Risk profiles and incidence of cardiovascular events across different cancer types.

BACKGROUND: Cancer survivors are at increased risk for cardiovascular (CV) disease, although additional data are needed to better understand the incidence of CV events across different malignancies. This study sought to characterize the incidence of major adverse CV events [myocardial infarction, stroke, unstable angina (MACE), or heart failure (HF)] across multiple cancer types after cancer diagnosis. PATIENTS AND METHODS: Patients were identified from a USA-based administrative claims database who had index cancer diagnoses of breast, lung, prostate, melanoma, myeloma, kidney, colorectal, leukemia, or lymphoma between 2011 and 2019, with continuous enrollment for ≥12 months before diagnosis. Baseline CV risk factors and incidence rates of CV events post-index were identified for each cancer. Multivariable Cox hazards models assessed the cumulative incidence of MACE, accounting for baseline risk factors. RESULTS: Among 839 934 patients across nine cancer types, CV risk factors were prevalent. The cumulative incidence of MACE was highest in lung cancer and myeloma, and lowest in breast cancer, prostate cancer, and melanoma. MACE cumulative incidence for lung cancer was 26% by 4 years (2.7-fold higher relative to breast cancer). The incidence of stroke was especially pronounced in lung cancer, while HF was highest in myeloma and lung cancer. CONCLUSIONS: CV events were especially increased following certain cancer diagnoses, even after accounting for baseline risk factors. Understanding the variable patient characteristics and associated CV events across different cancers can help target appropriate CV risk factor modification and develop strategies to minimize adverse CV events and improve patient outcomes.

R-CHOP appears to be the best first-line treatment for second primary diffuse large B cell lymphoma: a cancer registry study.

Second primary diffuse large B cell lymphoma (spDLBCL) is defined as a metachronous tumor occurring after a first primary cancer. To date, while R-CHOP is the standard first-line treatment for de novo DLBCL, no available data show that R-CHOP is the optimal treatment for spDLBCL. This exploratory study aimed to investigate treatment of spDLBCL. From 2008 to 2015, the Poitou-Charentes general cancer registry recorded 68 cases of spDLBCL ≤ 80 years old, having received a first-line treatment with either R-CHOP (78%) or other regimens (22%). Patients without R-CHOP have worse overall survival in univariate (HR 2.89 [1.33-6.24], P = 0.007) and multivariate (HR 2.98 [1.34-6.67], P = 0.008) analyses. Patients without R-CHOP more frequently had PS > 1 (67% vs. 28%, P = 0.007) and prior chemotherapy (60% vs. 26%, P = 0.02), which suggests that both of these factors influence a clinician's decision to not use R-CHOP. Prior chemotherapy had no prognostic impact in univariate and multivariate analyses; this result could call into question the risk-benefit balance of not using R-CHOP to prevent toxicity. In our study, one DLBCL out of ten occurred after a first primary cancer, and as regards de novo DLBCL, R-CHOP appeared to be the best first-line treatment. Larger series are needed to confirm these results.

Phylogenetic analyses of symbiotic genes and characterization of functional traits of Mesorhizobium spp. strains associated with the promiscuous species Acacia seyal Del.

AIMS: To assess the phenotypic, symbiotic and genotypic diversity scope of Mesorhizobium spp. strains associated with Acacia seyal (Del.) isolated from different agro-ecological zones in Senegal, and uses of susceptible microbial inoculum in a reafforestation process. METHODS AND RESULTS: A polyphasic approach including phenotypic and genotypic techniques was used to study the diversity and their relationships with other biovars and species of rhizobia. The geographical origins of the strains have limited effect on their phylogenetic and phenotypic classification. Nodulation tests indicated promiscuity of the strains studied, because they were capable of nodulating six woody legume species (Acacia auriculiformis, Acacia senegal, A. seyal, Acacia tortilis ssp. raddiana, Leucaena leucocephala and Prosopis juliflora). Sequencing and phylogenetic analyses of nodA, nodC and nifH genes pointed out that in contrast to nodA gene, the phylogenies of nodC and nifH genes were not consistent with that of 16S rRNA, indicating that these genes of the A. seyal-nodulating rhizobia might have different origins. Microbial inoculation on nonsterile soil had significant effect on the nodules number and the growth of the seedlings, indicating that these strains of rhizobia might be used as inoculum. CONCLUSIONS: The results indicated that A. seyal is a nonselective host that can establish effective symbiosis with Mesorhizobium spp. strains from diverse genomic backgrounds and that the selected A. seyal-nodulating rhizobia could enhance plant growth. SIGNIFICANCE AND IMPACT OF THE STUDY: These results showed the important role that A. seyal could play in the improvement of reafforestation process as a promiscuous host, which can establish effective symbiosis with rhizobia from diverse genomic backgrounds.

