Delayed abdominal aortic aneurysm sac rupture after open repair.

Open surgical repair of abdominal aortic aneurysm (AAA) is often regarded as a near-permanent operation with little long-term complications. Reported herein is a case of delayed rupture of an enlarging AAA sac after open repair requiring re-exploration in a patient presenting with flank pain and ipsilateral hydronephrosis. The natural history of a large, excluded aneurysm sac after open AAA repair, hypothesized etiology for this rare occurrence, and proposed diagnostic and therapeutic algorithm are described.

Supplemental Nutrition Assistance Program participation gaps within a pediatric leukemia clinical trial cohort.

Poverty-exposed children with cancer are more likely to experience adverse outcomes. Supplemental Nutrition Assistance Program (SNAP) benefits improve food insecurity and child health outcomes, and could be used to mitigate disparities. We conducted a secondary analysis of parent-reported data collected in a frontline pediatric leukemia trial (NCT03020030) to assess SNAP eligibility (proxied by other means-tested program participation) and participation. At diagnosis, 105/287 families (37%) were SNAP-eligible, of whom 53 (50%) were SNAP participants. At 6 months, 104/257 families (41%) were SNAP-eligible, and 59 (57%) were SNAP participants. Interventions to increase benefits participation during childhood cancer treatment represent an immediate opportunity to reduce disparities.

Genome-wide study identifies novel genes associated with bone toxicities in children with acute lymphoblastic leukaemia.

Bone toxicities are common among paediatric patients treated for acute lymphoblastic leukaemia (ALL) with potentially major negative impact on patients' quality of life. To identify the underlying genetic contributors, we conducted a genome-wide association study (GWAS) and a transcriptome-wide association study (TWAS) in 260 patients of European-descent from the DFCI 05-001 ALL trial, with validation in 101 patients of European-descent from the DFCI 11-001 ALL trial. We identified a significant association between rs844882 on chromosome 20 and bone toxicities in the DFCI 05-001 trial (p = 1.7 × 10-8). In DFCI 11-001 trial, we observed a consistent trend of this variant with fracture. The variant was an eQTL for two nearby genes, CD93 and THBD. In TWAS, genetically predicted ACAD9 expression was associated with an increased risk of bone toxicities, which was confirmed by meta-analysis of the two cohorts (meta-p = 2.4 × 10-6). In addition, a polygenic risk score of heel quantitative ultrasound speed of sound was associated with fracture risk in both cohorts (meta-p = 2.3 × 10-3). Our findings highlight the genetic influence on treatment-related bone toxicities in this patient population. The genes we identified in our study provide new biological insights into the development of bone adverse events related to ALL treatment.

The impact of comparative genomic hybridization/single-nucleotide polymorphism microarray in risk stratification of pediatric acute lymphoblastic leukemia.

BACKGROUND: The objective of this study is to assess the concordance and added value of combined comparative genomic hybridization plus single-nucleotide polymorphism microarray (CGH/SNP) analyses in pediatric acute lymphoblastic leukemia (ALL) risk stratification compared to conventional cytogenetic methods. PROCEDURE: This is a retrospective study that included patients aged 1-18 years diagnosed with de novo ALL at Sainte-Justine Hospital between 2016 and 2021. Results from conventional cytogenetic and molecular analyses were collected and compared to those of CGH/SNP. RESULTS: A total of 135 ALL patients were included. Sample failures or non-diagnostic analyses occurred in 17.8% cases with G-banding karyotypes versus 1.5% cases with CGH/SNP. The mean turnaround time for results was significantly faster for CGH/SNP than karyotype with 5.8 versus 10.7 days, respectively. The comparison of ploidy assessment by CGH/SNP and G-banding karyotype showed strong concordance (r = .82, p < .001, r2 = .68). Furthermore, G-banding karyotype did not detect additional clinically relevant aberrations that were missed by the combined analysis of CGH/SNP and fluorescence in situ hybridization. The most common gene alterations detected by CGH/SNP were deletions involving CDKN2A (35.8%), ETV6 (31.3%), CDKN2B (28.4%), PAX5 (20.1%), IKZF1 (12.7%), and copy-neutral loss of heterozygosity (CN-LOH) of 9p (9.0%). Among these, only ETV6 deletion was found to have a significant prognostic impact with superior event-free survival in both univariate and multivariate analyses (adjusted hazard ratio 0.08, 95% confidence interval: 0.01-0.50, p = .02). CONCLUSION: CGH/SNP provided faster, reliable, and highly concordant results than those obtained by conventional cytogenetics. CGH/SNP identified recurrent gene deletions in pediatric ALL, of which ETV6 deletion conferred a favorable prognosis.

