Temporal Trends and Outcomes of Abdominal Aortic Aneurysm Care in the United States.

BACKGROUND: Endovascular aortic aneurysm repair (EVAR) has had a dynamic impact on abdominal aortic aneurysm (AAA) care, often supplanting open AAA repair (OAR). Accordingly, US AAA management is often highlighted by disparities in patient selection and guideline compliance. The purpose of this analysis was to define secular trends in AAA care. METHODS: The Society for Vascular Surgery Vascular Quality Initiative was queried for all EVARs and OARs (2011-2021). End points included procedure utilization, change in mortality, patient risk profile, Society for Vascular Surgery-endorsed diameter compliance, off-label EVAR use, cross-clamp location, blood loss, in-hospital complications, and post-EVAR surveillance missingness. Linear regression was used without risk adjustment for all end points except for mortality and complications, for which logistic regression with risk adjustment was used. RESULTS: In all, 66 609 EVARs (elective, 85% [n=55 805] and nonelective, 15% [n=9976]) and 13 818 OARs (elective, 70% [n=9706] and nonelective, 30% [n=4081]) were analyzed. Elective EVAR:OAR ratios were increased (0.2 per year [95% CI, 0.01-0.32]), while nonelective ratios were unchanged. Elective diameter threshold noncompliance decreased for OAR (24%→17%; P=0.01) but not EVAR (mean, 37%). Low-risk patients increasingly underwent elective repairs (EVAR, +0.4%per year [95% CI, 0.2-0.6]; OAR, +0.6 points per year [95% CI, 0.2-1.0]). Off-label EVAR frequency was unchanged (mean, 39%) but intraoperative complications decreased (0.5% per year [95% CI, 0.2-0.9]). OAR complexity increased reflecting greater suprarenal cross-clamp rates (0.4% per year [95% CI, 0.1-0.8]) and blood loss (33 mL/y [95% CI, 19-47]). In-hospital complications decreased for elective (0.7% per year [95% CI, 0.4-0.9]) and nonelective EVAR (1.7% per year [95% CI, 1.1-2.3]) but not OAR (mean, 42%). A 30-day mortality was unchanged for both elective OAR (mean, 4%) and EVAR (mean, 1%). Among nonelective OARs, an increase in both 30-day (0.8% per year [95% CI, 0.1-1.5]) and 1-year mortality (0.8% per year [95% CI, 0.3-1.6]) was observed. Postoperative EVAR surveillance acquisition decreased (67%→49%), while 1-year mortality among patients without imaging was 4-fold greater (9.2% versus imaging, 2.0%; odds ratio, 4.1 [95% CI, 3.8-4.3]; P<0.0001). CONCLUSIONS: There has been an increase in EVAR and a corresponding reduction in OAR across the United States, despite established concerns surrounding guideline adherence, reintervention, follow-up, and cost. Although EVAR morbidity has declined, OAR complication rates remain unchanged and unexpectedly high. Opportunities remain for improving AAA care delivery, patient and procedure selection, guideline compliance, and surveillance.

Genetic Encoding of Fluoro-l-tryptophans for Site-Specific Detection of Conformational Heterogeneity in Proteins by NMR Spectroscopy.

The substitution of a single hydrogen atom in a protein by fluorine yields a site-specific probe for sensitive detection by 19F nuclear magnetic resonance (NMR) spectroscopy, where the absence of background signal from the protein facilitates the detection of minor conformational species. We developed genetic encoding systems for the site-selective incorporation of 4-fluorotryptophan, 5-fluorotryptophan, 6-fluorotryptophan, and 7-fluorotryptophan in response to an amber stop codon and used them to investigate conformational heterogeneity in a designed amino acid binding protein and in flaviviral NS2B-NS3 proteases. These proteases have been shown to present variable conformations in X-ray crystal structures, including flips of the indole side chains of tryptophan residues. The 19F NMR spectra of different fluorotryptophan isomers installed at the conserved site of Trp83 indicate that the indole ring flip is common in flaviviral NS2B-NS3 proteases in the apo state and suppressed by an active-site inhibitor.

