Baseline Sleep Characteristics in NCAA Division I Collegiate Athletes.

OBJECTIVE: The authors report no conflicts of interest.To determine baseline sleep characteristics of male/female student-athletes across multiple sports using objective and subjective measures. DESIGN: Prospective study. SETTING: Division I college. PARTICIPANTS: Eighty-two male and female Division I student-athletes. INTERVENTIONS: Participants completed 2 validated sleep questionnaires (Epworth Sleepiness Scale [ESS] and Single-Item Sleep Quality Scale [SISQS]) to assess subjective sleep. They also wore a validated sleep monitoring device (WHOOP 4.0 band) for at least 14 nights to collect objective data on total sleep time (TST) and sleep architecture. MAIN OUTCOME MEASURES: Overnight sleep variables, including TST, time spent awake in bed after falling asleep, time spent in light sleep, rapid eye movement (REM) sleep, and slow-wave sleep (SWS) cycles. Sleep quality and daytime sleepiness were also assessed. RESULTS: There were no statistical differences between male and female student-athletes in average TST, sleep architecture, sleep consistency, SISQS, and ESS scores. The average TST was 409.2 ± 36.3 minutes. Sleep architecture consisted of 25.6% REM, 19.9% SWS, and 54.4% light sleep. The average sleep consistency was 61.6% ± 8.9%. The average SISQS score was 6.48 ± 1.71, and the average ESS score was 7.57 ± 3.82. A significant difference was found in average wake time between males and females (55.0 vs 43.7 min, P = 0.020), with an overall average of 50.2 ± 16.2 minutes. CONCLUSIONS: College student-athletes do not typically obtain the recommended amount of sleep. Optimizing sleep can positively affect academic and athletic performance.

A predictive algorithm for perioperative complications and readmission after ankle arthrodesis.

PURPOSE: Ankle arthrodesis is a mainstay of surgical management for ankle arthritis. Accurately risk-stratifying patients who undergo ankle arthrodesis would be of great utility. There is a paucity of accurate prediction models that can be used to pre-operatively risk-stratify patients for ankle arthrodesis. We aim to develop a predictive model for major perioperative complication or readmission after ankle arthrodesis. METHODS: This is a retrospective cohort study of adult patients who underwent ankle arthrodesis at any non-federal California hospital between 2015 and 2017. The primary outcome is readmission within 30 days or major perioperative complication. We build logistic regression and ML models spanning different classes of modeling approaches, assessing discrimination and calibration. We also rank the contribution of the included variables to model performance for prediction of adverse outcomes. RESULTS: A total of 1084 patients met inclusion criteria for this study. There were 131 patients with major complication or readmission (12.1%). The XGBoost algorithm demonstrates the highest discrimination with an area under the receiver operating characteristic curve of 0.707 and is well-calibrated. The features most important for prediction of adverse outcomes for the XGBoost model include: diabetes, peripheral vascular disease, teaching hospital status, morbid obesity, history of musculoskeletal infection, history of hip fracture, renal failure, implant complication, history of major fracture. CONCLUSION: We report a well-calibrated algorithm for prediction of major perioperative complications and 30-day readmission after ankle arthrodesis. This tool may help accurately risk-stratify patients and decrease likelihood of major complications.

Hip and Knee Osteoarthritis, Not Nonsteroidal Anti-Inflammatory Drugs, are Linked to Cardiac Disease.

BACKGROUND: In 2005, the Food and Drug Administration placed a black-box warning (the most stringent warning for drugs) on all nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) stating that these agents may cause heart attacks and/or strokes. No level I evidence demonstrates that nonselective NSAIDs increase cardiovascular risk. An alternative hypothesis is that hip and knee osteoarthritis (OA) indirectly causes cardiovascular disease (CVD) through decreased activity and NSAIDs are correlated with CVD as an arthritis treatment. METHODS: Systematic reviews were conducted to find observational studies evaluating the association of hip and/or knee OA, CVD, activity, walking, and step counts. The systematic review found studies correlating hip and/or knee OA and CVD morbidity incidence (n = 2); CVD morbidity prevalence (n = 6); odds ratios, relative risks, or hazard ratios of CVD morbidity (n = 11); relative risk, standardized mortality ratios, or hazard ratios of CVD mortality (n = 14); and all-cause mortality hazard ratios associated with NSAID use (n = 3). RESULTS: Hip OA (5 studies), knee OA (9 studies), and hip and knee OA (6 studies) are linked to an increased risk of CVD morbidity and mortality. Cardiac risk increases with validated disability scores, use of walking aids, walking difficulties, longer follow-up times, younger ages of OA onset, numbers of joints involved, and OA severities. No study linked NSAID use to cardiac disease. CONCLUSIONS: All studies with more than 10-year follow-up linked cardiac disease with hip and knee OA. No study linked nonselective NSAID use to CVD. The Food and Drug Administration should reconsider the black-box warnings on naproxen, ibuprofen, and celecoxib.

