Development and validation of a machine-learning prediction model to improve abdominal aortic aneurysm screening.

OBJECTIVE: Despite recommendations by the United States Preventive Services Task Force and the Society for Vascular Surgery, adoption of screening for abdominal aortic aneurysms (AAAs) remains low. One challenge is the low prevalence of AAAs in the unscreened population, and therefore a low detection rate for AAA screenings. We sought to use machine learning to identify factors associated with the presence of AAAs and create a model to identify individuals at highest risk for AAAs, with the aim of increasing the detection rate of AAA screenings. METHODS: A machine-learning model was trained using longitudinal medical records containing lab results, medications, and other data from our institutional database. A retrospective cohort study was performed identifying current or past smoking in patients aged 65 to 75 years and stratifying the patients by sex and smoking status as well as determining which patients had a confirmed diagnosis of AAA. The model was then adjusted to maximize fairness between sexes without significantly reducing precision and validated using six-fold cross validation. RESULTS: Validation of the algorithm on the single-center institutional data utilized 18,660 selected patients over 2 years and identified 314 AAAs. There were 41 factors identified in the medical record included in the machine-learning algorithm, with several factors never having been previously identified to be associated with AAAs. With an estimated 100 screening ultrasounds completed monthly, detection of AAAs is increased with a lift of 200% using the algorithm as compared with screening based on guidelines. The increased detection of AAAs in the model-selected individuals is statistically significant across all cutoff points. CONCLUSIONS: By utilizing a machine-learning model, we created a novel algorithm to detect patients who are at high risk for AAAs. By selecting individuals at greatest risk for targeted screening, this algorithm resulted in a 200% lift in the detection of AAAs when compared with standard screening guidelines. Using machine learning, we also identified several new factors associated with the presence of AAAs. This automated process has been integrated into our current workflows to improve screening rates and yield of high-risk individuals for AAAs.

Outcomes of Aortobifemoral Bypass Based on Configuration of the Proximal Anastomosis.

BACKGROUND: Aortobifemoral bypass (ABF) remains an important treatment modality in the revascularization of aortoiliac occlusive disease. Despite ABF being performed for decades, questions remain regarding the preferred technique for the proximal anastomosis, specifically whether an end-to-end (EE) or an end-to-side (ES) configuration is superior. The goal of this study was to compare the outcomes of ABF based on proximal configuration. METHODS: We queried the Vascular Quality Initiative registry for ABF procedures performed between 2009 and 2020. Univariate and multivariate logistic regression analyses were used to compare perioperative and 1-year outcomes between EE and ES configurations. RESULTS: Of the 6,782 patients (median [interquartile range] age, 60.0 [54-66 years]) who underwent ABF, 3,524 (52%) had an EE proximal anastomosis and 3,258 (48%) had an ES proximal anastomosis. Postoperatively, the ES cohort had a higher frequency of extubation in the operating room (80.3% vs. 77.4%; P < 0.01), lower change in renal function (8.8% vs. 11.5%; P < 0.01), and lower use of vasopressors (15.6% vs. 19.1%; P < 0.01), but higher rates of unanticipated return to the operating room (10.2% vs. 8.7%; P = 0.037) compared with the EE configuration. At 1-year follow-up, the ES cohort had a significantly lower primary graft patency rate (87.5% vs. 90.2%; P < 0.01) and higher rates of graft revision (4.8% vs. 3.1%; P < 0.01) and claudication symptoms (11.6% vs. 9.9%; P < 0.01). The ES configuration was significantly associated with a higher rate of 1-year major limb amputations in univariate (1.6% vs. 0.9%; P < 0.01) and multivariate (odds ratio, 1.95, confidence interval, 1.18-3.23, P=<0.01) analyses. CONCLUSIONS: While the ES cohort seemed to have less physiologic insult immediately postoperatively, the EE configuration appeared to have improved 1-year outcomes. To our knowledge, this study is one of the largest population-based studies comparing the outcomes of the proximal anastomotic configurations. Longer-term follow-up is needed to determine which configuration is optimal.

The Use of Paclitaxel-Coated Devices in the Treatment of Peripheral Arterial Disease is Not Associated With Increased Mortality or Amputations.

