Clustering of pediatric onset inflammatory bowel disease in Finland : a nationwide register-based study

Peer reviewe

Late adverse effects of childhood acute lymphoblastic leukemia treatment on developing dentition

Background: Childhood cancer survivors show a variety of late adverse effects on dental health. The purpose of this study was to examine the prevalence and severity of dental abnormalities in permanent dentition in childhood leukemia survivors. Materials and methods: Retrospective analysis of panoramic radiographs was performed for 178 childhood leukemia survivors aged below 17 years at the time of diagnosis. Sex, age at diagnosis, interval between ALL diagnosis and the follow-up radiograph, treatment protocol, and risk grouping were recorded. Abnormalities of tooth development and defect index were used to assess the frequency and severity of dental abnormalities. Results: One hundred eight (61%) patients had no dental abnormalities at follow-up examination at a median of 6.1 years after diagnosis. Microdontia was more frequent in children under 6 years of age at the time of diagnosis (5.7% vs. 0.6%, p <.001). Significant differences were noted between distinct ALL treatment protocols with more common microdontia in patients treated according to the NOPHO ALL2008 protocol. Tooth agenesis was more frequent in patients that underwent therapy according to high-risk arms compared to intermediate- or standard-risk arms (3.8% vs. 1.4%, p =.01). Patients under 6 years of age at diagnosis had a significantly higher average defect index score than older patients (7.0 vs. 2.8, p =.01). Conclusions: Children and adolescents who received ALL treatment were at risk for dental damage. Young age and high-intensity therapy were associated with the severity of dental abnormalities.acceptedVersionPeer reviewe

Cancer morbidity and mortality after pediatric solid organ transplantation-a nationwide register study

Background The prevalence of malignancies after pediatric solid organ transplantation was evaluated in a nationwide study. Methods All patients who had undergone kidney, liver, or heart transplantation during childhood between the years 1982 and 2015 in Finland were identified. The inclusion criteria were age under 16 years at transplantation and age over 18 years at the last follow-up day. A total of 233 (137 kidney, 53 liver, and 43 heart) transplant recipients were enrolled. Controls (n = 1157) matched by the year of birth, gender, and hometown were identified using the Population Register Center registry. The cancer diagnoses were searched using the Finnish Cancer Registry. Results Altogether 26 individuals diagnosed with cancer were found, including 18 transplant recipients. Cancer was diagnosed at a median of 12.0 (IQR 7.8-17.8) years after the transplantation. The transplant recipients' risk for cancer was significantly higher when compared with the controls (HR 14.7; 95% CI 6.4-33.9). There was no difference for different graft types. Sixty-one percent of cancers among the transplant recipients were diagnosed at age older than 18 years. Conclusion The risk for cancer is significantly higher among young adults having undergone solid organ transplantation during childhood in comparison with population controls. Careful follow-up and attention to prevent cancers throughout adulthood are warranted.Peer reviewe

Survival Analysis and Cox Proportional Hazards Model Reporting in Pediatric Leukemia Studies : a Systematic Review

Survival (overall, event free, etc.) is the most-used outcome in clinical oncology studies. This study analyzed methodological reporting of survival analysis in pediatric leukemia studies, focusing on Cox proportional hazards (PH). We performed a systematic review of studies published between 2012 and 2021 in the five highest-ranking oncology and five highest-ranking hematology journals. The included studies had to focus on pediatric leukemia and utilize survival analyses. We extracted data on how the survival analysis methodology was reported and focused on Cox proportional hazards modeling and whether the PH assumption was checked. We screened 561 studies and included 103 in the analysis. The most-used crude survival analysis method was Kaplan–Meier, as 96 (94%) of the 103 studies applied it. Adjusted survival analysis was performed in 80 (78%) of the included studies, and the Cox PH model was used in 77 (96%) of these studies. The PH assumption was mentioned in 18 (23%) of the 77 studies that used the Cox PH model. Only nine studies (12%) stated how the PH assumption was assessed. We noted 10 (13%) studies with possible violations of the PH assumption. Overall, we found a need for improvement in the reporting of survival analysis and especially PH assumption in pediatric leukemia studies. The Cox PH model was the most-used adjusted survival analysis method but checking of the background assumption was not reported in most of the studies.publishedVersionPeer reviewe

Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.</p

Arginine Methyltransferase PRMT7 Deregulates Expression of RUNX1 Target Genes in T-Cell Acute Lymphoblastic Leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with no well-established prognostic biomarkers. We examined the expression of protein arginine methyltransferases across hematological malignancies and discovered high levels of PRMT7 mRNA in T-ALL, particularly in the mature subtypes of T-ALL. The genetic deletion of PRMT7 by CRISPR-Cas9 reduced the colony formation of T-ALL cells and changed arginine monomethylation patterns in protein complexes associated with the RNA and DNA processing and the T-ALL pathogenesis. Among them was RUNX1, whose target gene expression was consequently deregulated. These results suggest that PRMT7 plays an active role in the pathogenesis of T-ALL.publishedVersionPeer reviewe

Parental occupational exposure to low-frequency magnetic fields and risk of leukaemia in the offspring : findings from the Childhood Leukaemia International Consortium (CLIC)

OBJECTIVES: Previously published studies on parental occupational exposure to extremely low-frequency magnetic fields (ELF-MF) and risk of acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in their offspring were inconsistent. We therefore evaluated this question within the Childhood Leukemia International Consortium. METHODS: We pooled 11 case-control studies including 9723 childhood leukaemia cases and 17 099 controls. Parental occupational ELF-MF exposure was estimated by linking jobs to an ELF-MF job-exposure matrix (JEM). Logistic regression models were used to estimate ORs and 95% CIs in pooled analyses and meta-analyses. RESULTS: ORs from pooled analyses for paternal ELF-MF exposure >0.2 microtesla (µT) at conception were 1.04 (95% CI 0.95 to 1.13) for ALL and 1.06 (95% CI 0.87 to 1.29) for AML, compared with ≤0.2 µT. Corresponding ORs for maternal ELF-MF exposure during pregnancy were 1.00 (95% CI 0.89 to 1.12) for ALL and 0.85 (95% CI 0.61 to 1.16) for AML. No trends of increasing ORs with increasing exposure level were evident. Furthermore, no associations were observed in the meta-analyses. CONCLUSIONS: In this large international dataset applying a comprehensive quantitative JEM, we did not find any associations between parental occupational ELF-MF exposure and childhood leukaemia