Citations

Abstract Introduction : Plasma glial fibrillary acidic protein (GFAP) may be associated with amyloid burden, neurodegeneration, and stroke but its specificity for Alzheimer's disease (AD) in the general population is unclear. We examined associations of plasma GFAP with amyloid and tau positron emission tomography (PET), cortical thickness, white matter hyperintensities (WMH), and cerebral microbleeds (CMBs). Methods : The study included 200 individuals from the Mayo Clinic Study of Aging who underwent amyloid and tau PET and magnetic resonance imaging and had plasma GFAP concurrently assayed; multiple linear regression and hurdle model analyses were used to investigate associations controlling for age and sex. Results : GFAP was associated with amyloid and tau PET in multivariable models. After adjusting for amyloid, the association with tau PET was no longer significant. GFAP was associated with cortical thickness, WMH, and lobar CMBs only among those who were amyloid‐positive. Discussion : This cross‐sectional analysis demonstrates the utility of GFAP as a plasma biomarker for AD‐related pathologies.

Background: Dynamic supination is a well-recognized cause of congenital clubfoot deformity relapse. However, there is no consensus on how to diagnose it and there are varied approaches in its management. This study aims to define dynamic supination and indications for treatment by presenting consensus from an international panel of experts using a modified Delphi panel approach. Methods: An international panel of 15 pediatric orthopaedic surgeons with clinical and research expertise in childhood foot disorders participated in a modified Delphi panel on dynamic supination in congenital clubfoot. Panelists voted on 51 statements using a 4-point Likert scale on dynamic supination, clinical indications for treatment, operative techniques, and postoperative casting and bracing. All panelists participated in 2 voting rounds with an interim meeting for discussion. Responses were classified as unanimous consensus (100%), consensus (80% or above), near-consensus (70% to 79%), and indeterminate (69% or less). Results: Consensus was achieved for 34 of 51 statements. Panelists agreed dynamic supination is present when the forefoot is supinated during swing phase of gait with initial contact on the lateral border of the foot. There was also agreement that dynamic supination results from muscle imbalance between the tibialis anterior and the peroneus longus and brevis. There was no consensus on observation of hindfoot varus in dynamic supination, operative indications for posterior release of the ankle joint, or incisional approach for tibialis anterior tendon transfer. Reference to the calcaneopedal unit concept, planes of movement, and phases of gait were deemed important factors for consideration when evaluating dynamic supination. Conclusions: Consensus statements from the Delphi panel can guide diagnosis and treatment of dynamic supination in clubfoot deformity relapse, including clinical decision making regarding preoperative casting, surgical approach, and postoperative immobilization. Near-consensus and indeterminate statements may be used to direct future areas of investigation. Level of Evidence: Level V.

OBJECTIVE Combinations of certain social risk factors of race, sex, education, socioeconomic status (SES), insurance, education, employment, and one’s housing situation have been associated with poorer pain and disability outcomes after lumbar spine surgery. To date, an exploration of such factors in patients with cervical spine surgery has not been conducted. The objective of the current work was to 1) define the social risk phenotypes of individuals who have undergone cervical spine surgery for myelopathy and 2) analyze their predictive capacity toward disability, pain, quality of life, and patient satisfaction–based outcomes. METHODS The Cervical Myelopathy Quality Outcomes Database was queried for the period from January 2016 to December 2018. Race/ethnicity, educational attainment, SES, insurance payer, and employment status were modeled into unique social phenotypes using latent class analyses. Proportions of social groups were analyzed for demonstrating a minimal clinically important difference (MCID) of 30% from baseline for disability, neck and arm pain, quality of life, and patient satisfaction at the 3-month and 1-year follow-ups. RESULTS A total of 730 individuals who had undergone cervical myelopathy surgery were included in the final cohort. Latent class analysis identified 2 subgroups: 1) high risk (non-White race and ethnicity, lower educational attainment, not working, poor insurance, and predominantly lower SES), n = 268, 36.7% (class 1); and 2) low risk (White, employed with good insurance, and higher education and SES), n = 462, 63.3% (class 2). For both 3-month and 1-year outcomes, the high-risk group (class 1) had decreased odds (all p < 0.05) of attaining an MCID score in disability, neck/arm pain, and health-related quality of life. Being in the low-risk group (class 2) resulted in an increased odds of attaining an MCID score in disability, neck/arm pain, and health-related quality of life. Neither group had increased or decreased odds of being satisfied with surgery. CONCLUSIONS Although 2 groups underwent similar surgical approaches, the social phenotype involving non-White race/ethnicity, poor insurance, lower SES, and poor employment did not meet MCIDs for a variety of outcome measures. This finding should prompt surgeons to proactively incorporate socially conscience care pathways within healthcare systems, as well as to optimize community-based resources to improve outcomes and personalize care for populations at social risk.

PURPOSE CALGB 40603 ( NCT00861705 ), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points. PATIENTS AND METHODS The Kaplan-Meier method was used to estimate LTOs in 443 patients who initiated study treatment. Log-rank tests and Cox proportional hazards models evaluated the impact of clinical characteristics, pathologic response, calculated residual cancer burden (RCB) in patients with residual disease (RD), treatment assignment, and dose delivery during wP on LTOs, including event-free survival (EFS). Genomic predictors of treatment response and outcomes were assessed on pretreatment tumor samples by mRNA sequencing. RESULTS Among baseline characteristics, only the clinical stage was associated with LTOs. At a median follow-up of 7.9 years, LTOs were not significantly improved with either carboplatin or bevacizumab, overall or in patients with basal-like subtype cancers by genomic analysis. Patients with pCR (n = 205, 46.3%) had significantly higher 5-year EFS (85.5% v 56.6%, log-rank P < .0001) and overall survival (87.9% v 63.4%, P < .0001) rates compared with patients with RD, even those with RCB class I. Among clinical and genomic features, evidence of immune activation, including tumor-infiltrating lymphocytes and low B-cell receptor evenness, was associated with pCR and improved EFS. CONCLUSION Despite higher pCR rates, neither carboplatin nor bevacizumab appeared to improve LTOs although the study was not powered to assess these secondary end points. pCR was associated with superior LTOs even when compared with minimal RD. Markers of immune activation in pretreatment tumor biopsies were independently associated with higher pCR rates and improved survival.

Increasing antimicrobial resistance and medical device-related infections have led to a renewed interest in phage therapy as an alternative or adjunct to conventional antimicrobials. Expanded access and compassionate use cases have risen exponentially but have varied widely in approach, methodology, clinical situations in which phage therapy might be considered, dosing, route of administration, and outcomes.

AbstractBackgroundThe incidence of colorectal cancer (CRC) among individuals aged younger than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS) of 141 variants.MethodsRelying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3486 cases and 3890 controls aged younger than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve.ResultsIncreasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per SD of ERS = 1.14, 95% confidence interval [CI] = 1.08 to 1.20; odds ratio per SD of PRS = 1.59, 95% CI = 1.51 to 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615 to 0.647). Based on absolute risks, we can expect 26 excess cases per 10 000 men and 21 per 10 000 women among those scoring at the 90th percentile for both risk scores.ConclusionsPersonal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.

PURPOSE: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion. METHODS: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey, (2) systematic review, (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement. RESULTS: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment–related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential. CONCLUSION: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases.