Citations

Abstract Background Hemocompatibility‐related adverse events (HRAE) negatively influence survival. However, no study has examined the impact of these events on health‐related quality of life (HRQOL) and functional outcomes following continuous‐flow left ventricular assist device implantation (CF‐LVAD). We assessed the impact of HRAE events on HRQOL and hypothesized that HRAE's adversely impact HRQOL and functional outcomes. Methods INTERMACS database identified patients undergoing primary CF‐LVAD implantation from 2008 to 2017. HRAEs included stroke, non‐surgical bleeding, hemolysis, and pump thrombosis and were identified as defined in the literature. HRAEs were further stratified as Tier 1–2 and disabling stroke events. Time‐series analysis was executed for HRAE patients with values pre‐HRAE, post‐HRAE, and closest to 12 months follow up. Local polynomial regression curves modeling individual patients were superimposed into “spaghetti” plots. Results All HRQOL and functional metrics improved in patients over time, despite HRAE complications. However, these patient metrics were significantly reduced compared to the non‐HRAE cohort. Advanced data visualization techniques noted a decline after experiencing an HRAE with a subsequent recovery to baseline levels or higher. Six‐minute walk test (6MWT) was noted to be most affected in the post‐HRAE period but recovered similar to other metrics. Conclusions The burden of HRAE following CF‐LVAD implantation did not negatively impact the quality of life. However, the 6MWT did not increase in the post‐HRAE period in all HRAE patients. Improvement of heart failure symptoms after CF‐LVAD coupled with optimal management following the HRAE act to preserve the enhanced quality of life.

Abstract Chronic noncancer pain in children and adolescents can be impairing and results in substantial health care costs. Intensive interdisciplinary pain treatment (IIPT), an inpatient or day hospital treatment delivered by a team of 3 or more health professionals, may be an effective intervention for these children and adolescents. Based on previous reviews and meta-analyses, we updated findings regarding the description of available treatments and estimated the effectiveness of IIPT, overcoming methodological shortcomings of previous work by requesting and analyzing individual participant data. On June 26, 2021, we searched 5 literature databases (PubMed, PsycINFO, Web of Science, Cochrane Library, and PubPsych) for studies examining the effectiveness of IIPT. Included studies used a pre–post design, assessed patients younger than 22 years, and presented their results in English, German, French, or Spanish. We used standard methodological procedures expected by Cochrane to pool treatment effects and assess risk of bias. We identified 13 different treatment sites with similar treatment inclusion criteria and treatment components, but the descriptions of those treatments varied widely. Regarding treatment effectiveness, IIPT may result in large improvements in the mean pain intensity (g = −1.28), disability (g = −1.91), and number of missed school days at the 12-month follow-up (g = −0.99), as well as moderate improvements in anxiety (g = −0.77) and depression (g = −0.76). The certainty of the evidence, however, was graded from very low to low. We recommend that future researchers use more scientific rigor to increase the certainty of the evidence for IIPT and standardize treatment outcomes for children and adolescents with chronic pain.

The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

The NCCN Guidelines for Multiple Myeloma provide recommendations for diagnosis, initial workup, treatment, follow-up, and supportive care for patients with various plasma cell neoplasms, including multiple myeloma. These NCCN Guidelines Insights highlight some of the important updates/changes specific to the treatment of patients with multiple myeloma in the 2022 version of the guidelines.

Abstract The Worldwide Alzheimer's Disease Neuroimaging Initiative (WW‐ADNI) is a collaborative effort to investigate imaging and biofluid markers that can inform Alzheimer's disease treatment trials. It is a public‐private partnership that spans North America, Argentina, Australia, Canada, China, Japan, Korea, Mexico, and Taiwan. In 2004, ADNI researchers began a naturalistic, longitudinal study that continues today around the globe. Through several successive phases (ADNI‐1, ADNI‐GO, ADNI‐2, and ADNI‐3), the study has fueled amyloid and tau phenotyping and refined neuroimaging methodologies. WW‐ADNI researchers have successfully standardized analyses and openly share data without embargo, providing a rich data set for other investigators. On August 26, 2020, the Alzheimer's Association convened WW‐ADNI researchers who shared updates from ADNI‐3 and their vision for ADNI‐4.