BACKGROUND: Strategies for the most effective treatment for peripheral arterial disease (PAD) remain controversial among clinicians. Several trials have shown improved primary patency of femoropopliteal interventions with the utilization of paclitaxel-coated balloons or stents compared to conventional balloons or stents. However, a 2018 meta-analysis suggested an increased mortality risk for patients receiving drug-coated balloons or stents (DCBS), resulting in an international pause in the use of DCBS. A 2021 meta-analysis by the same group suggested an increased risk of major amputation following DCBS use in peripheral arterial revascularization procedures. Here we report our long-term institutional outcomes comparing uncoated devices to DCBS. METHODS: A retrospective review of all patients who underwent peripheral arterial angioplasty, stenting, atherectomy, or a combination between 2011 and 2020 within a regional healthcare system was performed. Univariate, multivariate, and survival analyses were performed using standard statistical methods to assess the primary end points of overall survival, 5-year survival, and amputation-free survival. RESULTS: A total of 2,717 patients were identified, of whom 1,965 were treated with conventional uncoated devices and 752 were treated with DCBS. A univariate analysis showed that patients treated with non-DCBS had higher rates of overall mortality, major amputations, and mortality at 1, 3, and 5 years. A multivariable analysis demonstrated that the use of conventional devices, age, diabetes, chronic kidney disease, myocardial infarction, transient ischemic attack, warfarin use, and atrial fibrillation all significantly increased the risk of 5-year mortality, overall mortality, and combined mortality and/or amputation. CONCLUSIONS: DCBS are not associated with increased mortality or worse amputation-free survival in this real-world cohort of patients treated for PAD. Our data suggest that mortality is more closely linked with pre-existing patient comorbidities rather than device selection at the time of revascularization.

ER Bodies Are Induced by Pseudomonas syringae and Negatively Regulate Immunity.

ER bodies are endoplasmic reticulum-derived organelles present in plants belonging to the Brassicales order. In Arabidopsis thaliana, ER bodies are ubiquitous in cotyledons and roots and are present only in certain cell types in rosette leaves. However, both wounding and jasmonic acid treatment induce the formation of ER bodies in leaves. Formation of this structure is dependent on the transcription factor NAI1. The main components of the ER bodies are ß-glucosidases (BGLUs), enzymes that hydrolyze specialized compounds. In Arabidopsis, PYK10 (BGLU23) and BGLU18 are the most abundant ER body proteins. In this work, we found that ER bodies are downregulated as a consequence of the immune responses induced by bacterial flagellin perception. Arabidopsis mutants defective in ER body formation show enhanced responses upon flagellin perception and enhanced resistance to bacterial infections. Furthermore, the bacterial toxin coronatine induces the formation of de novo ER bodies in leaves and its virulence function is partially dependent on this structure. Finally, we show that performance of the polyphagous beet armyworm herbivore Spodoptera exigua increases in plants lacking ER bodies. Altogether, we provide new evidence for the role of the ER bodies in plant immune responses.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Role of a Preoperative Catheter Regimen in Achieving Early Primary Endoscopic Valve Ablation in Neonates with Posterior Urethral Valves.

PURPOSE: Primary valve ablation is preferred to vesicostomy in the initial management of posterior urethral valves. However, some neonates have a prohibitively small urethra. We describe our experience with a preoperative urethral catheter regimen to enhance the likelihood of neonatal valve ablation. MATERIALS AND METHODS: We performed a retrospective review of 126 neonates with posterior urethral valves treated between 2003 and 2019 with valve ablation prior to 10 weeks of age. The preoperative indwelling catheter either was gradually upsized to an 8Fr (progressive urethral dilation), was not upsized (nondilated) or was initially larger bore (8Fr only). The primary outcome was the ability to perform primary ablation by neonatal resectoscope. The secondary objective was to establish the parameters for considering progressive urethral dilation as well as its associated risks. RESULTS: Overall 97% could be ablated. The progressive urethral dilation group had the lowest mean weight (p <0.001). Only a larger catheter at the time of ablation was significantly associated with feasible ablation (p <0.001) and not urethral dilation, the infant's weight or his gestational age. Progressive urethral dilation was associated with a longer duration of catheterization as well as double the rate of febrile urinary tract infections (8.5%) over the nondilated group (3.6%). CONCLUSIONS: A much higher rate of primary ablation is feasible (97%) than previously reported (82%). More important than the infant's weight is whether a 6Fr to 8Fr catheter is in place at ablation. If an initial 6Fr to 8Fr catheter cannot be placed, urethral dilation to 8Fr should be performed before attempting ablation. This is both a technique and preoperative assessment that is useful for operative planning.

