Young Adult Outcomes Research Articles

Acute Myeloid Leukemia in Western Kenya: Exploring Outcome Disparities through Cases

Introduction: For young adults with acute myeloid leukemia (AML) in the United States, 60-80% can achieve complete remission and 33% can be cured with intensive treatment; in India that figure drops to overall 1-year survival of 55.6%; in Western Kenya overall 1-year survival is less than 10%. In the United States, achievement of complete remission is an appropriate goal. As described in Wanjiku 2021, in western Kenya, patients are typically not treated with standard induction therapy due to lack of supportive care. Three cases of children and young adults in Eldoret, Kenya with AML in the month of April 2022 are discussed to elucidate barriers to successful treatment in resource-limited settings. Cases: Case 1 (WK) is a 19 year old man with symptoms of dizziness, fatigue, abdominal pain, and wasting for one year, referred from Kericho District Hospital with bone marrow aspirate suspicious for acute myeloid leukemia, referred for flow cytometry, cytogenic/molecular studies, chemotherapy and management of acute myeloid leukemia. Family paid in advance for flow cytometry. Prior to referral he received hydroxyurea, allopurinol, and 6 units of blood. Hemoglobin on arrival was 4.0 g/dL, white blood cells 64.5, platelets 16. Four units of blood were ordered, only one was available. His condition deteriorated and he died of respiratory failure. Case 2 (WC) is a 16 year old man with puffy face, severe pallor, nosebleeds, and exercise intolerance, referred from Kericho District Hospital with bone marrow aspirate suspicious for acute myeloid leukemia. Hemoglobin was 5.5 g/dL, white blood cells 15, platelets 52. Five units of blood were ordered, no blood was available. Family paid in advance for chemotherapy, and he was started on "prephase 1" etoposide 50mg/m2 IV infusion over 1 hour for 6 days, then discharged to follow up in oncology clinic in two weeks. Case 3 (MK) is a 25 year old woman local to Eldoret, with one week of generalized body pain, abdominal pain, and weakness. Peripheral blood smear demonstrated 90% blasts and reduced platelets, and she presented to the hospital for bone marrow aspiration and blood transfusion. Initial hemoglobin 2as 5.2 g/dL, WBC 28.9, platelets 71. Five units of blood were ordered, and she received four. Bone marrow aspirate reported nonspecific features of acute leukemia, flow cytometry reported 93% blasts, AML-M0. Discussion: Significant disparities and barriers exist in the treatment of acute myeloid leukemia in resource-limited settings. The first step is diagnosis, including awareness and access to early treatment and diagnostic capabilities. Anecdotally, the rate of AML in the Kericho region is attributed to environmental exposures related to tea farming. In the setting of Western Kenya, some patients especially in Eldoret and Kericho had access to bone marrow aspirate and referral capability to flow cytometry. The next major barrier identified was supportive care, including scarcity of blood products. In April, the blood shortage was reported to be related to federal holiday, meaning that classes of school students and military recruits were not coming to donate blood on a regular basis. The next major barrier was induction of chemotherapy, including the practice of low-dose chemotherapy (low-dose cytarabine or etoposide alone) without intent to cure, due to concerns of managing the complications of induction chemotherapy. On the far end of the treatment spectrum, bone marrow transplant was not an option in the country of Kenya, and patients seeking this treatment option were obligated to travel abroad. Conclusion: Key barriers exist to treatment of AML in western Kenya, which contribute to disparities in outcomes of young adults with AML in western Kenya compared to the United States. Barriers identified from examining cases included access to bone marrow aspiration and flow cytometry, availability of blood products, choice of chemotherapy approach (low-dose versus standard induction), supportive care environment, and availability of treatment options including bone marrow transplant. More research is needed to identify the causes of death for patients in this local population, and create a system that can reduce the international disparities and move towards equitable goals of remission and cure.

Efficacy of Interventions to Build Transition Readiness for Youth with Sickle Cell Disease: A 13-Year Evaluation of a Healthcare Transition Program

