Search

BACKGROUND High-sensitivity cardiac troponin (hs-cTn) levels are frequently elevated in elderly patients presenting to the emergency department for non-cardiac events. However, most studies on the role of elevated hs-cTn in elderly populations have investigated the prognostic value of hs-cTn in patients with a specific diagnosis or have assessed the relationship between hs-cTn and comorbidities. AIM To investigate the in-hospital prognosis of consecutive elderly patients admitted to the Internal Medicine Department with acute non-cardiac events and increased hs-cTnI levels. METHODS In this retrospective study, we selected patients who were aged ≥ 65 years and admitted to the Internal Medicine Department of our hospital between January 2019 and December 2019 for non-cardiac reasons. Eligible patients were those who had hs-cTnI concentrations ≥ 100 ng/L. We investigated the independent predictors of in-hospital mortality by multivariable logistic regression analysis. RESULTS One hundred and forty-six patients (59% female) were selected with an age range from 65 to 100 (mean ± SD: 85.4 ± 7.61) years. The median hs-cTnI value was 284.2 ng/L. For 72 (49%) patients the diagnosis of hospitalization was an infectious disease. The overall in-hospital mortality was 32% (47 patients). Individuals who died did not have higher hs-cTnI levels compared with those who were discharged alive (median: 314.8 vs 282.5 ng/L; P = 0.565). There was no difference in mortality in patients with infectious vs non-infectious disease (29% vs 35%). Multivariable analysis showed that age (OR 1.062 per 1 year increase, 95%CI: 1.000-1.127; P = 0.048) and creatinine levels (OR 2.065 per 1 mg/dL increase, 95%CI: 1.383-3.085; P < 0.001) were the only independent predictors of death. Mortality was 49% in patients with eGFR < 30 mL/min/1.73 m2. CONCLUSION Myocardial injury is a malignant condition in elderly patients admitted to the hospital for non-cardiac reasons. The presence of severe renal impairment is a marker of extremely high in-hospital mortality.

Introduction Clostridium difficile infection (CDI) has been reported to be a cause of flare-ups in patients with inflammatory bowel disease (IBD). Cytomegalovirus (CMV) infection can cause severe disease and complications in immunocompromised patients in consequence of disease or therapy. Aim Our aim was to describe the prevalence and clinical outcomes of CDI with concomitant CMV infection in IBD patients hospitalized for flare-ups in association with the disease itself and medication used. Methods We prospectively identified consecutive patients referred for CDI management during 2015-2017. Stool samples were tested for Clostridium difficile toxin A and/or B and Glutamate Dehydrogenase in patients with clinical symptoms. CDI patients with IBD history were tested for anti-CMV IgG and IgM antibodies by chemiluminescent microparticle immunoassay and underwent histological analysis for CMV on colon biopsies. Data were collected for demographic characteristics, treatment and outcome. Results 125 patients with CDI were enrolled. Among these patients, 14 (11.2%) were diagnosed with IBD. The mean patient age of IBD patients was 52.5±15.4 years at diagnosis of CDI, 85.7% had UC, 14.3% CD, while the age of patients was shared. Eleven of the total of 14 patients (78.6%) tested positive for anti-CMV IgG. Of these, 3 patients (21.4%) exhibited high CMV IgG avidity, without detectable anti-CMV IgM and biopsy-proven CMV colitis. Of the 14 IBD patients with CDI, 8 patients (57.1%) were receiving anti-tumor necrosis factor (anti-TNF) therapy (21.4 % infliximab or golimumab, 7.1% vedolizumab or adalimumab) and 43.5% of patients were being treated with systemic corticosteroids. Four UC patients (28.6%) on steroids of the 14 CDI patients underwent a colectomy whereas none of the not on steroids patients underwent colectomy (p=0.25). Among them, 1 patient (7.1%) had recurrent CDI after 5 months from the first episode of CDI.These patients were treated with vancomycin, metronidazole and fidaxomicin. The mean age of patients that had a colectomy 65.5±9.32 (n=4) was higher than the mean age of those 47.30±14.49 (n=10) who improved (UMann-Whitney=6. p=0.04). Conclusions Immunosuppressive medications and older age are associated with increased risk of CDI and poor outcome. Although, CMV is a rare colonic pathogen in the immunocompetent patient, it should be included and screened when exacerbation of IBD occurs in patients receiving any type of immunosuppressive therapy.

ESD robustness for self-protected advanced Silicon photonic components integrated into optical interposers is reported, including industry-first CDM data. HBM performance in reverse bias polarity is shown to be the limiting factor and is correlated to the optical component width. The Ge-EAM modulator with heater is found to be the weakest element CDM-wise.

Background and AimsThe HIV outbreak among People Who Inject Drugs (PWID) in Athens, Greece in 2011-2013 was the largest recent epidemic in Europe and North America. We aim to assess trends in HIV prevalence, drug use and access to prevention among PWID in Athens, to estimate HIV incidence and identify risk factors and to explore HIV-1 dispersal using molecular methods during 2014-2020.MethodsTwo community-based HIV/hepatitis C programs on PWID were implemented in 2012-2013 (N=3,320) and 2018-2020 (N=1,635) through consecutive Respondent-Driven Sampling (RDS) rounds. PWID were uniquely identified across rounds/programs. We obtained RDS-weighted HIV prevalence estimates per round for 2018-2020 and compared them to 2012-2013. We assessed changes in HIV status, behaviours, and access to prevention in PWID participating in both periods. We estimated HIV incidence in a cohort of seronegative PWID as the number of HIV seroconversions/100 persons-years during 2014-2020 and used Cox regression to identify associated risk factors. Molecular sequencing and phylogenetic analysis were performed in HIV seroconverters.ResultsHIV prevalence per round ranged between 12.0%-16.2% in 2012-2013 and 10.7%-11.3% in 2018-2020 with overlapping 95% Confidence Intervals (95% CI). Among PWID participating in both programs, HIV prevalence[95% CI] increased from 14.2%[11.7%-17.1%] in 2012-2013 to 22.0%[19.0%-25.3%] in 2018-2020 (pConclusionsThe ongoing HIV transmission among PWID in Athens provides empirical evidence that the current levels of prevention and treatment are inadequate to control the epidemic. Re-evaluation of prevention programs is urgently needed.

Granulomatosis with polyangiitis (GPA) is a rare systemic autoimmune disease of unknown etiology that is characterized by granulomatous inflammation, tissue necrosis, and vasculitis in small- and medium-sized vessels. Ocular and orbital manifestations are common in almost half of patients with GPA, affecting every structure of the eye, from the eyelid and orbit to the retina, the choroid, and the optic nerve, with a wide range of severity. Since imaging findings are not always specific for the diagnosis of GPA, biopsy is useful to confirm the diagnosis. Regarding treatment, a localized pharmaceutical and surgical approach may be helpful to achieve remission, while immunosuppressive therapy, corticosteroids, and cyclosporine are also useful. In any case, multidisciplinary intervention is required to reduce the rates of relapse and morbidity in patients with GPA.