The natural history of isolated common femoral endarterectomy for chronic limb-threatening ischemia.

OBJECTIVE: Occlusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated common femoral endarterectomy (CFE) is highly effective. Because CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization). METHODS: Consecutive CFEs performed in a large, urban hospital for CLTI between 2014 and 2021 were reviewed. Patient characteristics, limb, and anatomical stages using the Wound, Ischemia, foot Infection (WIfI) and Global Limb Anatomic Staging System were tabulated. Limb-specific and survival-related end points were analyzed. RESULTS: Fifty-eight patients presenting with CLTI underwent isolated CFE (mean age, 74 ± 10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% Global Limb Anatomic Staging Systems 3). After a median follow-up of 17 months (range, 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (P = .034). CONCLUSIONS: Isolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.

Morbidity and mortality of common femoral endarterectomy.

OBJECTIVE: Common femoral endarterectomy (CFE) comprises the current standard-of-care for symptomatic common femoral artery occlusive disease. Although it provides effective inflow revascularization via a single incision, it remains an invasive procedure in an often-frail patient population. The purpose of this retrospective clinical study was to assess the morbidity and mortality of CFE in a contemporary cohort. METHODS: Consecutive CFEs performed at a large, urban hospital were reviewed. Six-month mortality, local complications (hematoma, lymphatic leak, pseudoaneurysm, wound infection, and/or dehiscence), and systemic complications were analyzed using univariate and multivariate analyses. RESULTS: A total of 129 isolated CFEs were performed over 7 years for claudication (36%), rest pain (16%), tissue loss (29%), or acute on chronic limb ischemia (21%). Mean age was 75 ± 9 years, and 68% of patients were male. Comorbidities were prevalent, including coronary artery disease (54%), diabetes (41%), chronic pulmonary disease (25%), and congestive heart failure (22%). The majority of CFEs were performed under general anesthesia (98%) with patch angioplasty using bovine pericardium (73% vs 27% Dacron). Twenty-two patients (17%) sustained local complications following the procedure; their occurrence was significantly associated with obesity (P = .002) but no technical or operative factors. Nineteen patients (15%) sustained serious systemic complications; their occurrence was significantly associated with chronic limb-threatening ischemia (P < .001), and a high American Society of Anesthesiologists (ASA) class (P = .002). By 6 months, 17 patients (13%) had died. Being on dialysis, presenting with chronic limb-threatening ischemia, and being in a high ASA class at the time of operation were all associated with 6-month mortality; a high ASA class at the time of operation was independently predictive of mortality (odds ratio, 3.08; 95% confidence interval, 1.03-9.24; P = .044). CONCLUSIONS: Although commonly performed, CFE is not a benign vascular procedure. Disease presentation, anesthetic risk, and expected longevity play an important role in clinical outcomes. Evolving endovascular approaches to the common femoral artery could serve to reduce morbidity and mortality in the future.

Treatment completion, asparaginase completion, and oncologic outcomes among children, adolescents and young adults with acute lymphoblastic leukemia treated with DFCI Consortium Protocols.

