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Much attention has been given to determining whether an adolescent patient has the capacity to consent to research. This study explores the factors that influence adolescents' decisions to participate in a research study about youth violence and to determine positive or negative feelings elicited by being a research subject. The majority of subjects perceived their decision to participate to be free of coercion, and few felt badly about having participated. However, adolescents who were alone in the room during the assent process were more likely to report that they chose freely to be a research subject. This study may influence the ways physicians communicate with adolescent patients around research assent within a clinical care environment. [ABSTRACT FROM AUTHOR]

Abstract: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the Center for International Blood and Marrow Transplant Research registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART therapy between 2018 and 2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range, 1-7) prior therapies and were treated with axicabtagene ciloleucel (69%). At median follow-up of 23 months after CART therapy, 2-year overall and progression-free survival were 42% (95% confidence interval [CI], 27-57) and 29% (95% CI, 17-43), respectively. In univariable analysis, poor performance status before CART therapy was associated with higher mortality (hazard ratio, 2.35; 95%CI, 1.02-5.5). The 2-year cumulative incidences of relapse/progression and nonrelapse mortality were 69% and 2%, respectively. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurologic syndrome occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART therapy for R/R THRLBCL, ∼30% of patients were alive and progression free 2 years after CART therapy. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CARTs., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Importance: Suicide is the third-leading cause of death among US adolescents. Environmental and lifestyle factors influence suicidal behavior and can inform risk classification, yet quantifying and incorporating them in risk assessment presents a significant challenge for reproducibility and clinical translation., Objective: To quantify the aggregate contribution of environmental and lifestyle factors to youth suicide attempt risk classification., Design, Setting, and Participants: This was a cohort study in 3 youth samples: 2 national longitudinal cohorts from the US and the UK and 1 clinical cohort from a tertiary pediatric US hospital. An exposome-wide association study (ExWAS) approach was used to identify risk and protective factors and compute aggregate exposomic scores. Logistic regression models were applied to test associations and model fit of exposomic scores with suicide attempts in independent data. Youth from the Adolescent Brain Cognitive Development (ABCD) study, the UK Millennium Cohort Study (MCS), and the Children's Hospital of Philadelphia emergency department (CHOP-ED) were included in the study., Exposures: A single-weighted exposomic score that sums significant risk and protective environmental/lifestyle factors., Main Outcome and Measure: Self-reported suicide attempt., Results: A total of 40 364 youth were included in this analysis: 11 564 from the ABCD study (3 waves of assessment; mean [SD] age, 12.0 [0.7] years; 6034 male [52.2%]; 344 attempted suicide [3.0%]; 1154 environmental/lifestyle factors were included in the ABCD study), 9000 from the MCS cohort (mean [SD] age, 17.2 [0.3] years; 4593 female [51.0%]; 661 attempted suicide [7.3%]; 2864 environmental/lifestyle factors were included in the MCS cohort), and 19 800 from the CHOP-ED cohort (mean [SD] age, 15.3 [1.5] years; 12 937 female [65.3%]; 2051 attempted suicide [10.4%]; 36 environmental/lifestyle factors were included in the CHOP-ED cohort). In the ABCD discovery subsample, ExWAS identified 99 risk and protective exposures significantly associated with suicide attempt. A single weighted exposomic score that sums significant risk and protective exposures was associated with suicide attempt in an independent ABCD testing subsample (odds ratio [OR], 2.2; 95% CI, 2.0-2.6; P < .001) and explained 17.6% of the variance (based on regression pseudo-R2) in suicide attempt over and above that explained by age, sex, race, and ethnicity (2.8%) and by family history of suicide (6.3%). Findings were consistent in the MCS and CHOP-ED cohorts (explaining 22.6% and 19.3% of the variance in suicide attempt, respectively) despite clinical, demographic, and exposure differences. In all cohorts, compared with youth at the median quintile of the exposomic score, youth at the top fifth quintile were substantially more likely to have made a suicide attempt (OR, 4.3; 95% CI, 2.6-7.2 in the ABCD study; OR, 3.8; 95% CI, 2.7-5.3 in the MCS cohort; OR, 5.8; 95% CI, 4.7-7.1 in the CHOP-ED cohort)., Conclusions and Relevance: Results suggest that exposomic scores of suicide attempt provided a generalizable method for risk classification that can be applied in diverse samples from clinical or population settings.

Purpose: Although previous studies have examined the association between youth psychosocial risks and their perceptions of their neighborhood, it is unclear how objective neighborhood characteristics are associated with psychosocial risks and mental health symptoms among adolescents. We investigated how neighborhood characteristics moderate the relationship between youth psychosocial characteristics and mental health symptoms., Methods: This cross-sectional study examined 13,837 emergency department visits by 14-18-year-olds who completed a standardized Behavioral Health Screening in a tertiary pediatric hospital in Philadelphia from 2013 to 2020. Psychosocial risk factors and mental health symptoms were assessed based on self-reported survey responses. We characterized neighborhoods as low-, moderate-, and high-stress based on gun violence incidence from 2013 to 2020 and the census tract-level Child Opportunity Index. Mixed effects logistic regression and Poisson models were used to examine moderation effects., Results: The 9,814 included patients were 64% female and 64% non-Hispanic Black. The following psychosocial risk factors were associated with two to eight times higher odds of depressive symptoms and suicide risk: exposure to trauma, bullying at school, at-risk substance use, fighting, and retaliation. Adolescents living in high-stress neighborhoods were twice as likely to report fighting and retaliation and reported more psychosocial risk factors than those in low-stress neighborhoods. Odds of mental health symptoms increased with the number of psychosocial risk factors, particularly in youth from low-stress neighborhoods., Discussion: Objective neighborhood characteristics had a significant interaction effect on the relationship between psychosocial risks and depression and suicide risk among adolescents seeking care in a pediatric emergency department., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Recent reports have raised concerns about the association of chimeric antigen receptor T cell (CAR-T) with non-negligible cardiotoxicity, particularly atrial arrhythmias. First, we conducted a pharmacovigilance study to assess the reporting of atrial arrhythmias following CD19-directed CAR-T. Subsequently, to determine the incidence, risk factors and outcomes of atrial arrhythmias post-CAR-T, we compiled a retrospective single-centre cohort of non-Hodgkin lymphoma patients. Only commercial CAR-T products were considered. Atrial arrhythmias were nearly fourfold more likely to be reported after CAR-T therapy compared to all other cancer patients in the FAERS (adjusted ROR = 3.76 [95% CI 2.67-5.29]). Of the 236 patients in our institutional cohort, 23 (10%) developed atrial arrhythmias post-CAR-T, including 12 de novo arrhythmias, with most (83%) requiring medical intervention. Atrial arrhythmias frequently co-occurred with cytokine release syndrome and were associated with higher post-CAR-T infusion peak levels of IL-10, TNF-alpha and LDH, and lower trough levels of fibrinogen. In a multivariable analysis, risk factors for atrial arrhythmia were history of atrial arrhythmia (OR = 6.80 [2.39-19.6]) and using CAR-T product with a CD28-costimulatory domain (OR = 5.17 [1.72-18.6]). Atrial arrhythmias following CD19-CAR-T therapy are prevalent and associated with elevated inflammatory biomarkers, a history of atrial arrhythmia and the use of a CAR-T product with a CD28 costimulatory domain., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Abstract: B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T cells (CAR-Ts) used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (R/R) disease, and CAR-T expansion after infusion has been shown to inform depth and duration of response (DoR), but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 patients with relapsed MM treated with the BCMA-targeting agents ciltacabtagene autoleucel and idecabtagene vicleucel. Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and DoR. Patients with ALCmax >1.0 × 103/μL had a superior PFS (30.5 months vs 6 months; P < .001) compared with those with ≤1.0 × 103/μL, whereas patients with ALCmax ≤0.5 × 103/μL represent a high-risk group with early disease progression and short PFS (hazard ratio, 3.4; 95% confidence interval, 2-5.8; P < .001). In multivariate analysis, ALCmax >1.0 × 103/μL and nonparaskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for international staging systemic staging, age, CAR-T product, high-risk cytogenetics, and the number of previous lines. Moreover, our flow cytometry data suggest that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker. We report, to our knowledge, for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in patients with R/R MM., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objective: Prior evidence demonstrates that both firearm access and fighting can predict future violence and injury in adolescents. We aimed to examine associations between firearm access with fighting behavior and conflict perception in a sample of adolescents in an urban emergency department (ED) setting., Methods: In 2023, we conducted a secondary analysis of 13,610 adolescent encounters in the ED of a U.S. children's hospital from 2013 to 2020, using a universally applied, self-administered computerized behavioral health survey. We compared patient characteristics by reported firearm access and fighting behavior using chi-squared tests. Generalized estimating equations (GEE) were used to investigate associations between 1) fighting behavior and firearm access, and 2) between fighting behavior and respondent preference to and reporting of fighting incident to law enforcement after adjusting for race and ethnicity, age, and gender., Results: Approximately one-quarter of the sample reported past year fighting. Youth who reported fighting were more likely to report firearm access (AOR = 1.66, 95%CI = [1.49-1.86]). This association strengthened among youth who perceived continued conflict after a fight (AOR = 2.05, 95%CI = [1.73-2.43]). Youth who perceived continued conflict following a fight were more likely to report (AOR = 1.97, 95%CI = [1.65-2.36]) or want to report (AOR = 2.63, 95%CI = [1.81-3.81]) the fight to law enforcement., Conclusions: Those perceiving continued conflict after a fight were more likely to report access to firearms and endorse retaliation; however, they were more likely to want to report the fight to law enforcement. These findings highlight the potential for more comprehensive ED risk assessment to reduce retaliation and reinjury for adolescents reporting fighting behavior., Competing Interests: Declaration of competing interest The Behavioral Health Screening tool is owned by Children's Hospital of Philadelphia and licensed to MDLogix, Inc., a health science informatics and computer science engineering company who make the screening tool commercially available. Dr. Fein might one day receive a small royalty payment for his role in developing the tool. Mr. Mitchell and Drs. Jungwon Min, Amy Carroll-Scott, and Leah Brogan do not report financial interests or potential conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Optimizing natural killer (NK) cell alloreactivity could further improve outcome after allogeneic hematopoietic cell transplantation (alloHCT). The donor's Killer-cell Immunoglobulin-like Receptor (KIR) genotype may provide important information in this regard. In the past decade, different models have been proposed aiming at maximizing NK cell activation by activating KIR-ligand interactions or minimizing inhibitory KIR-ligand interactions. Alternative classifications intended predicting outcome after alloHCT by donor KIR-haplotypes. In the present study, we aimed at validating proposed models and exploring more classification approaches. To this end, we analyzed samples stored at the Collaborative Biobank from HLA-compatible unrelated stem cell donors who had donated for patients with acute myeloid leukemia (AML) or myelodysplastic neoplasm (MDS) and whose outcome data had been reported to EBMT or CIBMTR. The donor KIR genotype was determined by high resolution amplicon-based next generation sequencing. We analyzed data from 5,017 transplants. The median patient age at alloHCT was 56 years. Patients were transplanted for AML between 2013 and 2018. Donor-recipient pairs were matched for HLA-A, -B, -C, -DRB1, and -DQB1 (79%) or had single HLA mismatches. Myeloablative conditioning was given to 56% of patients. Fifty-two percent of patients received anti-thymocyte-globulin-based graft-versus-host disease prophylaxis, 32% calcineurin-inhibitor-based prophylaxis, and 7% post-transplant cyclophosphamide-based prophylaxis. We tested several previously reported classifications in multivariable regression analyses but could not confirm outcome associations. Exploratory analyses in 1,939 patients (39%) who were transplanted from donors with homozygous centromeric (cen) or telomeric (tel) A or B motifs, showed that the donor cen B/B -tel A/A diplotype was associated with a trend to better event-free survival (HR 0.84, p=.08) and reduced risk of non-relapse mortality (NRM) (HR 0.65, p=.01). When we further dissected the contribution of B subtypes, we found that only the cen B01/B01 - telA/A diplotype was associated with a reduced risk of relapse (HR 0.40, p=.04) while all subtype combinations contributed to a reduced risk of NRM. This exploratory finding has to be validated in an independent data set. In summary, the existing body of evidence is not (yet) consistent enough to recommend use of donor KIR genotype information for donor selection in routine clinical practice., Competing Interests: All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer TT declared shared affiliation with the author’s JSc and FH to the handling editor at the time of review., (Copyright © 2024 Schetelig, Baldauf, Heidenreich, Hoogenboom, Spellman, Kulagin, Schroeder, Sengeloev, Dreger, Forcade, Vydra, Wagner-Drouet, Choi, Paneesha, Miranda, Tanase, de Wreede, Lange, Schmidt, Sauter, Fein, Bolon, He, Marsh, Gadalla, Paczesny, Ruggeri, Chabannon and Fleischhauer.)

Acute graft-versus-host disease (aGvHD) is a serious complication of allogeneic hematopoietic stem-cell transplantation with limited treatment options. The gut microbiome plays a critical role in aGvHD pathogenesis. Fecal microbiota transplantation (FMT) has emerged as a potential therapeutic approach to restore gut microbial diversity. In this prospective pilot study, 21 patients with steroid-resistant or steroid-dependent lower gastrointestinal aGvHD received FMT in capsule form. At 28 days after the first FMT, the overall response rate was 52.4%, with 23.8% complete and 28.6% partial responses. However, sustained responses were infrequent, with only one patient remaining aGvHD-free long-term. FMT was generally well-tolerated. Microbiome analysis revealed dysbiosis in pre-FMT patient stool samples, with distinct microbial characteristics compared to donors. Following FMT, there was an increase in beneficial Clostridiales and a decrease in pathogenic Enterobacteriales. These findings highlight the potential of FMT as a treatment option for steroid-resistant aGvHD. Trial registration number NCT #03214289., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Abstract: In acute myeloid leukemia (AML), donor natural killer cell killer immunoglobulin-like receptors (KIR) and recipient HLA interactions may contribute to the graft-versus-leukemia effect of allogeneic hematopoietic cell transplantation (HCT). Analyses of individual KIR/HLA interactions, however, have yielded conflicting findings, and their importance in the HLA-matched unrelated donor (MUD) setting remains controversial. We systematically studied outcomes of individual donor-KIR/recipient-HLA interactions for HCT outcomes and empirically evaluated prevalent KIR genotypes for clinical benefit. Adult patients with AML (n = 2025) who received HCT with MUD grafts in complete remission reported to the Center for International Blood and Marrow Transplantation were evaluated. Only the donor-2DL2+/recipient-HLA-C1+ pair was associated with reduced relapse (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.67-0.93; P = .006) compared with donor-2DL2-/recipient-HLA-C1+ pair. However, no association was found when comparing HLA-C groups among KIR-2DL2+-graft recipients. We identified 9 prevalent donor KIR genotypes in our cohort and screened them for association with relapse risk. Genotype 5 (G5) in all recipients and G3 in Bw4+ recipients were associated with decreased relapse risk (HR, 0.52; 95% CI, 0.35-0.78; P = .002; and HR, 0.32; 95% CI, 0.14-0.72; P = .006; respectively) and G2 (HR 1.63, 95% CI, 1.15-2.29; P = .005) with increased relapse risk in C1-homozygous recipients, compared with other patients with the same ligand. However, we could not validate these findings in an external data set of 796 AML transplants from the German transplantation registry. Neither a systematic evaluation of known HLA-KIR interactions nor an empiric assessment of prevalent KIR genotypes demonstrated clinically actionable associations; therefore, these data do not support these KIR-driven strategies for MUD selection in AML., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Allogeneic hematopoietic cell transplantation (alloHCT) requires the comprehensive evaluation of patients across multiple dimensions. Among the factors considered, comorbidities hold great significance in the pretransplant assessment. As many as 40% of alloHCT recipients will have a high burden of comorbidities in contemporary cohorts. To ensure a standardized evaluation, several comorbidity scores have been developed; however, they exhibit variations in properties and performance. This review examines the strengths and weaknesses associated with these comorbidity scores, critically appraising these models and proposing a framework for their application in considering the alloHCT candidate. Furthermore, we introduce the concept that comorbidities may have specific effects depending on the chosen transplantation approach and outline the findings of key studies that consider the impact of individual comorbidities on alloHCT outcomes. We suggest that a personalized transplantation approach should not rely solely on the overall burden of comorbidities but should also take into account the individual comorbidities themselves, along with other patient, disease, and transplantation-related factors., (Copyright © 2023 by The American Society of Hematology.)

