Cerebral cortical microinfarcts in patients with internal carotid artery occlusion

Cerebral cortical microinfarcts (CMI) are small ischemic lesions that are associated with cognitive impairment and probably have multiple etiologies. Cerebral hypoperfusion has been proposed as a causal factor. We studied CMI in patients with internal carotid artery (ICA) occlusion, as a model for cerebral hemodynamic compromise. We included 95 patients with a complete ICA occlusion (age 66.2 +/- 8.3, 22% female) and 125 reference participants (age 65.5 +/- 7.4, 47% female). Participants underwent clinical, neuropsychological, and 3 T brain MRI assessment. CMI were more common in patients with an ICA occlusion (54%, median 2, range 1-33) than in the reference group (6%, median 0; range 1-7; OR 14.3; 95% CI 6.2-33.1; p<.001). CMI were more common ipsilateral to the occlusion than in the contralateral hemisphere (median 2 and 0 respectively; p<.001). In patients with CMI compared to patients without CMI, the number of additional occluded or stenosed cervical arteries was higher (p=.038), and cerebral blood flow was lower (B -6.2 ml/min/100 ml; 95% CI -12.0:-0.41; p=.036). In conclusion, CMI are common in patients with an ICA occlusion, particularly in the hemisphere of the occluded ICA. CMI burden was related to the severity of cervical arterial compromise, supporting a role of hemodynamics in CMI etiology.Cardiovascular Aspects of RadiologyNeuro Imaging Researc

Pathological complete response after neoadjuvant chemotherapy is an independent predictive factor irrespective of simplified breast cancer intrinsic subtypes: a landmark and two-step approach analyses from the EORTC 10994/BIG 1-00 phase III trial.

BACKGROUND: Pathological complete response (pCR) following chemotherapy is strongly associated with both breast cancer subtype and long-term survival. Within a phase III neoadjuvant chemotherapy trial, we sought to determine whether the prognostic implications of pCR, TP53 status and treatment arm (taxane versus non-taxane) differed between intrinsic subtypes. PATIENTS AND METHODS: Patients were randomized to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel then three cycles of eprirubicin/docetaxel (T-ET). pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in primary tumour and lymph nodes. We used a simplified intrinsic subtypes classification, as suggested by the 2011 St Gallen consensus. Interactions between pCR, TP53 status, treatment arm and intrinsic subtype on event-free survival (EFS), distant metastasis-free survival (DMFS) and overall survival (OS) were studied using a landmark and a two-step approach multivariate analyses. RESULTS: Sufficient data for pCR analyses were available in 1212 (65%) of 1856 patients randomized. pCR occurred in 222 of 1212 (18%) patients: 37 of 496 (7.5%) luminal A, 22 of 147 (15%) luminal B/HER2 negative, 51 of 230 (22%) luminal B/HER2 positive, 43 of 118 (36%) HER2 positive/non-luminal, 69 of 221(31%) triple negative (TN). The prognostic effect of pCR on EFS did not differ between subtypes and was an independent predictor for better EFS [hazard ratio (HR) = 0.40, P &lt; 0.001 in favour of pCR], DMFS (HR = 0.32, P &lt; 0.001) and OS (HR = 0.32, P &lt; 0.001). Chemotherapy arm was an independent predictor only for EFS (HR = 0.73, P = 0.004 in favour of T-ET). The interaction between TP53, intrinsic subtypes and survival outcomes only approached statistical significance for EFS (P = 0.1). CONCLUSIONS: pCR is an independent predictor of favourable clinical outcomes in all molecular subtypes in a two-step multivariate analysis. CLINICALTRIALSGOV: EORTC 10994/BIG 1-00 Trial registration number NCT00017095

Dayside induced magnetic field of the ionosphere of Mars

International audienceThe Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) onboard the Mars Express spacecraft has occasionally displayed surprising features. One such feature is the occurrence of a series of broadband, low-frequency echoes at equally spaced delay times after the sounder transmitter pulse. The interval between the echoes has been shown to be at the cyclotron period of electrons orbiting in the local magnetic field. The electrons are believed to be accelerated by the large voltages applied to the antenna by the sounder transmitter. Measurements of the period of these “electron cyclotron echoes” provide a simple technique for determining the magnitude of the magnetic field near the spacecraft. These measurements are particularly useful because Mars Express carries no magnetometer, so this is the only method available for measuring the magnetic field magnitude. Using this technique, results are presented showing the large scale structure of the draped field inside the magnetic pile-up boundary. The magnitude of the draped field is shown to vary from about 40 nT at a solar zenith angle of about 25°, to about 25 nT at a solar zenith angle of 90°. The results compare favorably with similar results from the Mars Global Surveyor spacecraft. A fitting technique is developed to derive the vector direction and magnitude of the draped magnetic field in cases where the spacecraft passes through regions with significant variation in the crustal field. The magnetic field directions are consistent with current knowledge of the draping geometry of the magnetic field around Mars

LAPATAX: A randomized phase II trial of FEC-docetaxel combined with lapatinib and/or trastuzumab as neoadjuvant therapy of HER2- positive breast cancer-EORTC 10054 trial.