Adolescents and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) face worse outcomes than children. While pediatric-inspired protocols have improved outcomes, the ability of patients to complete these intensive regimens and the reasons for discontinuation are unknown. We analyzed a cohort of 332 AYA patients (aged 15-49 years) and 1159 children (aged 1-14 years) with Ph-negative ALL treated on DFCI consortium protocols. We found that AYA patients completed treatment at lower rates than children (60.8% vs. 89.7%, p < 0.001), primarily due to higher rates of early treatment failure (14.5% vs. 2.4%, p < 0.001). Withdrawal from treatment for toxicity, social/personal, or unknown reasons was uncommon, but higher among AYA patients (9.3% vs 4.7%, p = 0.001). Patients who remained on assigned therapy for one year had favorable overall survival (AYA 5-year OS 88.9%; children 5-year OS 96.4%; p < 0.001). Among patients who continued treatment for 1 year, AYA patients completed asparaginase (defined as receiving 26+ weeks) at lower rates than children (79.1% vs. 89.6%, p < 0.001). Patients who received more weeks of consolidation asparaginase had higher overall and event-free survival. Efforts should focus on identifying patients at risk for early treatment failure and optimizing asparaginase delivery.

Surrogate Decision-Making After Stroke in a Community Setting: The OASIS Project.

BACKGROUND: Patients with severe stroke often rely on surrogate decision-makers for life-sustaining treatment decisions. We investigated ethnic differences between Mexican Americans (MAs) and non-Hispanic White (NHW) individuals in surrogate reports of physician quality of communication and shared decision-making from the OASIS study (Outcomes Among Surrogate Decision Makers in Stroke) project. METHODS: Patients had ischemic stroke or intracerebral hemorrhage in Nueces County, TX. Surrogates self-identified as being involved in decisions about do-not-resuscitate orders, brain surgery, ventilator, feeding tube, or hospice/comfort care. Surrogate reports of physician quality of communication (scale score, range from 0 to 10) and shared decision-making (CollaboRATE scale score, binary score 1 versus 0) were compared by ethnicity with linear or logistic regression using generalized estimating equations, adjusted for prespecified demographics, clinical factors, and confounders. RESULTS: Between April 2016 and September 2020, 320 surrogates for 257 patients with stroke enrolled (MA, 158; NHW, 85; and other, 14). Overall quality of communication score was better among surrogates of MA patients than NHW individuals after adjustment for demographics, stroke severity, and patient survival though the ethnic difference was attenuated (ß, 0.47 [95% CI, -0.17 to 1.12]; P=0.15) after adjustment for trust in the medical profession and frequency of personal prayer. High CollaboRATE scale scores were more common among surrogates of MA patients than NHW individuals (unadjusted odds ratio, 1.75 [95% CI, 1.04-2.95]). This association persisted after adjustment for demographic and clinical factors though there was an interaction between patient age and ethnicity (P=0.04), suggesting that this difference was primarily in older patients. CONCLUSIONS: Surrogate decision-makers of MA patients generally reported better outcomes on validated measures of quality of communication and shared decision-making than NHW individuals. Further study of outcomes among diverse populations of stroke surrogate decision-makers may help to identify sources of strength and resiliency that may be broadly applicable.

Slowly moving the needle away from Fistula First.

