Early predictors of outcome in comatose survivors of ventricular fibrillation and non-ventricular fibrillation cardiac arrest treated with hypothermia: a prospective study

OBJECTIVES: Current indications for therapeutic hypothermia (TH) are restricted to comatose patients with cardiac arrest (CA) due to ventricular fibrillation (VF) and without circulatory shock. Additional studies are needed to evaluate the benefit of this treatment in more heterogeneous groups of patients, including those with non-VF rhythms and/or shock and to identify early predictors of outcome in this setting. DESIGN: Prospective study, from December 2004 to October 2006. SETTING: 32-bed medico-surgical intensive care unit, university hospital. PATIENTS: Comatose patients with out-of-hospital CA. INTERVENTIONS: TH to 33 +/- 1 degrees C (external cooling, 24 hrs) was administered to patients resuscitated from CA due to VF and non-VF (including asystole or pulseless electrical activity), independently from the presence of shock. MEASUREMENTS AND MAIN RESULTS: We hypothesized that simple clinical criteria available on hospital admission (initial arrest rhythm, duration of CA, and presence of shock) might help to identify patients who eventually survive and might most benefit from TH. For this purpose, outcome was related to these predefined variables. Seventy-four patients (VF 38, non-VF 36) were included; 46% had circulatory shock. Median duration of CA (time from collapse to return of spontaneous circulation [ROSC]) was 25 mins. Overall survival was 39.2%. However, only 3.1% of patients with time to ROSC > 25 mins survived, as compared to 65.7% with time to ROSC < or = 25 mins. Using a logistic regression analysis, time from collapse to ROSC, but not initial arrest rhythm or presence of shock, independently predicted survival at hospital discharge. CONCLUSIONS: Time from collapse to ROSC is strongly associated with outcome following VF and non-VF cardiac arrest treated with therapeutic hypothermia and could therefore be helpful to identify patients who benefit most from active induced cooling.

Clinical relevance of L-carnitine-supplemented total parenteral nutrition in postoperative trauma. Metabolic effects of continuous or acute carnitine administration with special reference to fat oxidation and nitrogen utilization.

Carnitine-free total parenteral nutrition (TPN) is claimed to result in a carnitine deficiency with subsequent impairment of fat oxidation. The present study was designed to evaluate the possible benefit of carnitine supplementation on postoperative fat and nitrogen utilization. Sixteen patients undergoing total esophagectomy were evenly randomized and received TPN without or with L-carnitine supplementation (74 mumol.kg-1.d-1) during 11 postoperative days. On day 11, a 4-h infusion of L-carnitine (125 mumol/kg) was performed in both groups. The effect of supplementation was evaluated by indirect calorimetry, N balance, and repeated measurements of plasma lipids and ketone bodies. Irrespective of continuous or acute supplementation, respiratory quotient and fat oxidation were similarly maintained throughout the study in both groups whereas N balance appeared to be more favorable without carnitine. We conclude that carnitine-supplemented TPN does not improve fat oxidation or promote N utilization in the postoperative phase.

Population specific and up to date cardiovascular risk charts can be efficiently obtained with record linkage of routine and observational data.

BACKGROUND: Only few countries have cohorts enabling specific and up-to-date cardiovascular disease (CVD) risk estimation. Individual risk assessment based on study samples that differ too much from the target population could jeopardize the benefit of risk charts in general practice. Our aim was to provide up-to-date and valid CVD risk estimation for a Swiss population using a novel record linkage approach. METHODS: Anonymous record linkage was used to follow-up (for mortality, until 2008) 9,853 men and women aged 25-74 years who participated in the Swiss MONICA (MONItoring of trends and determinants in CVD) study of 1983-92. The linkage success was 97.8%, loss to follow-up 1990-2000 was 4.7%. Based on the ESC SCORE methodology (Weibull regression), we used age, sex, blood pressure, smoking, and cholesterol to generate three models. We compared the 1) original SCORE model with a 2) recalibrated and a 3) new model using the Brier score (BS) and cross-validation. RESULTS: Based on the cross-validated BS, the new model (BS = 14107×10(-6)) was somewhat more appropriate for risk estimation than the original (BS = 14190×10(-6)) and the recalibrated (BS = 14172×10(-6)) model. Particularly at younger age, derived absolute risks were consistently lower than those from the original and the recalibrated model which was mainly due to a smaller impact of total cholesterol. CONCLUSION: Using record linkage of observational and routine data is an efficient procedure to obtain valid and up-to-date CVD risk estimates for a specific population.

