Citations

Abstract Objective The objective was to determine if migraine is independently associated with a greater odds of spontaneous coronary artery dissection (SCAD) in a case–control study. Background There is growing evidence that migraine is associated with SCAD, a non‐atherosclerotic, non‐traumatic cause of myocardial infarction. However, few studies have examined the independent association between migraine and SCAD. Methods A total of 1295 SCAD cases and 1291 (1:1) age, sex, and race/ethnicity matched controls presenting to the Boston, Massachusetts area, using the International Classification of Diseases ninth revision and 10th revision codes from our Research Patient Data Registry, were identified between the years 1990 and 2022. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. For mediation, total effects, natural direct, and indirect effects were estimated using causal inference. Receiver operating characteristic (ROC) curves and area under the curve (AUC) was used to determine predictive power. Statistical significance was defined as p < 0.05. Results Adjusting for age, sex, and race/ethnicity, the data demonstrated an almost two‐fold increased odds of SCAD in patients with migraine (aOR 1.96, 95% CI 1.48–2.6; p < 0.001). There was no effect of aura phenotype on this association. Fibromuscular dysplasia (FMD) was found only in patients with SCAD ( n = 133). After accounting for vascular risk factors, there was no longer an independent association between migraine and SCAD (aOR 0.90, 95% CI 0.63–1.29; p = 0.568). Using a model that adjusted for only demographic variables produced a ROC curve with the lowest predictive power (AUC 0.55) for SCAD, while the vascular risk factor‐adjusted model had a higher predictive power (AUC 0.83). Hypertension appeared to mediate some of the effect of migraine on SCAD (proportion of effect mediated 0.70). FMD was highly associated with an increased risk of SCAD. There remained no independent association between SCAD and migraine when FMD was included in the model. Conclusions The migraine–SCAD association can be partially attributed to the connection between migraine and vascular comorbidities including hypertension and FMD.

Abstract Introduction: Low-dose computed tomography (CT) has been increasingly utilized in FAI due to its improved ability to characterize the complex and variable hip morphologies of FAI patients, compared to plain radiographs. This study defined FAI morphology between females and males as well as across adolescents, young adults, and older adults. Methods: A multi-center, prospective cohort of FAI patients undergoing primary arthroscopy was performed. Patients 14-45 years of age with idiopathic FAI were included. Low-dose CT was used for preoperative planning. Analysis focused on acetabular and femoral morphology and the differences between females/males and adolescents (A,14-18.9)/young adults (Y,19-24.9)/older adults (O,25+). Adolescents were the reference group during analysis. Results: There were 604 patients with CT data. Mean age was 24.9 years with 55.9% female. Males had more anterosuperior coverage (i.e. 64.2% vs 62.5% at 1:00), lower version (14.1° vs 18.0°), smaller femoral neck-shaft angles (130.9° vs 133.4°), and larger alpha angles (i.e. 72.1° vs 58.6° at 1:00) compared to females. Multivariable analysis demonstrated that females had associations with more femoral anteversion (OR: 1.05,CI: 1.03-1.07) and larger femoral neck-shaft angles (OR: 1.11,CI: 1.06-1.16). Males has associations with larger alpha angles at 1:00 (OR: 1.05,CI: 1.02-1.07) and 1:30 (OR: 1.03,CI: 1.00-1.06) as well as radial coverage at 1:00 (OR: 1.18,CI: 1.11-1.26). For females, adolescents had slightly less radial coverage at 2:00 (49.9%) compared to young (51.2%) and older adults (51.4%). Femoral neck-shaft angle decreased across age groups (A: 134.4°,Y: 133.0°,O: 132.7°). Alpha angles increased at 2:00 with age (A:54.6°,Y:55.3°,O:58.7°). Multivariable analysis had femoral neck-shaft angle decreasing for young (OR: 0.932,CI: 0.87) and older adults (OR:0.92,CI: 0.86-0.98) and it also had alpha angle at 1:15 increasing for young adults (OR: 1.03,CI: 1.00-1.06) and older adults (OR: 1.03,CI: 1.01-1.06). Males did not have any appreciable differences alpha angles, femoral version, or acetabular coverage across age groups. Conclusion: Differences in morphology identified on CT exist between females and males as well as across age groups for females. These differences may offer insight into disease pathomechanics between these patient populations. Further studies should confirm these findings and look at how they affect patient outcomes after treatment.

Abstract Background: Long-term outcomes of FAI surgery are critical to understand it’s hip preserving ability, yet few studies have reported mid to long-term survivorship following FAI surgery. The purpose of this study was to report rates of treatment failure after first-generation FAI surgery at an average 10- year follow-up. Methods: A prospective, multicenter cohort study assessed patients treated for FAI with hip arthroscopy or surgical dislocation by seven surgeons at four institutions from 2008 to 2012. Inclusion criteria included primary surgery and diagnosis of isolated cam or combined cam/pincer type FAI. At an average 10-year follow-up, 362/452 eligible hips (80.1%) achieved follow-up. Cox proportional hazards model was used to identify predictors of conversion to total hip arthroplasty (THA). Results: Three hundred and sixty two hips were evaluated at a mean of 10.0 ± 2.3 years follow-up. At time of final follow-up, 34 hips (9.2%) had undergone conversion to THA at a mean of 5.2 ± 3.1 years post-operatively. An additional 18 patients (4.9%) underwent non-arthroplasty revision preservation surgery at a mean of 2.0 ± 1.5 years post-operatively. The Kaplan Meier survivorship rates after 5 and 10 years of surgery were 94.9% and 95.2% for conversion to THA and 91 % and 95.2% for revision hip preservation. Older age (HR:1.06, CI: 1.01-1.10; p=0.009), BMI≥30 (HR:4.14, CI:1.52-11.24, p=0.005), male sex (HR:3.23, CI: 1.18-9.09, p=0.02), and lower baseline mHHS (HR:1.03, CI: 1.01-1.04, p=0.01) were significant predictors of conversion to THA. Conclusion: This study demonstrates that FAI surgery yields durable outcomes with the majority of patients (85.9%) not requiring revision surgery or conversion to total hip arthroplasty at an average 10 years. Age 30 years, male sex, and obesity were significantly associated with the risk of THA conversion.

Abstract External coxa saltans, or lateral snapping hip arises from the abnormal movement of the iliotibial band (ITB) over the greater trochanter. The ITB has two major muscular components: the tensor fascia lata and the gluteus maximus. Thickening of the posterior aspect of the ITB or the anterior aspect of the gluteus maximus as it traverses over the greater trochanter perpetuates the snapping phenomenon. Several open and endoscopic techniques have been described to successfully treat external coxa saltans, with release of the iliotibial band being the accepted treatment approach. This case report presents a previously undescribed etiology of coxa saltans externa whereby trochanteric enthesopathy in the setting of chronic abductor tendinopathy and tendon tearing resulted in pathologic snapping of the iliotibial band over the enthesopathic prominences on the greater trochanter (Video 1). This novel etiology required a novel approach to address the pathologic snapping. Rather than iliotibial band release, the appropriate treatment in this case required resection of the trochanteric enthesopathy with abductor tendon repair followed by complete closure of the iliotibial band which resulted in the resolution of the patient’s symptoms (Figure 1, Video 2). Patient reported outcomes measures (pre/post) including HOOS, PROMIS pain interference, PROMIS physical function and global pain scores demonstrated significant improvement 33 months post-surgery. Recognition of this unique etiology of external coxa saltans ensures the appropriate treatment is employed to address the underlying pathology. The ITB is an important stabilizer of the hip and the tensor fascia lata an important accessory abductor of the hip. Release of the iliotibial band in the setting of underlying abductor dysfunction could potentially lead to further dysfunction and ongoing mechanical symptoms. When patients present with external coxa saltans in the setting of underlying abductor dysfunction and trochanteric enthesopathy, consideration should be given to resection of the enthesophytes with abductor tendon repair as opposed to open or endoscopic ITB release alone.

Abstract Purpose: 1) To report the clinical outcomes and reoperation rates of arthro- and endo-scopic iliopsoas release at short-term follow-up following ipsilateral total hip arthroplasty from two separate medical institutions, and 2) to evaluate whether demographic and radiographic parameters are associated with postoperative patient reported outcomes. Methods: Patients with iliopsoas tendinitis in the setting of prior THA that underwent arthroscopic iliopsoas fractional lengthening from 1988 – 2023 were reviewed at two academic institutions. Patients were included if they had minimum 12-month follow-up and were evaluated for preoperative anterior acetabular component overhang, surgery satisfaction, postoperative subjective hip flexion strength and anterior groin pain improvement, modified Harris Hip Score (mHHS), Single Assessment Numeric Evaluation (SANE) score, Tegner activity scale, visual analog scale (VAS), and revision hip arthroplasty. Results: Sixty hips in 58 patients (19 males, 39 females) were followed for a mean of 39.3 (12.0-105.9) months postoperatively. 77% of patients reported feeling “much” or “slightly better”, 75% reported improved anterior groin pain, and 60% reported improved subjective hip flexion strength. Surgery satisfaction was 7.2 ± 3.3 (scale of 0 to 10). Mean postoperative mHHS, VAS pain at rest, VAS pain with use, and SANE scores were 73.9 ± 19.4, 1.3 ± 2.4, 3.8 ± 2.9, and 71.9 ± 21.9 respectively. Preoperative anterior acetabular component overhang was 3.3 ± 6.5 mm and didn’t significantly correlate with postoperative PROs (p ≥ 0.45). Tegner score improved to 2.9 ± 1.4 from 2.5 ± 1.7 preoperatively (p = 0.0253). Three patients underwent revision arthroplasty at a mean of 25.3 (11.6 – 40.4) months postoperatively, with an acetabular component revision rate of 3.3%. Conclusions: Satisfactory outcomes and low revision arthroplasty rates were observed in patients undergoing arthroscopic iliopsoas lengthening following THA. There was no statistically significant relationship between anterior acetabular component overhang and final PROs. Level of Evidence: IV; Retrospective Case Series

Abstract Studies have identified genetic and epidemiologic factors associated with mammographic density (MD) phenotypes. However, MD-associated genetic variants only account for a small proportion of the total estimated heritability. Interrogating interactions between genetic and epidemiologic factors could potentially identify additional MD-associated loci, expand our understanding of the genetic basis of MD phenotypes, and clarify how epidemiologic factors modulate relationships between genetic variants and MD. We conducted six separate genome-wide, gene–environment (GxE) interaction analyses, applying 2 degrees of freedom (df) and 1df interaction tests, for each of three MD phenotypes (percent density, dense area (DA), and nondense area (NDA)). The six epidemiologic factors considered were height, ever parous, parity, ever menopausal hormone therapy, ever breastfeeding, and months of breastfeeding. We included European ancestry participants from multiple studies within the Markers of Density consortium and the Breast Cancer Association Consortium (n = 4895-16 218 depending on specific analyses). We identified 11 loci with genome-wide significant (P &lt; 5 × 10−8) interaction tests including two novel common genetic signals interacting with parity (8p21.2) and ever breastfeeding (19p13.2) for NDA. Our results suggest that epidemiologic risk factors might influence relationships between common genetic variants and MD phenotypes at particular genomic loci.

Background and Aims: Immunotherapy has emerged as an effective treatment for advanced HCC. We aimed to investigate the real-world effectiveness of immunotherapy compared to lenvatinib in HCC. Approach and Results: From the TriNetX database, we used a target trial emulation framework and identified patients with HCC who received first-line treatment with immunotherapy (atezolizumab/bevacizumab or tremelimumab/durvalumab) or lenvatinib between or between August 2018 and December 2023. OS was compared using Kaplan-Meier analysis and Cox proportional hazards regression. After propensity score matching, 1203 patients were included in each group. Immunotherapy was associated with improved OS versus lenvatinib (median survival: 545 vs. 425 d; HR: 0.86, 95% CI: 0.76–0.97). Regarding treatment type, atezolizumab plus bevacizumab showed improved survival compared to lenvatinib (n=1070 in each group; HR: 0.87, 95% CI: 0.77–0.99), while the point estimate favored durvalumab plus tremelimumab versus lenvatinib (HR: 0.81, 95% CI: 0.59–1.12), though this difference was not statistically significant, likely due to small sample size. Regarding etiology, immunotherapy had improved OS compared to lenvatinib in viral hepatitis (n=510 in each group; HR: 0.74, 95% CI: 0.61–0.89) and alcohol-associated liver disease (n=190 in each group; HR: 0.65, 95% CI: 0.49–0.87), but not in metabolic dysfunction–associated steatotic liver diseases (n=156 in each group; HR: 0.96, 95% CI: 0.70–1.31). Conclusions: In this real-world analysis, immunotherapy was associated with improved OS compared to lenvatinib in advanced HCC, with consistent benefit across most subgroups. These findings support the use of immunotherapy as a first-line treatment for advanced HCC.

Key Points Activin A is implicated in profibrotic and prosenescent kidney injury and correlates with kidney injury markers in animals and humans. Follistatin, through activin A antagonism, reduces senescence burden, macrophage infiltration, and proinflammatory pathway activation in murine diabetic kidney disease. Follistatin and other antagonists of activin A signaling pathways may be promising, novel therapeutics for diabetic kidney disease. Background Circulating activin A, an inflammatory mediator implicated in profibrotic kidney injury and cellular senescence-induced adipose tissue dysfunction, is increased in human diabetic kidney disease (DKD) and directly correlates with kidney dysfunction. We tested the hypothesis that activin A increases kidney injury, senescent cell abundance, and macrophage infiltration in DKD and antagonism through follistatin (FS) therapy diminishes these effects. Methods An accelerated nephropathy type 2 diabetes (db/db) mouse model was generated by implantation of angiotensin II-loaded osmotic minipumps resulting in increased albuminuria and glomerular and tubular injury. Kidney repair effects of FS (5 µ g intraperitoneal; two doses) were assessed through markers of kidney injury, fibrosis, inflammation, cellular senescence, and macrophage infiltration. In vitro studies examined antiactivin effects of FS on high glucose-exposed human monocytes, renal fibroblasts, and renal tubule epithelial cells. Results Activin A antagonism with FS reduced senescence (p19), proinflammatory (including senescence-associated secretory phenotype), and profibrotic markers including activin A. FS improved kidney morphology, restored podocyte markers (nephrin and Wilms tumor-1), and reduced kidney injury biomarkers, albuminuria and kidney fibrosis. FS decreased kidney macrophage and leukocyte infiltration and absent in melanoma 2 inflammasome activation. FS seemed to suppress inflammation through the toll-like receptor-4/NF kappa-light-chain-enhancer of activated B cells pathway in vivo further supported in human macrophages in vitro . In addition, FS reduced hyperglycemia-induced renal fibroblast activation and renal tubule epithelial cell senescence in vitro . Conclusions Activin A is a mediator of kidney injury through macrophage-associated inflammation in murine DKD. FS acts through senomorphic activities which inhibit profibrotic, proinflammatory, and prosenescence signaling by activin A. Hence, antiactivin targeting may aid in the development of a promising, novel therapeutic for DKD.

Key Points Pooled discrimination metrics were acceptable (area under the receiver operating characteristic curve >0.70) for all AKI risk classification categories in both internal and external validation. Better performance was observed in most recently published studies and those with a low or unclear risk of bias. Significant heterogeneity in patient populations, definitions, clinical predictors, and methods limit implementation in real-world clinical scenarios. Background Artificial intelligence through machine learning models seems to provide accurate and precise AKI risk classification in some clinical settings, but their performance and implementation in real-world settings has not been established. Methods PubMed, Excerpta Medica (EMBASE) database, Web of Science, and Scopus were searched until August 2023. Articles reporting on externally validated models for prediction of AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric patients were searched using text words related to AKI, artificial intelligence, and machine learning. Two independent reviewers screened article titles, abstracts, and full texts. Areas under the receiver operating characteristic curves (AUCs) were used to compare model discrimination and pooled using a random-effects model. Results Of the 4816 articles initially identified and screened, 95 were included, representing 3.8 million admissions. The Kidney Disease Improving Global Outcomes (KDIGO)-AKI criteria were most frequently used to define AKI (72%). We identified 302 models, with the most common being logistic regression (37%), neural networks (10%), random forest (9%), and eXtreme gradient boosting (9%). The most frequently reported predictors of hospitalized incident AKI were age, sex, diabetes, serum creatinine, and hemoglobin. The pooled AUCs for AKI onset were 0.82 (95% confidence interval, 0.80 to 0.84) and 0.78 (95% confidence interval, 0.76 to 0.80) for internal and external validation, respectively. Pooled AUCs across multiple clinical settings, AKI severities, and post-AKI complications ranged from 0.78 to 0.87 for internal validation and 0.73 to 0.84 for external validation. Although data were limited, results in the pediatric population aligned with those observed in adults. Between-study heterogeneity was high for all outcomes (I 2 >90%), and most studies presented high risk of bias (86%) according to the Prediction Model Risk of Bias Assessment Tool. Conclusions Most externally validated models performed well in predicting AKI onset, AKI severity, and post-AKI complications in hospitalized adult and pediatric populations. However, heterogeneity in clinical settings, study populations, and predictors limits their generalizability and implementation at the bedside.