The combined use of thoracic and abdominal aortic stent grafts for endovascular repair of wide neck abdominal aortic aneurysms in high risk patients.

INTRODUCTION: Treatment of abdominal aortic aneurysms (AAA) with large (28 mm to 34 mm) and wide diameter (> 35 mm) necks remains a challenge in patients who are high-risk candidates for open repair. While several case reports describe the use of a thoracic stent graft in conjunction with a traditional modular bifurcated stent graft, most patients do not have the aortic length to accommodate such a configuration. We present our experience utilizing a distal unibody bifurcated aortic stent graft (Endologix, Irvine, CA) in conjunction with a proximal thoracic aortic stent graft (Medtronic, Minneapolis, MN) to treat wide-necked non-ruptured AAAs in patients who were otherwise poor candidates for open or fenestrated repair. METHODS: A single center retrospective review of patients treated with a combination of a distal unibody bifurcated aortic stent graft and a proximal thoracic aortic stent graft extension from 2013 to 2019 was performed. Demographics, perioperative details and long-term outcomes were collected and summarized. Standard statistical methods were utilized. RESULTS: We identified 7 patients who underwent this procedure during the study interval. Of these, all 7 (100%) were male with an average age of 69.1 ± 5.1 years. Average Charlson Comorbidity Index was 5.0. Average pre-operative maximum aortic and neck diameters were 57.9 mm (± 5.8) and 37.4 mm (± 4.5) respectively. All patients underwent repair with a distal 28 mm diameter unibody bifurcated aortic stent graft and proximal extension with a thoracic aortic stent graft that ranged from 40 to 46 mm in diameter. Technical success was achieved in all 7 patients. There were no perioperative mortalities or aorta-related deaths. Follow up was a mean of 1.98 years with a mean survival of 4.75 years (± 0.86). One patient required an aneurysm-related intervention for a late type III endoleak. CONCLUSION: The combined use of thoracic and abdominal aortic stent grafts is a safe and effective endovascular method to treat high-risk surgical candidates with wide-necked AAAs.

Defining Duplex Ultrasound Criteria for In-Stent Restenosis of the Superior Mesenteric Artery.

BACKGROUND: This study sought to define duplex ultrasound (DUS) velocity criteria predicting ≥70% stenosis in superior mesenteric artery (SMA) stents by correlating in-stent peak systolic velocity (PSV) with computed tomographic angiography (CTA) measurements of percent stenosis. METHODS: A retrospective review of 109 patients undergoing SMA stenting between 2003 and 2018 was conducted at a single institution. Thirty-seven surveillance duplex ultrasound studies were found to have a CTA performed within 30 days of study completion. Bare metal (n = 20) and covered stents (n = 17) were included. Velocities were paired to in-stent restenosis (ISR) measured by mean vessel diameter reduction on SMA centerline reconstructions from CTA. Receiver operating characteristic (ROC) curves was generated and logistic regression models for ≥70% ISR probability were used to define velocity criteria in the stented SMA. RESULTS: At a PSV of 300 cm/sec, the sensitivity is 100% and specificity 80% for a ≥70% in-stent SMA stenosis. At a PSV of 400 cm/sec, the sensitivity and positive predictive value (PPV) is 63% and the specificity and negative predictive value (NPV) is 90%. A PSV of 450 cm/sec was consistent with the highest specificity (100%) and PPV (100%) but lower sensitivity (50%) and NPV (87.9%). One patient with a PSV of 441 cm/sec on surveillance DUS died from complications of acute-on-chronic mesenteric ischemia. CONCLUSIONS: A PSV of 400 cm/sec on mesenteric DUS can predict ≥70% ISR with high sensitivity and should be considered as a diagnostic threshold for SMA in-stent restenosis.