Arteriovenous Access for Hemodialysis: A Review.

Importance: Hemodialysis requires reliable vascular access to the patient's blood circulation, such as an arteriovenous access in the form of an autogenous arteriovenous fistula or nonautogenous arteriovenous graft. This Review addresses key issues associated with the construction and maintenance of hemodialysis arteriovenous access. Observations: All patients with kidney failure should have an individualized strategy (known as Patient Life-Plan, Access Needs, or PLAN) for kidney replacement therapy and dialysis access, including contingency plans for access failure. Patients should be referred for hemodialysis access when their estimated glomerular filtration rate progressively decreases to 15 to 20 mL/min, or when their peritoneal dialysis, kidney transplant, or current vascular access is failing. Patients with chronic kidney disease should limit or avoid vascular procedures that may complicate future arteriovenous access, such as antecubital venipuncture or peripheral insertion of central catheters. Autogenous arteriovenous fistulas require 3 to 6 months to mature, whereas standard arteriovenous grafts can be used 2 to 4 weeks after being established, and "early-cannulation" grafts can be used within 24 to 72 hours of creation. The prime pathologic lesion of flow-related complications of arteriovenous access is intimal hyperplasia within the arteriovenous access that can lead to stenosis, maturation failure (33%-62% at 6 months), or poor patency (60%-63% at 2 years) and suboptimal dialysis. Nonflow complications such as access-related hand ischemia ("steal syndrome"; 1%-8% of patients) and arteriovenous access infection require timely identification and treatment. An arteriovenous access at high risk of hemorrhaging is a surgical emergency. Conclusions and Relevance: The selection, creation, and maintenance of arteriovenous access for hemodialysis vascular access is critical for patients with kidney failure. Generalist clinicians play an important role in protecting current and future arteriovenous access; identifying arteriovenous access complications such as infection, steal syndrome, and high-output cardiac failure; and making timely referrals to facilitate arteriovenous access creation and treatment of arteriovenous access complications.

Limited health literacy is common among vascular surgery patients.

BACKGROUND: Health literacy is a crucial aspect of informed decision-making, and limited health literacy has been associated with worse health care outcomes. To date, health literacy has not been examined in vascular surgery patients. Therefore, we conducted a prospective observational study to determine the prevalence and factors associated with poor health literacy in vascular surgery patients. METHODS: The Newest Vital Sign (Pfizer, New York, NY), a validated instrument, was used to appraise the health literacy of 150 patients who visited the outpatient vascular clinic at UF Health Shands Hospital between April 2022 and August 2022. Patients who scored a 4 (out of 6) or higher were classified as having adequate health literacy. Each study participant also completed a sociodemographic questionnaire. RESULTS: In total, 82 out of the 150 (54%) patients we screened had limited health literacy. The prevalence of limited health literacy varied and was independently associated with increased age (odds ratio 1.06; 95% [1.02 to 1.10], P = .004), having not attended college (high school diploma versus college+ odds ratio 3.5; 95% [1.26 to 10.1], P = .018), and African American race (odds ratio 5.3; 95% [1.59 to 22.3], P = .012). A total of 83% of African American patients had limited health literacy, compared to 49% of Asian and White patients. CONCLUSION: Most vascular surgery patients have limited health literacy. Increased age, fewer years of education, and African American race were associated with limited health literacy. Physicians caring for patients with lower health literacy should investigate and use communication strategies tailored to patients with limited health literacy.

Comparative outcomes of open mesenteric bypass after a failed endovascular or open mesenteric revascularization for chronic mesenteric ischemia.

