Francis Crick: A Singular Approach to Scientific Discovery.

Francis' office window (at the Salk) commanded a panorama of the Pacific. "This grand natural scene was a physical correlate of Francis's intellectual world: wide-ranging, brilliantly lit, a little overawing, but also immensely inviting and above all an exciting place to be." (Mitchison, 2004).

A bioenergy-focused versus a reforestation-focused mitigation pathway yields disparate carbon storage and climate responses.

Limiting global warming to 2 °C requires urgent action on land-based mitigation. This study evaluates the biogeochemical and biogeophysical implications of two alternative land-based mitigation scenarios that aim to achieve the same radiative forcing. One scenario is primarily driven by bioenergy expansion (SSP226Lu-BIOCROP), while the other involves re/afforestation (SSP126Lu-REFOREST). We find that overall, SSP126Lu-REFOREST is a more efficient strategy for removing CO2 from the atmosphere by 2100, resulting in a net carbon sink of 242 ~ 483 PgC with smaller uncertainties compared to SSP226Lu-BIOCROP, which exhibits a wider range of -78 ~ 621 PgC. However, SSP126Lu-REFOREST leads to a relatively warmer planetary climate than SSP226Lu-BIOCROP, and this relative warming can be intensified in certain re/afforested regions where local climates are not favorable for tree growth. Despite the cooling effect on a global scale, SSP226Lu-BIOCROP reshuffles regional warming hotspots, amplifying summer temperatures in vulnerable tropical regions such as Central Africa and Southeast Asia. Our findings highlight the need for strategic land use planning to identify suitable regions for re/afforestation and bioenergy expansion, thereby improving the likelihood of achieving the intended climate mitigation outcomes.

An exciting period of Drosophila developmental biology: Of imaginal discs, clones, compartments, parasegments and homeotic genes.

In this review we recall a number of important discoveries that took place in Drosophila during the seventies and eighties of the last century. The development of cell lineage methods and of powerful modifications of same, such as the Minute technique, led to the discovery of compartments and provided a clearer picture of the body organization: that came to be seen as a chain of metameric lineage units along the A/P body axis. Further, genetic screens allowed the identification of the genes involved in the establishment of the metameric scaffold - the segmentation genes- and also of Hox genes that are responsible for the specific development of individual body parts. As cloning methods became available, many of the most relevant of these developmental genes were cloned and a molecular analysis of development initiated. The discovery of the homeobox, a molecular mark of Hox and other relevant developmental genes, allowed the finding of Hox genes in animal species, like humans, in which they could not be identified by genetic methods. Analysis of the structure and function of Hox genes provided a general image of the genetic design of the metazoan body.

Factors associated with successful median arcuate ligament release in an international, multi-institutional cohort.

