Estrogen-modulating treatment among mid-life women and COVID-19 morbidity and mortality: a multiregister nationwide matched cohort study in Sweden.

BACKGROUND: It has been repeatedly shown that men infected by SARS-CoV-2 face a twofold higher likelihood of dying, being hospitalized or admitted to the intensive care unit compared to women, despite taking into account relevant confounders. It has been hypothesized that these discrepancies are related to sex steroid hormone differences with estrogens being negatively correlated with disease severity. The objective of this study was therefore to evaluate COVID-19-related mortality and morbidity among peri- and postmenopausal women in relation to estrogen-containing menopause hormonal treatments (MHT). METHODS: This is a national register-based matched cohort study performed in Sweden between January 1 to December 31, 2020. Study participants comprised women over the age of 53 years residing in Sweden. Exposure was defined as prescriptions of local estrogens, systemic estrogens with and without progestogens, progestogens alone, or tibolone. MHT users were then compared with a matched cohort of non-users. The primary outcome consisted of COVID-19 mortality, whereas the secondary outcomes included inpatient hospitalizations/outpatient visits and confirmed SARS-CoV-2 infection. Multivariable adjusted Cox regression-derived hazard ratios (HRs) were calculated. RESULTS: Use of systemic estrogens alone is associated with increased COVID-19 mortality among older women (aHR 4.73, 1.22 to 18.32), but the association is no longer significant when discontinuation of estrogen use is accounted for. An increased risk for COVID-19 infection is further observed for women using combined systemic estrogens and progestogens (aHR 1.06, 1.00 to 1.13) or tibolone (aHR 1.21, 1.01 to 1.45). Use of local estrogens is associated with an increased risk for COVID-19-related death (aHR 2.02,1.45 to 2.81) as well as for all secondary outcomes. CONCLUSIONS: Systemic or local use of estrogens does not decrease COVID-19 morbidity and mortality to premenopausal background levels. Excess risk for COVID-19 morbidity and mortality was noted among older women and those discontinuing systemic estrogens. Higher risk for death was also noted among women using local estrogens, for which non-causal mechanisms such as confounding by comorbidity or frailty seem to be the most plausible underlying explanations. TRIAL REGISTRATION DETAILS: Not applicable.

Fertility status in childhood cancer survivors of hematological malignancies: a systematic review.

Stunning advances in treatment modalities implemented in children with hematological malignancies have led to 5-year overall survival rates exceeding 85%. However, this growing population of long-term survivors has raised significant concerns about their fertility status throughout adulthood, while specific treatment- and non-treatment-related factors appear to possibly affect fertility through distinct mechanisms. We aimed to comprehensively review the published literature on the association between treatment-related factors and risk of impaired fertility in childhood hematological cancer survivors. We searched PubMed up to March 2021 to identify eligible studies published during the last two decades. A narrative synthesis of the results was performed, although no meta-analysis was feasible due to the small number of studies and the large heterogeneity of evidence. Five studies on 2020 survivors of childhood leukemia were deemed eligible. The qualitative data synthesis showed significant fertility deficits in survivors treated with cranial radiotherapy and chemotherapy for childhood leukemia. Two studies examined biochemical measures of reduced ovarian reserve, providing some evidence that the levels of anti-Müllerian hormone can be used as a proxy for diminished ovarian reserve. The current findings should facilitate the delivery of age- and gender-appropriate interventions to optimize reproductive outcomes in childhood hematological cancer survivors.

Earlier Age at Menarche Is Associated with Body Fat and Negative Body Image in Adult Life.

Earlier age at menarche is one of the well-documented antecedents of a range of adverse health effects in adulthood including obesity and psychopathological effects. Yet, few researchers have examined the potential association of menarcheal age with body fat distribution, self-perception, and body image. We retrospectively tested a sample (N = 392) of adult women (18-80 years) to examine the associations of age at menarche with body composition and body image indices. Analyses of covariance and multivariable logistic and linear regression were fitted adjusting for age, physical activity level, smoking, and alcohol consumption. Further adjustment was made for body mass index (BMI) and percentage of fat mass. Earlier age at menarche was associated with slightly increased odds of higher BMI and abdominal fat percentage; of note is the positive correlation with lower body composition indices including hip and calf circumferences/skinfolds. Additionally, earlier age at menarche was associated with higher scores in the negative body image scales, namely overweight preoccupation and self-classified weight, whereas lower risks were found for higher scores in the positive body image scales, namely appearance evaluation and body area satisfaction scales. These findings remained significant after correcting for body fat percentage. The present results showed positive associations for earlier age at menarche with gross indices of obesity with the associations mainly confined to distribution of body fat in the lower part of the body, whereas an increased risk of negative body image was also found. Future research could refine our understanding of the biological and psychological mechanisms underlying these associations.