Background Progress in pediatric care has improved survival into adulthood for children with sickle cell disease (SCD); however, mortality and acute care utilization rise among emerging adults. With unmet needs to improve health outcomes in young adults, SCD effective transition programs that transfer care from pediatric to adult providers are needed. Since 2007, the St. Jude Children's Research Hospital (SJCRH) SCD Transition to Adult care Program has served patients between 12-25 years of age by providing transition readiness-building activities, including in-person and online SCD education, experiential learning, academic planning, and introduction to adult providers at age 17 years. We tested the efficacy of individual components of the SJCRH Transition Program in ensuring optimal post-pediatric transition outcomes. Methods We retrospectively reviewed all patients with SCD treated at SJCRH who would have reached age 18 years between 2007 and 2020. Of the 722 patients, 142 (19.7%) died, relocated, or were lost to follow up before age 18 years and were excluded from the analysis. The association between pediatric transition intervention components and the following transition outcomes: 1) adult care transfer completion <6 months from completing pediatric care, 2) frequency of adult outpatient visits, 3) adult acute care utilization [emergency room (ER) and hospitalizations], and 4) quality of life (QoL) PedsQL™ SCDModule scores at ages 18 or 24 years was investigated using Wilcoxon rank sum, Fisher's exact, Spearman correlation (with spearman correlation coefficient ρ), or Kruskal Wallis tests. Analyses were adjusted for multiple comparisons to control for false discovery rate and q-value was calculated. Results Of the 580 pediatric patients who received transition services to age 18, 476 (82.1%) completed adult transfer of care. There was no difference in completion of a first adult visit relative to SCD genotype or sex, but longer exposure duration to any SCD-modifying therapy was associated with higher rate of adult care transfer completion (Table 1). Patients who successfully transferred to adult care had significantly higher participation in all components of the transition program and higher transition readiness scores (Table 1). Frequency of pediatric outpatient visits was not associated with completion of a first adult visit. However, patients with a transfer gap <6 months had higher frequency of pediatric visits than those with ≥6 months gap (median 77 vs 27 visits/patient, respectively, q<0.00001). Patients with HbSS/SB0-thalassemia attended more adult outpatient visits compared to those with HbSC/SB+thalassemia genotypes (median 62 vs 27 total visits/patient, q<0.0001). Longer exposure to any SCD-modifying therapy (ρ=0.44, q<0.00001), higher frequency of pediatric outpatient visits (ρ=0.61, q <0.00001), and adult provider introduction at 17 years (q=0.025) were associated with greater attendance to adult outpatient visits. Longer exposure to SCD-modifying therapies (ρ=0.26, q<0.0001) was associated with higher adult acute care utilization, while no association was observed with SCD genotype and adult acute care utilization. Higher frequency of academic planning (ρ=-0.23, q=0.0002) and disease education sessions (ρ=-0.28, q<0.0001, Fig 1) were negatively correlated with adult acute care utilization. QoL was lower among females than males (median q=0.002), but no differences were observed relative to SCD genotypes or duration of exposure to SCD therapies. The frequency of SCD education (ρ=0.19, q=0.008) and training on personal health history reporting (ρ=0.22, q=0.004) were positively correlated with QoL. More self-reported internalizing problems due to anxiety and depression (BASC-ESI scores) did not predict adult transfer completion but were associated with lower QoL in young adulthood (ρ=-0.32, q=0.008). Conclusion The transition program at SJRCH was effective in placing 82% of patients in adult care. Demographic factors (sex, SCD genotype) were not always predictive of transition outcomes. However, our results suggest transition interventions designed to increase transition readiness may promote improved transition outcomes. Future analyses will focus on building multivariable models to determine the optimal combination of transition interventions to improve transition outcomes in SCD. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Improved Survival of Adolescents and Young Adults (AYA) Patients Aged 14-40 Years with First Relapse of Acute Lymphoblastic Leukemia Using Pediatric-Inspired Chemotherapy Salvage Protocol (R3 induction protocol)

Background: Although survival of adolescent and young adults (AYA) with acute lymphoblastic leukemia (ALL) has improved using pediatric-inspired protocols, the outcomes of those who relapse remain poor using adult chemotherapy salvage-regimens that have historically incorporated high dose Ara-C based regimen, with long term-survival of less than 10%. The CR rate with blinatumomab for salvage in adult ALL is 34% with a median survival of 7.7 months, with an OS of less than 30% at 18 months. In contrast, pediatric salvage regimens have historically been based on multi-agent therapy and have reported superior outcomes. The ALLR3 protocol for relapsed ALL in patients up to the age of 18 years reported a CR rate of 97% and an overall survival of 72%. We therefore aimed to analyze the outcomes of young adolescents and adults treated on the R3 regimen +/- blinatumomab. Methods: Seventeen AYA patients with Philadelphia-negative ALL aged between 14 and 40 years who relapsed after first-line therapy and treated with ALLR3-protocol were identified. Relapses were classed as very early (<18 months from diagnosis) early (>18m from diagnosis and <6 months from end of therapy) and late (>6 months from end of therapy). The protocol consisted of vincristine (1.5mg/m2 IV D3,10,17,24); mitoxantrone ( 10mg/m2 IV d1 &2); PEG-asparaginase (1000 u/m2 IV d3 & 17); dexamethasone (10mg/m2 BID day d1-5 and d15-20); and intrathecal methotrexate (12mg d1 & d8) were identified. Patient aged 30-40 years received L-Asparaginase instead of PEG-Asparaginase, and 8mg/m2 of dexamethasone instead of 10mg/m2. Patients' characteristics, response rate (RR) and overall survival (OS) were analyzed. Patients who achieved minimal residual disease (MRD) negative CR proceeded with an allogeneic transplant. MRD-positive patients received blinatumomab followed by a transplant. Results: The median age at relapse was 16 years (14-40 years), 88.2% of patients were B-cell ALL and 11.8% were T-cell ALL. Most patient had standard cytogenetics on presentation (76.5%) and were CNS negative (82.4%). Relapses were very early, early or late in 2 (12%) , 5 (29%) , and 7 (41%) of cases, respectively. Relapses were isolated bone marrow (BM), isolated extramedullary (EMD) or combined BM and EMD in 14 (82%),1 (6%) and 2(12%) cases, respectively. Overall complete remission (CR) rate was 60% at the end of R3 induction; CR with negative minimal residual disease (MRD negative, <10−4 cells) at the end of R3-induction was achieved in 47.1% of patients, while 11.8% of patients had CR with positive MRD (≥10−4 cells) who received Blinatumumab thereafter with eradication of MRD. Refractory disease was seen in 41.2% of patients. Almost all patients who responded to R3 proceeded to allogeneic stem cell transplant (88.8%). Eight patients died (47%), but only one patient died because of treatment-related sepsis, while the other 7 patients died because of disease-related causes. At a median follow up of 4 years, OS was 47.3%. Conclusion: Compared to traditional adult-based chemotherapy regimens and antibody therapies used in relapsed ALL, the use of pediatric-inspired protocol (R3) in relapsed AYA-ALL patients showed favorable response rates and overall survival. Further trials are required of pediatric inspired salvage regimens, preferably incorporating antibody therapies in adult patients, especially in 1st relapse. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