Piloting the Sexual and Gender Minority Cancer Curricular Advances for Research and Education (SGM Cancer CARE) Workshop: Research Training in the Service of SGM Cancer Health Equity.

The purpose of this study is to describe the context, curriculum design, and pilot evaluation of the educational program "Sexual and Gender Minority Cancer Curricular Advances for Research and Education" (SGM Cancer CARE), a workshop for early-career researchers and healthcare providers interested in gaining knowledge and skills in sexual and gender minority (SGM) cancer research and healthcare advocacy. A needs assessment of a sample of clinicians and researchers (n = 104) and feedback from an Advisory Board informed the curriculum design of the SGM Cancer CARE workshop. Four SGM-tailored modules, focusing on epidemiology, clinical research, behavioral science and interventions, and community-based participatory approaches, were developed and tested in a 2.5-day virtual format among 19 clinicians and researchers. A fifth module to provide feedback to participants on brief presentations about their SGM cancer research ideas or related efforts was added later. A mixed-methods evaluation comprised of pre- and post-modular online evaluation surveys and virtual focus groups was used to determine the degree to which the workshop curriculum met participant needs. Compared to pre-module evaluations, participants reported a marked increase in SGM cancer research knowledge in post-module scores. Quantitative results were supported by our qualitative findings. In open field response survey questions and post-workshop focus groups, participants reported being extremely pleased with the content and delivery format of the SGM Cancer CARE workshop. Participants did regret not having the opportunity to connect with instructors, mentors, and colleagues in person. The SGM Cancer CARE curriculum was shown to increase the knowledge, skills, and level of preparedness of early-career clinicians and scientists to conduct culturally relevant and appropriate research needed to improve care for SGM persons across the cancer care continuum from prevention to survivorship.

Proximal seal dilatation following fenestrated endovascular repair for complex abdominal aortic aneurysms.

OBJECTIVE: Although proximal neck dilatation following infrarenal endovascular aneurysm repair (EVAR) is common and is associated with proximal graft failure, little is known about sealing zone dilatation and its clinical relevance following fenestrated EVAR (FEVAR). We studied proximal seal dilatation (PSD) dynamics following FEVAR and assessed its clinical significance. METHODS: We included all consecutive patients treated for a juxta-/supra-renal aneurysm with fenestrated EVAR using the Zenith Fenestrated Endovascular Graft (Cook Medical, Bloomington, Ind) from 2008 to 2018 in two large teaching hospitals in the Netherlands. The primary outcome was PSD over time and was determined using a linear mixed-effects model. Secondary outcomes included associations for early PSD and difference in aortic dilatation at the level of the covered stent compared with the bare stent. Proximal seal-related adverse events were also obtained. RESULTS: Our cohort included 84 patients with a median computed tomography angiography follow-up time of 24.5 months (interquartile range [IQR], 17-42 months). Maximum aneurysm diameter was 60.1 mm (IQR, 56.9-67.2 mm). Mean proximal seal diameter at baseline was 26.2 mm (standard deviation [SD], ±2.8 mm), mean stent oversizing was 20.1% (SD, ±9.1%), and mean proximal seal length was 29.5 mm (SD, ±11.7 mm). Proximal seal dilatation of 1.7 mm (95% confidence interval [CI], 1.4-2.1 mm) was found in the first year, decelerating thereafter (second year, 0.9 mm/year; 95% CI, 0.7-1.1 mm/y). Over 10% PSD at 1 year occurred in 22 patients (27%) and was associated with stent graft oversizing (odds ratio, 1.1; 95% CI, 1.03-1.2; P = .008) and a lower number of target vessels (four fenestrations/ref two fenestrations: odds ratio, 0.13; 95% CI, 0.02-0.74; P = .029). At last available imaging, dilatation difference was higher at the level of the covered stent compared with the bare stent (3.0 mm [IQR, 1.3-5.1 mm] vs 1.6 mm [IQR, 0.8-2.5 mm]; P < .001). During the study period, only one patient (1.2%) developed a proximal seal-related adverse event (type IA endoleak). CONCLUSIONS: PSD is present following FEVAR, occurring at a faster rate in the first year and subsequently decelerating thereafter, similarly to neck dilatation after standard infrarenal EVAR. Although its clinical implication seems to remain limited in the first years following implantation, further research is required to assess the effect of PSD on long-term FEVAR outcomes.

Minerals in edible seaweed: health benefits and food safety issues.