The exotic legume tree species Acacia holosericea alters microbial soil functionalities and the structure of the arbuscular mycorrhizal community.

The response of microbial functional diversity as well as its resistance to stress or disturbances caused by the introduction of an exotic tree species, Acacia holosericea, ectomycorrhized or not with Pisolithus albus, was examined. The results show that this ectomycorrhizal fungus promotes drastically the growth of this fast-growing tree species in field conditions after 7 years of plantation. Compared to the crop soil surrounding the A. holosericea plantation, this exotic tree species, associated or not with the ectomycorrhizal symbiont, induced strong modifications in soil microbial functionalities (assessed by measuring the patterns of in situ catabolic potential of microbial communities) and reduced soil resistance in response to increasing stress or disturbance (salinity, temperature, and freeze-thaw and wet-dry cycles). In addition, A. holosericea strongly modified the structure of arbuscular mycorrhizal fungus communities. These results show clearly that exotic plants may be responsible for important changes in soil microbiota affecting the structure and functions of microbial communities.

Arbuscular mycorrhizal colonization and nodulation improve flooding tolerance in Pterocarpus officinalis Jacq. seedlings.

Pterocarpus officinalis (Jacq.) seedlings inoculated with the arbuscular mycorrhizal fungus, Glomus intraradices, and the strain of Bradyrhizobium sp. (UAG 11A) were grown under stem-flooded or nonflooded conditions for 13 weeks after 4 weeks of nonflooded pretreatment under greenhouse conditions. Flooding of P. officinalis seedlings induced several morphological and physiological adaptive mechanisms, including formation of hypertrophied lenticels and aerenchyma tissue and production of adventitious roots on submerged portions of the stem. Flooding also resulted in an increase in collar diameter and leaf, stem, root, and total dry weights, regardless of inoculation. Under flooding, arbuscular mycorrhizas were well developed on root systems and adventitious roots compared with inoculated root systems under nonflooding condition. Arbuscular mycorrhizas made noteworthy contributions to the flood tolerance of P. officinalis seedlings by improving plant growth and P acquisition in leaves. We report in this study the novel occurrence of nodules connected vascularly to the stem and nodule and arbuscular mycorrhizas on adventitious roots of P. officinalis seedlings. Root nodules appeared more efficient fixing N(2) than stem nodules were. Beneficial effect of nodulation in terms of total dry weight and N acquisition in leaves was particularly noted in seedlings growing under flooding conditions. There was no additive effect of arbuscular mycorrhizas and nodulation on plant growth and nutrition in either flooding treatment. The results suggest that the development of adventitious roots, aerenchyma tissue, and hypertrophied lenticels may play a major role in flooded tolerance of P. officinalis symbiosis by increasing oxygen diffusion to the submerged part of the stem and root zone, and therefore contribute to plant growth and nutrition.

The ectomycorrhizal fungus Scleroderma bermudense alleviates salt stress in seagrape (Coccoloba uvifera L.) seedlings.

