Citations

Introduction We prospectively investigated the associations between diabetes-related family conflict, parent engagement in child type 1 diabetes (T1D) care, and child glycated hemoglobin (HbA1c) in 127 families of school-age children who we recruited within the first year of their T1D diagnosis. Research design and methods Parents completed the Diabetes Family Conflict Scale-Revised (DFCS-R) to assess for diabetes-related family conflict and the Diabetes Self-Management Questionnaire-Brief (DSMQ-Brief) to assess parent engagement in child T1D care at the initial study visit (T1) and at 12 (T2) and 27 (T3) months later. We also collected child HbA1c at these time points. Our analyses included Pearson correlations and repeated measures linear mixed models controlling for child age, sex, and T1D duration at T1. Results Parents’ DFCS-R scores negatively correlated with DSMQ-Brief scores (r=−0.13, p<0.05) and positively correlated with children’s HbA1c (r=0.26, p<0.001). In our linear mixed models, parents’ DSMQ-Brief scores were unchanged at T2 (β=−0.71, 95% CI −1.59 to 0.16) and higher at T3 (β=8.01, 95% CI 6.89 to 9.13) compared with T1, and there was an association between increasing DFCS-R and decreasing DSMQ-Brief scores (β=−0.14, 95% CI −0.21 to −0.06). Child HbA1c values were significantly higher at T2 (β=0.66, 95% CI 0.38 to 0.94) and T3 (β=0.95, 95% CI 0.63 to 1.27) compared with T1, and there was an association between increasing DFCS-R scores and increasing child HbA1c (β=0.04, 95% CI 0.02 to 0.06). Conclusions Increasing diabetes-specific family conflict early in T1D may associate with decreasing parent engagement in child T1D care and increasing child HbA1c, suggesting a need to assess and intervene on diabetes-specific family conflict. Trial registration number NCT03698708.

Abstract The role of haploidentical hematopoietic cell transplantation (HCT) using posttransplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariable analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) among haploidentical HCTs using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD), 7 /8 HLA-MUD, or umbilical cord blood (UCB) HCT. Comparing haploidentical HCT to MSD HCT, we found that OS, leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher in MSD HCT. Compared with MUD HCT, OS, LFS, and relapse were not different, but MUD HCT had increased NRM (hazard ratio [HR], 1.42; P = .02), grade 3 to 4 aGVHD (HR, 1.59; P = .005), and cGVHD. Compared with 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR, 1.38; P = .01) and increased NRM (HR, 2.13; P ≤ .001), grade 3 to 4 aGVHD (HR, 1.86; P = .003), and cGVHD (HR, 1.72; P ≤ .001). Compared with UCB HCT, late OS, late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months; HR, 1.93; P &lt; .001), worse early LFS (HR, 1.40; P = .007) and increased incidences of NRM (HR, 2.08; P &lt; .001) and grade 3 to 4 aGVHD (HR, 1.97; P &lt; .001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared with traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in complete remission.

Abstract Purpose The aim of the study was to appraise the current evidence on the optimal serum level for lamotrigine (LAM) in the treatment of mood disorders (major depressive disorder, bipolar disorder). Methods Major databases were searched for randomized controlled trials, open-label trials, and observational studies reporting serum LAM levels in adult patients treated with LAM for mood disorders. Results A total of 814 abstracts were screened and 24 articles were selected for full-text review. Seven studies (226 bipolar disorder and 17 major depressive disorder patients) including 1 randomized controlled trial (n = 43), 3 prospective (n = 53), and 3 retrospective (n = 147) studies met the study criteria with a study duration range from 6 to 96 weeks. Lamotrigine daily dosage varied from 25 to 425 mg/d among the studies. Studies reported inconsistent findings between LAM concentration and efficacy. Three studies did not identify a relationship between LAM levels and a significant improvement in mood symptoms. Two studies (n = 99) reported higher response rates with LAM serum levels of greater than 3.25 μg/mL and 1 study (n = 25) reported a wide therapeutic window of 5 to 11 μg/mL. Overall, LAM was well tolerated with no major significant adverse effects. Conclusions Most studies showed a minimum LAM threshold level of 3 μg/mL in patients with mood disorders; however, the data are inconsistent regarding the therapeutic range for LAM. Based on the pooled data, there is inconsistent evidence to make conclusive recommendations on therapeutic LAM serum levels for mood improvement. Further studies including larger sample sizes are required to address this relevant clinical question.

» In the United States, orthopaedic surgeons have a legal obligation to obtain informed consent from patients before performing surgery; it is a process that includes a signed written document. » There are specific legal requirements that vary somewhat by state but generally include disclosure and documentation of the diagnosis, an explanation of the recommended procedure, a conversation about the risks and benefits of the procedure, and a discussion about alternative treatments. » Inadequate disclosure of risks and alternatives is associated with increased indemnity risk. » Studies have shown that many consent processes and forms are suboptimal.

Objectives: Identification of gene variants of stroke subtypes is important for the development of tailored ischemic stroke therapies among various ethnic groups. Valid and reliable determination of ischemic stroke subtype is essential for achieving this goal and to standardize a classification scheme across multi-center studies and different populations. Causative Classification System for Ischemic Stroke (CCS) is a novel computerized subclassification tool developed to improve reliability and accuracy of classifying stroke types. The CCS algorithm relies on both phenotypic and causative stroke variables. A Hispanic subset of the SiGN, an important and distinct target population with greater risk of certain stroke subtypes, was evaluated with Trial of Org 10172 in Acute Stroke Treatment (TOAST) and CCS and the agreement between the two classification systems was analyzed. Methods: Over 6000 subjects at 15 sites across US and Europe were enrolled, with TOAST and CCS locally adjudicated. Blood collection and central data quality control (10% central readjudication) were performed on all participants. A subset of Hispanics was analyzed for the purpose of this study and the agreement between the TOAST and CCS were assessed by kappa statistic. Findings: Hispanics (n=595, 10.9%) compared to non-Hispanics (n=5457) were more likely to be younger (63.7 vs. 64.0), male (55% vs. 46%) and have fewer of the traditional stroke risk factors HTN (54% vs. 64%), Afib (11% vs. 14%), DM(23% vs. 25%), CAD(16% vs. 20%) and smoking(19% vs. 22%). While the TOAST showed no differences between stroke subtypes for Hispanic vs. non-Hispanics, in CCS, Hispanics were classified with more of large vessel (22% vs. 20%), cardioembolic (37% vs. 30%) and small vessel strokes (13% vs. 9%) and fewer with undetermined etiology (28% vs. 40%) as compared to non-Hispanics. TOAST and CCS offered moderate correlation across all stroke types in Hispanics: kappa of 0.66 for large artery atherosclerosis, 0.58 for cardioembolic, and 0.58 for small artery occlusion. Conclusion: CCS offers a more sensitive and accurate system for subphenotyping of strokes in Hispanics who tended to have relatively fewer risk factors and unclassified strokes. Further studies correlating the two classification systems and their relation to genotyping data are warranted.

Abstract There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P &lt; .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P &lt; .001). Long-term relapse was lower with FM (HR = 0.65, P &lt; .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

BACKGROUND Cytometry by time‐of‐flight (CyTOF) or mass cytometry is a form of flow cytometry. CyTOF uses antibodies bound to metal isotopes as tags instead of fluorochromes normally used in standard flow cytometry. These nonradioactive isotopes of heavy metals allow mass cytometry to analyze up to 50 different parameters without significant signal overlap. Due to the accuracy of mass cytometry, researches are able to investigate multiple cell markers at once, which is not possible with standard fluorescent flow cytometry (FFC). CyTOF works by feeding a cell sample tagged with conjugated antibodies into a nebulizer where cells are aerosolized. The aerosolized samples pass through an argon plasma torch and become an ionized atom cloud. This cloud passes through a quadrupole where low mass ions are filtered out resulting in a cloud enriched for the heavy metal reporter tags. The tags enter the time‐of‐flight chamber and further separated by mass as they reach the detector AIMS The main aim of this project was to optimize the stimulation conditions that are best suited for use with a CyTOF T cell functional panel. This would provide a method for decreased cell loss in sample preparation. METHODS T‐cell‐enriched samples underwent stimulation using 4 different condition: 4‐hour stimulation of PMA/Ionomycin, 1:1 ratio of Dynabeads at 24h, 48h, and 72h. Brefeldin A was placed in every well containing cells to act as transport inhibitor. FFC was used to test cell recovery and cell death between stimulation techniques and stimulation strength was observed using CyTOF. RESULTS There was no significant difference in 4h unstimulated cells and 24h unstimulated cells in both cell recovery and cell viability. However, comparing the PMA/Ionomycin unstimulated cells to the 4h stimulated cells did produce a significant decrease in cell recovery and cell death. Because this technique is a non‐physiological stimulation, this result was expected. The use of FFC also allowed us to see the significant loss of cells in recovery and death after 24h stimulation with the 48h and 72h Dynabead assays. The “sledge hammer” effect is clearly visible with the PMA/Ionomycin with 2.73% of IL‐4 cells being stimulated compared to only 0.28% in the 24h Dynabead sample. This trend of PMA/Ionomycin producing a strong stimulation signal was a trend. CONCLUSIONS We determined that T cell culture with Brefeldin A beyond 24 h significantly decreases cell viability and recovery. In observing the stimulation for Dynabeads at 24h, the cells are not directly affected while PMA/Ionomycin does cause a significant loss in cell viability and total cells recovered. PMA/Ionomycin is capable of stimulating the production of all measurable cytokines, even rare populations such as IL‐10‐ or IL‐6‐producing T cells. Dynabeads resemble a more physiological stimulation condition and is able to activate all T cell subsets except IL‐6‐producing T cells. Support or Funding Information The Berner Charitable and Scholarship Foundation, Funded by the Immune Monitoring Core and The Division of Hematology This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Walking tests, such as the 6-min walk test (6MWT), are popular methods of estimating peak oxygen uptake (VO2peak) in clinical populations. However, the strength of the distance vs. VO2peak relationship is not strong, and there are no equations for estimating ventilatory threshold (VT), which is important for training prescription and prognosis. Since the 6MWT is often limited by walking mechanics, prediction equations that include simple additional predictors, such as the terminal rating of perceived exertion (RPE), hold the potential for improving the prediction of VO2max and VT. Therefore, this study was designed to develop equations for predicting VO2peak and VT from performance during the 6MWT, on the basis of walking performance and terminal RPE. Clinically stable patients in a cardiac rehabilitation program (N = 63) performed the 6MWT according to the American Thoracic Society guidelines. At the end of each walk, the subject provided their terminal RPE on a 6–20 Borg scale. Each patient also performed a maximal incremental treadmill test with respiratory gas exchange to measure VO2peak and VT. There was a good correlation between VO2peak and 6MWT distance (r = 0.80) which was improved by adding the terminal RPE in a multiple regression formula (6MWT + RPE, R2 = 0.71, standard error of estimate, SEE = 1.3 Metabolic Equivalents (METs). The VT was also well correlated with walking performance, 6MWT distance (r = 0.80), and was improved by the addition of terminal RPE (6MWT + RPE, R2 = 0.69, SEE = 0.95 METs). The addition of terminal RPE to 6MWT distance improved the prediction of maximal METs and METs at VT, which may have practical applications for exercise prescription.