Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: a contemporary single-institution experience

alexandrossfakianakis shared this article with you from Inoreader Long-term outcomes and late toxicity of adult medulloblastoma treated with combined modality therapy: a contemporary single-institution experience via Neuro-Oncology Advance Access Abstract Background Medulloblastoma (MB) is a rare central nervous system malignancy of adults, with limited contemporary studies to define treatment guidelines and expected late toxicity. Methods A single-center, retrospective study was conducted of patients age ≥18-years from 1997-2019 with MB and who were treated with postoperative radiotherapy. Late toxicity was defined as a minimum of 18-months from diagnosis. Overall survival (OS) and progression-free survival (PFS) were characterized using Kaplan-Meier and Cox regression analyses. Results Fifty-nine patients met criteria, with median age of 25-years (range 18-62y) and median follow-up of 6.5-years (range 0.7-23.1y). At diagnosis, 68% were standard-risk, 88% Chang M0, and 22% with anaplastic histology. Gross total resection was achieved in 75%; median craniospinal irradiation dose was 30.6Gy(relative biological effectiveness [RBE]), median total dose was 54.0Gy(RBE), 80 % received proton radiotherapy; 81% received chemotherapy. 5-year PFS and OS were 86.5% and 95.8%, respectively; 10-year PFS and OS were 83.9% and 90.7%, respectively. Anaplastic histology was associated with worse PFS (p=0.04). Among eight recurrences, 25% presented after 5-years. Most common grade ≥2 late toxicities were anxiety/depressive symptoms (30%), motor dysfunction (25%), and ototoxicity (22%). Higher posterior fossa radiation dose was associated with increased risk of late toxicity, including worse cognitive dysfunction (p = 0.05). Conclusions Adults with MB have favorable survival outcomes, but late failures and toxicity are not uncommon. Better understanding of prognostic factors, possibly from molecular subtyping, may help to define more personalized treatments for patients with high risk of recurrence and long-term treatment sequelae. View on Web

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Effectiveness of root canal instrumentation for the treatment of apical periodontitis: A systematic review and meta‐analysis

alexandrossfakianakis shared this article with you from Inoreader Effectiveness of root canal instrumentation for the treatment of apical periodontitis: A systematic review and meta‐analysis via International Endodontic Journal Abstract Background The development of endodontic instruments has rapidly advanced but their impact on endodontic outcome parameters remain unclear. Objectives This systematic review aimed to answer the following PICOT questions: In patients with apical periodontitis (P) what is the effectiveness of root canal instrumentation [(Q1) performed with contemporary techniques (I) in comparison with "traditional" techniques (C)] and [(Q2) performed with contemporary engine-driven NiTi instruments (I) compared with other types of contemporary engine-driven NiTi instruments (with different design and/or technology) (C)] in terms of clinical and patient-related outcomes (O)? Methods After PROSPERO protocol registration, a literature search was conducted using Clarivate Analytics' Web of Science, Scopus, PubMed, and Cochrane Central Register of Controlled Trials. Grey literature and major journal contents were examined. Two independent reviewers performed the study selection, data extraction, and appraisal of included studies. A quantitative meta-analysis was considered and statistical heterogeneity and overall quality of evidence were assessed. Results Nine studies were identified showing substantial methodological differences. Five studies addressed PICOT 1 and three PICOT 2, whereas one study aimed both. A random-effects meta-analysis model was considered for the outcome "radiographic evidence of normal periodontal ligament space or reduction of apical lesion size" (PICOT 1) based in three studies with 332 evaluable participants and showed that contemporary instrumentation was associated with a more favourable outcome (p= .005) compared to root canal preparation with stainless steel instruments (odds ratio=2.07 [95%-confidence interval=1.25-3.44]) with no evidence of statistical heterogeneity (I2=0%) but low quality of evidence. Discussion Albeit a few studies fulfilled eligible criteria, no study had a low risk of bias. Compelling evidence indicating significantly different outcome rates using different endodontic instruments when treating teeth with apical periodontitis is lacking. Conclusions In terms of healing, the results of the meta-analysis determined the higher effectiveness of root canal instrumentation performed with contemporary techniques in comparison with conventional stainless steel instruments in patients with apical periodontitis followed for a minimum of 1 year with low quality of evidence. No differences could be demonstrated between preparations with traditional stainless steel and contemporary NiTi instruments for other clinical and patient-related outcomes. View on Web

