Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Targeting rural development interventions: Empirical agent-based modeling in Nigerien villages

The aim of this article is to analyze the impact of development interventions on the population of three Nigerien villages that differ in terms of their agro-ecological, social and economic characteristics. This is performed by simulating the behavior of individuals in an agent-based modeling framework which integrates the village characteristics as well as the family internal rules that condition access to economic and production activities. Villagers are differentiated according to the social and agro-ecological constraints they are subjected to. Two development project interventions are simulated, assuming no land scarcity: increasing the availability of inorganic fertilizers for farmers and an inventory credit technique based on millet grain. Two distinct approaches were used to model the rationale of farmers' decision making: gains or losses in economic value or gains or losses in within-village "reputation". Our results show that village populations do not respond en masse to development interventions. Reputation has little effect on the population behavior and should be considered more as a local proxy for wealth amongst villagers, suggesting the monetization of these societies. Populations involve themselves in the two simulated development interventions only at sites where savings are possible. Some level of household food security and investment capacity is actually required to take part in the development interventions, which are largely conditioned by family manpower and size. As long as uncultivated land remains available in the village territory, support for inorganic fertilizers has little impact in the absence of any intensification process. Inventory credit engages a maximum of 25% of the population at the site with medium agro-ecological conditions. Therefore, both interventions should be viewed as a potential support tool for a limited part of the population capable of going beyond the survival level, but not as a generic poverty-alleviation panacea.Farming systems Individual agent-based model Niger Sahel Development interventions

Overview of tensor decompositions with applications to communications

International audienceTensors decompositions are powerful tools for modeling wireless communication systems and for solving problems such as blind/semi-blind equalization, source/user separation, and channel estimation. Tensors have received great attention over the past decade. In the context of communication systems, the basic motivation for resorting to tensor-based signal processing comes from the multidimensional nature of transmitted and received signals (typical dimensions are symbol periods, time blocks, space, frequency, coding, etc) which translates into more powerful uniqueness and identifiability properties compared with matrix-based signal processing. This chapter has overviewed tensor signal models for three types of systems. First, we have discussed a tensor-based space-time-frequency (TSTF) coding model for MIMO systems, which unifies the model of different space-time and space-time-frequency schemes derived previously. Second, we have presented some tensor models for cooperative communication systems with AF-based relaying. Third, the application of tensors to multidimensional array processing has been discussed, with a focus on the problems of multidimensional model order selection, prewhitening, and parameter estimation. As already said, tensor models/decompositions are very useful for representing multidimensional data in various fields of application. Among the hot research topics on tensors for future works, we can mention the development of methods for sparse low-rank tensor approximation using compressive sensing techniques, with possible application to sparse massive MIMO channel estimation in the context of cooperative communications

Safety and Efficacy of Ipilimumab plus Nivolumab and Sequential Selective Internal Radiation Therapy in Hepatic and Extrahepatic Metastatic Uveal Melanoma.

To assess the safety and efficacy of ipilimumab plus nivolumab around selective internal radiation therapy (SIRT) in patients with metastatic uveal melanoma (mUM). We present a retrospective, single center study of 32 patients with mUM divided into two groups based on the treatment received between April 2013 and April 2021. The SIRT_IpiNivo cohort was treated with Yttrium-90 microspheres and ipilimumab plus nivolumab before or after the SIRT (n = 18). The SIRT cohort underwent SIRT but did not receive combined immunotherapy with ipilimumab plus nivolumab (n = 14). Twelve patients (66.7%) of the SIRT_IpiNivo arm received SIRT as first-line treatment and six patients (33.3%) received ipilimumab plus nivolumab prior to SIRT. In the SIRT group, seven patients (50.0%) received single-agent immunotherapy. One patient treated with combined immunotherapy 68 months after the SIRT was included in this group. At the start of ipilimumab plus nivolumab, 94.4% (n = 17) presented hepatic metastases and 72.2% (n = 13) had extra liver disease. Eight patients (44.4%) of the SIRT_IpiNivo group experienced grade 3 or 4 immune related adverse events, mainly colitis and hepatitis. Median overall survival from the diagnosis of metastases was 49.6 months (95% confidence interval (CI); 24.1-not available (NA)) in the SIRT_IpiNivo group compared with 13.6 months (95% CI; 11.5-NA) in the SIRT group (log-rank p-value 0.027). The presence of extra liver metastases at the time of SIRT, largest liver lesion more than 8 cm (M1c) and liver tumor volume negatively impacted the survival. This real-world cohort suggests that a sequential treatment of ipilimumab plus nivolumab and SIRT is a well-tolerated therapeutic approach with promising survival rates

Validation of Melanoma Immune Profile (MIP), a Prognostic Immune Gene Prediction Score for Stage II-III Melanoma.

Biomarkers are needed to stratify patients with stage II-III melanoma for clinical trials of adjuvant therapy because, while immunotherapy is protective, it also confers the risk of severe toxicity. We previously defined and validated a 53-immune gene melanoma immune profile (MIP) predictive both of distant metastatic recurrence and of disease-specific survival (DSS). Here, we test MIP on a third independent population. A retrospective cohort of 78 patients with stage II-III primary melanoma was analyzed using the NanoString assay to measure expression of 53 target genes, and MIP score was calculated. Statistical analysis correlating MIP with DSS, overall survival, distant metastatic recurrence, and distant metastasis-free interval was performed using ROC curves, Kaplan-Meier curves, and standard univariable and multivariable Cox proportional hazards models. MIP significantly distinguished patients with distant metastatic recurrence from those without distant metastatic recurrence using ROC curve analysis (AUC = 0.695; P = 0.008). We defined high- and low-risk groups based on the cutoff defined by this ROC curve and find that MIP correlates with both DSS and overall survival by ROC curve analysis (AUC = 0.719; P = 0.004 and AUC = 0.698; P = 0.004, respectively). Univariable Cox regression reveals that a high-risk MIP score correlates with DSS (P = 0.015; HR = 3.2). MIP identifies patients with low risk of death from melanoma and may constitute a clinical tool to stratify patients with stage II-III melanoma for enrollment in clinical trials

Real-life data for first-line combination immune-checkpoint inhibition and targeted therapy in patients with melanoma brain metastases.