OBJECTIVE: Prior research on median arcuate ligament syndrome has been limited to institutional case series, making the optimal approach to median arcuate ligament release (MALR) and resulting outcomes unclear. In the present study, we compared the outcomes of different approaches to MALR and determined the predictors of long-term treatment failure. METHODS: The Vascular Low Frequency Disease Consortium is an international, multi-institutional research consortium. Data on open, laparoscopic, and robotic MALR performed from 2000 to 2020 were gathered. The primary outcome was treatment failure, defined as no improvement in median arcuate ligament syndrome symptoms after MALR or symptom recurrence between MALR and the last clinical follow-up. RESULTS: For 516 patients treated at 24 institutions, open, laparoscopic, and robotic MALR had been performed in 227 (44.0%), 235 (45.5%), and 54 (10.5%) patients, respectively. Perioperative complications (ileus, cardiac, and wound complications; readmissions; unplanned procedures) occurred in 19.2% (open, 30.0%; laparoscopic, 8.9%; robotic, 18.5%; P < .001). The median follow-up was 1.59 years (interquartile range, 0.38-4.35 years). For the 488 patients with follow-up data available, 287 (58.8%) had had full relief, 119 (24.4%) had had partial relief, and 82 (16.8%) had derived no benefit from MALR. The 1- and 3-year freedom from treatment failure for the overall cohort was 63.8% (95% confidence interval [CI], 59.0%-68.3%) and 51.9% (95% CI, 46.1%-57.3%), respectively. The factors associated with an increased hazard of treatment failure on multivariable analysis included robotic MALR (hazard ratio [HR], 1.73; 95% CI, 1.16-2.59; P = .007), a history of gastroparesis (HR, 1.83; 95% CI, 1.09-3.09; P = .023), abdominal cancer (HR, 10.3; 95% CI, 3.06-34.6; P < .001), dysphagia and/or odynophagia (HR, 2.44; 95% CI, 1.27-4.69; P = .008), no relief from a celiac plexus block (HR, 2.18; 95% CI, 1.00-4.72; P = .049), and an increasing number of preoperative pain locations (HR, 1.12 per location; 95% CI, 1.00-1.25; P = .042). The factors associated with a lower hazard included increasing age (HR, 0.99 per increasing year; 95% CI, 0.98-1.0; P = .012) and an increasing number of preoperative diagnostic gastrointestinal studies (HR, 0.84 per study; 95% CI, 0.74-0.96; P = .012) Open and laparoscopic MALR resulted in similar long-term freedom from treatment failure. No radiographic parameters were associated with differences in treatment failure. CONCLUSIONS: No difference was found in long-term failure after open vs laparoscopic MALR; however, open release was associated with higher perioperative morbidity. These results support the use of a preoperative celiac plexus block to aid in patient selection. Operative candidates for MALR should be counseled regarding the factors associated with treatment failure and the relatively high overall rate of treatment failure.

Outcomes of Median Arcuate Ligament Release: A Single Institution Retrospective Review.

BACKGROUND: Median arcuate ligament syndrome (MALS) is an uncommon diagnosis that is often associated with variable clinical presentation and inconsistent response to treatment. Due to the nature of MALS, the optimal treatment modality and predictors of outcomes remain unclear. METHODS: A retrospective review was performed of all median arcuate ligament release (MALR) procedures at a single academic institution between 2000 and 2020. Variables examined included patient demographics, symptom characteristics, operative technique (open, robotic, laparoscopic), patient symptoms before release, symptom relief within 1 year, and recurrence of symptoms between release and last clinical follow-up. RESULTS: During the study period, 47 patients (75% female, mean age 42.1 years) underwent MALR with 19 (36%) robotic, 18 (34%) open, 14 (26%) laparoscopic, and 2 (4%) laparoscopic converted to open procedures. Abdominal pain, weight loss, and nausea and vomiting were the most common symptoms. Postoperatively, 19 (40%) had complete symptom relief within 1 year, 18 (38%) had partial relief, and 10 (21%) had no symptom improvement. 6 were excluded due to loss of follow-up. Laparoscopic and open procedures had the highest rate of complete symptom relief by year 1 with 7 (58%) and 8 (50%) respectively. Twenty-one (57%) patients had recurrence with the greatest rate of recurrence seen among laparoscopic (80%), compared to robotic (57%) and open (38%). Patients reporting a weight loss of 20 pounds or more before surgery were more likely to have partial or complete symptom relief after 1 year compared to those reporting less than 20-pound weight loss (92% vs. 64%). Furthermore, 84% of patients younger than 60 years old reported partial or complete symptom relief compared to only 56% of those older than 60. CONCLUSIONS: MALS continues to be a rare disorder with widely variable surgical outcomes, requiring further study. While our patients presented with several gastrointestinal symptoms, the most common was postprandial pain. Our center employed laparoscopic, open, and robotic operative techniques with varying success rates, in terms of symptom relief and recurrence. Consistent with current literature, our study found greater surgical success among patients younger than 60 years regardless of operative technique. This suggests the need for better predictors to determine which patients are the most likely to have complete or prolonged remission of symptoms following MALR.

Mechanochemical Endovenous Ablation of the Saphenous Vein: A Look at Contemporary Outcomes.