Survival patterns of childhood neuroblastoma: an analysis of clinical data from Southern-Eastern European countries.

The prognosis of children with neuroblastoma (NBL) can be dismal with significant variations depending on the stage and biology of the tumor. We assessed the event-free (EFS) and overall (OS) survival using harmonized data from three Southern-Eastern European (SEE) countries. Data for 520 incident NBL cases (2009-2018) were collected from Greece, Slovenia and Russia. Kaplan-Meier curves were fitted, and EFS/OS were derived from Cox proportional models by study variables including the protocol-based risk-group (low/observation, intermediate, high). Over one-third of cases were coded in the high-risk group, of which 23 children (4.4%) received treatment with anti-ganglioside 2 (GD2) mAb. Survival rates were inferior in older (OS 5-year; 1.5-4.9 years: 61%; EFS 5-year; 1.5-4.9 years: 48%) compared to children younger than 1.5 years (OS 5-year; <1.5 years: 91%; EFS 5-year; <1.5 years: 78%). Predictors of poor OS included stage 4 (hazard ratio, HR OS : 18.12, 95% confidence intervals, CI: 3.47-94.54), N-myc amplification (HR OS : 2.16, 95% CI: 1.40-3.34), no surgical excision (HR OS : 3.27, 95% CI: 1.91-5.61) and relapse/progression (HR OS : 5.46, 95% CI: 3.23-9.24). Similar unfavorable EFS was found for the same subsets of patients. By contrast, treatment with anti-GD2 antibody in high-risk patients was associated with decreased risk of death or unfavorable events (HR OS : 0.11, 95% CI: 0.02-0.79; HR EFS : 0.19, 95% CI: 0.07-0.52). Our results confirm the outstanding prognosis of the early NBL stages, especially in children <1.5 years, and the improved outcomes of the anti-GD2 treatment in high-risk patients. Ongoing high-quality clinical cancer registration is needed to ensure comparability of survival across Europe and refine our understanding of the NBL biology.

The Interplay of Cesarean-Section Delivery and First-Birth Order as Risk Factors in Acute Lymphoblastic Leukemia.

BACKGROUND: Childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has been associated with early-life exposures, including birth by cesarean section (C-section), and a deficit of social exposure (first child). These exposures as proxies for microbiome acquisition in infancy are essential to prime the immune system and restrain later dysregulated immune responses that can trigger ALL in susceptible individuals. We tested risk factors pertaining to immune stimulation that may impact BCP-ALL development. METHODS: Cases comprised 1,126 children (0-12 years) with ALL (BCP-ALL: 78.5%) from the EMiLI study group in Brazil (2002-2020). Age- and sex-matched controls (n = 2,252) were randomly selected from healthy children whose mothers participated in the National Placental and Umbilical Cord Blood Bank donation. Multiple logistic regression was run fitted and adjusted for selected covariates models. RESULTS: C-section delivery was associated with increased risk for ALL [odds ratio (OR) ALL: 1.10; 95% confidence intervals (CI), 1.04-1.15; ORBCP-ALL: 1.09; 95% CI, 1.03-1.14], as well as being the firstborn child. Interaction analysis showed a significant effect of first birth on the observed C-section associations (P < 0.0001). Indeed, high-risk children, namely, firstborn children delivered via C-section were at increased risk for ALL (OR: 2.33; 95% CI, 2.40-4.84) compared with non-first, vaginally born children. An increased risk was found for firstborn children delivered by C-section and non-breastfed with ALL (ORALL: 2.32; 95% CI, 1.27-4.24; ORBCP-ALL: 2.37; 95% CI, 1.18-4.76). CONCLUSIONS: Our observations are in accord with the prediction that exposures determining microbiome composition and adrenal pathway in infancy contribute to the risk of BCP-ALL. IMPACT: These findings encourage the exploration of potential preventive interventions. See related commentary by Wiemels and Gallant, p. 292.