COVID-19 Vaccination Outcomes in Children, Adolescents, and Young Adults with Acute Lymphoblastic Leukemia

Background:While several studies have shown that less than half of adults on active therapy for chronic hematological malignancies develop an immune response to COVID-19 vaccination, little is known about the efficacy of COVID-19 vaccines in the midst of active therapy for acute lymphoblastic leukemia (ALL). Furthermore, COVID-19 vaccine outcomes in pediatric leukemia remain uncharacterized. Given the differences in the intensity of chemotherapy regimens between pediatric ALL and adult chronic hematological malignancies as well as age related immune differences, there is a need to specifically define vaccination outcomes in pediatric ALL. This study aims to define the safety and efficacy of COVID-19 vaccination in children and adolescents and young adults with ALL, the most common pediatric leukemia. Methods: We conducted a prospective single center Institutional Review Board approved study. Eligible patients were ages 5-25 years with a diagnosis of ALL or receiving ALL-like therapy who had received COVID-19 vaccination. Pediatric oncology patients at our center undergo universal surveillance for COVID-19 via nasopharyngeal PCR regardless of symptom status, prior to any sedation or hospitalization. Labs were drawn at 3,6-, and 12-months post-vaccination for anti-COVID-19 spike (S) and nucleocapsid (N) IgG ELISA and anti S neutralizing antibody assays, in vitro COVID-19 peptide stimulation T-cell response studies, and T-cell receptor (TCR) sequencing for COVID specific TCR. These tests were validated in healthy COVID-19 infection convalescent and healthy post-vaccination cohorts. Results: Between April 2021 and April 2022, the study enrolled 21 patients (median age 12.5 years). Diagnoses included high risk B-ALL (n=13), mixed-phenotype acute leukemia (MPAL) (n=2), and standard risk B-ALL (n=6). Three had relapsed ALL. All were in complete remission and receiving chemotherapy at the time of vaccination (17 receiving maintenance therapy and 4 in an intensive chemotherapy phase). Twenty received the BNT162b2 mRNA vaccine (10mcg dose n=11 and 30mcg dose, n=9); one received the Ad26.COV2.S vaccine. One patient received one dose (excluded from efficacy analysis), 17 received 2 doses, and 2 received three doses (i.e. a booster dose) of BNT162b2. Vaccinations were well tolerated with no patient experiencing anaphylaxis or an allergic reaction, including 10 patients with PEG-asparaginase allergy (BNT162b2 contains PEG). Three patients presented to the emergency department with fever; one of those was hospitalized for hypotension. Thirteen of 20 patients (65%) were positive for spike (S) anti-COVID-10 IgG following two doses of BNT162b2 (n=12) or one dose of Ad26.COV2.S (n=1). Eleven of these 13 were negative for N IgG, an antibody profile (S IgG+, N IgG-) consistent with an immune response to vaccination rather than a prior undiagnosed COVID-19 infection. All three patients with ≥ 6 months post-vaccination data continue to be positive for S IgG. Notably, 6 of 12 lymphopenic patients (absolute lymphocyte count <500 at the time of vaccination) and 3 of 4 patients in an intense phase of therapy during vaccination showed an immune response. Six of 8 patients with PEG-allergy had an immune response. All patients with positive S IgG showed presence of neutralizing anti-S antibodies. There was no difference in immune response based on vaccine dose. Five of 20 patients (3 of 13 patients who were S IgG+ following vaccination) developed COVID-19 infection following vaccination; one of these occurred after the third dose. Hospitalization was needed in one of five cases of COVID-19. All infections occurred during the omicron wave and included 3 sequencing confirmed omicron infections (variant testing not done for 2). Conclusions: In our study, two doses of COVID-19 vaccination induced a neutralizing antibody response in over half of the children and AYA actively receiving ALL chemotherapy including those who were receiving intensive chemotherapy or had PEG allergy. Adverse events were uncommon. Omicron infections occurred in our study, a finding consistent with the occurrence of breakthrough omicron variant infections in immunocompetent vaccinated individuals. T-cell response studies for our cohort are ongoing. Additional long-term follow-up and larger studies are needed to investigate durability of immune response and optimal vaccine frequency especially in the setting of omicron variants. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Long-Term Outcome of Adolescents and Young Adults with Chronic Primary Immune Thrombocytopenia (ITP)

Long-Term Outcome of Adolescents and Young Adults with Chronic Primary Immune Thrombocytopenia (ITP)

Systematic Intention to Treat Analysis of Real-World Outcomes in Children and Young Adults Receiving Tisagenlecleucel: From Elegibility through Treatment Failure