An adequate daily intake of minerals is essential for the prevention of chronic nutrition-related and degenerative diseases, including cancer, cardiovascular disease, and obesity. Seaweeds are marine aquatic vegetable that are rich in nutrients. They also have a natural and sustainable origin and clean and renewable sources when they come from marine aquaculture or controlled fisheries. Seaweeds have high nutritional value as a source of polyunsaturated fatty acids, proteins, carbohydrates, vitamins, and especially minerals. They are known for their high mineral content, which is gathered from seawater depending on the seasonal variation and the environment. Seaweeds are consequently rich in macro-elements and trace elements, with a mineral content at least 10 times higher than terrestrial plants and reaching 20-50% of its dry weight. Therefore, seaweeds can make an important contribution to the daily intake of minerals and are a promising source of essential minerals for functional food, food supplements, and nutraceuticals. The aim of the present review is to compare the contents of essential minerals (K, Ca, Na, P, Cu, Fe, Se, Mn, Zn, Mg, Cr, and I) as well as potential toxic minerals (Hg, Pb, Cd, As, and Al) in 14 main edible seaweeds that have availability of biomass from harvest and aquaculture. Another goal is to establish their safety in foods and contributions to the Recommended Dietary Allowance (RDA) and adequate intake (AI) values.

Machine learning-driven identification of novel patient factors for prediction of major complications after posterior cervical spinal fusion.

PURPOSE: Posterior cervical fusion is associated with increased rates of complications and readmission when compared to anterior fusion. Machine learning (ML) models for risk stratification of patients undergoing posterior cervical fusion remain limited. We aim to develop a novel ensemble ML algorithm for prediction of major perioperative complications and readmission after posterior cervical fusion and identify factors important to model performance. METHODS: This is a retrospective cohort study of adults who underwent posterior cervical fusion at non-federal California hospitals between 2015 and 2017. The primary outcome was readmission or major complication. We developed an ensemble model predicting complication risk using an automated ML framework. We compared performance with standard ML models and logistic regression (LR), ranking contribution of included variables to model performance. RESULTS: Of the included 6822 patients, 18.8% suffered a major complication or readmission. The ensemble model demonstrated slightly superior predictive performance compared to LR and standard ML models. The most important features to performance include sex, malignancy, pneumonia, stroke, and teaching hospital status. Seven of the ten most important features for the ensemble model were markedly less important for LR. CONCLUSION: We report an ensemble ML model for prediction of major complications and readmission after posterior cervical fusion with a modest risk prediction advantage compared to LR and benchmark ML models. Notably, the features most important to the ensemble are markedly different from those for LR, suggesting that advanced ML methods may identify novel prognostic factors for adverse outcomes after posterior cervical fusion.

National Network of Depression Centers' Recommendations on Harmonizing Clinical Documentation of Electroconvulsive Therapy.

ABSTRACT: Electroconvulsive therapy (ECT) is a highly therapeutic and cost-effective treatment for severe and/or treatment-resistant major depression. However, because of the varied clinical practices, there is a great deal of heterogeneity in how ECT is delivered and documented. This represents both an opportunity to study how differences in implementation influence clinical outcomes and a challenge for carrying out coordinated quality improvement and research efforts across multiple ECT centers. The National Network of Depression Centers, a consortium of 26+ US academic medical centers of excellence providing care for patients with mood disorders, formed a task group with the goals of promoting best clinical practices for the delivery of ECT and to facilitate large-scale, multisite quality improvement and research to advance more effective and safe use of this treatment modality. The National Network of Depression Centers Task Group on ECT set out to define best practices for harmonizing the clinical documentation of ECT across treatment centers to promote clinical interoperability and facilitate a nationwide collaboration that would enable multisite quality improvement and longitudinal research in real-world settings. This article reports on the work of this effort. It focuses on the use of ECT for major depressive disorder, which accounts for the majority of ECT referrals in most countries. However, most of the recommendations on clinical documentation proposed herein will be applicable to the use of ECT for any of its indications.

"Register-shift" insulin analogs uncover constraints of proteotoxicity in protein evolution.

Globular protein sequences encode not only functional structures (the native state) but also protein foldability, i.e. a conformational search that is both efficient and robustly minimizes misfolding. Studies of mutations associated with toxic misfolding have yielded insights into molecular determinants of protein foldability. Of particular interest are residues that are conserved yet dispensable in the native state. Here, we exploited the mutant proinsulin syndrome (a major cause of permanent neonatal-onset diabetes mellitus) to investigate whether toxic misfolding poses an evolutionary constraint. Our experiments focused on an invariant aromatic motif (PheB24-PheB25-TyrB26) with complementary roles in native self-assembly and receptor binding. A novel class of mutations provided evidence that insulin can bind to the insulin receptor (IR) in two different modes, distinguished by a "register shift" in this motif, as visualized by molecular dynamics (MD) simulations. Register-shift variants are active but defective in cellular foldability and exquisitely susceptible to fibrillation in vitro Indeed, expression of the corresponding proinsulin variant induced endoplasmic reticulum stress, a general feature of the mutant proinsulin syndrome. Although not present among vertebrate insulin and insulin-like sequences, a prototypical variant ([GlyB24]insulin) was as potent as WT insulin in a rat model of diabetes. Although in MD simulations the shifted register of receptor engagement is compatible with the structure and allosteric reorganization of the IR-signaling complex, our results suggest that this binding mode is associated with toxic misfolding and so is disallowed in evolution. The implicit threat of proteotoxicity limits sequence variation among vertebrate insulins and insulin-like growth factors.