Prevalence of visceral leishmaniasis among people with HIV: a systematic review and meta-analysis.

Leishmaniasis is a parasitic infection expressing different clinical phenotypes. Visceral leishmaniasis (VL) is considered an opportunistic infection among people with human immunodeficiency virus (HIV). The objective of this review was to identify published data on the prevalence of Leishmania spp. infection among PWH and to define particular determinants that affect critically the epidemiological characteristics of VL-HIV coinfection and, potentially, its burden on public health. Two independent reviewers conducted a systematic literature search until June 30, 2022. Meta-analyses were conducted using random-effects models to calculate the summary prevalence and respective 95% confidence intervals (CI) of leishmaniasis among PWH. Meta-regression analysis was performed to investigate the impact of putative effect modifiers, such as the mean CD4 cell count, on the major findings. Thirty-four studies were eligible, yielding a summary prevalence of 6% (95%CI, 4-11%) for leishmaniasis (n = 1583) among PWH (n = 85,076). Higher prevalence rates were noted in Asia (17%, 95%CI, 9-30%) and America (9%, 95%CI, 5-17%) than in Europe (4%, 95%CI, 2-8%). Prevalence rates were significantly mediated by the age, sex, and CD4 cell count of participants. Heterogeneity remained significant in all meta-analyses (p < 0.0001). In the majority of included studies, people were coinfected with HIV and Leishmania species associated with VL, as opposed to those associated with cutaneous leishmaniasis. No sign of publication bias was shown (p = 0.06). Our summary of published studies on leishmaniasis among PWH is important to provide prevalence estimates and define potential underlying factors that could guide researchers to generate and further explore specific etiologic hypotheses.

Central nervous system cystic echinococcosis: a systematic review.

Central nervous system (CNS) cystic echinococcosis (CE) is a rare disease caused by Echinococcus which especially exists in agricultural endemic areas. This condition is more frequent in the pediatric and adolescent population and it can be associated with hydatid cyst in other localizations. A literature search was conducted up to April 28, 2021 by two independent reviewers. This study focused on clinical, imaging, therapeutic features as well as on complications of CNS CE among children and adults. Fifteen studies from seven different countries were included. A significant prevalence in males (ranging from 51% to 100%) was observed with an average rate of 60%. CNS CE was mainly single and located in the parietal region. The predominant symptoms were those of increased intracranial pressure. All patients were treated surgically, and the most common post-surgical complication was cyst rupture (prevalence: [3.3-37.5%], average: 12.9%). Furthermore, the outcomes were worse amongst patients with cyst ruptures and multiple recurrences. The average proportion of deaths due to CNS CE was 5.6% (range: 2.5-14.8%). This review highlights the necessity of including CNS CE in the differential diagnosis of patients with cystic lesions, especially in those residing in endemic areas. Early gross total cyst removal is the mainstay of treatment yielding the best outcomes.

Nutritional Status at Diagnosis as Predictor of Survival from Childhood Cancer: A Review of the Literature.

Few studies so far have examined the impact of nutritional status on the survival of children with cancer, with the majority of them focusing on hematological malignancies. We summarized published evidence reporting the association of nutritional status at diagnosis with overall survival (OS), event-free survival (EFS), relapse, and treatment-related toxicity (TRT) in children with cancer. Published studies on children with leukemia, lymphoma, and other solid tumors have shown that both under-nourished and over-nourished children at cancer diagnosis had worse OS and EFS. Particularly, the risk of death and relapse increased by 30-50% among children with leukemia with increased body mass index at diagnosis. Likewise, the risk of TRT was higher among malnourished children with osteosarcoma and Ewing sarcoma. Nutritional status seems to play a crucial role in clinical outcomes of children with cancer, thus providing a significant modifiable prognostic tool in childhood cancer management. Future studies with adequate power and longitudinal design are needed to further evaluate the association of nutritional status with childhood cancer outcomes using a more standardized definition to measure nutritional status in this population. The use of new technologies is expected to shed further light on this understudied area and give room to person-targeted intervention strategies.