Abstract Background: A major cause of mortality in patients receiving hematopoietic stem cell transplantation (HCT) is acute graft-versus-host disease (GVHD), a multiorgan disorder that includes the skin, liver and gastrointestinal tract. We have previously identified elafin, a protease inhibitor overexpressed in inflamed epidermis, as a diagnostic biomarker of GVHD in the skin, the most commonly involved GVHD organ. However, our initial study was limited to a subset of patients with isolated skin GVHD. The main driver of nonrelapse mortality (NRM) in HCT patients is GI GVHD. Two biomarkers, Regenerating islet-derived 3a (REG3α) and Suppressor of tumorigenesis 2 (ST2), have since been validated as biomarkers of GI GVHD that predict long-term outcomes in patients treated for GVHD. We undertook this study to determine the utility of elafin as a prognostic biomarker of acute GVHD in the general population of previously unstudied acute GVHD patients, and to compare it to ST2 and REG3α. Study Design: 526 patients who received systemic corticosteroid treatment for skin GVHD were analyzed from the Mount Sinai Acute GVHD International Consortium (MAGIC), which includes patients from 25 HCT centers. We used ELISA to measure serum concentrations of elafin, ST2 and REG3α. Patients were divided randomly into equal training and validation sets; and we developed a competing risk regression model for 6-month NRM using elafin concentration in the training set. We developed additional models for 6-month NRM using concentrations of ST2 and REG3α, or the combination of all three biomarkers as predictors. We then constructed ROC curves to evaluate the predictive accuracy of each model and to analyze the ability of each model to stratify patients into high- and low-risk groups. We analyzed the cumulative incidence of 6-month NRM and overall survival in each model and compared the accuracy of each model in the validation set. Results: The area under the receiver operating curve (AUROC) for elafin alone was 0.55 whereas it was 0.75 and statistically superior (P = 0.02) for the combination of ST2 and REG3α. The combination of 3 biomarkers produced an AUROC of 0.76 that was not significantly better than the two biomarker model (P = 0.10). Elafin concentrations, either alone or in combination with ST2 and REG3α, did not produce higher hazard ratios of NRM (data not shown). Patients in the low-risk elafin group paradoxically demonstrated a higher incidence of 6-month NRM, although this difference was not statistically significant (17% vs. 11%, P=0.19), and both overall survival at 6 months (68% vs. 68%, P>0.99) and four-week response (78% vs. 78%, P=0.98) were similar in the low- and high-risk elafin groups (Figure 1). As demonstrated in previous data sets, the combination of ST2 and REG3α divided patients into two groups with a nearly five-fold difference in NRM (6.7% vs. 31%, P <0.001). Conclusion: We demonstrated that serum elafin concentrations measured at the initiation of systemic treatment for acute GVHD in a multicenter population of patients treated systemically for acute GVHD do not predict 6-month NRM, overall survival, or treatment response. As seen in previous studies, serum concentrations of the GI GVHD biomarkers ST2 and REG3α were significant predictors of NRM and the addition of elafin levels did not improve their accuracy. These results underscore the importance of GI disease in driving NRM in patients who develop acute GVHD. Figure 1. Cumulative incidence of nonrelapse mortality and overall survival in high and low risk groups Six-month cumulative incidences of nonrelapse mortality (NRM) in high (solid line) and low (dotted line) risk groups defined by optimized biomarker thresholds (upper panels) and six-month overall survival estimated using the Kaplan-Meier method (lower panels). (A) Cumulative incidence of NRM (14%) and overall survival (75%) in the total validation set (N=263). (B) Cumulative