Background Since the approval of Tisagenlecleucel for R/R B-ALL, a UK CAR T cell panel was established to ensure equity of access, assess elegibility and allocate to JACIE-FACT approved IEC centres. This framework uniquely tracks patients from allocation to infusion and after therapy failure. We report outcomes for ALL patients allocated to receive Tisagenlecleucel nationally, including on an intention to treat (ITT) basis and for those patients who fail CAR T cell therapy. Methods All patients discussed up to the 15th of June 2022 were included against a national panel. Retrospective data collection was on a standardised datasheet. Survival outcomes were assessed using Kaplan-Meier survival from infusion. These included overall survival (OS; interval to death from any cause) and event-free survival as defined in the ELIANA study (classic EFS; interval to death, relapse, or failure to respond by day 30, censoring patients receiving further therapy). For ITT survival, outcomes were assessed from allocation. A more comprehensive EFS measure capturing all clinically relevant events (interval to molecular or frank relapse, further therapy, death or treatment failure was analysed; stringent EFS). Data analysis was carried out in R (version 4.1.2). Results 147 patients were screened. Five were ineligible due to CD19 disease (n=1), lymphopaenia (n=2) and GVHD(n=2). Of 142 eligible patients, 12 were not apheresed and 13 not infused, see Figure 1. The ITT cohort included 128 eligible patients, excluding patients lost to follow-up or had insufficient data provided for survival analysis. 57.8% (74) patients were male, median age at infusion was 11.3 years (IQR 6.9-16). Cytogenetic status (n=98) included high risk (n=35, 35.7%), favourable (n=25, 25.5%); and intermediate (n=39, 39.7%). Prior refractory disease was noted in 55 (42%). Median relapses were 2 (IQR 1-2) and lines of therapy was 3 (2-3 IQR). 52 patients (45.2% out of 115) additionally had prior SCT. 34 (26.6%) of patients had received blinatumomab and 13 (10.2%) inotuzumab prior to CART. Median CART dose infused was 1.3E+06 cells/kg (IQR 3 -2.85E+06). Of 114 infused patients, 101 (88.6%) were in CR/Cri at day 30; 72 (78.3%) were MRD negative. Overall survival (infused cohort) was 79.9% (95% CI: 72-89%) at 1y and 67.7% at 2y (95%CI: 57-80%, median OS not reached). EFS by the classic / ELIANA definition was 70.9% (95%CI: 62-81%) and 50% (95%CI: 38-67%) at 1 and 2 years respectively. Median EFS was 22 months. Stringent EFS was 45% (95%CI: 36-56%) at 1y and 37.8% (95%CI: 28-51%) at 2y, median 214 days. For the ITT cohort, OS at 1 and 2 years was 78.6% (95%CI: 71-87%) and 65.3% (95%CI:55-77%) , standard EFS 67.2% (58.2-77.5%) and 44.7% (95%CI: 32-61%) and stringent EFS 44.5% (95%CI: 36-55%) and 34.8% (95%CI: 26-47% median stringent EFS 270 days). Of 111 infused patients, two died prior to day 30, 8 patients did not respond, 5 died of disease shortly after. Three patients had not achieved day 30 to assess response. Of 101 responding patients, 17 had MRD relapse and went on to further therapy, a further 19 had therapy for early loss of B-cell aplasia, 11 had frank relapse of which 6 were CD19 negative. Outcomes are shown in Figure 1. At a median follow-up of 16.5 months from infusion, 12/17 patients with loss of B Cell aplasia, 9/17 patients with MRD and 2/11 with frank relapse are alive and in MRD neg remission. CART cell therapy was well tolerated, 91 patients (79.8%) had mainly mild CRS, 77 grade 1-2 (84.6%) and 14 grade 3-4 (15.4%). Neurotoxicity occurred in 21 patients (18.4%) (13 (62%) grade 1-2 and 7 (33.3%) grade 3-4). One patient died from severe neurotoxicity, possibly Fludarabine related. 44 (39%) received tocilizumab. Further toxicity outcomes will be presented. Conclusion We present a unique systematic outcome analysis for paediatric and young adult patients with B-ALL allocated to receive tisagenlecleucel treatment under a national access scheme in the UK. Outcomes are based on standard OS and EFS, as well as more stringent EFS definition capturing all clinically meaningful endpoints, for both the infused and ITT cohorts. We track all patients beyond failure of therapy, observing a 50% chance of effective salvage post event (23/50 events including loss B cell aplasia, MRD or frank relapse). These data are relevant for clinicians counselling patients for CART therapy and the likelihood of survival, from the point of being eligible through outcomes after failure of CART therapy. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Treatment Patterns and Outcomes in Adolescent and Young Adults with Nodular Lymphocyte Predominant Hodgkin Lymphoma: An Impact Cohort Population-Based Study