INTRODUCTION: Clinical practice guidelines have recommended an endovascular-first approach (ENDO) for the management of patients with chronic mesenteric ischemia (CMI), whereas an open mesenteric bypass (OMB) is proposed for subjects deemed to be poor ENDO candidates. However, the impact of a previous failed endovascular or open mesenteric reconstruction on a subsequent OMB is unknown. Accordingly, this study was designed to examine the results of a remedial OMB (R-OMB) after a failed ENDO or a primary OMB (P-OMB) for patients with recurrent CMI. METHODS: All patients who underwent an OMB from 2002 to 2022 at the University of Florida were reviewed. Outcomes after an R-OMB (ie, history of a failed ENDO or P-OMB) and P-OMB were compared. The primary end point was 30-day mortality, whereas secondary outcomes included complications, reintervention, and survival. The Kaplan-Meier methodology was used to estimate freedom from reintervention and all-cause mortality, whereas multivariable Cox proportional hazards modeling identified predictors of death. RESULTS: A total of 145 OMB procedures (R-OMB, n = 48 [33%]; P-OMB, n = 97 [67%]) were analyzed. A majority of R-OMB operations were performed for a failed stent (prior ENDO, n = 39 [81%]; prior OMB, n = 9 [19%]). R-OMB patients were generally younger (66 ± 9 years vs P-OMB, 69 ± 11 years; P = .09) and had lower incidence of smoking exposure (29% vs P-OMB, 48%; P = .07); however, there were no other differences in demographics or comorbidities. R-OMB was associated with less intraoperative transfusion (0.6 units vs P-OMB, 1.4 units; P = .01), but there were no differences in conduit choice or bypass configuration.The overall 30-day mortality and complication rates were 7% (n = 10/145) and 53% (n = 77/145), respectively, with no difference between the groups. Notably, R-OMB had decreased cardiac (6% vs P-OMB, 21%; P < .01) and bleeding complication rates (2% vs P-OMB, 15%; P = .01). The freedom from reintervention (1 and 5 years: R-OMB: 95% ± 4%, 83% ± 9% vs P-OMB: 97% ± 2%, 93% ± 5%, respectively; log-rank P = .21) and survival (1 and 5 years: R-OMB: 82% ± 6%, 68% ± 9% vs P-OMB: 84% ± 4%, 66% ± 7%; P = .91) were similar. Independent predictors of all-cause mortality included new postoperative hemodialysis requirement (hazard ratio [HR], 7.4, 95% confidence interval [CI], 3.1-17.3; P < .001), pulmonary (HR, 2.7, 95% CI, 1.4-5.3; P = .004) and cardiac (HR, 2.4, 95% CI, 1.1-5.1; P = .04) complications, and female sex (HR, 2.1, 95% CI, 1.03-4.8; P = .04). Notably, R-OMB was not a predictor of death. CONCLUSIONS: The perioperative and longer-term outcomes for a remedial OMB after a failed intraluminal stent or previous open bypass appear to be comparable to a P-OMB. These findings support the recently updated clinical practice guideline recommendations for an endovascular-first approach to treating recurrent CMI due to the significant perioperative complication risk of OMB. However, among the subset of patients deemed ineligible for endoluminal reconstruction after failed mesenteric revascularization, R-OMB results appear to be acceptable and highlight the utility of this strategy in selected patients.

Tumor Contact With Internal Mammary Perforator Vessels as Risk Factor for Gross Internal Mammary Lymph Node Involvement in Patients With Breast Cancer.

PURPOSE: The identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in patients with breast cancer. The current study aims to investigate whether tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. METHODS AND MATERIALS: We included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases as well as 230 patients without lymph node metastases. Based on pretreatment dynamic contrast-enhanced magnetic resonance imaging, we assessed contact of the tumor with the internal mammary perforating vessels (IMPV). RESULTS: A total of 59 patients had ipsilateral IMN+ (iIMN+), 10 patients had contralateral IMN+ (cIMN+), and 228 patients had ipsilateral axillary metastases without IMN; 230 patients had node-negative breast cancer. In patients with iIMN+, 100% of tumors had contact with ipsilateral IMPV, with 94.9% (n = 56) classified as major contact. In iIMN- patients, major IMPV contact was observed in only 25.3% (n = 116), and 36.2% (n = 166) had no IMPV contact at all. Receiver operating characteristic analysis revealed that "major IMPV contact" was more accurate in predicting iIMN+ (area under the curve, 0.85) compared with a multivariate model combining grade of differentiation, tumor site, size, and molecular subtype (area under the curve, 0.65). Strikingly, among patients with cIMN+, 100% of tumors had contact with a crossing contralateral IMPV, whereas in cIMN- patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively. CONCLUSIONS: Tumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of patients with breast cancer for irradiation of the internal mammary lymph nodes.