Incidence patterns of childhood non-Wilms renal tumors: Comparing data of the Nationwide Registry of Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST), Greece, and the Surveillance, Epidemiology, and End Results Program (SEER), USA.

BACKGROUND: We used, for the first time, data registered in the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST)-Greece to estimate incidence/time trends of the rare childhood (0-14 years) non-Wilms tumors (non-WT), and compared the results of malignant non-WT to those from the Surveillance, Epidemiology, and End Results Program (SEER)-USA. METHODS: Fifty-five cases (n = 33 malignant-only) were extracted from NARECHEM-ST (2001-2020) and 332 malignant cases from SEER (1990-2017). To allow between-country comparisons, age-standardized incidence rates (AIR) of malignant-only non-WT were calculated, and temporal trends were evaluated using Poisson and joinpoint regressions. RESULTS: In NARECHEM-ST, malignant and non-malignant non-WT accounted for 22.6% of all renal tumors. Among malignant tumors, the AIR was 1.0/106 children in Greece, similar to that calculated for SEER, USA (AIR=0.9/106). The proportion of infant malignant and non-malignant non-WT was 27% (20% before 6 months) in NARECHEM-ST. Most common non-WT in Greece were congenital mesoblastic nephromas (CMN) diagnosed mainly in infancy (CIR=7.2/106). The proportion of infant malignant non-WT was 20% in SEER (AIRinfancy=2.5/106), mainly attributed to rhabdoid tumors (CIR=1.6/106). The male-to-female (M:F) ratio of malignant non-WT was 0.9 in NARECHEM-ST vs. 1.2 in SEER, whereas boys outnumbered girls with clear cell sarcoma in NARECHEM-ST (M:F=4.0). Lastly, significantly increasing trends in incidence rates were noted in NARECHEM-ST [+ 6.8%, 95% confidence intervals (CI): 0.5, 13.3] and in SEER (+7.3%, 95%CI: 5.6, 9.0). CONCLUSIONS: Observed incidence, time trends and sociodemographic variations of non-WT may reflect differential registration practices and healthcare delivery patterns including differences regarding surveillance, coding and treatment practices.

Maternal lifestyle factors and risk of neuroblastoma in the offspring: A meta-analysis including Greek NARECHEM-ST primary data.

The etiology of childhood neuroblastoma remains largely unknown. In this systematic review and meta-analysis, we summarized and quantitatively synthesized published evidence on the association of maternal modifiable lifestyle factors with neuroblastoma risk in the offspring. We searched MEDLINE up to December 31, 2020 for eligible studies assessing the association of maternal smoking, alcohol consumption and nutritional supplementation during pregnancy with childhood (0-14 years) neuroblastoma risk. Random-effects models were run, and summary odds ratios (OR) and 95% confidence intervals (95% CI) on the relevant associations were calculated, including estimates derived from primary data (n = 103 cases and n = 103 controls) of the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) case control study (2009-2017) in Greece. Twenty-one eligible studies amounting 5163 cases participating in both case-control and cohort/linkage studies were included in the meta-analysis. Maternal smoking and alcohol consumption were not statistically significantly associated with neuroblastoma risk (summary ORsmoking: 1.08, 95% CI: 0.96-1.22, I2 =12.0%, n = 17 studies; summary ORalcohol: 1.01, 95% CI: 0.82-1.18, I2 =0.0%, n = 8 studies). By contrast, maternal vitamin intake during pregnancy was associated with significantly lower neuroblastoma risk (summary OR: 0.57, 95% CI: 0.34-0.95, I2 =58.9%, n = 4 studies). The results of the largest to-date meta-analysis point to an inverse association between vitamin intake during pregnancy and childhood neuroblastoma risk. Future longitudinal studies are needed to confirm and further specify these associations as to guide preventive efforts on modifiable maternal risk factors of childhood neuroblastoma.

Exposure to pesticides and childhood leukemia risk: A systematic review and meta-analysis.

