Age-related transcript changes in type I interferon signaling in children and adolescents with long COVID.

SARS-CoV-2 typically causes mild symptoms in children, but evidence suggests that persistent immunopathological changes may lead to long COVID (LC). To explore the interplay between LC and innate immunity, we assessed the type I interferon (IFN-I) response in children and adolescents with LC symptoms (LC; n = 28). This was compared with age-matched SARS-CoV-2 recovered participants without LC symptoms (MC; n = 28) and healthy controls (HC; n = 18). We measured the mRNA expression of IFN-I (IFN-α/ß/ε/ω), IFN-I receptor (IFNAR1/2), and ISGs (ISG15, ISG56, MxA, IFI27, BST2, LY6E, OAS1, OAS2, OAS3, and MDA5) in PBMCs collected 3-6 months after COVID-19. LC adolescents (12-17 years) had higher transcript levels of IFN-ß, IFN-ε, and IFN-ω than HC, whereas LC children (6-11 years) had lower levels than HC. In adolescents, increased levels of IFN-α, IFN-ß, and IFN-ω mRNAs were found in the LC group compared with MC, while lower levels were observed in LC children than MC. Adolescents with neurological symptoms had higher IFN-α/ß mRNA levels than MC. LC and MC participants showed decreased expression of ISGs and IFNAR1, but increased expression of IFNAR2, than HC. Our results show age-related changes in the expression of transcripts involved in the IFN-I signaling pathway in children and adolescents with LC.

Mindfulness meditation enhances interbrain synchrony of adolescents when experiencing different emotions simultaneously.

Mindfulness is considered to benefit social behavior and interpersonal communication. However, the underlying neural mechanism has not been fully examined. This study aimed to explore how mindfulness practice affected the interbrain synchrony within adolescent peer dyads when sharing emotional experience together by using the electroencephalograph hyperscanning approach. Thirty adolescent dyads were randomly assigned to a mindfulness group or a non-mindfulness group. Mindfulness group performed a 20-min mindfulness exercise. Non-mindfulness group were instructed to rest. Simultaneously, electroencephalograph was recorded when they completed a picture-processing task. Phase-locking-value in the gamma band was used to calculate adolescent dyads' brain-to-brain synchrony. Results showed that greater interbrain synchrony in the frontal region was observed when viewing different emotional stimuli together after the mindfulness than before the mindfulness in the mindfulness group. However, there was no significant difference in the interbrain synchrony in the non-mindfulness group. Moreover, greater interbrain synchrony was observed in the mindfulness group than in the non-mindfulness group after mindfulness or rest in the frontal region. However, there was no significant difference between the mindfulness and non-mindfulness group before mindfulness or rest. The findings are discussed in light of the broader theoretical questions of how mindfulness may promote interpersonal functioning from a psychophysiological perspective.

Strength and resilience of developing brain circuits predict adolescent emotional and stress responses during the COVID-19 pandemic.

The COVID-19 pandemic has had profound but incompletely understood adverse effects on youth. To elucidate the role of brain circuits in how adolescents responded to the pandemic's stressors, we investigated their prepandemic organization as a predictor of mental/emotional health in the first ~15 months of the pandemic. We analyzed resting-state networks from n = 2,641 adolescents [median age (interquartile range) = 144.0 (13.0) months, 47.7% females] in the Adolescent Brain Cognitive Development study, and longitudinal assessments of mental health, stress, sadness, and positive affect, collected every 2 to 3 months from May 2020 to May 2021. Topological resilience and/or network strength predicted overall mental health, stress and sadness (but not positive affect), at multiple time points, but primarily in December 2020 and May 2021. Higher resilience of the salience network predicted better mental health in December 2020 (ß = 0.19, 95% CI = [0.06, 0.31], P = 0.01). Lower connectivity of left salience, reward, limbic, and prefrontal cortex and its thalamic, striatal, amygdala connections, predicted higher stress (ß = -0.46 to -0.20, CI = [-0.72, -0.07], P < 0.03). Lower bilateral robustness (higher fragility) and/or connectivity of these networks predicted higher sadness in December 2020 and May 2021 (ß = -0.514 to -0.19, CI = [-0.81, -0.05], P < 0.04). These findings suggest that the organization of brain circuits may have played a critical role in adolescent stress and mental/emotional health during the pandemic.