We tested whether exposure to gun or knife violence over two decades is a cause of depression in young adulthood using data from a nationally representative sample in the United States. The National Longitudinal Study of Adolescent to Adult Health is a sample of 20,745 adolescents, assessed in 1994-95 with follow-ups in 1995-1996 ( n = 14,738), 2001-2002 ( n = 15,197) and 2007-2008 ( n = 15,701; 24 to 32 years old). At each wave, respondents reported exposure to gun or knife violence and symptoms of depression. Regression and sibling fixed effects analyses were conducted to test whether cumulative exposure to gun or knife violence was associated with depression. In fully adjusted models, greater cumulative exposure to gun or knife violence was associated with more symptoms of depression ( b = 0.12, 95% C. I. = 0.05; 0.19, p < 0.01) and higher risk for clinically significant depression in young adulthood ( OR = 1.07, 95% C. I. = 1.02; 1.13, p < 0.01). Results replicated in sibling fixed effects models ( b = 0.21, 95% C. I. = 0.01; 0.42, p < 0.05). These quasi-experimental data suggest that exposure to gun or knife violence is a cause of depression in young adulthood.

Objectives: To examine how timing of the first outpatient mental health (MH) visit after a pediatric firearm injury varies by sociodemographic and clinical characteristics., Methods: We retrospectively studied children aged 5 to 17 years with a nonfatal firearm injury from 2010 to 2018 using the IBM Watson MarketScan Medicaid database. Logistic regression estimated the odds of MH service use in the 6 months after injury, adjusted for sociodemographic and clinical characteristics. Cox proportional hazard models, stratified by previous MH service use, evaluated variation in timing of the first outpatient MH visit by sociodemographic and clinical characteristics., Results: After a firearm injury, 958 of 2613 (36.7%) children used MH services within 6 months; of these, 378 of 958 (39.5%) had no previous MH service use. The adjusted odds of MH service use after injury were higher among children with previous MH service use (adjusted odds ratio, 10.41; 95% confidence interval [CI], 8.45-12.82) and among non-Hispanic white compared with non-Hispanic Black children (adjusted odds ratio, 1.29; 95% CI, 1.02-1.63). The first outpatient MH visit after injury occurred sooner among children with previous MH service use (adjusted hazard ratio, 6.32; 95% CI, 5.45-7.32). For children without previous MH service use, the first MH outpatient visit occurred sooner among children with an MH diagnosis made during the injury encounter (adjusted hazard ratio, 2.72; 95% CI, 2.04-3.65)., Conclusions: More than 3 in 5 children do not receive MH services after firearm injury. Previous engagement with MH services and new detection of MH diagnoses during firearm injury encounters may facilitate timelier connection to MH services after injury., (Copyright © 2023 by the American Academy of Pediatrics.)

Older age and a high burden of comorbidities often drive the selection of low-intensity conditioning regimens in allogeneic hematopoietic stem cell transplantation recipients. However, the impact of comorbidities in the low-intensity conditioning setting is unclear. We sought to determine the contribution of individual comorbidities and their cumulative burden on the risk of nonrelapse mortality (NRM) among patients receiving low-intensity regimens. In a retrospective analysis of adults (≥18 years) who underwent transplantation for acute myeloid leukemia in the first complete remission between 2008 and 2018, we studied recipients of low-intensity regimens as defined by the transplantation conditioning intensity (TCI) scale. Multivariable Cox models were constructed to study associations of comorbidities with NRM. Comorbidities identified as putative risk factors in the low-TCI setting were included in combined multivariable regression models assessed for overall survival, NRM, and relapse. A total of 1663 patients with a median age of 61 years received low-TCI regimens. Cardiac comorbidity (including arrhythmia/valvular disease) and psychiatric disease were associated with increased NRM risk (hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.13-2.09 and HR, 1.69; 95% CI, 1.02-2.82, respectively). Moderate pulmonary dysfunction, though prevalent, was not associated with increased NRM. In a combined model, cardiac, psychiatric, renal, and inflammatory bowel diseases were independently associated with adverse transplantation outcomes. These findings may inform patient and regimen selection and reinforce the need for further investigation of cardioprotective transplantation approaches., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Importance: Screening adolescents in emergency departments (EDs) for suicidal risk is a recommended strategy for suicide prevention. Comparing screening measures on predictive validity could guide ED clinicians in choosing a screening tool., Objective: To compare the Ask Suicide-Screening Questions (ASQ) instrument with the Computerized Adaptive Screen for Suicidal Youth (CASSY) instrument for the prediction of suicidal behavior among adolescents seen in EDs, across demographic and clinical strata., Design, Setting, and Participants: The Emergency Department Study for Teens at Risk for Suicide is a prospective, random-series, multicenter cohort study that recruited adolescents, oversampled for those with psychiatric symptoms, who presented to the ED from July 24, 2017, through October 29, 2018, with a 3-month follow-up to assess the occurrence of suicidal behavior. The study included 14 pediatric ED members of the Pediatric Emergency Care Applied Research Network and 1 Indian Health Service ED. Statistical analysis was performed from May 2021 through January 2023., Main Outcomes and Measures: This study used a prediction model to assess outcomes. The primary outcome was suicide attempt (SA), and the secondary outcome was suicide-related visits to the ED or hospital within 3 months of baseline; both were assessed by an interviewer blinded to baseline information. The ASQ is a 4-item questionnaire that surveys suicidal ideation and lifetime SAs. A positive response or nonresponse on any item indicates suicidal risk. The CASSY is a computerized adaptive screening tool that always includes 3 ASQ items and a mean of 8 additional items. The CASSY's continuous outcome is the predicted probability of an SA., Results: Of 6513 adolescents available, 4050 were enrolled, 3965 completed baseline assessments, and 2740 (1705 girls [62.2%]; mean [SD] age at enrollment, 15.0 [1.7] years; 469 Black participants [17.1%], 678 Hispanic participants [24.7%], and 1618 White participants [59.1%]) completed both screenings and follow-ups. The ASQ and the CASSY showed a similar sensitivity (0.951 [95% CI, 0.918-0.984] vs 0.945 [95% CI, 0.910-0.980]), specificity (0.588 [95% CI, 0.569-0.607] vs 0.643 [95% CI, 0.625-0.662]), positive predictive value (0.127 [95% CI, 0.109-0.146] vs 0.144 [95% CI, 0.123-0.165]), and negative predictive value (both 0.995 [95% CI, 0.991-0.998], respectively). Area under the receiver operating characteristic curve findings were similar among patients with physical symptoms (ASQ, 0.88 [95% CI, 0.81-0.95] vs CASSY, 0.94 [95% CI, 0.91-0.96]). Among patients with psychiatric symptoms, the CASSY performed better than the ASQ (0.72 [95% CI, 0.68-0.77] vs 0.57 [95% CI, 0.55-0.59], respectively)., Conclusions and Relevance: This study suggests that both the ASQ and the CASSY are appropriate for universal screening of patients in pediatric EDs. For the small subset of patients with psychiatric symptoms, the CASSY shows greater predictive validity.