Size thresholds for repair of abdominal aortic aneurysms warrant reconsideration.

BACKGROUND: The historical size threshold for abdominal aortic aneurysm (AAA) repair is widely accepted to be 5.5 cm for men and 5.0 cm for women. However, contemporary AAA rupture risks may be lower than historical benchmarks, which has implications for when AAAs should be repaired. Our objective was to use contemporary AAA rupture rates to inform optimal size thresholds for AAA repair. METHODS: We used a Markov chain analysis to estimate life expectancy for patients with AAA. The primary outcome was AAA-related mortality. We estimated survival using Social Security Administration life tables and published contemporary AAA rupture estimates. For those undergoing repair, we modified survival estimates using data from the Vascular Quality Initiative and Medicare on complications, late rupture, and open conversion. We used this model to estimate the AAA repair size threshold that minimizes AAA-related mortality for 60-year-old average-health men and women. We performed a sensitivity analysis of poor-health patients and 70- and 80-year-old base cases. RESULTS: The annual risk of all-cause mortality under surveillance for a 60-year-old woman presenting with a 5.0 cm AAA using repair thresholds of 5.5 cm, 6.0 cm, 6.5 cm, and 7.0 cm was 1.7%, 2.3%, 2.7%, and 2.8%, respectively. The corresponding risk for a man was 2.3%, 2.9%, 3.3%, and 3.4% for the same repair thresholds, respectively. For a 60-year-old average-health woman, an AAA repair size of 6.1 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 5.7 cm to 7.1 cm. For a 60-year-old average-health man, an AAA repair size of 6.9 cm was the optimal threshold to minimize AAA-related mortality. Life expectancy varied by <2 months for repair at sizes from 6.0 cm to 7.4 cm. Women in poor health, at various age strata, had optimal AAA repair size thresholds that were >6.5 cm, whereas men in poor health, at all ages, had optimal repair size thresholds that were >8.0 cm. CONCLUSIONS: The optimal threshold for AAA repair is more nuanced than a discrete size. Specifically, there appears to be a range of AAA sizes for which repair is reasonable to minmized AAA-related mortality. Notably, they all are greater than current guideline recommendations. These findings would suggest that contemporary AAA size thresholds for repair should be reconsidered.

Evaluating Treatment Response in GEJ Adenocarcinoma: The Role of Pretherapeutic and Posttherapeutic Iodine Mapping.

BACKGROUND: Neoadjuvant therapy regimens have significantly improved the prognosis of GEJ (gastroesophageal junction) cancer; however, there are a significant percentage of patients who benefit from earlier resection or adapted therapy regimens, and the true response rate can only be determined histopathologically. Methods that allow preoperative assessment of response are lacking. PURPOSE: The purpose of this retrospective study is to assess the potential of pretherapeutic and posttherapeutic spectral CT iodine density (IoD) in predicting histopathological response to neoadjuvant chemotherapy in patients diagnosed with adenocarcinoma of the GEJ. METHODS: In this retrospective cohort study, a total of 62 patients with GEJ carcinoma were studied. Patients received a multiphasic CT scan at diagnosis and preoperatively. Iodine-density maps were generated based on spectral CT data. All tumors were histopathologically analyzed, and the tumor regression grade (TRG) according to Becker et al ( Cancer . 2003;98:1521-1530) was determined. Two experienced radiologists blindly placed 5 defined ROIs in the tumor region of highest density, and the maximum value was used for further analysis. Iodine density was normalized to the aortic iodine uptake. In addition, tumor response was assessed according to standard RECIST measurement. After assessing interrater reliability, the correlation of IoD values with treatment response and with histopathologic TRG was evaluated. RESULTS: The normalized ΔIoD (IoD at diagnosis - IoD after neoadjuvant treatment) and the normalized IoD after neoadjuvant treatment correlated significantly with the TRG. For the detection of responders and nonresponders, the receiver operating characteristic (ROC) curve for normalized ΔIoD yielded the highest area under the curve of 0.95 and achieved a sensitivity and specificity of 92.3% and 92.1%, respectively. Iodine density after neoadjuvant treatment achieved an area under the curve of 0.88 and a sensitivity and specificity of 86.8% and 84.6%, respectively (cutoff, 0.266). Iodine density at diagnosis and RECIST did not provide information to distinguish responders from nonresponders. Using the cutoff value for IoD after neoadjuvant treatment, a reliable classification of responders and nonresponders was achieved for both readers in a test set of 11 patients. Intraclass correlation coefficient revealed excellent interrater reliability (intraclass correlation coefficient, >0.9). Lastly, using the cutoff value for normalized ΔIoD as a definition for treatment response, a significantly longer survival of responders was shown. CONCLUSIONS: Changes in IoD after neoadjuvant treatment of GEJ cancer may be a potential surrogate for therapy response.