Autoimmune comorbidity in type 1 diabetes and its association with metabolic control and mortality risk in young people: a population-based study.

AIMS/HYPOTHESIS: This register-based study aimed to describe autoimmune comorbidity in children and young adults from type 1 diabetes onset, and to investigate whether such comorbidity was associated with a difference in HbA1c or mortality risk compared with children/young adults with type 1 diabetes without autoimmune comorbidity. METHODS: A total of 15,188 individuals from the Swedish National Diabetes Register, registered with type 1 diabetes before 18 years of age between 2000 and 2019, were included. Five randomly selected control individuals from the Swedish population (Statistics Sweden) were matched to each individual with type 1 diabetes (n=74,210 [346 individuals with type 1 diabetes were not found in the Statistics Sweden register at the date of type 1 diabetes diagnosis, so could not be matched to control individuals]). The National Patient Register was used to attain ICD-10 codes on autoimmune diseases and the Cause of Death Register was used to identify deceased individuals. RESULTS: In the total type 1 diabetes cohort, mean±SD age at onset of type 1 diabetes was 9.5±4.4 years and mean disease duration at end of follow-up was 8.8±5.7 years. Of the individuals with type 1 diabetes, 19.2% were diagnosed with at least one autoimmune disease vs 4.0% of the control group. The HRs for comorbidities within 19 years from onset of type 1 diabetes were 11.6 (95% CI 10.6, 12.6) for coeliac disease, 10.6 (95% CI 9.6, 11.8) for thyroid disease, 1.3 (95% CI 1.1, 1.6) for psoriasis, 4.1 (95% CI 3.2, 5.3) for vitiligo, 1.7 (95% CI 1.4, 2.2) for rheumatic joint disease, 1.0 (95% CI 0.8, 1.3) for inflammatory bowel disease, 1.0 (95% CI 0.7, 1.2) for systemic connective tissue disorder, 1.4 (95% CI 1.1, 1.9) for uveitis, 18.3 (95% CI 8.4, 40.0) for Addison's disease, 1.8 (95% CI 0.9, 3.6) for multiple sclerosis, 3.7 (95% CI 1.6, 8.7) for inflammatory liver disease and 19.6 (95% CI 4.2, 92.3) for atrophic gastritis. Autoimmune disease in addition to type 1 diabetes had no statistically significant effect on HbA1c or mortality risk. CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first comprehensive study where young individuals with type 1 diabetes were followed regarding development of a wide spectrum of autoimmune diseases, from onset of type 1 diabetes. In this nationwide and population-based study, there was already a high prevalence of autoimmune diseases in childhood, especially coeliac and thyroid disease. The presence of autoimmune comorbidity did not have a statistically significant effect on metabolic control or mortality risk.

Prospective exploratory evaluation of Cepheid Xpert Mycobacterium tuberculosis host response cartridge: a focus on adolescents and young adults.

BACKGROUND: An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed. METHODS: A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24). RESULTS: A total of 497 participants, ages 6-83, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95%CI 28-37) when compared to Xpert MTB/RIF Ultra, 29% (95%CI 25-34) when compared to a bacteriological confirmation, and 22% (95%CI 18-26) when compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95%CI 74-89) when compared to Xpert MTB/RIF Ultra, 84% (95%CI 75-90) when compared to a bacteriological confirmation, and 54% (95%CI 44-64) when compared to a composite clinical diagnosis. CONCLUSIONS: While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.

Pharmaco-virological outcomes and genotypic resistance profiles among children and adolescents receiving a DTG-based regimen in Togo.

BACKGROUND: Few data are available on the real-world efficacy of receiving tenofovir-lamivudine-dolutegravir (DTG) as HIV treatment, particularly among young people in West Africa. Here, we evaluated pharmaco-virological outcomes and resistance profiles among Togolese children and adolescents. METHODS: A cross-sectional study was conducted in Lomé, Togo, enrolling antiretroviral-treated people with HIV aged from 18 months to 24 years. Plasma HIV-1 viral load and antiretroviral concentrations were measured. Next-Generation Sequencing (NGS) of protease, Reverse Transcriptase (RT) and integrase was performed on all samples with viral load >200 c/mL. Drug resistance mutations (DRMs) were identified and interpreted using the ANRS-MIE algorithm. RESULTS: 264 participants were enrolled (median age=17 years), 226 received a DTG-based regimen for a median of 20.5 months. Among them, virological suppression at the 200 c/mL threshold in 80.0% of the participants. Plasma DTG concentrations were adequate (i.e., >640 ng/mL), suboptimal and below the limit of quantification in 74.1%, 6.7% and 19.2% of participants receiving DTG, respectively. Overall, viruses resistant to any of Nucleoside RT Inhibitors, Non-NRTIs, and protease inhibitors were found in 52%, 66% and 1.6% of participants, respectively. A major integrase inhibitor DRM was observed in 9.4% (n=3/32, R263K, E138A-G140A-Q148R, and N155H) of participants with a viral load >200 c/mL. CONCLUSIONS: These first findings in such a large series of adolescents in a low-income country, showed a good virological response of 80% and the presence of an integrase DRM in 9.4% of the virological failures, supporting the need to monitor DTG drug resistance to reduce the risk of resistance acquisition.