Anti-CD19 chimeric antigen receptor T cell (CAR-T) therapy has transformed the care of patients with relapsed/refractory large B cell lymphoma (LBCL). However, approximately 60% of CAR-T recipients ultimately will experience disease recurrence or progression. Salvage therapies after CAR-T treatment failures are of limited efficacy and have a short duration of response. The objective of the present study was to evaluate the role of allogeneic hematopoietic cell transplantation (allo-HCT) after CAR-T therapy in LBCL patients. This was a multicenter observational study reporting the outcome of 39 adult LBCL patients who underwent allo-HCT following anti-CD19 CAR-T therapy. The median patient age was 47 years (range, 20 to 68 years). HLA-matched sibling, HLA-matched unrelated, and alternative donors were used in 36%, 36%, and 28% of transplantations, respectively. Conditioning regimens were primarily of low or intermediate intensity. Disease status at allo-HCT was complete response in 41%, partial response in 38%, and progressive disease in 21%. Allo-HCT was performed at a median of 127 days (range, 82 to 206 days) after CAR-T therapy. A high incidence of hepatic toxicity (28%), including sinusoidal obstruction syndrome (15.4%; 95% confidence interval; [CI], 6.2% to 28.5%), was observed. The 1-year cumulative incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) was 38.5% (95% CI, 23.2% to 53.6%) and 15.4% (95% CI, 6.1% to 28.5%), respectively. The 2-year cumulative incidence of moderate-severe chronic GVHD was 11.1% (95% CI, 3.3% to 24.3%). Overall, 2-year nonrelapse mortality and relapse/progression incidence were 26% (95% CI, 13% to 41%) and 43% (95% CI, 27% to 59%), respectively. With a median follow-up of 32 months, the 2-year overall survival (OS) and progression-free survival (PFS) were 45% (95% CI, 31% to 66%) and 31% (95% CI, 19% to 50%), respectively. In multivariable analyses, pre-HCT elevated lactate dehydrogenase level and transformed lymphoma were predictive of OS and PFS, respectively. Our data suggest that allo-HCT after anti-CD19 CAR-T treatment failure is feasible with a relatively promising efficacy but possibly high toxicity rate., Competing Interests: Declaration of Competing Interest R.S. has served as a consultant for Medexus and MyBiotics. M.A.P. has received honoraria from AbbVie, Astellas, Bristol-Myers Squibb, Celgene, Equilium, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Novartis, Nektar Therapeutics, Omeros, Takeda, VectivBio AG, and Vor Biopharma; has served on data safety and monitoring boards for Cidara Therapeutics, Medigene, Sellas Life Sciences, and Servier and the scientific advisory board of NexImmune; has ownership interests in NexImmune and Omeros; has received research support for clinical trials from Incyte, Kite/Gilead, Miltenyi Biotec, and Novartis; and serves in a volunteer capacity as a member of the Board of Directors of the American Society for Transplantation and Cellular Therapy and Be the Match (National Marrow Donor Program), as well as on the Center for International Blood and Marrow Transplant Research's Cellular Immunotherapy Data Resource executive committee. A.S. has served on scientific advisory boards for Jazz Pharmaceutical, Gilead, Novartis, AbbVie, Bristol-Myers Squibb, and Medac. A.A. reports honoraria from Gilead, Novartis, Takeda, Roche, Bristol-Myers Squibb, and Sanofi. C.S.S. has served as a paid consultant on advisory boards for Juno Therapeutics, Sanofi-Genzyme, Spectrum Pharmaceuticals, Novartis, Genmab, Precision Biosciences, Kite/Gilead, Celgene/BMS, Gamida Cell, Karyopharm, Ono Pharmaceuticals, and GSK and has received research funds for clinical trials from Juno Therapeutics, Celgene/BMS, Bristol-Myers Squibb, Precision Biosciences, Actinium Pharmaceuticals, and Sanofi-Genzyme. G.L.S. has received research funding from Janssen, Amgen, and Beyond Spring., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Persistence or recurrence of large B-cell lymphoma after CD19-CAR-T is common, yet data guiding management are limited. We describe outcomes and features following CAR-T treatment failure. Of 305 adults who received CD19-CAR-T, 182 experienced disease recurrence or progression (1-year cumulative incidence 63% [95%CI: 57-69]). Of 52 post-CAR-T biopsies evaluated by flow cytometry, 49 (94%) expressed CD19. Subsequent anti-cancer treatment was administered in 135/182 (74%) patients with CAR-T treatment failure. Median OS from the first post-CAR-T treatment was 8 months (95%CI 5.6-11.0). Polatuzumab-, standard chemotherapy-, and lenalidomide-based treatments were the most common approaches after CAR-T. No complete responses (CRs) were observed with conventional chemotherapy, while CR rates exceeding 30% were seen following polatuzumab- or lenalidomide-based therapies. Factors associated with poor OS among patients treated post-CAR-T were pre-CAR-T bulky disease (HR 2.27 [1.10-4.72]), lack of response to CAR-T (2.33 [1.02-5.29]), age >65 years (HR 2.65 [1.49-4.73]) and elevated LDH at post-CAR-T treatment (HR 2.95 [1.61-5.38]). The presence of ≥2 of these factors was associated with inferior OS compared to ≤1 (56% vs. 19%). In this largest analysis to date of patients who progressed or relapsed after CD19-CAR-T, survival is poor, though novel agents such as polatuzumab and lenalidomide may have hold promise., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: This study compares current suicidal ideation, prior suicide attempt and associated self-reported risk factors in adolescents with and without access to firearms., Methods: Using data from a clinically applied behavioral health assessment completed by adolescents presenting to a tertiary children's hospital emergency department (ED; N = 15,806), we evaluated the association between firearm access (ie, firearm in the home or ability to obtain one within 24 hours), each of the included suicide risk factors (ie, depressive symptoms, trauma victimization, bullying victimization), and our primary outcomes (ie, current suicidal ideation and prior suicide attempt). We performed regression analyses on 3 groups: 1) The overall population; 2) Only the participants with firearm access; and 3) Only the participants without firearm access., Results: Fourteen percent (2179/15,806) of the sample reported a firearm in the home or ability to access one within 24 hours. Overall, 6.8% of participants reported current suicidal ideation and 9.1% reported prior suicide attempt. Youth with firearm access had 1.52 times higher odds of current suicidal ideation and 1.61 times higher odds of prior suicide attempt compared to youth without firearm access. All included suicide risk factors were found to significantly increase the odds of current suicidal ideation and prior suicide attempt in the overall sample; this increase was similar in the groups with and without firearm access., Conclusions: Adolescents with firearm access have higher odds of suicidal ideation and prior attempt compared to those without firearm access, highlighting the need for universal ED-based screening for suicidality and lethal means., (Copyright © 2022 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Tisagenlecleucel (tisa-cel) is an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for patients with relapsed/refractory large B-cell lymphoma. Outcomes of patients with out-of-commercial specification (OOS) CAR T products are not well characterized. We therefore assessed 37 adult patients who underwent leukapheresis for tisa-cel therapy in a single center. In nine (24%) patients, manufactured tisa-cel was considered OOS. Three of them (33%) received tisa-cel after institutional review board approval; 2/9 (22%) did not receive tisa-cel due to disease progression; and 4/9 (44%) received academic point-of-care (POC) CAR T-cell as salvage therapy, at a median of 35 days following OOS notification. Three of those four patients achieved a complete response. In univariate analysis, risk factors for OOS were ≥ 4 prior therapies or previous bendamustine exposure. In conclusion, we report high OOS incidence of 24% in real-life setting. Forty-four percent of those patients received POC CAR T-cell as salvage therapy.