Introduction: Cancer cachexia is a common associate of cancer and has a negative impact on both patients' quality of life and overall survival. Nonetheless its management remains suboptimal in clinical practice. Provision of medical recommendations in websites is of extreme importance for medical decision making and translating evidence into clinical practice. Aim of the study: To scrutinize the magnitude, consistency and changes over time of cancer-cachexia recommendations for physicians on the Web among oncology related societies. Intercontinental, continental, national and socioeconomic variations were further analyzed. Material and methods: Web identification of oncology related societies and prospective analyses of relative Web guideline recommendations for physicians on cancer-cachexia at different time-points. Results: In June 2011, we scrutinized 144,000 Web pages. We identified 275 societies, of which 270 were eligible for analyses: 67 were international (African, American, Asian, European, Oceania and Intercontinental), 109 belonged to the top 10 countries with the highest development index and 94 pertained to 10 countries with a long lasting tradition in medical oncology. Conclusions: The magnitude of cancer cachexia recommendations for physicians on the Web at a global level was scant both for coverage and consistency, and at any time-point considered: 3.7% (10/270) in 2011 and 8.1% (22/270) in 2018. The proportion of societies giving evidence-based and updated recommendations for cancer cachexia for physicians was only 1.1% (3/270) in 2011 and 2.96% (8/270) in 2018. Continent, national highest developmental index, oncology tradition and economic-geographic areas were not found to influence Web guideline provision.

Background Uterine sarcomas consist a heterogeneous group of mesenchymal gynecological malignancies with unclear therapeutic recommendations and unspecific but poor prognosis, since they usually metastasize and tend to recur very often, even in early stages. Methods We retrospectively analyzed all female patients with uterine sarcomas treated in our institution over the last 17 years. Clinico-pathological data, treatments and outcomes were recorded. Kaplan-Meier curves were plotted and time-to-event analyses were estimated using Cox regression. Results Data were retrieved from 61 women with a median age of 53 (range: 27–78) years, at diagnosis. Fifty-one patients were diagnosed with leiomyosarcoma (LMS), 3 with high grade endometrial stromal sarcoma (ESS), 5 with undifferentiated uterine sarcoma (UUS), 1 with Ewing sarcoma (ES) and 1 with Rhabdomyosarcoma (RS). 24 cases had stage I, 7 stage II, 14 stage III and 16 stage IV disease. Median disease-free survival (DFS) in adjuvant approach was 18.83 months, and median overall survival (OS) 31.07 months. High mitotic count (> 15 mitoses) was significantly associated with worse OS (P

Sensory-perceptual difficulties are a common characteristic in Autism Spectrum Disorders (ASD). Studies in children with ASD describe an array of challenging behaviors regarding sensory simulation. Parents, special educators, and therapists are often witnessing these behaviors throughout the day. This study aimed to use an Augmented Reality (AR) system for the simulation of the sensory overload that children with ASD experience. A total of seventy (N=70) parents, special educators, and therapists of children with ASD responded to researchers’ invitation for this study. Researchers held individual sessions with each participant who wore a head-mounted AR device (Magic Leap OneTM). Six visual and two auditory stimuli were individually and consecutively administered via the AR device. Participants experienced autism-like sensory overload under controlled conditions. Their acceptance and experience of the AR device were measured with the use of three online questionnaires (Temple Presence Inventory, TPI; Simulator Sickness Questionnaire, SSQ; Technology Acceptance Model, TAM). An open-ended question was also administered to measure the overall AR experience. In regard to the study’s findings for participants’ experience, the results from the TPI (Cronbach's Alpha = .84) suggested that the AR system offered a convincing blended environment. Also, low scores in SSQ indicated that the use of the AR system was comfortable. The results from the TAM showed in their majority high internal consistency (> .70) and high mean scores. This indicated that the participants accepted the AR system. In the open-ended question, participants reported overall satisfaction from their experience with the AR system. The study’s findings suggested that the AR device enabled participants to experience a sensory overload similar to the one child with ASD report. Participants’ experience was deemed to be convincing, comfortable, and user-friendly. The results of this study are encouraging and highlight the potential of AR in autism research. Future studies are needed to incorporate richer and more interactive AR simulations for authentic real-life experiences.

Background and Aims The structure and function of the left ventricle (LV) are affected since the early stages of chronic kidney disease (CKD). Our cross-sectional study aimed to estimate the echocardiographic indices of the LV diastolic function and the evaluation of their potential correlation with indices of kidney injury in patients with CKD, before initiation of renal replacement therapy. Method 99 patients with CKD (stage 2 CKD: 31 patients (27%), stage 3 CKD: 47 patients (40.9%) and stage 4 CKD: 37 patients (32.1%)) were enrolled in the study. Anthropometric data, indices of renal function (eGFR-CKD-EPI, urinary protein excretion in mg/24h), biochemical laboratory parameters, comorbidities [hypertension (HT), diabetes mellitus (DM), coronary heart disease (CAD)] and echocardiographic indices of LV diastolic function were recorded. In specific, left atrial (LA) dimensions were measured in M-Mode and were expressed both as absolute values in mm as well as indexed to body surface area ((BSA) and expressed as the LA index in mm/m2. The study sample, after taking into account patient gender, was further divided into separate groups according to the presence or not of LA dilation. Results The average patient age was 62 +/- 13 years and average eGFR (CKD-EPI) was 44.1+/-21.4 ml/min/1.73m2. With regard to comorbidities, 59.3% of the sample population had arterial hypertension, 24.3% had diabetes mellitus and 10.4% had known coronary artery disease. Regarding anti-hypertensive and hypolipidemic treatment, 22.6% of the patients were on ARB and 24% on ACEi, 51.3% on CCB, 29.6% on β-blockers, 37.4% on diuretics and 28.7% of the patients were receiving statin treatment. 28.2% of the patients had dilated LA in terms of absolute value and 13.8% had dilated LA following indexing to BSA (LA index). A positive correlation was observed between the LA size and age (p=0.001), BMI (p=0.041), uric acid levels (p=0.022), PTH (p=0.029), fibrinogen (p=0.035), LV mass (p=0.006) and LV mass/BSA (p=0.005), whereas a negative correlation was observed with serum LDL (p=0.027). Additionally, there was observed a negative correlation of LA index with eGFR (p=0.05), as well as an inverse relationship between LA index and PTH (p=0.012), age (p=0.004), BMI (p=0.037) and LV mass/BSA (p=0.005). No significant correlations between LA size and LA index with proteinuria or with co-morbidities (DM, HT, CAD) were observed. Conclusion In a population of patients with stage 2-4 CKD, LA size correlated to indices of CKD. Larger studies are required in order to further confirm these correlations.

Tuberculosis (TB) can manifest prolonged fever or fever of unknown origin, especially when it is located extrapulmonary. We report a case of disseminated TB complicated by iliac bone osteolysis and a gluteal abscess in a 75-year-old female patient with fever and bone marrow dysplasia. Diagnosis of TB was made despite transient false-positive high-titer agglutination tests and ELISA antibodies to Brucella. The case presented shows that in a highly suggestive case of TB, positive agglutination tests or ELISA antibodies to Brucella should be interpreted with caution, and repeated testing should be performed to assess their persistence and fluctuation over time.

