Crizotinib in c-MET- or ROS1-positive NSCLC: results of the AcSé phase II trial.

BACKGROUND: In 2013, the French National Cancer Institute initiated the AcSé program to provide patients with secure access to targeted therapies outside of their marketed approvals. Efficacy and safety was then assessed using a two-stage Simon phase II trial design. When the study design was designed, crizotinib was approved only as monotherapy for adults with anaplastic lymphoma kinase plus non-small-cell lung cancers (NSCLC). PATIENTS AND METHODS: Advanced NSCLC patients with c-MET ≥6 copies, c-MET-mutated, or ROS-1-translocated tumours were enrolled in one of the three cohorts. Patients were treated with crizotinib 250 mg twice daily. Efficacy was assessed using the objective response rate (ORR) after two cycles of crizotinib as primary outcome. Secondary outcomes included disease control rate at four cycles, best ORR, progression-free survival, overall survival, and drug tolerance. RESULTS: From August 2013 to March 2018, 5606 patients had their tumour tested for crizotinib targeted molecular alterations: 252 patients had c-MET ≥6 copies, 74 c-MET-mutation, and 78 ROS-1-translocated tumour. Finally, 25 patients in the c-MET ≥6 copies cohort, 28 in the c-MET-mutation cohort, and 37 in the ROS-1-translocation cohort were treated in the phase II trial. The ORR was 16% in the c-MET ≥6 copies cohort, 10.7% in the mutated, and 47.2% in the ROS-1 cohort. The best ORR during treatment was 32% in the c-MET-≥6 copies cohort, 36% in the c-MET-mutated, and 69.4% in the ROS-1-translocation cohort. Safety data were consistent with that previously reported. CONCLUSIONS: Crizotinib activity in patients with ROS1-translocated tumours was confirmed. In the c-MET-mutation and c-MET ≥6 copies cohorts, despite insufficient ORR after two cycles of crizotinib, there are signs of late response not sufficient to justify the development of crizotinib in this indication. The continued targeting of c-MET with innovative therapies appears justified. CLINICAL TRIAL NUMBER: NCT02034981.

Review: Associations among goods, impacts and ecosystem services provided by livestock farming.

Livestock is a major driver in most rural landscapes and economics, but it also polarises debate over its environmental impacts, animal welfare and human health. Conversely, the various services that livestock farming systems provide to society are often overlooked and have rarely been quantified. The aim of analysing bundles of services is to chart the coexistence and interactions between the various services and impacts provided by livestock farming, and to identify sets of ecosystem services (ES) that appear together repeatedly across sites and through time. We review three types of approaches that analyse associations among impacts and services from local to global scales: (i) detecting ES associations at system or landscape scale, (ii) identifying and mapping bundles of ES and impacts and (iii) exploring potential drivers using prospective scenarios. At a local scale, farming practices interact with landscape heterogeneity in a multi-scale process to shape grassland biodiversity and ES. Production and various ES provided by grasslands to farmers, such as soil fertility, biological regulations and erosion control, benefit to some extent from the functional diversity of grassland species, and length of pasture phase in the crop rotation. Mapping ES from the landscape up to the EU-wide scale reveals a frequent trade-off between livestock production on one side and regulating and cultural services on the other. Maps allow the identification of target areas with higher ecological value or greater sensitivity to risks. Using two key factors (livestock density and the proportion of permanent grassland within utilised agricultural area), we identified six types of European livestock production areas characterised by contrasted bundles of services and impacts. Livestock management also appeared to be a key driver of bundles of services in prospective scenarios. These scenarios simulate a breakaway from current production, legislation (e.g. the use of food waste to fatten pigs) and consumption trends (e.g. halving animal protein consumption across Europe). Overall, strategies that combine a reduction of inputs, of the use of crops from arable land to feed livestock, of food waste and of meat consumption deliver a more sustainable food future. Livestock as part of this sustainable future requires further enhancement, quantification and communication of the services provided by livestock farming to society, which calls for the following: (i) a better targeting of public support, (ii) more precise quantification of bundles of services and (iii) better information to consumers and assessment of their willingness to pay for these services.

