Midterm Outcomes and Aneurysm Sac Dynamics Following Fenestrated Endovascular Aneurysm Repair after Previous Endovascular Aneurysm Repair.

OBJECTIVE: Fenestrated endovascular aneurysm repair (FEVAR) is a feasible option for aortic repair after endovascular aneurysm repair (EVAR), due to improved peri-operative outcomes compared with open conversion. However, little is known regarding the durability of FEVAR as a treatment for failed EVAR. Since aneurysm sac evolution is an important marker for success after aneurysm repair, the aim of the study was to examine midterm outcomes and aneurysm sac dynamics of FEVAR after prior EVAR. METHODS: Patients undergoing FEVAR for complex abdominal aortic aneurysms from 2008 to 2021 at two hospitals in The Netherlands were included. Patients were categorised into primary FEVAR and FEVAR after EVAR. Outcomes included five year mortality rate, one year aneurysm sac dynamics (regression, stable, expansion), sac dynamics over time, and five year aortic related procedures. Analyses were done using Kaplan-Meier methods, multivariable Cox regression analysis, chi square tests, and linear mixed effect models. RESULTS: One hundred and ninety-six patients with FEVAR were identified, of whom 27% (n = 53) had had a prior EVAR. Patients with prior EVAR were significantly older (78 ± 6.7 years vs. 73 ± 5.9 years, p < .001). There were no significant differences in mortality rate. FEVAR after EVAR was associated with a higher risk of aortic related procedures within five years (hazard ratio [HR] 2.6; 95% confidence interval [CI] 1.1 - 6.5, p = .037). Sac dynamics were assessed in 154 patients with available imaging. Patients with a prior EVAR showed lower rates of sac regression and higher rates of sac expansion at one year compared with primary FEVAR (sac expansion 48%, n = 21/44, vs. 8%, n = 9/110, p < .001). Sac dynamics over time showed similar results, sac growth for FEVAR after EVAR, and sac shrinkage for primary FEVAR (p < .001). CONCLUSION: There were high rates of sac expansion and a need for more secondary procedures in FEVAR after EVAR than primary FEVAR patients, although this did not affect midterm survival. Future studies will have to assess whether FEVAR after EVAR is a valid intervention, and the underlying process that drives aneurysm sac growth following successful FEVAR after EVAR.

A Ratio Between Infrarenal and Suprarenal Aortic Diameters Corrects for Absolute Aortic Diameter Variations due to Patients' Sex and Body Size.

OBJECTIVES: Aortic diameters may differ significantly between patients with different gender and body size. The aim of this study was to relate absolute aortic diameters to age, sex, height, and weight of the patients and to correct for these factors by calculating the ratio between the infrarenal and the suprarenal aortic diameters. METHODS: A total of 458 patients who underwent elective endovascular aneurysm repair (EVAR) between 2004 and 2018 were included. The aortic anatomy in this group of elective EVAR patients was compared with a control group of 75 patients without an abdominal aortic aneurysm (AAA). The aortic diameter was measured at 4 suprarenal points and 4 infrarenal points. Ratios were calculated by dividing the mean infrarenal neck diameter by 4 suprarenal measurements. RESULTS: Patients in the aneurysm group had significantly larger suprarenal and infrarenal aortic diameters. The ratios between the mean infrarenal neck diameter and all 4 suprarenal measurements were larger in the AAA group than in the control group. In both groups, there was a significant correlation between the mean infrarenal neck diameter and sex, height, weight, and body surface area (BSA). However, in both groups, all 4 ratios between the mean infrarenal neck diameter and suprarenal aortic diameters were not correlated with age, sex, height, weight, or BSA, except for the ratio between the mean infrarenal neck diameter and the aortic diameter measurement proximal to the upper renal artery, which was correlated to weight and BSA in the control group. CONCLUSION: The mean infrarenal neck diameter is correlated with sex, height, weight, and BSA. However, when the suprarenal aortic diameter was used as an internal control for the mean infrarenal neck diameter, we were able to correct for these variations in aortic diameters due to sex and body size. The clinical relevance of this ratio in patients treated by EVAR has yet to be assessed in future research. CLINICAL IMPACT: In the assessment for EVAR suitability the absolute diameter of the aneurysm neck is taken into account. We believe that using absolute diameters is not the appropriate way to assess this suitability, but that patient characteristics such as age, gender and body size, should be factored into this assessment. In this paper, we show that suprarenal and infrarenal aortic diameters are both significantly increased in patients with an aneurysm compared with patients without an aneurysm. Besides, we found that mean infrarenal aortic diameter is correlated with sex, height, weight, and body surface area. Finally, we propose a new ratio system, using suprarenal diameters as an internal control, to correct for aortic diameter variations due to sex and body size.