Background Kidney cancer is a lethal neoplasm that affects several thousands of people every year. Renal cell carcinoma (RCC) is the most common histologic type. Recent developments in the therapeutic approach include antiangiogenic targeted approaches and Immunotherapy. Thus, the therapeutic algorithm of RCC patients and the survival outcomes have changed dramatically. Methods Herein we present a retrospective study of the patients treated in our Department with an antiangiogenic agent -Axitinib, a tyrosine kinase inhibitor- as a third or further line treatment. Statistical analysis was performed with SPSS, including the available clinicopathological data of the patients included. Results Axitinib was found to be active in patients who received this treatment beyond second line. The toxicity profile of this regimen did not reveal any unknown adverse events. Conclusions Our real world data reflect that axitinib is a safe and effective option, even beyond the second line.

There is a growing recognition that social support can potentially exert consistent or opposing effects in influencing health behaviours. The present paper presents a cross-sectional study, including 2,064 adults from Italy, Spain and Greece, who were participants in a multi-centre randomised controlled trial (C4H study), aiming to examine whether social support is correlated with adherence to a healthy Mediterranean diet and physical activity. Social support data were available for 1,572 participants. The majority of the sample reported emotional support availability (84·5 %), financial support availability (72·6 %) and having one or more close friends (78·2 %). Mediterranean diet adherence was significantly associated with emotional support (P = 0·009) and social network support (P = 0·021). No statistically significant associations were found between participant physical activity and the social support aspects studied. In conclusion, emotional and social network support may be associated with increased adherence to the Mediterranean diet. However, further research is needed to evaluate the role of social support in adherence to healthy Mediterranean diet.

Neoadjuvant Chemotherapy (NACT) followed by Interval Debulking Surgery (IDS) is an accepted frontline treatment in patients with advanced Epithelial Ovarian Cancer (EOC). Histopathologic assessment of tumor post NACT may provide a surrogate for response to treatment. The present study aims to characterize the pathological response and to examine its prognostic significance in these patients. Medical records of women with EOC treated in our institution from 2011 to 2016 were retrospectively identified. IDS specimens were reviewed by study pathologist and Chemotherapy Response Score (CRS), lymphocytic infiltration, necrosis and mitosis were assessed. 55 patients with EOC treated with NACT were identified and 48 had complete clinical and pathological data. Median age was 63 years. CRS assessed at omentum predicted PFS when adjusted for age, stage, debulking status (complete, optimal, suboptimal) and post IDS bevacizumab administration (mPFS CRS 1 vs 2 vs 3: 10.3–14–18.7 months 95% CI [7.4–15.7], [12.2–22.9], [13.5–31.3]). Presence of lymphocytic infiltration was associated with improved OS (log-rank test P = 0.015). Post IDS bevacizumab was associated with shorter PFS in patients with lymphocytic infiltration. BRCA status was known for 25 patients and presence of BRCA1/2 mutations was strongly correlated with lymphocytic infiltration (P = 0.011) but not CRS omentum (P = 0.926). Our study confirms the predictive value of CRS in EOC patients treated with NACT and IDS, but also demonstrates the prognostic significance of lymphocytic infiltration as well as its possible interaction with bevacizumab treatment.

Background Venous thromboembolic events (VTEs) frequently occur in cancer patients. Risk assessment models (RAMs) for cancer-associated thrombosis have been proposed. However, advanced urinary tract cancer (aUTC) was not adequately represented in these models. We studied the incidence of VTEs, the risk factors, and the applicability of recently described RAMs. Patients and Methods Data from 335 patients with aUTC treated with chemotherapy between April 1995 and September 2015 in a single institution were analyzed. Results A total of 95.2% received platinum-based first-line chemotherapy. Twenty-nine patients (8.7%) experienced VTEs. The 6-, 12-, and 24-month VTE incidence was 7.4% (95% confidence interval [CI], 4.8-10.6), 8.1% (95% CI, 5.4-11.5) and 9.4% (95% CI, 6.4-13.1), respectively. No significant association of VTE incidence with the Khorana risk score was observed. History of vascular event (VTE and/or arterial thromboembolic event) was significantly associated with the development of VTE. Patients with such history had a 6-, 12-, and 24-month VTE incidence of 16.2% (95% CI, 6.6-29.7), 19.2% (95% CI, 8.4-33.3), and 25.2% (95% CI, 12.5-40.1) compared to 6.2% (95% CI, 3.7-9.4), 6.6% (95% CI, 4.1-10), and 7.1% (95% CI, 4.4-10.6) of those who did not. The discriminatory ability of this factor adjusted for leucocyte count, sex, Eastern Cooperative Oncology Group performance status, and type of chemotherapy reached 0.79 (95% CI, 0.71-0.87) compared to the 0.58 (95% CI, 0.49-0.66) for the Khorana risk score. Conclusion Development of tumor-specific algorithms for the risk of VTEs is advisable. Patients with aUTC and a history of vascular events are at high risk for VTE development, and prophylaxis should be prospectively studied in this group.

Introduction/Background Ovarian cancer (OC) is one of the most lethal gynecological malignancies. Primary Debulking Surgery (PDS) followed by chemotherapy has been the standard of care. However, two randomized trials have demonstrated that Neoadjuvant Chemotherapy(NACT) followed by Interval Debulking Surgery(IDS) is not inferior to PDS. Therefore, we conducted a retrospective analysis to determine patterns of practice in our institution. Methodology Medical records of women with epithelial OC treated at Alexandra Hospital from 2011 to 2016 were retrospectively identified. Clinicopathological data, treatment and survival data were analyzed. Kaplan-Meier Survival curves were generated using IBM SPSS version 20; survival differences were estimated using the long-rank test. Results 198 patients were identified. Median age was 60.8 years. 169 patients had serous carcinoma, 10 clear cell, 10 endometrial, 3 mucous and 4 adenocarcinoma. 171 had advanced (stage III/IV) disease. PDS was performed in 128 patients, while 70 received NACT. 48 performed IDS, while 6 had LDS. No surgery was performed in 16 patients. With a median follow-up of 27.3 months, mPFS was 21.8 months and mOS was 58.5 months. Patients treated with NACT-IDS had statistical significant shorter mPFS and mOS than those treated with PDS (PFS: 16.2 m vs 25.9 m P Conclusion NACT followed by IDS is frequently used in the treatment of ovarian cancer patients in a tertiary centre in Greece and was correlated with adverse outcome. A selection bias favoring NACT for patients with high risk for perioperative morbidity may affect the results of this retrospective analysis. Large randomized trials to address this issue are underway. Disclosure Nothing to disclose.