Toxoplasma gondii Infections and Associated Factors in Female Children and Adolescents, Germany.

In a representative sample of female children and adolescents in Germany, Toxoplasma gondii seroprevalence was 6.3% (95% CI 4.7%-8.0%). With each year of life, the chance of being seropositive increased by 1.2, indicating a strong force of infection. Social status and municipality size were found to be associated with seropositivity.

Global burden of 34 cancers among women in 2020 and projections to 2040: Population-based data from 185 countries/territories.

Globally women face inequality in cancer outcomes; for example, smaller improvements in life expectancy due to decreased cancer-related deaths than men (0.5 vs 0.8 years, 1981-2010). However, comprehensive global evidence on the burden of cancer among women (including by reproductive age spectrum) as well as disparities by region, remains limited. This study aimed to address these evidence gaps by considering 34 cancer types in 2020 and their projections for 2040. The cancer burden among women in 2020 was estimated using population-based data from 185 countries/territories sourced from GLOBOCAN. Mortality to Incidence Ratios (MIR), a proxy for survival, were estimated by dividing the age-standardised mortality rates by the age-standardised incidence rates. Demographic projections were performed to 2040. In 2020, there were an estimated 9.3 million cancer cases and 4.4 million cancer deaths globally. Projections showed an increase to 13.3 million (↑44%) and 7.1 million (↑60%) in 2040, respectively, with larger proportional increases in low- and middle-income countries. MIR among women was higher (poorer survival) in rare cancers and with increasing age. Countries with low Human Development Indexes (HDIs) had higher MIRs (69%) than countries with very high HDIs (30%). There was inequality in cancer incidence and mortality worldwide among women in 2020, which will further widen by 2040. Implementing cancer prevention efforts and providing basic cancer treatments by expanding universal health coverage through a human rights approach, expanding early screening opportunities and strengthening medical infrastructure are key to improving and ensuring equity in cancer control and outcomes.

State-level structural racism and adolescent mental health in the United States.

We explored state-level indicators of structural racism on internalizing symptoms of depressive affect among US adolescents. We merged 16 indicators of state-level structural racism with 2015-19 Monitoring the Future surveys (N=41,258) examining associations with loneliness, self-esteem, self-derogation, and depressive symptoms using regression analyses. Students racialized as Black in states with bans on food stamp eligibility and temporary assistance for drug felony conviction had 1.37 times the odds of high depressive symptoms (95% C.I. 1.01-1.89) compared to students in states without bans. In contrast, students racialized as White living in states with more severe disenfranchisement of people convicted of felonies had lower odds of high self-derogation (OR=0.89, 95% C.I. 0.78-1.02) and high depressive symptoms (OR=0.83, 95% C.I. 0.70-0.99) compared to states with less severe disenfranchisement. These findings demonstrate the need to address the legacy of structural racism at the state level to reduce mental distress for US youth.

Is nicotine vaping associated with subsequent initiation of cannabis or other substances from adolescence into young adulthood?