Feasibility of Therapeutic Drug Monitoring (TDM) for Imatinib: Preliminary considerations on the dosage adjustment approach for CML patients enrolled in the Imatinib Concentration Monitoring (I-COME) study

Background: As imatinib pharmacokinetics are highly variable, plasma levels differ largely between patients under the same dosage. Retrospective studies in chronic myeloid leukemia (CML) patients showed significant correlations between low levels and suboptimal response, and between high levels and poor tolerability. Monitoring of plasma levels is thus increasingly advised, targeting trough concentrations of 1000 μg/L and above. Objectives: Our study was launched to assess the clinical usefulness of systematic imatinib TDM in CML patients. The present preliminary evaluation questions the appropriateness of dosage adjustment following plasma level measurement to reach the recommended trough level, while allowing an interval of 4-24 h after last drug intake for blood sampling. Methods: Initial blood samples from the first 9 patients in the intervention arm were obtained 4-25 h after last dose. Trough levels in 7 patients were predicted to be significantly away from the target (6 <750 μg/L, and 1 >1500 μg/L with poor tolerance), based on a Bayesian approach using a population pharmacokinetic model. Individual dosage adjustments were taken up in 5 patients, who had a control measurement 1-4 weeks after dosage change. Predicted trough levels were confronted to anterior model-based extrapolations. Results: Before dosage adjustment, observed concentrations extrapolated at trough ranged from 359 to 1832 μg/L (median 710; mean 804, CV 53%) in the 9 patients. After dosage adjustment they were expected to target between 720 and 1090 μg/L (median 878; mean 872, CV 13%). Observed levels of the 5 recheck measurements extrapolated at trough actually ranged from 710 to 1069 μg/L (median 1015; mean 950, CV 16%) and had absolute differences of 21 to 241 μg/L to the model-based predictions (median 175; mean 157, CV 52%). Differences between observed and predicted trough levels were larger when intervals between last drug intake and sampling were very short (~4 h). Conclusion: These preliminary results suggest that TDM of imatinib using a Bayesian interpretation is able to bring trough levels closer to 1000 μg/L (with CV decreasing from 53% to 16%). While this may simplify blood collection in daily practice, as samples do not have to be drawn exactly at trough, the largest possible interval to last drug intake yet remains preferable. This encourages the evaluation of the clinical benefit of a routine TDM intervention in CML patients, which the randomized Swiss I-COME study aims to.

Appropriateness of therapy for active Crohn's disease: results of a multidisciplinary international expert panel-EPACT II

The increasing number of trials testing management strategies for luminal Crohn's disease (CD) has not fitted all the gaps in our knowledge and thus, in clinical. practice, many decisions for CD patients have to be taken without the benefit of high-quality evidence. Methods: A multidisciplinary European expert panel used the RAND Appropriateness Method to develop and rate explicit criteria for the management of individual patients with active, steroid-dependent (ST-D) and steroid-refractory (ST-R) CD. Results: Overall., 296 indications pertaining to mild-to-moderate, severe, ST-D, and ST-R CD were rated. In anti-TNF naive patients, budesonide and prednisone were found to be appropriate for mild-moderate CD, and infliximab (IFX) was appropriate when these had previously failed or had not been tolerated. In patients with a prior successful treatment by IFX, this drug, with or without co-administration of a thiopurine analog, was favoured. Other anti-TNFs were appropriate in the presence of intolerance or resistance to IFX. High-dose steroids, IFX or adlimumab were appropriate in severe active CD. For the 105 indications for ST-D or ST-R disease, the panel considered the thiopurine analogs, methotrexate, IFX, adalimumab, and surgery for limited resection, to be appropriate, depending on the outcome of prior therapies. Anti-TNFs were generally considered appropriate in ST-R. Conclusion: Steroids, including budesonide for mild-to-moderate CD, remain the first-line therapy for active luminal CD. Anti-TNFs, in particular IFX as shown by the amount of available evidence, remain the second-line therapy for most indications. Thiopurine analogs, methotrexate and anti-TNFs are favoured in ST-D patients and ST-R patients. (C) 2009 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

Use of nitrification inhibitor DMPP to improve nitrogen recovery in irrigated wheat on a calcareous soil

