Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P <.05) and less refractoriness (4.5% vs 14.1%; P <.05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P <.05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P <.001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX

Real-world effectiveness of caplacizumab vs the standard of care in immune thrombotic thrombocytopenic purpura

Immune thrombotic thrombocytopenic purpura (iTTP) is a thrombotic microangiopathy caused by anti-ADAMTS13 antibodies. Caplacizumab is approved for adults with an acute episode of iTTP in conjunction with plasma exchange (PEX) and immunosuppression. The objective of this study was to analyze and compare the safety and efficacy of caplacizumab vs the standard of care and assess the effect of the concomitant use of rituximab. A retrospective study from the Spanish TTP Registry of patients treated with caplacizumab vs those who did not receive it was conducted. A total of 155 patients with iTTP (77 caplacizumab, 78 no caplacizumab) were included. Patients initially treated with caplacizumab had fewer exacerbations (4.5% vs 20.5%; P < .05) and less refractoriness (4.5% vs 14.1%; P < .05) than those who were not treated. Time to clinical response was shorter when caplacizumab was used as initial treatment vs caplacizumab used after refractoriness or exacerbation. The multivariate analysis showed that its use in the first 3 days after PEX was associated with a lower number of PEX (odds ratio, 7.5; CI, 2.3-12.7; P < .05) and days of hospitalization (odds ratio, 11.2; CI, 5.6-16.9; P < .001) compared with standard therapy. There was no difference in time to clinical remission in patients treated with caplacizumab compared with the use of rituximab. No severe adverse event was described in the caplacizumab group. In summary, caplacizumab reduced exacerbations and refractoriness compared with standard of care regimens. When administered within the first 3 days after PEX, it also provided a faster clinical response, reducing hospitalization time and the need for PEX

Low-quality carbon and lack of nutrients result in a stronger fungal than bacterial home-field advantage during the decomposition of leaf litter

Decomposition of litter is a key biochemical process that regulates the rate and magnitude of CO2 fluxes from biosphere to atmosphere and determines soil nutrient availability. Although several studies have shown that plant litter decomposition accelerated in their native compared to a foreign environment, that is, a home-field advantage (HFA) for litter degradation, to date HFA has only been considered in terms of respiration or litter mass loss. The competitive success of the decomposer micro-organism will be determined by its ability to transform used OM into population growth. Therefore, we hypothesized that HFA for microbial growth would be more pronounced than that for decomposition. We also expected that HFA effect for decomposition and microbial growth would increase with lower quality litter, which the fungal role in litter decomposition would be more dominant than that of bacteria, and that HFA effects would strengthen with more pronounced differences between ‘home’ and ‘away’ environments. We designed a 2-month microcosm reciprocal transplant experiment with litter from two sites with contrasting climates (Atlantic and Sub-Mediterranean climates) and including three tree species (Quercus robur, Pinus sylvestris and Fagus sylvatica). We found a stronger HFA for microbial growth than for decomposition, that the nutrient content and C-quality of litter influenced the microbial HFA and that interactions between bacterial and fungal communities during litter decomposition modulated the HFA for litter degradation. Low litter nutrient content, strong nutrient limitations and low C-qualities all favoured fungal over bacterial decomposers, and our results suggest a dominant functional role of the fungal community and gave rise to HFA effect for fungal growth but that this translated to only marginal implications for overall decomposition of litter. A free Plain Language Summary can be found within the Supporting Information of this article

Potential indicators of soil quality in temperate forest ecosystems: a case study in the Basque Country