Aneurysm Volumes After Endovascular Repair of Ruptured vs Intact Aortic Aneurysms: A Retrospective Observational Study.

PURPOSE: To compare changes in abdominal aortic aneurysm (AAA) sac volume between endovascular aneurysm repairs (EVAR) performed for ruptured (rEVAR) vs intact (iEVAR) AAAs and to determine the impact of early volume shrinkage on future complications. MATERIALS AND METHODS: A retrospective analysis was performed of all patients undergoing standard infrarenal EVAR from 2002 to 2016 at a tertiary referral institution. Only patients with degenerative AAAs and with 30-day and 1-year computed tomography angiography (CTA) imaging were included. Early sac shrinkage was defined as a volume sac reduction >10% between the first (<30-day) and the 1-year CTA. The primary endpoint was to compare AAA sac volume changes between patients undergoing rEVAR (n=51; mean age 71.0±8.5 years; 46 men) vs iEVAR (n=393; mean age 72.3±7.5 years; 350 men). Results are reported as the mean difference with the interquartile range (IQR Q1, Q3). The secondary endpoint was freedom from aneurysm-related complications after 1 year as determined by regression analysis; the results are presented as the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: At baseline, the rEVAR group had larger aneurysms (p<0.001) and shorter (p<0.001) and more angulated (p=0.028) necks. Aneurysm sac volume decreased more in the rEVAR group during the first year [-26.3% (IQR -38.8%, -12.5%)] vs the iEVAR group [-11.9% (IQR -27.5%, 0); p<0.001]. However, after the first year, the change in sac volume was similar between the groups [-3.8% (IQR -32.9%, 31.9%) for rEVAR and -1.5% (IQR -20.9%, 13.6%) for iEVAR, p=0.74]. Endoleak occurrence during follow-up was similar between the groups. In the overall population, patients with early sac shrinkage had a lower incidence of complications after the 1-year examination (adjusted HR 0.59, 95% CI 0.39 to 0.89, p=0.01). CONCLUSION: EVAR patients treated for rupture have more pronounced aneurysm sac shrinkage compared with iEVAR patients during the first year after EVAR. Patients presenting with early shrinkage are less likely to encounter late complications. These parameters may be considered when tailoring surveillance protocols.

Long Term Outcomes of Post-Implantation Syndrome After Endovascular Aneurysm Repair.

OBJECTIVE: The aim of this study was to investigate the association between post-implantation syndrome (PIS) and long term outcomes, with emphasis on cardiovascular prognosis. METHODS: One hundred and forty-nine consecutive patients undergoing EVAR in a tertiary institution were previously included in a study investigating the risk factors and short term consequences of PIS (defined as tympanic temperature ≥ 38°C and CRP > 10 mg/L, after excluding complications with an effect on inflammatory markers). This study was based on a prospectively maintained database. Survival status was derived from inquiry of civil registry database information and causes of death from the Dutch Central Bureau of Statistics. The primary endpoint was cardiovascular events. Secondary endpoints were overall and specific cause mortality (cardiovascular, ischaemic heart disease, AAA, and cancer related mortality). Aneurysm sac dynamics and occurrence of endoleaks were also analysed. Survival estimates were obtained using Kaplan-Meier plots and a multivariable model was constructed to correct for confounders. RESULTS: The PIS incidence was 39% (58/149). At the time of surgery, patients had a mean age of 73 ± 7 years and were predominantly male. There were no baseline differences between the PIS and non-PIS groups. The median follow up was 6.4 years (3.2 - 8.3), similar in both groups (p = .81). There was no difference in cardiovascular events for PIS and non-PIS patients (p = .63). However, Kaplan-Meier plots suggest a trend towards a higher rate of cardiovascular events in PIS patients during the first years: freedom from cardiovascular events at one year was 94% vs. 89% and at three years 90% vs. 82%. No differences were found in overall and specific cause mortality. There was a higher rate of type II endoleaks for non-PIS patients (28% vs. 9%, p = .005). Sac dynamics were similar in both groups. CONCLUSION: The results suggest that PIS is not associated with a statistically significantly higher risk of cardiovascular events. PIS had no impact on mortality. Lastly, PIS patients had fewer type II endoleaks, but sac dynamics were analogous.

Risk Factors, Dynamics, and Clinical Consequences of Aortic Neck Dilatation after Standard Endovascular Aneurysm Repair.

OBJECTIVE: Aortic neck dilatation (AND) occurs after endovascular aneurysm repair (EVAR) with self expanding stent grafts (SESs). Whether it continues, ultimately exceeding the endograft diameter leading to abdominal aortic aneurysm (AAA) rupture, remains uncertain. Dynamics, risk factors, and clinical relevance of AND were investigated after EVAR with standard SESs. METHODS: All intact EVAR patients treated from 2000 to 2015 at a tertiary institution were included. Demographic, anatomical, and device related characteristics were investigated as risk factors for AND. Outer to outer diameters were measured at a single standardised aortic level on reconstructed computed tomography (CT) images. RESULTS: A total of 460 patients were included (median follow up 5.2 years, interquartile range [IQR] 3.0, 7.7 years; CT imaging follow up 3.3 years, IQR 1.3, 5.4). Baseline neck diameter was 24 mm (IQR 22, 26) and increased 11.1% (IQR 1.5%, 21.9%) at last CT imaging. Endograft oversizing was 20.0% (IQR 13.6, 28.0). AND was greater during the first year (5.2% [IQR 0, 11.7]) decreasing subsequently (two to four years to 1.4%/year [IQR 0.0, 4.5%], p ≤ .001) and was associated with suprarenal fixation endografts (t value = 7.9, p < .001) and oversizing (t value = 4.4, p < .001). AND exceeding the endograft was 3.5% (95% CI 2.2% - 4.8%) and 14.4% (95% CI 11.0% - 17.8%) at five and eight years, respectively. Excessive AND was associated with baseline neck diameter (OR 1.2/mm, 95% CI 1.05 - 1.41) while the Excluder endograft had a protective effect (OR 0.15, 95% CI 0.04 - 0.58). Excessive AND was associated with type 1A endoleak (HR 3.3, 95% CI 1.1 - 9.7) and endograft migration > 5 mm (HR 3.1, 95% CI 1.4 - 6.9). CONCLUSION: AND after EVAR with SES is associated with endograft oversizing and radial force but decelerates after the first post-operative year. Baseline aortic neck diameter and suprarenal stent bearing endografts were associated with an increased risk of AND beyond nominal stent graft diameter. However, it remains unclear whether patient selection, differences in endograft radial force or the suprarenal stent are accountable for this difference.

Development of a Novel, Potentially Universal Machine Learning Algorithm for Prediction of Complications After Total Hip Arthroplasty.

BACKGROUND: As the prevalence of hip osteoarthritis increases, the number of total hip arthroplasty (THA) procedures performed is also projected to increase. Accurately risk-stratifying patients who undergo THA would be of great utility, given the significant cost and morbidity associated with developing perioperative complications. We aim to develop a novel machine learning (ML)-based ensemble algorithm for the prediction of major complications after THA, as well as compare its performance against standard benchmark ML methods. METHODS: This is a retrospective cohort study of 89,986 adults who underwent primary THA at any California-licensed hospital between 2015 and 2017. The primary outcome was major complications (eg infection, venous thromboembolism, cardiac complication, pulmonary complication). We developed a model predicting complication risk using AutoPrognosis, an automated ML framework that configures the optimally performing ensemble of ML-based prognostic models. We compared our model with logistic regression and standard benchmark ML models, assessing discrimination and calibration. RESULTS: There were 545 patients who had major complications (0.61%). Our novel algorithm was well-calibrated and improved risk prediction compared to logistic regression, as well as outperformed the other four standard benchmark ML algorithms. The variables most important for AutoPrognosis (eg malnutrition, dementia, cancer) differ from those that are most important for logistic regression (eg chronic atherosclerosis, renal failure, chronic obstructive pulmonary disease). CONCLUSION: We report a novel ensemble ML algorithm for the prediction of major complications after THA. It demonstrates superior risk prediction compared to logistic regression and other standard ML benchmark algorithms. By providing accurate prognostic information, this algorithm may facilitate more informed preoperative shared decision-making.

Long-term results after standard endovascular aneurysm repair with the Endurant and Excluder stent grafts.

