Citations

OBJECTIVE The Woven EndoBridge (WEB) device was approved to treat wide-necked bifurcation aneurysms. The device is designed as an intrasaccular flow disruptor covering aneurysm widths up to 10 mm. Although prior studies combined all aneurysm sizes, it is known that aneurysms behave differently in response to endovascular treatment based on their size. Therefore, the authors’ objective was to identify ideal middle cerebral artery (MCA) aneurysm width and neck sizes most suitable for WEB treatment. METHODS The WorldWideWEB consortium is a large multicenter retrospective database that analyzes intracranial aneurysms treated with the WEB device. In this study, all unruptured MCA bifurcation aneurysms with available measurements were included. Cutoff values based on aneurysm width and neck in relation to aneurysm occlusion status were measured using the receiver operating characteristic (ROC) curve. Propensity score matching (PSM) was then used to compare treatment outcomes between aneurysms smaller and larger than the cutoff value for both width and neck size. RESULTS The ideal cutoff values for MCA bifurcation aneurysm width and neck were 6.1 mm and 4.6 mm, respectively. On PSM, 87 matched pairs were compared based on width size (≤ 6.1 mm and > 6.1 mm), and 77 matched pairs were compared based on neck size (≤ 4.6 mm and > 4.6 mm). There was a significant difference in adequate aneurysm occlusion between aneurysms smaller and larger than those cutoff values for both widths (93% vs 76%, p = 0.0017) and neck sizes (90% vs 70%, p = 0.0026). The retreatment rate was also significantly higher for larger aneurysms in both parameters. CONCLUSIONS This study shows that MCA bifurcation aneurysms ≤ 6.1 mm in width and ≤ 4.6 mm in neck size are significantly better candidates for WEB treatment, leading to improved occlusion status and reduced retreatment rate, which are important considerations when using WEB devices.

BACKGROUND AND OBJECTIVES: We aimed to develop and validate a prediction score for futile recanalization (FR) for large vessel occlusion (LVO) presenting low Alberta Stroke Program Early Computed Tomography Score (ASPECTS) for patients who underwent endovascular thrombectomy (EVT). METHODS: Patients with anterior circulation LVO with low ASPECTS (<6) who underwent successful EVT (modified treatment in cerebral ischemia score ≥2b) from Stroke Thrombectomy and Aneurysm Registry were retrospectively analyzed. FR was defined as 90-day modified Rankin Scale (mRS) scores ≥4 despite successful EVT. Multivariable logistic regression was used to identify independent predictors of FR, and they were used to create a clinical score. The performance of the score was assessed by receiver operating characteristic curve analyses. RESULTS: Of 219 patients, 170 and 49 patients were randomly assigned to the training and validation cohort, respectively. Independent predictors of FR identified in the training cohort were used to construct the SNAP score: site of occlusion (middle cerebral artery = 0, internal carotid artery = 1), National Institutes of Health Stroke Scale score at admission (≤10 = 0, 10 to 19 = 1, ≥20 = 2), age (<75 = 0, ≥75 = 2), and prestroke mRS score (0-3). Receiver operating characteristic curve analyses of the SNAP score in the training and validation cohorts showed areas under the curve of 0.79 (95% CI 0.72-0.86) and 0.79 (95% CI 0.65-0.92) for predicting FR, respectively. A SNAP score ≥5 had a positive predictive value of 92.1% [95% CI 78.8%-97.3%] for FR. CONCLUSION: The SNAP score may be useful in predicting FR after EVT in low-ASPECTS patients with LVO. It can provide patients, family members, and physicians with reliable outcome expectations among patients with acute ischemic stroke with large infarcts.

Abstract Many patients in the emergency department present with signs and symptoms that arouse concern for sepsis; however, other explanations are also possible. There are currently no rapid tests used in clinical practice that reliably distinguish the presence of a bacterial or viral infection vs. a non-infectious etiology and can predict a patient’s likelihood to decompensate. The diagnostic and prognostic uncertainty in “gray zone” patients complicates the decision to begin therapy as clinicians need to balance the risk of withholding therapy vs. the risk of the therapy itself (e.g., overtreatment with antibiotics and hospitalization, which is costly, potentially harmful, and contributes to antibiotic resistance). The TriVerity™ Test uses isothermal amplification and machine-learning algorithms to quantify and interpret mRNA expression levels to determine both likelihood of bacterial infection, viral infection, or no infection, and whether the patient will likely require one or more critical interventions within 7 days. The three scores each fall into one of five interpretation bands ranging from Very high to Very low. Testing takes approximately 30 minutes using the proprietary Myrna™ Instrument with an operator hands-on-time of under one minute. We enrolled 1,222 patients from 22 emergency departments (ED) to validate the performance of the TriVerity Test. Patients were treated as per local standard of care and were followed for 28 days. Bacterial and viral TriVerity results were validated against clinically adjudicated infection status; the illness severity TriVerity result was validated against the need for at least one critical interventions within 7 days. The bacterial TriVerity result had high AUROC for the diagnosis of bacterial infection (0.83; 80% CI 0.81–0.85) and divided bacterial infection likelihood scores into five interpretation bands with increasing likelihood ratios of infection ranging from Very low (LR- 0.08, 80% CI 0.06–0.11) to Very high (LR + 8.04, 80% CI 5.72–11.78). The AUROC for the bacterial TriVerity result was significantly higher compared to AUROCs for C-reactive protein, procalcitonin or white blood cell count. Similarly, the viral TriVerity score showed high AUROC for the diagnosis of viral infection (0.91; 80% CI 0.90–0.93) and likelihood ratios from Very low (LR- 0.09, 80% CI 0.05–0.14) to Very high (LR + 40.93; 80% CI 29.11–79.23). The TriVerity Illness Severity score showed a high AUROC for the prediction of illness severity (0.77; 80% CI 0.77–0.81) with scores divided into five interpretation bands with increasing likelihood ratios ranging from Very low (LR- 0.22; 80% CI 0.14–0.33) to Very high (LR + 11.33; 80% CI 7.31–17.00). TriVerity illness severity results allowed marked re-classification of the risk for “ICU-level care” as compared to clinical assessment (qSOFA scores) alone. In conclusion, TriVerity provides rapid, highly accurate and actionable results for the diagnosis and prognosis of patients with suspected acute infection and/or sepsis, supporting a major unmet medical need. TriVerity may improve personalized management of patients with suspected acute infections and suspected sepsis for improved overall healthcare outcomes.

Objectives: Injury to the Medial Ulnar Collateral Ligament (MUCL) is a common setback experienced by many throwing athletes often requiring reconstruction with 12-18 months of rehabilitation. Current reconstructive techniques fail to anatomically restore the MUCL which may contribute to the prolonged course of rehabilitation. In recent years, we described an anatomic MUCL reconstruction with internal brace augmentation which demonstrated improved biomechanical strength when compared to the docking technique in cadaveric specimens. The purpose of this study was to evaluate the postoperative course of both amateur and professional throwing athletes that underwent anatomic MUCL reconstruction with internal brace augmentation. We hypothesized that throwers would return to the same level of play and that return to play (RTP) would be a shorter duration compared to current reported outcomes. Methods: In this surgical technique, the native MUCL is formally repaired. The graft and a suture tape are folded over a suspensory loop and secured in a socket of the medial epicondyle of the humerus to maximize tendon to bone contact. On the ulnar side, the graft and internal brace are secured proximally by two suture anchors on either side of the sublime tubercle and further secured across the sublime tubercle ridge distally to re-create the anatomic triangular insertion of the native ligament. All surgeries were performed by a single surgeon. Patient reported outcomes in addition to date of RTP, level of play, and functional outcomes were retrospectively gathered. All patients initially followed an Accelerated Rehabilitation Protocol and were converted to a Standard Paced protocol if setbacks were encountered. Results: A total of 26 baseball players underwent primary (n=23) or revision (n=3) MUCL reconstruction with the Anatomic Technique. Of these, 15 were professional and 11 were amateur athletes. 92% of throwers returned to play at a mean of 9.9 months following reconstruction. 89% were able to advance through the accelerated postoperative protocol without issues and 85% returned to the same role and level of play. Post injury KJOC scores improved from 41 to 86.9 and SANE scores improved from 32.5 to 95.5. No significant difference was identified in pre-injury versus post-reconstruction throwing velocity, ball spin rate, or horizontal/vertical ball movement. Conclusions: Anatomic reconstruction of the MUCL with internal bracing is a viable option for MUCL injuries. Advantages include increased tendon-bone contact of the reconstruction, multiple fixation points, and anatomic restoration of the MUCL. This technique allowed an expedited return to sport for these baseball athletes.

Importance Historically, women with aortic stenosis have experienced worse outcomes and inadequate recognition compared to men, being both underdiagnosed and undertreated, while also facing underrepresentation in clinical trials. Objective To determine whether women with small aortic annuli undergoing transcatheter aortic valve replacement have better clinical and hemodynamic outcomes with a self-expanding valve (SEV) or balloon-expandable valve (BEV). Design, Setting, Participants The Small Annuli Randomized to Evolut or SAPIEN Trial (SMART) was a large-scale randomized clinical trial focusing on patients with small aortic annuli undergoing transcatheter aortic valve replacement, randomized to receive SEVs or BEVs and included 716 patients treated at 83 centers in Canada, Europe, Israel, and the US from April 2021 to October 2022. This prespecified secondary analysis reports clinical and hemodynamic findings for all 621 women enrolled in SMART. Data for this report were analyzed from February to April 2024. Interventions Transcatheter aortic valve replacement with an SEV or a BEV. Main Outcomes and Measures The composite coprimary clinical end point comprised death, disabling stroke, or heart failure–related rehospitalization. The coprimary valve function end point was the incidence of bioprosthetic valve dysfunction, both assessed through 12 months. Secondary end points included the incidence of moderate or severe prosthesis-patient mismatch. Results A total of 621 women (mean [SD] age, 80.2 [6.2] years; 312 randomized to the SEV group and 309 to the BEV group) were included in the present analysis. At 12 months, there were no significant differences in the coprimary clinical end point between the SEV and BEV groups (9.4% vs 11.8%, absolute risk difference −2.3%; 95% CI −7.2 to 2.5, P = .35). However, SEV implantation was associated with less bioprosthetic valve dysfunction (8.4% vs 41.8%; absolute risk difference, −33.4%; 95% CI, −40.4 to −26.4; P &amp;lt; .001). SEV implantation resulted in lower aortic valve gradients and larger effective orifice areas at 30 days and 12 months and less mild or greater aortic regurgitation at 12 months compared to BEV implantation. Prosthesis-patient mismatch was significantly lower with SEVs, regardless of the definition used and adjustment for body mass index. Use of SEVs was associated with better quality of life outcomes as assessed by the Valve Academic Research Consortium-3 ordinal quality of life measure. Conclusions and Relevance Among women with severe symptomatic aortic stenosis and small aortic annuli undergoing transcatheter aortic valve replacement, the use of SEVs, compared to BEVs, resulted in similar clinical outcomes and a markedly reduced incidence of bioprosthetic valve dysfunction through 12 months, including a lower risk of prosthesis-patient mismatch and better 12-month quality of life. Trial Registration ClinicalTrials.gov Identifier: NCT04722250

Key Points Sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists were superior to dipeptidyl peptidase-4 inhibitor and sulfonylurea for preventing kidney complications in patients with type 2 diabetes at moderate cardiovascular disease risk. Sodium-glucose cotransporter 2 inhibitor therapy compared favorably with glucagon-like peptide-1 receptor agonists for kidney disease outcomes. Background CKD is a serious diabetes-related complication. While guidelines recommend use of sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1RA) therapies to mitigate cardiorenal risk in high-risk patients, the benefit of early initiation of these agents relative to other commonly prescribed glucose-lowering agents in patients at lower baseline cardiovascular disease (CVD) risk remains less clear. Methods This retrospective observational study emulated an idealized target trial using claims data from OptumLabs data warehouse to test the comparative association of treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4i), SGLT2i, GLP-1RA, or sulfonylurea (SU) on a primary kidney composite outcome of incident CKD stages 3–5, kidney failure, or need for KRT in patients with type 2 diabetes and moderate CVD risk. A secondary composite outcome included all components of the primary composite outcome plus death. Results A total of 364,714 adults aged 21 years or older initiating treatment with a DPP-4i ( N =78,843), GLP-1RA ( N =42,049), SGLT2i ( N =45,466), or SU ( N =198,356) were identified. Relative to DPP-4i, SGLT2i (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.67 to 0.74; P < 0.001) and GLP-1RA (HR, 0.87; 95% CI, 0.83 to 0.92; P < 0.001) treatment was superior for the primary composite outcome. Similarly, SGLT2i (HR, 0.69; 95% CI, 0.66 to 0.73) and GLP-1RA (HR, 0.86; 95% CI, 0.82 to 0.91) treatment was associated with risk reductions for the primary outcome relative to SU treatment. When comparing SGLT2i with GLP-1RA therapy, SGLT2is were superior for the primary composite outcome (HR, 0.81; 95% CI, 0.75 to 0.86; P < 0.001). Similar findings were observed for the secondary composite outcome across all comparisons. Conclusions SGLT2is and GLP-1RAs were superior to DPP-4is and SUs for preventing kidney complications in a type 2 diabetes population with moderate baseline CVD risk. Clinical Trial registry name and registration number: NCT05214573.

Abstract Disclosure: K. Yu: None. J. Saini: None. J.N. Farr: None. F. Vanessa: None. S. Khosla: None. I. Bancos: Advisory Board Member; Self; AstraZeneca, Adrenas, Neurocrine, Spruce, Recordati, Xeris, Novo Nordisk, HRA Pharmaceuticals, Sparrow, Diurnal, Corcept. Research Investigator; Self; HRA Pharmaceuticals, Recordati. Importance: Patients with both mild autonomous cortisol secretion (MACS) and overt Cushing syndrome (CS) demonstrated high prevalence of aging-related morbidity and an increased mortality. Objective: To determine whether p16INK4a in T cell, a cell cycle enzyme that associated with chronological aging and cell senescence, is associated with hypercortisolism and hypercortisolism-related comorbidities. Design, Setting, and Participants: In this single-center cross-sectional study, we prospectively recruited consecutive patients with hypercortisolism between July 1, 2020 and August 24 2022. Patients were included if they were diagnosed with Cushing syndrome (CS) or mild autonomous cortisol secretion (MACS). Age- (± 2 years) and sex-matched referent subjects without known adrenal disorders were included if abdominal imaging was available. Participants on exogenous glucocorticoids within 3 months prior were excluded. Exposure: Presence of hypercortisolism (MACS and CS). Main Outcomes and Measures: Primary outcomes included p16INK4a, advanced glycation end products (AGE) reader result, Frailty Index score, frailty (defined as frailty index&gt;0.31), and physical performances in patients and matched referents at index date. Secondary outcomes included correlation between biological age markers, hormonal workup and the risk of comorbidities. p16INK4a expression analysis was adjusted for age, sex, smoking, and alcohol use for all analyses except for associations with CVD and frailty. Results: Of 85 patients (87% women, mean age 53 years), 51 (60%) had MACS (34 had matched referents), 34 (40%) had overt CS (16 had matched referents). Patients with CS demonstrated a median 1.9-fold higher p16INK4a expression (P&lt;.001), and patients with MACS showed a median of 1.70-fold p16INK4a expression (P=.013), when compared to referent subjects. Age- and sex-adjusted p16INK4a expression was associated with frailty index score (r=0.23, P=.035), time-up-and-go test (r=0.28, P=.048), gait speed (r=-0.36, P=.035), but not with AGE reader result, 6-minute walk test, or hand grip measurement. The p16INK4a expression was associated with history of cardiovascular disease (age-adjusted odds ratio (aOR)=3.70, 95% confidence interval (CI), 1.20-11.43) and frailty (aOR=2.27, 95%CI, 1.04-4.98). Conclusion and relevance: We demonstrated evidence of cell senescence in both patients with CS and patients with MACS. Further studies need to determine the impact of surgical, cortisol-lowering, and senolytic medical therapies in MACS on cell senescence and associated aging-related comorbidities. Presentation: 6/1/2024

Abstract Disclosure: M.D. Hurtado: None. E. Tama: None. D. Hodge: None. A. Weston: None. S. Fahad: None. K. Ruddy: None. J. Olson: None. F. Coach: None. R. Carter: None. S. D'Andre: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. Background: Breast cancer (BC) is the most common cancer in women. Weight gain after treatment for early-stage BC is associated with a higher risk of recurrence. Excess adiposity is also a major risk factor for cardiovascular disease, the leading cause of non-BC related death in BC survivors. This study aimed to describe weight trends in a large cohort of BC survivors and to identify predictors of weight gain after BC diagnosis. Methods: This was a retrospective study of BC survivors from the prospectively consented Mayo Clinic Breast Cancer Registry, which has enrolled &gt;10,000 patients seen at least once at Mayo Clinic Rochester for a BC diagnosed within the prior year. We extracted data on weights at baseline, and years 1, 4, and 6 after BC diagnosis to generate longitudinal weight trajectory curves on the change from baseline. Weights were either reported by patients in the registry questionnaires or extracted from the electronic health records. We identified BC survivors with weight gain &gt;10% from baseline weight at years 1, 4, and 6. We then conducted univariable logistic regression analyses to identify predictors of &gt;10% weight gain. Variables considered included: demographics, anthropometrics, BC clinical and pathologic characteristics, BRCA 1 and 2 genetic mutation status, and treatment (surgery, neoadjuvant or adjuvant chemotherapy, and/or radiotherapy). Results: We included 4744 BC survivors, mostly white (95%) and non-Hispanic (91%), with a mean age and weight at BC diagnosis of 58 ± 13 years and 76 ± 18 kg. Most patients had clinical stage I (43%) and ER+ and PR+ BC (83% and 76%, respectively). Most patients underwent breast preserving surgery (62%), half received radiation (54%), one third (36%) received systemic chemotherapy, and two thirds (61%) received endocrine therapy. At one year after BC diagnosis the average weight change was negligible compared to baseline (mean difference -0.2 ± 8 kg), but there were small but significant average increases by years 4 and 6 (0.5 ± 9 kg, p=0.002; and 0.8 ± 10 kg, p&lt;0.001; respectively). At years 1, 4, and 6, the percentage of BC survivors gaining &gt;10% of their baseline weight was 10%, 15%, and 18%, respectively. Baseline characteristics associated with &gt;10% weight gain at 6 years included lower baseline weight (p&lt;0.001), younger age at BC diagnosis (p&lt;0.001), more advanced clinical and pathologic BC stage (p=0.008), ER+ and PR+ tumor biology (p=0.02 for both), BRCA2 mutation (p&lt;0.001), mastectomy (compared to breast preserving surgeries, p=0.008), the use of systemic chemotherapy treatment (p&lt;0.001), and the use of endocrine therapy (p=0.03). Conclusion: While most BC survivors do not experience weight gain after survivorship, 1 out 5 may experience excessive weight gain of more than 10%. Baseline anthropometric and BC-related variables are associated with excessive weight gain and could be used as predictors of weight gain in this population. Presentation: 6/3/2024

Abstract ➤ The COVID-19 pandemic created a persistent surgical backlog in elective orthopedic surgeries. ➤ Artificial intelligence (AI) uses computer algorithms to solve problems and has potential as a powerful tool in health care. ➤ AI can help improve current and future orthopedic backlogs through enhancing surgical schedules, optimizing preoperative planning, and predicting postsurgical outcomes. ➤ AI may help manage existing waitlists and increase efficiency in orthopedic workflows.

Importance In 2022, the US House of Representatives passed a bipartisan resolution (House of Representatives Resolution 1118 at the 117th Congress [2021-2022]) calling for meaningful nutrition education for medical trainees. This was prompted by increasing health care spending attributed to the growing prevalence of nutrition-related diseases and the substantial federal funding via Medicare that supports graduate medical education. In March 2023, medical education professional organizations agreed to identify nutrition competencies for medical education. Objective To recommend nutrition competencies for inclusion in medical education to improve patient and population health. Evidence Review The research team conducted a rapid literature review to identify existing nutrition-related competencies published between July 2013 and July 2023. Additional competencies were identified from learning objectives in selected nutrition, culinary medicine, and teaching kitchen curricula; dietetic core competencies; and research team–generated de novo competencies. An expert panel of 22 nutrition subject matter experts and 15 residency program directors participated in a modified Delphi process and completed 4 rounds of voting to reach consensus on recommended nutrition competencies, the level of medical education at which they should be included, and recommendations for monitoring implementation and evaluation of these competencies. Findings A total of 15 articles met inclusion criteria for competency extraction and yielded 187 competencies. Through review of gray literature and other sources, researchers identified 167 additional competencies for a total of 354 competencies. These competencies were compiled and refined prior to voting. After 4 rounds of voting, 36 competencies were identified for recommendation: 30 at both undergraduate and graduate levels, 2 at the undergraduate level only, and 4 at the graduate level only. Competencies fell into the following nutrition-related themes: foundational nutrition knowledge, assessment and diagnosis, communication skills, public health, collaborative support and treatment for specific conditions, and indications for referral. A total of 36 panelists (97%) recommended nutrition competencies be assessed as part of licensing and board certification examinations. Conclusions and Relevance These competencies represent a US-based effort to use a modified Delphi process to establish consensus on nutrition competencies for medical students and physician trainees. These competencies will require an iterative process of institutional prioritization, refinement, and inclusion in current and future educational curricula as well as licensure and certification examinations.