Introduction: Firearm injuries are a leading cause of morbidity among children, but data on healthcare utilization and expenditures after injury are limited. This study sought to analyze healthcare encounters and expenditures for 2 years after a nonfatal firearm injury., Methods: A retrospective cohort study was conducted between 2020 and 2022 of children aged 0-18 years with International Classification of Diseases, Ninth Revision/ICD-10 diagnosis codes for firearm injury from 2010 to 2016 in the Medicaid MarketScan claims database. Outcomes included the difference in healthcare encounters and expenditures, including mental health. Descriptive statistics characterized patient demographics and healthcare utilization. Changes in health expenditures were evaluated with Wilcoxon sign rank tests., Results: Among 911 children, there were 12,757 total healthcare encounters in the year before the index firearm injury, 15,548 1 encounters in the year after (p<0.001), and 10,228 total encounters in the second year (p<0.001). Concomitantly, there was an overall increase of $14.4 million in health expenditures ($11,415 per patient) 1 year after (p<0.001) and a $0.8 million decrease 2 years after the firearm injury (p=0.001). The children with low previous expenditures (majority of sample) had sustained increases throughout the second year after injury. There was a 31% and 37% absolute decrease in mental health utilization and expenditures, respectively, among children 2 years after the firearm injury., Conclusions: Children who experience nonfatal firearm injury have an increased number of healthcare encounters and healthcare expenditures in the year after firearm injury, which is not sustained for a second year. Mental health utilization and expenditures remain decreased up to 2 years after a firearm injury. More longitudinal research on the morbidity associated with nonfatal firearm injuries is needed., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Vitamin D insufficiency is a potentially modifiable risk factor for poor outcomes in newly diagnosed large B-cell lymphoma (LBCL). However, the role of circulating vitamin D concentrations in relapsed/refractory LBCL treated with CD19-directed chimeric antigen receptor T-cell therapy (CAR-T) is currently unknown. This was a single-center, observational study that evaluated the association of pre-CAR-T 25-hydroxyvitamin D (25-OHD) status with 100-day complete response, progression-free survival, overall survival, and CAR-T-related toxicity in 111 adult relapsed/refractory LBCL patients. Vitamin D insufficiency was defined as ≤30 ng/mL in accordance with the Endocrine Society guidelines. The median pre-CAR-T 25-hydroxyvitamin D concentration was 24 ng/mL (interquarile range = 18-34). Vitamin D-insufficient patients (≤30 ng/mL; n = 73 [66%]) were significantly younger than their vitamin D-replete (>30 ng/mL; n = 38 [34%]) counterparts (P= .039). The vitamin D-insufficient cohort was enriched for de novo LBCL as the histological subtype (P= .026) and had a higher proportion of tisagenlecleucel as the CAR-T product (P= .049). There were no other significant differences in the baseline characteristics between the two groups. In vitamin D-insufficient compared to -replete patients, 100-day complete response was 55% versus 76% (P= .029), and 2-year overall survival was 41% versus 71% (P= .061), respectively. In multivariate analysis, vitamin D insufficiency remained significantly associated with 100-day complete response (odds ratio 2.58 [1.05-6.83]; P= .045) and overall survival (hazard ratio 2.24 [1.08-4.66], P= .030). In recipients of tisagenlecleucel, vitamin D insufficiency was associated with significantly lower cell viability of the infused CAR-T product (P= .015). Finally, pretreatment vitamin D insufficiency did not predict for subsequent CAR-T-related toxicity. This is the first report to demonstrate that vitamin D insufficiency is associated with inferior clinical outcomes in CAR-T recipients. Further study into the mechanistic insights of this finding, and the potential role of vitamin D supplementation to optimize CAR-T are warranted., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Mentoring is considered an evidence-based practice for violence prevention. This study presents a partial replication of the Take Charge! program implemented in partnership with Big Brothers Big Sisters of America (BBBS). One hundred and eighty-eight early adolescents (M age = 12.87; 61.17% male) who were treated for peer-related assault injury in two urban mid-Atlantic emergency departments were randomly assigned to receive a mentor from two BBBS affiliates. Mentors and organization staff were trained in the Take Charge! violence prevention curriculum, which had previously shown evidence of efficacy. Intent-to-treat analyses showed statistically significant improvements in conflict avoidance self-efficacy for the intervention group at 9 months and reductions in fighting at 21 months, but an increase in parental report of aggression at 9 months. Complier average causal effect models revealed evidence of an additional effect for reduced problem behavior at 21 months for intervention adolescents who received a mentor. No effects were found for youth-reported aggression, retaliatory attitudes, deviance acceptance, or commitment to learning. Sensitivity analyses suggested increased aggressive behavior for adolescents in the intervention group who did not receive a mentor (i.e., non-compliers). These findings extend the evidence-base for Take Charge! as a violence prevention curriculum for youth already engaged in violence to "real-world" implementation settings. However, they also suggest that challenges associated with providing youth with mentors can be consequential and that additional supports may be needed for these youth/parents. Clinical trials number: clinicaltrials.gov NCT01770873., (© 2022. Society for Prevention Research.)