incidence of NRM in the low (N=150) and high (N=113) elafin group (17% vs. 11%, P=0.19). Overall survival in the low and high elafin group (68% vs. 68%, P > 0.99). (C) Cumulative incidence of NRM in the low (N=175) and high (N=88) ST2 + REG3a group (6.7 vs. 31%, P < 0.001). Overall survival in the low and high ST2 + REG3a group (77% vs. 51%, P < 0.001). (D) Cumulative incidence of NRM in the low (N=180) and high (N=83) elafin + ST2 + REG3a group (7.0 vs. 30%, P < 0.001). Overall survival in the low and high elafin + ST2 + REG3a group (79% vs. 64%, P < 0.001). Figure 1 Figure 1. Disclosures Ozbek: Viracor: Patents & Royalties: GVHD biomarker patent with royalties from Viracor. DeFilipp: Omeros, Corp.: Consultancy; Incyte Corp.: Research Funding; Regimmune Corp.: Research Funding; Syndax Pharmaceuticals, Inc: Consultancy. Grupp: Novartis, Kite, Vertex, and Servier: Research Funding; Jazz Pharmaceuticals: Consultancy, Other: Steering committee, Research Funding; Novartis, Roche, GSK, Humanigen, CBMG, Eureka, and Janssen/JnJ: Consultancy; Novartis, Adaptimmune, TCR2, Cellectis, Juno, Vertex, Allogene and Cabaletta: Other: Study steering committees or scientific advisory boards. Hexner: Blueprint medicines: Membership on an entity's Board of Directors or advisory committees, Research Funding; Tmunity Therapeutics: Research Funding; PharmaEssentia: Membership on an entity's Board of Directors or advisory committees. Kitko: Co-investigator on two NIH grants as part of the cGVHD consortium: Research Funding; Vanderbilt University Medical Center: Current Employment; PER: Other: PER - CME educational talks about GVHD; Horizon: Membership on an entity's Board of Directors or advisory committees. Qayed: Novartis: Honoraria; Mesoblast: Honoraria; Medexus: Honoraria. Reshef: ilead, BMS, Precision, Immatics, Atara, Takeda, Shire, Pharmacyclics, Incyte: Research Funding; Bayer: Consultancy; Gilead and Novartis: Honoraria; BMS, Regeneron, TScan, Synthekine, Atara, Jasper, Bayer: Consultancy. Levine: Incyte: Consultancy, Research Funding; Viracor: Patents & Royalties: GVHD biomarker patent with royalties from Viracor; Mesoblast: Consultancy, Research Funding; Equillium Bio: Membership on an entity's Board of Directors or advisory committees; X4 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Talaris Therapeutics: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees; Symbio: Membership on an entity's Board of Directors or advisory committees; Biogen: Research Funding; Kamada: Research Funding. Ferrara: Eurofins Viracor: Consultancy, Other: Royalties. Chen: Incyte: Consultancy; Gamida: Consultancy.

Motor learning principles guide treatment of childhood apraxia of speech (CAS). Previous studies found children to benefit from higher-intensity conditions; however, they did not control for the total amount of therapy time. The aims of the article are to examine the effects of high versus low treatment frequency in intervention for CAS in German-speaking children. An alternating single-subject design with multiple baselines was applied to compare frequent, short sessions with fewer, longer sessions in terms of speech production accuracy in four children with CAS while keeping the total therapy time constant. We administered a version of integral stimulation treatment. Despite inter-individual differences, changes under both treatment conditions showed similar positive trajectories for all four children. Untreated control targets also improved across participants and conditions. Maintenance and generalization to untreated targets were observed two weeks and three months post treatment, independent of treatment intensity. Our results show no significant advantage of more intensive treatment when the total therapy time is held constant. This study contributes to the evidence base for the use of integral stimulation in treating children with CAS, and in particular those who speak languages other than English.