The 3,4-dimethyilpyirazole phosphate (DMPP), commercialized as Entec, is a nitrification inhibitor developed by BASF (Germany) that may help to minimize N losses and to obtain a higher profit from N fertilizers. A two-year field trial was established in 2001 in the Northeast of Spain to assess the effects of DMPP on N use efficiency (NUE) and to determine the economic returns. Seven treatments have been carried out comparing the effect of DMPP on pig slurry and on mineral fertilizers. The application of DMPP resulted in better efficiency indexes on mineral fertilizers. An apparent nitrogen recovery of 0.465 kg kg-1, on average, was obtained for the Entec treatment. A net benefit of € 809 ha-1, on average, was obtained for the Entec treatment compared with € 607 ha-1 for the control treatment. The results of this study suggest that the nitrification inhibitor could improve farmer profit in irrigated wheat on a calcareous soil.

Signalling value of maternal and paternal melanism in the barn owl : implication for the resolution of the lek paradox

Secondary sexual characters often signal qualities such as physiological processes associated with resistance to various sources of stress. When the expression of an ornament is not sex-limited, we can identify the costs and benefits of displaying a trait that is typical of its own sex or of the other sex. Indeed, the magnitude and sign of the covariation between physiology and the extent to which an ornament is expressed could differ between males and females if, for instance, the regulation of physiological processes is sensitive to sex hormones. Using data collected over 14 years in the nocturnal barn owl Tyto alba, we investigated how nestling body mass covaries with a heritable melanin-based sex-trait, females displaying on average larger black feather spots than males. Independently of nestling sex, year and time of the day large-spotted nestlings were heavier than small-spotted nestlings. In contrast, the magnitude and sign of the covariation between nestling body mass and the size of parental spots varied along the day in a way that depended on the year and parental gender. In poor years, offspring of smaller-spotted mothers were heavier throughout the resting period; in the morning, offspring sired by larger-spotted fathers were heavier than offspring of smaller-spotted fathers, while in the evening the opposite pattern was found. Thus, maternal and paternal coloration is differentially associated with behaviour or physiology, processes that are sensitive to time of the day and environmental factors. Interestingly, the covariation between offspring body mass and paternal coloration is more sensitive to these environmental factors than the covariation with maternal coloration. This indicates that the benefit of pairing with differently spotted males may depend on environmental conditions, which could help maintain genetic variation in the face of intense directional (sexual) selection.

Breeding, genetic and genomic of citrus for disease resistance

Although the citriculture is one of the most important economic activities in Brazil, it is based on a small number of varieties. This fact has contributed for the vulnerability of the culture regarding the phytosanitary problems. A higher number of varieties/genotypes with potential for commercial growing, either for the industry or fresh market, has been one of the main objectives of citrus breeding programs. The genetic breeding of citrus has improved, in the last decades, due to the possibility of an association between biotechnological tools and classical methods of breeding. The use of molecular markers for early selection of zygotic seedlings from controlled crosses resulted in the possibility of selection of a high number of new combination and, as a consequence, the establishment of a great number of hybrids in field experiments. The faster new tools are incorporated in the program, the faster is possibility to reach new genotypes that can be tested as a new variety. Good traits should be kept or incorporate, whereas bad traits have to be excluded or minimized in the new genotype. Scion and rootstock can not be considered separately, and graft compatibility, fruit quality and productivity are essential traits to be evaluated in the last stages of the program. The mapping of QTLs has favored breeding programs of several perennial species and in citrus it was possible to map several characteristics with qualitative and quantitative inheritance. The existence of linkage maps and QTLs already mapped, the development of EST and BAC library and the sequencing of the Citrus complete genome altogether make very demanding and urgent the exploration of such data to launch a wider genetic study of citrus. The rising of information on genome of several organisms has opened new approaches looking for integration between breeding, genetic and genome. Genome assisted selection (GAS) involves more than gene or complete genome sequencing and is becoming an import support in breeding programs of annual and perennial species. An huge information amount can be derivate from genome analysis. The use and benefit of such informations will depend on the genetic basis of the breeding program.

Chemotherapy and radiotherapy in nasopharyngeal carcinoma: an update of the MAC-NPC meta-analysis.

BACKGROUND: A previous individual patient data meta-analysis by the Meta-Analysis of Chemotherapy in Nasopharynx Carcinoma (MAC-NPC) collaborative group to assess the addition of chemotherapy to radiotherapy showed that it improves overall survival in nasopharyngeal carcinoma. This benefit was restricted to patients receiving concomitant chemotherapy and radiotherapy. The aim of this study was to update the meta-analysis, include recent trials, and to analyse separately the benefit of concomitant plus adjuvant chemotherapy. METHODS: We searched PubMed, Web of Science, Cochrane Controlled Trials meta-register, ClinicalTrials.gov, and meeting proceedings to identify published or unpublished randomised trials assessing radiotherapy with or without chemotherapy in patients with non-metastatic nasopharyngeal carcinoma and obtained updated data for previously analysed studies. The primary endpoint of interest was overall survival. All trial results were combined and analysed using a fixed-effects model. The statistical analysis plan was pre-specified in a protocol. All data were analysed on an intention-to-treat basis. FINDINGS: We analysed data from 19 trials and 4806 patients. Median follow-up was 7·7 years (IQR 6·2-11·9). We found that the addition of chemotherapy to radiotherapy significantly improved overall survival (hazard ratio [HR] 0·79, 95% CI 0·73-0·86, p<0·0001; absolute benefit at 5 years 6·3%, 95% CI 3·5-9·1). The interaction between treatment effect (benefit of chemotherapy) on overall survival and the timing of chemotherapy was significant (p=0·01) in favour of concomitant plus adjuvant chemotherapy (HR 0·65, 0·56-0·76) and concomitant without adjuvant chemotherapy (0·80, 0·70-0·93) but not adjuvant chemotherapy alone (0·87, 0·68-1·12) or induction chemotherapy alone (0·96, 0·80-1·16). The benefit of the addition of chemotherapy was consistent for all endpoints analysed (all p<0·0001): progression-free survival (HR 0·75, 95% CI 0·69-0·81), locoregional control (0·73, 0·64-0·83), distant control (0·67, 0·59-0·75), and cancer mortality (0·76, 0·69-0·84). INTERPRETATION: Our results confirm that the addition of concomitant chemotherapy to radiotherapy significantly improves survival in patients with locoregionally advanced nasopharyngeal carcinoma. To our knowledge, this is the first analysis that examines the effect of concomitant chemotherapy with and without adjuvant chemotherapy as distinct groups. Further studies on the specific benefits of adjuvant chemotherapy after concomitant chemoradiotherapy are needed. FUNDING: French Ministry of Health (Programme d'actions intégrées de recherche VADS), Ligue Nationale Contre le Cancer, and Sanofi-Aventis.

Effect of corticosteroids on the clinical course of community-acquired pneumonia: a randomized controlled trial

Introduction The benefit of corticosteroids as adjunctive treatment in patients with severe community-acquired pneumonia (CAP) requiring hospital admission remains unclear. This study aimed to evaluate the impact of corticosteroid treatment on outcomes in patients with CAP. Methods This was a prospective, double-blind and randomized study. All patients received treatment with ceftriaxone plus levofloxacin and methyl-prednisolone (MPDN) administered randomly and blindly as an initial bolus, followed by a tapering regimen, or placebo. Results Of the 56 patients included in the study, 28 (50%) were treated with concomitant corticosteroids. Patients included in the MPDN group show a more favourable evolution of the pO2/FiO2 ratio and faster decrease of fever, as well as greater radiological improvement at seven days. The time to resolution of morbidity was also significantly shorter in this group. Six patients met the criteria for mechanical ventilation (MV): five in the placebo group (22.7%) and one in the MPDN group (4.3%). The duration of MV was 13 days (interquartile range 7 to 26 days) for the placebo group and three days for the only case in the MPDN group. The differences did not reach statistical significance. Interleukin (IL)-6 and C-reactive protein (CRP) showed a significantly quicker decrease after 24 h of treatment among patients treated with MPDN. No differences in mortality were found among groups. Conclusions MPDN treatment, in combination with antibiotics, improves respiratory failure and accelerates the timing of clinical resolution of severe CAP needing hospital admission.

Survival after surgical drainage of malignant pericardial effusion.

