Citations

Background: Despite mounting clinical evidence for the utility of orthobiologics in nonoperative management of orthopaedic pathology, the market for orthobiologic therapies remains largely unregulated by the Food and Drug Administration, giving rise to a wide range of pricing for these therapeutics by different provider types. Purpose: To determine the availability and pricing for platelet-rich plasma (PRP), amniotic or adipose “stem cell,” and bone marrow aspirate concentrate (BMC) injections for the treatment of knee osteoarthritis among orthopaedic sports medicine and alternative providers (eg, chiropractic clinics and stand-alone “regenerative medicine” clinics) in a major metropolitan city. Study Design: Cross-sectional study. Methods: Orthopaedic sports medicine providers in the Chicagoland area were identified through the American Orthopaedic Society for Sports Medicine (AOSSM) and Arthroscopy Association of North America (AANA) surgeon databases. Alternative clinics offering orthobiologic injections were systematically compiled using Yelp! and Google search listings and reviews. Clinics were contacted using a standardized telephone script. Data were collected for each site on the types of injections offered, whether price was disclosed over the telephone, the price of injections offered, and the source of stem cell injections if they were provided. Mann-Whitney U tests were used to compare the mean price between practices. F tests for equality of variances were used to compare the variability in prices between practice types. Results: A total of 25 unique orthopaedic sports medicine practices (comprising 80 AOSSM/AANA surgeons) and 40 alternative clinics offered PRP, stem cell, and/or BMC injections, as indicated over the telephone. There was no difference in likelihood of offering PRP ( P = .698) or BMC injections ( P = .340). However, alternative clinics were significantly more likely to offer stem cell injections ( P < .001). There was no difference in the willingness to disclose the price for PRP ( P = .269), stem cell injections ( P = .302), and BMC ( P = .528) or the source of what each clinic advertised as stem cell injections ( P = .630). The mean price for a single PRP injection was significantly higher ( P = .011) and significantly more variable ( F statistic = .139; P < .001) at alternative clinics. Similarly, the mean price for a single stem cell injection was significantly higher ( P < .001) and significantly more variable ( F statistic = 0.080; P = .025) at alternative clinics. Conclusion: This study demonstrates that orthobiologic knee injections are highly prevalent for in-clinic use within the Chicago metropolitan area, with PRP being the most commonly used therapeutic. When compared with orthopaedic sports medicine providers, alternative clinics were more likely to offer stem cell injections and charge a significantly greater and more variable amount per PRP and stem cell treatment.

Objective: We aimed to estimate the prevalence of cardiovascular diseases (CVDs) and cardiometabolic diseases (CMB) in Brazil, and their relationship with a healthy lifestyle score based on the six pillars of lifestyle medicine proposed by the American College of Lifestyle Medicine. Methods: Data were derived from the 2019 Brazilian National Health Survey, a nationwide cross-sectional study. The prevalence of CVDs/CMB was based on medical-endorsed, self-reported diagnoses and weighted for sample strata. A healthy lifestyle score (0-14 points; the higher the score, the better) incorporates physical activity, diet, sleep, mental health, risky substance use, and social connections. Results: Among 88,531 adults included in the analysis (mean age: 47.1 years; 52.9% female), the weighted prevalence of CVDs/CMB ranged from 1.9% (stroke) to 25.9% (hypertension). Weighted Poisson regression models, adjusted for age, sex, socioeconomic status, and geographic disparities, showed an inverse linear relationship between lifestyle score and CVDs/CMB prevalence. Participants in the highest lifestyle score quartile exhibited lower prevalence for heart diseases [0.48 (95% CI: 0.43, 0.53)], stroke [0.35 (95% CI: 0.29, 0.43)], hypertension [0.85 (95% CI: 0.80, 0.90)], diabetes [0.80 (95% CI: 0.70, 0.91)], dyslipidemia [0.73 (95% CI: 0.66, 0.80)], and obesity [0.81 (95% CI: 0.74, 0.88)], compared to the lowest quartile ( P < 0.001 for all). Conclusions: Higher scores on the six pillars of lifestyle medicine are associated with a lower prevalence of major CVDs/CMB in Brazil.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45–1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28–2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35–5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53–20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18–0.88]; P interaction =0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

(1) Burn injuries demand multidisciplinary, evidence-based care, yet the extensive literature complicates timely decision making. Retrieval-augmented generation (RAG) synthesizes research while addressing inaccuracies in pretrained models. However, citation bias in sourcing for RAG often prioritizes highly cited studies, overlooking less-cited but valuable research. This study examines RAG’s performance in burn management, comparing citation levels to enhance evidence synthesis, reduce selection bias, and guide decisions. (2) Two burn management datasets were assembled: 30 highly cited (mean: 303) and 30 less-cited (mean: 21). The Gemini-1.0-Pro-002 RAG model addressed 30 questions, ranging from foundational principles to advanced surgical approaches. Responses were evaluated for accuracy (5-point scale), readability (Flesch–Kincaid metrics), and response time with Wilcoxon rank sum tests (p < 0.05). (3) RAG achieved comparable accuracy (4.6 vs. 4.2, p = 0.49), readability (Flesch Reading Ease: 42.8 vs. 46.5, p = 0.26; Grade Level: 9.9 vs. 9.5, p = 0.29), and response time (2.8 vs. 2.5 s, p = 0.39) for the highly and less-cited datasets. (4) Less-cited research performed similarly to highly cited sources. This equivalence broadens clinicians’ access to novel, diverse insights without sacrificing quality. As plastic surgery evolves, RAG’s inclusive approach fosters innovation, improves patient care, and reduces cognitive burden by integrating underutilized studies. Embracing RAG could propel the field toward dynamic, forward-thinking care.

ABSTRACTBackground/ObjectivesImmune‐mediated skin disorders, such as immunobullous dermatoses and leukocytoclastic vasculitis, rarely affect children. While direct immunofluorescence (DIF) biopsy is a standard diagnostic tool, limited data exist on pediatric DIF patterns, rates of positivity, pretest diagnostic concordance, and the relevance of biopsy site. This study sought to address these gaps.MethodsDIF data from all skin and mucosal specimens interpreted at Mayo Clinic's reference immunodermatology laboratory for patients aged 0–18 years (August 22, 2017 to November 30, 2023) were reviewed. DIF results were classified as positive if a characteristic pattern was seen and negative if the findings were negative or nondiagnostic.ResultsOf 986 pediatric DIF studies, 153 (15.5%) were positive and comparable to adult positivity rates (20.9%) during the same period. The most frequent DIF patterns were IgA‐predominant vasculitis (N = 85/153; 55.5%) and lichenoid tissue reaction (N = 21/153;13.7%). Concordance between pretest diagnosis and positive DIF results was highest for linear IgA bullous dermatosis (N = 7/7; 100%) and dermatitis herpetiformis (N = 6/6; 100%). Excluding these entities, DIF changed the pretest diagnosis in 16.7% (N = 19/114) of cases. While lower extremity biopsies were initially more likely to yield positive DIF results, this association disappeared when IgA vasculitis cases were excluded.ConclusionThe most frequent DIF pattern in children was that of IgA‐predominant vasculitis. Pediatric DIF positivity rates closely mirrored those of adults, supporting similar biopsy thresholds. DIF results differed from the pretest impression in a substantial percentage, supporting the value of DIF in select situations in the pediatric population. After controlling for IgA vasculitis, biopsy site was not associated with DIF positivity.

BACKGROUND AND IMPORTANCE: Basilar artery fenestration aneurysms (BAFAs) present significant clinical challenges because of their high rupture risk and complex anatomy. Comprehensive management strategies are required, including thorough vascular assessment and post-treatment surveillance. Integration of complementary analyses such as computational fluid dynamics (CFD) holds promise in facilitating preoperative planning for these intricate lesions. CLINICAL PRESENTATION: A 60-year-old female was diagnosed with a BAFA during evaluation for headaches. Digital subtraction angiography revealed the aneurysm projecting posteriorly with a neck predominantly based on the right limb of the fenestration. After initial treatment with a pipeline embolization device, the aneurysm remained patent, requiring further treatment. A secondary approach with stent-assisted loose-packing coil embolization was then performed, resulting in complete occlusion of the aneurysm. Analysis of pretreatment 3-dimensional rotational angiogram images with CFD provided critical hemodynamic insights. It identified that 38.89% of the aneurysm area was exposed to low wall shear stress (WSS) and 11.5% was exposed to high WSS, indicating a high rupture risk profile with significant areas of both low and high WSS. In addition, low WSS was observed in regions corresponding to daughter sacs, suggesting a higher rupture risk. Streamline analysis indicated increased inflow through the right vertebral artery and the right limb of the fenestration, supporting the initial angiographic impression and guiding the choice of therapeutic strategy. CONCLUSION: This is the first study to analyze the morphology and pretreatment hemodynamics of a BAFA using CFD, illustrating the potential for future development of individualized therapeutic approach–based CFD in complex aneurysms.

Abstract Background and Aims Accurate differentiation of cardiac amyloidosis (CA) from phenotypic mimics remains challenging using current clinical and echocardiographic techniques. The accuracy of a novel artificial intelligence (AI) screening algorithm for echocardiography-based CA detection was assessed. Methods Utilizing a multisite, multiethnic dataset (n = 2612, 52% CA), a convolutional neural network was trained to differentiate CA from phenotypic controls using transthoracic apical four-chamber video clips. External validation was conducted globally across 18 sites including 597 CA cases and 2122 controls. Classification accuracy was assessed on the entire external validation dataset, and subgroup analyses were performed both on technetium pyrophosphate scintigraphy referrals, and individuals matched for age, sex, and wall thickness. Model accuracy was also compared with the transthyretin CA score and the increased wall thickness score within a subset of older heart failure with preserved ejection fraction patients with increased wall thickness. Results Cardiac amyloidosis patients and controls displayed similar age, sex, race, and comorbidities. After the removal of uncertain AI predictions (13%), model discrimination and classification were excellent for the entire external validation dataset [area under the receiver operating characteristic curve (AUROC) 0.93, sensitivity 85%, specificity 93%], irrespective of CA subtype (sensitivity: light-chain = 84%, wild-type transthyretin = 85%, and hereditary transthyretin = 86%). Performance was maintained in subgroup analysis in patients clinically referred for technetium pyrophosphate scintigraphy imaging (AUROC 0.86, sensitivity 77%, specificity 86%) and matched patients (AUROC 0.92, sensitivity 84%, specificity 91%). The AI model (AUROC 0.93) also outperformed transthyretin CA score (AUROC 0.73) and increased wall thickness (AUROC 0.80) scores. Conclusions This AI screening model—using only an apical four-chamber view—effectively differentiated CA from other causes of increased left ventricular wall thickness.

AbstractINTRODUCTIONThis study investigated the role of the ubiquitin–proteasome system (UPS) in dominantly inherited Alzheimer's disease (DIAD) by examining cerebrospinal fluid (CSF) levels of UPS proteins.METHODThe SOMAscan assay was used to detect changes in UPS proteins in mutation carriers (MCs) relative to disease progression; imaging and CSF biomarkers of amyloid, tau, and neurodegeneration measures; and Clinical Dementia Rating scale.RESULTSSubtle increases in specific ubiquitin enzymes were detected in MCs up to two decades before symptom onset, with more pronounced elevations in UPS‐activating enzymes near symptom onset. Significant correlations were found between UPS proteins and Alzheimer's disease (AD) biomarkers, especially between autophagy markers and late‐stage tau biomarkers, microglia, and axonal degeneration.DISCUSSIONThe rise in UPS proteins alongside tau‐related markers suggests UPS involvement in tau neurofibrillary tangles. Elevated CSF UPS proteins in DIAD MCs may serve as indicators of disease progression, and may support the UPS as a therapeutic target in AD.Highlights This study investigates the ubiquitin‐proteasome system (UPS) in Dominantly Inherited Alzheimer's Disease (DIAD), highlighting early molecular changes linked to disease progression. Using SOMAscan proteomics, we identified significant UPS protein alterations in cerebrospinal fluid of mutation carriers, notably up to 20 years before clinical symptom onset. Correlations between UPS protein levels and Alzheimer's biomarkers, particularly tau and neurodegeneration markers, suggest a strong association between UPS dysregulation and tau pathology in DIAD. Dynamic UPS changes align with A/T biological staging: UPS proteins were shown to increase across Aβ/tau (A/T) groups, with largest increases in the A+/T+ group, reinforcing their role in late‐stage tau pathology and disease progression. These findings underscore the potential of UPS proteins as early biomarkers for Alzheimer's disease progression and as novel therapeutic targets, especially in tau‐pathology‐driven neurodegeneration. This work contributes to understanding AD pathogenesis, by emphasizing the importance of protein quality control systems and by offering avenues for future biomarker discovery and therapeutic development in Alzheimer's disease.

Abstract Background Cardiac sarcoidosis (CS) is an infiltrative cardiomyopathy characterized by myocardial granulomatous inflammation, leading to conduction system abnormalities and ventricular arrhythmias. Cardiac resynchronization therapy (CRT) outcomes in CS patients are controversial. The efficacy of CRT with left bundle branch area pacing (LBBAP) in these patients has not yet been elucidated. Objective To evaluate electrocardiographic, echocardiographic and long-term clinical outcomes after CRT with LBBAP in CS patients. Methods In this retrospective multicenter study, conducted between June 2020 and March 2024, patients with a histopathologically confirmed diagnosis of CS with an indication for CRT were included in the analysis. The primary outcome was a composite of all-cause mortality, heart failure related hospitalizations, implantable cardioverter defibrillator shocks and requirement of left ventricular assist device/heart transplant. The primary safety outcome was procedure-related complications. Secondary outcomes included pre- and post-procedural electrocardiographic and echocardiographic parameters and change in NYHA functional class. Results A total of 16 patients were included in the analysis (mean age 66.2 ± 9.4 years; 62.5% female; body mass index 30.4 ± 8.5 kg/m2). Four patients (25%) had isolated CS. The median follow-up was 579 [Q1: 295.5 – Q3: 797.5] days. Five patients (31.25%) experienced the composite outcome. Among these, two patients (12.5%) had acute heart failure related hospitalizations, two patients (12.5%) died due to severe pulmonary hypertension and sepsis complicated by cardiorenal syndrome, respectively; and one patient (6.25%) presented an episode of ventricular tachycardia that was successfully terminated with an implantable cardioverter defibrillator shock. No patients required advanced heart failure therapies. There were no procedure-related complications. There was a significant improvement in paced QRS duration (Pre 156.8 ± 36.2 vs. Post 128.3 ± 22.3 milliseconds, p=0.003), left ventricular ejection fraction (Pre 36.5 ± 10.6% vs. Post 50.4 ± 12.2%, p&lt;0.001), left ventricular end systolic diameter (Pre 52 [39.5 – 84.3] vs. Post 41 [29 – 72] millimeters, p=0.011) and left ventricular end diastolic diameter (Pre 66.7 [48 – 159] vs. Post 61 [44 – 135] millimeters, p=0.023). Ten (62.5%) patients exhibited an improvement ≥ I in NYHA functional class post procedure. Conclusion In CS patients, CRT with LBBAP was associated with significant improvements in electrocardiographic and echocardiographic parameters, as well as NYHA functional class, alongside favorable long-term clinical outcomes by optimizing interventricular dyssynchrony.Graphical abstract ECG and Echo parameters