BACKGROUND: Endovenous ablation techniques have replaced greater saphenous vein (GSV) ligation and stripping for treatment of venous insufficiency. Our objective was to investigate our initial procedural experience and clinical presentation of patients undergoing mechanochemical ablation (MOCA) at a single institution. We hypothesized that closure level and success rate improved over time and were comparable to other endovenous ablation techniques. METHODS: We retrospectively reviewed all MOCA procedures performed at the Greater Los Angeles Veterans Affairs Hospital from 2015 - 2020. Variables included CEAP and VCSS scores, patient symptoms, post procedure duplex ultrasound, closure level, and need for anticoagulation. Success was defined as GSV thrombosis on initial post procedure duplex ultrasound. Procedure associated extension of thrombus into the deep veins was defined using the American Venous Forum (AVF) endothermal heat induced thrombosis (EHIT) classification. RESULTS: 104 venous ablation procedures were performed on 86 patients. Eleven (12.8%) patients received bilateral interventions, and six (7%) patients had asynchronous interventions on the same leg. The average age was 58.4 years (SD 12) and 93% were male. Pre-procedural symptoms included pain (102, 98.1%), varicose veins (87, 83.7%), edema (58, 55.8%), and active ulcers (19, 18.3%). A CEAP category of C2 was the most common indication (34.6%), followed by C3 (22.1%) and C6 (21.2%). Forty-five (43.2%) patients had deep system reflux, and 53% had concomitant phlebectomies. Average VCSS score was 7.5 (SD 3.5).We observed a GSV ablation rate of 92.7% (n = 89) in the 96 procedures which had post-procedure follow up, with no temporal evidence of a learning curve. On post procedure duplex of the 89 technically successful ablations, 77 (86.5%) patients had AVF EHIT level 1 closure, three (3.4%) had level 2 closure, eight (8.9%) had level 3 closure, and one had a level 4 closure. Fourteen (15.7%) patients were newly started on anticoagulation for an average of 33.2 days (SD 34.1). Of the 19 legs treated for active venous ulcers, 13 (68.4%) had improvement or resolution of their venous ulcers. No pulmonary embolic complications were reported. CONCLUSIONS: We observed a successful GSV thrombosis rate of 92.7% using MOCA without evidence of a learning curve and comparable to that reported in the literature. The rate of thrombus extension into the deep veins was 14.6%, with no adverse effects associated with anticoagulation or clinically significant sequelae of AVF EHIT level 2 or greater. Comparisons with MOCA associated thrombus extension into deep veins in the literature are limited as post procedure screening duplex are not standard of care. However, we demonstrated that MOCA ablation of the GSV is a safe procedure that may be performed with good technical success.

The association between maternal perinatal mental health and perfectionism: A systematic review and meta-analysis.

BACKGROUND: Perfectionism is an important feature of adult psychopathology. In the absence of a prior review of the role of perfectionism in perinatal psychopathology, we aimed to ascertain whether perfectionism was associated with symptoms of maternal perinatal depression and anxiety. METHOD: We followed PRISMA guidance (PROSPERO: 42019143369), estimated weighted effect sizes and tested possible moderators: timing (pre or post- natal), scales used to measure constructs, infant gender, temperament and age; and rated study quality. RESULTS: Fourteen studies met eligibility criteria. Perfectionism as a whole, and the perfectionistic concerns dimension, were moderately correlated with common maternal perinatal mental health difficulties r = .32 (95% Confidence Interval = 0.23 to 0.42). In sub-group analyses, perfectionistic concerns were associated with depression (r = .35, 95% CI = 0.26-0.43). We found no evidence of significant moderation of associations. LIMITATIONS: Included studies had methodological and conceptual limitations. All studies examined depression and two examined anxieties; all examined perfectionistic concerns and four examined perfectionist strivings. CONCLUSIONS: Perfectionism, namely perfectionistic concerns, is potentially associated with common maternal perinatal mental health problems. While further research is warranted, identification of perfectionism in the perinatal period may help focus resources for intervention, reducing the prevalence of perinatal mental health difficulties.