The purpose of this study was to test the capacity of the ectomycorrhizal (ECM) fungus, Scleroderma bermudense, to alleviate saline stress in seagrape (Coccoloba uvifera L.) seedlings. Plants were grown over a range (0, 200, 350 and 500 mM) of NaCl levels for 12 weeks, after 4 weeks of non-saline pre-treatment under greenhouse conditions. Growth and mineral nutrition of the seagrape seedlings were stimulated by S. bermudense regardless of salt stress. Although ECM colonization was reduced with increasing NaCl levels, ECM dependency of seagrape seedlings increased. Tissues of ECM plants had significantly increased concentrations of P and K but lower Na and Cl concentrations than those of non-ECM plants. Higher K concentrations in the leaves of ECM plants suggested a higher osmoregulating capacity of these plants. Moreover, the water status of ECM plants was improved despite their higher evaporative leaf surface. The results suggest that the reduction in Na and Cl uptake together with a concomitant increase in P and K absorption and a higher water status in ECM plants may be important salt-alleviating mechanisms for seagrape seedlings growing in saline soils.

Nitrogen-fixing nodules from rose wood legume trees (Dalbergia spp.) endemic to Madagascar host seven different genera belonging to alpha- and beta-Proteobacteria.

Although legume biodiversity is concentrated in tropical regions, the majority of studies on legume nodulating bacteria (LNB) are focused on cultivated leguminous plants from temperate regions. However, recent works on tropical regions tend to indicate that the actual diversity of LNB is largely underestimated. In this study, we report the isolation and characterization of 68 nitrogen-fixing root nodule bacteria collected from eight endemic tree species of Dalbergia in Madagascar. The isolates were characterized by (i) restriction fragment length polymorphism (RFLP) analysis of 16S-IGS rDNA, (ii) 16S rDNA gene sequencing and (iii) nodulation tests. Results revealed a wide diversity of bacteria present in the nodules of Dalbergia. Among the 68 isolated bacteria, 65 belonged to Bradyrhizobium, Mesorhizobium, Rhizobium, Azorhizobium and Phyllobacterium from the alpha-class of Proteobacteria, and three isolates belonged to Burkholderia and Ralstonia from the beta-class of Proteobacteria. Our results also show for the first time that a strain belonging to the Burkholderia cepacia complex is able to induce efficient nodules on a legume plant.

Contrasting responses to ectomycorrhizal inoculation in seedlings of six tropical African tree species.

Five caesalpinioid legumes, Afzelia africana, Afzelia bella, Anthonotha macrophylla, Cryptosepalum tetraphylum and Paramacrolobium coeruleum, and one Euphorbiaceae species, Uapaca somon, with a considerable range in seed sizes, exhibited different responses to inoculation by four species of ectomycorrhizal (ECM) fungi, Scleroderma dictyosporum, S. verrucosum, Pisolithus sp. and one thelephoroid sp. in greenhouse conditions. Thelephoroid sp. efficiently colonized seedlings of all of the five caesalpinioid legumes except U. somon, but provided no more growth benefit than the other fungi. Thelephoroid sp. and S. dictyosporum colonized seedlings of U. somon poorly, but stimulated plant growth more than the other fungi. The relative mycorrhizal dependency (RMD) values of the caesalpinioid legumes were never higher than 50%, whilst U. somon had RMD values ranging from 84.6 to 88.6%, irrespective of the fungal species. The RMD values were negatively related to seed mass for all plant species. Potassium concentrations in leaves were more closely related than phosphorus to the stimulation of seedling biomass production by the ECM fungi. Our data support the hypothesis that African caesalpinioid legumes and euphorbe tree species with smaller seeds show higher RMD values than those with the larger seeds.

The last common ancestor of Sarcolaenaceae and Asian dipterocarp trees was ectomycorrhizal before the India-Madagascar separation, about 88 million years ago.

Phylogenetic studies comparing the Dipterocarpaceae and the Sarcolaenaceae, a tree family endemic to Madagascar, have shown that the Sarcolaenaceae share a common ancestor with Asian dipterocarps. This suggests that Asian dipterocarps drifted away from Madagascar with the India-Seychelles landmass and then dispersed through Asia. Although all dipterocarps examined so far have been found to be ectomycorrhizal, the ectomycorrhizal status of Sarcolaenaceae had not been investigated. Here we establish the ectomycorrhizal status of Sarcolaenaceae using histological and molecular methods. This indicates that the common ancestor of the Sarcolaenaceae and Asian dipterocarps was ectomycorrhizal, at least before the separation of the Madagascar-India landmass, 88 million years ago.

The early-stage ectomycorrhizal Thelephoroid fungal sp. is competitive and effective on Afzelia africana Sm. in nursery conditions in Senegal.

This study was conducted to evaluate the competitiveness and effectiveness of Thelephoroid fungal sp. ORS.XM002 against native ectomycorrhizal fungal species colonizing potted Afzelia africana seedlings during 3 months of growth in different forest soils collected from under mature trees. Using morphotyping and restriction fragment length polymorphism (RFLP) analysis of the nuclear rDNA internal transcribed spacer (ITS), we were able to distinguish the introduced Thelephoroid fungal sp. ORS.XM002 among native ectomycorrhizal fungal species that form ectomycorrhizae in A. africana seedlings. The morphotype (MT) of the introduced fungus showed some color variation, with a shift from light- to dark-brown observed from younger to older mycorrhizal tips. We were able to differentiate the ITS type xm002 of the introduced fungus from the 14 ITS-RFLP types characterizing the 9 native MT that occurred in forest soils. The frequency of ITS type xm002 ranged from 40% to 49% depending on the forest soil used, and was always higher than those of ITS types from native dark-brown MT that occurred in inoculated seedlings 3 months after inoculation. We considered Thelephoroid fungal sp. ORS.XM002 to be responsible for stimulation of mycorrhizal colonization of inoculated A. africana seedlings when compared with control seedlings in forest soils. This fungus appeared to be more effective in increasing the root dry weight of A. africana seedlings. To identify the unknown introduced fungal species and native MT, we sequenced the ML5/ML6 region of the mitochondrial large subunit rRNA. Sequence analysis showed that these fungi belong to three ML5/ML6 groups closely related to the Cortinarioid, Thelephoroid, and Sclerodermataceous taxa. The molecular evidence for the persistence of Thelephoroid fungal sp. ORS.XM002 despite competition from native fungi argues in favor of using this fungus with A. africana in nursery soil conditions in Senegal.

Transplantation in Waldenstrom's macroglobulinemia--the French experience.

Published data on transplantation in Waldenstrom's macroglobulinemia (WM) are still limited. We present a retrospective multicentric study of 27 WM patients who underwent 19 autologous (median age, 54 years) and 10 allogeneic (median age, 46 years) transplantations. Median time between diagnosis and transplantation was 36 months; 66% of patients had received three or more treatment lines and 72 % had chemosensitive disease. High-dose therapy (HDT) and autologous transplantation induced a 95% response rate (RR), including 10 major responses. With a median follow-up of 18 months, 12 patients are alive at 10 to 81 months and eight are free of disease progression at 10 to 34 months. The toxic mortality rate (TRM) was 6%. Allogeneic transplantation was preceded by HDT in nine patients and by a nonmyeloablative regimen in one patient. The RR was 80%, including seven major responses. With a median follow-up of 20.5 months, six patients are alive and free of progression at 3 to 76 months. Four patients died, all from toxicity, resulting in a TRM of 40%. HDT followed by autologous transplantation is feasible in WM, even in heavily pretreated patients, with some prolonged responses but a high relapse rate. Conversely, allogeneic transplantation is more toxic, but likely induces a graft-versus-WM effect and may, for some patients, result in long-term disease control.

Randomized comparison of fludarabine, CAP, and ChOP in 938 previously untreated stage B and C chronic lymphocytic leukemia patients.

To comparatively assess first-line treatment with fludarabine and 2 anthracycline-containing regimens, namely CAP (cyclophosphamide, doxorubicin plus prednisone) and ChOP (cyclophosphamide, vincristine, prednisone plus doxorubicin), in advanced stages of chronic lymphocytic leukemia (CLL), previously untreated patients with stage B or C CLL were randomly allocated to receive 6 monthly courses of either ChOP, CAP, or fludarabine (FAMP), stratified based on the Binet stages. End points were overall survival, treatment response, and tolerance. From June 1, 1990 to April 15, 1998, 938 patients (651 stage B and 287 stage C) were randomized in 73 centers. Compared to ChOP and FAMP, CAP induced lower overall remission rates (58.2%; ChOP, 71.5%; FAMP; 71.1%; P <.0001 for each), including lower clinical remission rates (CAP, 15.2%; ChOP, 29.6%; FAMP, 40.1%; P =.003). By contrast, median survival time did not differ significantly according to randomization (67, 70, and 69 months in the ChOP, CAP, and FAMP groups, respectively). Incidences of infections (< 5%) and autoimmune hemolytic anemia (< 2%) during the 6 courses were similar in the randomized groups, whereas fludarabine induced, compared to ChOP and CAP, more frequent protracted thrombocytopenia (P =.003) and less frequent nausea-vomiting (P =.003) and hair loss (P <.0001). For patients with stage B and C CLL first-line fludarabine and ChOP regimens both provided similar overall survival and close response rates, and better results than CAP. However, there was an increase in clinical remission rate and a trend toward a better tolerance of fludarabine over ChOP that may influence the choice between these regimens as front-line treatments in patients with CLL.

[ Nodulation of certain legumes of the genus Crotalaria by the new species Methylobacterium]. / Certaines légumineuses du genre Crotalaria sont spécifiquement nodulées par une nouvelle espèce de Methylobacterium.

We studied a collection of 126 rhizobial isolates from eight species of Crotalaria (C. comosa, C. glaucoides, C. goreensis, C. hyssopifolia, C. lathyroides, C. perrottetii, C. podocarpa, and C. retusa) growing in Senegal. Nodulation and nitrogen-fixation tests on nine Crotalaria species revealed two specificity groups within the genus Crotalaria. Group I consists of plants solely nodulated by very specific fast-growing strains. Group II plants are nodulated by slow-growing strains similar to promiscuous Bradyrhizobium spp. strains already reported to nodulate many tropical legumes. SDS-PAGE studies showed that slow-growing strains grouped with Bradyrhizobium while fast-growing strains constituted a homogeneous group distinct from all known rhizobia. Amplified ribosomal DNA restriction analysis (ARDRA) of 10 representative strains of this group using four restriction enzymes showed a single pattern for each enzyme confirming the high homogeneity of group I. The 16S rDNA sequence analysis revealed that this specific group belonged to the genus Methylobacterium, thus constituting a new branch of nodulating bacteria.

Nodulation of legumes by members of the beta-subclass of Proteobacteria.

Members of the Leguminosae form the largest plant family on Earth, with around 18,000 species. The success of legumes can largely be attributed to their ability to form a nitrogen-fixing symbiosis with specific bacteria known as rhizobia, manifested by the development of nodules on the plant roots in which the bacteria fix atmospheric nitrogen, a major contributor to the global nitrogen cycle. Rhizobia described so far belong exclusively to the alpha-subclass of Proteobacteria, where they are distributed in four distinct phylogenetic branches. Although nitrogen-fixing bacteria exist in other proteobacterial subclasses, for example Herbaspirillum and Azoarcus from the phylogenetically distant beta-subclass, none has been found to harbour the nod genes essential for establishing rhizobial symbiosis. Here we report the identification of proteobacteria from the beta-subclass that nodulate legumes. This finding shows that the ability to establish a symbiosis with legumes is more widespread in bacteria than anticipated to date.

Characterization of the common nodulation genes of the photosynthetic Bradyrhizobium sp. ORS285 reveals the presence of a new insertion sequence upstream of nodA.

We isolated and characterized nodA genes from photosynthetic and non-photosynthetic rhizobia nodulating the legume genus Aeschynomene, and found that the nodA sequence from photosynthetic stem-nodulating bacteria was phylogenetically distant from the other already described nodA genes. Characterization of the photosynthetic strain ORS285 common nod gene cluster (nodABC) showed, upstream of nodA, the presence of a new insertion sequence element belonging to the IS3 family and specific to a group of photosynthetic strains from Aeschynomene.

Methylotrophic Methylobacterium bacteria nodulate and fix nitrogen in symbiosis with legumes.

Rhizobia described so far belong to three distinct phylogenetic branches within the alpha-2 subclass of Proteobacteria. Here we report the discovery of a fourth rhizobial branch involving bacteria of the Methylobacterium genus. Rhizobia isolated from Crotalaria legumes were assigned to a new species, "Methylobacterium nodulans," within the Methylobacterium genus on the basis of 16S ribosomal DNA analyses. We demonstrated that these rhizobia facultatively grow on methanol, which is a characteristic of Methylobacterium spp. but a unique feature among rhizobia. Genes encoding two key enzymes of methylotrophy and nodulation, the mxaF gene, encoding the alpha subunit of the methanol dehydrogenase, and the nodA gene, encoding an acyltransferase involved in Nod factor biosynthesis, were sequenced for the type strain, ORS2060. Plant tests and nodA amplification assays showed that "M. nodulans" is the only nodulating Methylobacterium sp. identified so far. Phylogenetic sequence analysis showed that "M. nodulans" NodA is closely related to Bradyrhizobium NodA, suggesting that this gene was acquired by horizontal gene transfer.

Effect of Bradyrhizobium photosynthesis on stem nodulation of Aeschynomene sensitiva.

Some leguminous species of the genus Aeschynomene are specifically stem-nodulated by photosynthetic bradyrhizobia. To study the effect of bacterial photosynthesis during symbiosis, we generated a photosynthesis-negative mutant of the Bradyrhizobium sp. strain ORS278 symbiont of Aeschynomene sensitiva. The presence of a functional photosynthetic unit in bacteroids and the high expression of the photosynthetic genes observed in stem nodules demonstrate that the bacteria are photosynthetically active during stem symbiosis. Stem inoculation by the photosynthetic mutant gave a 50% decrease in stem-nodule number, which reduced nitrogen fixation activity and plant growth in the same proportion. These results indicate an important role of bacterial photosynthesis in the efficiency of stem nodulation.

Photosynthetic bradyrhizobia are natural endophytes of the African wild rice Oryza breviligulata.

We investigated the presence of endophytic rhizobia within the roots of the wetland wild rice Oryza breviligulata, which is the ancestor of the African cultivated rice Oryza glaberrima. This primitive rice species grows in the same wetland sites as Aeschynomene sensitiva, an aquatic stem-nodulated legume associated with photosynthetic strains of Bradyrhizobium. Twenty endophytic and aquatic isolates were obtained at three different sites in West Africa (Senegal and Guinea) from nodal roots of O. breviligulata and surrounding water by using A. sensitiva as a trap legume. Most endophytic and aquatic isolates were photosynthetic and belonged to the same phylogenetic Bradyrhizobium/Blastobacter subgroup as the typical photosynthetic Bradyrhizobium strains previously isolated from Aeschynomene stem nodules. Nitrogen-fixing activity, measured by acetylene reduction, was detected in rice plants inoculated with endophytic isolates. A 20% increase in the shoot growth and grain yield of O. breviligulata grown in a greenhouse was also observed upon inoculation with one endophytic strain and one Aeschynomene photosynthetic strain. The photosynthetic Bradyrhizobium sp. strain ORS278 extensively colonized the root surface, followed by intercellular, and rarely intracellular, bacterial invasion of the rice roots, which was determined with a lacZ-tagged mutant of ORS278. The discovery that photosynthetic Bradyrhizobium strains, which are usually known to induce nitrogen-fixing nodules on stems of the legume Aeschynomene, are also natural true endophytes of the primitive rice O. breviligulata could significantly enhance cultivated rice production.