Modelling interacting plant and livestock renewal dynamics helps disentangle equilibrium and nonequilibrium aspects in a Mongolian pastoral system.

The interplay of livestock density dependence drivers and climate hazards is thought to cause pasture deterioration and poverty in Mongolian pastoral systems. We assessed their relative weights in a system of the Gobi exposed to high rainfall variability and harsh winters, which suggests that climate is the main system's driver. In this aim we modelled how interacting plant and livestock renewal dynamics impact herder performances, under the influence of climate. Plant dynamics was studied through an underground biomass sub-model because local pastures are dominated by perennial species. This approach enabled us studying pastoral issues in a holistic way, by integrating plant underground organs, livestock populations, herder income, and climate drivers. Models described that current grazing practices can significantly reduce underground biomass (-30% after 20years), but not entirely deplete it. They also showed that competition between herders could trap the smallest ones in poverty, by preventing the growth of their herds. This competition operates through density dependent factors affecting livestock productivity and vulnerability to climate shocks. This competition effect is all the more important since small herders could grow their herd and escape poverty if they were alone in the system. This result shows that density dependent factors could significantly impact herder performances and suggests that forage resource allocation is a driver as powerful as climate, even in the local harsh bioclimatic configuration of the Mongolian Gobi.

[Double J stent removal's cost estimate using a re-sterilizable fibroscope in a French private structure]. / Évaluation du coût en structure privée d'une ablation de sonde double J en externe à l'aide d'un fibroscope re-stérilisable.

In front of the arrival of new devices intended to simplify the removal of double J stent, it poses the problem of the knowledge of the real cost of such an ablation under the current conditions of realization. MATERIAL AND METHOD: This is a monocentric economic evaluation of cost and remuneration needed data-gathering of quotation (CCAM, GHS/SE, …), estimate of the associated costs of wear and damping of the endoscopic equipments (endoscopes, cables, …), estimate of the cost of sterilization, estimate of the associated costs to the intervention of staff (Auxiliary nurse [AS] and Nurse [IDE]) with timing of the various tasks. RESULTS: Quotation CCAM JCGE004 (48€) gives access to fixed price SE1 (73.71€ for private clinic, and 75.89€ for public institution) without hospitalization nor anaesthesia. The costs were reported to an act of single double J removal. Concerning the equipments: 4.42€HT for the fibroscopes, graspers, cable and light. The costs of sterilization were: 17.95€HT. The timed workforce's costs were: 7.61-9.51€ for AS and 9.92-10.84€ for IDE. The cost of consumable was about 1.37 €HT, by excluding the common base from the extractions (1.876€HT). The total costs in France in 2016 were thus about 47.4 to 50.496€ including all taxes. CONCLUSIONS: This estimate will be used certainly for reflection on the investments and the future studies of the economic impact of the new devices of extraction, by correlating it of course with the various maintenance contracts from each institution. LEVEL OF PROOF: 4.

Adjuvant chemotherapy in pT1ab node-negative triple-negative breast carcinomas: Results of a national multi-institutional retrospective study.

BACKGROUND: Triple-negative breast cancers (TNBCs) are considered as associated with poor outcome, but prognosis of subcentimetric, node-negative disease remains controversial and evidence that adjuvant chemotherapy (CT) is effective in these small tumours remains limited. PATIENTS AND METHODS: Our objective was to investigate the impact of CT on survival in pT1abN0M0 TNBC. Patients were retrospectively identified from a cohort of 22,475 patients who underwent primary surgery in 15 French centres between 1987 and 2013. As rare pathological types may display very particular prognoses in these tumours, we retained only the invasive ductal carcinomas of no special type according to the last World Health Organisation (WHO) classification which is the most common TNBC histological type. End-points were disease-free survival (DFS) and metastasis-free survival (MFS). A propensity score for receiving CT was estimated using a logistic regression including age, tumour size, Scarff Bloom and Richardson (SBR) grade and lymphovascular invasion. RESULTS: Of a total of 284 patients with pT1abN0M0 ductal TNBC, 144 (51%) received CT and 140 (49%) did not. Patients receiving CT had more adverse prognostic features, such as tumour size, high grade, young age, and lymphovascular invasion. CT was not associated with a significant benefit for DFS (Hazard ratio, HR = 0.77 [0.40-1.46]; p = 0.419, log-rank test) or MFS (HR = 1.00 [0.46-2.19]; p = 0.997), with 5-year DFS and MFS in the group with CT versus without of 90% [81-94%] versus 84% [74-90%], and 90% [81-95%] versus 90% [83%-95%], respectively. Results were consistent in all supportive analyses including multivariate Cox model and the use of the propensity score for adjustment and as a matching factor for case-control analyses. CONCLUSIONS: This study did not identify a significant DFS or MFS advantage for CT in subcentimetric, node-negative ductal TNBC. Although current consensus guidelines recommend consideration of CT in all TNBC larger than 5 mm, clinicians should carefully discuss benefit/risk ratio with patients, given the unproven benefits.

