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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.

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

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.

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.

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: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...

This study examines the electrical brain activity of visually impaired individuals. Its aim is to identify differences in latency and signal amplitude between visually and non-visually impaired individuals in order to improve the school experience of students with visual impairment. The experiment included five visually impaired and five non-visually impaired subjects. Auditory stimuli included words with and without semantic content, i.e. actual words and pseudo-words, and Auditory Evoked Potentials were recorded. Results show that visually impaired individuals process auditory stimuli faster, regardless if the words lack semantic content, in comparison to their non-visually impaired counterparts. The study also showed variations in signal amplitude between the two groups.

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.

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.

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

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.

A significant increase in HIV-1 diagnoses was reported among Injecting Drug Users (IDUs) in the Athens (17-fold) and Bucharest (9-fold) metropolitan areas starting 2011.Molecular analyses were conducted on HIV-1 sequences from IDUs comprising 51% and 20% of the diagnosed cases among IDUs during 2011-2013 for Greece and Romania, respectively. Phylodynamic analyses were performed using the newly developed birth-death serial skyline model which allows estimating of important epidemiological parameters, as implemented in BEAST programme.Most infections (90%) occurred within four and three IDU local transmission networks in Athens and Bucharest, respectively. For all Romanian clusters, the viral strains originated from local circulating strains, whereas in Athens, the local strains seeded only two of the four sub-outbreaks. Birth-death skyline plots suggest a more explosive nature for sub-outbreaks in Bucharest than in Athens. In Athens, two sub-outbreaks had been controlled (Re1.0) by 2013 and two appeared to be endemic (Re∼1). In Bucharest one outbreak continued to expand (Re1.0) and two had been controlled (Re1.0). The lead times were shorter for the outbreak in Athens than in Bucharest.Enhanced molecular surveillance proved useful to gain information about the origin, causal pathways, dispersal patterns and transmission dynamics of the outbreaks that can be useful in a public health setting.

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

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.

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

Co-infection of human immunodeficiency virus (HIV) with hepatitis C virus (HCV) is rather common. In the era of highly active antiretroviral therapy (HAART), viral hepatitis could result in adverse outcomes in HIV+ patients. The current meta-analysis aims to evaluate the impact of HCV on immunological and virological responses after HAART initiation in HIV/HCV co-infected individuals by synthesizing the existing scientific evidence. A comprehensive search of electronic databases was performed. Eligible studies were analysed using univariate and multivariate meta-analytic methods. Totally, 21 studies involving 22533 individuals were eligible. The estimated summary difference in CD4 cell counts increase between HIV and HIV/HCV co-infected subjects after 3-12 months on HAART was 34.86 cells/mm3 [95% confidence interval (CI): 16.82-52.89]. The difference was more prominent in patients with baseline CD4 counts below 350 cells/mm3 (38.97, 95% CI: 20.00-57.93) and attenuated 2 years later (13.43, 95% CI: 0.83-26.04). The analysis of ratio measures yielded similar findings. The virological control remained unaffected by the presence of HCV (adjusted Hazard Ratio for co-infected patients vs those with HIV alone: 0.99, 95% CI: 0.91-1.07). The bivariate meta-analytic method confirmed the results of the univariate approaches. This meta-analysis supports the adverse effect of HCV on immune recovery of HIV+ patients initiating HAART, especially of those with initially impaired immunologic status. Although this effect diminishes over time, early administration of HAART in the setting of co-infection seems to be justified. © 2013 John Wiley & Sons Ltd. 20 10 715 724

A significant increase (more than 10-fold) in the number of newly diagnosed HIV-1 infections among injecting drug users (IDUs) was observed in Greece during the first seven months of 2011. Molecular epidemiology results revealed that a large proportion (96%) of HIV-1 sequences from IDUs sampled in 2011 fall within phylogenetic clusters suggesting high levels of transmission networking. Cases originated from diverse places outside Greece supporting the potential role of immigrant IDUs in the initiation of this outbreak.

Introduction. Nicotinic acid (NA) and statins have been associated with reductions in blood pressure (BP). Patients and Methods. We recruited 68 normotensive and hypertensive dyslipidemic patients who were treated with a conventional statin dose and had not achieved lipid targets. Patients were randomized to switch to high-dose rosuvastatin (40 mg/day) or to add-on current statin treatment with extended release (ER) NA/laropiprant (1000/20 mg/day for the first 4 weeks followed by 2000/40 mg/day for the next 8 weeks) for 3 months. Results. Switching to rosuvastatin 40 mg/day was not associated with significant BP alterations. In contrast, the addition of ER-NA/laropiprant to current statin treatment resulted in a 7% reduction of systolic BP (from 1 3 4 ± 1 2 to 1 2 5 ± 1 0 mmHg, 𝑃 . 0 0 1 versus baseline and 𝑃 = . 0 1 versus rosuvastatin group) and a 5% reduction of diastolic BP (from 8 1 ± 9 to 7 7 ± 6 mmHg, 𝑃 = . 0 0 9 versus baseline and 𝑃 = . 0 1 versus rosuvastatin group). These reductions were significant only in the subgroup of hypertensives and were independent of the hypolipidemic effects of ER-NA/laropiprant. Conclusions. Contrary to the switch to high-dose rosuvastatin, the addition of ER-NA/laropiprant to statin treatment was associated with significant reductions in both systolic and diastolic BP.

Primary plasma cell (PCL) leukemia is a rare lymphoproliferative disorder characterized by a malignant proliferation of plasma cells in the bone marrow and peripheral blood. Survival with standard therapy using melphalan is very poor. Doxorubicin encapsulated with liposomes has less cardiotoxicity, is at least as efficient and has fewer side effects than conventional doxorubicin. Two female patients (69 and 54 yr old) with primary PCL are described in this study. They both received a modified form of VAD (vincristine, doxorubicin and dexamethasone), a regimen which includes liposomal doxorubicin (40 mg/m2 for 1 d), vincristine (2 mg for 1 d) and dexamethasone 40 mg per os on days 1-4, 9-12 and 17-20. A disease evaluation of the first patient after six courses of the modified \VAD regimen showed no plasma cells in the peripheral blood, a decrease in the serum M protein level and a plasma cell infiltration in the bone marrow of less than 5%. The patient died from a cardiac episode 24 months post-diagnosis, while she was in complete hematological remission. The second patient also exhibited good tolerance to liposomal doxorubicin with no side effects, achieved complete haematological remission and remains in good condition 7 months after the last VAD administration. These results suggest that this modified form of VAD regimen also seems to work in PCL and is well tolerated with no side effects.

Aim: To assess the use of post-exposure prophylaxis after a non-occupational exposure to HIV in Greece. Methods: We analysed the data that were reported to the Hellenic Centre for Disease Control and Prevention by physicians who requested non-occupational post-exposure to HIV prophylaxis (NONOPEP). Results: During the period January 1996-June 2005 inclusive, 159 persons received NONOPEP (116 males, 42 females and 1 unknown). Fifty-three per cent of the males sought NONOPEP because of an exposure to sperm and vaginal secretions, while 35.7% of the females were exposed to sperm. Unprotected sex was the main reported cause of exposure to HIV (38.36%) followed by condom rupture (35.85%). For 110 (69.18%) persons, it was the first time they were prescribed NONOPEP. Conclusion: The current surveillance system in Greece should be further developed to include the documentation of potential drug-toxicity, side effects and adherence to the prophylaxis. The health educational role of the nurse in HIV prevention in Greece should be developed. © 2008 International Council of Nurses. 55 1 68 72

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case-control studies and three cohort studies). The case-control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858-1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353-0.775), but the estimated effect size was insignificant when cohort and case-control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662-1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation. © 2007 Lippincott Williams & Wilkins, Inc. 18 5 497 504

Objective: Many developed countries have implemented surveillance systems for monitoring occupational exposure to HIV. The aim of the present study was to analyze surveillance data on HIV postexposure prophylaxis (PEP) for health care workers (HCWs) in Greece. Design: All data reported to the Hellenic Centre for Disease Control and Prevention between January 1996 and June 2005 were analyzed. Sample and measurement: 188 reported occupational exposures to HIV were analyzed, retrospectively. Results: Most exposures were in the physicians (37.8%), followed by the nursing personnel (18.6%). Nearly 38% of the HCWs were males and the predominant type of biological material involved in the exposure was blood (74.5%). Two drugs were used for PEP in 23.4% of the HCWs, and 3 drugs in 66.5% of the reported cases. Conclusions: Greek guidelines provide guidance for treating HCWs after occupational exposure to HIV. In our study, antiretroviral treatment, a three-drug regimen in the majority of the cases, was prescribed after evaluation of specially appointed physicians. The surveillance system of occupational exposure to HIV in HCWs should be further developed and enhanced in order to monitor and evaluate the risk factors surrounding the incidents. © 2007, Blackwell Publishing, Inc. 24 4 337 342

Objective To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. Methods HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-β-1a) plus natalizumab 300mg (n = 589), or IFN-β-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. Results Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. Interpretation HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab. Ann Neurol 2007

Leuk Lymphoma

Background: Patients with chronic idiopathic myelofibrosis (CIMF) usually present with anaemia. Treatment is often palliative and the majority of patients receive regular red blood cell (RBC) transfusions. Although recombinant human erythropoietin (rhu-EPO) has been proved effective for the treatment of anaemia in several chronic diseases, including haematological malignancies, its role in the treatment of the anaemia in CIMF is not well established. We report the beneficial effect of rhu-EPO administration in 20 patients with CIMF and discuss the parameters predicting favourable response. Patients: Twenty patients with CIMF (9 women and 11 men) regularly treated with supportive RBC transfusions were included in the study. The median age was 70 years (range 45–81 years). Rhu-EPO, 10,000 U, was given subcutaneously 3 times a week. The median duration of therapy was 83 months, ranging from 13 to 87 months. Results: Treatment was considered effective if haemoglobin levels increased over 2 g/dl within 12 weeks after enrolment or the RBC transfusion requirements were reduced by 50% within the same interval. Twelve patients (60%) responded to therapy. Responders were mainly female, had smaller spleen size (p = 0.024), low RBC transfusion requirements (≤1–2 units per month), and significantly lower endogenous serum erythropoietin (EPO) and β2-microglobulin (β2-M) levels when compared with non-responders (p < 0.0001 and 0.00001, respectively). Treatment was well tolerated and none of the patients was withdrawn from the treatment protocol because of side effects. Conclusions: Rhu-EPO administration is an effective, safe and well-tolerated treatment for patients with CIMF and anaemia leading to a significant reduction in RBC transfusion requirements. Factors predicting favourable response are low endogenous EPO and β2-M serum levels and slight to moderate splenomegaly.

Large-scale trials established that statin administration in hypercholesterolaemic individuals and patients with coronary heart disease (CHD) significantly reduces the risk of vascular events and death. This benefit was primarily attributed to their actions on lipids. This review focuses on the benefits (clinical and experimental) of statins observed soon (approximately 12 weeks) after their administration. Statins rapidly increase nitric oxide production and improve endothelial function (e.g. increased flow-mediated dilatation). Similarly, antioxidant properties decrease the susceptibility of low density lipoprotein cholesterol to oxidation. Statins inhibit the migration of macrophages and smooth muscle cell proliferation leading to an antiproliferative effect and the stabilisation of atherosclerotic plaques. Anti-inflammatory effects include a reduction in serum C-reactive protein levels, inflammatory and proinflammatory cytokines (e.g. IL-6, IL-8), adhesion molecules (e.g. ICAM-1, VCAM-1) and other acute phase proteins. Statins influence the haemostatic system. They reduce tissue factor expression and platelet activity, whereas fibrinolysis can be enhanced. Statins improve microalbuminuria, renal function, hypertension and arterial wall stiffness. A significant reduction of the carotid intima media thickness (IMT) was also reported early after statin treatment. These early effects of statins probably contribute to the significant reduction in vascular events seen in some 'short-term' studies. There is a need to further elucidate the rapid and non-lipid lowering properties of statins.