Dynamic Computed Tomography Angiography as Imaging Method for Endoleak Classification after Endovascular Aneurysm Repair: A Case Series and Systematic Review of the Literature.

INTRODUCTION: This study evaluated our experience with dynamic computed tomography angiography (dCTA) as a diagnostic tool after endovascular aortic aneurysm repair (EVAR) with respect to the endoleak classification and the available literature. METHODS: We reviewed all patients who underwent dCTA because of suspected endoleaks after the EVAR and classified the endoleaks in these patients based on standard CTA (sCTA) and dCTA. We systematically reviewed all available publications that investigated the diagnostic accuracy of dCTA compared with other imaging techniques. RESULTS: In our single-center series, 16 dCTAs were performed in 16 patients. In 11 patients, the undefined endoleaks that appeared on sCTA scans were successfully classified using dCTA. In three patients with a type II endoleak and aneurysm sac growth, inflow arteries were successfully identified using dCTA, and in two patients, aneurysm sac growth was observed without a visible endoleak on both sCTA and dCTA scans. The dCTA revealed four occult endoleaks, all of which were type II endoleaks. The systematic review identified six series comparing dCTA with other imaging methods. All articles reported an excellent outcome regarding the endoleak classification. In published dCTA protocols, the number and timing of phases varied greatly, affecting radiation exposure. Time attenuation curves of the current series show that some phases do not contribute to the endoleak classification and that the use of a test bolus improves the timing of the dCTA. CONCLUSIONS: The dCTA is a valuable additional tool that can identify and classify endoleaks more accurately than the sCTA. Published dCTA protocols vary greatly and should be optimized to decrease radiation exposure as long as accuracy can be maintained. The use of a test bolus to improve the timing of the dCTA is recommended, but the optimal number of scanning phases is yet to be determined.

A stable aneurysm sac after endovascular aneurysm repair as a predictor for mortality: An in-depth analysis.

OBJECTIVE: The aim of the present study was to compare the long-term survival of patients with a stable aneurysm sac vs those with aneurysm sac regression after endovascular aneurysm repair (EVAR) and to identify the independent risk factors for aneurysm sac regression and mortality after EVAR. METHODS: We reviewed all the patients who had undergone EVAR from 2005 to 2018 with computed tomography angiography available at 1 year of follow-up. Aneurysm sac regression was defined as a diameter decrease of >10%. We used multivariable regression to identify the independent risk factors for sac regression. Kaplan-Meier analysis and Cox regression were performed to test the differences in 5-year mortality between a stable sac diameter and sac regression. RESULTS: The inclusion criteria were met by 325 patients, with 185 in the sac regression group and 140 in the stable sac group. Multivariable logistic regression analysis showed that treatment of a ruptured aneurysm was an independent risk factor for aneurysm sac regression (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.07-0.96). Age (HR, 1.05; 95% CI, 1.01-1.09), ischemic heart disease (HR, 1.94; 95% CI, 1.13-3.31), neck thrombus (HR, 2.72; 95% CI, 1.07-6.95), and a type II endoleak (HR, 19.21; 95% CI, 7.32-50.40) were independent risk factors for a stable aneurysm sac diameter. Multivariable Cox regression showed a significantly increased risk of mortality for patients with a stable aneurysm sac after EVAR (odds ratio, 2.25; 95% CI, 1.36-3.72). No significant differences were found in cause of death between the two groups. CONCLUSIONS: A stable aneurysm sac after EVAR was associated with increased mortality. Age, ischemic heart disease, neck thrombus, and a type II endoleak were independent risk factors for a stable aneurysm sac. However, a well-founded explanation for this finding is still lacking. Future research should focus on aggressive treatment of type II endoleaks and inflammatory processes as potential pathophysiologic mechanisms.

Sequence of the Mitochondrial Genome of Lactuca virosa Suggests an Unexpected Role in Lactuca sativa's Evolution.