Axillary lymph node micrometastases decrease triple-negative early breast cancer survival.

BACKGROUND: Triple-negative breast cancers (TNBCs) are the most deadly form of breast cancer (BC) subtypes. Axillary lymph node involvement (ALNI) has been described to be prognostic in BC taken as a whole, but its prognostic value in each subtype is unclear. We explored the prognostic impact of ALNI and especially of small size axillary metastases in early TNBCs. METHODS: We analysed in this multicentre study all patients treated for early TNBC in 12 French cancer centres. We explored the correlation between clinicopathological data and ALNI, with a specific focus on the dichotomisation between macrometastases and occult metastases, which is defined as the presence of isolated tumour cells or micrometastases. The prognostic value of ALNI both in terms of disease-free survival (DFS) and overall survival (OS) was also explored. RESULTS: We included 1237 TNBC patients. Five-year DFS and OS were 83.7% and 88.5%, respectively. The identified independent prognostic features for DFS were tumour size >20 mm (hazard ratio (HR)=1.86; 95% CI: 1.11-3.10, P=0.018), lymphovascular invasion (HR=1.69; 95% CI: 1.21-2.34, P=0.002) and ALNI both in case of macrometastases (HR=1.97; 95% CI: 1.38-2.81, P<0.0001) and occult metastases (HR=1.72; 95% CI: 1.1-2.71, P=0.019). DFS and OS were similar between tumours with occult metastases and macrometastases. Tumours presenting at least two pejorative features (out of ALNI, lymphovascular invasion and large tumour size) displayed a significantly poorer DFS in both the training set and validation set, independently of chemotherapy administration. Tumours with no more than one of the above-cited pejorative features had a 5-year OS of ⩾90% vs 70% for other cases (P<0.0001). CONCLUSIONS: Axillary lymph node involvement is a key prognostic feature for early TNBC when isolated tumour cells were identified in lymph nodes. This impact is independent of chemotherapy use.

Highly favorable outcome in BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study.

BACKGROUND: Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations. METHODS: Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis. RESULTS: After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS. CONCLUSIONS: Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.

Trade-offs between pasture production and farmland bird conservation: exploration of options using a dynamic farm model.

In European grassland landscapes, grazing and mowing play a key role for the maintenance of high-quality habitats that host important bird populations. As grasslands are also key resources for cattle feeding, there is a need to develop management strategies that achieve the double objective of production and biodiversity conservation. The objective of this study was to use a modelling approach to generate recognisable patterns of bird dynamics in farms composed of different land use proportions, and to compare their production and ecological dimensions. We developed a dynamic model, which linked grassland management to bird population dynamics at the field and farm levels. The model was parameterised for two types of suckling farms corresponding to contrasting levels of grassland intensification and for two bird species of high conservation value. A viability algorithm was used to define and assess viable management strategies for production and ecological performance so as to draw the shape of the relationship between both types of performances for the two types of farms. Our results indicated that, at the farm level, there was a farming system effect with a negative and non-linear relationship linking performance. Improving bird population maintenance was less costly in extensive farms compared with intensive farms. At the field level, the model predicted the timing and intensity of land use, maximising either production or ecological performance. The results suggested that multi-objective grassland management would benefit from public policies that consider levels of organisation higher than the field level, such as the farm or the landscape.

