Role of non-chromosomal birth defects on the risk of developing childhood Hodgkin lymphoma: A Children's Oncology Group study.

BACKGROUND: Non-chromosomal birth defects are an important risk factor for several childhood cancers. However, these associations are less clear for Hodgkin lymphoma (HL). Therefore, we sought to more fully elucidate the association between non-chromosomal birth defects and HL risk. PROCEDURE: Information on cases (n = 517) diagnosed with HL (ages of 0-14) at Children's Oncology Group Institutions for the period of 1989-2003 was obtained. Control children without a history of cancer (n = 784) were identified using random digit dialing and individually matched to cases on sex, race/ethnicity, age, and geographic location. Parents completed comprehensive interviews and answered questions including whether their child had been born with a non-chromosomal birth defect. To test the association between birth defects and HL risk, conditional logistic regression was applied to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: Children born with any non-chromosomal birth defect were not more likely to be diagnosed with HL at 0-14 years of age (aOR: 0.91; 95% CI: 0.69-1.21). No associations were detected between major or minor birth defects and HL (aOR: 1.34; 95% CI: 0.67-2.67 and aOR: 0.88; 95% CI: 0.57-1.34, respectively). Similarly, no association was observed for children born with any birth defect and EBV-positive HL (aOR: 0.57; 95% CI: 0.25-1.26). CONCLUSIONS: Previous assessments of HL in children with non-chromosomal birth defects have been limited. Using data from the largest case-control study of HL in those <15 years of age, we did not observe strong associations between being born with a birth defect and HL risk.

Personal history of autoimmune disease and other medical conditions and risk of myelodysplastic syndromes.

BACKGROUND: Autoimmune diseases and hematopoietic malignancies are known to cluster within individuals, suggesting intertwined etiologies. A limited number of studies have evaluated pre-existing medical conditions as risk factors for myelodysplastic syndromes (MDS). We evaluated associations between autoimmune disease and other medical conditions and risk of MDS. METHODS: Cases were identified through the Minnesota Cancer Reporting System. Controls were identified through the Minnesota State driver's license/identification card list. History of autoimmune disease and other medical conditions was based on self-report; proxy interviews were not conducted. Unconditional logistic regression was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CI). RESULTS: We included 395 cases and 694 controls. Cases were significantly more likely to report a diagnosis of any autoimmune disease when compared with controls (aOR=1.41, 95% CI: 1.05-1.89) after adjustment for age, sex, education, NSAID use, exposure to benzene and body mass index. When we evaluated specific autoimmune conditions, a statistically significant association was observed for hypothyroidism (aOR=2.16, 95% CI: 1.39-3.34) and odds ratios were elevated for inflammatory bowel disease (aOR=1.75) and systemic lupus erythematosus (SLE; aOR=3.65), although these associations did not reach statistical significance. Presence of an autoimmune condition did not impact overall survival (p = 0.91). CONCLUSION: Our results validate previous findings of an association between autoimmune disease and MDS. Further studies are required to determine whether this association is due to shared etiology, treatment for autoimmune diseases, or altered immune surveillance or bone marrow damage caused by the autoimmune condition.

Quality Indicators for Children With Traumatic Brain Injury After Transition to an American College of Surgeons Level I Pediatric Trauma Center.

OBJECTIVE: The aim of the study was to compare quality indicators, including frequency of acute surgical and emergent interventions, and resource utilization before and after American College of Surgeons (ACS) level I trauma verification among children with moderate or severe traumatic brain injury (TBI). METHODS: This is a retrospective review of patients younger than 18 years treated for moderate or severe TBI, as determined by International Classification of Disease codes. Our institution obtained ACS level I trauma verification in 2013. Outcomes during the pre-ACS (June 2003-May 2008), interim (June 2008-May 2013), and post-ACS (June 2013-May 2018) periods were compared via nonparametric tests. Tests for linear trend were conducted using Cochran-Armitage tests for categorical data and by linear regression for continuous variables. RESULTS: There were 677 children with moderate or severe TBIs (pre-ACS, 125; interim, 198; post-ACS, 354). Frequency of any surgical intervention increased significantly in the post-ACS period (12.2%) compared with interim (5.1%) and pre-ACS periods (5.6%, P = 0.007). More children in the post-ACS period required intracranial pressure monitoring (P = 0.017), external ventricular drain placement (P = 0.003), or endotracheal intubation (P = 0.001) compared with interim and pre-ACS periods. There was no significant change in time to operating room (P = 0.514), frequency of decompression (P = 0.096), or time to decompression (P = 0.788) between study periods. The median time to head CT decreased significantly in the post-ACS period (26 minutes; interquartile range [IQR], 9-60) compared with interim (36 minutes; IQR, 21-69) and pre-ACS periods (53 minutes; IQR, 36-89; P < 0.001). Frequency of repeat head computed tomography decreased significantly in the post-ACS period (30.2%) compared with interim (56.1%) and pre-ACS periods (64.0%, Ptrend = 0.044). CONCLUSIONS: Transition to an ACS level I trauma verification was associated with improvements in quality indicators for children with moderate or severe TBI.

Learning and Attention Deficit/Hyperactivity Disorders as Risk Factors for Prolonged Concussion Recovery in Children and Adolescents.

OBJECTIVE: Examine pre-existing learning disorders (LD) and attention deficit/hyperactivity disorders (ADHD) as risk factors for prolonged recovery and increased symptomology following pediatric mild traumatic brain injury (mTBI). METHODS: We conducted a retrospective cohort study of children/adolescents (5-17 years) with mTBI who presented to a Children's Minnesota Concussion Clinic between April 2018 and March 2019. Differences across strata of pre-existing conditions (present vs. absent) in time to recovery measures were estimated via Kaplan-Meier and Cox proportional hazards analyses and differences in symptom trajectories were examined via linear mixed-effects regression models. Regression models were adjusted for age, sex and other confounders. RESULTS: In our cohort of 680 mTBI patients, those with LD (n = 70) or ADHD (n = 107) experienced significantly longer median durations of symptoms (58 and 68 days, respectively) than those without (43 days). Accordingly, LD was significantly associated with delayed symptom recovery (adjusted hazard ratio (aHR) = 1.63, 95% CI: 1.16-2.29), return to school (1.47, 1.08-2.00), and return to physical activity (1.50, 1.10-2.04). Likewise, ADHD was associated with delayed recovery (1.69, 1.28-2.23), return to school (1.52, 1.17-1.97) and physical activity (1.55, 1.19-2.01). Further, patients with LD or ADHD reported, on average, significantly more concussion symptoms and higher vision symptom scores throughout recovery versus those without. There was no evidence that concussion or vision symptom recovery trajectories varied over time between those with/without LD or ADHD (joint P-interactions > 0.05). CONCLUSION: Pre-existing LD and ADHD are risk factors for prolonged and more symptomatic mTBI recovery in youth. These results can inform clinical concussion management and recovery expectations.

Emergency Department Visits for Pediatric Firearm Injuries by Trauma Center Type.

OBJECTIVES: This study aimed to characterize pediatric visits to emergency departments (EDs) for firearm injuries and examine differences by trauma center type. METHODS: Analyses included all patients younger than 19 years from the National Trauma Data Bank, years 2009 to 2014. Trauma centers were categorized as adult, mixed adult and pediatric, or pediatric based on certification level. Baseline characteristics were compared between subgroups using χ2 tests. Multivariable logistic regression was used to examine risk of death. RESULTS: Of 466,403 pediatric ED visits, 21,416 (4.6%) resulted from a firearm injury. Most firearm injuries were treated at an adult (64.9%) or mixed trauma center (29.1%) and involved patients that were male (87.1%), in the 15- to 18-year age group (83.2%), and black or African American (61.3%). Most visits were for injuries resulting from assault (78.1%), followed by unintentional (12.6%) and self-inflicted (4.7%) injuries, undetermined intent (3.7%), and legal intervention (0.8%). Patients visiting EDs for firearm injuries had more than 7 times the odds of dying compared with patients with other injuries (odds ratio, 7.30; 95% confidence interval, 6.82-7.72), and firearm injuries were responsible for more than a quarter (26.1%) of the total pediatric deaths in the National Trauma Data Bank (n = 2866). Assault-related injuries resulted in the most deaths (n = 2010; 70.1%), but the case fatality rate was highest for self-inflicted (n = 453; 44.6%). CONCLUSION: We identified more than 20,000 firearm-related ED visits by pediatric patients from 2009 to 2014, averaging nearly 10 visits per day. Findings from this study can inform strategic planning in hospitals focused on preventing firearm injuries in children and adolescents.