Background:Metabolic pathways are important regulators of immune differentiation and activation in kidneys. Kidneys directly impact systemic metabolism, circulating metabolite levels, and express intrinsic metabolic activity. The integration of renal metabolomic and transcriptomic profiles may unravel unique gene-metabolite pairs of biological significance in lupus nephritis (LN).Objectives:To decipher gene-metabolite signatures at both pre-nephritic and nephritic stages of lupus.Methods:Kidneys were isolated and snap-frozen after perfusion from female NZB/NZW-F1 lupus mice at the pre-nephritic (3-month-old) and nephritic (6-month-old exhibiting ≥100 ng/dL of urine protein) stage of lupus (n=6/group). Age-matched female C57BL/6 mice were used as healthy controls. Sample extracts were used for RNA sequencing and 1H-NMR spectroscopy metabolic profiling. DESeq2 was used to identify differentially expressed genes. Univariate analysis was used to reveal metabolic differences characteristic for nephritis.Results:Comparative transcriptomic analyses uncovered multiple transcripts related to metabolic pathways: In pre-nephritic kidneys, lipid metabolism, cellular respiration, TCA cycle, amino acid metabolism processes were overrepresented in the upregulated genes while in nephritic kidneys, amino acid metabolism processes were overrepresented among the downregulated genes (Figure 1). 1H-NMR analysis revealed a total of 49 metabolites. Comparison of the metabolic levels of nephritic and pre-nephritic animals revealed that ADP, ATP, NAD+, Taurine and Myo-inositol decreased, while Thr increased significantly. The comparison to corresponding control animals, demonstrated that only myo-inositol increased significantly. Integration of kidney metabolomics and transcriptomics indicated the involvement of processes related to glutathione metabolism, leukocyte trans-endothelial migration and antigen presentation during the established renal disease stage.Conclusion:The combined transcriptomics and metabolomics analysis revealed metabolic derangements in lupus-affected kidneys both during subclinical and overt LN. Deregulated tissue-levels of taurine and myo-inositol at the subclinical stage of the disease suggest aberrant renal biochemistry preceding the development of overt LN that may directly impact systemic metabolism and circulating metabolite levels.Figure 1.Pathways linked to cell metabolism were overrepresented among 3-month upregulated and 6-month lupus mice (F1) downregulated DEGS (differentially expressed genes) compared to controls (C57BL/6).Acknowledgements:This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 742390).Disclosure of Interests:None declared

Cerebral venous sinus thrombosis is a relatively rare type of stroke which can be complicated by intracerebral haemorrhage resulting often in poor prognosis. Antiphospholipid syndrome and systemic lupus erythematosus both have been associated with cerebral venous sinus thrombosis. Furthermore, a few cases combining heparin-induced thrombocytopenia with cerebral venous sinus thrombosis have been described in the literature. We present a 57-year-old female patient who was admitted reporting confusion and fever for 4 days. She was immobilized due to a thoracic vertebral fracture and received enoxaparin as a prophylaxis for deep venous thrombosis. A computed tomography scan demonstrated extensive cerebral venous sinus thrombosis and two ipsilateral haemorrhagic infarcts. Moreover, the patient was serum-positive for heparininduced thrombocytopenia antibodies and had persistent fever. A thorough immunological and serological investigation turned out consistent with antiphospholipid syndrome with possible systemic lupus erythematosus. The patient was treated accordingly and was finally discharged one month later, afebrile, with mild neurological deficits.

Aim To investigate the value of CHADS 2 and CHA 2 DS 2 -VASc scores in predicting atrial fibrillation (AF) among dyslipidemic individuals and assess the additional value of incorporating low levels of high-density lipoprotein cholesterol (HDL-C). Methods This observational study included 1241 individuals attending a lipid clinic. Models including clinical and laboratory parameters were constructed to test the predictive value of CHADS 2 and CHA 2 DS 2 -VASc scores as well as low HDL-C levels for incident AF. Low HDL-C levels were defined as Results After excluding 18 patients with AF at baseline, 1223 subjects were followed-up for a median period of 6years (IQR: 4–10), and 34 (2.8%) developed AF. Baseline CHADS 2 (OR: 1.71; 95% CI: 1.28–2.29, p 2 DS 2 -VASc scores (OR: 1.56; 95% CI: 1.26–1.92, p p 2 and CHA 2 DS 2 -VASc scores were significant predictors for new-onset AF (C-Statistic: CHADS 2 0.679, p 2 DS 2 -VASc 0.698, p 2 scores were associated with reduced event-free survival from AF (log-rank=10.62, p =0.001) with differences potentiated if stratified by CHA 2 DS 2 -VASc score (log-rank=22.29, p p Conclusions CHADS 2 and CHA 2 DS 2 -VASc scores predict new AF in dyslipidemic patients. Risk prediction improved modestly when low HDL-C levels were included.

Background: The Hippo pathway is a developmental pathway recently discovered in Drosophila melanogaster; in mammals it normally controls organ development and wound healing. Hippo signaling is deregulated in breast cancer (BC). MST1/2 and LATS1/2 kinases are the upstream molecular elements of Hippo signaling which phosphorylate and regulate the two effectors of Hippo signaling, YAP1 and TAZ cotranscriptional activators. The two molecular effectors of the Hippo pathway facilitate their activity through TEAD transcription factors. Several molecular pathways with known oncogenic functions cross-talk with the Hippo pathway. Methods: A systematic review studying the correlation of the Hippo pathway with BC tumorigenesis, prognosis, and treatment was performed. Results: Recent literature highlights the critical role of Hippo signaling in a wide spectrum of biological mechanisms in BC. Discussion: The Hippo pathway has a crucial position in BC molecular biology, cellular behavior, and response to treatment. Targeting the Hippo pathway could potentially improve the prognosis and outcome of BC patients.

Numerous studies suggest that digital technology has an important role to play in physical and mental functioning and generally in the quality of life of elderly people. Many digital serious games have been developed to enhance cognitive functions. These games incorporate a multitude of multimedia elements that are perceived as sensory stimuli. To implement an effective digital environment, all sensory representations have to be investigated in order to be compatible with the visual, acoustic and tactile perception of the user. An effective way to examine those stimuli is to study the users’ brain functioning and especially the electric activity by using electroencephalographic recording systems. In recent years, there has been a growth of low-cost EEG systems. These are used in various fields such as educational research, serious games, mental and physical health, entertainment, etc. This study investigates whether a wireless low-cost EEG system (EPOC EMOTIV) can deliver qualitative results compared to a research system (G.tec) while recording the EEG data at an event-related brain potentials setup regarding the differentiation of the semantic content of two image categories. Our results show that, in terms of signal quality, the Emotiv system lags G.tec, however, based on the answers of the participants in the questionnaire, Emotiv excels in terms of ease of use. It can be used in continuous EEG recordings in game environments and could be useful for applications such as games in ageing.

Background:Metastatic RCC (mRCC) treatment has been revolutionized with 11 approved targeted agents. We report patterns of practice, outcomes and pharmacoeconomic analyses after the introduction of...