Outcome of rectus femoris muscle flaps performed by vascular surgeons for the management of complex groin wounds after femoral artery reconstructions.

OBJECTIVE: Groin wound complications after femoral artery reconstructions are highly morbid and notoriously difficult to treat. Successful techniques include long-term antibiotic therapy, operative débridement, and muscle flap coverage. Historically, more complex muscle flap coverage, such as a rectus femoris muscle flap (RFF), has been performed by plastic and reconstructive surgeons. In this study, the experience of vascular surgeons performing RFF in the management of wound complications after femoral artery reconstructions is reported. METHODS: Clinical data between 2012 and 2018 were retrospectively analyzed. Data were summarized, and standard statistical analysis was performed. RESULTS: There were 23 patients who underwent 24 RFFs for coverage of complex groin wounds after femoral artery reconstructions. One of the 23 patients underwent bilateral RFFs. In this study cohort, patients had a median age of 67.5 years, and 79% (n = 19) were male. Median body mass index was 28.0 kg/m2, and 38% of patients were classified as obese on the basis of body mass index criteria. A history of tobacco use was present in 88%; however, only 29% were current smokers. Diabetes was present in 38% of patients and chronic kidney disease in 29%. Of the 24 RFFs, 14 (58%) were constructed in patients with reoperative groin surgery resulting in the need for muscle flap coverage. Femoral endarterectomy was the most common index procedure (46%), followed by infrainguinal leg bypass surgery (17%) and aortobifemoral bypass (17%). Grafts used during the original reconstruction included 12 bovine pericardial patches (50%), 6 Dacron grafts (25%), 4 PTFE grafts (17%), and 2 autogenous reconstructions (8%). Microbiology data identified 33% of patients (n = 8) to have gram-positive bacterial infections alone, 21% (n = 5) to have gram-negative infections alone, and 29% (n = 7) to have polymicrobial infections; 4 patients (13%) had negative intraoperative culture data. Median hospital stay after RFF was 8 days, and median follow-up time was 29.3 months. Major amputation was avoided in 20 of 24 limbs (83%) undergoing RFF. Eight patients underwent intentional graft or patch explantation (33%) before RFF, whereas 14 of the remaining 15 patients (93%) had successful salvage of the graft or patch after RFF. Two of the patients (13%) who underwent RFF with the intention of salvaging a prosthetic graft or patch required later graft excision. After RFF, 30-day and 1-year survival was 96% and 87%, respectively. CONCLUSIONS: RFF coverage of complex groin wounds after femoral artery reconstructions may safely be performed by vascular surgeons with excellent outcomes.

Outcomes of familial abdominal aortic aneurysm repair in the Vascular Quality Initiative.

OBJECTIVE: Recent investigations have reported increased rates of aneurysm-related complications after endovascular aneurysm repair (EVAR) in familial abdominal aortic aneurysm (fAAA) patients. The purpose of this study was to evaluate the outcomes of open aortic repair (OAR) and EVAR in sporadic AAA (spAAA) and fAAA patients in the Society for Vascular Surgery Vascular Quality Initiative. METHODS: This was a retrospective review of all AAA repairs in the Vascular Quality Initiative from 2003 to 2017. Patients' data were summarized, and standard statistical analysis was performed. Patients with known genetic syndromes and centers with long-term follow-up of <50% of patients were excluded. RESULTS: From 2003 to 2017, there were 1997 fAAA patients compared with 18,185 spAAA patients undergoing OAR and EVAR during the same study period. Compared with their spAAA counterparts, fAAA patients were younger (P < .001), were more likely to be living at home before surgery (P = .008), and demonstrated a lower incidence of coronary artery disease (P = .001) and hypertension (P = .039). Rates of smoking and end-stage renal disease did not differ between groups. However, fAAA patients were more likely to have aneurysmal degeneration of their iliac arteries (P < .001) and to undergo OAR (P < .001). When analyzing patients undergoing OAR, we found that fAAA patients were more likely to require concomitant renal bypass surgery (P = .012) but were extubated sooner (P = .005), received fewer blood transfusions (P < .001), and had a shorter length of stay (P = .018). Although individual complication rates did not differ between fAAA and spAAA groups after OAR, a composite end point of all early postoperative complications was decreased in fAAA patients (P = .020). When comparing fAAA and spAAA patients who underwent EVAR, we found a greater incidence of early lumbar branch endoleaks (type II) in fAAA patients; however, the rate of proximal type IA endoleaks (P = .279) and the rate of late reintervention for sac growth (P = .786), any endoleak (P = .439), or rupture (P = .649) did not differ between the groups. Whereas spAAA patients undergoing EVAR required longer postoperative intensive care unit stays (P < .001) and had a greater incidence of blood transfusions (P < .001), fAAA and spAAA patients had similar rates of postoperative complications (P = .510), 30-day mortality (P = .177), and long-term mortality (P = .259). CONCLUSIONS: This study shows that patients with a familial form of AAA do not have increased morbidity or mortality after AAA repair. Our findings suggest that EVAR and OAR are both safe and effective for fAAA patients. Further studies with longer follow-up are needed to best care for this unique cohort of patients.