Planar cell polarity: two genetic systems use one mechanism to read gradients.

Our aim in this short Primer is to explain the principles of planar cell polarity (PCP) in animal development. The literature in this small field is complex and specialized, but we have extracted a simple and central story from it. We explain our hypothesis that polarity, initially cued by the direction of slope of a multicellular gradient, is interpreted at the cellular level so that each cell becomes molecularly polarised. The mechanism involves a comparison between a cell and its neighbours. To achieve this comparison there are (at least) two disparate and independent molecular systems, each depending on molecular bridges that span between neighbouring cells. Even though the two systems are made up of different molecules, we argue that both systems function in a logically equivalent way.

Planar cell polarity: the prickle gene acts independently on both the Ds/Ft and the Stan/Fz systems.

Epithelial cells are polarised within the plane of the epithelium, forming oriented structures that have a coordinated and consistent polarity (planar cell polarity, PCP). In Drosophila, at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the 'core' or Starry night/Frizzled system. Here, we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Starry night/Frizzled system. We investigate whether this view is correct and how the prickle gene relates to the two systems. We find that prickle can affect, separately, both systems; however, neither Prickle nor Spiny leg are essential components of the Dachsous/Fat or the Starry night/Frizzled system, nor do they act as a functional link between the two systems.

Artificial shorelines lack natural structural complexity across scales.

From microbes to humans, habitat structural complexity plays a direct role in the provision of physical living space, and increased complexity supports higher biodiversity and ecosystem functioning across biomes. Coastal development and the construction of artificial shorelines are altering natural landscapes as humans seek socio-economic benefits and protection from coastal storms, flooding and erosion. In this study, we evaluate how much structural complexity is missing on artificial coastal structures compared to natural rocky shorelines, across a range of spatial scales from 1 mm to 10 s of m, using three remote sensing platforms (handheld camera, terrestrial laser scanner and uncrewed aerial vehicles). Natural shorelines were typically more structurally complex than artificial ones and offered greater variation between locations. However, our results varied depending on the type of artificial structure and the scale at which complexity was measured. Seawalls were deficient at all scales (approx. 20-40% less complex than natural shores), whereas rock armour was deficient at the smallest and largest scales (approx. 20-50%). Our findings reinforce concerns that hardening shorelines with artificial structures simplifies coastlines at organism-relevant scales. Furthermore, we offer much-needed insight into how structures might be modified to more closely capture the complexity of natural rocky shores that support biodiversity.

Endovascular interventions for claudication do not meet minimum standards for the Society for Vascular Surgery efficacy guidelines.

OBJECTIVE: Because the treatment of intermittent claudication (IC) is elective, good short- and long-term outcomes are imperative. The objective of the present study was to examine the outcomes of endovascular management of IC reported in the Vascular Quality Initiative and compare them with the Society for Vascular Surgery guidelines for IC treatment to determine whether real-world results are within the guidelines. METHODS: Patients undergoing peripheral vascular intervention for IC from 2004 to 2017 with complete data and >9 month follow-up were included. The primary outcome measures were IC recurrence and repeat procedures performed ≤2 years after the initial treatment. RESULTS: A total of 16,152 patients met the inclusion criteria, with a mean age of 66 years. Of the 16,152 patients, 61% were men, 45% were current smokers, and 28% had been discharged without antiplatelet or statin medication. Adjusted analyses revealed that treatment of more than two arteries was associated with a shorter time to IC recurrence (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.09-1.31) and a shorter time to repeat procedures (HR, 1.25; 95% CI, 1.09-1.45). The use of atherectomy was also associated with a shorter time to IC recurrence (HR, 1.29; 95% CI, 1.08-1.33) and a shorter time to repeat procedures (HR, 1.31; 95% CI, 1.13-1.52). Discharge with antiplatelet and statin medications was associated with a longer time to IC recurrence (HR, 0.84; 95% CI, 0.78-0.91) and a longer time to repeat procedures (HR, 0.77; 95% CI, 0.69-0.87). Life-table analysis at 2 years revealed that only 32% of patients were free from IC recurrence, although 76% had not undergone repeat procedures. Stratified by anatomic treatment level, 37% of isolated aortoiliac interventions, 22% of aortoiliac and femoropopliteal interventions, 30% of isolated femoropopliteal interventions, and 20% of femoropopliteal and tibial interventions had remained free from IC recurrence at 2 years. CONCLUSIONS: Most patients treated with an endovascular approach to IC did not meet the Society for Vascular Surgery guidelines for long-term freedom from recurrent symptoms of >50% at 2 years. Many lacked preprocedure optimization of medical management. The use of atherectomy and treatment of more than two arteries were associated with poor outcomes after peripheral vascular intervention for IC, because only 32% of these patients were free from recurrent symptoms at 2 years. Even when risk factor modification is optimized before the procedure, vascular specialists should be aware of the association between atherectomy and multivessel interventions with poorer long-term outcomes and counsel patients appropriately before intervention.