Objectives: The aim of this study was to compare demographic characteristics, medical care, and outcomes among patients with assault-related concussion (ARC) versus sports and recreation-related concussion (SRC)., Methods: We conducted a retrospective chart review of 124 patients (62 ARC, 62 SRC) aged 8 to 17 years presenting to the care network of a large tertiary care pediatric hospital between July 1, 2012, and June 30, 2014 with a concussion diagnosis at time of presentation. We abstracted patient demographics, initial medical care visit characteristics, and outcome data, and compared proportions using χ2 testing and Fisher exact test and medians using Wilcoxon rank sum test., Results: Patients with ARC were more likely to be Black, publicly insured, and present first for care to the emergency department. Significantly fewer patients with ARC received visio-vestibular testing at initial visit (27% vs 74%, P < 0.001). During recovery, the total number of reported physical, cognitive, emotional, and sleep symptoms did not differ between groups; however, more than twice as many patients with ARC reported decline in grades postinjury compared with patients with SRC (47% vs 20%, P = 0.012). There were trends toward prolonged symptom recovery and time to physician clearance for full return to activities among patients with ARC compared with SRC., Conclusions: This study highlights potential disparities in the initial evaluation and outcomes of pediatric concussion patients based on mechanism of injury. Patients with ARC were less likely to receive a concussion-specific diagnostic evaluation and reported a greater impact on educational outcomes, suggesting differences in concussion diagnosis and management among assault-injured patients. Further examination in larger populations with prospective studies is needed to address potential inequities in concussion care and outcomes among patients with ARC., Competing Interests: Disclosure: The author declares no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To compare new mental health diagnoses (NMHD) in children after a firearm injury versus following a motor vehicle collision (MVC)., Background: A knowledge gap exists regarding childhood mental health diagnoses following firearm injuries, notably in comparison to other forms of traumatic injury., Methods: We utilized Medicaid MarketScan claims (2010-2016) to conduct a matched case-control study of children ages 3 to 17 years. Children with firearm injuries were matched with up to 3 children with MVC injuries. Severity was determined by injury severity score and emergency department disposition. We used multivariable logistic regression to measure the association of acquiring a NMHD diagnosis in the year postinjury after firearm and MVC mechanisms., Results: We matched 1450 children with firearm injuries to 3691 children with MVC injuries. Compared to MVC injuries, children with firearm injuries were more likely to be black, have higher injury severity score, and receive hospital admission from the emergency department ( P <0.001). The adjusted odds ratio (aOR) of NMHD diagnosis was 1.55 [95% confidence interval (95% CI): 1.33-1.80] greater after firearm injuries compared to MVC injuries. The odds of a NMHD were higher among children admitted to the hospital compared to those discharged. The increased odds of NMHD after firearm injuries was driven by increases in substance-related and addictive disorders (aOR: 2.08; 95% CI: 1.63-2.64) and trauma and stressor-related disorders (aOR: 2.07; 95% CI: 1.55-2.76)., Conclusions: Children were found to have 50% increased odds of having a NMHD in the year following a firearm injury as compared to MVC. Programmatic interventions are needed to address children's mental health following firearm injuries., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Individual comorbidities have distinct contributions to nonrelapse mortality (NRM) following allogeneic hematopoietic cell transplantation (allo-HCT). We studied the impact of comorbidities individually and in combination in a single-center cohort of 573 adult patients who underwent CD34-selected allo-HCT following myeloablative conditioning. Pulmonary disease, moderate to severe hepatic comorbidity, cardiac disease of any type, and renal dysfunction were associated with increased NRM in multivariable Cox regression models. A Simplified Comorbidity Index (SCI) composed of the 4 comorbidities predictive of NRM, as well as age >60 years, stratified patients into 5 groups with a stepwise increase in NRM. NRM rates ranged from 11.4% to 49.9% by stratum, with adjusted hazard ratios of 1.84, 2.59, 3.57, and 5.38. The SCI was also applicable in an external cohort of 230 patients who underwent allo-HCT with unmanipulated grafts following intermediate-intensity conditioning. The area under the receiver operating characteristic curve (AUC) of the SCI for 1-year NRM was 70.3 and 72.0 over the development and external-validation cohorts, respectively; corresponding AUCs of the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) were 61.7 and 65.7. In summary, a small set of comorbidities, aggregated into the SCI, is highly predictive of NRM. The new index stratifies patients into distinct risk groups, was validated in an external cohort, and provides higher discrimination than does the HCT-CI., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Purpose: Tumor-intrinsic features may render large B-cell lymphoma (LBCL) insensitive to CD19-directed chimeric antigen receptor T cells (CAR-T). We hypothesized that TP53 genomic alterations are detrimental to response outcomes in LBCL treated with CD19-CAR-T., Materials and Methods: Patients with LBCL treated with CD19-CAR-T were included. Targeted next-generation sequencing was performed on pre-CAR-T tumor samples in a subset of patients. Response and survival rates by histologic, cytogenetic, and molecular features were assessed. Within a cohort of newly diagnosed LBCL with genomic and transcriptomic profiling, we studied interactions between cellular pathways and TP53 status., Results: We included 153 adults with relapsed or refractory LBCL treated with CD19-CAR-T (axicabtagene ciloleucel [50%], tisagenlecleucel [32%], and lisocabtagene maraleucel [18%]). Outcomes echoed pivotal trials: complete response (CR) rate 54%, median overall survival (OS) 21.1 months (95% CI, 14.8 to not reached), and progression-free survival 6 months (3.4 to 9.7). Histologic and cytogenetic LBCL features were not predictive of CR. In a subset of 82 patients with next-generation sequencing profiling, CR and OS rates were comparable with the unsequenced cohort. TP53 alterations (mutations and/or copy number alterations) were common (37%) and associated with inferior CR and OS rates in univariable and multivariable regression models; the 1-year OS in TP53 -altered LBCL was 44% (95% CI, 29 to 67) versus 76% (65 to 89) in wild-type ( P = .012). Transcriptomic profiling from a separate cohort of patients with newly diagnosed lymphoma (n = 562) demonstrated that TP53 alterations are associated with dysregulation of pathways related to CAR-T-cell cytotoxicity, including interferon and death receptor signaling pathway and reduced CD8 T-cell tumor infiltration., Conclusion: TP53 is a potent tumor-intrinsic biomarker that can inform risk stratification and clinical trial design in patients with LBCL treated with CD19-CAR-T. The role of TP53 should be further validated in independent cohorts., Competing Interests: Roni ShouvalConsulting or Advisory Role: Medexus, MyBiotics Michal J. BesserEmployment: Envizion Medical (I)Leadership: Envizion Medical (I)Stock and Other Ownership Interests: Envizion Medical (I)Consulting or Advisory Role: Biological Industries (a Sartorius Company), Gilboa TherapeuticsPatents, Royalties, Other Intellectual Property: Patents at Envizion Medical (I), Royalties at Biological Industries (Inst)Travel, Accommodations, Expenses: Lonza Connie Lee BatleviStock and Other Ownership Interests: Moderna Therapeutics, Novavax, Pfizer, Bristol Myers Squibb, Regeneron, ViatrisHonoraria: DAVA OncologyConsulting or Advisory Role: LifeSci Capital, GLG, Juno Therapeutics, Celgene, Seattle Genetics, Kite, a Gilead company, TG Therapeutics, Karyopharm TherapeuticsResearch Funding: Janssen Biotech (Inst), Novartis (Inst), Epizyme (Inst), Xynomic Pharma (Inst), Bayer (Inst), Roche (Inst), Autolus (Inst)Open Payments Link: https://openpaymentsdata.cms.gov/physician/2778694 Parastoo B. DahiConsulting or Advisory Role: Kite, a Gilead company Sean M. DevlinThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript. Sergio A. GiraltHonoraria: Celgene, Takeda, Amgen, Jazz Pharmaceuticals, Sanofi,Consulting or Advisory Role: Celgene, Takeda, Sanofi, Jazz Pharmaceuticals, Amgen, Janssen, Actinuum, Bristol Myers Squibb, Johnson & Johnson, PfizerResearch Funding: Celgene (Inst), Miltenyi Biotec, Johnson & Johnson, Amgen, Actinuum, SanofiTravel, Accommodations, Expenses: Celgene, Sanofi, Amgen, Jazz Pharmaceuticals Richard J. LinEmployment: Pfizer (I)Consulting or Advisory Role: Kite/Gilead Gal MarkelEmployment: 4C Biomed, Ella TherapeuticsLeadership: 4C Biomed, Ella TherapeuticsStock and Other Ownership Interests: Purple Biotech, Biond Biologics, Nucleai, Staburo GmbH, Ella Therapeutics, 4C BiomedHonoraria: BMS, MSD, Novartis, Medison, RocheConsulting or Advisory Role: MSD, NovartisSpeakers' Bureau: MSD, BMSResearch Funding: Novartis (Inst), Immunicom (Inst)Patents, Royalties, Other Intellectual Property: Patent on anti-CEACAM1 blocking antibodiesTravel, Accommodations, Expenses: BMS, Novartis, MSD Gilles SallesHonoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSysConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, BMS, BeiGene, Incyte, Miltenyi Biotec, Ipsen Craig S. SauterConsulting or Advisory Role: Spectrum Pharmaceuticals, Juno Therapeutics, Sanofi, Gilead Sciences, Novartis¸ Precision BioSciences, Gamida Cell, Karyopharm Therapeutics, GlaxoSmithKline, GenmabResearch Funding: Juno Therapeutics (Inst), Sanofi (Inst), Precision BioSciences (Inst), BMS (Inst), Actinium Pharmaceuticals (Inst)Travel, Accommodations, Expenses: Juno Therapeutics, Sanofi, Gilead Sciences, Novartis Michael ScordoHonoraria: i3 CMEConsulting or Advisory Role: McKinsey & Company, Angiocrine Bioscience, OmerosResearch Funding: Angiocrine Bioscience, Omeros (Inst)Travel, Accommodations, Expenses: Kite/Gilead Gunjan L. ShahResearch Funding: Amgen (Inst), Janssen (Inst) Marcel van den BrinkHonoraria: Seres Therapeutics, Merck, Magenta Therapeutics, WindMIL, Rheos Medicines, Frazier Healthcare Partners, Nektar, Notch Therapeutics, Forty Seven, Priothera, Ceramedix, LyGenesis, Pluto Therapeutics, GlaxoSmithKline, Da Volterra, Novartis (I), Synthekine (I), BeiGene (I)Consulting or Advisory Role: Seres TherapeuticsResearch Funding: Seres TherapeuticsPatents, Royalties, Other Intellectual Property: Dr van den Brink receives royalties from Wolters Kluwer, and he has intellectual property Licensing with Seres Therapeutics and Juno TherapeuticsTravel, Accommodations, Expenses: Rheos MedicinesOther Relationship: DKMSUncompensated Relationships: Seres therapeutics, Notch Therapeutics, Pluto Therapeutics Miguel-Angel PeralesStock and Other Ownership Interests: NexImmuneHonoraria: MorphoSysConsulting or Advisory Role: Incyte, Merck, Servier/Pfizer, NexImmune, Novartis, MolMed, Medigene, Takeda, Nektar, AbbVie, Cidara Therapeutics, Celgene, Kite/Gilead, Bristol Myers Squibb, Omeros, Vor BiopharmaResearch Funding: Incyte (Inst), Miltenyi Biotec (Inst), Novartis (Inst), Kite, a Gilead company (Inst), Nektar (Inst) Maria Lia PalombaStock and Other Ownership Interests: Seres Therapeutics (I)Honoraria: Flagship Biosciences (I), Evelo Therapeutics (I), Jazz Pharmaceuticals (I), Therakos (I), Amgen (I), Merck (I), Seres Therapeutics (I)Consulting or Advisory Role: Flagship Biosciences (I), Novartis (I), Evelo Therapeutics (I), Jazz Pharmaceuticals (I), Therakos (I), Amgen (I), Merck (I), Seres Therapeutics (I), Kite, a Gilead company, Novartis, BeiGene, SynthekineResearch Funding: Seres Therapeutics (I)Patents, Royalties, Other Intellectual Property: Intellectual Property Rights (I), Juno intellectual property rights (Inst)No other potential conflicts of interest were reported.

Objectives: This study evaluates the relationship between substance use and impairment and current suicidal thoughts or behaviors in adolescent patients screened in a pediatric emergency department (ED)., Methods: Data were collected between June 2013 and February 2018 from adolescent patients who presented to a single, urban, pediatric ED. Adolescents completed a computerized, self-administered assessment that evaluates depression, suicide, posttraumatic stress, violence, traumatic exposure, bullying, and substance use. Assessments are administered as standard care to all ED patients aged 14 to 18 years. We used binary logistic regression to estimate the odds of reporting current suicidal thoughts or behaviors associated with patient demographics (ie, age, sex, and race), substance use in the past month, and substance-related impairment., Results: A total of 11,623 adolescent patients (65.4% female and 52.9% African American) completed the assessment. Participants were, on average, 15.7 years old (SD = 1.27). Younger age (odds ratio [OR], 0.79; 95% confidence interval [CI], 0.74-0.84) and substance use impairment (OR, 0.44; 95% CI, 0.33-0.58) decreased the odds of reporting current suicidal thoughts or behaviors, whereas male sex (OR, 1.51; 95% CI, 1.28-1.79) and those with past-month substance use (OR, 1.85; 95% CI, 1.51-2.26) increased the odds., Conclusions: Recent substance use and male sex are associated with a higher likelihood of adolescents reporting current suicidal thoughts or behaviors during an ED visit. Standardized screening during pediatric ED visits may allow for more efficient evaluation of patients in higher-risk groups., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We observed high rates of bloodstream infections (BSIs) following fecal microbiota transplantation (FMT) for graft-versus-host-disease (33 events in 22 patients). To trace the BSIs' origin, we applied a metagenomic bioinformatic pipeline screening donor and recipient stool samples for bacteremia-causing strains in 13 cases. Offending strains were not detected in FMT donations. Enterococcus faecium, Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii could be detected in stool samples before emerging in the blood. In this largest report of BSIs post-FMT, we present an approach that may be applicable for evaluating BSI origin following microbiota-based interventions. Our findings support FMT safety in immunocompromised patients but do not rule out FMT as an inducer of bacterial translocation., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Objectives: This study aimed to identify factors associated with urban youth and parent's perception of the preventability of medically attended youth assault injuries to guide future violence prevention strategies., Methods: Assault-injured youth (n = 188; ages, 10-15 years; 60% male; 96% black) and their parents were recruited from 2 pediatric emergency departments in 2 cities. Mental health, injury severity, circumstances of injury, and family composition were some of the factors explored as cross-sectional predictors of the perception of the preventability of youth assault injury. Separate models were developed using stepwise regression for youth and parents., Results: Sixty-eight (38%) youth and 123 parents (68%) reported that the injury was definitely preventable (χ2 = 9.6250, P < 0.05). For youth, identifying themselves as the aggressor (odds ratio [OR], 0.23, 95% confidence interval [CI], 0.07-0.70) or having been hospitalized for psychiatric illness (OR, 0.21; 95% CI, 0.05-0.85) was associated with lower odds of perceiving their injury as preventable, while being under the care of a mental health professional (OR, 3.87; 95% CI, 1.21-12.39) was associated with higher odds. For parents, being in a household with grandparents (OR, 0.21; 95% CI, 0.04-0.99) or having a child with a learning disability (OR, 0.16; 95% CI, 0.05-0.57) was associated with lower odds of perceiving the injury as preventable., Conclusions: Several factors in youth and parents were identified as being associated with perception of preventability of injuries in this high-risk population of youth. Youth and parents identified different factors. In addition, although most parents reported that the assault injury sustained by their child was preventable, the opposite was true for youth perceptions. Future violence prevention programs should consider youth and parent perspectives and develop unique strategies to address both their needs., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Many children and adolescents in the United States are exposed to neighborhood gun violence. Associations between violence exposure and children's short-term mental health are not well understood., Objective: To examine the association between neighborhood gun violence and subsequent mental health-related pediatric emergency department (ED) utilization., Design, Setting, and Participants: This location-based cross-sectional study included 128 683 ED encounters for children aged 0 to 19 years living in 12 zip codes in Philadelphia, Pennsylvania, who presented to an urban academic pediatric ED from January 1, 2014, to December 31, 2018. Children were included if they (1) had 1 or more ED visits in the 60 days before or after a neighborhood shooting and (2) lived within a quarter-mile radius of the location where this shooting occurred. Analysis began August 2020 and ended May 2021., Exposure: Neighborhood violence exposure, as measured by whether a patient resided near 1 or more episodes of police-reported gun violence., Main Outcomes and Measures: ED encounters for a mental health-related chief complaint or primary diagnosis., Results: A total of 2629 people were shot in the study area between 2014 and 2018, and 54 341 children living nearby had 1 or more ED visits within 60 days of a shooting. The majority of these children were Black (45 946 [84.5%]) and were insured by Medicaid (42 480 [78.1%]). After adjusting for age, sex, race and ethnicity, median household income by zip code, and insurance, children residing within one-eighth of a mile (2-3 blocks) of a shooting had greater odds of mental health-related ED presentations in the subsequent 14 days (adjusted odds ratio, 1.86 [95% CI, 1.20-2.88]), 30 days (adjusted odds ratio, 1.49 [95% CI, 1.11-2.03]), and 60 days (adjusted odds ratio, 1.35 [95% CI, 1.06-1.72])., Conclusions and Relevance: Exposure to neighborhood gun violence is associated with an increase in children's acute mental health symptoms. City health departments and pediatric health care systems should work together to provide community-based support for children and families exposed to violence and trauma-informed care for the subset of these children who subsequently present to the ED. Policies aimed at reducing children's exposure to neighborhood gun violence and mitigating the mental symptoms associated with gun violence exposure must be a public health priority.

Risk stratification is important for balancing potential risks and benefits of allogeneic hematopoietic stem cell transplantation (HSCT) for hematological malignancies. We retrospectively studied 1119 patients undergoing allogenic-HSCT in a single center for five hematological indications assessing the prognostic role of LDH at admission for survival (OS), progression-free survival (PFS), relapse incidence (RI), and nonrelapse mortality (NRM). In non-Hodgkin lymphoma (NHL) and acute myeloid leukemia (AML), higher than median LDH had an adverse effect on survival. The prognostic significance was strongest in AML, with higher LDH levels having lower 1-and 3-year survival 69.2% vs. 50.8%, P < 0.001 and 51.9% vs. 39.2%, P < 0.001, respectively, reduced 1-and 3-year PFS 62.4% vs. 42.1%, P < 0.001 48% vs. 35.2%, P < 0.001, respectively, higher cumulative incidence of 1-and 3-year NRM 11% vs. 17.3%, p = 0.01 and 15.7% vs. 19.6%, P = 0.04, and higher 1-and 3-year relapse incidence (RI) 26.7% vs. 40.7%, p < .0001 36.2% vs. 40.7%, respectively, P < 0.0001). In multivariate analysis LDH maintained significant prognostic capacity in OS, PFS and RI. These findings in AML, validated in an independent cohort, suggest that LDH is a readily available tool that could be integrated into transplant risk assessments to aid decision-making and identify high-risk patients who may benefit from post-transplant pharmacological or cellular strategies., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objectives: The aim of this study was to understand the prevalence of alcohol and other substance use among teenagers in generalized samples., Methods: This study compared the alcohol and other substance use of adolescents enrolled in a screening study across 16 Pediatric Emergency Care Applied Research Network emergency departments (EDs) (ASSESS) with those sampled in 2 nationally representative surveys, the Youth Risk Behavior Surveillance System (YRBSS) and the National Survey of Drug Use and Health (NSDUH). The analysis includes 3362 ASSESS participants and 11,142 YRBSS and 12,086 NSDUH respondents., Results: The ASSESS patients had a similar profile to the NSDUH sample, with small differences in marijuana and cocaine use and age at first tobacco smoking and smoking within the last 30 days and higher use of snuff or chewing tobacco. The YRBSS participants had higher rates of using marijuana, snuff/chewing tobacco, methamphetamine, and hallucinogens and higher smoking rates compared with ASSESS and NSDUH., Conclusions: Adolescents visiting Pediatric Emergency Care Applied Research Network EDs have substantial rates of substance use, similar to other nationally representative studies on this topic, although not as high as a school-based survey. Future ED studies should continue to investigate adolescent substance use, including exploring optimal methods of survey administration., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Previous work links witnessing adult violence in the home during childhood ("witnessing") and adolescent relationship violence, but studies are limited to recent experiences with one or two outcomes, missing the holistic viewpoint describing lifetime experiences across multiple types of violence. We measured associations between witnessing and victimization (being harmed by violence) and perpetration (causing harm by violence) among males and females for the three most common types of adolescent relationship violence (physical, sexual, and emotional), and we assessed whether students experienced multiple outcomes ("polyvictimization/ polyperpetration"). We also compared sex-specific differences to assess for additive effect modification. We used an anonymous, cross-sectional survey with 907 undergraduates attending randomly selected classes at three urban East Coast colleges. Multiple logistic regression and marginal standardization were used to estimate predicted probabilities for each outcome among witnesses and non-witnesses; additive interaction by sex was assessed using quantifiable measures. 214 (24%) students reported witnessing and 403 (44%) students experienced adolescent relationship violence, with 162 (17.9%) and 37 (4.1%) experiencing polyvictimization and polyperpetration, respectively. Witnesses had higher risk than non-witnesses for physical, sexual, and emotional victimization and perpetration. Notably, witnesses also had higher risk for polyvictimization and polyperpetration. Additive effect modification by sex was insignificant at 95% confidence bounds, but distinct patterns emerged for males and females. Except for sexual victimization, female witnesses were more likely than female non-witnesses to experience all forms of victimization, including polyvictimization; they also had higher risk for perpetration, particularly physical perpetration. In contrast, victimization outcomes did not differ for male witnesses, but male witnesses were more likely than male non-witnesses to perpetrate all forms of violence, including polyperpetration.

Objective: Firearm injuries are one of the leading preventable causes of morbidity and mortality among children. Limited information exists about the impact of nonfatal firearm injuries on utilization and expenditures. Our objective was to compare health care encounters and expenditures 1 year before and 1 year following a nonfatal firearm injury., Methods: This was a retrospective cohort study of children 0 to 18 years with ICD-9/ICD-10 diagnosis codes for firearm injury (excluding nonpowder) in the emergency department or inpatient setting from 2010 to 2016 in the Medicaid MarketScan claims database. Outcomes included: (1) difference in health care encounters for 1 year before and 1 year after injury, (2) difference in health care expenditures, and (3) difference in complex chronic disease status. Descriptive statistics characterized patient demographics and health care utilization. Health expenditures were evaluated with Wilcoxon signed-rank tests., Results: Among 1,821 children, there were 22,398 health care encounters before the injury and 28,069 after. Concomitantly, there was an overall increase of $16.5 million in health expenditures ($9,084 per patient). There was a 50% increase in children qualifying for complex chronic condition status after firearm injury., Conclusions: Children who experience nonfatal firearm injury have increased number of health care encounters, chronic disease classification, and health care expenditures in the year following the injury. Prevention of firearm injuries in this vulnerable age group may result in considerable reductions in morbidity and health care costs., (© 2021 by the Society for Academic Emergency Medicine.)