Outcomes of endovascular treatments for in-stent restenosis in patients with mesenteric atherosclerotic disease.

OBJECTIVE: Mesenteric angioplasty and stenting (MAS) has surpassed open revascularization as the treatment of choice for mesenteric ischemia. Despite the lower perioperative mortality associated with MAS, the need for reintervention is not infrequent. The purpose of this study was to review the outcomes of patients treated for mesenteric artery in-stent restenosis (MAISR). METHODS: Clinical data from a single center between 2004 and 2017 were retrospectively analyzed. Standard statistical analysis including Kaplan-Meier estimate for time-dependent outcomes, χ2 test for categorical variables, and two-sample t-test for continuous variables was performed. Primary end points included stent patency and reintervention rate. Secondary end points included mortality and morbidity. RESULTS: During the study period, 91 patients underwent primary MAS. In total, 113 mesenteric vessels were treated with 20 covered stents and 93 bare-metal stents. Overall primary patency was 69% at 2 years. At 2 years, primary patency was 83% for covered stents compared with 65% for bare-metal stents (P = .17). Of these 91 primary MAS patients, 27 (30%) were treated for MAISR (32 vessels). Two covered stent patients developed significant restenosis (11%) compared with 25 (34%) bare-metal stent patients (P = .02). The mean age of patients requiring reintervention was 69 years (36% male), with the majority having a history of tobacco use (85%), hypertension (75%), and hyperlipidemia (78%). Fourteen reintervention patients (52%) presented with recurrent symptoms, 10 (37%) had asymptomatic restenosis, and 3 (11%) developed intestinal ischemia. Twelve patients (44%) underwent reintervention with balloon angioplasty alone and 15 (56%) underwent repeated stent placement. Of the 15 patients who had repeated stent placement, 7 patients had covered stents placed. The 30-day mortality rate after reintervention for mesenteric stent restenosis was 0%. Postoperative complications occurred in 15% of patients (myocardial infarction, 4%; reversible kidney injury, 4%; and bowel ischemia requiring surgical exploration, 7%). There was no difference in the perioperative morbidity in comparing symptomatic and asymptomatic patients undergoing reintervention. Mean follow-up after mesenteric reintervention was 31 months, with one-third of patients (n = 9) requiring another reintervention because of either recurrence of symptoms or asymptomatic high-grade restenosis. Assisted primary patency at 2 years was 92% after reintervention with balloon angioplasty and 87% for repeated stent placement, with no statistically significant difference between the groups (P = .66). CONCLUSIONS: Treatment of MAISR is associated with low mortality and acceptable morbidity. The initial use of covered stents may reduce the need for reintervention.

A systematic review and meta-analysis of bivalirudin application in peripheral endovascular procedures.