The involvement of the different Lactuca species in the domestication and diversification of cultivated lettuce is not totally understood. Lactuca serriola is considered as the direct ancestor and the closest relative to Lactuca sativa, while the other wild species that can be crossed with L. sativa, Lactuca virosa, and Lactuca saligna, would have just contributed to the latter diversification of cultivated typologies. To contribute to the study of Lactuca evolution, we assembled the mtDNA genomes of nine Lactuca spp. accessions, among them three from L. virosa, whose mtDNA had not been studied so far. Our results unveiled little to no intraspecies variation among Lactuca species, with the exception of L. serriola where the accessions we sequenced diverge significantly from the mtDNA of a L. serriola accession already reported. Furthermore, we found a remarkable phylogenetic closeness between the mtDNA of L. sativa and the mtDNA of L. virosa, contrasting to the L. serriola origin of the nuclear and plastidial genomes. These results suggest that a cross between L. virosa and the ancestor of cultivated lettuce is at the origin of the actual mitochondrial genome of L. sativa.

Anterior Thoracic Spinal Cord Herniation: Surgical Treatment and Postoperative Course. An Individual Participant Data Meta-Analysis of 246 Cases.

BACKGROUND: Anterior thoracic spinal cord herniation (ATSCH) is a rare cause of progressive myelopathy. Early surgery is essential, but there is no agreement about the best surgical approach. OBJECTIVE: To identify factors that determine surgical results and to find evidence for the most favorable technique to correct ATSCH. METHODS: To find relevant literature, computed databases of PubMed, EMBASE, and ISI Web of Science were searched. The study comprised case reports published between 1974 and 2018, and the data set was completed with 12 cases treated in our own institute. Patient characteristics were analyzed following the principles of an individual participant data meta-analysis. RESULTS: Brown-Séquard-like neurologic deficit before surgery was associated with postoperative motor function improvement compared with patients with paraparesis (P = 0.04). In the univariate analysis, widening of the dura defect (WDD) was more prevalent among improved patients, whereas anterior dura patch and application of intraoperative neurophysiologic monitoring were not. In the multivariate analysis, the favorable association with WDD disappeared, which is explained by the dominant influence of a Brown-Séquard-like deficit on outcome. CONCLUSIONS: In general, postoperative results after surgery for ATSCH are favorable, with a high percentage of patients experiencing postoperative improvement. Postoperative motor function improvement is more likely to occur in patients with a Brown-Séquard-like neurologic deficit. The WDD should be favored above the application of a patch as the technique of choice in surgical treatment of ATSCH.

Genetic Components of Root Architecture Remodeling in Response to Salt Stress.

Salinity of the soil is highly detrimental to plant growth. Plants respond by a redistribution of root mass between main and lateral roots, yet the genetic machinery underlying this process is still largely unknown. Here, we describe the natural variation among 347 Arabidopsis thaliana accessions in root system architecture (RSA) and identify the traits with highest natural variation in their response to salt. Salt-induced changes in RSA were associated with 100 genetic loci using genome-wide association studies. Two candidate loci associated with lateral root development were validated and further investigated. Changes in CYP79B2 expression in salt stress positively correlated with lateral root development in accessions, and cyp79b2 cyp79b3 double mutants developed fewer and shorter lateral roots under salt stress, but not in control conditions. By contrast, high HKT1 expression in the root repressed lateral root development, which could be partially rescued by addition of potassium. The collected data and multivariate analysis of multiple RSA traits, available through the Salt_NV_Root App, capture root responses to salinity. Together, our results provide a better understanding of effective RSA remodeling responses, and the genetic components involved, for plant performance in stress conditions.

Mapping quantitative trait loci for heat tolerance of reproductive traits in tomato (Solanum lycopersicum).

Global warming has become a worldwide concern due to its adverse effects on agricultural output. In particular, long-term mildly high temperatures interfere with sexual reproduction and thus fruit and seed set. To uncover the genetic basis of observed variation in tolerance against heat, a bi-parental F2 mapping population from two contrasting cultivars, i.e. Nagcarlang and NCHS-1, was generated and phenotyped under continuous mild heat conditions for a number of traits underlying reproductive success, i.e. pollen viability, pollen number, style length, anther length, style protrusion, female fertility and flowering characteristics, i.e. inflorescence number and flowers per inflorescence. Quantitative trait loci (QTLs) were identified for most of these traits, including a single, highly significant one for pollen viability, which accounted for 36% of phenotypic variation in the population and modified pollen viability under high temperature with around 20%. QTLs for some traits colocalised, indicating trait dependency or pleiotropic-effect loci. We conclude that a limited set of major genes determines differences in performance of reproductive traits under continuous mild heat in tomato. The results contribute to our fundamental understanding of pollen thermotolerance and may support development of more heat-tolerant tomato varieties.

Assessment of natural variation in the first pore domain of the tomato HKT1;2 transporter and characterization of mutated versions of SlHKT1;2 expressed in Xenopus laevis oocytes and via complementation of the salt sensitive athkt1;1 mutant.