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Polygenic early‐onset colorectal cancer in pediatric patients

alexandrossfakianakis shared this article with you from Inoreader Polygenic early‐onset colorectal cancer in pediatric patients via Pediatric Blood & Cancer Abstract Colorectal cancer in the pediatric population is a rare but transpirable phenomenon. The occurrence should prompt suspicion for underlying genetic mutations in the setting of a hereditary cancer predisposition syndrome. In this series, we outline three pediatric patients with colonic adenocarcinoma who were found to have one or more germline mutations. The presence of compound mutations may lead to a hypermutator phenotype resulting in earlier presentation of colorectal cancer in childhood and adolescence. The diagnosis of colorectal cancer in pediatric patients warrants timely recognition, multigene panel testing, genetic counseling for the patient and family, and increased surveillance for intestinal and extra-intestinal tumors. View on Web

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Cumulative erythemal ultraviolet radiation and risk of cancer in three large US prospective cohorts

alexandrossfakianakis shared this article with you from Inoreader Cumulative erythemal ultraviolet radiation and risk of cancer in three large US prospective cohorts via American Journal of Epidemiology - Advance Access Abstract Ultraviolet radiation (UVR) exposure is the major risk factor for melanoma. However, epidemiologic studies on UVR and non-cutaneous cancers have reported inconsistent results, with some suggesting an inverse relationship potentially mediated by vitamin D. To address this, we examined three U.S. prospective cohorts, the Health Professionals Follow-Up Study (HPFS) (1986) and Nurses' Health Study (NHS) I and II (1976 and 1989), for associations between cumulative erythemal UVR and incident cancer risk, excluding non-melanoma skin cancer. We used a validated spatiotemporal model to calculate erythemal UVR. Participants (47,714 males; 212,449 females) were stratified into quintiles by cumulative average erythemal UVR, using the first quintile as reference for Cox proportional hazards regression analysis. In the multivariable-adjusted meta-analysis of all cohorts, compared to the lowest quintile, risk of any cancer was slightly increased across all o ther quintiles [highest quintile Hazard Ratio (HR),1.04; 95% Confidence Interval (CI),1.01,1.07; P-heterogeneity (P-het)=0.41]. All UVR quintiles were associated with similarly increased risk of any cancer excluding melanoma. As expected, erythemal UVR was positively associated with risk of melanoma (highest quintile HR,1.17; 95% CI,1.04,1.31; P-het=0.83). These findings suggest that elevated UVR is associated with increased risk of both melanoma and non-cutaneous cancers. View on Web

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Prenatal Exposure to Insecticides and Weight Trajectories Among South African Children in the VHEMBE Birth Cohort

alexandrossfakianakis shared this article with you from Inoreader Prenatal Exposure to Insecticides and Weight Trajectories Among South African Children in the VHEMBE Birth Cohort via Epidemiology - Current Issue Background: Dichlorodiphenyltrichloroethane (DDT) or pyrethroid insecticides are sprayed inside dwellings for malaria vector control, resulting in high exposure to millions of people, including pregnant women. These chemicals disrupt endocrine function and may affect child growth. To our knowledge, few studies have investigated the potential impact of prenatal exposure to DDT or pyrethroids on growth trajectories. Methods: We investigated associations between gestational insecticide exposure and child growth trajectories in the Venda Health Examination of Mothers, Babies and their Environment, a birth cohort of 751 children born between 2012 and 2013 in South Africa. Based on child weight measured at follow-up and abstracted from medical records, we modeled weight trajectories from birth to 5 years using SuperImposition, Translation and Rotation, which estimated two child-specific parameters: size (average weight) and tempo (age at peak weight velocity). We estimated associations between peripartum maternal concentrations of serum DDT, dichlorodiphenyldichloroethylene, or urinary pyrethroid metabolites and SuperImposition, Translation and Rotation parameters using marginal structural models. Results: We observed that a 10-fold increase in maternal concentrations of the pyrethroid metabolite trans-3-(2,2,-dicholorvinyl)-2,2-dimethyl-cyclopropane carboxylic acid was associated with a 21g (95% confidence interval = −40, −1.6) smaller size among boys but found no association among girls (Pinteraction = 0.07). Estimates suggested that pyrethroids may be associated with earlier tempo but were imprecise. We observed no association with serum DDT or dichlorodiphenyldichloroethylene. Conclusions: Inverse associations between pyrethroids and weight trajectory parameters among boys are consistent with hypothesized disruption of androgen pathways and with our previous research in this population, and support the endocrine-disrupting potential of pyrethroids in humans. View on Web

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Prenatal Antidepressant Exposure and the Risk of Attention-deficit/Hyperactivity Disorder in Childhood: A Cohort Study With Triangulation

alexandrossfakianakis shared this article with you from Inoreader Prenatal Antidepressant Exposure and the Risk of Attention-deficit/Hyperactivity Disorder in Childhood: A Cohort Study With Triangulation via Epidemiology - Current Issue Background: Uncontrolled confounding from maternal depression and genetic and environmental factors is expected in studies investigating the effect of prenatal antidepressant exposure on the risk of attention-deficit/hyperactivity disorder (ADHD) in childhood and may explain inconsistencies in the existing evidence. We aimed to assess this effect using triangulation. Methods: Using population-based health registries, we conducted a nationwide cohort study of all children born in Denmark between 1997 and 2017 and followed through 2018 for ADHD. We assessed the effect of prenatal antidepressant exposure on the risk of ADHD in childhood by comparing children with and without prenatal antidepressant exposure in terms of adjusted incidence rate ratios (IRRs), adjusted incidence rate differences (IRDs), and adjusted risk differences (RDs) and the associated 95% confidence intervals (CIs). We triangulated results from four different analytic approaches: an overall analysis, a negative control analysis, a sibling analysis, and a former-user analysis. Results: The overall study cohort consisted of 1,253,362 children, among whom 28,910 (2.3%) had prenatal antidepressant exposure. ADHD during follow-up was diagnosed among 1,411 (4.9%) of the exposed and in 37,196 (3.0%) of the unexposed children. Triangulation suggested an IRR of 1.09–1.15; an IRD less than 1 case/1,000 person-years, and an RD of 0.9%–2.2% over an up to 18-year period. Conclusions: Based on triangulation, we estimated a modest effect of prenatal antidepressant exposure on the risk of ADHD in childhood. However, considering the limitations of our approaches, this observed association may be partially due to residual biases. See video abstract at, http://links.lww.com/EDE/B935. View on Web

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Beyond Vaccination Rates: A Synthetic Random Proxy Metric of Total SARS-CoV-2 Immunity Seroprevalence in the Community

alexandrossfakianakis shared this article with you from Inoreader Beyond Vaccination Rates: A Synthetic Random Proxy Metric of Total SARS-CoV-2 Immunity Seroprevalence in the Community via Epidemiology - Current Issue Background: Explicit knowledge of total community-level immune seroprevalence is critical to developing policies to mitigate the social and clinical impact of SARS-CoV-2. Publicly available vaccination data are frequently cited as a proxy for population immunity, but this metric ignores the effects of naturally acquired immunity, which varies broadly throughout the country and world. Without broad or random sampling of the population, accurate measurement of persistent immunity post-natural infection is generally unavailable. Methods: To enable tracking of both naturally acquired and vaccine-induced immunity, we set up a synthetic random proxy based on routine hospital testing for estimating total immunoglobulin G (IgG) prevalence in the sampled community. Our approach analyzed viral IgG testing data of asymptomatic patients who presented for elective procedures within a hospital system. We applied multilevel regression and poststratification to adjust for demographic and geographic discrepancies between the sample and the community population. We then applied state-based vaccination data to categorize immune status as driven by natural infection or by vaccine. Results: We validated the model using verified clinical metrics of viral and symptomatic disease incidence to show the expected biologic correlation of these entities with the timing, rate, and magnitude of seroprevalence. In mid-July 2021, the estimated immunity level was 74% with the administered vaccination rate of 45% in the two counties. Conclusions: Our metric improves real-time understanding of immunity to COVID-19 as it evolves and the coordination of policy responses to the disease, toward an inexpensive and easily operational surveillance system that transcends the limits of vaccination datasets alone. View on Web