OBJECTIVE: In 2019, the management of end-stage kidney disease (ESKD) shifted away from "Fistula First" (FF) to "ESKD Life-Plan: Patient Life-Plan First then Access Needs." Indeed, some patients exhibit such excessive comorbidity that even relatively minor vascular surgery may be complicated. The purpose of this study was to retrospectively assess complications and mortality (and delineate operative futility) in patients undergoing arteriovenous fistula (AVF) creation in the FF era. METHODS: Consecutive AVFs created in a single institution before 2021 were retrospectively reviewed. Operative futility was defined as never-accessed fistula, no initiation of dialysis, failure of access maturation (despite secondary intervention), hemodialysis access-induced distal ischemia requiring ligation, early loss of secondary patency, and/or patient mortality within the first 6 postoperative months. RESULTS: A total of 401 AVFs were created including radial-cephalic (44%), brachial-cephalic (41%), and brachial-basilic (15%) constructions. Patients exhibited a mean age of 69 ± 15 years; 63% were male, and most (74%) were already being hemodialyzed at the time of fistula creation. Forty-five patients (11%) suffered a cardiac event, and five patients died (1%) within 90 days of their access surgery. Perioperative cardiac events were significantly more common after age 80 (19% vs 8%; P = .004); age >80 years was an independent predictor of major 90-day complications (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.04-3.39; P = .036) and the sole independent predictor of major morbidity defined as cardiopulmonary complications, stroke, or death within the first year (OR, 2.01; 95% CI, 1.24-3.25; P = .004). Operative futility was encountered in 52% of the cohort (n = 208 patients): 40% (n = 160) of primary AVFs failed to mature despite assistance, 19% (n = 77) had lost secondary patency by 6 months, 13% of patients (n = 53) were never started on dialysis after access creation, 4% (n = 16) were dead by 6 months, 2% of AVFs (n = 10) matured but were never accessed, and 2% (n = 9) required ligation for hemodialysis access-induced distal ischemia. Not surprisingly, the sole independent protector against operative futility was that catheter-based dialysis had been established prior to AVF creation (OR, 0.36; 95% CI, 0.22-0.59; P < .01). CONCLUSIONS: Approximately 50% of primary AVF operations performed in the aggressive FF era were deemed futile. Octogenarians were particularly prone to futility and complications during this era. A paradigm shift, from FF to an "ESKD Life-Plan" will, hopefully, more thoughtfully match vascular access strategies to individual patient needs.

The Risk of Lymphedema After Breast Cancer Surgery Should Not Restrict Necessary Hand Surgery Interventions.

BACKGROUND: The purpose of this study was to evaluate the incidence of lymphedema onset or exacerbation in patients undergoing upper extremity interventions, both nonoperative and operative, after breast cancer surgery. METHODS: The study inclusion criteria were the following: (1) prior history of breast cancer surgery or lymphedema from the cancer; (2) upper extremity intervention, ipsilateral to the breast cancer side; and (3) follow-up of at least 1 month. Patients were evaluated for demographic information, type of breast cancer procedure and hand intervention, number of lymph nodes dissected, preexisting lymphedema, exacerbation of lymphedema, and new-onset lymphedema. RESULTS: A total of 161 patients undergoing 385 hand interventions (300 injections, 85 surgeries) were reviewed. Median follow-up was 31 months (range: 1-110). Nineteen patients had preexisting lymphedema ipsilateral to the hand procedure and none experienced an exacerbation of their lymphedema. Three patients developed new-onset lymphedema ipsilateral to their hand intervention at an average follow-up of 30 months (range: 4-67). One patient had a single injection and developed lymphedema over 5 years later. One had 2 injections in the same hand on the same date and developed lymphedema 3 months later. The third patient had 2 injections in the right hand, 1 injection and 1 surgery in the left hand, and developed either lymphedema or swelling due to rheumatoid arthritis in the right hand 1 year after the injections. CONCLUSIONS: Patients who have undergone breast cancer surgery can safely undergo upper extremity intervention with low risk of lymphedema exacerbation or onset.

Clinical and molecular heterogeneity of syndromic hypothalamic hamartoma.

Two children are presented who have a distinct syndrome of multiple buccolingual frenula, a stiff and short fifth finger with small nails, a hypothalamic hamartoma, mild to moderate neurological impairment, and mild endocrinological symptoms. No variant assessed to be pathogenic or likely pathogenic was detected in the GLI3 gene in either child. This syndrome appears to be distinct from the inherited Pallister-Hall syndrome associated with GLI3 variants, which is characterized by hypothalamic hamartoma, mesoaxial polydactyly, and other anomalies. In the individuals described here, manifestations outside of the central nervous system were milder and the mesoaxial polydactyly, which is common in individuals with Pallister-Hall syndrome, was absent. Instead, these children had multiple buccolingual frenula together with the unusual appearance of the fifth digit. It remains unclear whether these two individuals represent a separate nosologic entity or if they represent a milder manifestation of one of the more severe syndromes associated with a hypothalamic hamartoma.