OBJECTIVE: Many endografts are currently available for standard endovascular repair of infrarenal abdominal aortic aneurysms. Comparison of long-term outcomes between devices might aid in this decision process, but comparative data are scarce. The purpose of this study was to report long-term clinical outcomes of two commercially available endoprosthesis, the Endurant (Medtronic Vascular, Inc, Minneapolis, Minn) and the Excluder (W. L. Gore & Associates, Flagstaff, Ariz) stent grafts. METHODS: Patients undergoing standard endovascular repair from July 2004 to December 2011 in a single institution with the Endurant or the Low-Porosity Excluder endografts were eligible. Only patients treated for intact degenerative abdominal infrarenal aneurysms were included. All measurements were performed on center-lumen line reconstructions obtained on dedicated software. The primary end point was primary clinical success, defined as clinical success without the need for an additional or secondary surgical or endovascular procedure. Neck-related events (a composite of type IA endoleak, neck-related secondary intervention, or migration of >5 mm), neck morphology changes, renal function, and overall survival were secondary end points. RESULTS: The study included 277 patients (156 Endurants; 121 Excluders). The median follow-up was 5.8 years (range, 0.1-12.4 years) and did not differ between groups (P = .18). Patients treated with the Endurant stent graft had wider (neck diameter of >28 mm, 27.3% vs 1.7% [P < .001]; neck diameter of 27 mm, [interquartile range (IQR), 24-29 mm] for Endurant and 24 mm [IQR, 22-25 mm] for Excluder; P < .001) and more angulated necks (ß-angle of >60°, 26.7% vs 12.5%; P = .004). Oversizing was greater in the Endurant group (16% [IQR, 12%-22%] vs 13% [IQR, 8%-17%], respectively; P < .001). Patients were treated outside device instructions for use regarding proximal neck: 16.7% in the Endurant and 17.3% in the Excluder group (P = .720). The 7-year primary clinical success was 54.7% for the Endurant and 58.1% for the Excluder groups (P = .53). Freedom from neck-related events at 7 years was 76.7% for the Endurant and 78.8% for Excluder group (P = .94). The Endurant stent graft (hazard ratio [HR], 2.7; 95% confidence interval [CI], 1.3-5.8; P = .009) was an independent predictor of significant renal function decline. Neck dilatation was greater in Endurant-implanted patients (13% [95% CI, 2%-22%] vs 4% [95% CI, 0%-10%]; P < .001). Overall survival at 7 years was 61.4% in the Endurant and 50.3% (n = 50; standard error, 0.047) in the Excluder group (P = .39). CONCLUSIONS: This study reveals that durable and sustainable results can be obtained with either of these late generation devices. This finding suggests that careful planning and a tailored device selection taking into account the patient's anatomy are more relevant determinants than the graft model itself to obtain clinical success. The Endurant endoprosthesis seems to be associated with a higher rate of neck dilatation and faster decrease in the estimated glomerular filtration rate, but further studies with longer follow-up are necessary to determine the clinical relevance of these findings.

Comparison of midterm results of endovascular aneurysm repair for ruptured and elective abdominal aortic aneurysms.

OBJECTIVE: Endovascular aneurysm repair (EVAR) became an increasingly preferred modality for abdominal aortic aneurysm (AAA) repair both in elective AAA repair (el-EVAR) and EVAR of a ruptured AAA (r-EVAR) setting. Ruptured AAAs usually have more hostile anatomies and less time for planning. Consequently, more complications may arise after r-EVAR. The purpose of this study was to compare mi-term outcomes between r-EVAR and el-EVAR. METHODS: A retrospective cohort analysis of patients undergoing EVAR from 2000 to 2015 at a tertiary institution was performed. Patients with previous aortic surgery, nonatherosclerotic AAA and isolated iliac aneurysms were excluded. In-hospital casualties or patients who were intraoperatively converted to open repair were also excluded. For the midterm outcome analysis, only patients with at least two postoperative examinations (a 30-day computed tomography scan and a second postoperative examination performed 6 months or later) were considered. The primary end point was freedom from aneurysm-related complications (a composite of type I or III endoleak, aneurysm sac growth, migration of more than 5 mm, device integrity failure, AAA-related death, late postimplant rupture, or AAA-related secondary intervention). Freedom from secondary interventions, neck-related events (defined as a composite of type IA endoleak, migration of more than 5 mm, or preemptive neck-related secondary intervention) and late survival were secondary end points. The impact of device instructions for use (IFU) compliance on neck events was also assessed. RESULTS: The study included 565 patients (65 r-EVAR and 500 el-EVAR). Eighty-two patients were treated outside proximal neck IFU, 13 in the r-EVAR group (21.3%) and 69 (14.5%) in the el-EVAR (P = .16). During the index hospitalization, there were more complications (12.3% vs 3.2%; P = .001) and reinterventions (12.3% vs 2.8%; P < .001) in the r-EVAR group. After discharge, median clinical follow-up time was 4.3 years (interquartile range, 2.1-7.0 years) without differences between both groups. Five-year freedom from AAA-related complications was 53.9% in the r-EVAR group and 65.4% in the el-EVAR (P = .21). In multivariable analysis the r-EVAR group was not at increased risk for late complications (hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.54-1.61; P = .81). Five-year freedom from neck-related events was 74% in r-EVAR and 82% in the el-EVAR group (P = .345). Patients treated outside neck IFU were at greater risk for neck-related events both in r-EVAR (HR, 6.5; 95% CI, 1.8-22.9; P = .004) and el-EVAR group (HR, 2.6; 95% CI, 1.5-4.5; P < .001). Freedom from secondary interventions at 5 years was 63.0% for r-EVAR and 76.9% for el-EVAR (P = .16). Survival at 5 years was 68.8% in the r-EVAR group and 73.3% in the el-EVAR group (P = .30). CONCLUSIONS: Durable and sustainable midterm outcomes were found for both r-EVAR and el-EVAR patients who survived the postoperative period. Patients treated outside the IFU are at greater risk for late complications. Surveillance protocols may be tailored according to individual anatomy and IFU compliance rather than timing of repair.