Introduction: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma distinct from classical HL (cHL). NLPHL treatment is not standardized. Adolescents and young adults (AYA) are a vulnerable subpopulation of cancer patients whose care is dispersed among both pediatric and adult institutions. We leveraged a population-based database of linked clinical and healthcare data to identify treatment patterns and long-term outcomes among younger AYA with NLPHL. Methods: The IMPACT Cohort comprises all Ontario, Canada AYA aged 15-21 years diagnosed with one of six common cancers (including HL) between 1992-2012. Detailed demographic, disease, treatment, and outcome data were collected through chart abstraction and validated by content experts. Linkage to population-based health administrative data identified additional cancer events (second malignant neoplasms [SMN], relapses, deaths). Demographic, disease, and treatment variables were compared between AYA with cHL vs. NLPHL, including treatment modalities received (surgery alone vs. radiation vs. chemotherapy vs. combined modality treatment [CMT]). Among AYA with NLPHL, treatment patterns were also compared between those treated at pediatric vs. adult centers. Event-free (EFS) and overall survival (OS) were compared between cHL and NLPHL patients using Kaplan-Meier estimates. Predictors of outcome among AYA with NLPHL were determined using multivariable Cox proportional hazard models. Events included disease progression, relapse, death, and SMN. The cumulative incidence of SMN and major cardiac events (determined through validated algorithms using healthcare data) was determined. Results: Of 1,014 AYA with HL, 54 (5.3%) had NLPHL. AYA with NLPHL were more likely to be male [42/54 (77.8%) vs. 458/960 (47.7%); p<0.001] and to have limited stage disease [33/54 (61.1%) vs. 397/960 (41.4%); p<0.01]. Compared to AYA with cHL, AYA with NLPHL were more likely to be treated with radiation only [16/54 (29.6%) vs. 58/960 (6.0%); p<0.001]. Among those who received radiation, the median dose administered was higher in AYA with NLPHL (35Gy vs. 30Gy; p=0.04). Conversely, among those who received chemotherapy, cumulative doses were lower in NLPHL. Of the 54 patients with NLPHL, 15 (27.8%) were treated at a pediatric center. No pediatric center patient received radiation only vs. 16 (41.0%) of adult center patients. Treatment consisting of surgery only was more common in pediatric centers (Table 1). Median radiation doses were also lower among pediatric centers (21Gy vs. 35Gy; p=0.007). Though cumulative doses of doxorubicin and bleomycin were lower at pediatric centers, the differences were not statistically significant. The 10- and 20-year EFS for AYA with NLPHL was 82.9%±5.2% and 77.4%±7.2% respectively, which did not significantly differ from cHL (p=0.52; Figure 1). The 20-year OS was 100.0% among AYA with NLPHL vs. 90.1%±1.2% among those with cHL (p=0.04). Among patients with NLPHL, only advanced stage (HR 4.9, 95CI 1.3-18.4; p=0.02) was significantly associated with inferior EFS in univariate analyses. In multivariable analyses neither stage nor treatment modality was significantly associated with EFS. OS models were not possible given the low number of deaths. The 15-year EFS and OS for AYA with NLPHL treated with surgery only were both 100%. The 25-year cumulative incidence of SMN among AYA with NLPHL was 19.3%±9.6%. These included cases of thyroid carcinoma, squamous cell carcinoma, and diffuse large B-cell lymphoma (N≤5 each). Though higher than the equivalent cumulative incidence among AYA with cHL (14.9%±3.0%), this difference was not statistically significant. There were no SMN among AYA with NLPHL treated with surgery only. There were no episodes of major cardiac events among AYA with NLPHL. Conclusions: Overall, AYA with NLPHL have an outstanding long-term survival. However, treatment patterns vary considerably. Resection alone was rare outside of pediatric institutions, though such patients had excellent outcomes, while radiation alone was common in adult institutions. Given substantial long-term burden of SMN, more widespread use of chemotherapy and radiation-sparing strategies for appropriate subsets of AYA with NLPHL is warranted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 14362: A Case of a Primary Malignant Pericardial Myxoid Sarcoma in a Young Adult

Introduction: Primary pericardial malignant tumors are rare clinical entities with an incidence of 0.001%. The symptoms depend on the location and size of the mass, typically causing chest pain, dyspnea, or syncope. We present the case of a young man with atypical chest pain, rapidly progressing to cardiac arrest from a primary pericardial myxoid chondrosarcoma. Case Presentation: A 31-year-old man presented with atypical chest pain. Subsequently, he had a cardiac arrest with pulseless electrical activity. CT chest revealed a 9.5 x 10 cm epicardial mass (Figure 1a, 1b) found to be a myxoid sarcoma on CT-guided biopsy. The morphology was suggestive of a high-grade extra-skeletal myxoid chondrosarcoma. Cardiac MRI had normal function and no myocardial invasion. The staging MRI did not show any other primary source. Due to the large size of the mass, a decision was made to perform surgical resection. Most of the tumor was excised but had positive margins from the part adherent to the inferior vena cava. In the absence of clear guidelines, multiple chemotherapy regimens including doxorubicin, ifosfamide, and etoposide were tried. The initial response was complicated by eventual recurrence and metastasis to the chest wall and mediastinum (Figure 1c, 1d). Further, genetic testing with next-generation sequencing demonstrated MAP3K1 gene mutation. As MAP3K1 mutations have shown sensitivity to MEK inhibition, targeted chemotherapy with trametinib was initiated in combination with pazopanib, a multikinase inhibitor. With the progression of metastatic disease despite treatment, the patient decided to pursue palliative care. Discussion: Malignant pericardial myxoid chondrosarcoma is a rare tumor that may lead to fatal outcomes in young adults. Despite numerous surgical and chemotherapeutic interventions, they have a guarded prognosis. Increased clinician awareness and a wide differential while evaluating cardiac masses are key for early detection and timely treatment.

Habitual intakes of sugar-sweetened beverages associated with gut microbiota-related metabolites and metabolic health outcomes in young Chinese adults

Background and aimsReducing consumption of sugar-sweetened beverages (SSBs) is a global public health priority because of their limited nutritional value and associations with increased risk of obesity and metabolic diseases. Gut microbiota-related metabolites emerged as quintessential effectors that may mediate impacts of dietary exposures on the modulation of host commensal microbiome and physiological status. Methods and resultsThis study assessed the associations among SSBs, circulating microbial metabolites, and gut microbiota–host co-metabolites, as well as metabolic health outcomes in young Chinese adults (n = 86), from the Carbohydrate Alternatives and Metabolic Phenotypes study in Shaanxi Province. Five principal component analysis-derived beverage drinking patterns were determined on self-reported SSB intakes, which were to a varying degree associated with 143 plasma levels of gut microbiota-related metabolites profiled by untargeted metabolomics. Moreover, carbonated beverages, fruit juice, energy drinks, and bubble tea exhibited positive associations with obesity-related markers and blood lipids, which were further validated in an independent cohort of 16,851 participants from the Regional Ethnic Cohort Study in Northwest China in Shaanxi Province. In contrast, presweetened coffee was negatively associated with the obesity-related traits. A total of 79 metabolites were associated with both SSBs and metabolic markers, particularly obesity markers. Pathway enrichment analysis identified the branched-chain amino acid catabolism and aminoacyl-tRNA biosynthesis as linking SSB intake with metabolic health outcomes. ConclusionOur findings demonstrate the associations between habitual intakes of SSBs and several metabolic markers relevant to noncommunicable diseases, and highlight the critical involvement of gut microbiota-related metabolites in mediating such associations.