Prior studies estimating longitudinal associations between nicotine vaping and subsequent initiation of cannabis and other substances (e.g., cocaine, heroin) have been limited by short follow-up periods, convenience sampling, and possibly inadequate confounding control. We sought to address some of these gaps using the nationally representative Population Assessment of Tobacco and Health Study (PATH) to estimate longitudinal associations between nicotine vaping and the initiation of cannabis or other substances among adolescents transitioning to adulthood from2013 to 2019, adjusting for treatment-confounder feedback. Estimands like the longitudinal average treatment effect were not identified because of extensive practical positivity violations. Therefore, we estimated longitudinal incremental propensity score effects, which were identified. We found that reduced odds of nicotine vaping were associated with decreased risks of cannabis or other substance initiation; these associations strengthened over time. For example, by the final wave (2018-19), cannabis and other substance initiation risks were 6.2 (95%CI:4.6-7.7) and 1.8 (95%CI:0.4-3.2) percentage points lower when odds of nicotine vaping were reduced to be 90% lower in all preceding waves (2013-14 to 2016-18), as compared with observed risks. Strategies to lower nicotine vaping prevalence during this period may have resulted in fewer young people initiating cannabis and other substances.

Assessing Trends in Internalizing Symptoms among Racialized and Minoritized Adolescents: Results from the Monitoring the Future Survey 2005-2020.

Depressive symptoms have rapidly accelerated among recent US adolescent birth cohorts, yet there remains little understanding of trends among racialized and minoritized groups. These groups may experience depressive symptoms due to the deleterious effects of structural racism. Using 2005-2020 Monitoring the Future survey data, we examine all racialized groups using within-group analyses to observe trends in high depressive symptoms across cohorts. Generally, across racialized groups and ages, the odds of high depressive symptoms increased in recent birth cohorts. For example, among 15-16-year-old students racialized as American Indian or Alaska Native and Black-Hispanic/Latine, the 2003-2006 birth cohort had 3.08 (95% CI: 2.00, 4.76) and 6.95 (95% CI: 2.70, 17.88) times higher odds, respectively, of high depressive symptoms compared to the 1987-1990 birth cohorts. Moreover, in a given year 15-16-year-olds generally experienced the highest depressive symptoms compared to 13-14 and 17-18-year-olds, suggesting that age-effects peaked during mid-adolescence. Depressive symptoms increased among US adolescents by birth cohort, within all racialized and minoritized groups assessed. Public health efforts to reduce disparities may consider barriers such as structural racism that may impact the mental health of racialized/minoritized adolescents while increasing access to culturally competent mental health providers and school-based services.

Mediating effects of inequitable gender norms on intimate partner violence and contraceptive use in a cluster randomized control trial in Niger.

Previous research has demonstrated that the Reaching Married Adolescents intervention (RMA) was associated with changes in inequitable gender norms, intimate partner violence (IPV), and modern contraceptive use. This study seeks to understand if changes in inequitable gender norms mediate the RMA intervention's effects on contraceptive use and intimate partner violence (IPV). A four-arm cluster randomized control trial was conducted to evaluate effects of the RMA intervention (household visits, small groups, combination, control) on married adolescent girls and their husbands in Dosso, Niger (baseline: 1042 dyads; 24m follow-up: 737 dyads; 2016-2019). Mediation was assessed using inverse odds ratio weighting. In the small group intervention, of the total effect on IPV prevalence (8% reduction), indirect effects via inequitable gender norms is associated with a 2% decrease (95% CI: -0.07, 0.12) and direct effects with a 6% decrease (95% CI: -0.20, -0.02). For household visits, of the total effect on contraceptive use (20% increase), the indirect effect accounts for an 11% decrease (95% CI: -0.18, -0.01) and direct effect, a 32% increase (95% CI: 0.13, 0.44); similar to findings for the combination arm. This experimental evidence informs the value of changing underlying social norms to reduce IPV and increase contraception use.

Pediatric kidney dimensions and risk of persistent albuminuria in Mexican adolescents.

In Mexico, chronic kidney disease of unknown origin is highly prevalent. Screening studies in adolescents have shown persistent microalbuminuria (pACR), adaptive podocytopathy and decreased kidney volume (KV). Here, we sought to develop normality tables of kidney dimensions by ultrasound in the Mexican state of Aguascalientes pediatric population (0 to 18y) and evaluate the relationship between the KV and pACR among the region's adolescents in a cross-sectional study. Kidney length (KL) and KV were determined by ultrasound. Our findings were compared with those in international literature of different populations where tables and graphs of normal kidney dimensions by ultrasound were reported. We compared organ dimensions in individuals above the age of 11 without albuminuria with those in patients with pACR recruited through screening studies in adolescents in Aguascalientes. This included 1068 individuals to construct percentile tables and graphs of the KL. Kidney dimensions were significantly lower when compared with all international comparisons. From a total 14,805 screen individuals, we compared 218 adolescents with pACR and 377 individuals without significant albuminuria. The Total KV adjusted to body surface (TKVBS) was significantly associated with pACR (odds ratio 1.03, 95% confidence interval 1.02-1.03). The upper quartile of TKVBS was highly associated with pACR (7.57, 4.13-13.87), hypertension (2.53, 1.66-3.86), and hyperfiltration (26 vs 11.5%). Thus, TKVBS is directly associated with pACR while greater KV, arterial hypertension, and hyperfiltration in patients with pACR suggest that the increase in volume is secondary to kidney hypertrophy. Additionally, the adaptative podocytopathy with low fibrosis seen on kidney biopsy which was performed in a subset of patients, and the smaller kidney dimensions in our population point to prenatal oligonephronia as the primary cause of the detected kidney disease.