Surgeon Factors Have a Larger Effect on Vascular Access Type and Outcomes than Patient Factors.

BACKGROUND AND OBJECTIVES: Though patient factors are frequently linked to hemodialysis vascular access selection and outcomes, variability by surgeon and surgeon specialty may play a role as well. The objective of this study is to examine the extent to which individual surgeons influence selection of vascular access type, removal of tunneled hemodialysis catheter (THC), and repeat vascular access. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A national claims database was used to identify patients initiating hemodialysis via a THC between 2011 and 2017. Likelihood of repeat AVF/AVG was analyzed using mixed-effects logistic regression. Time from initial arteriovenous fistula (AVF)/graft (AVG) to THC removal and time to repeat AVF/AVG were analyzed using Weibull proportional hazard models. Individual surgeon identifier served as the random effect in all models. RESULTS: 6,908 AVF/AVG met the inclusion criteria: 5366 (78%) AVF and 1,542 (22%) AVG. Surgeon specialty only had a significant influence on access type, with vascular surgeons having 26% greater odds of performing AVG compared to general surgeons (P = 0.006). Relative to the other independent variables, individual surgeon identifier had the greatest magnitude of effect on access type (median odds ratio, 2.36; 95% CI, 2.09-2.72). Individual surgeon identifier had the second greatest magnitude of effect likelihood of THC removal (median hazard ratio, 1.66; 95% CI, 1.58-1.77) and second access (median hazard ratio, 1.83; 95% CI, 1.66-2.05), in both cases second only to the effect of AVG, which was associated with greater likelihood of THC removal (hazard ratio 1.91; 95% CI, 1.77-2.07) and lower likelihood of second access (hazard ratio 0.44; 95% CI, 0.38-0.52). CONCLUSION: Individual surgeons are associated with greater variation in vascular access type and likelihood of repeat access than surgeon specialty and measurable patient demographics/co-morbidities. Future research should focus on identifying which surgeon factors are associated with improved outcomes.

Emergent Freshwater Insects Serve as Subsidies of Methylmercury and Beneficial Fatty Acids for Riparian Predators Across an Agricultural Gradient.

Aquatic-to-terrestrial subsidies have the potential to provide riparian consumers with benefits in terms of physiologically important organic compounds like omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs). However, they also have a "dark side" in the form of exposure to toxicants such as mercury. Human land use intensity may also determine whether subsidies provide benefits or come at a cost for riparian predators. We sampled insects as well as Eastern Phoebe (Sayornis phoebe) chicks in 2015-2016 within the southern Finger Lakes region to understand how food quality, in terms of n-3 LCPUFAs and methylmercury (MeHg), of emergent freshwater insects compared with that of terrestrial insects and how land use affected the quality of prey, predator diet composition, and MeHg exposure. Across the landscape, freshwater insects had a significantly higher percentage of the n-3 LCPUFA eicosapentaenoic acid (EPA) compared to terrestrial insects and contained significantly more MeHg than terrestrial insects did. In spite of differences in MeHg concentrations between aquatic and terrestrial insects, chick MeHg concentrations were not related to diet composition. Instead, chick MeHg concentrations increased with several metrics of human land use intensity, including percent agriculture. Our findings suggest that freshwater subsidies provide predators with both risks and benefits, but that predator MeHg exposure can vary with human land use intensity.