A protocol of situation-dependent transfusion, erythropoietin and tranexamic acid reduces transfusion in fronto-orbital advancement for metopic and coronal craniosynostosis.

PURPOSE: Assess the effect of a protocol of preoperative erythropoietin (EPO) and ferrous sulfate in addition to perioperative tranexamic acid (TXA) on blood transfusions in patients with coronal or metopic craniosynostosis undergoing cranial vault remodeling (CVR) with fronto-orbital advancement (FOA). METHODS: Retrospective review of all coronal and metopic craniosynostosis patients undergoing CVR and FOA from March 2010 to June 2019 was performed. Before 2014 ("Control group"), all patients received blood transfusion at the start of surgery. In 2014, a protocol of preoperative EPO and ferrous sulfate with perioperative TXA and non-automatic transfusion was instituted ("Study group"). Patient demographics and anthropometrics, perioperative hemoglobin (Hb) levels, and transfusion details were collected and compared. RESULTS: Thirty-six patients met inclusion criteria. Twenty-one patients were in the control group, and 15 in the Study group. Nineteen patients had metopic synostosis, 11 had unicoronal synostosis, and 6 had bicoronal synostosis. There were no significant differences between groups in demographics, operative time, intraoperative crystalloid volume, craniofacial syndromes, or sutures affected. The Study group had higher preoperative Hb (13.9 ± 1.0 vs. 12.6 ± 0.8 g/dL, p < 0.001), lower intraoperative Hb nadir (7.4 ± 1.8 vs. 9.2 ± 1.2 g/dL) lower intraoperative transfusion rate (66.7% vs. 100%, p = 0.008), lower postoperative transfusion rate (0% vs 28.6%, p = 0.03), and exposure to fewer unique units of packed red blood cells (0.7 ± 0.6 vs. 1.5 ± 0.9 units). CONCLUSION: Our protocol resulted in decreased transfusion needs. These results add valuable information to the growing body of work on transfusion reduction in craniosynostosis surgery.

Effects of proactive and rescue enteral tube feedings on weight change in children undergoing treatment for high-grade CNS tumors.

BACKGROUND: Children with high-grade CNS cancers frequently experience malnutrition during treatment. We assessed the effects of proactive enteral tube (ET) placement/enteral tube feedings (ETF) on weight in infants/children with high-grade CNS tumors treated with aggressive chemotherapy. METHODS: We conducted a retrospective study of patients age 0 to 19 years treated for new high-grade CNS tumors between 2002 and 2017 at a tertiary pediatric hospital system. Patients underwent placement of proactive ET (≤ 31 days postdiagnosis; n = 45), rescue ET (> 31 days, due to weight loss; n = 9), or no ET (n = 18). Most received surgically placed ET (98%), with percutaneous endoscopic gastrojejunostomy or gastrojejunostomy tubes favored to allow jejunal feeding. The majority of patients with ET used ETF (91%). Using mixed-effects regression models, we examined differences in mean weights between ET/ETF groups across the first year of treatment. We also evaluated observed weight changes. RESULTS: All infants (n = 22, median age, 1.5 years) had proactive ET placed and 21 of 22 used proactive ETF. Infants showed an initial increase in mean percentage weight change that eventually leveled off, for an estimated increase of 10.4% over the year. For the pediatric cohort (n = 50, median, 8.1 years), those receiving proactive ETF experienced weight increases (+9.9%), those with rescue ETF experienced an initial decline and eventually rebounded for no net change (0.0%), and those with no ETF demonstrated an initial decline that persisted (-11.9%; P interaction < .001). Analysis of observed weights revealed nearly identical patterns. CONCLUSIONS: Proactive ETF was effective at maintaining weight and/or facilitating weight gain over the first year of treatment and was acceptable to patients/families.

Concussion symptomology and recovery in children and adolescents with pre-existing anxiety.

OBJECTIVE: To examine pre-existing anxiety disorders as a risk factor for increased concussion symptomology and prolonged recovery in children and adolescents. METHODS: In this retrospective cohort study, we abstracted medical record data for 637 children/adolescents (5-17 years) presenting to three tertiary concussion clinics between April 2018 and March 2019. Primary outcomes were mean concussion symptom and vision symptom severity scores measured at clinic visits. Linear mixed-effects regression models were employed to investigate differences in average symptom load, vision symptom score and symptom recovery trajectories across anxiety strata, adjusted for random effects (time), age and sex. Secondary outcomes, time to concussion symptom recovery and time to return to academics and sports, respectively, were examined via log-rank tests and multivariable Cox regression. RESULTS: Among 637 eligible concussion patients, 155 (24%) reported pre-existing anxiety. On average, patients with anxiety reported an additional 2.64 (95% CI 1.84 to 3.44) concussion symptoms and 7.45 (95% CI 5.22 to 9.68) higher vision symptom severity scores throughout recovery versus those without, after adjusting for age and sex. There was no evidence that concussion or vision symptom trajectories varied over time between those with/without anxiety after accounting for baseline dissimilarities in symptom scores (all pinteraction >0.05). Anxiety was significantly associated with delayed symptom recovery (adjusted HR 3.34, 95% CI 2.18 to 5.12), return to school (adjusted HR 2.01, 95% CI 1.59 to 2.53) and return to physical activity (adjusted HR 1.88, 95% CI 1.49 to 2.37). CONCLUSIONS: Pre-existing anxiety disorders were associated with more severe symptomology and prolonged recovery after concussion in children and adolescents. These results can be referenced by providers to manage patients' recovery expectations.

Correction to: Sleep-disordered breathing: an under-recognized problem in infants with myelomeningocele defects regardless of timing of repair.

Since the online publication of this article, the authors have noted an error in Table 1. The correct table is provided. The authors apologise for any inconvenience caused.

Sleep-disordered breathing: an under-recognized problem in infants with myelomeningocele defects regardless of timing of repair.

OBJECTIVE: To evaluate the prevalence of sleep-disordered breathing (SDB) in infants with myelomeningocele (MMC) and the effect of fetal repair on SDB. STUDY DESIGN: We conducted a retrospective cohort study of infants with MMC admitted to a pediatric hospital (2007-2017). Pneumocardiogram (PCG) results, a measure of SDB, were compared between infants who underwent fetal MMC (fMMC) versus postnatal MMC repair. RESULT: Of 118 eligible infants, 17 (14%) underwent fetal repair. Of these, 106 (90%) had PCG studies; abnormal PCG results were common but not different between fMMC (n = 12, 92%) and postnatal repair groups (n = 72, 77%, p = 0.22). Among infants with abnormal results, central apnea events >10 s (median 16 vs. 3 events, p = 0.02) and percentage of time spent in periodic breathing (median 15% vs. 7%, p = 0.01) were greater in the fMMC group. CONCLUSION: SDB was common among all MMC infants regardless of repair timing, indicating a need for standard screening recommendations.

Unintentional Injuries in Primary and Secondary Schools in the United States, 2001-2013.

BACKGROUND: Unintentional injuries are the leading cause of youth morbidity. However, limited nationally representative data are available to characterize the occurrence of unintentional injuries at US schools. Given this paucity, we characterized secular trends in unintentional injuries at schools that led to emergency department (ED) visits. METHODS: A retrospective analysis of the National Electronic Injury Surveillance System-All Injury Program from 2001 to 2013 compared injuries occurring at schools to injuries occurring elsewhere in youth ages 5-18 years. Incidence rates were calculated using weighted frequency estimates as numerators and US population estimates as denominators. RESULTS: School injuries accounted for 21% of unintentional injury-related ED visits, with an estimated annual incidence rate of 1385 injuries per 100,000 5- to 18-year-olds. Middle school-aged youth (10-13 years) had the highest annual incidence rate (1640 per 100,000 youth) compared with younger and older counterparts. School injuries were more likely to be due to sports/recreation than nonschool injuries (55% vs 41%, p < .0001). Importantly, no detectable change in incidence rates of school injuries between 2001 and 2013 was found (p = .11). CONCLUSIONS: Stagnant annual incidence rates of unintentional injuries at schools and large numbers of school-based injuries demonstrate that school-based injuries are a notable opportunity for future prevention efforts.

Cranial Rhabdomyosarcoma Masquerading as Infectious Mastoiditis: Case Report and Literature Review.

BACKGROUND: Rhabdomyosarcoma originating in the mastoid is rare and may be misdiagnosed as an infectious mastoiditis due to overlapping clinical and imaging features. We aimed to identify distinguishing characteristics to facilitate earlier diagnosis and treatment. METHOD: Here we describe a case report and a systematic review of 23 reports describing previous cases of mastoid rhabdomyosarcoma. We compare these patients to a systematic review of patients with infectious mastoiditis and identify distinguishing clinical features. RESULTS: A total of 43 patients with rhabdomyosarcoma of the mastoid were identified and compared with patients with mastoiditis. Rhabdomyosarcoma patients were more likely to present with a mass (86%) or cranial nerve dysfunction (83.7%), while mastoiditis patients were more likely to have fever (72.4%), pain (48.2%), and present at a younger age (4.4 vs. 6.1 years). The average lifespan with rhabdomyosarcoma of the mastoid was 7.1 months after diagnosis, with 41.7% of patients alive at the time of report. CONCLUSIONS: Based on abstracted and aggregated information, we identified unique features observed more frequently in each of rhabdomyosarcoma and mastoiditis. These predictive features allow for the differentiation of each diagnosis and avoid the delay of proper treatment.

Emergency Department Use of Neuroimaging in Children and Adolescents Presenting with Headache.

OBJECTIVES: To evaluate emergency department use and outcomes of neuroimaging for headache in a free-standing children's hospital system. STUDY DESIGN: We prospectively enrolled children aged 6-18 years who presented to the emergency department with a chief complaint of headache from September 2015 to September 2016. Standardized data collection was performed in real time, including telephone follow-up as needed, and imaging outcome was determined through a chart review. Using multivariable logistic regression, we estimated the associations between clinically important patient characteristics and neuroimaging. RESULTS: Of 294 enrolled patients, 53 (18%) underwent neuroimaging (computed tomography or magnetic resonance imaging) and 2 (0.7%) had clinically important intracranial findings. Presenting with abnormal neurologic examination findings (OR, 11.55; 95% CI, 3.24-41.22), no history of similar headaches (OR, 2.13; 95% CI, 1.08-4.18), and white race (OR, 3.04; 95% CI, 1.51-6.12) were significantly associated with an increased odds of undergoing imaging in multivariable regression models. CONCLUSIONS: Our observed emergency department imaging rate was 26.5 times higher than our positive result rate, suggesting there is room to decrease unnecessary neuroimaging. Associations for abnormal examination and new headache type are consistent with the American Academy of Neurology clinical imaging recommendations. The increased odds of imaging white patients suggests bias that should be addressed. The low rate of positive findings supports the need for an evidence-based clinical decision tool for neuroimaging in the acute care setting.

Multiple pilomatrixomas in a survivor of WNT-activated medulloblastoma leading to the discovery of a germline APC mutation and the diagnosis of familial adenomatous polyposis.

Because children diagnosed with WNT-activated medulloblastoma have a 10-year overall survival rate of 95%, active long-term follow-up is critically important in reducing mortality from other causes. Here, we describe an 11-year-old adopted female who developed multiple pilomatrixomas 3 years after diagnosis of WNT-activated medulloblastoma, an unusual finding that prompted deeper clinical investigation. A heterozygous germline APC gene mutation was discovered, consistent with familial adenomatous polyposis. Screening endoscopy revealed numerous precancerous polyps that were excised. This case highlights the importance of long-term follow-up of pediatric cancer survivors, including attention to unexpected symptoms, which might unveil an underlying cancer predisposition syndrome.

Soluble MICA is elevated in pancreatic cancer: Results from a population based case-control study.

Pancreatic cancer is diagnosed at a late stage and has one of the highest cancer mortality rates in the United States, creating an urgent need for novel early detection tools. A candidate biomarker for use in early detection is the soluble MHC class I-related chain A (s-MICA) ligand, which pancreatic tumors shed to escape immune detection. The objective of this study was to define the association between s-MICA levels and pancreatic cancer, in a population-based case-control study. S-MICA was measured in 143 pancreatic cancer cases and 459 controls. Unconditional logistic regression was used to calculate odds ratio (OR) for pancreatic cancer and 95% confidence intervals (CI). There was a positive association between increasing s-MICA levels and pancreatic cancer: compared to the lowest tertile, the ORs for pancreatic cancer were 1.25 (95%CI: 0.75-2.07) and 2.10 (95%CI: 1.29-3.42) in the second and highest tertiles, respectively (P-trend = 0.02). Our study supports previous work demonstrating a positive association between plasma s-MICA levels and pancreatic cancer.

Circulating Beta-2 Microglobulin and Risk of Cancer: The Atherosclerosis Risk in Communities Study (ARIC).

BACKGROUND: Serum ß-2 microglobulin (B2M), a major histocompatibility complex class I molecule that is a biomarker of kidney filtration and increased cell turnover, is elevated at the time of diagnosis in hematological and some solid cancers. However, serum B2M was not examined prospectively as a marker for cancer risk. We hypothesized that in a population without a prior cancer diagnosis, serum B2M is associated with risk of cancer (n = 2,436), including colorectal (n = 255), lung (n = 298), breast (n = 424), and prostate (n = 524) cancers, and hematological (n = 176) malignancies. METHODS: The analytical cohort (n = 12,300) was followed for incident cancers from 1990 through 2006. B2M (range, 0.9-57.8 mg/L) was measured in stored serum collected in 1990-1992. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals for cancer incidence and mortality in relation to quartiles of B2M. RESULTS: Adjusting for age, sex, race, center, education, body mass index, smoking, aspirin, and hormone therapy (in women) and comparing highest to lowest B2M quartiles, HRs were 1.25 (1.06-1.47; Ptrend = 0.002) for total cancer risk and 2.21 (1.32-3.70; Ptrend=0.001) for colorectal cancer risk, with similar HRs for colon and rectal cancers. These associations remained after adjustment for an inflammatory biomarker, C-reactive protein, and after excluding the first three years of follow-up. Significant associations were also observed for mortality from total, lung, and hematological cancers. CONCLUSIONS: These findings provide the first evidence that higher serum B2M is associated with increased colorectal cancer risk. IMPACT: This study supports B2M as a potential biomarker for colorectal cancer risk. Cancer Epidemiol Biomarkers Prev; 25(4); 657-64. ©2016 AACR.

Family history of cancer and risk of pediatric and adolescent Hodgkin lymphoma: A Children's Oncology Group study.

Family history of lymphoid neoplasm (LN) is a strong and consistently observed Hodgkin lymphoma (HL) risk factor, although it has been only marginally examined in pediatric/adolescent patients. Here, healthy control children identified by random digit dialing were matched on sex, race/ethnicity and age to HL cases diagnosed at 0-14 years at Children's Oncology Group institutions in 1989-2003. Detailed histories were captured by structured telephone interviews with parents of 517 cases and 783 controls. Epstein-Barr virus (EBV) RNA detection was performed for 355 available case tumors. Two analytic strategies were applied to estimate associations between family cancer history and pediatric/adolescent HL. In a standard case-control approach, multivariate conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (CIs). In a reconstructed cohort approach, each relative was included as a separate observation, and multivariate proportional hazards regression was used to produce hazard ratios (HRs) and 95% CIs. Using the latter, pediatric/adolescent HL was associated with a positive family history (HR = 1.20, 95% CI: 1.06-1.36), particularly early-onset cancers (HR = 1.30, 95% CI: 1.06-1.59) and those in the paternal lineage (HR = 1.38, 95% CI: 1.16-1.65), with a suggested association for LN in first-degree relatives (HR = 3.61, 95% CI: 0.87-15.01). There were no discernable patterns for EBV+ versus EBV- HL. The clustering of LN within pedigrees may signal shared genetic susceptibility or common environmental exposures. Heritable genetic risk variants have only recently begun to be discovered, however. These results are consistent with other studies and provide a compelling rationale for family-based studies to garner information about genetic susceptibility to HL.

Immune-related conditions and acute leukemia in children with Down syndrome: a Children's Oncology Group report.

BACKGROUND: Children with Down syndrome have unique immune profiles and increased leukemia susceptibility. METHODS: Mothers of 158 children with Down syndrome diagnosed with acute leukemia at 0 to 19 years in 1997 to 2002 and 173 children with Down syndrome but no leukemia were interviewed. Associations were evaluated via multivariable unconditional logistic regression. RESULTS: No associations were detected for asthma, eczema, allergies, or hypothyroidism. Diabetes mellitus associated with leukemia (OR = 9.23; 95% confidence interval 2.33-36.59); however, most instances occurred concurrent with or after the leukemia diagnosis. CONCLUSIONS AND IMPACT: Children with Down syndrome who develop leukemia have increased diabetes risk, likely due to treatment and underlying susceptibility factors.

The Children's Oncology Group Childhood Cancer Research Network (CCRN): case catchment in the United States.

BACKGROUND: The Childhood Cancer Research Network (CCRN) was established within the Children's Oncology Group (COG) in July 2008 to provide a centralized pediatric cancer research registry for investigators conducting approved etiologic and survivorship studies. The authors conducted an ecological analysis to characterize CCRN catchment at >200 COG institutions by demographic characteristics, diagnosis, and geographic location to determine whether the CCRN can serve as a population-based registry for childhood cancer. METHODS: During 2009 to 2011, 18,580 US children newly diagnosed with cancer were registered in the CCRN. These observed cases were compared with age-specific, sex-specific, and race/ethnicity-specific expected numbers calculated from Surveillance, Epidemiology, and End Results (SEER) Program cancer incidence rates and 2010 US Census data. RESULTS: Overall, 42% of children (18,580 observed/44,267 expected) who were diagnosed with cancer at age <20 years were registered in the CCRN, including 45%, 57%, 51%, 44%, and 24% of those diagnosed at birth, ages 1 to 4 years, ages 5 to 9 years, ages 10 to 14 years, and ages 15 to 19 years, respectively. Some malignancies were better represented in the CCRN (leukemia, 59%; renal tumors, 67%) than others (retinoblastoma, 34%). There was little evidence of differences by sex or race/ethnicity, although rates in nonwhites were somewhat lower than rates in whites. CONCLUSIONS: Given the low observed-to-expected ratio, it will be important to identify challenges and barriers to registration to improve case ascertainment, especially for rarer diagnoses and older age groups; however, it is encouraging that some diagnoses in younger children are fairly representative of the population. Overall, the CCRN is providing centralized, real-time access to cases for research and could be used as a model for other national cooperative groups.

Allergic diseases and risk of hematopoietic malignancies in a cohort of postmenopausal women: a report from the Iowa Women's Health Study.

BACKGROUND: Allergic diseases signify immune dysregulation attributable to underlying genetics and environmental exposures. Associations between various allergies and hematopoietic cancers have been observed, albeit inconsistently; however, few prospective studies have examined the risk, and even fewer among older adults. METHODS: We examined risk of incident hematopoietic cancers in those reporting allergic diseases in a population-based cohort of 22,601 older women (Iowa Women's Health Study). Self-reported allergic status, including asthma, hay fever, eczema, and/or other allergies, was determined via questionnaire in 1997 (mean age, 72 years; range, 63-81 years). Incident cancers were ascertained by linkage with the Iowa Cancer Registry from 1997 to 2011. Cox proportional hazards regression was performed to estimate multivariate-adjusted HR and 95% confidence intervals (CI) for myeloid (N = 177) and lymphoid (N = 437) malignancies, respectively. RESULTS: Allergic diseases were not associated with risk of myeloid (HR, 1.00; 95% CI, 0.72-1.37) or lymphoid (HR, 0.99; 95% CI, 0.81-1.22) malignancies overall, or for most allergic and malignant subtypes examined. Self-reported asthma was positively associated with development of myelodysplastic syndrome (MDS; HR, 2.00; 95% CI, 0.93-4.32). In addition, there was a 30% to 40% decrease in risk of both lymphoid and myeloid cancers in those reporting rural residences but no association in those reporting urban residences; the interaction between residence and allergy was statistically significant for lymphoid malignancies (Pinteraction = 0.05). CONCLUSIONS AND IMPACT: These results suggest that asthma may contribute to the pathogenesis of MDS, a finding consistent with the chronic antigen stimulation hypothesis. Susceptibility differences by location of residence are concordant with the hygiene hypothesis and merit additional exploration.