OBJECTIVE: The direct thrombin inhibitor bivalirudin (BIV) was shown to be superior to unfractionated heparin (UFH) in percutaneous coronary interventions for reducing procedural blood loss. The aim of this study was to compare outcome profiles of BIV and UFH in peripheral endovascular procedures (PEPs) by synthesizing the currently available data. METHODS: Following the PRISMA statement, we conducted a comprehensive literature search using Medline, Cochrane CENTRAL, PubMed, EMBASE, CINAHL Google scholar, and clinicaltrials.gov. We recruited randomized, controlled trials and well-conducted observational studies that compared UFH and BIV in PEPs requiring anticoagulation, excluding endovascular cardiac procedures and coronary interventions. Random-effects meta-analyses were conducted to compare the outcome profiles of these two agents. RESULTS: Thirteen articles containing 14 studies involving a total of 21,057 patients were enrolled. Of these, 2 were randomized controlled trials, 2 were prospective cohort studies, and 10 were retrospective studies. There were no significant differences between BIV and UFH in terms of procedural success rates, major and minor perioperative bleeding, transfusion, perioperative transient ischemic attack, or hemorrhagic strokes. However, compared with UFH, BIV had significantly lower odds ratios (OR) of perioperative mortality (OR, 0.58; 95% confidence interval [CI], 0.40-0.86), major adverse cardiovascular events (OR, 0.65; 95% CI, 0.51-0.83), net adverse clinical events (OR, 0.75; 95% CI, 0.63-0.88), perioperative myocardial infarction (OR, 0.73; 95% CI, 0.55-0.98), major vascular complications (OR, 0.59; 95% CI, 0.39-0.91), and minor vascular complications (OR, 0.58; 95% CI, 0.40-0.84). CONCLUSIONS: Compared with UFH, PEPs using BIV had comparable procedural success rates and odds of perioperative transient ischemic attack and hemorrhagic stroke. However, procedures with BIV had a lower but nonsignificant odds of perioperative bleeding and transfusion. Depending on the procedures conducted, the patients who received BIV will have reduced or comparable odds of perioperative mortality, myocardial infarction, major adverse cardiovascular events, net adverse clinical events, and major and minor vascular complications. Therefore, BIV may be chosen solely as an alternative procedural anticoagulant to UFH for PEPs.

Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.

RATIONALE: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. OBJECTIVE: To identify additional AAA risk loci using data from all available genome-wide association studies. METHODS AND RESULTS: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. CONCLUSIONS: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.

Genetic risk models: Influence of model size on risk estimates and precision.

Disease risk estimation plays an important role in disease prevention. Many studies have found that the ability to predict risk improves as the number of risk single-nucleotide polymorphisms (SNPs) in the risk model increases. However, the width of the confidence interval of the risk estimate is often not considered in the evaluation of the risk model. Here, we explore how the risk and the confidence interval width change as more SNPs are added to the model in the order of decreasing effect size, using both simulated data and real data from studies of abdominal aortic aneurysms and age-related macular degeneration. Our results show that confidence interval width is positively correlated with model size and the majority of the bigger models have wider confidence interval widths than smaller models. Once the model size is bigger than a certain level, the risk does not shift markedly, as 100% of the risk estimates of the one-SNP-bigger models lie inside the confidence interval of the one-SNP-smaller models. We also created a confidence interval-augmented reclassification table. It shows that both more effective SNPs with larger odds ratios and less effective SNPs with smaller odds ratios contribute to the correct decision of whom to screen. The best screening strategy is selected and evaluated by the net benefit quantity and the reclassification rate. We suggest that individuals whose upper bound of their risk confidence interval is above the screening threshold, which corresponds to the population prevalence of the disease, should be screened.

A Cysteine-Rich Protein Kinase Associates with a Membrane Immune Complex and the Cysteine Residues Are Required for Cell Death.

Membrane-localized proteins perceive and respond to biotic and abiotic stresses. We performed quantitative proteomics on plasma membrane-enriched samples from Arabidopsis (Arabidopsis thaliana) treated with bacterial flagellin. We identified multiple receptor-like protein kinases changing in abundance, including cysteine (Cys)-rich receptor-like kinases (CRKs) that are up-regulated upon the perception of flagellin. CRKs possess extracellular Cys-rich domains and constitute a gene family consisting of 46 members in Arabidopsis. The single transfer DNA insertion lines CRK28 and CRK29, two CRKs induced in response to flagellin perception, did not exhibit robust alterations in immune responses. In contrast, silencing of multiple bacterial flagellin-induced CRKs resulted in enhanced susceptibility to pathogenic Pseudomonas syringae, indicating functional redundancy in this large gene family. Enhanced expression of CRK28 in Arabidopsis increased disease resistance to P. syringae Expression of CRK28 in Nicotiana benthamiana induced cell death, which required intact extracellular Cys residues and a conserved kinase active site. CRK28-mediated cell death required the common receptor-like protein kinase coreceptor BAK1. CRK28 associated with BAK1 as well as the activated FLAGELLIN-SENSING2 (FLS2) immune receptor complex. CRK28 self-associated as well as associated with the closely related CRK29. These data support a model where Arabidopsis CRKs are synthesized upon pathogen perception, associate with the FLS2 complex, and coordinately act to enhance plant immune responses.