Melanoma brain metastases (MBM) have a poor prognosis. Systemic treatments that have improved outcomes in advanced melanoma have been shown to have an intracranial (IC) effect. We studied the efficacy and outcomes of combined immune checkpoint inhibitor ipilimumab/nivolumab (Combi-ICI) or targeted therapy (Combi-TT) as first-line treatment in MBM. MBM patients treated with Combi-ICI or Combi-TT within 3 months after MBM diagnosis. Endpoints were progression-free survival (PFS) and overall survival (OS). 53 patients received Combi-ICI, 32% had symptomatic MBM and 33.9% elevated LDH. 71.7% required local treatment. The disease control rate was 60.3%. IC response rate (RR) was 43.8% at 3-months with durable responses at 6- (46.5%) and 12-months (53.1%). Extracranial (EC) RR was 44.7% at 3-months and 50% at 12-months. Median PFS was 9.6 months (95% CI 3.6-NR) and median overall survival (mOS) 44.8 months (95% CI; 26.2-NR). 63 patients received Combi-TT, 55.6% of patients had symptomatic MBM, 57.2% of patients had elevated LDH and 68.3% of patients required local treatment. The disease control rate was 60.4%. ICRR was 50% at 3-months, but dropped at 6-months (20.9%). ECRR was 69.2% at 3-months and 17.6% at 12-months. Median PFS was 5.8 months (95% CI 4.2-7.6) and mOS 14.2 months (95% CI 8.99-26.8). In BRAFV600 patients, 26.7% of patients received Combi-ICI and 73.3% Combi-TT with OS (p = 0.0053) and mPFS (p = 0.03) in favour to Combi-ICI. Combi-ICI showed prolonged mOS with sustainable IC and EC responses. Despite the initially increased efficacy, Combi-TT responses at 12 months were low. Combi-ICI appeared superior to Combi-TT for OS and PFS in BRAFV600 patients. Other clinical factors are determinants for first-line treatment choice

The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study.

Evidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients' and disease characteristics as predictors of OS in patients treated with SRS. We identified patients with BM from cutaneous or unknown primary origin melanoma treated with SRS between 2011 and 2018. We included 84 patients. The median OS was 12 months (95% CI 9-20 months). The median follow-up was 30 months (95% CI 28-49). Twenty-eight patients with newly diagnosed BM initiated anti-PD-1 +/-CTLA-4 therapy (n = 18), ipilimumab monotherapy (n = 10) or BRAF+/- MEK inhibitors (n = 11), during the 9 weeks before or after SRS. Patients who received anti-PD-1 +/-CTLA-4 mAb showed an improved survival in comparison to ipilimumab monotherapy (OS 24 vs. 7.5 months; HR 0.32, 95% 0.12-0.83, p = 0.02) and BRAF +/-MEK inhibitors (OS 24 vs. 7 months, respectively; HR 0.11, 95% 0.04-0.34, p = 0.0001). This benefit remained significant when compared to the subgroup of patients treated with dual BRAF/MEK inhibition (BMi) (n = 5). In a multivariate Cox regression analysis an age > 65, synchronous BM, > 2 metastatic sites, > 4 BM, and an ECOG > 1 were correlated with poorer prognosis. A treatment with anti-PD-1+/-CTLA-4 mAbs within 9 weeks of SRS was associated with better outcomes. The presence of serum lactate dehydrogenase (LDH) levels ≥ 2xULN at BM diagnosis was associated with lower OS (HR 1.60, 95% CI 1.03-2.50; p = 0.04). The concurrent administration of anti-PD-1+/-CTLA-4 mAbs with SRS was associated with improved survival in melanoma patients with newly diagnosed BM. In addition to CNS tumor burden, the extension of systemic disease retains its prognostic value in patients treated with SRS. Elevated serum LDH levels are predictors of poor outcome in these patients

Breeding annual legumes for sustainable agricultures must target for new and more complex variety ideotypes

International audienceAlthough yield and total biomass produced by annual legumes remain major objectives for breeders, environment-friendly, resource use efficient including symbiotic performance, resilient production in the context of climate change, adaptation to sustainable cropping systems (reducing leaching and glasshouse gas emissions), adaptation to diverse uses (seeds for feeds foods, non-food, forage or green manures), and finally new ecological services such as pollinator protection, imply the development of innovative genotypes, definition of new ideotypes and acceptance of their commercialisation. Taken as a whole, this means more complex and integrated objectives for breeders. Several illustrations will be given of breeding such complex traits for different annual legume species. Genetic diversity for root development and for ability to establish efficient symbioses with rhizobia and mycorrhiza can contribute to better resource management (N, P, water). Shoot architectures and phenologies can contribute to yield and biotic protection (weeds, disease, parasitic insects). Long winter cycles or short cycles, tolerance to biotic or abiotic stresses, are key features for the introduction of annual legumes in low input cropping systems. Adaptation to intercropping requires adapted genotypes. Improved health and nutritional value for humans are key objectives for developing new markets. Modifying product composition often requires the development of specific varieties and sometimes the need to break negative genetic correlations with yield. A holistic approach in legume breeding is important for defining objectives with farmers, processors and consumers. The varietal structures may be more complex, combining genotypes, plant species and associated symbionts. New tools to build, evaluate and register them are important