integration of TKIs in ovarian cancer therapy remains elusive. Furthermore, emerging challenges and directions for the future research are critically discussed.

The association between pulse wave velocity and peripheral neuropathy in patients with type 2 diabetes mellitus

AIMS Diabetic peripheral neuropathy (DPN) is the most common diabetic complication, affecting up to half of the patients with type 2 diabetes mellitus (T2DM). Increased aortic stiffness, measured with the carotid-femoral pulse wave velocity (PWV), has been associated with incidence of cardiovascular disease independently of traditional risk factors. Previous data showed associations between risk factors for macroangiopathy and DPN in diabetes. However, the association between PWV and DPN is not well known. In this study we examined the association between PWV and presence as well as severity of DPN in subjects with T2DM. MATERIAL AND METHODS A total of 381 patients with T2DM were recruited. Participants were classified as having DPN and not having DPN. PWV was measured at the carotid-femoral segment with a non-invasive method using applanation tonometry. DPN was assessed by determination of the Neuropathy Symptom Score (NSS) and the Neuropathy Disability Score (NDS). RESULTS A hundred and seven participants (28.1%) had DPN. Patients with DPN were significantly more often male and older, had longer diabetes duration, higher height, larger waist circumference, higher systolic arterial blood pressure (SBP) and higher PWV (all P<0.05). Furthermore, participants with DPN were treated more often with statins and had lower low density lipoprotein cholesterol; in addition, they were treated more often with antiplatelets, b-blockers and insulin than those without DPN. Univariative logistic regression analysis demonstrated that presence of DPN was significantly associated with age, male gender, longer diabetes duration, height, waist circumference, SBP, PWV, dyslipidemia, HbA1c, retinopathy, nephropathy and peripheral arterial disease. Multivariate logistic regression analysis, after adjustment for age, gender, waist circumference, SBP, nephropathy and use of b-blockers, demonstrated that the odds [OR (95% confidence intervals)] of peripheral neuropathy were associated significantly and independently only with diabetes duration [1.044 (1.009-1.081), P=0.013], height [1.075 (1.041-1.110), P<0.001], HbA1c [1.468 (1.164-1.851), P<0.001], PWV [1.174 (1.054-1.309), P=0.004], dyslipidemia [1.941 (1.015-3.713), P=0.045], retinopathy [4.426 (2.217-8.837), P<0.001] and peripheral arterial disease [4.658 (2.264-9.584), P<0.001]. In addition, multivariate linear regression analysis, after controlling for age, gender, diabetes duration, SBP, HbA1c and nephropathy, demonstrated that an increased NDS was significantly and independently associated with height [standardized regression coefficient (beta=0.229, P<0.001)], PWV (beta=0.197, P<0.001), retinopathy (beta=0.268, P<0.001) and peripheral arterial disease (beta=0.374, P<0.001). CONCLUSION Increased PWV is associated strongly and independently not only with the presence but also with the severity of DPN in patients with T2DM, irrespective of known risk factors.