Employment outcomes of adolescent and young adult cancer survivors and their partners: A Dutch population-based study.

BACKGROUND: The aim of this population-based registry study was to examine the impact of cancer on employment outcomes in adolescent and young adult (AYA) survivors and their partners and associated sociodemographic and clinical characteristics. METHODS: A total of 2456 AYA cancer patients, diagnosed in 2013 and aged 18 through 39 years old, were selected from the Netherlands Cancer Registry and linked to employment data from Statistics Netherlands, from which 1252 partners of AYAs could be identified. For both patients and their partners, a control group with same age, migration background, and sex was selected. The impact (i.e., causal effect) was estimated by implementing a doubly robust difference-in-differences method, from 3 years before to 5 years after cancer diagnosis. RESULTS: Patients suffered a reduced employment probability (3.8 percentage points) and number of hours worked when employed (3.8%). This effect was larger for females, and individuals with a migration background, high tumor stage, or diagnosed with a central nervous system tumor/hematologic malignancy. In regard to employment, no significant effect could be found for the patients' partners, although a 5.5 percentage-point increase in employment probability was found in partners who were either unemployed or worked fewer than 400 hours. CONCLUSIONS: A cancer diagnosis significantly affects employment outcomes of AYA patients with cancer. Patients at risk should have access to services such as job counseling to help them return into society in the best possible way. No objective impact on partners' employment outcomes was found; however, subjective well-being was not taken into account. PLAIN LANGUAGE SUMMARY: This study estimated the causal effect of a cancer diagnosis on employment outcomes. Adolescent and young adult cancer survivors face a reduction in both employment probability and the number of hours worked when employed. Partners that were unemployed or worked the least number of hours a year before diagnosis had a 5.5 percentage-point increased employment probability, but for other partners effects are small.

Ten-year follow-up of outcomes, patterns of care, and psychosocial burden in adolescent and young adult (AYA) patients with bone sarcomas from a large cohort in a low-income and middle-income country (LMIC).

BACKGROUND: The care of adolescents and young adults (AYAs) with bone sarcomas involves unique challenges. The objectives of this study were to identify challenges and evaluate long-term outcomes of these patients from India who received treatment with novel protocols. METHODS: This prospective cohort study included AYA patients (aged 15-39 years) with osteosarcoma and Ewing sarcoma (ES), who were treated uniformly at the authors' institute using unique protocols (OGS-12 and EFT-2001) from 2011 to 2021 and from 2013 to 2018, respectively. RESULTS: The cohorts included 688 of 748 (91.9%) treatment-naive AYA patients with osteosarcoma and 126 of 142 (88.7%) treatment-naive AYA patients with ES. Among 481 of 561 patients (85.7%) who had nonmetastatic osteosarcoma treated according to protocol, at a median follow-up of 59.7 months, the 5-year event-free survival (5-EFS) rate was 58.6% (95% confidence interval, 54.1%-63.5%) and for 142 patients (20.6%) who had metastatic osteosarcoma, the 5-EFS rate was 18.7%. The 5-EFS rate was 66.4% and 21.9% for 104 patients (73%) with nonmetastatic ES and 38 patients (27%) with metastatic ES, respectively. Treatment-naive patients had better outcomes, similar to compliance in the form of protocol completion (hazard ratio, 1.93 [p = .0043] and 2.66 [p < .0001], respectively. Only 230 of 377 (61.0%) male patients and 10 of 134 (7.4%) female patients reached out to fertility specialists. In addition, 17 of 161 (10.6%) eligible male survivors and 14 of 61 (22.9%) eligible female survivors got married posttreatment. Furthermore, 14 of 17 (82.4%) males and 14 of 14 (100%) females conceived. Among 311 patients who were working or attending school during diagnosis, greater than 90% had interruptions. CONCLUSIONS: Homogenous treatment with the OGS-12 and EFT-2001 protocols resulted in internationally comparable long-term outcomes in the cohorts with nonmetastatic and metastatic AYA bone sarcomas. Treatment compliance, timely referral to sarcoma reference centers (avoiding prior inadvertent treatment), and streamlining fertility-preservation practices constitute unmet needs that demand prioritization.

Efficacy and safety of recombinant human thrombopoietin for the treatment of chronic primary immune thrombocytopenia in children and adolescents: A multicentre, randomized, double-blind, placebo-controlled phase III trial.

The efficacy and safety of recombinant human thrombopoietin (rhTPO) in children and adolescent patients with chronic primary immune thrombocytopenia (ITP) remains unclear. A multicentre, randomized, double-blind, placebo-controlled phase III trial was performed. Patients aged 6-17 years, diagnosed with ITP and resistant or relapsed to corticosteroid treatment were included. For the trial, part 1 was exploratory and part 2 was the main analysis, with part 1 determining whether part 2 was stratified by age. Patients in part 1 were treated with rhTPO (the 6- to 11-/12- to 17-year-old groups; 1:1). Patients in part 2 were randomized (3:1) to receive either rhTPO treatment or placebo. Patients received rhTPO or placebo at a dose of 300 U/kg once daily for up to 14 days. A total of 68 patients were included [part 1 (12 patients), part 2 (56 patients)]. The total response rate (TRR) in part 1 was 50.0% (95% CI: 21.09%-78.91%). For part 2, the TRR was 58.5% (95% CI: 42.11%-73.68%) and 13.3% (95% CI: 1.66%-40.46%) in the rhTPO and placebo groups (FAS) respectively. The difference in TRR between the rhTPO group and placebo group was 45.2% (95% CI: 22.33%-68.08%) and 44.6% (95% CI: 21.27%-67.85%) on the FAS and per-protocol set (PPS), respectively, which indicates the superiority of rhTPO treatment.

Haematopoietic stem cell transplantation after reduced intensity conditioning in children and adolescents with chronic myeloid leukaemia: A prospective multicentre trial of the I-BFM Study Group.

This prospective multicentre trial evaluated the safety and the efficacy of a thiotepa/melphalan-based reduced intensity conditioning (RIC) haematopoietic stem cell transplantation (HSCT) in children and adolescents with chronic myeloid leukaemia (CML) in chronic phase (CP). Thirty-two patients were transplanted from matched siblings or matched unrelated donors. In 22 patients, HSCT was performed due to insufficient molecular response or loss of response to first- or second-generation tyrosine kinase inhibitor (TKI), with pretransplant BCR::ABL1 transcripts ranging between 0.001% and 33%. The protocol included a BCR::ABL1-guided intervention with TKI retreatment in the first year and donor lymphocyte infusions (DLI) in the second-year post-transplant. All patients engrafted. The 1-year transplant-related mortality was 3% (confidence interval [CI]: 0%-6%). After a median follow-up of 6.3 years, 5-year overall survival and event-free survival are 97% (CI: 93%-100%) and 91% (CI: 79%-100%) respectively. The current 5-year leukaemia-free survival with BCR::ABL1 <0.01% is 97% (CI: 88%-100%) and the current TKI- and DLI-free survival is 95% (CI: 85%-100%). The incidence of chronic graft-versus-host disease (GvHD) was 32%, being severe in four patients (13%). At last follow-up, 31 patients are GvHD-free and have stopped immunosuppression. RIC HSCT following pretreatment with TKI is feasible and effective in children and adolescents with CP-CML with an excellent disease-free and TKI-free survival.

Patient-Reported Outcomes of Accelerated Aging: A Novel Approach to Investigate Second Cancer Risk in Adolescent and Young Adult (18-39 Years) Cancer Survivors.