The effect of the COVID-19 pandemic on headache-related disability among young adults with migraine.

The present study aimed to explore the relationship between the COVID-19 pandemic and headache-related disability among a sample of young adults with migraine. Comorbid psychological symptoms compound migraine-related disability. Due to COVID-19 pandemic procedures, many students experienced institutional closures and corresponding increases in depression, stress, and anxiety. The present study sought to examine changes in headache-related disability before (Spring and Fall of 2019) and during (Fall of 2020 and Spring 2021) the COVID-19 pandemic and whether psychological symptoms mediated such changes. A cross-sectional study at a southern U.S. university assessed 365 individuals with migraine on headache and psychological variables, comparing those surveyed before COVID-19 with another group surveyed during the pandemic. The direct and indirect effects of COVID-19 status (pre- versus during COVID-19) on headache-related disability through depression, anxiety, and stress symptoms were assessed. Statistically higher levels of depression, (M=13.9 [SD=12.2] vs. M=8.7 [SD=8.7], p < 0.001), anxiety (12.3 [10.0] vs. 9.7 [8.2], p=0.01), and stress symptoms (17.6 [10.2] vs. 13.2 [7.9], p < 0.001) were endorsed during the COVID-19 pandemic. The direct path from COVID-19 status to headache-related disability was significant and negative, c'=-1.6 (95% CI: -3.1, -0.1). Anxiety (b=0.3 [95% CI:0.01, 0.9]) and depression (b=0.7 [95% CI: 0.07, 1.4]) symptoms acted as mediators of this relationship, rendering the total effect nonsignificant and negating the lowered disability observed during the pandemic. Only depression symptoms remained a significant mediator after controlling for headache frequency (b=0.7 [95% CI: 0.09, 1.4]). Increased depression and anxiety symptoms attenuated the improvements in disability associated with the pandemic. As such, interventions that address comorbid psychological symptoms may hold value in reducing headache-related disability and improving outcomes for young adults whose headache developed or worsened during the COVID-19 pandemic.

Long-Term Virological Treatment Outcomes in Adolescents and Young Adults With Perinatally and Non-Perinatally Acquired Human Immunodeficiency Virus

Long-term viral suppression on antiretroviral therapy (ART) is not established among all people with human immunodeficiency virus (PWH). Young adults (18-24 years) are recognized as a group vulnerable for suboptimal virological treatment outcomes. The aim of this study is to evaluate longitudinal virological treatment outcomes and to identify risk factors for virological failure (VF) among young adults with non-perinatally and perinatally acquired human immunodeficiency virus (HIV) in the Netherlands. We included individuals registered in the national ATHENA observational cohort from 2000 until 2020 who had entered care before the age of 25 years, who had received ART for at least 6 months with at least 2 available HIV ribonucleic acid measurements between the age of 18 and 24 years. We compared VF between age groups 12-17, 18-24, and 25-30 years. A multivariable generalized linear mixed model was used to evaluate risk factors for VF. Analyses were stratified by HIV acquisition mode. In total, 1174 non-perinatally PWH and 157 perinatally PWH were included. In 2020, VF rate was 7% in non-perinatally PWH young adults and 19% in perinatally PWH young adults. The adjusted risk for VF was significantly higher in those aged 18-24 compared to 25-30 years in both non-perinatally PWH (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.07-1.50) and perinatally PWH (OR, 2.34; 95% CI, 1.48-3.71). Young adulthood is a vulnerable period, with increased risk for VF, especially for perinatally PWH. The probability of VF decreased over time, but less for perinatally PWH compared to non-perinatally PWH.

Circadian preference in young adults: Associations with sleep and mental health outcomes from a national survey of Norwegian university students

ABSTRACT Individual preferred timing of sleep and activity patterns, known as circadian preference, ranges from definitely morning types to definitely evening types. Being an evening type has been linked to adverse sleep and mental health outcomes. This study aimed to explore the associations between circadian preference and self-reported sleep, depression, anxiety, quality of life, loneliness, and self-harm/suicidal thoughts. Data stem from a national survey of students in higher education in Norway (the SHoT-study). All 169,572 students in Norway were invited to participate, and 59,554 students (66.5% women) accepted (response rate = 35.1%). Circadian preference was associated with sleep and mental health outcomes in a dose–response manner. For both genders, being an evening type (either definitely evening or more evening than morning) was associated with an increase in age-adjusted relative risk (RR-adjusted; range = 1.44 to 2.52 vs. 1.15 to 1.90, respectively) across all outcomes compared with definitely morning types. Overall, the present study provides further evidence that evening circadian preference is associated with adverse sleep and mental health outcomes in young adults. As such, future efforts to improve sleep and mental health in young adults should consider their circadian preferences.

Sports-related sudden cardiac arrest in young adults.

Data on sports-related sudden cardiac arrest (SrSCA) among young adults in the general population are scarce. We aimed to determine the overall SrSCA incidence, characteristics, and outcomes in young adults. Prospective cohort study of all cases of SrSCA between 2012 and 2019 in Germany and Paris area, France, involving subjects aged 18-35 years. Detection of SrSCA was achieved via multiple sources, including emergency medical services (EMS) reporting and web-based screening of media releases. Cases and aetiologies were centrally adjudicated. Overall, a total of 147 SrSCA (mean age 28.1 ± 4.8 years, 95.2% males) occurred, with an overall burden of 4.77 [95% confidence interval (CI) 2.85-6.68] cases per million-year, including 12 (8.2%) cases in young competitive athletes. While bystander cardiopulmonary resuscitation (CPR) was initiated in 114 (82.6%), automated external defibrillator (AED) use by bystanders occurred only in a minority (7.5%). Public AED use prior to EMS arrival (odds ratio 6.25, 95% CI 1.48-43.20, P = 0.02) was the strongest independent predictor of survival at hospital discharge (38.1%). Among cases that benefited from both immediate bystander CPR and AED use, survival rate was 90.9%. Coronary artery disease was the most frequent aetiology (25.8%), mainly through acute coronary syndrome (86.9%). Sports-related sudden cardiac arrest in the young occurs mainly in recreational male sports participants. Public AED use remains disappointingly low, although survival may reach 90% among those who benefit from both bystander CPR and early defibrillation. Coronary artery disease is the most prevalent cause of SrSCA in young adults.

Radioiodine Therapy in Pediatric Differentiated Thyroid Cancer: Dosimetry, Clinical Care, and Future Challenges.

Thyroid cancer is very rare in children. 131 I therapy after thyroidectomy is established in pediatric differentiated thyroid cancer (DTC). Pediatric DTC guideline is silent on the optimum amount of 131 I that could be safely and effectively administered to children who are more radiosensitive. Like adult DTC, children are also given 131 I therapy empirically based either on age or body weight. Pediatric DTC guideline recommends that patient-specific dosimetry is important in children. Still, due to the low incidence rate and the practical difficulties of dosimetry, it has neither been established nor adopted in routine practice. This review article aims to discuss current approaches of 131 I therapy in children and young adult patients with DTC and dosimetric data obtained by several investigators. Efforts are required to simplify dosimetric procedures and precise results, especially in determining lesion size. We prefer 3-dimensional dosimetry over planar dosimetry, where lesion size could be measured accurately. 124 I PET/CT-based dosimetry is expected to give accurate dosimetric results. The most challenging aspect is that no randomized controlled trials are available to compare the empiric 131 I therapy results versus dosimetry-based treatment outcomes in children and young adults. Suppose dosimetry-based 131 I therapy could be shown to have better outcomes, namely, successful ablation rate, better disease-free survival, and lesser treatment-emergent adverse events than empirical 131 I treatment. In that case, one can argue in favor of the former. Unfortunately, no convincing study is currently available. Thus, there is a need for a randomized control trial to settle this issue.

Unaccompanied refugee minors from the Democratic Republic of the Congo, Eritrea, Myanmar, and Somalia: Educational attainment, economic well-being, and social ties in the United States

In 2019, there were 21.3 million refugees around the globe. A small number of these are accepted to the United States each year under the Unaccompanied Refugee Minor Foster Care Program. There is currently limited research on the outcomes of young adults served through this unique program. In this paper, we share outcomes (educational attainment, economic well-being, and social ties) for young adults who leave care from the countries of the Democratic Republic of the Congo, Eritrea, Myanmar, and Somalia. The authors report descriptive statistics for young adults who discharged from the foster care program (n = 388) as well as Pearson’s Chi-square tests to test correlations between outcomes and country of origin. Results show that youth from Myanmar is most likely to be enrolled in college at time of discharge. Youth from the DRC is equally likely to be enrolled in college or to have only completed a GED or high school diploma. Youth from Myanmar is more likely to be employed than youth from other countries. Eritrean youth was more likely to be lacking economic self-sufficiency at time of discharge than youth from other countries. Results from this study suggest ways that service providers can tailor service plans to help youth from different countries achieve the best outcomes, and pose questions for future research.

Socioeconomic outcomes beyond 30 years of age in a cohort born with very low birth weight.

As survival of infants born prematurely has increased dramatically, questions on long-term consequences have emerged. Our aim was to investigate long-term effects of very low birth weight on socioeconomic outcomes. One hundred and fifty very low birth weight infants (VLBW) born from 1980 to 1982 at Rigshospitalet, Denmark, who had previously been followed up at age 2, 4 and 18 years, were compared to cohorts of low birth weight, normal birth weight (NBW) and a national population-based reference cohort. From the Danish national registers we obtained data regarding educational level, financial independence and living arrangements. In addition, we used the previously published results from the three cohorts. The VLBW cohort had lower intelligence quotient and higher risk of significant school difficulties evaluated at age 4 and 18 years. When compared to the NBW cohort, at 30-36 years of age the VLBW cohort tended to have lower educational level, OR 1.7, 95% CI 0.8-3.9, were not financially independent OR 1.5, 95% CI 0.6-3.7, lived alone OR 2.0, 95% CI 1.0-3.8 and had higher rates of the combination of all three outcomes, OR 3.2, 95% CI 0.7-15.8. We found trends towards poor socioeconomic outcomes in young adults born with VLBW. The relative disadvantages appeared smaller than that in childhood.

Language and developmental plasticity after perinatal stroke

The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

Favorable long-term outcome in young adults undergoing surgery for lumbar disc herniation

PurposeThe purpose of the study was to evaluate the long-term outcome after surgery for lumbar disc herniation in a young adult population.MethodsA total of 526 consecutive patients between 18 and 40 years of age who underwent surgery for lumbar disc between 1990 and 2005 were included in the study. The primary outcomes were the need for new lumbar spine surgery during the follow-up and secondary outcomes were short-term subjective outcome, the Oswestry Disability Index (ODI) score, and the ability to carry out employment at the end of the long-term follow-up.ResultsA total of 96% of the patients had a reduction in their symptoms at the clinical follow-up (median of 50 days post-surgery). Twenty-one patients (4.0%) had a reoperation within 28 days. Excluding these early reoperations, 136 patients (26%) had additional lumbar spine surgery and 18 patients (3.4%) underwent lumbar fusion during the follow-up of median 18 years. The annual risk for new surgery was 1.4%. In total, 316 patients (60%) returned the ODI questionnaire, and their mean score was 8.1. Patients with a higher number of additional lumbar spine surgeries (p < 0.001) reported deteriorating ODI scores.ConclusionPatients showed excellent short-term recovery from their symptoms. In the long term, the mean ODI score for the patients was comparable to the normative population. However, a notable proportion of the patients required additional lumbar surgery during the follow-up period, and a higher number of lumbar surgeries was associated with poor ODI scores.

Association of Attending a High-Performing High School With Substance Use Disorder Rate and Health Outcomes in Young Adults

Interventions directly targeting social factors, such as education, may have the potential to greatly improve health. To examine the association of attending a high-performing public charter high school with rates of substance use disorder and physical and mental health. This cohort study used the random school admissions lottery system of high-performing public charter high schools in low-income neighborhoods of Los Angeles, California, to examine the health outcomes of students who applied to at least 1 of 5 of these high schools. Participants attended 147 different high schools and were randomly selected from those who won the admissions lottery (intervention group) and those who were placed on a waiting list (control group). Participants were surveyed at the end of grade 8 through transition into grade 9 and then from grade 10 through 3 years after high school completion (at age 21 years). Surveys were conducted from March 2013 through November 2021. Attendance at a high-performing public charter high school. Self-reported alcohol use disorder and cannabis misuse, delinquent behaviors, physical and mental health, and body mass index. Of the 1270 participants at baseline (mean [SD] age, 14.2 [0.47] years; 668 female individuals [52.6%]). The control group included 576 individuals (45.4%), and 694 individuals (54.6%) were in the intervention group. Both groups were similar in almost all characteristics at baseline, and the median (IQR) follow-up was 6.4 (6.0-6.7) years. Participants attending a high-performing public charter high school had a 53.33% lower rate of hazardous or dependent alcohol use disorder compared with those in the control group (5.43% vs 11.64%; difference, -6.21% [95% CI, -11.87% to -0.55%]; P = .03). Among male participants, the intervention group had a 42.05% lower rate of self-reported fair or poor physical health (13.33% vs 23.01%; difference, -9.67% [95% CI, -18.30% to -1.05%]; P = .03) and a 32.94% lower rate of obesity or overweight (29.28% vs 43.67%; difference, -14.38% [95% CI, -25.74% to -3.02%]; P = .02) compared with the control group. Among female participants, attending a high-performing public charter high school was associated with worse physical health outcomes (30.29% vs 13.47% reporting fair or poor health; difference, 16.82% [95% CI, 0.36% to 33.28%]; P = .045) and higher rates of overweight or obesity (52.20% vs 32.91%; difference, 19.30% [95% CI, 3.37% to 35.22%]; P = .02) at age 21 years. Few differences in mental health outcomes were observed. Adjusting for educational outcomes did not significantly change these findings. Results of this study suggest that attending a high-performing public charter high school was associated with lower rates of substance use disorder independent of academic achievement. Physical health and obesity outcomes were also better but only for young men; the intervention group had worse physical health outcomes among young women for unclear reasons. Schools are a potent social determinant of health and an important target for future health interventions.

Outcome expectancies and resistance self-efficacy mediate the relationship between asthma diagnosis and e-cigarette use among youth and young adults

Introduction The use of electronic cigarettes (e-cigarettes) may exacerbate pulmonary complications in youth and young adults with asthma. We sought to identify the cognitive mechanisms that might explain e-cigarette use in this population. We hypothesized that e-cigarette outcome expectancies and e-cigarette resistance self-efficacy would mediate the relationship between asthma diagnosis and e-cigarette use in youth and young adults. Methods We enrolled youth and young adults (15–25 years old) in Alabama with a clinical diagnosis of asthma (n = 130) or without a diagnosis of any chronic pulmonary disease (n = 115; reference group). Author-constructed and validated questionnaires (young adult e-cigarette use outcome expectancies and modified Self-efficacy Scale for Adolescent Smoking) were administered to collect demographic data and assess susceptibility to e-cigarette use as well as current use of e-cigarettes, e-cigarette outcome expectancies, and e-cigarette resistance self-efficacy. We then conducted structural equation modeling to test whether e-cigarette expectancies and e-cigarette resistance self-efficacy mediate the relationship between asthma and susceptibility to e-cigarette use as well as current e-cigarette use. Results The frequency of the susceptibility to e-cigarette use and current e-cigarette use was lower among those with clinically diagnosed asthma than among those without asthma (35.8% vs. 59.8% for susceptibility and 6.0% vs. 18.2% for current use). Individuals with asthma reported weaker expectancies that e-cigarettes would make them feel relaxed which, in turn, was a significant predictor of lower susceptibility to e-cigarette use and current e-cigarette use, suggesting mediation. Finally, individuals with asthma demonstrated greater e-cigarette resistance self-efficacy in the context of social opportunities and friends’ influence to use e-cigarettes. This self-efficacy was associated with lower susceptibility to e-cigarette use as well as current e-cigarette use. Conclusion Although longitudinal studies are needed to determine relationships prospectively, targeted interventions that reduce outcome expectancies and increase resistance self-efficacy to e-cigarette use may further reduce e-cigarette use among youth and young adults with asthma.