Robustness and management adaptability in tropical rangelands: a viability-based assessment under the non-equilibrium paradigm.

Rangelands provide the main forage resource for livestock in many parts of the world, but maintaining long-term productivity and providing sufficient income for the rancher remains a challenge. One key issue is to maintain the rangeland in conditions where the rancher has the greatest possibility to adapt his/her management choices to a highly fluctuating and uncertain environment. In this study, we address management robustness and adaptability, which increase the resilience of a rangeland. After reviewing how the concept of resilience evolved in parallel to modelling views on rangelands, we present a dynamic model of rangelands to which we applied the mathematical framework of viability theory to quantify the management adaptability of the system in a stochastic environment. This quantification is based on an index that combines the robustness of the system to rainfall variability and the ability of the rancher to adjust his/her management through time. We evaluated the adaptability for four possible scenarios combining two rainfall regimes (high or low) with two herding strategies (grazers only or mixed herd). Results show that pure grazing is viable only for high-rainfall regimes, and that the use of mixed-feeder herds increases the adaptability of the management. The management is the most adaptive with mixed herds and in rangelands composed of an intermediate density of trees and grasses. In such situations, grass provides high quantities of biomass and woody plants ensure robustness to droughts. Beyond the implications for management, our results illustrate the relevance of viability theory for addressing the issue of robustness and adaptability in non-equilibrium environments.

Could thyroid dysfunction influence outcome in sunitinib-treated metastatic renal cell carcinoma?

BACKGROUND: Sunitinib is a standard of care for metastatic renal cell carcinoma (mRCC). Hypothyroidism is frequently observed under sunitinib therapy. This study was conducted to prospectively determine the correlation between thyroid function and progression-free survival (PFS) in this population. PATIENTS AND METHODS: One hundred and eleven mRCC patients treated with sunitinib were evaluated for serum thyroid-stimulating hormone (TSH) and T4 levels before treatment and every 6 weeks during treatment. Survival was analysed according to a landmark method with a cut-off of 6 months, excluding early progressive or early-censored patients. RESULTS: Out of the 102 patients with normal baseline thyroid function, 53% developed thyroid dysfunction, including 95% hypothyroidisms out of which 90.9% received L-thyroxine replacement. Median time to TSH alteration was 5.4 months. Median PFS was 11.7 months for the entire population. Median PFS was not different between the groups with abnormal or normal thyroid function after 6 months of treatment (18.9 and 15.9 months, respectively, log-rank P = 0.94, hazard ratio = 1.02, 95% confidence interval = 0.54-1.93). There was no difference even after adjustment for Memorial Sloan-Kettering Cancer Centre classification and therapy line. CONCLUSIONS: Abnormal thyroid function with hormonal substitution did not increase survival in our population, independent of initial prognosis and previous treatments. Larger comparative studies are deserved to validate these conclusions.

A seven-gene prognostic model for platinum-treated ovarian carcinomas.

BACKGROUND: Prognosis of ovarian carcinoma is poor, heterogeneous, and not accurately predicted by histoclinical features. We analysed gene expression profiles of ovarian carcinomas to identify a multigene expression model associated with survival after platinum-based therapy. METHODS: Data from 401 ovarian carcinoma samples were analysed. The learning set included 35 cases profiled using whole-genome DNA chips. The validation set included 366 cases from five independent public data sets. RESULTS: Whole-genome unsupervised analysis could not distinguish poor from good prognosis samples. By supervised analysis, we built a seven-gene optimal prognostic model (OPM) out of 94 genes identified as associated with progression-free survival. Using the OPM, we could classify patients in two groups with different overall survival (OS) not only in the learning set, but also in the validation set. Five-year OS was 57 and 27% for the predicted 'Favourable' and 'Unfavourable' classes, respectively. In multivariate analysis, the OPM outperformed the individual current prognostic factors, both in the learning and the validation sets, and added independent prognostic information. CONCLUSION: We defined a seven-gene model associated with outcome in 401 ovarian carcinomas. Prospective studies are warranted to confirm its prognostic value, and explore its potential ability for better tailoring systemic therapies in advanced-stage tumours.