Single Nucleotide Polymorphisms (SNPs) within the coding sequence of HKT transporters are important for the functioning of these transporters in several plant species. To unravel the functioning of HKT transporters analysis of natural variation and multiple site-directed mutations studies are crucial. Also the in vivo functioning of HKT proteins, via complementation studies performed with athkt1;1 plants, could provide essential information about these transporters. In this work, we analyzed the natural variation present in the first pore domain of the HKT1;2 coding sequence of 93 different tomato accessions, which revealed that this region was conserved among all accessions analyzed. Analysis of mutations introduced in the first pore domain of the SlHKT1;2 gene showed, when heterologous expressed in Xenopus laevis oocytes, that the replacement of S70 by a G allowed SlHKT2;1 to transport K(+), but also caused a large reduction in both Na(+) and K(+) mediated currents. The study of the transport characteristics of SlHKT1;2 revealed that Na(+)-transport by the tomato SlHKT1;2 protein was inhibited by the presence of K(+) at the outside of the membrane. GUS expression under the AtHKT1;1 promoter gave blue staining in the vascular system of transgenic Arabidopsis. athkt1;1 mutant plants transformed with AtHKT1;1, SlHKT1;2, AtHKT1;1S68G, and SlHKT1;2S70G indicated that both AtHKT1;1 and SlHKT1;2 were able to restore the accumulation of K(+) in the shoot, although the low accumulation of Na(+) as shown by WT plants was only partially restored. The inhibition of Na(+) transport by K(+), shown by the SlHKT1;2 transporter in oocytes (and not by AtHKT1;1), was not reflected in Na(+) accumulation in the plants transformed with SlHKT1;2. Both AtHKT1;1-S68G and SlHKT1;2-S70G were not able to restore the phenotype of athkt1;1 mutant plants.

Capturing Arabidopsis root architecture dynamics with ROOT-FIT reveals diversity in responses to salinity.

The plant root is the first organ to encounter salinity stress, but the effect of salinity on root system architecture (RSA) remains elusive. Both the reduction in main root (MR) elongation and the redistribution of the root mass between MRs and lateral roots (LRs) are likely to play crucial roles in water extraction efficiency and ion exclusion. To establish which RSA parameters are responsive to salt stress, we performed a detailed time course experiment in which Arabidopsis (Arabidopsis thaliana) seedlings were grown on agar plates under different salt stress conditions. We captured RSA dynamics with quadratic growth functions (root-fit) and summarized the salt-induced differences in RSA dynamics in three growth parameters: MR elongation, average LR elongation, and increase in number of LRs. In the ecotype Columbia-0 accession of Arabidopsis, salt stress affected MR elongation more severely than LR elongation and an increase in LRs, leading to a significantly altered RSA. By quantifying RSA dynamics of 31 different Arabidopsis accessions in control and mild salt stress conditions, different strategies for regulation of MR and LR meristems and root branching were revealed. Different RSA strategies partially correlated with natural variation in abscisic acid sensitivity and different Na(+)/K(+) ratios in shoots of seedlings grown under mild salt stress. Applying root-fit to describe the dynamics of RSA allowed us to uncover the natural diversity in root morphology and cluster it into four response types that otherwise would have been overlooked.

Role of Na+, K+, Cl-, proline and sucrose concentrations in determining salinity tolerance and their correlation with the expression of multiple genes in tomato.

One of the major abiotic stresses affecting agriculture is soil salinity, which reduces crop yield and, consequently, revenue for farmers. Although tomato is an important agricultural species, elite varieties are poor at withstanding salinity stress. Thus, a feasible way of improving yield under conditions of salinity stress is to breed for improved salt tolerance. In this study, we analysed the physiological and genetic parameters of 23 tomato accessions in order to identify possible traits to be used by plant breeders to develop more tolerant tomato varieties. Although we observed a wide range of Na(+) concentrations within the leaves, stems and roots, the maintenance of growth in the presence of 100 mM NaCl did not correlate with the exclusion or accumulation of Na(+). Nor could we correlate the growth with accumulation of sugars and proline or with the expression of any gene involved in the homoeostasis of Na(+) in the plant. However, several significant correlations between gene expression and Na(+) accumulation were observed. For instance, Na(+) concentrations both in the leaves and stems were positively correlated with HKT1;2 expression in the roots, and Na(+) concentration measured in the roots was positively correlated with HKT1;1 expression also in the roots. Higher and lower Na(+) accumulation in the roots and leaves were significantly correlated with higher NHX3 and NHX1 expression in the roots, respectively. These results suggest that, in tomato, for a particular level of tolerance to salinity, a complex relationship between Na(+) concentration in the cells and tissue tolerance defines the salinity tolerance of individual tomato accessions. In tomato it is likely that tissue and salinity tolerance work independently, making tolerance to salinity depend on their relative effects rather than on one of these mechanisms alone.