Outlier Expression of Isoforms by Targeted or Total RNA Sequencing Identifies Clinically Significant Genomic Variants in Hematolymphoid Tumors.

Recognition of aberrant gene isoforms due to DNA events can impact risk stratification and molecular classification of hematolymphoid tumors. In myelodysplastic syndromes, KMT2A partial tandem duplication (PTD) was one of the top adverse predictors in the International Prognostic Scoring System-Molecular study. In B-cell acute lymphoblastic leukemia (B-ALL), ERG isoforms have been proposed as markers of favorable-risk DUX4 rearrangements, whereas deletion-mediated IKZF1 isoforms are associated with adverse prognosis and have been extended to the high-risk IKZF1plus signature defined by codeletions, including PAX5. In this limited study, outlier expression of isoforms as markers of IKZF1 intragenic or 3' deletions, DUX4 rearrangements, or PAX5 intragenic deletions were 92.3% (48/52), 90% (9/10), or 100% (9/9) sensitive, respectively, and 98.7% (368/373), 100% (35/35), or 97.1% (102/105) specific, respectively, by targeted RNA sequencing, and 84.0% (21/25), 85.7% (6/7), or 81.8% (9/11) sensitive, respectively, and 98.2% (109/111), 98.4% (127/129), or 98.7% (78/79) specific, respectively, by total RNA sequencing. Comprehensive split-read analysis identified expressed DNA breakpoints, cryptic splice sites associated with IKZF1 3' deletions, PTD of IKZF1 exon 5 spanning N159Y in B-ALL with mutated IKZF1 N159Y, and truncated KMT2A-PTD isoforms. Outlier isoforms were also effective targeted RNA markers for PAX5 intragenic amplifications (B-ALL), KMT2A-PTD (myeloid malignant cancers), and rare NOTCH1 intragenic deletions (T-cell acute lymphoblastic leukemia). These findings support the use of outlier isoform analysis as a robust strategy for detecting clinically significant DNA events.

Impairment of health-related quality of life for children with acute lymphoblastic leukemia over the first year of therapy: A report from the DFCI ALL Consortium.

BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) receive prolonged treatment, resulting in toxicities that affect health-related quality of life (HR-QoL). Longitudinal assessment of HR-QoL allows improved understanding of experiences with ALL. PROCEDURE: Parent-proxy and child self-report HR-QoL over the first year of chemotherapy were evaluated in the context of DFCI Protocol 05-001, a phase 3 therapeutic trial for childhood ALL. HR-QoL was assessed with the Pediatric Quality-of-Life inventory (PedsQL) domains for Pain and Hurt, Procedural Anxiety, Treatment Anxiety, Emotional Functioning, General Fatigue, and Sleep/Rest Fatigue. RESULTS: Total of 281 subjects participated, with 141 contributing at least one child report and 280 at least one parent report. Children with ALL experienced impairment in HR-QoL by both patient and parent report compared to the published PedsQL reference population at each time point on each subscale. Agreement between parent and child assessment of HR-QoL impairment was high, particularly among those for whom HR-QoL was not impaired. During the consolidation phase, which included intensive asparaginase administration, multivariable models demonstrated more impairment in Treatment Anxiety and Procedural Anxiety for children treated with intramuscular asparaginase than intravenous asparaginase, but randomized groups were otherwise similar in HR-QoL. Impairments in fatigue, both General and Sleep/Rest, were evident throughout and worse during intensive asparaginase therapy. CONCLUSIONS: This report examines HR-QoL for children with ALL during treatment longitudinally by parent and patient report across multiple domains. Children with ALL demonstrated substantial impairment in HR-QoL, particularly related to fatigue during intensive consolidation therapy including asparaginase.