• Assessment of forest sustainability requires reliable soil quality indicators. The present study evaluated the use of several potential such indicators in forests in the Basque Country under different types of management, involving: (i) species change and (ii) heavily mechanised forest operations. • Five adjacent forest stands were selected for study: (i) two unmanaged forests (Quercus robur, Fagus sylvatica) and one (40-year-old) Pinus radiata plantation, to investigate the effect of species change; and (ii) a chronosequence of mechanised radiata pine plantations (3 and 16 years old), to investigate heavy mechanisation. • Several physical, chemical and biological parameters were analysed in the mineral soil. Species change could not be assessed with chemical parameters, but parameters related to organic matter indicated the disturbance caused by heavy mechanisation. The Least Limiting Water Range was a good indicator of soil physical degradation induced by heavy mechanisation. Biological parameters proved sensitive indicators: (i) the fungal phospholipid fatty acid biomarker 18:2$\omega$6 for species change; and (ii) the ratio of Gram-positive/Gram-negative bacteria for heavy mechanisation. Nevertheless, these parameters are complementary, and monitoring programmes should include physical, chemical and biological parameters. • Further studies are required to assess natural boundaries of variation in soil quality indicators, and their resistance and resilience.Indicateurs potentiels de la qualité des sols dans les écosystèmes forestiers tempérés : une étude de cas dans le Pays Basque. • L'évaluation de la durabilité des forêts nécessite des indicateurs fiables de la qualité des sols. La présente étude a évalué l'utilisation de plusieurs de ces indicateurs potentiels dans les forêts du Pays Basque sous différents types de gestion, comprenant : (i) le changement des espèces et (ii) les opérations forestières fortement mécanisées. • Cinq peuplements forestiers voisins ont été sélectionnés pour l'étude : (i) deux forêts non gérées (Quercus robur, Fagus sylvatica) et une plantation (âgée de 40 ans) de Pinus radiata, pour examiner l'effet des changements d'espèces, (ii) une chronoséquence de plantations mécanisées de Pinus radiata (âgées de 3 et 16 ans), pour enquêter sur la mécanisation lourde. • Plusieurs caractéristiques physiques, chimiques et biologiques ont été analysées dans le sol minéral. Le changement d'espèce ne peut être évaluée avec des paramètres chimiques, mais les paramètres liés à la matière organique ont indiqué des perturbations causées par la forte mécanisation. Le Least Limiting Water Range est un bon indicateur de la dégradation des sols induite par la forte mécanisation. Paramètres biologiques qui se sont révélés des indicateurs sensibles : (i) le biomarqueur acide gras phospholipide fongique 18$:$2$\omega$6 pour le changement d'espèces, (ii) le rapport bactérien Gram-positive/Gram-negative pour la mécanisation lourde. Néanmoins, ces paramètres sont complémentaires, et des programmes de suivi devraient inclure des paramètres physiques, chimiques et biologiques. • D'autres études sont nécessaires pour évaluer les limites naturelles de la variation des indicateurs de la qualité des sols, de leur résistance et de leur résilience

Mineral control of organic carbon storage in acid temperate forest soils in the Basque Country

International audienceAbstract Soil carbon dynamics is strongly controlled by depth globally, with increasingly slow dynamics found at depth. The mechanistic basis remains however controversial, limiting our ability to predict carbon cycle-climate feedbacks. Here we combine radiocarbon and thermal analyses with long-term incubations in absence/presence of continuously 13 C/ 14 C-labelled plants to show that bioenergetic constraints of decomposers consistently drive the depth-dependency of soil carbon dynamics over a range of mineral reactivity contexts. The slow dynamics of subsoil carbon is tightly related to both its low energy density and high activation energy of decomposition, leading to an unfavourable ‘return-on-energy-investment’ for decomposers. We also observe strong acceleration of millennia-old subsoil carbon decomposition induced by roots (‘rhizosphere priming’), showing that sufficient supply of energy by roots is able to alleviate the strong energy limitation of decomposition. These findings demonstrate that subsoil carbon persistence results from its poor energy quality together with the lack of energy supply by roots due to their low density at depth

Multi-criteria analysis to compare multiple risks associated with management alternatives in planted forests

*Aim of study: Adaptation of silviculture in planted forest may help to mitigate damage due to biotic and abiotic hazards. However, compromises have to be found because it is not possible to minimize the risk from all hazards through application of a single forest management approach. The objective of this study was to improve a multi-criteria risk analysis (MCRA) method that makes it possible to rank forest management alternatives (FMAs) according to multiple risks. *Material and Methods: We defined eight FMAs for maritime pine forests in France, Spain and Portugal. We used as the definition of risk the combination of hazard, susceptibility and exposure. Hazard level was estimated using archive data on occurrence and severity of damaging agents over the last few decades. Forest susceptibility to hazards was evaluated by experts who scored the effect on stand resistance of eleven silvicultural operations characterizing each FMA. Exposure was estimated as value at stake, which combined forest standing volume, simulated with forest growth models, and wood prices.*Main Results: Using the PROMETHEE algorithm, we found that the overall ranking of FMAs was consistent across all countries, with short rotation plantations to produce pulpwood or energy wood were the least at risk. The ranking was mainly driven by forest values at stake. We found that by improving the accuracy of forest values exposed to damage, based on growth models and representative wood prices, the MCRA outcomes were more useful and realistic.*Research highlights: Our methodology provides a relevant framework to design FMAs that would minimize risks while maintaining income

Multi-criteria analysis to compare multiple risks associated with management alternatives in planted forests

Aim of study: Adaptation of silviculture in planted forest may help to mitigate damage due to biotic and abiotic hazards. However, compromises have to be found because it is not possible to minimize the risk from all hazards through application of a single forest management approach. The objective of this study was to improve a multi-criteria risk analysis (MCRA) method that makes it possible to rank forest management alternatives (FMAs) according to multiple risks. Material and Methods: We defined eight FMAs for maritime pine forests in France, Spain and Portugal. We used as the definition of risk the combination of hazard, susceptibility and exposure. Hazard level was estimated using archive data on occurrence and severity of damaging agents over the last few decades. Forest susceptibility to hazards was evaluated by experts who scored the effect on stand resistance of eleven silvicultural operations characterizing each FMA. Exposure was estimated as value at stake, which combined forest standing volume, simulated with forest growth models, and wood prices. Main Results: Using the PROMETHEE algorithm, we found that the overall ranking of FMAs was consistent across all countries, with short rotation plantations to produce pulpwood or energy wood were the least at risk. The ranking was mainly driven by forest values at stake. We found that by improving the accuracy of forest values exposed to damage, based on growth models and representative wood prices, the MCRA outcomes were more useful and realistic. Research highlights: Our methodology provides a relevant framework to design FMAs that would minimize risks while maintaining income

Red para la innovación en la selvicultura y los sistemas de integración de riesgos en la gestión forestal

La forêt, en plus de ses fonctions économiques reconnues par tous les acteurs du milieu rural tels que le développement de l'emploi rural et le marché local du bois pour la transformation ou pour l'énergie, rend de nombreux autres services. Cependant, de multiples risques sont identifiables et doivent être gérés dans et pourront éventuellement être aggravés par les changements climatiques: futures sécheresses favorables aux pathogènes et ravageurs ainsi qu'à la propagation des incendies, et le risque de la modification du vent. Le projet FORRISK se focalisera ainsi sur les risques en forêt dont l'intensité est modulée par le changement climatique. L'histoire des forêts du sud de l'Europe nous rappelle que pour de nombreux problèmes, une approche seulement nationale n'a pas de sens. C'est-à-dire, les risques concernés, les réponses à apporter peuvent être soit au niveau technique soit au niveau de l'organisation des institutions. Pour cette raison, FORRISK vise à coordonner et mettre en réseau trois communautés différentes que sont les acteurs politiques, les gestionnaires et les scientifiques, dans le but d'obtenir que la gestion des risques soit partie intégrante des décisions prises à tous les niveaux du secteur forestier. Cela permettra d'initier une plateforme européenne sur les risques forestiers en facilitant des recommandations et des informations pertinentes à tous les niveaux. Pour y parvenir, le projet analysera et comparera les outils institutionnels, les systèmes et organisations liés à la gestion de risques dans les régions étudiées. Ensuite, FORRISK développera sur le terrain des techniques de lutte écologique, génétique et sylvicole, dont les résultats feront l'objet de guides de bonne pratique. Les outils produits consisteront à des cartes de risques à l'échelle régionale ou subrégionale, ainsi que à des modèles informatiques permettant de faire des diagnostics sur le terrain et de modéliser la propagation du fomès dans les peuplements de pin maritime. Ainsi, décideurs politiques, gestionnaires et scientifiques auront entre leurs mains des outils adaptés à la gestion de nombreux risques menaçant la forêt dans leurs régions