Differences in shoot Na+ accumulation between two tomato species are due to differences in ion affinity of HKT1;2.

HKT1 has been shown to be essential in Na(+) homeostasis in plants. In this paper, we report the analysis of Na(+) accumulation in different plant organs of two tomato species with contrasting salt tolerances: Solanum lycopersicum and Solanum pennellii. Furthermore, we relate these differences in Na(+) accumulation between the two species to the differences in HKT1;2 transport kinetics and HKT1;2 expression. S. lycopersicum showed "Na(+) excluder" behaviour, whereas S. pennellii showed "Na(+) includer" behaviour. SlHKT1;2 expression, in contrast to SpHKT1;2 expression showed a significant effect of NaCl treatment, especially stems had a high increase in SlHKT1;2 expression. SlHKT1;2 promoter-GUS reporter gene analysis showed that SlHKT1;2 is expressed in the vasculature surrounding the roots and shoots of transformed Arabidopsis plants. In this paper, we present HKT1;2 protein sequences of both tomato species and provide evidence that both SlHKT1;2 and SpHKT1;2 are Na(+) transporters. Our kinetic studies showed that SpHKT1;2, in comparison with SlHKT1;2, had a lower affinity for Na(+). This low affinity of SpHKT1;2 correlated with higher xylem Na(+) and higher accumulation of Na(+) in stems and leaves of S. pennellii. Our findings demonstrate the importance of the understanding of transport characteristics of HKT1;2 transporters to improve the understanding of Na(+) homeostasis in plants.

Brassinosteroid biosynthesis and signalling in Petunia hybrida.

Brassinosteroids (BRs) are steroidal plant hormones that play an important role in the growth and development of plants. The biosynthesis of sterols and BRs as well as the signalling cascade they induce in plants have been elucidated largely through metabolic studies and the analysis of mutants in Arabidopsis and rice. Only fragmentary details about BR signalling in other plant species are known. Here a forward genetics strategy was used in Petunia hybrida, by which 19 families with phenotypic alterations typical for BR deficiency mutants were identified. In all mutants, the endogenous BR levels were severely reduced. In seven families, the tagged genes were revealed as the petunia BR biosynthesis genes CYP90A1 and CYP85A1 and the BR receptor gene BRI1. In addition, several homologues of key regulators of the BR signalling pathway were cloned from petunia based on homology with their Arabidopsis counterparts, including the BRI1 receptor, a member of the BES1/BZR1 transcription factor family (PhBEH2), and two GSK3-like kinases (PSK8 and PSK9). PhBEH2 was shown to interact with PSK8 and 14-3-3 proteins in yeast, revealing similar interactions to those during BR signalling in Arabidopsis. Interestingly, PhBEH2 also interacted with proteins implicated in other signalling pathways. This suggests that PhBEH2 might function as an important hub in the cross-talk between diverse signalling pathways.

Fatty acid export from the chloroplast. Molecular characterization of a major plastidial acyl-coenzyme A synthetase from Arabidopsis.

Acyl-coenzyme A (CoA) synthetases (ACSs, EC 6.2.1.3) catalyze the formation of fatty acyl-CoAs from free fatty acid, ATP, and CoA. Essentially all de novo fatty acid synthesis occurs in the plastid. Fatty acids destined for membrane glycerolipid and triacylglycerol synthesis in the endoplasmic reticulum must be first activated to acyl-CoAs via an ACS. Within a family of nine ACS genes from Arabidopsis, we identified a chloroplast isoform, LACS9. LACS9 is highly expressed in developing seeds and young rosette leaves. Both in vitro chloroplast import assays and transient expression of a green fluorescent protein fusion indicated that the LACS9 protein is localized in the plastid envelope. A T-DNA knockout mutant (lacs9-1) was identified by reverse genetics and these mutant plants were indistinguishable from wild type in growth and appearance. Analysis of leaf lipids provided no evidence for compromised export of acyl groups from chloroplasts. However, direct assays demonstrated that lacs9-1 plants contained only 10% of the chloroplast long-chain ACS activity found for wild type. The residual long-chain ACS activity in mutant chloroplasts was comparable with calculated rates of fatty acid synthesis. Although another isozyme contributes to the activation of fatty acids during their export from the chloroplast, LACS9 is a major chloroplast ACS.