Application of bioluminescence resonance energy transfer to quantitate cell-surface expression of membrane proteins.

We report a bioluminescence resonance energy transfer (BRET) assay to quantitate the fraction of an engineered membrane protein at the cell surface versus inside the cell. As test cases, we engineered two different G protein-coupled receptors (GPCRs) in which a NanoLuc luciferase (NLuc) and a HaloTag are fused to the extracellular amino-terminal tail of the receptors. We then employed a pulse-chase labeling approach relying on two different fluorescent dyes with distinctive cell permeability properties. The dyes are efficiently excited by luminescence from NLuc, but are spectrally distinct. Measuring BRET from the chemiluminescence of the NLuc to the fluorophores bound to the HaloTag minimizes the limitations of in-cell fluorescence resonance energy transfer (FRET)-based approaches such as photobleaching and autofluorescence. The BRET surface expression assay can quantitatively differentiate between the labeling of receptors at the cell surface and receptors inside of the cell. The assay is shown to be quantitative and robust compared with other approaches to measure cell surface expression of membrane proteins such as enzyme-linked immunosorbent assay or immunoblotting, and significantly increases the throughput because the assay is designed to be carried out in microtiter plate format.

Multi-variate coding for possession: methodology and preliminary results.

In this work we are presenting a database structure to encode the phenomenon of differential possession across languages, considering noun possession classes and possessive constructions as independent but linked. We show how this structure can be used to study different dimensions of possession: semantics, noun valence, and possessive constructions. We present preliminary survey results from a global sample of 120 languages and show that there is a universal semantic core in both inalienable and non-possessible noun classes. Inalienables are centered on body parts and kinship. Non-possessibles are centered on animals, humans, and natural elements.

Sharpness of the Berezinskii-Kosterlitz-Thouless Transition in Disordered NbN Films.

We present a comprehensive investigation of the Berezinskii-Kosterlitz-Thouless transition in ultrathin strongly disordered NbN films. Measurements of resistance, current-voltage characteristics, and kinetic inductance on the very same device reveal a consistent picture of a sharp unbinding transition of vortex-antivortex pairs that fit standard renormalization group theory without extra assumptions in terms of inhomogeneity. Our experiments demonstrate that the previously observed broadening of the transition is not an intrinsic feature of strongly disordered superconductors and provide a clean starting point for the study of dynamical effects at the Berezinskii-Kosterlitz-Thouless transition.

Electrostatic Contribution to 19F Chemical Shifts in Fluorotryptophans in Proteins.

DFT calculations indicate that the 19F chemical shifts of aromatic rings containing single fluorine substituents are sensitive to the electric fields and electric field gradients at the position of the fluorine atom. The present work explores whether long-range structure restraints can be gained from changes in 19F chemical shifts following mutations of charged to uncharged residues. 19F chemical shifts of fluorotryptophan residues were measured in two different proteins, GB1 and the NT* domain, following mutations of single asparagine residues to aspartic acid. Four different versions of fluorotryptophan were investigated, including 4-, 5-, 6-, and 7-fluorotryptophan, which were simultaneously installed by cell-free protein synthesis using 4-, 5-, 6-, and 7-fluoroindole as precursors for the tryptophan synthase present in the S30 extract. For comparison, the 1H chemical shifts of the corresponding nonfluorinated protein mutants produced with 13C-labeled tryptophan were also measured. The results show that the 19F chemical shifts respond more sensitively to the charge mutations than the 1H chemical shifts in the nonfluorinated references, but the chemical shift changes were much smaller than predicted by DFT calculations of fluoroindoles in the electric field of a partial charge in vacuum, indicating comprehensive dielectric shielding by water and protein. No straightforward correlation with the location of the charge mutation could be established.

Rethinking leadership approaches for community-wide opioid crisis intervention: harnessing positive inquiry to unearth front-line insight.

BACKGROUND/AIM: The opioid crisis presents a complex and widespread health challenge for communities, necessitating a deeper exploration beyond simple solutions. To address this crisis, it is crucial to identify and disseminate best practices. In this study, we focused on positive deviance narratives from Columbus, Ohio, a community deeply affected by the opioid crisis. METHODS: Employing an appreciative inquiry framework, we conducted purposive sampling to interview 47 frontline professionals and individuals grappling with opioid use disorder (OUD). RESULTS: Our research revealed several key insights, highlighting successful themes through positive narratives. First, perceiving OUD as a chronic disease emerged as a critical perspective, acknowledging the long-term nature of the condition and the need for sustained care. Second, re-humanising and de-stigmatising opioid users played a vital role in facilitating their recovery and reintegration into society. Embracing inclusive care delivery was another important aspect, ensuring that individuals from diverse backgrounds receive equitable access to effective treatment. Moreover, re-energising professionals to combat burnout proved essential, emphasising the importance of supporting and motivating healthcare providers in their efforts. Finally, fostering cross-institutional relationship building and collaboration emerged as a significant factor, as it encouraged a coordinated approach to addressing the crisis. Designing adaptive organisational structures also played a crucial role, enabling healthcare institutions to respond effectively to evolving challenges. CONCLUSIONS: Using a positive deviance approach to a challenging public health crisis like OUD can help us discover new and innovative care management approaches for community wide interventions.

Genetic Encoding of 7-Aza-l-tryptophan: Isoelectronic Substitution of a Single CH-Group in a Protein for a Nitrogen Atom for Site-Selective Isotope Labeling.

Genetic encoding of a noncanonical amino acid (ncAA) in an in vivo expression system requires an aminoacyl-tRNA synthetase that specifically recognizes the ncAA, while the ncAA must not be recognized by the canonical protein expression machinery. We succeeded in genetically encoding 7-aza-tryptophan (7AW), which is isoelectronic with tryptophan. The system is fully orthogonal to protein expression in Escherichia coli, enabling high-yielding site-selective isotope labeling in vivo. 7AW is readily synthesized from serine and 7-aza-indole using a tryptophan synthetase ß-subunit (TrpB) mutant, affording easy access to isotope-labeled 7AW. Using labeled 7AW produced from 15N/13C-labeled serine, we produced 7AW mutants of the 25 kDa Zika virus NS2B-NS3 protease. 15N-HSQC spectra display single cross-peaks at chemical shifts near those observed for the wild-type protein labeled with 15N/13C-tryptophan, confirming the structural integrity of the protein and yielding straightforward NMR resonance assignments for site-specific probing.

Cell-free synthesis of proteins with selectively 13C-labelled methyl groups from inexpensive precursors.

The novel eCell system maintains the activity of the entire repertoire of metabolic Escherichia coli enzymes in cell-free protein synthesis. We show that this can be harnessed to produce proteins with selectively 13C-labelled amino acids from inexpensive 13C-labelled precursors. The system is demonstrated with selective 13C labelling of methyl groups in the proteins ubiquitin and peptidyl-prolyl cis-trans isomerase B. Starting from 3-13C-pyruvate, 13C-HSQC cross-peaks are obtained devoid of one-bond 13C-13C scalar couplings. Starting from 2-13C-methyl-acetolactate, single methyl groups of valine and leucine are labelled. Labelling efficiencies are 70 % or higher, and the method allows us to produce perdeuterated proteins with protonated methyl groups in a residue-selective manner. The system uses the isotope-labelled precursors sparingly and is readily scalable.

"Redirecting an anti-IL-1ß antibody to bind a new, unrelated and computationally predicted epitope on hIL-17A".

Antibody engineering technology is at the forefront of therapeutic antibody development. The primary goal for engineering a therapeutic antibody is the generation of an antibody with a desired specificity, affinity, function, and developability profile. Mature antibodies are considered antigen specific, which may preclude their use as a starting point for antibody engineering. Here, we explore the plasticity of mature antibodies by engineering novel specificity and function to a pre-selected antibody template. Using a small, focused library, we engineered AAL160, an anti-IL-1ß antibody, to bind the unrelated antigen IL-17A, with the introduction of seven mutations. The final redesigned antibody, 11.003, retains favorable biophysical properties, binds IL-17A with sub-nanomolar affinity, inhibits IL-17A binding to its cognate receptor and is functional in a cell-based assay. The epitope of the engineered antibody can be computationally predicted based on the sequence of the template antibody, as is confirmed by the crystal structure of the 11.003/IL-17A complex. The structures of the 11.003/IL-17A and the AAL160/IL-1ß complexes highlight the contribution of germline residues to the paratopes of both the template and re-designed antibody. This case study suggests that the inherent plasticity of antibodies allows for re-engineering of mature antibodies to new targets, while maintaining desirable developability profiles.

Self-pay insurance status is associated with failure of medical therapy in patients with acute uncomplicated type B aortic dissection.

BACKGROUND: Traditionally, acute uncomplicated type B aortic dissections are managed medically, and acute complicated dissections are managed surgically. Self-pay patients with medically managed acute uncomplicated type B aortic dissections may fare worse than their insured counterparts. METHODS: In this single-center, retrospective cohort study, demographics, follow-up, and outcomes of patients with acute type B aortic dissections from 2011 to 2020 were analyzed. RESULTS: In total, 159 patients presented with acute type B aortic dissections; 102 were complicated and managed with thoracic endovascular aortic repair, and 57 were uncomplicated and managed medically. A total of 32% (n = 51) were self-pay. Self-pay patients were from areas with worse area deprivation indices (71% vs 63%, P = .024). They more often reported alcohol abuse (28% vs 7%, P < .001), cocaine/methamphetamine use (16% vs 5%, P = .028), and nonadherence to home antihypertensives (35% vs 11%, P < .001). Self-pay patients less often had a primary care physician (65% vs 7%, P < .001) or took antihypertensives before admission (31% vs 58%, P = .003). Self-pay patients frequently required financial assistance at discharge (63%), most often using charity funds (46%). Few patients (7%) qualified for our hospital's financial assistance program, and most (78%) remained uninsured at the first follow-up. Self-pay acute uncomplicated type B aortic dissections patients had the lowest rate of follow-up (31% vs 66%, P < .001) and were more likely to represent emergently (75% vs 0%, P = .033) compared to insured acute uncomplicated type B aortic dissections patients. Self-pay patients were more likely to follow up after thoracic endovascular aortic repair for acute complicated type B aortic dissections (82% vs 31%, P < .001). CONCLUSION: Self-pay patients have multiple, interconnected, complex socioeconomic factors that likely influence preadmission risk for dissection and post-discharge adherence to optimal medical management. Further research is needed to clarify treatment strategies in this high-risk group.

Presentation and Outcomes of Elective and Nonelective Complex Endovascular Repair for Thoracoabdominal and Juxtarenal Aortic Aneurysms.

BACKGROUND: Endovascular repair of thoracoabdominal aortic aneurysms (TAAA) and juxtarenal aortic aneurysms (JAA) with fenestrated and/or branched endografts (B/FEVAR) has become common. Physician modified endografts for patients presenting with symptomatic or contained ruptures has made B/FEVAR a feasible option in nonelective settings. The purpose of this study was to describe our 10-year institutional experience with endovascular interventions for TAAA in elective and nonelective cases to evaluate differences in outcomes and the clinical risk factors associated with nonelective presentation. METHODS: A prospectively maintained database was retrospectively queried for patients undergoing B/FEVAR for TAAA and JAA at a single tertiary care academic institution between 1/2011 and 12/2020. Data collected included demographics, comorbidities, presenting symptoms, aneurysm characteristics, and clinical outcomes. Nonelective repair was defined as any patient that presented through the Emergency Department, as a hospital transfer, or as a direct admission from clinic and had aortic repair performed during the same admission. Univariate analyses were used to compare patients. The primary outcomes were 30-day and 1-year mortality. Secondary outcomes included perioperative complications and nonhome discharge. RESULTS: Between 1/201 and 12/2020, a total of 208 patients underwent B/FEVAR for TAAA (173) and JAA (35). Nonelective repair was performed in 44 (21%) patients with 39 for TAAA (23%) and 5 for JAA (14%). Nonelective patients were younger (71 ± 11 vs. 74 ± 7 years, P = 0.03), more likely to be self-pay or have Medicaid (11% vs. 2%, P = 0.02) and had a different race distribution compared to the elective cohort (P < 0.01). Thirty-day mortality was 4% (n = 6) in elective repairs and 7% (n = 3) in nonelective repairs. One-year mortality was 13% (n = 22) in elective repairs and 18% (n = 8) in nonelective repairs. There were no differences between patients receiving elective versus nonelective repair in 30-day (P = 0.40) or 1-year mortality (P = 0.47). Nonelective patients had longer median duration of stay (11 interquartile range (IQR) 6-15 vs. 5 IQR 4-8, P < 0.01), postoperative length of stay (7 IQR 5-12 vs. 4 IQR 3-7, P < 0.01), and more intensive care unit days (6 IQR 3-8 vs. 3 IQR 2-5, P < 0.01). There were no differences in other secondary outcomes between elective and nonelective patients including inpatient and access-related complications, re-interventions, and nonhome discharge (P > 0.05 for all comparisons). A composite "any complication" occurred more frequently in patients with nonelective repair (50% vs. 35%, P = 0.03). CONCLUSIONS: Endovascular repair for TAAA or JAA is a good option in patients undergoing nonelective surgical intervention, with comparable 30-day mortality, 1-year mortality, and perioperative morbidity to that of patients undergoing elective B/FEVAR.

The State Urge to be Physically Active-Questionnaire (SUPA-Q): Development and validation of a state measure of activity urges in patients with eating disorders.

OBJECTIVE: Many people, including patients with eating disorders (EDs), experience an increased urge for physical activity. "Trait"-like activity in patients with EDs is assessed by existing questionnaires, but there are few clinically validated assessments of a "state" urge to be physically active. Here, we developed and validated the State Urge to be Physically Active-Questionnaire (SUPA-Q). METHODS: After developing and piloting the items, N = 126 patients with EDs (mostly anorexia nervosa and bulimia nervosa) took part in our mixed-longitudinal validation study with one primary assessment for all patients and a secondary assessment for a subsample of patients. Cronbach's α and split-half-methods served as measures of consistency and reliability. Correlations with other questionnaires were used to determine convergent and divergent validity, and confirmatory factor analysis was used for investigating factorial validity. We used paired-samples t-tests for repeated assessments to investigate change sensitivity. RESULTS: We found the SUPA-Q to be highly consistent, and reliable and to demonstrate convergent, divergent, and factorial validity. The comparison of SUPA-Q scores from repeated assessments within a subsample of patients demonstrated the questionnaire's change sensitivity, Cohen's d = 0.48. Moreover, an increase in SUPA-Q scores was associated with a less positive mood, more anxiety, more body dissatisfaction, more tenseness, less feelings of control, and more stress. DISCUSSION: The newly developed SUPA-Q may help to accentuate the necessity to evaluate and address the acute urge to engage in physical activity in patients with EDs in clinical practice and ultimately support tailoring treatments to patients' unique symptom patterns. The questionnaire is available at https://doi.org/10.17605/OSF.IO/G2YBC.