Trainee Experience in Simulation-Based Education of Open Vascular Surgery.

BACKGROUND: Simulation continues to be an important adjunct to vascular surgery training, yet the optimal implementation of simulation to complement conventional surgical training continues to evolve. This study aims to find areas for improvement in current simulation-based training of open vascular skills by characterizing the experience of vascular trainees attending a national simulation-based course. METHOD: This was a survey study conducted at the simulation course of the Annual UCLA/SVS Symposium: A Comprehensive Review and Update of What's New in Vascular and Endovascular Surgery, a national vascular surgery meeting. The survey consisted of 17 questions and was administered on paper or electronically via the Audience Response System, before the start of the course. The survey assessed the participants' experience in formal training, simulation training, and comfort with open surgical procedures. RESULTS: Between 2013 and 2018, the survey was completed by 150 participants of which 65% were vascular fellows. Only 48% of the participants had formal training in suturing and surgical instruments. Most participants had formal training in basic vascular techniques and advanced vascular operations. In 71%, simulation was incorporated into basic technique training and 60% in open surgical training. Simulation training was most commonly utilized in learning anastomotic techniques and open abdominal aortic aneurysm repair. Simulation skills were deemed translatable to the operating room by 59% of participants. Most participants were comfortable performing open vascular procedures. However, 68% of participants were uncomfortable performing an abdominal aortic aneurysm repair. CONCLUSIONS: There continues to be a significant portion of trainees who do not undergo a simulation-based education. Current simulation training is being targeted to meet trainee needs in open vascular surgery, specifically open aneurysm repair. Nonetheless, trainees continue to have doubts regarding applicability of simulation-based skills to the operating theater. Further studies investigating access to simulation education as well as its translatability are needed.

Why do children and adolescents (not) seek and access professional help for their mental health problems? A systematic review of quantitative and qualitative studies.

Mental health disorders in children and adolescents are highly prevalent yet undertreated. A detailed understanding of the reasons for not seeking or accessing help as perceived by young people is crucial to address this gap. We conducted a systematic review (PROSPERO 42018088591) of quantitative and qualitative studies reporting barriers and facilitators to children and adolescents seeking and accessing professional help for mental health problems. We identified 53 eligible studies; 22 provided quantitative data, 30 provided qualitative data, and one provided both. Four main barrier/facilitator themes were identified. Almost all studies (96%) reported barriers related to young people's individual factors, such as limited mental health knowledge and broader perceptions of help-seeking. The second most commonly (92%) reported theme related to social factors, for example, perceived social stigma and embarrassment. The third theme captured young people's perceptions of the therapeutic relationship with professionals (68%) including perceived confidentiality and the ability to trust an unknown person. The fourth theme related to systemic and structural barriers and facilitators (58%), such as financial costs associated with mental health services, logistical barriers, and the availability of professional help. The findings highlight the complex array of internal and external factors that determine whether young people seek and access help for mental health difficulties. In addition to making effective support more available, targeted evidence-based interventions are required to reduce perceived public stigma and improve young people's knowledge of mental health problems and available support, including what to expect from professionals and services.

Intrusive imagery in anxiety disorders in adolescents.

BACKGROUND: Mental imagery plays an important role in models of anxiety disorders in adults. This understanding rests on qualitative and quantitative studies. Qualitative studies of imagery in anxious adolescents have not been reported in the literature. AIMS: To address this gap, we aimed to explore adolescents' experiences of spontaneous imagery in the context of anxiety disorders. METHOD: We conducted one-to-one semi-structured interviews, with 13 adolescents aged 13-17 years with a DSM-5 anxiety disorder, regarding their experiences of spontaneous imagery. We analysed participants' responses using thematic analysis. RESULTS: We identified five superordinate themes relating to adolescents' influences on images, distractions from images, controllability of images, emotional responses to imagery and contextual influences on imagery. CONCLUSIONS: Our findings suggest that spontaneous images are an important phenomenon in anxiety disorders in adolescents, associated with negative emotions during and after their occurrence. Contextual factors and adolescents' own cognitive styles appear to influence adolescents' experiences of images in anxiety disorders.