Long-term comparative effectiveness of carotid stenting versus carotid endarterectomy in a large tertiary care vascular surgery practice.

OBJECTIVE: Carotid interventional trials have strict inclusion and exclusion criteria that make translation of their results to the real-world population challenging. Furthermore, the specialty of the operating surgeon and the role of clinical decision-making are not well studied. This study compares the effectiveness of carotid endarterectomy (CEA) vs carotid artery stenting (CAS) in a real-world setting when the procedure is performed by fellowship-trained vascular surgeons. METHODS: A retrospective study was conducted of all consecutive patients undergoing CEA and CAS performed by vascular surgeons in a large rural tertiary health care system from 2004 to 2014. Postoperative outcomes of stroke, acute myocardial infarction (AMI), and death were analyzed at 30 days and during the long term (median follow-up of 5.5 years for CEA and 4.8 years for CAS). Standard statistical analysis was performed. Differences in long-term outcomes were expressed as cumulative incidence functions for nondeath outcomes (stroke and AMI), which account for the high death rate in this population of vascular patients, and as Kaplan-Meier curves for death itself. RESULTS: From January 1, 2004, through December 31, 2014, there were 2331 carotid interventions performed (CEA, 1853; CAS, 478), all by fellowship-trained vascular surgeons. The average age of the patients was 71 years, and 63% were male, with more men in the CAS group (61.5% vs 67.8%; P = .011). Preoperatively, 30% of patients were symptomatic, and 77% of patients had high-grade stenosis in the 70% to 99% range. CEA patients were more likely to have preoperative hypertension (89.7% vs 86.2%; P = .029) and were less likely to have a history of cardiovascular disease (53.4% vs 59.4%; P = .018). There were no significant differences in 30-day outcomes between CEA and CAS (stroke, 1.1% vs 1.3% [P = .743]; AMI, 2.2% vs 1.7% [P = .474]; death, 0.7% vs 0.6% [P = .859]) or long-term outcomes (stroke, 6.8% vs 7.7% [P = .321]; AMI, 22.7% vs 21.0% [P = .886]; death, 28.4% vs 28.2% [P = .122]). CONCLUSIONS: The short- and long-term outcomes after CEA vs CAS are similar when the procedure is performed in a real-world setting by fellowship-trained vascular surgeons.

Nurses' moral experiences of assisted death: A meta-synthesis of qualitative research.

BACKGROUND:: Legislative changes are resulting in assisted death as an option for people at the end of life. Although nurses' experiences and perspectives are underrepresented within broader ethical discourses about assisted death, there is a small but significant body of literature examining nurses' experiences of caring for people who request this option. AIM:: To synthesize what has been learned about nurses' experiences of caring for patients who request assisted death and to highlight what is morally at stake for nurses who undertake this type of care. DESIGN:: Qualitative meta-synthesis. METHODS:: Six databases were searched: CINAHL, Medline, EMBASE, Joanna Briggs Institute, PsycINFO, and Web of Science. The search was completed on 22 October 2014 and updated in February 2016. Of 879 articles identified from the database searches, 16 articles were deemed relevant based on inclusion criteria. Following quality appraisal, 14 studies were retained for analysis and synthesis. RESULTS:: The moral experience of the nurse is (1) defined by a profound sense of responsibility, (2) shaped by contextual forces that nurses navigate in everyday end-of-life care practice, and (3) sustained by intra-team moral and emotional support. DISCUSSION:: The findings of this synthesis support the view that nurses are moral agents who are deeply invested in the moral integrity of end-of-life care involving assisted death. The findings further demonstrate that to fully appreciate the ethics of assisted death from a nursing standpoint, it is necessary to understand the broader constraints on nurses' moral agency that operate in everyday end-of-life care. ETHICAL CONSIDERATIONS:: Research ethics board approval was not required for this synthesis of previously published literature. CONCLUSION:: In order to understand how to enact ethical practice in the area of assisted death, the moral experiences of nurses should be investigated and foregrounded.

Bacterial AvrRpt2-Like Cysteine Proteases Block Activation of the Arabidopsis Mitogen-Activated Protein Kinases, MPK4 and MPK11.

To establish infection, pathogens deliver effectors into host cells to target immune signaling components, including elements of mitogen-activated protein kinase (MPK) cascades. The virulence function of AvrRpt2, one of the first identified Pseudomonas syringae effectors, involves cleavage of the plant defense regulator, RPM1-INTERACTING PROTEIN4 (RIN4), and interference with plant auxin signaling. We show now that AvrRpt2 specifically suppresses the flagellin-induced phosphorylation of Arabidopsis (Arabidopsis thaliana) MPK4 and MPK11 but not MPK3 or MPK6. This inhibition requires the proteolytic activity of AvrRpt2, is associated with reduced expression of some plant defense genes, and correlates with enhanced pathogen infection in AvrRpt2-expressing transgenic plants. Diverse AvrRpt2-like homologs can be found in some phytopathogens, plant-associated and soil bacteria. Employing these putative bacterial AvrRpt2 homologs and inactive AvrRpt2 variants, we can uncouple the inhibition of MPK4/MPK11 activation from the cleavage of RIN4 and related members from the so-called nitrate-induced family as well as from auxin signaling. Thus, this selective suppression of specific mitogen-activated protein kinases is independent of the previously known AvrRpt2 targets and potentially represents a novel virulence function of AvrRpt2.

Patency and limb salvage after femoral endarterectomy and iliac stenting are not affected by severity of iliac disease.

OBJECTIVE: The hybrid procedure of femoral endarterectomy and iliac artery stenting (FEIS) has been used as an alternative to traditional open surgical repair of iliofemoral arterial occlusive disease, but whether the severity of the iliac disease component affects long-term results is not well understood. METHODS: This was a retrospective cohort study of patients undergoing FEIS at Geisinger Health System from January 1, 2004, through December 31, 2013, for the treatment of symptomatic iliofemoral atherosclerotic occlusive disease. The cohort was stratified according to the severity of the iliac occlusive disease component into patients with mild iliac disease (group 1) and patients with severe iliac disease (group 2). RESULTS: Between January 1, 2004, and December 31, 2013, 99 patients underwent 111 total FEIS procedures. The mean age of the cohort was 67.4 years. Men composed 61% of patients. Indications for surgery were claudication (41%), ischemic rest pain (36%), and tissue loss (23%). At 5 years of follow-up, there was no difference in primary patency (73% in group 1 vs 68% in group 2 [P = .67]) and limb salvage (90% in group 1 vs 92% in group 2 [P = .51]). There was a trend toward higher overall mortality in group 2 patients vs group 1 patients (53% vs 81%; P = .08), but this did not reach statistical significance. Univariate analysis did not identify any device-related or anatomic factors predictive of patency. CONCLUSIONS: When combined iliofemoral arterial occlusive disease is treated with FEIS, the severity of the iliac disease component does not affect long-term patency or limb salvage.

Engaging with patients who desire death: Interpretation, presence, and constraint.

Canadian end-of-life care is changing. Given recent legislative changes concerning assisted death (euthanasia and assisted suicide), it is vital to examine the perspectives of nurses regarding their care of patients who want to die. This qualitative descriptive study reports findings from interviews with 11 oncology nurses about their experiences of engaging with patients who desire death. Findings provide important insights about how oncology nurses interpret patients' desire-for-death and enact therapeutic presence with these patients. Findings further speak to contextual forces that constrain therapeutic engagement. Interviews were conducted before laws changed in Canada, generating insights that are relevant now more than ever, as increasing numbers of patients will contemplate and receive assisted death in the new landscape of Canadian end-of-life care.