OBJECTIVES: Management of malignant pericardial effusion (PE) is complex. Cardiac surgeons are not necessarily familiar with or are challenged by the many underlying etiologies. Analyzing risk factors for mortality may help to estimate the benefit of surgery in high-risk patients. METHODS: Patients undergoing a surgical pericardiotomy for malignant PE, between 2001 and 2011, were included. The influence of tumor type, disease extension, intra-pericardial tumor infiltration on early mortality and long-term survival as well as freedom from symptoms after drainage, and the use of sclerosing agents on PE recurrence rates was analyzed. RESULTS: PE drainage was performed on 46 patients 12 ± 30 months after tumor diagnosis. Malignant diseases were lung cancers (50 %), breast cancers (15 %), lymphoma and leukemia (13 %), cancers of the digestive tract (13 %), and others (9 %). 80 % of patients were symptomatic and symptom relief was achieved in 65 %. Nobody died during surgery. Recurrence rate was 4 %. Early in-hospital mortality was 22 %. After 1 year, 29 % of patients were alive. Eleven patients (24 %) had a complete tumor regression. Metastatic spread (p < 0.001), pericardial infiltration (p = 0.02), and intra-pericardial Bleomycin (p = 0.01) injection were associated with increased mortality. Hematological malignancies had a better prognosis for survival. CONCLUSION: Surgical pericardiotomy is safe, associated with a low recurrence rate and symptom relief in the majority of dyspneic patients. Intra-pericardial Bleomycin may reduce recurrent effusion but does not ameliorate survival. Long-term survival rate was low with an increased mortality in cases of metastatic spreading, pericardial infiltration, and as the tumor of origin: breast cancers. Leukemic and lymphatic tumors have better prognosis.

Competitive Analysis of the Northwest Russian Transport Logistics Cluster – Finnish Perspective

Tutkimus tarkastelee Luoteis-Venäjän liikennelogistiikkaklusteria. Tarkoitus on selvittää klusterin nykyinen rakenne ja kilpailukyky sekä klusterin tarjoamat liiketoimintamahdollisuudet suomalaisille logistiikkayrityksille. Työssä käsitellään neljää perusliikennemuotoa: rautatie-, maantie-, meri- ja sisävesi-, sekä ilmaliikennettä. Tutkimuksen aineisto on kerätty tutkimusta varten laadituista kyselyistä, haastatteluista sekä aiemmin julkaistusta materiaalista. Venäjä on suunnitellut kehittävänsä voimakkaasti liikenneinfrastruktuuria, mm. julkaisemalla protektionistisen liikennestrategiasuunnitelman. Ongelmana ovat olleet toteutukset, jotka ovat jääneet yleensä puutteellisiksi. Tällä hetkellä todellista kilpailukykyä löytyy ainoastaan rautatieliikenteestä, muut kolme liikennemuotoa omaavat potentiaalisen kilpailukyvyn. Venäjällä on mahdollisuus hyötyä laajasta pinta-alastaan Aasian ja Euroopan liikenteen yhdistäjänä. Yksi konkreettisimmista esimerkeistä on Trans Siperian rautatie, joka kaipaisi vielä lisäkehitystä. Suomi on toiminut Venäjän liikenteessä arvotavaran kauttakulkumaana, vuonna 2003 noin 30–40 % Venäjän tuonnin arvosta kulki Suomen kautta. Venäjälle tullaan tuomaan arvotavaraa vielä useita vuosia, mutta reittien osalta kilpailu on tiukentunut. Suomalaisten yritysten liiketoimintamahdollisuuksiin esitetään kaksi mallia: kauttakulkuliikenteen lisäarvologistiset (VAL) operaatiot Suomessa tai etabloituminen Venäjän logistisiin ketjuihin. Suomalaisten olisi syytä parantaa yhteistyötään yritysten ja yliopistojen ym. koulutuslaitosten välillä. Myös yhteistyökumppaneiden hakeminen esimerkiksi Ruotsista voisi tuoda merkittäviä etuja. Suomalaista osaamista voitaisiin hyödyntää parhaiten etabloitumalla Venäjän markkinoille, esimerkiksi keskittymällä Venäjän logististen ketjujen johtamiseen. Myös VAL palveluiden johtamiseen Venäjällä olisi erittäin hyvä tilaisuus, koska Venäjän oma tietotaito logistiikassa ei ole vielä kehittynyt kansainväliselle tasolle, mutta kustannustaso on alhaisempi kuin Suomessa.