Investigating uncommon vascular diseases using the Vascular Low Frequency Disease Consortium.

BACKGROUND: Standardized databases such as the Vascular Quality Initiative and National Surgical Quality Improvement Project assess the quality of care related to common vascular surgery procedures, but are not designed for uncommon vascular diseases. We describe a method of assessing uncommon vascular diseases using a multi-institutional collaboration, the Vascular Low Frequency Disease Consortium (VLFDC). METHODS: Uncommon vascular diseases are identified through a systematic literature review. A disease-specific database is developed and tested at a single institution, then refined and circulated to participating VLFDC investigators. Detailed inclusion and exclusion criteria and data point definitions are provided, allowing for standardized data collection across institutions. Each participating institution identifies all patients over a specific time period and enters the data into a VLFDC-provided database. The data are then de-identified and transmitted to our centralized data center for analysis. RESULTS: Since 2003, the VLFDC has conducted and published nine studies and enrolled 4532 patients, involving 232 institutions and 271 investigators. The studies include renal artery aneurysms, isolated femoral artery aneurysms, spontaneous mesenteric dissection, adventitial cystic disease, carotid body tumors, and vascular Ehlers-Danlos syndrome. Each published study reported on a minimum of 10 times the number of patients collected in previously published studies over the same time period, allowing stronger conclusions to be drawn from the larger sample size. Each study both confirmed previous management principles, which were based on small single-institution experiences, and challenged conventional management paradigms. CONCLUSIONS: When only small clinical series exist to provide guidance in managing uncommon vascular diseases, and/or where conflicting recommendations are made on the treatment of uncommon vascular diseases, a multi-institutional consortium can provide high-volume standardized data that either confirm or changes prior management principles.

Intermodality feature fusion combining unenhanced computed tomography and ferumoxytol-enhanced magnetic resonance angiography for patient-specific vascular mapping in renal impairment.

OBJECTIVE: The purpose of this study was to establish the feasibility of fusing complementary, high-contrast features from unenhanced computed tomography (CT) and ferumoxytol-enhanced magnetic resonance angiography (FE-MRA) for preprocedural vascular mapping in patients with renal impairment. METHODS: In this Institutional Review Board-approved and Health Insurance Portability and Accountability Act-compliant study, 15 consecutive patients underwent both FE-MRA and unenhanced CT scanning, and the complementary high-contrast features from both modalities were fused to form an integrated, multifeature image. Source images from CT and MRA were segmented and registered. To validate the accuracy, precision, and concordance of fused images to source images, unambiguous landmarks, such as wires from implantable medical devices or indwelling catheters, were marked on three-dimensional (3D) models of the respective modalities, followed by rigid co-registration, interactive fusion, and fine adjustment. We then compared the positional offsets using pacing wires or catheters in the source FE-MRA (defined as points of interest [POIs]) and fused images (n = 5 patients, n = 247 points). Points within 3D image space were referenced to the respective modalities: x (right-left), y (anterior-posterior), and z (cranial-caudal). The respective 3D orthogonal reference axes from both image sets were aligned, such that with perfect registration, a given point would have the same (x, y, z) component values in both sets. The 3D offsets (Δx mm, Δy mm, Δz mm) for each of the corresponding POIs represent nonconcordance between the source FE-MRA and fused images. The offsets were compared using concordance correlation coefficients. Interobserver agreement was assessed using intraclass correlation coefficients and Bland-Altman analyses. RESULTS: Thirteen patients (aged 76 ± 12 years; seven female) with aortic valve stenosis and chronic kidney disease and two patients with thoracoabdominal vascular aneurysms and chronic kidney disease underwent FE-MRA for preprocedural vascular assessment, and unenhanced CT examinations were available in all patients. No ferumoxytol-related adverse events occurred. There were 247 matched POIs evaluated on the source FE-MRA and fused images. In patients with implantable medical devices, the mean offsets in spatial position were 0.31 ± 0.51 mm (ρ = 0.99; Cb = 1; 95% confidence interval [CI], 0.99-0.99) for Δx, 0.27 ± 0.69 mm (ρ = 0.99; Cb = 0.99; 95% CI, 0.99-0.99) for Δy, and 0.20 ± 0.59 mm (ρ = 1; Cb = 1; 95% CI, 0.99-1.00) for Δz. Interobserver agreement was excellent (intraclass correlation coefficient, >0.99). The mean difference in offset between readers was 1.5 mm. CONCLUSIONS: Accurate 3D feature fusion is feasible, combining luminal information from FE-MRA with vessel wall information on unenhanced CT. This framework holds promise for combining the complementary strengths of magnetic resonance imaging and CT to generate information-rich, multifeature composite vascular images while avoiding the respective risks and limitations of both modalities.

A multi-institutional experience in vascular Ehlers-Danlos syndrome diagnosis.

OBJECTIVE: Vascular Ehlers-Danlos syndrome (vEDS) is a rare disorder and 1 of 13 types of EDS. The syndrome results in aortic and arterial aneurysms and dissections at a young age. Diagnosis is confirmed with molecular testing via skin biopsy or genetic testing for COL3A1 pathogenic variants. We describe a multi-institutional experience in the diagnosis of vEDS from 2000 to 2015. METHODS: This is a multi-institutional cross-sectional retrospective study of individuals with vEDS. The institutions were recruited through the Vascular Low Frequency Disease Consortium. Individuals were identified using the International Classification of Diseases-9 and 10-CM codes for EDS (756.83 and Q79.6). A review of records was then performed to select individuals with vEDS. Data abstraction included demographics, family history, clinical features, major and minor diagnostic criteria, and molecular testing results. Individuals were classified into two cohorts and then compared: those with pathogenic COL3A1 variants and those diagnosed by clinical criteria alone without molecular confirmation. RESULTS: Eleven institutions identified 173 individuals (35.3% male, 56.6% Caucasian) with vEDS. Of those, 11 (9.8%) had nonpathogenic alterations in COL3A1 and were excluded from the analysis. Among the remaining individuals, 86 (47.7% male, 68% Caucasian, 48.8% positive family history) had pathogenic COL3A1 variants and 76 (19.7% male, 19.7% Caucasian, 43.4% positive family history) were diagnosed by clinical criteria alone without molecular confirmation. Compared with the cohort with pathogenic COL3A1 variants, the clinical diagnosis only cohort had a higher number of females (80.3% vs 52.3%; P < .001), mitral valve prolapse (10.5% vs 1.2%; P = .009), and joint hypermobility (68.4% vs 40.7%; P < .001). Additionally, they had a lower frequency of easy bruising (23.7% vs 64%; P < .001), thin translucent skin (17.1% vs 48.8%; P < .001), intestinal perforation (3.9% vs 16.3%; P = .01), spontaneous pneumothorax/hemothorax (3.9% vs 14%, P.03), and arterial rupture (9.2% vs 17.4%; P = .13). There were no differences in mortality or age of mortality between the two cohorts. CONCLUSIONS: This study highlights the importance of confirming vEDS diagnosis by testing for pathogenic COL3A1 variants rather than relying on clinical diagnostic criteria alone given the high degree of overlap with other forms genetically triggered arteriopathies. Because not all COL3A1 variants are pathogenic, the interpretation of the genetic testing results by an individual trained in variant assessment is essential to confirm the diagnosis. An accurate diagnosis is critical and has serious implications for lifelong screening and treatment strategies for the affected individual and family members.

Managing central venous access during a health care crisis.

OBJECTIVE: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic. METHODS: We conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19. RESULTS: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group). CONCLUSIONS: Implementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises.