Citations

Background: Quantitative magnetic resonance (qMR) can be used to measure macromolecules in tissues and is a potential method of observing early cartilage changes in the development of posttraumatic osteoarthritis. Hypothesis/Purpose: We hypothesized that specific patient and surgical factors affecting cartilage matrix composition after anterior cruciate ligament (ACL) reconstruction (ACLR) can be detected using T1ρ and T2 relaxation times. Our purpose was to demonstrate this ability in a multicenter feasibility study. Study Design: Case series; Level of evidence, 4. Methods: A total of 54 patients who underwent ACLR underwent bilateral MRI at baseline before surgery and 6 months postoperatively. Operative findings were recorded. T1ρ and T2 relaxation times were calculated for 6 cartilage regions: the medial femur, lateral femur, medial tibia, lateral tibia, patella, and trochlea. A paired t test compared relaxation times at baseline and 6 months, univariate regression identified regions that influenced patient-reported outcome measures, and analysis of covariance was used to determine the surgical factors that resulted in elevated relaxation times at 6 months. Results: The injured knee had significantly prolonged T1ρ and T2 relaxation times in the tibiofemoral compartment at baseline and 6 months but had shorter values in the patellofemoral compartment compared with the uninjured knee. Prolonged T1ρ and T2 times at 6 months were noted for both the injured and uninjured knees. At 6 months, prolongation of T1ρ and T2 times in the tibial region was associated with lower patient-reported outcome measures. ACLR performed within 30 days of injury had significantly shorter T1ρ times in the tibial regions, and lateral meniscal tears treated with repair had significantly shorter T1ρ times than those treated with excision. Conclusion: Prolonged relaxation times in multiple regions demonstrate how the injury affects the entire joint after an ACL tear. Changes observed in the uninjured knee may be caused by increased loading during rehabilitation, especially in the patellofemoral articular cartilage and distal femur. Relaxation times in the tibial regions may be predictive of patient symptoms at 6 months. These same regions are affected by surgical timing as early as 30 days after injury, but this may partially be reflective of the severity of the preoperative injury and the choice of treatment of meniscal tears.

BACKGROUNDTo evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes post‐transplantation.METHODSWe analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre‐HCT depression requiring treatment versus those without pre‐HCT depression. Using Cox regression models, we compared overall survival (OS) between patients with or without depression. We compared the number of days alive and out of the hospital in the first 100 days post‐HCT using Poisson models. We also compared the incidence of grade 2‐4 acute and chronic graft‐versus‐host disease (GVHD) in allogeneic HCT.RESULTSThe study included 1116 (15%) patients with pre‐transplant depression and 6317 (85%) without depression who underwent allogeneic HCT between 2008 and 2012. Pre‐transplant depression was associated with lower OS (hazard ratio [HR], 1.13; 95% confidence interval [CI], 1.04‐1.23; P = 0.004) and a higher incidence of grade 2‐4 acute GVHD (HR, 1.25; 95% CI, 1.14‐1.37; P < 0.0001), but similar incidence of chronic GVHD. Pre‐transplant depression was associated with fewer days‐alive‐and‐out‐of‐the hospital (means ratio [MR] = 0.97; 95% CI, 0.95‐0.99; P = 0.004). There were 512 (13.5%) patients with Pre‐transplant depression and 3274 (86.5%) without depression who underwent autologous HCT. Pre‐transplant depression in autologous HCT was not associated with OS (HR, 1.15; 95% CI, 0.98‐1.34; P = 0.096) but was associated with fewer days alive and out of the hospital (MR, 0.98; 95% CI, 0.97‐0.99; P = 0.002).CONCLUSIONPre‐transplant depression was associated with lower OS and higher risk of acute GVHD among allogeneic HCT recipients and fewer days alive and out of the hospital during the first 100 days after autologous and allogeneic HCT. Patients with pre‐transplant depression represent a population that is at risk for post‐transplant complications. Cancer 2017;123:1828–1838. © 2017 American Cancer Society.

Key Points HSCT after PD-1 blockade is feasible, although may be associated with increased early immune toxicity. PD-1 blockade may cause persistent depletion of PD1+ T cells and alterations in T-cell differentiation impacting subsequent treatment.

Purpose To determine the effects of carfilzomib, lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone (Rd) on health-related quality of life (HR-QoL) in the Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone for the Treatment of Patients With Relapsed Multiple Myeloma (ASPIRE) trial. Methods Patients with relapsed multiple myeloma were randomly assigned to receive KRd or Rd. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and myeloma-specific module were administered at baseline; day 1 of cycles 3, 6, 12, and 18; and after treatment. The Global Health Status/Quality of Life (GHS/QoL) scale and seven subscales (fatigue, nausea and vomiting, pain, physical functioning, role functioning, disease symptoms, and adverse effects of treatment) were compared between groups using a mixed model for repeated measures. The percentages of responders with ≥ 5- or 15-point GHS/QoL improvement at each cycle were compared between groups. Results Baseline questionnaire compliance was excellent (94.1% of randomly assigned patients). KRd patients had higher GHS/QoL scores versus Rd patients over 18 treatment cycles (two-sided P < .001). The minimal important difference was met at cycle 12 (5.6 points) and approached at cycle 18 (4.8 points). There was no difference between groups for the other prespecified subscales from ASPIRE. A higher proportion of KRd patients met the GHS/QoL responder definition (≥ 5-point improvement) with statistical differences at cycle 12 (KRd v Rd patients, 25.5% v 17.4%, respectively) and 18 (KRd v Rd patients, 24.2% v 12.9%, respectively). Conclusion KRd improves GHS/QoL without negatively affecting patient-reported symptoms when compared with Rd. These data further support the benefit of KRd in patients with relapsed multiple myeloma.