Total Luminal Volume Predicts Risk after Endovascular Aneurysm Repair.

OBJECTIVE: Large aneurysm diameter represents a well known predictor of late complications after endovascular aneurysm repair (EVAR). However, the role of the thrombus free lumen inside the abdominal aortic aneurysm (AAA) sac is not clear. It was hypothesised that greater luminal volume represents a relevant risk factor for late complications after EVAR. METHODS: A retrospective cohort analysis was performed including all patients undergoing EVAR from 2005 to 2016 at a tertiary referral institution. Pre-operative AAA lumen volume was measured in centre lumen line reconstructions and patients were stratified into quartiles according to luminal volume. The primary endpoint was freedom from AAA related complications. Secondary endpoints were freedom from neck events (type 1A endoleak, migration >5 mm or any pre-emptive neck related intervention), iliac related events (type 1B endoleak or pre-emptive iliac related intervention), and overall survival. RESULTS: Four hundred and four patients were included: 101 in the first quartile (Q1; <61 cm3). Patients with higher luminal volumes had wider, shorter, and more angulated proximal necks. There were more ruptured AAAs, more aorto-uni-iliac implanted devices and patients outside neck instructions for use in the 4th quartile. Five year freedom from AAA related complications was 79%, 66%, 58% and 56%, respectively (p = .007). At five years, freedom from neck related events was 86%, 84%, 73%, and 71%, respectively, for the four groups (p = .009), and freedom from iliac related events was 96%, 91%, 88%, and 88%, respectively (p = .335). On multivariable analysis, luminal volume was an independent predictor of late complications (Q4 vs. Q1 - hazard ratio: 1.91, 95% confidence interval 1.01-3.6, p = .046). Overall survival at five years was not affected by lumen volume (p = .75). CONCLUSION: AAA luminal volume represents an important risk factor for AAA related complications. This information may be considered when deciding tailoring surveillance protocols after EVAR. However, larger studies are needed to validate this hypothesis.

Risk Adjustment in the California Joint Replacement Registry: Is Patient Complexity Accurately Assessed in Academic Versus Nonacademic Hospitals?

BACKGROUND: We sought to report on the differences in observed versus expected arthroplasty outcomes between academic and nonacademic hospitals in a large joint registry. We utilized the California Joint Replacement Registry's data and risk adjustment model. METHODS: Observed versus expected hip and knee arthroplasty complications were utilized to assess hospital and surgeon risk-adjusted complication rates (RACRs). Based on a hospital and surgeon RACR, each was assigned a performance rating ("worse," "expected," "better"). Associations between academic status and performance ratings, rates of individual complications, prevalence of risk factors associated with increased complication rates, and differences in complication rates were calculated. RESULTS: A higher percentage of academic providers had "worse" than expected ratings, whereas a higher percentage of nonacademic providers had "expected" and "better" than expected ratings (P = .011) based on the observed versus expected complication rates. There was a higher incidence of patients with congestive heart failure and an elevated American Society of Anesthesiologists classification in academic institutions (P = .0001). The complication rate was higher in academic institutions for all total knee arthroplasties (P < .0016). CONCLUSIONS: We identified disparities in RACRs between nonacademic and academic institutions. This may reflect the difficulty of fully adjusting for medical risk and surgical complexity in a large arthroplasty database.

Nutritional Enhancement of Farmed Salmon Meat via Non-GMO Nannochloropsis Gaditana: Eicosapentaenoic Acid (EPA, 20:5 n-3), Docosapentaenoic Acid (DPA, 22:5 n-3) and Vitamin D3 for Human Health.

Omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and vitamin D3 are essential components of human nutrition. A regular human diet is highly deficient in n-3 LC PUFAs. Fish like salmon are highly recommended in the human diet as they are a major source of high-value n-3 LC PUFAs and vitamin D3. The levels of these nutrients have been decreasing over the last few years in farmed salmon, whose production urgently needs sustainable sources of these nutrients. The microalga Nannochloropsis gaditana (NG) is known for its naturally high potential for the production of eicosapentaenoic (EPA, 20:5 n-3) fatty acid. A commercial diet for Atlantic salmon was supplemented with 1% and 10% of spray-dried NG grown under controlled conditions for a high EPA content. Salmon were harvested on day 49, following which, boneless and skinless salmon meat was recovered from fish and analyzed for the fatty acid profile, total fat, and vitamin D3. Vitamin D3, EPA, and docosapentaenoic fatty acid (DPA, 22:5 n-3) levels were significantly increased (p < 0.05) by supplementing the basal diet with 10% NG, thus, NG represents a novel, functional, natural ingredient and a sustainable source of n-3 LC-PUFAs that can raise the levels of healthy fats and vitamin D3 in farmed salmon meat.

Structure-based stabilization of insulin as a therapeutic protein assembly via enhanced aromatic-aromatic interactions.

Key contributions to protein structure and stability are provided by weakly polar interactions, which arise from asymmetric electronic distributions within amino acids and peptide bonds. Of particular interest are aromatic side chains whose directional π-systems commonly stabilize protein interiors and interfaces. Here, we consider aromatic-aromatic interactions within a model protein assembly: the dimer interface of insulin. Semi-classical simulations of aromatic-aromatic interactions at this interface suggested that substitution of residue TyrB26 by Trp would preserve native structure while enhancing dimerization (and hence hexamer stability). The crystal structure of a [TrpB26]insulin analog (determined as a T3Rf3 zinc hexamer at a resolution of 2.25 Å) was observed to be essentially identical to that of WT insulin. Remarkably and yet in general accordance with theoretical expectations, spectroscopic studies demonstrated a 150-fold increase in the in vitro lifetime of the variant hexamer, a critical pharmacokinetic parameter influencing design of long-acting formulations. Functional studies in diabetic rats indeed revealed prolonged action following subcutaneous injection. The potency of the TrpB26-modified analog was equal to or greater than an unmodified control. Thus, exploiting a general quantum-chemical feature of protein structure and stability, our results exemplify a mechanism-based approach to the optimization of a therapeutic protein assembly.

Anatomic predictors for late mortality after standard endovascular aneurysm repair.

OBJECTIVE: Abdominal aortic aneurysm (AAA) management involves a decision process that takes into account anatomic characteristics, surgical risks, patients' preferences, and expected survival. Whereas larger AAA diameter has been associated with increased mortality after both standard endovascular aneurysm repair (EVAR) and open repair, it is unclear whether survival after EVAR is influenced by other anatomic characteristics. The purpose of this study was to determine the importance of baseline anatomic features on survival after EVAR. METHODS: All patients treated at a tertiary teaching center with EVAR for intact standard infrarenal AAA from 2000 to 2014 were included. The civil data registry was queried to determine survival status; causes of death were obtained from death certificates. The primary study end point was to determine the impact of baseline morphologic features on all-cause and cardiovascular mortality after EVAR. RESULTS: This study included 404 EVAR patients (12.1% women; mean age, 73 years) with a median follow-up of 5.8 years (interquartile range, 3.1-7.4 years). The 5- and 10-year overall survival rates for the entire population after EVAR were 70% (95% confidence interval [CI], 66%-75%) and 43% (95% CI, 37%-50%), respectively. Only AAA diameter >70 mm (hazard ratio [HR], 1.75; 95% CI, 1.20-3.56) was identified as an independent anatomic predictor of all-cause mortality. Death due to cardiovascular causes occurred in 60 (38.5%) patients. Aneurysm-related mortality was responsible for six of the cardiovascular-related deaths. In multivariable analysis, both neck diameter ≥30 mm (HR, 2.16; 95% CI, 1.05-4.43) and AAA diameter >70 mm (HR, 2.45; 95% CI, 1.34-4.46) were identified as independent morphologic risk factors for cardiovascular mortality, whereas >25% circumferential neck thrombus (HR, 0.32; 95% CI, 0.13-0.77) was protective. CONCLUSIONS: This study suggests that patients with AAA diameters >70 mm are at increased risk of all-cause and cardiovascular mortality. In addition, patients with infrarenal neck diameters ≥30 mm have a greater risk of cardiovascular mortality, although AAA-related deaths were not more frequent in this group of patients. Consequently, a more aggressive management of cardiovascular medical comorbidities may be warranted to improve survival after standard EVAR in these patients.