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Use of Recently Vaccinated Individuals to Detect Bias in Test-Negative Case–Control Studies of COVID-19 Vaccine Effectiveness

alexandrossfakianakis shared this article with you from Inoreader Use of Recently Vaccinated Individuals to Detect Bias in Test-Negative Case–Control Studies of COVID-19 Vaccine Effectiveness via Epidemiology - Current Issue Postauthorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. Although bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper, we introduce a theoretical framework to describe the interpretation of such a bias indicator in test-negative studies, and outline strong assumptions that would allow vaccine effectiveness among recently vaccinated individuals to serve as a negative control exposure. View on Web

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Incretin-Based Drugs and the Incidence of Prostate Cancer Among Patients With Type 2 Diabetes

alexandrossfakianakis shared this article with you from Inoreader Incretin-Based Drugs and the Incidence of Prostate Cancer Among Patients With Type 2 Diabetes via Epidemiology - Current Issue Background: There is some evidence that glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have chemopreventive effects on prostate cancer cells but real-world evidence for this possible effect is lacking. Thus, the objective of this study was to estimate whether use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, is associated with a decreased risk of prostate cancer among patients with type 2 diabetes. Methods: We assembled two new-user, active-comparator cohorts using the UK Clinical Practice Research Datalink (2007 to 2019). The first cohort included 5,063 initiators of GLP-1 receptor agonists and 112,955 of sulfonylureas. The second cohort included 53,529 initiators of DPP-4 inhibitors and 114,417 of sulfonylureas. We fit Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer. We weighted the models using propensity score fine stratification, which considered over 50 potential confounders. Results: GLP-1 receptor agonists were associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 156.4 vs. 232.0 per 100,000 person-years, respectively; HR = 0.65; 95% CI = 0.43, 0.99). DPP-4 inhibitors were also associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 316.2 vs. 350.5 events per 100,000 person-years, respectively; HR = 0.90; 95% CI = 0.81, 1.00). Conclusions: The results of this study are consistent with the hypothesis that the use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, may decrease the risk of prostate cancer when compared with the use of sulfonylureas. View on Web

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Gestational hypertensive disorders and maternal breast cancer risk in a nationwide cohort of 40,720 parous women

alexandrossfakianakis shared this article with you from Inoreader Gestational hypertensive disorders and maternal breast cancer risk in a nationwide cohort of 40,720 parous women via Epidemiology - Published Ahead-of-Print Background: Pre-eclampsia and gestational hypertension are hypothesized to be associated with reduced maternal breast cancer risk, but the epidemiologic evidence is inconclusive. Our objective was to examine associations between gestational hypertensive disorders and breast cancer in a nationwide cohort of women with a family history of breast cancer. Methods: Women ages 35-74 years who had a sister previously diagnosed with breast cancer, but had never had breast cancer themselves, were enrolled in the Sister Study from 2003-2009 (N=50,884). At enrollment, participants reported diagnoses of eclampsia, pre-eclampsia, or gestational hypertension in each pregnancy. We used Cox proportional hazards models to estimate HRs and 95% CIs for the association between history of a gestational hypertensive disorder and incident invasive breast cancer or ductal carcinoma in situ among 40,720 parous women. We used age as the time scale and adjusted for birth cohort, race–ethnicity, and reproductive, socioeconomic, and behavioral factors. We examined effect measure modification by risk factors for gestational hypertensive disease and breast cancer and assessed possible etiologic heterogeneity across tumor characteristics. Results: The prevalence of gestational hypertensive disease was 12%. During follow-up (mean=10.9 years), 3198 eligible women self-reported a breast cancer diagnosis. History of a gestational hypertensive disorder was not associated with breast cancer risk (HR=1.0, 95% CI 0.90, 1.1). We did not observe clear evidence of effect measure modification or etiologic heterogeneity. Conclusions: History of a gestational hypertensive disorder was not associated with breast cancer risk in a cohort of women with a first-degree family history of breast cancer. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved. View on Web

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