Objectives: We compared the magnitude and direction of associations between forgiveness and pain, mental and physical health, quality of life, and anger in a sample of fibromyalgia syndrome (FM) participants and healthy controls. In addition, we compared FM and controls on mean levels of these variables. Materials and Methods: A total of 173 individuals with FM and 81 controls completed this study. FM participants and controls were residents of Germany recruited with the support of the German Fibromyalgia Patient Association and several self-help groups. FM participants and controls were about 53 years of age, mostly married (70%), Christians (81%), with levels of education ranging from 9 to 13+ years. All participants completed assessments of forgiveness, pain, health, quality of life, and anger. Results: Analyses revealed that FM participants reported higher pain and anger and poorer health and quality of life. FM participants also reported lower levels of both forgiveness of self and others. Size and direction of associations of forgiveness with pain, health, quality of life, and anger in were not significantly different between healthy individuals and individuals with FM. Discussion: Forgiveness of self and others is beneficially associated with pain, health, quality of life, and anger in FM participants at levels that are of similar size and direction as in healthy controls. However, FM participants manifest lower levels of forgiveness of self and others. Therapeutic promotion of forgiveness as a psychosocial coping strategy may help patients with FM to better manage psychological and physical symptoms, thereby enhancing well-being.

Objective: Infobuttons appear as small icons adjacent to electronic health record (EHR) data (e.g., medications, diagnoses, or test results) that, when clicked, access online knowledge resources tailored to the patient, care setting, or task. Infobuttons are required for “Meaningful Use” certification of US EHRs. We sought to evaluate infobuttons’ impact on clinical practice and identify features associated with improved outcomes. Methods: We conducted a systematic review, searching MEDLINE, EMBASE, and other databases from inception to July 6, 2015. We included and cataloged all original research in any language describing implementation of infobuttons or other context-sensitive links. Studies evaluating clinical implementations with outcomes of usage or impact were reviewed in greater detail. Reviewers worked in duplicate to select articles, evaluate quality, and abstract information. Results: Of 599 potential articles, 77 described infobutton implementation. The 17 studies meriting detailed review, including 3 randomized trials, yielded the following findings. Infobutton usage frequency ranged from 0.3 to 7.4 uses per month per potential user. Usage appeared to be influenced by EHR task. Five studies found that infobuttons are used less often than non–context-sensitive links (proportionate usage 0.20–0.34). In 3 studies, users answered their clinical question in &gt; 69% of infobutton sessions. Seven studies evaluated alternative approaches to infobutton design and implementation. No studies isolated the impact of infobuttons on objectively measured patient outcomes. Conclusions: Weak evidence suggests that infobuttons can help providers answer clinical questions. Research on optimal infobutton design and implementation, and on the impact on patient outcomes and provider behaviors, is needed.

Abstract Introduction: Small studies have indicated a possible correlation between a HER2 gene polymorphism at codon 655 and trastuzumab-associated cardiotoxicity. Association between a synonymous coding variant rs7853758 within the SLC28A3 gene and anthracycline induced cardiotoxicity has also been reported. This study aimed to validate these correlations and assess for any relationship with prognosis. Methods: Genomic DNA was isolated from 666 patients enrolled in a large trial of adjuvant chemotherapy in HER2 amplified early breast cancer (BCIRG 006). Genotyping was conducted using Sequenom MassARRAY System for HER2 G-&gt;A polymorphism at amino acid codon 655 (rs1136201) and variant rs7853758 (L461L) within the SLC28A3 gene. Results: Of the 666 patients analyzed, 216 patients were treated with anthracycline based therapy, 226 with trastuzumab based therapy, and 224 with regimens containing both an anthracycline and trastuzumab. Compared with the overall results of the BCIRG006 study (N=3,222), in the subset of patients genotyped in this analysis, a less robust improvement in disease free survival (DFS) was observed for the trastuzumab arms than control arm (HR, 0.821). When stratified for prognostic features, the hazard ratio in favor of trastuzumab was consistent with that of the overall study (HR, 0.674). Samples from 662 patients were successfully genotyped for rs1136201. Of these, 424 (64%) were AA, 30 (4.5%) were GG, 208 (31%) were AG genotype. Samples from 665 patients were successfully genotyped for rs7853758. Of these, 19 (3%) were AA, 475 (71%) were GG, and 171 (26%) were AG genotype. There was no correlation seen between mean left ventricular ejection fraction (LVEF) and HER2 genotype at codon 655 in patients treated with trastuzumab. Of patients tested for the HER2 polymorphism, cardiac dysfunction [defined as &gt; 10% decline in LVEF or clinical congestive heart failure (CHF)] developed in 16% of patients with AA, 17% of patients with GG and 20% of patients with AG. There was also no correlation between mean LVEF and variant rs7853758 in patients treated with anthracyclines. The percentage of patients who developed cardiac dysfunction was 13%, 17% and 21% in AA, GG, and AG genotypes respectively. No correlation between disease free survival and any of the genotypes was seen. Conclusion: In the largest analysis to date to evaluate for relationship between cardiac toxicity and HER2 polymorphism, we did not find a correlation with rs1136201 HER2 polymorphism and trastuzumab induced cardiac toxicity. Our study also did not show a correlation between variant rs7853758 (L461L) and anthracycline induced cardiotoxicity. Neither polymorphism correlated with prognosis. Citation Format: Peddi PF, Hurvitz SA, Fasching PA, Wang L, Cunningham J, Weinshilboum RM, Liu D, Quinaux E, Fourmanoir H, Robert NJ, Valero V, Crown J, Falkson C, Brufsky A, Pienkowski T, Eiermann W, Martin M, Bee V, Slamon DJ. Genetic polymorphism and correlation with treatment induced cardiotoxicity and prognosis in HER2 amplified early breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-03-09.