Activated platelets play a role in the pathogenesis of coronary heart disease (CHD). Following activation, platelets change shape, aggregate, and release several bioactive substances. The aim of this review is to identify if there is a simple and cost-effective method that indicates platelet activation and predicts the risk of CHD and vascular events. The rationale for identifying high-risk patients is to reduce their risk of vascular events by administering appropriate and effective antiplatelet treatment, like aspirin, clopidogrel, or combination regimens. Many laboratory tests estimating platelet activity have been described. Some are relatively simple, such as spontaneous or agonist-induced platelet aggregation. Other tests include measuring the mean platelet volume (MPV) or plasma soluble P-selectin levels. Some more complex tests include flow cytometry to determine platelet GP Ilb/Illa receptors, platelet surface P-selectin, plateletmonocyte aggregates, and microparticles. Only few prospective studies assessed the predictive value of platelet activation in healthy individuals. Although the MPV seems an 'easy method, there are insufficient data supporting its ability to predict the risk of a vascular event in healthy adults. Platelet aggregation, in whole blood or in platelet-rich plasma was not consistently predictive of vascular risk. Soluble P-selectin measurement is a promising method but it needs further evaluation. Flow cytometry methods are costly, time-consuming, and need specialized equipment. Thus, they are unlikely to be useful in estimating the risk in large numbers of patients. There is as yet no ideal test for the detection of platelet activation. Each currently available test has merits and disadvantages. Simple methods such as the MPV and the determination of platelet release products need further evaluation.

The risk of secondary leukemia in breast cancer patients who receive adjuvant chemotherapy is an open question. We describe the case a 38-year-old woman who developed acute leukemia 18 months after completion of intense adjuvant chemotherapy with prophylactic granulocyte colony-stimulating factor (G-CSF) support and chest wall irradiation. The diagnosis of biphenotypic T-cell acute myeloid leukemia (AML) was based on morphologic and immunophenotypic criteria. Chromosomal analysis of blasts revealed multiple trisomies and tetrasomies. The patient failed to respond to induction and salvage chemotherapy and died 4 months later. This case of acute leukemia occurred in a cohort of 65 high-risk breast cancer patients who were given intense adjuvant chemotherapy during the last 5 years in our hospital. This is the first case reported in the literature of acute leukemia following intense adjuvant chemotherapy with continuous prophylactic G-CSF, which is an actively investigated therapeutic strategy. Vigilance and investigation are needed to determine the leukemogenic potential of intense adjuvant chemotherapy plus radiotherapy in breast cancer patients. A brief review of the literature that deals with acute leukemia that develops after adjuvant chemotherapy for breast cancer and with secondary biphenotypic acute leukemia is presented. Breast J

Headache is one of the most common neurological symptoms that lead patients to the ED. The latest data show that 50-75% of adults globally, have experienced headache at least once during the past year and about 1-4% can be affected for several days per month, resulting in a huge disease load that increases the cost of health care worldwide.

Following the administration of the human anti-CD20 monoclonal antibody IDEC-C2B8 (rituximab), a 31-year-old woman with B-prolymphocytic leukemia, who had been resistant to CHOP, fludarabine, pentostatin and 2-CdA, achieved complete remission. Rituximab was administered intravenously once a week for 4 weeks. The patient only had mild but tolerable side effects during the first cycle of therapy. She remains in complete remission 8 months following the discontinuation of treatment.