Mechanisms of tumor immune surveillance and immune escape have been recently elucidated and led to the development of a new therapeutic field in oncology, that of immunotherapy. Immunotherapy aims to reactivate the immune system against cancer. Neoplasias like non-small cell lung cancer (NSCLC) are of particular interest and clinical studies with immunotherapeutic agents have shown significant survival benefit. Several agents have gained corresponding regulatory approvals. In particular, nivolumab, pembrolizumab and atezolizumab have been approved for second-line treatment of NSCLC, pembrolizumab is the only immune checkpoint inhibitor that has been approved in the first-line treatment and durvalumab is approved in the locally advanced disease. In this review, we aim to present the implementation of immunotherapy in the treatment of advanced NSCLC. We will discuss not only the approved regimens but also the future perspectives, the serious adverse events such as hyperprogression and the possible predictive markers that will aid the selection of the patients that will benefit from immunotherapy.

session: Monolithic 3D 3; International audience; In this study we investigate the effect of some of the steps during a low temperature gate stack process flow, necessary for 3D sequential integration. These are: the nitridation of the high-k layer, the post nitridation annealing temperature and finally, the back end forming gas. Using Time Dependent Defect Spectroscopy, we could evaluate the impact of pre-existing traps on the quality of the gate stack (t 0 reliability) which shows no major differences between the splits, since they all have a low temperature dopant activation process. However, by applying Negative Bias Temperature Instability measurements, we observe that with the split of N 2 /H 2 nitridation, we have the best compromise of a small Equivalent Oxide Thickness and a low degradation. At the same time we see no difference at the stress impact between the two Post Nitridation Anneal temperatures. In that way we are able to move to lower temperatures. Finally, using the Deuterium as a back end forming gas we can have a set of guidelines, for some of the major process steps, to achieve high performance and low degradation, necessary for future scaling.

Aims To (i) describe an intervention implemented in response to the HIV-1 outbreak among people who inject drugs (PWIDs) in Greece (ARISTOTLE programme), (ii) assess its success in identifying and testing this population and (iii) describe socio-demographic characteristics, risk behaviours and access to treatment/prevention, estimate HIV prevalence and identify risk factors, as assessed at the first participation of PWIDs. Design A ‘seek, test, treat, retain’ intervention employing five rounds of respondent-driven sampling. Setting Athens, Greece (2012–13). Participants A total of 3320 individuals who had injected drugs in the past 12 months. Intervention ARISTOTLE is an intervention that involves reaching out to high-risk, hard-to-reach PWIDs (‘seek’), engaging them in HIV testing and providing information and materials to prevent HIV (‘test’) and initiating and maintaining anti-retroviral and opioid substitution treatment for those testing positive (‘treat’ and ‘retain’). Measurements Blood samples were collected for HIV testing and personal interviews were conducted. Findings ARISTOTLE recruited 3320 PWIDs during the course of 13.5 months. More than half (54%) participated in multiple rounds, resulting in 7113 visits. HIV prevalence was 15.1%. At their first contact with the programme, 12.5% were on opioid substitution treatment programmes and the median number of free syringes they had received in the preceding month was 0. In the multivariable analysis, apart from injection-related variables, homelessness was a risk factor for HIV infection in male PWIDs [odds ratio (OR) yes versus no = 1.89, 95% confidence interval (CI) = 1.41, 2.52] while, in female PWIDS, the number of sexual partners (OR for > 5 versus one partner in the past year = 4.12, 95% CI = 1.93, 8.77) and history of imprisonment (OR yes versus no = 2.76, 95% CI = 1.43, 5.31) were associated with HIV. Conclusions In Athens, Greece, the ARISTOTLE intervention for identifying HIV-positive people among people who inject drugs (PWID) facilitated rapid identification of a hidden population experiencing an outbreak and provided HIV testing, counselling and linkage to care. According to ARISTOTLE data, the 2011 HIV outbreak in Athens resulted in 15% HIV infection among PWID. Risk factors for HIV among PWID included homelessness in men and history of imprisonment and number of sexual partners in women.

Background A "seek-test-treat" intervention (ARISTOTLE) was implemented in response to an outbreak of human immunodeficiency virus (HIV) infection among persons who inject drugs (PWID) in Athens. We assess trends in HIV incidence, prevalence, risk behaviors and access to prevention/treatment. Methods Methods included behavioral data collection, provision of injection equipment, HIV testing, linkage to opioid substitution treatment (OST) programs and HIV care during 5 rounds of respondent-driven sampling (2012-2013). HIV incidence was estimated from observed seroconversions. Results Estimated coverage of the target population was 88% (71%-100%; 7113 questionnaires/blood samples from 3320 PWID). The prevalence of HIV infection was 16.5%. The incidence per 100 person-years decreased from 7.8 (95% confidence interval, 4.6-13.1) (2012) to 1.7 (0.55-5.31) (2013; P for trend = .001). Risk factors for seroconversion were frequency of injection, homelessness, and history of imprisonment. Injection at least once daily declined from 45.2% to 18.8% (P < .001) and from 36.8% to 26.0% (P = .007) for sharing syringes, and the proportion of undiagnosed HIV infection declined from 84.3% to 15.0% (P < .001). Current OST increased from 12.2% to 27.7% (P < .001), and 48.4% of unlinked seropositive participants were linked to HIV care through 2013. Repeat participants reported higher rates of adequate syringe coverage, linkage to HIV care and OST. Conclusions Multiple evidence-based interventions delivered through rapid recruitment in a large proportion of the population of PWID are likely to have helped mitigate this HIV outbreak.

International audience; The time dependent defect spectroscopy method has been used to analyze the impact of low thermal budget (TB) processes on the quality of high-k/metal gate stacks. For n-type metal-oxide-semiconductor field-effect transistors (MOSFETs), it is shown that reducing the TB of the process does not seem to degrade the t0-reliability of the gate oxide. The density of pre-existing high-k defects responsible for random telegraph noise (RTN) has a small increase for the low temperature (LT) process, and, at the same time, the location of the traps, inside the oxide, remains the same. On the other hand, for p-type MOSFETs, the gate stack reliability is affected by the thermal budget, and there is a large increase in the density of RTN defects for the LT process compared to the high temperature reference. Finally, it is observed that, for low thermal budget, the nature of the traps changes and there is a modification of the depth of the traps within the interfacial layer which are, now, closer to the Si interface. This study gives guidelines to achieve good trade off performance/reliability for a 3D CoolCube™ integration process.

SUMMARYThis analysis assessed the utility of the limiting antigen avidity assay (LAg). Samples of people who inject drugs (PWID) in Greece with documented duration of HIV-1 infection were tested by LAg. A LAg-normalized optical density (ODn) ⩽1·5 corresponds to a recency window period of 130 days. The proportion true recent (PTR) and proportion false recent (PFR) were estimated in 28 seroconverters and in 366 samples collected >6 months after HIV diagnosis, respectively. The association between LAg ODn and HIV RNA level was evaluated in 232 persons. The PTR was 85·7%. The PFR was 20·8% but fell to 5·9% in samples from treatment-naive individuals with long-standing infection (>1 year), and to 0 in samples with the circulating recombinant form CRF35 AD. A LAg-based algorithm with a PFR of 3·3% estimated a similar incidence trend to that calculated by analyses based on HIV-1 seroconversions. In recently infected persons indicated by LAg, the median log10HIV RNA level was high (5·30, interquartile range 4·56–5·90). LAg can help identify highly infectious HIV(+) individuals as it accurately identifies recent infections and is correlated with the HIV RNA level. It can also produce reliable estimates of HIV-1 incidence.