Background: Patients with HER2 +ve breast cancer suitable for neoadjuvant chemotherapy (NAC) have been shown in a series of clinical trials to have the best outcome when treated with anthracyclines (A), taxanes (T), and trastuzumab (Tz). Recent evidence confirms that adjuvant Tz is more effective when given concomitantly rather than sequentially with T (Perez SABCS 2009). Whilst there remains uncertainty as to the most efficacious A-T regimen and duration of Tz, there is widespread use in Europe of FEC-D [3 cycles of 5-FU 500 mg/m2, epirubicin 100 mg/m2 and cyclophosphamide 500 mg/m2 (FEC100) followed by 3 cycles of docetaxel 100 mg/m2 (D) q3w] following the results of PACS-01. The advent of TKI anti-HER2 agents such as L could offer superior outcomes if combined with NAC. However, a phase I study in heavily pre-treated advanced breast cancer reported difficulties in combining lapatinib (L) with D 100 mg/m2 (LoRusso JCO 2008). Methods: EORTC 10054 is designed as a two-part study to compare FEC-D with either Tz, L or their combination as NAC for patients with HER2 +ve large operable or locally advanced breast cancer. Before and on-treatment frozen tumor and blood samples will be taken to better define which tumours are particularly sensitive to either Tz and/or L. Stage 1: (complete) a dose- finding study has confirmed that with primary prophylactic G-CSF, D 100 mg/m2 can be safely and effectively given with L 1,250 mg daily continuously. The dose-limiting toxicity was myelosuppression, and there was no significant diarrhoea or cardiac toxicity (ESMO 2009 abstr P- 5073). Stage 2: (opening Q1 2010) will enroll 150 patients from European centres into a 3-arm randomized trial whose primary endpoint is pathological complete response. All patients will receive FEC-D before primary surgery: 3 cycles of FEC (without anti-HER2 therapy) followed by 3 cycles of D plus either Tz (conventional weekly schedule), monotherapy L, or the combination of Tz and L, using doses based on the EGF100161 dose-finding study in 1st line metastatic therapy of D+L+Tz. After surgery all patients will receive standard 3-weekly Tz, radiotherapy and endocrine therapy as per local guidelines

Utility and appropriateness of the fatty liver inhibition of progression (FLIP) algorithm and steatosis, activity, and fibrosis (SAF) score in the evaluation of biopsies of nonalcoholic fatty liver disease

Biopsy is still the gold standard for the diagnosis of nonalcoholic steatohepatitis but the definition may vary among pathologists, a drawback especially in evaluation of biopsies for clinical trials. We previously developed a scoring system (steatosis, activity, fibrosis [SAF]) allowing the use of an algorithm (fatty liver inhibition of progression [FLIP]) for the classification of liver injury in morbid obesity. The aim of this study was to determine whether the use of the SAF score and FLIP algorithm can decrease interobserver variations among pathologists. In a first session, pathologists categorized 40 liver biopsies of patients with nonalcoholic fatty liver disease (NAFLD) according to their own experience. In a second reading session, each pathologist reclassified the same slides by using the FLIP algorithm and SAF score, blinded to their first evaluation. The experiment was repeated with two different groups of pathologists at varying levels of training in liver pathology. The percentage of biopsy interpretation concordant with reference evaluation increased from 77% to 97% in Group 1 and from 42% to 75% in Group 2 after the use of the SAF score and FLIP algorithm. The strength of concordance in classification increased in Group 1 from moderate (κ=0.54) to substantial (κ=0.66) and from fair (κ=0.35) to substantial (κ=0.61) in Group 2 with application of the algorithm. With regard to the SAF score, concordance was substantial in Group 1 for steatosis (κ=0.61), activity (κ=0.75), and almost perfect for fibrosis (κ=0.83 after pooling 1a, 1b, and 1c together into a single score F1). Similar trends were observed in Group 2 (κ=0.54 for S, κ=0.68 for A, and κ=0.72 for F). Conclusion: The FLIP algorithm based on the SAF score should decrease interobserver variations among pathologists and are likely to be implemented in pathology practice. (Hepatology 2014;60:565-575) © 2014 by the American Association for the Study of Liver Diseases

Hypothermia following Pediatric Traumatic Brain Injury

Preclinical as well as clinical studies in traumatic brain injury (TBI) have established the likely association of secondary injury and outcome in adults in children following severe injury. Similarly, there is growing evidence in experimental laboratory studies that moderate hypothermia has a beneficial effect on outcome, though the exact mechanisms remain to be absolutely defined. The Pediatric TBI Guidelines provided the knowledge and background for standard management of children following severe TBI and highlighted that there are very few clinical studies to date. In particular with respect to temperature regulation and the use of hypothermia, initial findings of case series of small numbers were promising. Further preliminary randomized clinical trials, both single institution and multicenter, have provided the initial data on safety and efficacy, though larger, Phase III studies are necessary to ensure both the safety and efficacy of hypothermia in pediatric TBI prior to implementation as part of the standard of care. It is expected that hypothermia initiated early after severe TBI will have a protective effect on the pediatric brain and can be done safely, but this still remains to be definitively tested