PROVISIONING OF MIDLETS

Java™ 2 Platform, Micro Edition on eräs johtava sovellusalusta, joka mahdollistaa kolmannen osapuolen sovellusten luomisen matkapuhelimiin, kommunikaattoreihin ja taskutietokoneisiin. Java-alusta keskeinen etu on sovellusten dynaaminen asentaminen. Käyttäjä ei ole rajoitettu esiasennettuihin sovelluksiin vaan voi asentaa niitä itse tarpeen mukaan. Tämän diplomityö käsittelee erilaisia Java sovellusten (MIDlettien) lataus ja asennusmenetelmiä. Diplomityö antaa yhteenvedon merkittävimmistä asennus teknologioista. Pääpaino on MIDP-standardin mukaisella langattomalle asennuksella (Over-The-Air provisioning) sillä se on kaikkein laajimmin käytetty menetelmä. Muita käsiteltäviä menetelmiä ovat WAP Push ja paikallinen asennus Bluetoothin ja Infrapunalinkin avulla. MIDletit, kuten mitkä tahansa ohjelmat, ovat alttiita laittomalle kopioinnille. Tämä diplomityö kuvaa menetelmiä, joilla laiton kopiointi voidaan estää. Yksi esimerkki on OMA™ DRM standardi. Diplomityö kuvaa myös kuinka kopiointisuojaus voidaan yhdistää olemassa oleviin asennusmenetelmiin. Java sovelluksia, MIDlettejä, käytetään yhä erilaisimpiin tarkoituksiin jolloin tarvitaan myös uusia asennusmenetelmiä. Yksi tällainen menetelmä on asentaminen erillisistä laitteista. Diplomityö kuvaa useita menetelmiä asentamiseen erillisistä laitteista. Käsitellyr menetelmät pohjautuvat Bluetooth teknologiaan ja yhtä lukuun ottamatta perustuvat standardin määrittelemiin Bluetooth profiileihin File Transfer Profile, Personal Area Networking Profile ja Object Push Profile. Toinen asennustapa on sovellusten edelleen lähettäminen toiseen puhelimeen. Diplomityö kuvaa kuinka OMA DRM standardi voidaan yhdistää tällaisen asennuksen ja ehdottaa kahta vaihtoehtoista menetelmää. Yksi perustuu Bluetoothin Object Push Profiiliin ja toinen Infrapunalinkin käyttöön. Toinen perustuu multimediaviestiin ja sähköpostiin.

Early transjugular intrahepatic portosystemic shunt in cirrhotic patients with acute variceal bleeding: a systematic review and meta-analysis of controlled trials.

INTRODUCTION: There is conflicting evidence on the benefit of early transjugular intrahepatic portosystemic shunt (TIPSS) on the survival of patients with acute variceal bleeding (AVB). AIM: To assess the effect of early TIPSS on patient prognosis. MATERIALS AND METHODS: We carried out a meta-analysis of trials evaluating early TIPSS in cirrhotic patients with AVB. RESULTS: Four studies were included. Early TIPSS was associated with fewer deaths [odds ratio (OR)=0.38, 95% confidence interval (CI)=0.17-0.83, P=0.02], with moderate heterogeneity between studies (P=0.15, I=44%). Early TIPSS was not significantly associated with fewer deaths among Child-Pugh B patients (OR=0.35, 95% CI=0.10-1.17, P=0.087) nor among Child-Pugh C patients (OR=0.34, 95% CI=0.10-1.11, P=0.074). There was no heterogeneity between studies in the Child-Pugh B analysis (P=0.6, I=0%), but there was a high heterogeneity in the Child-Pugh C analysis (P=0.06, I=60%). Early TIPSS was associated with lower rates of bleeding within 1 year (OR=0.08, 95% CI=0.04-0.17, P<0.001) both among Child-Pugh B patients, (OR=0.15, 95% CI=0.05-0.47, P=0.001) and among Child-Pugh C patients (OR=0.05, 95% CI=0.02-0.15, P<0.001), with no heterogeneity between studies. Early TIPSS was not associated with higher rates of encephalopathy (OR=0.84, 95% CI=0.50-1.42, P=0.5). CONCLUSION: Cirrhotic patients with AVB treated with early TIPSS had lower death rates and lower rates of clinically significant bleeding within 1 year compared with patients treated without early TIPSS. Additional studies are required to identify the potential risk factors leading to a poor prognosis after early TIPSS in patients with AVB and to determine the impact of the degree of liver failure on the patient's prognosis.

Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies.