Citations

Introduction: The relationship between aortic stenosis (AS) severity, AS-related symptoms, and clinical outcomes is poorly understood. Research Question: Does a history of AS-related symptoms at the time of diagnosis affect clinical outcomes including death and AS-related hospitalization? Methods: Using a combination of natural language processing algorithms and administrative codes, we ascertained physician-assessed AS, AS severity, and AS-related symptoms (chest pain, acute coronary syndrome, syncope, presyncope, orthopnea, dyspnea, PND, and worsening heart failure) in the year prior or up to 60 days after an initial AS diagnosis among 602,821 adults with echocardiograms in a large, integrated health system from 2010-2019. We examined multivariable associations between AS severity and recent AS-related symptoms for the outcomes of death and AS-related hospitalizations using Cox models. Results: Among 40,333 patients identified with incident AS, the majority had recent AS-related symptoms (mild: 80%, mild-moderate: 77%, moderate: 77%, moderate-severe: 85%, and severe AS: 87%). Patients with recent symptoms were older (mean [SD] age 78 [10] vs 75 [11] years; p<0.01), more likely female (51% vs 47%; p<0.01), and had a higher comorbidity burden. In unadjusted analyses, symptom status was a strong discriminator of risk over a median (IQR) of 2.2 (0.8-4.3) years of follow-up ( Figure ). After multivariable adjustment, AS-related symptoms remained strongly associated with death and AS-related hospitalization across the spectrum of AS severity, with moderate symptomatic patients having risk similar to severe asymptomatic patients. Conclusions: The majority of patients diagnosed with AS have recent and/or active AS-related symptoms, which is associated with a significantly increased risk of adverse outcomes. Incorporating symptom status across the individual grades of AS may improve risk stratification beyond AS severity alone.

Abstract Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. Patients and Methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy “graduates” if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. Results: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%–99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. Conclusions: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority &gt;90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

Study Design: Retrospective review of a prospectively maintained database. Objective: Assess differences in preoperative status and postoperative outcomes among patients of different educational backgrounds undergoing surgical management of cervical spondylotic myelopathy (CSM). Summary of Background Data: Patient education level (EL) has been suggested to correlate with health literacy, disease perception, socioeconomic status (SES), and access to health care. Methods: The CSM data set of the Quality Outcomes Database (QOD) was queried for patients undergoing surgical management of CSM. EL was grouped as high school or below, graduate-level, and postgraduate level. The association of EL with baseline disease severity (per patient-reported outcome measures), symptoms >3 or ≤3 months, and 24-month patient-reported outcome measures were evaluated. Results: Among 1141 patients with CSM, 509 (44.6%) had an EL of high school or below, 471 (41.3%) had a graduate degree, and 161 (14.1%) had obtained postgraduate education. Lower EL was statistically significantly associated with symptom duration of >3 months (odds ratio=1.68), higher arm pain numeric rating scale (NRS) (coefficient=0.5), and higher neck pain NRS (coefficient=0.79). Patients with postgraduate education had statistically significantly lower Neck Disability Index (NDI) scores (coefficient=-7.17), lower arm pain scores (coefficient=−1), and higher quality-adjusted life-years (QALY) scores (coefficient=0.06). Twenty-four months after surgery, patients of lower EL had higher NDI scores, higher pain NRS scores, and lower QALY scores (P<0.05 in all analyses). Conclusions: Among patients undergoing surgical management for CSM, those reporting a lower educational level tended to present with longer symptom duration, more disease-inflicted disability and pain, and lower QALY scores. As such, patients of a lower EL are a potentially vulnerable subpopulation, and their health literacy and access to care should be prioritized.

PURPOSE There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer. METHODS We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity. RESULTS Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship ( Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2–enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity. CONCLUSION This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.

Case: This report describes the case of an athletic 12-year-old boy who presented with a 64° left proximal humeral varus angulation deformity and physeal bar secondary to multiple operations for a proximal humeral metaphyseal cystic lesion and pathologic fracture. Using a combined lateral closing and medial opening-wedge osteotomy, a 68° valgus correction was achieved with excellent clinical and functional outcomes at 16-month follow-up. Forward flexion increased from 120 to 170° preoperatively to postoperatively while abduction improved from 110° preoperatively to 170° postoperatively. Conclusion: A combined lateral closing and medial opening-wedge osteotomy of the proximal humerus can successfully treat cases of extreme proximal humerus varus in the growing shoulder where unilateral or dome osteotomies are not suitable.