Despite the abundance of epidemiological evidence concerning the association between pesticide exposure and adverse health outcomes including acute childhood leukemia (AL), evidence remains inconclusive, and is inherently limited by heterogeneous exposure assessment and multiple statistical testing. We performed a literature search of peer-reviewed studies, published until January 2021, without language restrictions. Summary odds ratios (OR) and 95% confidence intervals (CI) were derived from stratified random-effects meta-analyses by type of exposure and outcome, exposed populations and window of exposure to address the large heterogeneity of existing literature. Heterogeneity and small-study effects were also assessed. We identified 55 eligible studies (n = 48 case-control and n = 7 cohorts) from over 30 countries assessing >200 different exposures of pesticides (n = 160,924 participants). The summary OR for maternal environmental exposure to pesticides (broad term) during pregnancy and AL was 1.88 (95%CI: 1.15-3.08), reaching 2.51 for acute lymphoblastic leukemia (ALL; 95%CI: 1.39-4.55). Analysis by pesticide subtype yielded an increased risk for maternal herbicide (OR: 1.41, 95%CI: 1.00-1.99) and insecticide (OR: 1.60, 95%CI: 1.11-2.29) exposure during pregnancy and AL without heterogeneity (p = 0.12-0.34). Meta-analyses of infant leukemia were only feasible for maternal exposure to pesticides during pregnancy. Higher magnitude risks were observed for maternal pesticide exposure and infant ALL (OR: 2.18, 95%CI: 1.44-3.29), and the highest for infant acute myeloid leukemia (OR: 3.42, 95%CI: 1.98-5.91). Overall, the associations were stronger for maternal exposure during pregnancy compared to childhood exposure. For occupational or mixed exposures, parental, and specifically paternal, pesticide exposure was significantly associated with increased risk of AL (ORparental: 1.75, 95%CI: 1.08-2.85; ORpaternal: 1.20, 95%CI: 1.07-1.35). The epidemiological evidence, supported by mechanistic studies, suggests that pesticide exposure, mainly during pregnancy, increases the risk of childhood leukemia, particularly among infants. Sufficiently powered studies using repeated biomarker analyses are needed to confirm whether there is public health merit in reducing prenatal pesticide exposure.

Overall and event-free survival of childhood lymphoma in Greece: analysis of harmonized clinical data over a 24-year active registration period.

We assessed event-free (EFS) and overall (OS) survival in 676 incident cases of childhood Hodgkin (HL) and non-Hodgkin (NHL) lymphoma actively registered in Greece (1996-2019). HL-OS5-year was 96% and NHL-OS5-year 85%, whereas HL-EFS5-year was 86% and NHL-EFS5-year was 81%, notably similar to the respective OS rates (HL: 95%, NHL: 85%) in developed countries. For HL, older age at diagnosis, high maternal education and close proximity to treatment centers were linked to remarkably favorable outcomes. By contrast, stage IV patients showed worse OS and EFS. HL patients with low levels of hemoglobin were associated with worse EFS (hazard ratio: 2.81, 95% confidence intervals: 1.09-7.22). OS (76%) and EFS (73%) were poor among high-risk NHL patients and those with increased LDH (71%). The identified predictors of poor disease outcome point to the need for intensification of individualized treatments. Ongoing clinical cancer registration entailing clinical components could contribute to use of state-of-the-art treatments.

Deep Brain Stimulation-Related Surgical Site Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: Over the last decades, the increased use of deep brain stimulation (DBS) has raised concerns about the potential adverse health effects of the treatment. Surgical site infections (SSIs) following an elective surgery remain a major challenge for neurosurgeons. Few studies have examined the prevalence and risk factors of DBS-related complications, particularly focusing on SSIs. OBJECTIVES: We systematically searched published literature, up to June 2020, with no language restrictions. MATERIALS AND METHODS: Eligible were studies that examined the prevalence of DBS-related SSIs, as well as studies that examined risk and preventive factors in relation to SSIs. We extracted information on study characteristics, follow-up, exposure and outcome assessment, effect estimate and sample size. Summary odds ratios (sOR) and 95% confidence intervals (CI) were calculated from random-effects meta-analyses; heterogeneity and small-study effects were also assessed. RESULTS: We identified 66 eligible studies that included 12,258 participants from 27 countries. The summary prevalence of SSIs was estimated at 5.0% (95% CI: 4.0%-6.0%) with higher rates for dystonia (6.5%), as well as for newer indications of DBS, such as epilepsy (9.5%), Tourette syndrome (5.9%) and OCD (4.5%). Similar prevalence rates were found between early-onset and late-onset hardware infections. Among risk and preventive factors, the perioperative implementation of intra-wound vancomycin was associated with statistically significantly lower risk of SSIs (sOR: 0.26, 95% CI: 0.09-0.74). Heterogeneity was nonsignificant in most meta-analyses. CONCLUSION: The present study confirms the still high prevalence of SSIs, especially for newer indications of DBS and provides evidence that preventive measures, such as the implementation of topical vancomycin, seem promising in reducing the risk of DBS-related SSIs. Large clinical trials are needed to confirm the efficacy and safety of such measures.

Survival and prognostic factors for childhood malignant liver tumors: analysis of harmonized clinical data.

BACKGROUND: Despite overall striking advances in survival of childhood liver tumors, outcomes remain poor for specific patient segments. We aimed to assess overall survival (OS) of this rare disease and evaluate the generalizability of prognostic variables included in international collaborative systems using, for the first time, harmonized clinical data from two geographically different cohorts (Greece and Moscow). METHODS: Data for children (0-14 years) with liver tumors were retrieved from two Southern-Eastern European areas (Greece; 2001-2019 and Moscow; 2012-2019). Kaplan-Meier curves were constructed, and OS values were derived from Cox proportional models controlling for study variables. RESULTS: A total of 171 newly diagnosed cases (54.4% males) were included. The OS5-year exceeded 80% in patients <5 years, reaching 85% among 133 patients with hepatoblastoma (HBL). By contrast, children with other than HBL histology, especially hepatocellular carcinoma (HCC) had significantly worse prognosis (hazard ratio [HR] HCC: 7.09, 95% confidence intervals [CI]: 2.56-19.65; HR other liver tumors: 5.18; 95%CI: 2.15-12.49). The OS5-year was poorer (40%-60%) in patients with extensive local, metastatic or relapsed disease. By contrast, a significantly lower risk of death was shown in case of microscopically margin-negative resection (HR: 0.06, 95%CI: 0.02-0.17) and liver transplantation (HR: 0.12, 95% CI: 0.02-0.63) compared to the non- operated group. CONCLUSIONS: Outcomes of patients with liver tumors registered in two SEE areas were comparable to those reported by major collaborative trials. Ongoing clinical cancer registration could facilitate comparison of outcomes between different study groups in order to shape state of the art of treatment.

Age-, sex- and disease subtype-related foetal growth differentials in childhood acute myeloid leukaemia risk: A Childhood Leukemia International Consortium analysis.

AIM: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases. METHODS: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed. RESULTS: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers. CONCLUSIONS: Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.

Birth seasonality of childhood central nervous system tumors: Analysis of primary data from 16 Southern-Eastern European population-based registries.

Season of birth, a surrogate of seasonal variation of environmental exposures, has been associated with increased risk of several cancers. In the context of a Southern-Eastern Europe (SEE) consortium, we explored the potential association of birth seasonality with childhood (0-14 years) central nervous system (CNS) tumors. Primary CNS tumor cases (n = 6,014) were retrieved from 16 population-based SEE registries (1983-2015). Poisson regression and meta-analyses on birth season were performed in nine countries with available live birth data (n = 4,987). Subanalyses by birth month, age, gender and principal histology were also conducted. Children born during winter were at a slightly increased risk of developing a CNS tumor overall [incidence rate ratio (IRR): 1.06, 95% confidence intervals (CI): 0.99-1.14], and of embryonal histology specifically (IRR: 1.13, 95% CI: 1.01-1.27). The winter peak of embryonal tumors was higher among boys (IRR: 1.24, 95% CI: 1.05-1.46), especially during the first 4 years of life (IRR: 1.33, 95% CI: 1.03-1.71). In contrast, boys <5 years born during summer seemed to be at a lower risk of embryonal tumors (IRR: 0.73, 95% CI: 0.54-0.99). A clustering of astrocytomas was also found among girls (0-14 years) born during spring (IRR: 1.23, 95% CI: 1.03-1.46). Although the present exploratory results are by no means definitive, they provide some indications for age-, gender- and histology-related seasonal variations of CNS tumors. Expansion of registration and linkage with cytogenetic reports could refine if birth seasonality is causally associated with CNS tumors and shed light into the complex pathophysiology of this lethal disease.

Coffee and tea consumption during pregnancy and risk of childhood acute myeloid leukemia: A Childhood Leukemia International Consortium (CLIC) study.

BACKGROUND: Dietary habits during pregnancy have been inconsistently linked to childhood acute myeloid leukemia (AML), given the putative intrauterine onset of the disease as a result of triggering events during the critical period of fetal hematopoiesis. We investigated the potential association of maternal coffee and tea consumption during pregnancy with childhood AML risk, pooling primary data from eight case-control studies participating in the Childhood Leukemia International Consortium. METHODS: Information on coffee and/or tea consumption was available for 444 cases and 1255 age- and sex-matched controls, on coffee consumption for 318 cases and 971 controls and on tea consumption for 388 cases and 932 controls. Categories for cups of daily coffee/tea consumption were created in order to explore potential dose-response associations. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. RESULTS: Associations were found neither in the analysis on coffee or tea nor in the analysis on coffee only consumption (any versus no). A positive association with increasing coffee intake was observed (>1 cup per day; OR: 1.40, 95% CI: 1.03-1.92, increment of one cup per day; OR: 1.18, 95% CI: 1.01-1.39). No associations were observed with tea consumption. Interaction analyses showed non-significant associations between coffee/tea and smoking. Hyperdiploidy was inversely associated with tea consumption, with other cytogenetic markers having no association with coffee/tea. CONCLUSION: Given the widespread consumption of caffeinated beverages among pregnant women, our finding is of important public health relevance, suggesting adverse effects of maternal coffee consumption during pregnancy in the offspring.

Wiskott-Aldrich Syndrome Misdiagnosed as Immune Thrombocytopenic Purpura: A Case Report.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency characterized by various clinical phenotypes. We report the case of a 3-year-old immigrant boy presenting with persistent infant-onset thrombocytopenia treated for refractory immune thrombocytopenic purpura. Sequence analysis confirmed the diagnosis of WAS. The patient responded neither to IV infusions of immunoglobulin (Ig) nor a thrombopoietin receptor agonist and is currently planned for stem cell transplantation. Raised awareness is thus vital of this potentially misdiagnosed and lethal disorder. The diagnosis of WAS should be considered in all males with infant-onset immune thrombocytopenic purpura-like features, especially, if mean platelet volume is decreased (<7 fL) and good increment to platelet transfusions are evident.

The role of depression and personality traits in patients with melanoma: a South-European study.

We explored the potential association of depression history and personality, evaluated through a robust questionnaire tool, namely the Eysenck Personality Scale, with disease risk and progression among Greek patients. A total of 106 melanoma patients and their 1 : 1 sex-matched controls were interviewed on the basis of a questionnaire comprising phenotypic, sociodemographic, lifestyle and medical history variables, as well as information on history of lifetime major depression. The Eysenck Personality Questionnaire, measuring the four personality dimensions (extraversion, neuroticism, psychoticism, lie), was thereafter completed. Adjusted odds ratios (ORs) for melanoma risk were derived through multiple logistic regression analyses, whereas potential predictors of survival were explored using Cox proportional hazards models. Sun sensitivity score [OR: 1.55, 95% confidence interval (CI): 1.16-2.06] and major depression history (OR: 5.72, 95% CI: 1.38-23.73) were significantly associated with melanoma, whereas inverse associations of extraversion (OR: 0.90, 95% CI: 0.83-0.97) and psychoticism score (OR: 0.88, 95% CI: 0.78-1.00) were noted. These associations were more pronounced and remained solely among female patients; notably, decreased extraversion (OR: 0.86, 95% CI: 0.76-0.98) and psychoticism score (OR: 0.63, 95% CI: 0.43-0.91), as well as increased depression history (OR: 10.69, 95% CI: 1.43-80.03) were evident. Cox-derived hazard ratios showed nonsignificant associations of depression history and personality with disease outcome. Our data support the hypotheses that depression history and personality are associated with melanoma risk. No effect on survival after cancer diagnosis was observed. If confirmed in future studies, these associations may contribute toward better understanding the etiology of melanoma, enhancing health-related quality of life.