Dasatinib with intensive chemotherapy in de novo paediatric Philadelphia chromosome-positive acute lymphoblastic leukaemia (CA180-372/COG AALL1122): a single-arm, multicentre, phase 2 trial.

BACKGROUND: The outcome of children with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukaemia significantly improved with the combination of imatinib and intensive chemotherapy. We aimed to investigate the efficacy of dasatinib, a second-generation ABL-class inhibitor, with intensive chemotherapy in children with newly diagnosed Ph-positive acute lymphoblastic leukaemia. METHODS: CA180-372/COG AALL1122 was a joint Children's Oncology Group (COG) and European intergroup study of post-induction treatment of Ph-positive acute lymphoblastic leukaemia (EsPhALL) open-label, single-arm, phase 2 study. Eligible patients (aged >1 year to <18 years) with newly diagnosed Ph-positive acute lymphoblastic leukaemia and performance status of at least 60% received EsPhALL chemotherapy plus dasatinib 60 mg/m2 orally once daily from day 15 of induction. Patients with minimal residual disease of at least 0·05% after induction 1B or who were positive for minimal residual disease after the three consolidation blocks were classified as high risk and allocated to receive haematopoietic stem-cell transplantation (HSCT) in first complete remission. The remaining patients were considered standard risk and received chemotherapy plus dasatinib for 2 years. The primary endpoint was the 3-year event-free survival of dasatinib plus chemotherapy compared with external historical controls. The trial was considered positive if one of the following conditions was met: superiority over chemotherapy alone in the AIEOP-BFM 2000 high-risk group; or non-inferiority (with a margin of -5%) or superiority to imatinib plus chemotherapy in the EsPhALL 2010 cohort. All participants who received at least one dose of dasatinib were included in the safety and efficacy analyses. This trial was registered with ClinicalTrials.gov, NCT01460160, and recruitment is closed. FINDINGS: Between March 13, 2012, and May 27, 2014, 109 patients were enrolled at 69 sites (including 51 COG sites in the USA, Canada, and Australia, and 18 EsPhALL sites in Italy and the UK). Three patients were ineligible and did not receive dasatinib. 106 patients were treated and included in analyses (49 [46%] female and 57 [54%] male; 85 [80%] White, 13 [12%] Black or African American, five [5%] Asian, and three [3%] other races; 24 [23%] Hispanic or Latino ethnicity). All 106 treated patients reached complete remission; 87 (82%) were classified as standard risk and 19 (18%) met HSCT criteria and were classified as high risk, but only 15 (14%) received HSCT in first complete remission. The 3-year event-free survival of dasatinib plus chemotherapy was superior to chemotherapy alone (65·5% [90% Clopper-Pearson CI 57·7 to 73·7] vs 49·2% [38·0 to 60·4]; p=0·032), and was non-inferior to imatinib plus chemotherapy (59·1% [51·8 to 66·2], 90% CI of the treatment difference: -3·3 to 17·2), but not superior to imatinib plus chemotherapy (65·5% vs 59·1%; p=0·27). The most frequent grade 3-5 adverse events were febrile neutropenia (n=93) and bacteraemia (n=21). Nine remission deaths occurred, which were due to infections (n=5), transplantation-related (n=2), due to cardiac arrest (n=1), or had an unknown cause (n=1). No dasatinib-related deaths occurred. INTERPRETATION: Dasatinib plus EsPhALL chemotherapy is safe and active in paediatric Ph-positive acute lymphoblastic leukaemia. 3-year event-free survival was similar to that of previous Ph-positive acute lymphoblastic leukaemia trials despite the limited use of HSCT in first complete remission. FUNDING: Bristol Myers Squibb.

Effect of BMI on toxicities and survival among adolescents and young adults treated on DFCI Consortium ALL trials.

Adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL) treated with asparaginase-containing pediatric regimens are commonly overweight or obese. We studied the association of body mass index (BMI) on outcomes of 388 AYAs aged 15 to 50 years treated on Dana-Farber Cancer Institute (DFCI) consortium regimens (2008-2021). BMI was normal in 207 (53.3%) and overweight/obese in 181 (46.7%). Patients who were overweight or obese experienced higher nonrelapse mortality (NRM; 4-year, 11.7% vs 2.8%, P = .006), worse event-free survival (4-year, 63% vs 77%, P = .003), and worse overall survival (OS; 4-year, 64% vs 83%, P = .0001). Because younger (aged 15-29 years) AYAs more frequently had a normal BMI (79% vs 20%, P < .0001), we conducted separate analyses in each BMI group. We found excellent OS among younger and older (30-50 years) AYAs with normal BMI (4-year OS, 83% vs 85%, P = .89). Conversely, in AYAs who were overweight/obese, worse outcomes were seen in older AYAs (4-year OS, 55% vs 73%, P = .023). Regarding toxicity, AYAs who were overweight/obese experienced higher rates of grade 3/4 hepatotoxicity and hyperglycemia (60.7% vs 42.2%, P = .0005, and 36.4% vs 24.4%, P = .014, respectively) but had comparable rates of hypertriglyceridemia (29.5% vs 24.4%, P = .29). In a multivariable analysis, higher BMI was associated with worse OS, hypertriglyceridemia was associated with improved OS, and age was not associated with OS. In conclusion, among AYAs treated on DFCI Consortium ALL regimens, elevated BMI was associated with increased toxicity, increased NRM, and decreased OS. The deleterious effect of elevated BMI was more pronounced in older AYAs.

Disparities in parental distress in a multicenter clinical trial for pediatric acute lymphoblastic leukemia.

BACKGROUND: Parent psychological distress during childhood cancer treatment has short- and long-term implications for parent, child, and family well-being. Identifying targetable predictors of parental distress is essential to inform interventions. We investigated the association between household material hardship (HMH), a modifiable poverty-exposure defined as housing, food, or utility insecurity, and severe psychological distress among parents of children aged 1-17 years with acute lymphoblastic leukemia (ALL) enrolled on the multicenter Dana-Farber ALL Consortium Trial 16-001. METHODS: This was a secondary analysis of parent-reported data. Parents completed an HMH survey within 32 days of clinical trial enrollment (T0) and again at 6 months into therapy (T1). The primary exposure was HMH at T0 and primary outcome was severe parental distress at T0 and T1, defined as a score greater than or equal to 13 on the Kessler-6 Psychological Distress Scale. Multivariable models were adjusted for ALL risk group and single parent status. RESULTS: Among 375 evaluable parents, one-third (32%; n = 120/375) reported HMH at T0. In multivariable analyses, T0 HMH was associated with over twice the odds of severe psychological distress at T0 and T1 HMH was associated with over 5 times the odds of severe distress at T1. CONCLUSIONS: Despite uniform clinical trial treatment of their children at well-resourced pediatric centers, HMH-exposed parents-compared with unexposed parents-experienced statistically significantly increased odds of severe psychological distress at the time of their child's leukemia diagnosis, which worsened 6 months into therapy. These data identify a high-risk parental population who may benefit from early psychosocial and HMH-targeted interventions to mitigate disparities in well-being.

Stroke Outcomes Among English- and Spanish-Speaking Mexican American Patients.

OBJECTIVES: We examined whether language preference was associated with 90-day poststroke outcomes among Mexican American (MA) patients. METHODS: Patients with ischemic stroke and intracerebral hemorrhage from the population-based Brain Attack Surveillance in Corpus Christi project (2009-2018) were compared by language preference in 90-day neurologic, functional, and cognitive outcomes using weighted Tobit regression. Models were adjusted for demographics, initial NIH Stroke Scale (NIHSS), medical history, stroke characteristics, and insurance status. RESULTS: Of 1,096 stroke patients, 926 were English-speaking and 170 were Spanish-only-speaking. Spanish speakers were older (p < 0.01), received less education (p < 0.01), had higher initial NIHSS values (p = 0.02), had higher prevalence of atrial fibrillation (p < 0.01), and had lower prevalence of smoking (p = 0.01) than English speakers. In fully adjusted models, Spanish-only speakers had worse neurologic outcome (NIHSS, range 0-44 [higher worse], mean difference: 1.93, p < 0.01) but no difference in functional outcome measured by activities of daily living/instrumental activities of daily living or cognitive outcome compared with English speakers. DISCUSSION: This population-based study found worse neurologic but similar functional and cognitive stroke outcomes among Spanish-only-speaking MA patients compared with English-speaking MA patients.

A systems approach points to a therapeutic role for retinoids in asparaginase-associated pancreatitis.

Among drug-induced adverse events, pancreatitis is life-threatening and results in substantial morbidity. A prototype example is the pancreatitis caused by asparaginase, a crucial drug used to treat acute lymphoblastic leukemia (ALL). Here, we used a systems approach to identify the factors affecting asparaginase-associated pancreatitis (AAP). Connectivity Map analysis of the transcriptomic data showed that asparaginase-induced gene signatures were potentially reversed by retinoids (vitamin A and its analogs). Analysis of a large electronic health record database (TriNetX) and the U.S. Federal Drug Administration Adverse Events Reporting System demonstrated a reduction in AAP risk with concomitant exposure to vitamin A. Furthermore, we performed a global metabolomic screening of plasma samples from 24 individuals with ALL who developed pancreatitis (cases) and 26 individuals with ALL who did not develop pancreatitis (controls), before and after a single exposure to asparaginase. Screening from this discovery cohort revealed that plasma carotenoids were lower in the cases than in controls. This finding was validated in a larger external cohort. A 30-day dietary recall showed that the cases received less dietary vitamin A than the controls did. In mice, asparaginase administration alone was sufficient to reduce circulating and hepatic retinol. Based on these data, we propose that circulating retinoids protect against pancreatic inflammation and that asparaginase reduces circulating retinoids. Moreover, we show that AAP is more likely to develop with reduced dietary vitamin A intake. The systems approach taken for AAP provides an impetus to examine the role of dietary vitamin A supplementation in preventing or treating AAP.

"There's no playbook for when your kid has cancer": Desired elements of an electronic resource to support pediatric cancer communication.

INTRODUCTION: Acute lymphoblastic leukemia (ALL), the most common childhood malignancy, has a relatively favorable long-term prognosis. Yet the complexity of treatment and the emotionality of the diagnosis leave families feeling unprepared for many aspects of therapy. This qualitative study aimed to identify desired elements and format of a communication resource to support patients and families facing a diagnosis of ALL. METHODS: Semi-structured interviews of 12 parents of children receiving ALL treatment, 10 parents of survivors of ALL, and eight adolescent and young adult (AYA) survivors of ALL were conducted between February and June 2021. The interviews focused on communication experiences throughout treatment and identified domains to be addressed in a resource in development. RESULTS: All participants supported the development of an interactive, electronic health (eHealth) resource to help navigate ALL treatment. They felt a website would be helpful in addressing information gaps and mitigating pervasive feelings of overwhelm. Participants specifically sought: (a) information resources to address feelings of cognitive overload; (b) practical tips to help navigate logistical challenges; (c) clear depictions of treatment choices and trajectories to facilitate decision-making; and (d) additional psychosocial resources and support. Two overarching themes that families felt should be interwoven throughout the eHealth resource were connections with other patients/families and extra support at transitions between phases of treatment. CONCLUSIONS: A new diagnosis of ALL and its treatment are extremely overwhelming. Patients and families unanimously supported an eHealth resource to provide additional information and connect them with emotional support, starting at diagnosis and extending throughout treatment.