Are we turning to more than a first line treatment of metastatic colorectal cancer with high dose irinotecan?: A monocentric institution safety analysis of 46 patients.

PURPOSE: Irinotecan (CPT11) at 180 mg/m(2) with LV5FU2 for metastatic colorectal cancer (MCRC) has response rates (RRs) of 56 and 4% as first- and second-line treatments, respectively [1-2], and higher doses of CPT11 result in higher RRs. The present cohort analysis aimed to evaluate the effect of increasing doses of this combination treatment in clinical practice. METHODS: Chemo-naive and pretreated patients with MCRC received CPT11 and LV5FU2 (5FU 48-h CI 2400 mg/m(2), D1 bolus leucovorin 200 mg/m(2)), followed by 5FU 400 mg/m(2) (cycles d1-d15). CPT11 dose was increased by 20 mg/m(2) at each cycle, from 180 mg/m(2) up to 260 mg/m(2), unless grade 3 toxicities other than alopecia arose. RESULTS: Between March 2002 and September 2005, 46 patients were recruited (median age: 62.3 years). A total of 512 cycles of chemotherapy were administered (median: 9 cycles/patient; range: 3-41). Median follow-up was 16.2 months. Altogether, 27 patients had received prior chemotherapy: 24 with an oxaliplatin-based regimen; seven with CPT11; and five with LV5FU2 or oral 5FU. Doses of 260 mg/m(2) were used in 17 patients, 240 mg/m(2) in seven, 220 mg/m(2) in six and 200 mg/m(2) in five, while 11 remained at 180 mg/m(2); 121 cycles used 260 mg/m(2) (24%), with 76 cycles at 240 mg/m(2) (14%), 78 cycles at 220 mg/m(2) and 58 cycles at 200mg/m(2). The objective response (OR) was 40%, with stable disease (SD) in 45% and disease progression (DP) in 11%. In the first-line therapy group, partial/complete responses were 55%, with SD in 30% and DP in 15%. In pretreated patients, OR was 30.5%, SD was 58.5% and DP was 11%. Nine patients (20%) had a therapeutic break (median: 5.1 months; range: 3-10). Overall median survival was 17 months, with 16.5 months in pretreated patients and 19.6 months in the first-line group. Toxicity grades 3-4 and overall incidence per cycle were: neutropenia, 3-22%; diarrhea, 4-22%; vomiting, 2-20%; alopecia, 20-26%; anemia, 0.2-2%; thrombocytopenia, 0-0%; and mucositis, 0.4-2.2%. CONCLUSION: The toxicity of high-dose CPT11+LV5FU2 chemotherapy was well tolerated when the dose was progressively increased according to individual tolerability, with 37% of patients receiving CPT11 at 260 mg/m(2). Progression-free survival (PFS) increased with higher doses of CPT11. In the chemo-naive and pretreated subgroups, the median PFS was 10.9 and 8.8 months, respectively (P=0.698, NS). Optimization of CPT11 doses in pretreated patients appears to pave the way for new treatment options.

[DNA microarrays and prediction of clinical outcome in ovarian carcinoma patients]. / Puces à ADN et prédiction de l'évolution clinique des cancers ovariens.

Despite debulking surgery and taxane/platinum-based chemotherapy, ovarian cancer is the most lethal pelvic gynaecological cancer in western countries, with a 25% 5-years survival. Current histo-clinical prognostic factors are insufficient to capture the heterogeneous clinical outcome of patients. A better molecular characterization of the disease is crucial to refine the prognostic classifications and to identify new therapeutic targets. DNA microarrays, which allow the quantitative measurement of expression level of the whole genome simultaneously in a single tumor sample, have been recently used towards this objective with promising results. Here, we present and discuss the main published studies and the issues to address in the future to allow the expected transfer to clinical practice.

Did the introduction of maize into Europe provide enemy-free space to Ostrinia nubilalis? Parasitism differences between two sibling species of the genus Ostrinia.

