Cottonandersson0721
Older AML patients have low remission rates and poor survival outcomes with standard chemotherapy. Microtransplantation (MST) refers to infusion of allogeneic hematopoietic stem cells without substantial engraftment. MST has been shown to improve clinical outcomes compared with chemotherapy alone. This is the first trial reporting on broad correlative studies to define immunologic mechanisms of action of MST in older AML patients. Older patients with newly diagnosed AML were eligible for enrollment, receiving induction chemotherapy with cytarabine (100 mg/m2) on days 1-7 and idarubicin (12 mg/m2) on days 1-3 (7 + 3). MST was administered 24 hours later. Patients with complete response (CR) were eligible for consolidation with high dose cytarabine (HiDAC) and a second cycle of MST. Responses were evaluated according to standard criteria per NCCN. Immune correlative studies were performed. Sixteen patients were enrolled and received 7 + 3 and MST (median age 73 years). Nine (56%) had high-risk and seven (44%) had standard-risk cytogenetics. Ten episodes of CRS were observed. Auranofin research buy No cases of GVHD or treatment-related mortality were reported. Event-free survival (EFS) was 50% at 6 months and 19% at 1 year. Overall survival (OS) was 63% at 6 months and 44% at 1 year. Donor microchimerism was not detected. Longitudinal changes were noted in NGS, TCR sequencing, and cytokine assays. Addition of MST to induction and consolidation chemotherapy was well tolerated in older AML patients. Inferior survival outcomes in our study may be attributed to a higher proportion of very elderly patients with high-risk features. Potential immunologic mechanisms of activity of MST include attenuation of inflammatory cytokines and emergence of tumor-specific T cell clones. © 2020 Wiley Periodicals, Inc.The objective of this study was to find the effect of hallux valgus (HV) deformity on the inter-segmental motion of the foot using an MFM with a 15-marker set (DuPont Foot Model, DuFM) in comparison with age and sex controlled healthy adults. Fifty-eight female symptomatic HV patients and 50 female asymptomatic older female volunteers were included in this study. According to the radiographic hallux valgus angle (HVA), the study population was divided into severe HV (SHV, HVA ≥ 40°, n = 25), moderate HV (MHV, 20° ≤ HVA less then 40°, n = 47), and control (CON, n = 36). MHV group was divided into symptomatic MHV group (S-MHV, n = 33) and asymptomatic MHV group (A-MHV, n = 14) according to the symptoms associated with HV. For temporal parameters, gait speed and stride length were diminished according to the severity of HV deformity. Sagittal range of motion of hallux and hindfoot decreased significantly in SHV group. Loss of push-off during the preswing phase was observed and forefoot adduction motion during terminal stance was decreased in SHV group. In a subgroup analysis of MHV, asymptomatic HV minimally affects gait and inter-segmental motion during gait. HV deformity affects gait parameters and inter-segmental motion of the foot during gait in proportion to the severity of the deformity. However, the effect of MHV itself on foot kinematics might be limited while pain or arthritic change of the joint might cause changes in gait in patients with symptomatic HV. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.The failure of total hip arthroplasty (THA) is commonly associated with the necrosis of the periprosthetic tissue. To date, there is no established method to noninvasively quantify the progression of such necrosis. Magnetic resonance imaging (MRI) of soft tissues near implants has undergone a recent renaissance due to the development of multispectral metal-artifact reduction techniques. Advanced analysis of multispectral MRI has been shown capable of detecting small magnetism effects of metallic debris in periprosthetic tissue. The purpose of this study is to demonstrate the diagnostic utility of these MRI-based tissue-magnetism signatures. Together with morphological MRI metrics, such as synovial volume and thickness, these measurements are utilized as biomarkers to noninvasively detect soft-tissue necrosis in symptomatic THA patients ( N = 78 ). All subjects underwent an advanced MRI scan before revision surgery and tissue biopsies utilized for necrosis grading. Statistical analyses demonstrated a weak, but significant positive correlation (P = .04) between MRI magnetism signatures and necrosis scores, while indicating no meaningful association between the latter and serum cobalt and chromium ion levels. Receiver-operating characteristic (ROC) analyses were then performed based on uni- and multivariate logistic regression models utilizing the measured MRI biomarkers as predictors of severe necrosis. The area under the curve of the ROC plots for MRI biomarkers as combined predictors were found to be 0.70 and 0.84 for cross-validation and precision-recall tests, respectively. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.BACKGROUND There is great interest in understanding whether interventions on sugar-sweetened beverage (SSB) consumption through pregnancy and early childhood affect adolescent body mass index (BMI). Without data from randomised trials, unbiased estimation of such effects might be achieved with observational data given sufficient and appropriate adjustment for both baseline and time-varying confounders. OBJECTIVES To illustrate the use of inverse probability (IP) weighting of marginal structural models (MSM) for estimating the effects of SSB consumption through pregnancy and early childhood on the mean early adolescent BMI z-score. METHODS Our baseline sample consisted of 1584 pregnant women from a pre-birth cohort. We defined 6 intervention intervals early pregnancy, late pregnancy, 3, 4, 5, and 6 years. We fitted a MSM via a weighted linear regression with IP exposure and censoring weights to estimate the mean difference in BMI z-score under interventions "maintain SSB consumption below (vs above) 0.5 servin in similar causal questions. © 2020 John Wiley & Sons Ltd.