BACKGROUND: Adolescent and young adult cancer survivors (AYAs, aged 18-39 years at first diagnosis) have a higher second cancer risk. Accelerated aging is hypothesized as underlying mechanism and has been described clinically by 6 indicators; fatigue, low quality of sleep, low mood, lack of motivation, subjective memory complaints, and poor exercise tolerance. Using patient-reported outcomes, we aimed to identify clusters of accelerated aging among AYA cancer survivors and to investigate their association with second cancer development. PATIENTS AND METHODS: Patient, tumor, and treatment data were obtained from the Netherlands Cancer Registry. Patient-reported clinical indicators and second cancer data were obtained from the SURVivors (5-20 years) of cancer in AYAs (SURVAYA) questionnaire study between 1999 and 2015. Latent class and multivariable logistic regression analyses were performed. RESULTS: In total, n = 3734 AYA survivors with known second cancer status (n = 278 [7.4%] second cancers) were included. Four latent clusters were identified and named based on their clinical indicator features; (1) high accelerated aging (31.3%), (2) intermediate accelerated aging without poor exercise tolerance (15.1%), (3) intermediate accelerated aging without lack of motivation (27.4%), and (4) low accelerated aging (26.2%). AYAs in the high accelerated aging cluster were more likely to have second cancer (odds ratio: 1.6; 95% CI, 1.1-2.3) compared to the low accelerated aging cluster. CONCLUSION: AYAs with a higher burden of accelerated aging were more likely to develop a second cancer. Validation of the clinical indicators and how to best capture them is needed to improve (early) detection of AYAs at high risk of developing second cancer.

Differential correlates of fear and anxiety in salience perception: A behavioral and ERP study with adolescents.

Anxiety disorders are the most common psychopathologies among adolescents. Their diagnostic criteria include both fear and anxiety symptomatology, although according to the literature, we can find evidence for some distinction between these two emotions. The present study contribute to this distinction, exploring the effects of trait fear and trait anxiety on behavioral and neural correlates. Thirty-two participants (aged 11-16 years) performed two experimental tasks of salient target detection, including visual stimuli that were manipulated to become salient, while reaction times and EEG were recorded. Results of both tasks revealed differential effects of trait fear and trait anxiety assessed through the Fear Survey Schedule for Children-Revised and the Youth Anxiety Measure for DSM-5 on reaction times and ERP components amplitudes. Specifically, higher symptoms from Separation Anxiety Disorder increased early neural visual processing and decreased reaction times for more salient stimuli. Also, trait fear reduced later neural visual processing of salient stimuli. These findings may provide a significant contribution to guiding psychological interventions, especially with adolescents presenting higher levels of anxiety-related symptomatology.

Associations between vaping and self-reported respiratory symptoms in young people in Canada, England and the US.

BACKGROUND: Prevalence of youth nicotine vaping has increased, heightening concerns around negative health effects. This study aimed to compare self-reported respiratory symptoms among youth by vaping behaviours. METHODS: Participants (n = 39,214) aged 16-19 from the 2020 and 2021 International Tobacco Control Policy Evaluation Project (ITC) Youth Tobacco and Vaping Surveys (Canada, England, US). Weighted multivariable logistic regression assessed associations between reporting any of five respiratory symptoms in the past week (shortness of breath, wheezing, chest pain, phlegm, cough) and: past 30-day smoking and/or vaping; lifetime/current vaping. Among past-30-day vapers (n = 4644), we assessed associations between symptoms and vaping frequency, use of nicotine salts, usual flavour and device type(s). RESULTS: Overall, 27.8% reported experiencing any of the five respiratory symptoms. Compared with youth who had only vaped, those who had only smoked had similar odds of symptoms [adjusted odds ratio, OR (95% confidence interval, CI): 0.97 (0.85-1.10)], those who both smoked and vaped had higher odds [1.26 (1.12-1.42)], and those who had done neither, lower odds [0.67 (0.61-0.72)]. Compared with those who had never vaped, past use, experimentation and current regular or occasional use were all associated with higher odds. Reporting usually using nicotine salts was associated with higher odds of symptoms [1.43 (1.22-1.68)] than non-salt but was often uncertain. Compared with tobacco flavour (including with menthol), menthol/mint and sweets flavours were associated with similar odds; fruit [1.44 (1.07-1.93)], multiple [1.76 (1.30-2.39)] and 'other' [2.14 (1.45-3.16)] flavours with higher odds. All device types were associated with similar odds. CONCLUSIONS: Among youth, vaping was associated with increased reporting of past-week respiratory symptoms. Among those who vaped, some flavour types and potentially nicotine salts were associated with respiratory symptoms.