We examined whether maize offers enemy-free space (EFS) to its pest Ostrinia nubilalis, and may thereby have contributed to its divergence from the sibling species, Ostrinia scapulalis, feeding mainly on mugwort, when introduced into Europe five centuries ago. We collected Ostrinia larvae on maize (70 populations, 8425 individuals) and mugwort (10 populations, 1184 individuals) and recorded parasitism using both traditional (counting emerging parasitoids) and molecular methods (detection by specific polymerase chain reaction). The main parasitoid was Macrocentrus cingulum (Braconidae). On mugwort, parasitism was twice that on maize, and parasitoid-related mortality was 8 times higher. This suggests that maize affords substantial EFS to Ostrinia feeding on it. The lower Mortality:Infestation ratio in maize suggests that O. nubilalis' immune response might be stronger than that of O. scapulalis. If so, adapting to maize and diverging from O. scapulalis would decrease the impact of parasitism on O. nubilalis at both ecological and evolutionary levels.

Neuroanatomical localisation and clinical correlates of white matter lesions in the elderly.

BACKGROUND: White matter lesions (WML) in elderly people co-occur with hypertension, depression, and cognitive impairment. Little is known about the density and distribution of WML in normal elderly people, whether they occur randomly in the aging brain or tend to cluster in certain areas, or whether patterns of WML aggregation are linked to clinical symptoms. OBJECTIVES: To describe patterns of WML distribution in a large representative population of elderly people using non-inferential cluster analysis; and to determine the extent to which such patterns are associated with clinical symptomatology. METHOD: A population sample of 1077 elderly people was recruited. Multiple analysis of correspondence followed by automatic classification methods was used to explore overall patterns of WML distribution. Correspondence was then sought between these patterns and a range of cerebrovascular, psychiatric, and neurological symptoms. RESULTS: Three distinct patterns of spatial localisation within the brain were observed, corresponding to distinct clusters of clinical symptoms. In particular WML aggregation in temporal and occipital areas was associated with greater age, hypertension, late onset depressive disorder, poor global cognitive function, and overall WML frequency. CONCLUSIONS: WML localisation is not random in the aging brain, and their distribution is associated with age and the presence of clinical symptoms. Age differences suggest there may be patterns of progression across time; however, this requires confirmation from longitudinal imaging studies.

Large intracoronary thrombi with good TIMI flow during acute myocardial infarction: four cases of successful aggressive medical management in patients without angiographically detectable coronary atherosclerosis.

Four cases of young patients with acute myocardial infarction are discussed in which urgent angiography showed large intracoronary thrombus and TIMI (thrombolysis in myocardial infarction) flow > or = 2 in the infarct related artery. The rest of the coronary tree appeared to be free of detectable atherosclerosis. Percutaneous transluminal coronary angioplasty was not performed and an aggressive antiplatelet/anticoagulant treatment was administered (acetylsalicylic acid, clopidogrel, abciximab, and heparin). In all cases early angiographic control (1-12 days after AMI) showed disappearance of thrombus, no significant residual stenosis, and normal flow. No deterioration of left ventricular function was observed and the clinical course both in hospital and at five months' follow up was uneventful.

A method of age estimation using Raman microspectrometry imaging of the human dentin.

The aim of this work is to establish a correlation between ageing and Raman spectra imaging of human teeth. Raman spectrum of an analysed sample is characteristic of its chemical components. By exploring the different dentinal areas on each tooth, we sought to find a correlation between noticeable variability on Raman spectra and the stages of dentinal evolution with advancing age. A study on 30 teeth analysed by Raman microspectrometry was used to select predictors of age, and it allowed us to determine a regression formula, with age as a dependent variable. Our data were computed by means of a statistical method called partial least squares (PLS) regression. This method was specially adapted for this kind of situation, where we have numerous predictors and relatively few observations. The regression formula was performed on a test sample of four more teeth, and we obtained a correct age estimation, with a mean error of more or less than 5 years. The main benefits of this method was a minimal and non-destructive tooth preparation, which led to an efficient age prediction, for any age group.