383 Background: Venous thromboembolism (VTE) is a frequent complication of cancer or its treatment. Khorana (KRS) and Compass scores are two Risk Assessment Models for VTE. However, aUTC was not adequately represented and arterial events were not included, in these models. Methods: Data from pts with aUTC treated with at least one line of chemotherapy in our institution were analyzed. VaTE definition included: DVT and PE defined as venous events and peripheral arterial thrombosis or embolus, ischemic stroke and coronary events, grouped as arterial events. The association of baseline and treatment-related factors with the development of VaTE was assessed using competing-risk regressions. According to the results of our multivariate analysis we stratified patients according to the number of the identified risk factors. Results: 354 aUTC pts treated between 4/1995 and 9/2015 entered our study. 53% of pts had received cisplatin and 42% carboplatin-based regimens. 44 pts (12.4%) suffered 45 VaTEs (13 arterial, 32 venous) within a median time of 3.3 months. The cumulative and 6-month incidence was 14.8% (95% CI: 10.9-19.4) and 9.7% (95% CI: 6.8-13.1), [venous 10.5% (95% CI: 7.3-14.3)/7.5% (95% CI: 5-10.7); arterial 5.3% (95% CI: 2.8-9)/2.7% (95% CI: 1.3-5), respectively]. No association of the KRS and the COMPASS score with the incidence of VaTEs was observed. In the univariate and multivariate analysis, cumulative VaTE incidence was significantly increased in pts with “peripheral arterial disease (PAD) or history of VΤE” (adjusted SHR: 3.29; 95% CI: 1.65-6.55; p=0.001) and pts with other solid tumor (SHR: 2.20; 95% CI: 1.05-4.62; p=0.038). There was a strong correlation between the number of risk factors and the risk for VaTE development (p

Several studies have reported the prognostic strength of HIV-1 DNA with variable results however. The aims of the current study were to estimate more accurately the ability of HIV-1 DNA to predict progression of HIV-1 disease toward acquired immunodeficiency syndrome (AIDS) or death, and to compare the prognostic information obtained by HIV-1 DNA with that derived from plasma HIV-1 RNA. Eligible articles were identified through a comprehensive search of Medline, ISI Web of Science, Scopus, and Google Scholar. The analysis included univariate and bivariate random-effects models. The univariate meta-analysis of six studies involving 1074 participants showed that HIV-1 DNA was a strong predictive marker of AIDS [relative risk (RR): 3.01, 95% confidence interval (CI): 1.88-4.82] and of all-cause mortality (RR: 3.49, 95% CI: 2.06-5.89). The bivariate model using the crude estimates of primary studies indicated that HIV-1 DNA was a significantly better predictor than HIV-1 RNA of either AIDS alone (ratio of RRs=1.47, 95% CI: 1.05-2.07) or of combined (AIDS or death) progression outcomes (ratio of RRs=1.51, 95% CI: 1.11-2.05). HIV-1 DNA is a strong predictor of HIV-1 disease progression. Moreover, there is some evidence that HIV-1 DNA might have better predictive value than plasma HIV-1 RNA. © 2012, Mary Ann Liebert, Inc. 28 4 366 373

Objective: This systematic review and meta-analysis aimed to reassess the effectiveness of condoms in reducing heterosexual transmission of HIV. Methods: Medline, Scopus, and the ISI Web of Science databases were searched up to June 2014. Eligible studies were synthesized using random-effects models. Results: Twenty-five studies with 10,676 HIV serodiscordant heterosexual couples were analyzed. The risk of HIV transmission was considerably lower among couples that were always using condoms compared to never-users (RR: 0.29, 95% CI: 0.20–0.43) or inconsistent users (RR: 0.23, 0.13–0.40). The protective effect was slightly higher when the male rather than the female partner was infected (RR: 0.31, 0.20–0.48; vs. RR: 0.44, 0.24–0.80), and very high in Asian settings (RR: 0.06, 0.01–0.46). Conclusions: Though imperfect, condoms reduce HIV transmission by more than 70% when used consistently by HIV serodiscordant heterosexual couples. Social, cultural and biological differences need to be studied further to inform projection modelers and policy makers. © 2015 Informa UK Limited, trading as Taylor & Francis Group. 16 4 489 499

Immune thrombocytopenic purpura (ITP) is an immune-mediated platelet disorder. Although early studies suggest that the main feature is antiplatelet antibody production and increased platelet clearance, more recent evidence implies that defective platelet production and suppressed maturation and differentiation of megakaryocytes also occurs. In this context, second-generation thrombopoietic agents, romiplostim and eltrombopag, have been developed for patients with chronic resistant/relapsing ITP. Eltrombopag has shown safety and efficacy in three double-blind randomized placebo-controlled multicenter studies. In these studies, a dose-dependent platelet increase to over 50 × 109/l was achieved in 58–60% of the patients. Bleeding episodes were significantly less in patients receiving eltrombopag relative to placebo. Platelet counts returned to baseline within 2 weeks of discontinuation of eltrombopag. Adverse events were mild and similar in eltrombopag- and placebo-treated groups. Transaminases increased, an...

Targeting genomic alterations, such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements, have radically changed the treatment of patients with non-small cell lung cancer (NSCLC). In the case of ALK-rearranged gene, subsequent rapid development of effective genotype-directed therapies with ALK tyrosine kinase inhibitors (TKIs) triggered major advances in the personalized molecularly based approach of NSCLC. Crizotinib was the first-in-class ALK TKI with proven superiority over standard platinum-based chemotherapy for the 1st-line therapy of ALK-rearranged NSCLC patients. However, the acquired resistance to crizotinib and its diminished efficacy to the central nervous system (CNS) relapse led to the development of several novel ALK inhibitors, more potent and with different selectivity compared to crizotinib. To date, four ALK TKIs, crizotinib, ceritinib, alectinib and brigatinib have received approval from the Food and Drug Administration (FDA) and/or the European Medicines Agency (EMA) and even more agents are currently under investigation for the treatment of ALK-rearranged NSCLC. However, the optimal frontline approach and the exact sequence of ALK inhibitors are still under consideration. Recently announced results of phase III trials recognized higher efficacy of alectinib compared to crizotinib in first-line setting, even in patients with CNS involvement. In this review, we will discuss the current knowledge regarding the biology of the ALK-positive NSCLC, the available therapeutic inhibitors and we will focus on the raised issues from their use in clinical practise.

Methylation is now established as a fundamental regulator of gene transcription. To investigate this in haematologic malignancies, we evaluated the aberrant promoter methylation of two imprinted genes (MEG3 and SNRPN) in 43 MDS and 42 AML patients. MEG3 hypermethylation occurred in 15 MDS patients (34.9%), and in 20 AML patients (47.6%). SNRPN hypermethylation was observed in 15 MDS patients (34.9%), and in 21 AML patients (50%). There were no significant correlations between WHO subtype, WPSS score, karyotype, haemoglobin levels, white blood cell count, platelet count and CpG methylation of any gene. MEG3 hypermethylation was associated with significantly reduced overall survival in individuals with AML (HR=1.98, p=0.04), while SNRPN CpG methylation was not associated with survival (HR=0.94, p=0.87). In addition, no association between survival and aberrant MEG3 (HR=2.15, p=0.072) or SNRPN methylation (HR=1.08, p=0.85) was observed in patients MDS. Our findings suggest that these genes are abnormally methylated in AML and MDS patients, and methylation of MEG3 confers worse overall prognosis. The MEG3 methylation status may serve as a useful biomarker in leukemia. Leuk Res

Whereas beta-2-microglobulin (beta2M) has mainly been used as a prognostic factor in patients with lymphoproliferative disorders, some studies have reported the value of beta2M in myeloproliferative disorders (MPD). In order to investigate a potential role in the pathogenesis of MPD and to find a possible value as indicators in monitoring the course of the disease, we measured beta2M, TNF-alpha, IL-1alpha, IL-1beta, IL-2, sIL-2R, IL-6 and IL-10 in 55 patients with MPD, at diagnosis and during the course of the disease. In progressive disease and particularly when transformation to acute leukemia occurred, high levels of beta2M, IL-2 and sIL-2R were found in all patients; the elevation was progressive, which suggests a potential prognostic usefulness in the individual patient.

The management of idiopathic thrombocytopenic purpura (ITP) during pregnancy can be challenging. The diagnosis and distinction between gestational thrombocytopenia and ITP is important and requires assessment of the timing and degree of thrombocytopenia. Exclusion of thrombocytopenia of another origin and of secondary causes of ITP is also vital before embarking on treatment, and current therapeutic options are discussed in this chapter. The mode of delivery should be dictated by obstetric indications and not related to the platelet count. Fetal blood sampling is not recommended as the incidence of neonatal bleeding remains low, but a cord-derived blood count should be taken at birth. In babies who are thrombocytopenic, intravenous immunoglobulin treatment is recommended and counts should be repeated daily until normalization of the platelet count.

Beyond the already well-established strong causative relationship with cancer, smoking increases the risk for vascular disease. Smoking may act directly or adversely influence risk factors contributing to the development of vascular disease. Smoking causes endothelial dysfunction, dyslipidemia (decreased high-density lipoprotein cholesterol levels, hypertri glyceridemia and increased oxidation of low-density lipoprotein cholesterol) and platelet acti vation leading to a prothrombotic state. Smoking increases emerging risk factors (eg, fibrinogen, homocysteine, and high-sensitivity C-reactive protein) and increases insulin resis tance and the risk of developing type 2 diabetes mellitus. The beneficial effects of statins and antioxidants (eg, vitamins C and E, β-carotene) are counteracted by smoking. Smoking-induced alterations in growth factors, adhesion molecules, and even in genes can accelerate the progression of atherosclerosis. The aim of this review is to consider the adverse consequences of smoking on the factors predisposing to vascular disease and to emphasize the beneficial effects of smoking cessation.

Background Cancer cachexia is a common associate of cancer and has a negative impact on patients’ survival. Nonetheless, cancer cachexia assessment and management are frequently less than satisfactory in daily practice. Aim To scrutinise global cancer cachexia awareness and relative web guideline implementation among oncology societies. Methods Systematical identification of scientific and policymaker oncology societies and their guideline implementation on cancer cachexia. Assessment of the general level of awareness on cancer cachexia and evaluation of intercontinental and national variations on guideline implementation. Results 144 000 web pages were scrutinised, and 275 oncology societies identified covering a large array of oncology setting (educational/clinical/research/policymaker); 71 were international (African, American, Asian, European, Oceania and Intercontinental), 110 belonged to the top 10 countries with the highest development index and 94 pertained to 10 countries with a long lasting tradition in medical oncology (not included in the top 10 high developed countries). Overall, only 10/275 web sites provided guidelines; six of them (2.2%) provided guidelines for physicians and four (0.7%) for patients. Half of the guidelines (4/10) were outdated. All guidelines for physicians reported references, while only one of the recommendations for patients reported references to support its sentences. Conclusions Cancer cachexia global awareness appears extremely low; guideline implementation on the web was inconsistent for any category analysed (nation vs continent vs international vs society type vs physician vs patient oriented) and for updating.

Background: The circulating levels of plasminogen activator inhibitor type 1 (PAI-1) are increased in individuals carrying the 4G allele at position -675 of the PAI-1 gene. In turn, overexpression of PAI-1 has been found to affect both atheroma and thrombosis. However, the association between PAI-1 levels and the incidence of myocardial infarction (MI) is complicated by the potentially confounding effects of well-known cardiovascular risk factors. The current study tried to investigate in parallel the association of PAI-1 activity with the PAI-1 4G/5G polymorphism, with MI, and some components of metabolic syndrome (MetS). Methods: Using meta-analytical Mendelian randomization approaches, genotype-disease and genotype-phenotype associations were modeled simultaneously. Results: According to an additive model of inheritance and the Mendelian randomization approach, the MI-related odd ratio for individuals carrying the 4G allele was 1.088 with 95% confidence interval (CI) 1.007, 1.175. Moreover, the 4G carriers had, on average, higher PAI-1 activity than 5G carriers by 1.136 units (95% CI 0.738, 1.533). The metaregression analyses showed that the levels of triglycerides (p =0.005), cholesterol (p=0.037) and PAI-1 (p =0.021) in controls were associated with the MI risk conferred by the 4G carriers. Conclusions: The Mendelian randomization meta-analysis confirmed previous knowledge that the PAI-1 4G allele slightly increases the risk for MI. In addition, it supports the notion that PAI-1 activity and established cardiovascular determinants, such as cholesterol and triglyceride levels, could lie in the etiological pathway from PAI-1 4G allele to the occurrence of MI. Further research is warranted to elucidate these interactions. 52 7 937 950

The effects of complimentary compound feeds with varying protein levels on growth performance, feed utilization, and whole body composition were studied in golden grey mullet, Liza aurata. Fish of initial weight 51.15.2 g were raised in hapas in a coastal lagoon and fed four iso-energetic diets containing 25%, 30%, 35% or 45% of crude protein for 20 weeks. L. aurata reared on the experimental diets showed relatively low growth rates (SGR ranged from 0.40 to 0.48%/day, and feed utilization parameters (FE ranged from 0.27 to 0.34) among dietary groups consistent with the known slow growth rate of the species. The growth performance and feed utilization of L. aurata was not significantly affected by dietary protein level, despite the fact that there was a trend indicating better fish growth and feed efficiency with increasing dietary protein level. This is indicative of the low protein requirements of L. aurata, although it could be that higher dietary protein concentrations could possibly improve growth performance. The farming of low-trophic species such as L. aurata allows under-utilized trophic resources to be better exploited for fish production. Thus any future advances in understanding the nutrition and feeding of L. aurata under culture conditions, could improve further the potential of this species, especially in regional and coastal aquaculture.

Objectives: Recombinant human erythropoietin (rHuEpo) improves anemia in 25% of patients with myelodysplastic syndromes (MDS). The variable and sometimes low response rate to rHuEpo treatment raises the question whether the existence of autoantibodies against erythropoietin (epo) is partially responsible. In the present study we investigated the presence of anti-epo autoantibodies in MDS patients. Methods: Forty-three patients with MDS were studied. Sixteen patients had refractory anemia (RA), 13 had RA with ringed sideroblasts, 3 had RA with excess of blasts (RAEB), 9 had RAEB in transformation and 2 patients had chronic myelomonocytic leukemia. They were divided in 3 groups according to rHuEpo treatment. Group A consisted of 10 patients who did not receive rHuEpo treatment. Group B included 13 patients who were on rHuEpo treatment (150 IU/kg subcutaneously, 3 times weekly) showing an increase of hemoglobin (Hb) values or reduction of transfusion requirements and Group C consisted of 20 patients who did not respond or stopped responding to rHuEpo treatment. Laboratory studies consisted of a complete blood cell count, measurement of serum epo and determination of anti-epo antibodies using ELISA. Results: There were no significant differences with regard to age and sex among the three groups. No autoantibodies against epo were found in the examined sera, apart from a female patient from group A who showed a low positive titer. Conclusion: We suggest that anti-epo autoantibodies do not contribute to the development of MDS-related anemia and are not responsible for the modest response to rHuEpo treatment. Further investigation is needed to identify possible reasons for the low response rate to rHuEpo treatment.

For elderly patients with multiple myeloma (MM), conventional melphalan and prednisone (MP) therapy has been the treatment of choice; the vincristine, doxorubicin and dexamethasone (VAD) regimen is preferred for younger patients who also receive high-dose melphalan in combination with autologous or allogeneic bone marrow transplantation (BMT). Although survival time is similar in both the MP and VAD regimens, the continuous infusion of doxorubicin which the latter treatment entails constitutes a disadvantage along with the 4-day hospitalization required. Doxorubicin also induces cardiotoxicity, particularly in the elderly. A modified form of VAD therapy includes liposomal doxorubicin (Caelyx) (40 mg/m2 for 1 d) [corrected], oncovin (2 mg for 1 d) and dexamethasone 40 mg for 4 d per os. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is more efficient and has fewer side effects than conventional doxorubicin, and it can be administered on an outpatient basis: dexamethasone can be given orally and vincristine in bolus infusion. In order to estimate its efficacy and tolerability, we administered this regimen to 12 patients (first-line treatment in 6 patients, salvage therapy in 6 patients). All patients exhibited good tolerance to liposomal doxorubicin with no severe side effects. Eight patients achieved complete hematological remission and three partial response. One patient died before completing the treatment. In conclusion, compared to other therapies, this modified VAD regimen containing liposomal doxorubicin can be more easily administered to MM patients, without severe side effects and with increased full remission rates, almost similar to those with the conventional VAD treatment.

Objectives: The aim of this study was to investigate the efficacy of recombinant human erythropoietin (rHuEpo) in postpartum anemia. Study design: At the University Hospital of Ioannina, rHuEpo was administrated subcutaneously to twenty anemic women (hemoglobin [Hb] U -test was used for the comparison of hematological indices between the two groups, on days 1, 3, 5, 10, 15 and 40 postdelivery. Results: On day 3, reticulocyte counts were significantly higher in the women who received rHuEpo, as compared to the controls ( P 2 g/dl in the group undergoing rHuEpo therapy as compared to 0.7 g/dl in the control group on day 5 ( P Conclusions: rHuEpo administration is useful for a more rapid amelioration of hematological indices in women with postpartum anemia. Further, the dose given in this study was not associated with significant side-effects.

Pleural effusion in 4 patients with chronic myelomonocytic leukemia (CMML) is described in this report. According to the literature, pleural effusion in CMML is a poorly understood and rare occurrence. Two of our patients presented with pleural effusion as an initial symptom while the other 2 developed it during the course of the disease. In only 1 patient was the pleural effusion due to leukemic infiltration while in the other 3 it was a reactive phenomenon. Peripheral lymphadenopathy was observed only in the former patient who died of acute leukemia. After prednisolone therapy the pleural effusions resolved in the other 3 patients.

Background: During 2011, a dramatic increase (1600%) of reported HIV-1 infections among injecting drug users (IDUs) was noted in Athens, Greece. We herein assess the potential causal pathways associated with this outbreak. Methods: Our study employed high resolution HIV-1 phylogenetic and phylogeographic analyses. We examined also longitudinal data of ecological variables such as the annual growth of gross domestic product (GDP) of Greece in association with HIV-1 and HCV sentinel prevalence in IDUs, unemployment and homelessness rates and HIV transmission networks in Athens IDUs before and during economic recession (2008-2012). Results: IDU isolates sampled in 2011 and 2012 suggested transmission networks in 94.6% and 92.7% of the cases in striking contrast with the sporadic networking (5%) during 1998-2009. The geographic origin of most HIV-1 isolates was consistent with the recently documented migratory waves in Greece. The decline in GDP was inversely correlated with annual prevalence rates of HIV and HCV and with unemployment and homelessness rates in IDUs (all p

Seven patients, 3 men and 4 women 48-72 years of age and suffering from idiopathic myelofibrosis were given a combination of recombinant human erythropoietin (r-hu-Epo), interferon-alpha-2b (IFN) and GM-CSF, in an attempt to treat their pancytopenia and marrow fibrosis. The dose of r-hu-Epo was 200 U/kg 3 times weekly, that of IFN was 3 x 10(6)/U 3 times weekly, and that of GM-CSF was 250 micrograms/m2/daily. The duration of therapy ranged from 3 to 6 months for r-hu-Epo and IFN and was 3 weeks for GM-CSF. The treatment regimen had a beneficial effect on all patients. The levels of hemoglobin increased in all patients but particularly in 5 (2 of whom had been dependent on red blood cell transfusions). Splenomegaly decreased significantly in 4 patients. Fibrosis in the bone marrow decreased in 2 patients. Three patients also had an increase in the number of white blood cells during the therapy with GM-CSF. We observed mild side effects in 6 of our patients. One patient had severe side effects from IFN and treatment was discontinued. In conclusion, the combination of r-hu-Epo, IFN and GM-CSF may improve the anemia (due to r-hu-Epo), increase the white blood cell count (due to GM-CSF) and reduce the marrow fibrosis (probably due to IFN) in patients with idiopathic myelofibrosis.

Inferferon alfa-2b (IFN) plays a major role in the current management of previously untreated patients with chronic myelogenous leukemia (CML) as well as patients with CML who have relapsed after bone marrow transplantation. Hydroxyurea (HU) is the best conventional drug for treatment of CML in the chronic phase. Ten patients, six men and four women, 40-70 years of age, were treated during the accelerated phase of CML with a combination of IFN and HU. Patients had received only HU during the chronic phase of the disease. All patients were positive for the Philadelphia chromosome and had an excess number of blasts in peripheral blood smears (more than 10%), as well as increased numbers of basophils and eosinophils but a low leukocyte level of alkaline phosphatase. Eight of them had splenomegaly. Five patients (50%) survived for 1-3 years, achieving complete hematological remission. Three patients had a partial hematological response and died within 1-2 years. Two patients with aggressive disease died within 3 months of the blastic crisis. It appears that combination therapy with IFN and HU might be a useful alternative for patients in the accelerated phase of CML who have failed to respond to HU alone. Acta Haematol