Cancer Stem Cells Sensitivity Assay (STELLA) in Patients with Advanced Lung and Colorectal Cancer: A Feasibility Study.

Cancer stem cells represent a population of immature tumor cells found in most solid tumors. Their peculiar features make them ideal models for studying drug resistance and sensitivity. In this study, we investigated whether cancer stem cells isolation and in vitro sensitivity assay are feasible in a clinical setting. METHODS: Cancer stem cells were isolated from effusions or fresh cancer tissue of 23 patients who progressed after standard therapy failure. Specific culture conditions selected for immature tumor cells that express markers of stemness. These cells were exposed in vitro to chemotherapeutic and targeted agents. RESULTS: Cancer stem cells were extracted from liver metastases in 6 cases (25%), lung nodules in 2 (8%), lymph node metastases in 3 (12.5%) and pleural/peritoneal/pericardial effusion in 13 (54%). Cancer stem cells were successfully isolated in 15 patients (63%), including 14 with lung cancer (93.3%). A sensitivity assay was successfully performed in 7 patients (30.4%), with a median of 15 drugs/combinations tested (range 5-28) and a median time required for results of 51 days (range 37-95). CONCLUSION: The approach used for the STELLA trial allowed isolation of cancer stem cells in a consistent proportion of patients. The low percentage of cases completing the full procedure and the long median time for obtaining results highlights the need for a more efficient procedure. TRIAL REGISTRATION: ClinalTrials.gov NCT01483001

The Gray Needle: Large Grains in the HD 15115 Debris Disk from LBT/PISCES/Ks and LBTI/LMIRcam/L' Adaptive Optics Imaging

We present diffraction-limited \ks band and \lprime adaptive optics images of the edge-on debris disk around the nearby F2 star HD 15115, obtained with a single 8.4 m primary mirror at the Large Binocular Telescope. At \ks band the disk is detected at signal-to-noise per resolution element (SNRE) \about 3-8 from \about 1-2\fasec 5 (45-113 AU) on the western side, and from \about 1.2-2\fasec 1 (63-90 AU) on the east. At \lprime the disk is detected at SNRE \about 2.5 from \about 1-1\fasec 45 (45-90 AU) on both sides, implying more symmetric disk structure at 3.8 \microns . At both wavelengths the disk has a bow-like shape and is offset from the star to the north by a few AU. A surface brightness asymmetry exists between the two sides of the disk at \ks band, but not at \lprime . The surface brightness at \ks band declines inside 1\asec (\about 45 AU), which may be indicative of a gap in the disk near 1\asec. The \ks - \lprime disk color, after removal of the stellar color, is mostly grey for both sides of the disk. This suggests that scattered light is coming from large dust grains, with 3-10 \microns -sized grains on the east side and 1-10 \microns dust grains on the west. This may suggest that the west side is composed of smaller dust grains than the east side, which would support the interpretation that the disk is being dynamically affected by interactions with the local interstellar medium.Comment: Apj-accepted March 27 2012; minor correction

Mechanical Ventricular Assistance as Destination Therapy for End-Stage Heart Failure: Has it Become a First Line Therapy?

Patients with end-stage heart failure have poor quality of life and prognosis.Therapeutic options are scarce and not available for all:only few patients can be transplanted and several medical and surgical strategies have shown limited ability to influence prognosis and quality of life. In the past years, technological progress has realized devices capable of providing appropriate hemodynamic stabilization and recovery of secondary organ failure.In the recent years,these devices are assessed and discussed as definitive treatment for patients who do not qualify for transplantation or/and instead to transplantation (destination therapy).This indication is increasingly considered following the results of newest clinical study reporting long-term survival without device correlated adverse events using last generation devices, and acceptable quality of life.The current knowledge about Destination Therapy and some original data from the DAVID Study (an Italian multicenter prospective study designed to evaluate the patient’s survival rate and quality of life of patients implanted with these new devices as long-term support or destination therapy) are summarized

Deep sternal infections after in situ bilateral internal thoracic artery grafting for left ventricular myocardial revascularization: predictors and influence on 20-year outcomes

Background: The incidence and potential factors influencing deep sternal wound infection (DSWI) in a cohort of patients undergoing coronary artery bypass grafting (CABG) using skeletonized bilateral internal thoracic artery (BITA) was explored. Furthermore, we studied influence of DSWI on long-term survival, major adverse cardiac events (MACEs) and repeat coronary revascularization (RCR).Methods: The study cohort consisted of 1,325 consecutive patients who were divided in two groups: patients experiencing DSWI (n=33, group 1) and those who did not have sternal infection (n=1,292, group 2). A logistic regression model was employed to find predictors of DSWI whereas Cox regression and a competing risk models were carried out to test predictors of late death, MACE and RCR, respectively. Follow up was 100% complete and ranged from 1 to 245 months. Median follow-up was 103 months (IQR, 61 to 189 months). Cumulative follow-up was 16,430 patient years.Results: The incidence of DSWI was 2.4%. Multivariable logistic regression analysis found any single independent predictor of DSWI. However, the association of peripheral vascular disease (PVD) and diabetes increased the risk by 1.4 and 1.6 times. When DM was associated with obesity the risk increased by 2.1 and 2.6 times compared to the single factors, respectively. Obese female patients were at a 1.6-fold higher risk when compared to the association of DM with obesity. DSWI was not an independent predictor of long-term survival (HR, 2.31; 95% CI: 0.59–9.12), RCR (SHR, 2.89; 95% CI: 0.65–10.12), or MACE (SHR, 1.98; 95% CI: 0.44–8.56).Conclusions: With an accurate patient selection (i.e., exclusion of obese diabetic females) and strict DM control BITA represents a first choice for most of CABG patients, even at high risk for DSWI. The occurrence of DSWI does not influence long-term survival and late outcomes. Our findings should be confirmed by further larger research.</br

Measurement of the t-channel single top quark production cross section in pp collisions at √s =7 TeV

Peer reviewe

Impacts of the Tropical Pacific/Indian Oceans on the Seasonal Cycle of the West African Monsoon

The current consensus is that drought has developed in the Sahel during the second half of the twentieth century as a result of remote effects of oceanic anomalies amplified by local land–atmosphere interactions. This paper focuses on the impacts of oceanic anomalies upon West African climate and specifically aims to identify those from SST anomalies in the Pacific/Indian Oceans during spring and summer seasons, when they were significant. Idealized sensitivity experiments are performed with four atmospheric general circulation models (AGCMs). The prescribed SST patterns used in the AGCMs are based on the leading mode of covariability between SST anomalies over the Pacific/Indian Oceans and summer rainfall over West Africa. The results show that such oceanic anomalies in the Pacific/Indian Ocean lead to a northward shift of an anomalous dry belt from the Gulf of Guinea to the Sahel as the season advances. In the Sahel, the magnitude of rainfall anomalies is comparable to that obtained by other authors using SST anomalies confined to the proximity of the Atlantic Ocean. The mechanism connecting the Pacific/Indian SST anomalies with West African rainfall has a strong seasonal cycle. In spring (May and June), anomalous subsidence develops over both the Maritime Continent and the equatorial Atlantic in response to the enhanced equatorial heating. Precipitation increases over continental West Africa in association with stronger zonal convergence of moisture. In addition, precipitation decreases over the Gulf of Guinea. During the monsoon peak (July and August), the SST anomalies move westward over the equatorial Pacific and the two regions where subsidence occurred earlier in the seasons merge over West Africa. The monsoon weakens and rainfall decreases over the Sahel, especially in August.Peer reviewe

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia