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The fatty acid profiles of patients with idiopathic nephrotic syndrome (INS) are different from that of healthy controls, even during remission, revealing an increase of the pro-inflammatory omega 6 series. It is still unknown whether the concomitance of nephrotic syndrome affects the potential positive effects of the Mediterranean diet on the levels of omega 3 and 6 fatty acids. We performed a cross-sectional study to evaluate the association between the adherence to the Mediterranean diet and fatty acid profile in 54 children with INS. The dietary habits were assessed through the validated Kidmed questionnaire. Patients with higher adherence had lower levels of linoleic acid and total omega-6. Moreover, a negative correlation between proteinuria and the anti-inflammatory omega-3 series was found. In conclusion, patients with INS with proteinuria and low adherence to the Mediterranean diet have an imbalance in the omega-6/omega-3 ratio that may benefit from following the Mediterranean diet.

Background: Training of machine learning algorithms on dish images collected in other countries requires possible sources of systematic discrepancies, including country-specific food composition databases (FCDBs), to be tackled. The US Nutrition5k project provides for ~5000 dish images and related dish- and ingredient-level information on mass, energy, and macronutrients from the US FCDB. The aim of this study is to (1) identify challenges/solutions in linking the nutritional composition of Italian foods with food images from Nutrition5k and (2) assess potential differences in nutrient content estimated across the Italian and US FCDBs and their determinants. Methods: After food matching, expert data curation, and handling of missing values, dish-level ingredients from Nutrition5k were integrated with the Italian-FCDB-specific nutritional composition (86 components); dish-specific nutrient content was calculated by summing the corresponding ingredient-specific nutritional values. Measures of agreement/difference were calculated between Italian- and US-FCDB-specific content of energy and macronutrients. Potential determinants of identified differences were investigated with multiple robust regression models. Results: Dishes showed a median mass of 145 g and included three ingredients in median. Energy, proteins, fats, and carbohydrates showed moderate-to-strong agreement between Italian- and US-FCDB-specific content; carbohydrates showed the worst performance, with the Italian FCDB providing smaller median values (median raw difference between the Italian and US FCDBs: −2.10 g). Regression models on dishes suggested a role for mass, number of ingredients, and presence of recreated recipes, alone or jointly with differential use of raw/cooked ingredients across the two FCDBs. Conclusions: In the era of machine learning approaches for food image recognition, manual data curation in the alignment of FCDBs is worth the effort.

ObjectiveTo summarize the latest evidence on head and neck cancer epidemiology from the International Head and Neck Cancer Epidemiology (INHANCE) consortium.Subjects and methodsINHANCE was established in 2004 to elucidate the etiology of head and neck cancer through pooled analyses of individual-level data on a large scale. We summarize results from recent INHANCE-based publications updating our 2015 overview.ResultsSeventeen papers were published between 2015 and May 2020. These studies further define the nature of risks associated with tobacco and alcohol, and occupational exposures on head and neck cancer. The beneficial effects on incidence of head and neck cancer were identified for good oral health, endogenous and exogenous hormonal factors, and selected aspects of diet related to fruit and vegetables. INHANCE has begun to develop risk prediction models and to pool follow-up data on their studies, finding that ~30% of cases had cancer recurrence and 9% second primary cancers, with overall- and disease-specific 5-year-survival of 51% and 57%, respectively.ConclusionsThe number and importance of INHANCE scientific findings provides further evidence of the advantages of large-scale internationally collaborative projects and will support the development of prevention strategies.

Abstract Background Peritoneal dialysis (PD) is the preferred dialysis modality in children. Its major drawback is the limited technique survival due to infections and progressive ultrafiltration failure. Conventional PD solutions exert marked acute and chronic toxicity to local tissues. Prolonged exposure is associated with severe histopathological alterations including vasculopathy, neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial cell layer. Recently, more biocompatible PD solutions containing reduced amounts of toxic glucose degradation products (GDPs) and buffered at neutral pH have been introduced into clinical practice. These solutions contain lactate, bicarbonate or a combination of both as buffer substance. Increasing evidence from clinical trials in adults and children suggests that the new PD fluids may allow for better long-term preservation of peritoneal morphology and function. However, the relative importance of the buffer in neutral-pH, low-GDP fluids is still unclear. In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD fluids. The BIOKID trial is designed to clarify the clinical significance of the buffer choice in biocompatible PD fluids. Methods/design The objective of the study is to test the hypothesis that bicarbonate based PD solutions may allow for a better preservation of peritoneal transport characteristics in children than solutions containing lactate buffer. Secondary objectives are to assess any impact of the buffer system on acid-base status, peritoneal tissue integrity and the incidence and severity of peritonitis. After a run-in period of 2 months during which a targeted cohort of 60 patients is treated with a conventional, lactate buffered, acidic, GDP containing PD fluid, patients will be stratified according to residual renal function and type of phosphate binding medication and randomized to receive either the lactate-containing Balance solution or the bicarbonate-buffered Bicavera® solution for a period of 10 months. Patients will be monitored by monthly physical and laboratory examinations. Peritoneal equilibration tests, 24-h dialysate and urine collections will be performed 4 times. Peritoneal biopsies will be obtained on occasion of intraabdominal surgery. Changes in small solute transport rates, markers of peritoneal tissue turnover in the effluent, acid-base status and peritonitis rates and severity will be analyzed.

BackgroundAlcohol is a well-established risk factor for head and neck cancer (HNC). This study aims to explore the effect of alcohol intensity and duration, as joint continuous exposures, on HNC risk.MethodsData from 26 case-control studies in the INHANCE Consortium were used, including never and current drinkers who drunk ≤10 drinks/day for ≤54 years (24234 controls, 4085 oral cavity, 3359 oropharyngeal, 983 hypopharyngeal and 3340 laryngeal cancers). The dose-response relationship between the risk and the joint exposure to drinking intensity and duration was investigated through bivariate regression spline models, adjusting for potential confounders, including tobacco smoking.ResultsFor all subsites, cancer risk steeply increased with increasing drinks/day, with no appreciable threshold effect at lower intensities. For each intensity level, the risk of oral cavity, hypopharyngeal and laryngeal cancers did not vary according to years of drinking, suggesting no effect of duration. For oropharyngeal cancer, the risk increased with durations up to 28 years, flattening thereafter. The risk peaked at the higher levels of intensity and duration for all subsites (odds ratio = 7.95 for oral cavity, 12.86 for oropharynx, 24.96 for hypopharynx and 6.60 for larynx).ConclusionsPresent results further encourage the reduction of alcohol intensity to mitigate HNC risk.

High dietary glycaemic index (GI) and glycaemic load (GL) may increase cancer risk. However, limited information was available on GI and/or GL and head and neck cancer (HNC) risk. We conducted a pooled analysis on 8 case-control studies (4081 HNC cases; 7407 controls) from the International Head and Neck Cancer Epidemiology (INHANCE) consortium. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) of HNC, and its subsites, from fixed- or mixed-effects logistic models including centre-specific quartiles of GI or GL. GI, but not GL, had a weak positive association with HNC (ORQ4 vs. Q1 = 1.16; 95% CI = 1.02-1.31). In subsites, we found a positive association between GI and laryngeal cancer (ORQ4 vs. Q1 = 1.60; 95% CI = 1.30-1.96) and an inverse association between GL and oropharyngeal cancer (ORQ4 vs. Q1 = 0.78; 95% CI = 0.63-0.97). This pooled analysis indicates a modest positive association between GI and HNC, mainly driven by laryngeal cancer.

BackgroundTobacco use is a well-established risk factor for head and neck cancer (HNC). However, less is known about the potential impact of exposure to tobacco at an early age on HNC risk.MethodsWe analyzed individual-level data on ever tobacco smokers from 27 case-control studies (17,146 HNC cases and 17,449 controls) in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using random-effects logistic regression models.ResultsWithout adjusting for tobacco packyears, we observed that younger age at starting tobacco use was associated with an increased HNC risk for ever smokers (OR

Introduction Nurses frequently place a peripheral venous catheter during children’s hospitalisation. Many studies suggest treatment of venipuncture-related pain. The administration of an equimolar mixture of oxygen and nitrous oxide (EMONO) is employed for pain control; however, no studies have analysed the association between EMONO and audiovisuals.The purpose of the study is to evaluate the effect of EMONO administration when combined with audiovisuals (EMONO+Audiovisual) versus EMONO alone on perceived pain, side effects and level of cooperation during peripheral venous access placement in children aged 2–5 years.Methods and analysis The first 120 eligible children admitted to the paediatric ward of the Lodi Hospital and presenting the indication for peripheral venous access will be enrolled. Sixty children will be randomly assigned to the experimental group (EMONO+Audiovisual) and 60 to the control group (EMONO alone).The Face, Legs, Activity, Cry, Consolability scale will be used to assess pain in the children aged 2-years old; pain in the children aged 3–5 years will be assessed using the Wong-Baker scale. The cooperation throughout the procedure will be measured using the Groningen Distress Rating Scale.Ethics and dissemination The Milan Area 1 Ethics Committee approved the study protocol (Experiment Registry No. 2020/ST/295). The trial results will be presented at conferences and published in peer-reviewed journals.Trial registration number NCT05435118.

ObjectivesThis study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.Materials and methodsWe pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.ResultsFor oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30  years. In former smokers who quit ≥10  years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.ConclusionReferring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.

BackgroundA few papers have considered reproducibility of a posteriori dietary patterns across populations, as well as pattern associations with head and neck cancer risk when multiple populations are available.MethodsWe used individual-level pooled data from seven case-control studies (3844 cases; 6824 controls) participating in the International Head and Neck Cancer Epidemiology consortium. We simultaneously derived shared and study-specific a posteriori patterns with a novel approach called multi-study factor analysis applied to 23 nutrients. We derived odds ratios (ORs) and 95% confidence intervals (CIs) for cancers of the oral cavity and pharynx combined, and larynx, from logistic regression models.ResultsWe identified three shared patterns that were reproducible across studies (75% variance explained): the Antioxidant vitamins and fiber (OR = 0.57, 95% CI = 0.41, 0.78, highest versus lowest score quintile) and the Fats (OR = 0.80, 95% CI = 0.67, 0.95) patterns were inversely associated with oral and pharyngeal cancer risk. The Animal products and cereals (OR = 1.5, 95% CI = 1.1, 2.1) and the Fats (OR = 1.8, 95% CI = 1.4, 2.3) patterns were positively associated with laryngeal cancer risk, whereas a linear inverse trend in laryngeal cancer risk was evident for the Antioxidant vitamins and fiber pattern. We also identified four additional study-specific patterns, one for each of the four US studies examined. We named them all as Dairy products and breakfast cereals, and two were associated with oral and pharyngeal cancer risk.ConclusionMulti-study factor analysis provides insight into pattern reproducibility and supports previous evidence on cross-country reproducibility of dietary patterns and on their association with head and neck cancer risk. See video abstract at, http://links.lww.com/EDE/B430.

Abstract Background and objectives Children with multi-drug resistant idiopathic nephrotic syndrome (MDR-INS) usually progress to end-stage kidney disease with a consistent risk of disease recurrence after transplantation. New therapeutic options are needed for these patients. Mesenchymal stromal cells (MSCs) are multipotential non-hematopoietic cells with several immunomodulatory properties and growing clinical applications. Cord blood-derived MSC have peculiar anti-inflammatory and immunosuppressive properties. We aimed at assessing safety and efficacy of cord-blood-derived MSCs (CB-MSCs) in children with MDR-INS. Design, setting, participants Prospective, open-label, single arm phase I–II pilot study. Pediatric patients with MDR-INS, resistant to at least two lines of therapy, were enrolled. Allogenic CB-MSCs were administered intravenously on days 0, 14, and 21 at a dose of 1.5 × 106 cells/kg. Patients were followed for at least 12 months. The primary outcomes were safety and toxicity. The secondary outcome was remission at 12 months evaluated by urinary protein/urinary creatinine ratio (uPr/uCr). Circulating regulatory T cells (Tregs) were monitored. Results Eleven pediatric patients with MDR-INS (10 females, median age 13 years) resistant to a median of 3 previous lines of therapy were enrolled. All patients completed the CB-MSC infusion schedule. No patient experienced any infusion-related adverse event or toxicity. Nine patients were assessable for efficacy. At the 12 months follow-up after the treatment, the median uPr/uCr did not change significantly from baseline (8.13 vs. 9.07; p = 0.98), while 3 patients were in partial or complete remission. A lower baseline uPr/uCr was a predictor of remission (2.55 vs. 8.74; p = 0.0238). Tregs count was not associated with CB-MSCs therapy. Conclusions CB-MSCs are safe and may have a role in the immunosuppressive therapy of pediatric patients with MDR-INS. This preliminary experience paves the way toward further phase II studies addressing MSC efficacy in immune-mediated kidney diseases.

Background: Training of machine learning algorithms on dish images collected in other countries requires possible sources of systematic discrepancies, including country-specific food composition databases (FCDBs), to be tackled. The US Nutrition5k project provides for ~5000 dish images and related dish- and ingredient-level information on mass, energy, and macronutrients from the US FCDB. The aim of this study is to (1) identify challenges/solutions in linking the nutritional composition of Italian foods with food images from Nutrition5k and (2) assess potential differences in nutrient content estimated across the Italian and US FCDBs and their determinants. Methods: After food matching, expert data curation, and handling of missing values, dish-level ingredients from Nutrition5k were integrated with the Italian-FCDB-specific nutritional composition (86 components); dish-specific nutrient content was calculated by summing the corresponding ingredient-specific nutritional values. Measures of agreement/difference were calculated between Italian- and US-FCDB-specific content of energy and macronutrients. Potential determinants of identified differences were investigated with multiple robust regression models. Results: Dishes showed a median mass of 145 g and included three ingredients in median. Energy, proteins, fats, and carbohydrates showed moderate-to-strong agreement between Italian- and US-FCDB-specific content; carbohydrates showed the worst performance, with the Italian FCDB providing smaller median values (median raw difference between the Italian and US FCDBs: −2.10 g). Regression models on dishes suggested a role for mass, number of ingredients, and presence of recreated recipes, alone or jointly with differential use of raw/cooked ingredients across the two FCDBs. Conclusions: In the era of machine learning approaches for food image recognition, manual data curation in the alignment of FCDBs is worth the effort. [ABSTRACT FROM AUTHOR]

To our knowledge, no studies so far have investigated the role of pizza and its ingredients in modulating disease activity in rheumatoid arthritis (RA). We assessed this question via a recent cross-sectional study including 365 participants from Italy, the birthplace of pizza. Multiple robust linear and logistic regression models were fitted with the tertile consumption categories of each available pizza-related food item/group (i.e., pizza, refined grains, mozzarella cheese, and olive oil) as independent variables, and each available RA activity measure (i.e., the Disease Activity Score on 28 joints with C-reactive protein (DAS28-CRP), and the Simplified Disease Activity Index (SDAI)) as the dependent variable. Stratified analyses were carried out according to the disease severity or duration. Participants eating half a pizza >1 time/week (vs. ≤2 times/month) reported beneficial effects on disease activity, with the significant reductions of ~70% (overall analysis), and 80% (the more severe stratum), and the significant beta coefficients of −0.70 for the DAS28-CRP, and −3.6 for the SDAI (overall analysis) and of −1.10 and −5.30 (in long-standing and more severe RA, respectively). Among the pizza-related food items/groups, mozzarella cheese and olive oil showed beneficial effects, especially in the more severe stratum. Future cohort studies are needed to confirm this beneficial effect of pizza and related food items/groups on RA disease activity.

The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend

Food and nutrition play an important role in head and neck cancer (HNC) etiology; however, the role of carotenoids remains largely undefined. We explored the relation of HNC risk with the intake of carotenoids within the International Head and Neck Cancer Epidemiology Consortium. We pooled individual-level data from 10 case-control studies conducted in Europe, North America, and Japan. The analysis included 18,207 subjects (4414 with oral and pharyngeal cancer, 1545 with laryngeal cancer, and 12,248 controls), categorized by quintiles of carotenoid intake from natural sources. Comparing the highest with the lowest quintile, the risk reduction associated with total carotenoid intake was 39 % (95 % CI 29-47 %) for oral/pharyngeal cancer and 39 % (95 % CI 24-50 %) for laryngeal cancer. Intakes of β-carotene equivalents, β-cryptoxanthin, lycopene, and lutein plus zeaxanthin were associated with at least 18 % reduction in the rate of oral and pharyngeal cancer (95 % CI 6-29 %) and 17 % reduction in the rate of laryngeal cancer (95 % CI 0-32 %). The overall protective effect of carotenoids on HNC was stronger for subjects reporting greater alcohol consumption (p

Few observational studies investigated the relationship between single food groups and disease activity in rheumatoid arthritis (RA). Within a recent Italian cross-sectional study (365 patients, median age: 58.46 years, 78.63% females), we focused on two food groups, olive oil and nuts, representing vegetable sources of fatty acids. Disease activity was measured with Disease Activity Score on 28 joints based on C-reactive protein (DAS28-CRP) and the Simplified Disease Activity Index (SDAI). Robust linear and logistic regression models included tertile-based consumption categories of each food group and several confounders. Stratified analyses were performed by disease severity or duration. Higher consumption of both food groups exerted a favorable effect on disease activity, significant only for olive oil (Beta: −0.33, p-value: 0.03) in the linear regression on the overall sample. This favorable effect was stronger in the more severe or long-standing forms of RA (p-value for heterogeneity

Background Sociocultural issues play a key role in children needing kidney replacement therapy (KRT). Methods Data of incident patients < 18 years treated with chronic dialysis or preemptive kidney transplantation (pTx) between 2007 and 2016 were retrospectively collected from the Italian Pediatric Dialysis Registry; KRT modality and outcome were compared between patients with at least one non-Italian parent ('resident foreign patients,' RFPs) and those from native parents ('domestic patients,' DPs) and between the quinquennium 2007-2011 (period 1) and 2012-2016 (period 2). Results We included 448 children (26.8% RFPs). The percentage of RFPs increased from 23 to 30.3% (p = 0.08) from periods 1 to 2. They were younger (6.7 vs. 9.4 years, p = 0.025) and less often treated with pTx (3.3 vs. 13.4%, p = 0.009) than DPs. The percentage of pTx increased from period 1 to 2 in RFPs only (8.4-18.6%, p = 0.006). Independent predictors of a lower probability of pTx were lower age, belonging to RFPs group, starting KRT in period 1 and focal segmental glomerulosclerosis or glomerulopathy as primary kidney disease. Peritoneal dialysis was the preferred dialysis modality in both groups. Age, primary kidney disease, and center size were independently associated with dialysis modality choice. Patient survival, waiting time to Tx, and dialysis modality survival were not different between the two groups. Conclusions The proportion of patients receiving KRT born from immigrant families increased in recent years in Italy. They were younger and less often treated with pTx than domestic patients. In case of dialysis, the outcome was not different between the two groups., Author(s): Fabio Paglialonga [sup.1] , Silvia Consolo [sup.1] , Enrico Vidal [sup.2] , Mattia Parolin [sup.3] , Bruno Minale [sup.4] , Mario Giordano [sup.5] , Isabella Guzzo [sup.6] , Chiara [...]

Background COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic. Methods A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics. Results Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines. Conclusions As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists' response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US., Author(s): Fabian Eibensteiner [sup.1] , Valentin Ritschl [sup.2] , Gema Ariceta [sup.3] , Augustina Jankauskiene [sup.4] , Günter Klaus [sup.5] , Fabio Paglialonga [sup.6] , Alberto Edefonti [sup.6] , Bruno [...]

Evidence of associations between single nutrients and head and neck cancer (HNC) is still more limited and less consistent than that for fruit and vegetables. However, clarification of the protective mechanisms of fruit and vegetables is important to our understanding of HNC etiology. We investigated the association between vitamin C intake from natural sources and cancer of the oral cavity/pharynx and larynx using individual-level pooled data from ten case-control studies (5,959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. After harmonization of study-specific exposure information via the residual method, adjusted odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using unconditional multiple logistic regression models on quintile categories of 'non-alcohol energy-adjusted' vitamin C intake. In the presence of heterogeneity of the estimated ORs among studies, we derived those estimates from generalized linear mixed models. Higher intakes of vitamin C were inversely related to oral and pharyngeal (OR = 0.54, 95% CI: 0.45-0.65, for the fifth quintile category versus the first one, p for trend

BackgroundEvidence for the possible effect of vitamin E on head and neck cancers (HNCs) is limited.MethodsWe used individual-level pooled data from 10 case-control studies (5959 cases and 12 248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium to assess the association between vitamin E intake from natural sources and cancer of the oral cavity/pharynx and larynx. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models applied to quintile categories of non-alcohol energy-adjusted vitamin E intake.ResultsIntake of vitamin E was inversely related to oral/pharyngeal cancer (OR for the fifth vs the first quintile category=0.59, 95% CI: 0.49-0.71; P for trend

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Research from different sources supports a link between nutrition and neurodevelopment, but evidence is still sparse regarding the relationship between a posteriori dietary patterns (DPs) and cognitive performance in school-aged children. Within the Northern Adriatic Cohort II, Friuli Venezia Giulia, Italy, 379 7-year-old children were cross-sectionally evaluated. Dietary patterns were identified through a principal component factor analysis based on 37 nutrients from children’s 3-day dietary records. The Wechsler Intelligence Scale of Children (WISC-IV) test provided measures of cognitive performance, including the full-scale intelligence quotient (FSIQ) and single index scores. Each DP was related to FSIQ or single index scores through multiple robust linear regression models. We identified five DPs named “Dairy Products”, “Plant-based Foods”, “Fats”, “Meat and Potatoes”, and “Seafood” (63% of variance explained). After adjustment, no significant relationship was observed with the FSIQ score; positive associations were found between the “Seafood” DP and Verbal Comprehension Index or Perceptual Reasoning Index. The “Meat and Potatoes” and “Dairy Products” DPs were inversely associated with the Verbal Comprehension Index and Processing Speed Index scores, respectively. In the absence of a relation with the overall FSIQ score, single DPs might influence specific cognitive functions, including verbal and reasoning abilities, as targeted by single indexes, in the expected direction.

Background: A great majority of children with idiopathic nephrotic syndrome will relapse after successful treatment of the initial episode. The possibility that different steroid dosing regimens at onset, adjusted for risk factors, can reduce the rate of relapse represents an interesting option to investigate.Objectives: To evaluate the effect of the initial steroid regimen, adjusted for time to remission (TTR), on the frequency of relapses and steroid dependence, and to verify the influence of prognostic factors on disease course.Methods: A multicentre, prospective, cohort study. Children with nephrotic syndrome, with TTR ≤ 10 days (Group A), were given a 20-week prednisone regimen (2,828 mg/m2) and those with a TTR >10 days, a 22-week regimen (3,668 mg/m2) (Group B). Previously published retrospective data from the same centers were also evaluated. Main outcomes were: relapse rate, number of frequent relapsers + steroid dependent children and total prednisone dose after induction.Results: 143 children were enrolled. Rate of relapsed subjects (77 vs. 79%) and frequent relapsers + steroid dependent subjects (40 vs. 53%) did not differ between Groups A and B, or between the retrospective and prospective cohorts. The cumulative prednisone dose taken after the induction treatment was similar in both groups and in the retrospective and prospective cohorts. TTR was not associated with relapse risk. Age at onset and total serum protein were significantly lower in relapsing patients. At ROC analysis, the best cut-off was 5.3 years for age at onset and 4.2 g/dL for total serum protein. According to these cut-offs, older children with higher total serum protein had a higher relapse free survival rate (58%) than younger children with lower total serum protein (17%).Conclusions: TTR was not found to be a prognostic factor of relapse; because of this, different steroid regimens, adjusted for TTR, did not modify the relapse rate in any relevant measure. Conversely, younger age and low total serum protein were independent predictors of relapse risk, however this outcome was not modified by higher prednisone regimens.Clinical Trial Registration:https://www.ClinicalTrials.gov/, identifier: NCT01386957 (www.nefrokid.it).

Treatment of chronic kidney disease (CKD) mineral bone disorder (MBD) is challenging in growing children due to the high amount of calcium needed for normal bone mineralization and the required dietary phosphate restriction, which often includes intake of calcium-rich products such as milk. Therefore, enteral calcium-intake (Ca-I) was calculated.Patients: We looked at pediatric CKD-Patients aged 0–6 years.Design: We used a retrospective analysis of Ca-I from dietary data collections. Ca-I below 60% or above 100% of the D-A-CH and the KDOQI reference values were considered as severe Ca deficiency or Ca overload, respectively.Results: We had 41 children, median age 1.1 (range 0-5.8) years, body weight 7.3 (2.4–19.9) kg, and length 68 (48-105) cm at the time of first dietary data collection. Renal function was classified as CKD stage III in 20, IV in 28, V in 44, and VD in 142 dietary data collections. At the first dietary data collection, 5 children were in the CKD stage III, 10 in IV, 9 in V, and 17 were on dialysis. Only one child progressed to a higher CKD stage. In total, 234 dietary data collections were analyzed, and 65 follow-up collections were available from 33 children after a time interval of 26 (1–372) days. The median caloric intake was 120 (47–217)% of D-A-CH RDI. In 149 (63.6%) of the dietary data collections, enteral Ca-I was below the target (

Examples of innovative research in pediatric nephrology include: a) the typically pediatric field of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT), which has benefited from the discovery of numerous gene mutations responsible for the various malformations and the demonstration of the congenital origin of most of the renal damage, resulting in a decrease of invasive imaging, antibiotic prophylaxis and surgery; b) the approach to glomerular diseases that appear in childhood, like idiopathic nephrotic syndrome (INS), IgA nephropathy (IgAN) and C3 glomerulopathies (C3G). B and T lymphocyte disregulations and molecular podocyte alterations of immunological and genetic origin have been described in INS as main determinants of proteinuria. In IgAN, the discovery of an abnormal IgA glycosilation in the mucosal B cells has driven to new trials with Budesonide and Sparsentan and to innovative therapies, like atacicept. A new classification of C3G has been proposed after the description of genetic mutations of factors inhibiting activation of the alternative complement pathway, and monoclonal anti-C5 antibody Eculizumab has consequently entered the therapeutic armamentarium; c) the initial attempts at gene therapy, with promising results obtained in Alport syndrome, nephropathic cystinosis and Dent syndrome. Moreover, a clear example of precision medicine is represented by the refinement of the dosage of Eculizumab in the treatment of atypical HUS, while slow-medicine recommendations exist for common clinical conditions, like urinary tract infections, microscopic hematuria and proteinuria.

Objectives In a previously published Delphi exercise the European Pediatric Dialysis Working Group (EPDWG) reported widely variable counteractive responses to COVID-19 during the first week of statutory public curfews in 12 European countries with case loads of 4–680 infected patients per million. To better understand these wide variations, we assessed different factors affecting countermeasure implementation rates and applied the capability, opportunity, motivation model of behaviour to describe their determinants.Design We undertook this international mixed methods study of increased depth and breadth to obtain more complete data and to better understand the resulting complex evidence.Setting This study was conducted in 14 paediatric nephrology centres across 12 European countries during the COVID-19 pandemic.Participants The 14 participants were paediatric nephrologists and EPDWG members from 12 European centres.Main outcome measures 52 countermeasures clustered into eight response domains (access control, patient testing, personnel testing, personal protective equipment policy, patient cohorting, personnel cohorting, suspension of routine care, remote work) were categorised by implementation status, drivers (expert opinion, hospital regulations) and resource dependency. Governmental strictness and media attitude were independently assessed for each country and correlated with relevant countermeasure implementation factors.Results Implementation rates varied widely among response domains (median 49.5%, range 20%–71%) and centres (median 46%, range 31%–62%). Case loads were insufficient to explain response rate variability. Increasing case loads resulted in shifts from expert opinion-based to hospital regulation-based decisions to implement additional countermeasures despite increased resource dependency. Higher governmental strictness and positive media attitude towards countermeasure implementation were associated with higher implementation rates.Conclusions COVID-19 countermeasure implementation by paediatric tertiary care centres did not reflect case loads but rather reflected heterogeneity of local rules and of perceived resources. These data highlight the need of ongoing reassessment of current practices, facilitating rapid change in ‘institutional behavior’ in response to emerging evidence of countermeasure efficacy.

Steroid-sensitive nephrotic syndrome is an immunological disorder mediated by still poorly defined circulating factor(s) that target the podocyte and damage the filtration barrier. Fatty acids (FA) have several biological roles and, in particular, are strictly involved in cell to cell communication, inflammatory processes and regulation of lymphocyte pools. Studies of FAs during INS have been mainly focused on biochemical changes during the phase of proteinuria; while no information is available about FA profile in patients with idiopathic nephrotic syndrome (INS) on stable remission. Aim of this study is to assess differences in blood FA profile between pediatric patients with INS during the phase of stable remission. Blood fatty acid profile of 47 pediatric patients on stable remission and 47 matched healthy controls were evaluated with gas chromatography. Patients with INS on stable remission had significantly higher levels of PUFA and omega-6 than controls (40.17 vs. 37.91% and 36.95 vs. 34.79%), lower levels of SFA and MUFA. Considering the single fatty acids, levels of omega-6 18:2n6 linoleic acid and omega-6 20:4n6 arachidonic acid were significantly higher in patients with INS than in controls (23.01 vs. 21.55%, p-value 0.003 and 10.37 vs. 9.65%, p-value 0.01). Moreover, patients with INS showed lower levels of SFA 14:0 (0.74 vs. 0.92%) and 18:0 (10.74 vs. 11.74%) and MUFA 18:1n9 oleic acid (18.50 vs. 19.83%). To the best of our knowledge this is the first study assessing FAs profile in children with INS in stable remission. In a population of 47 patients, we were able to demonstrate a higher blood level of linoleic and arachidonic acid, and consequently of omega-6 and PUFA, compared to controls. Persistently higher than normal levels of either linoleic or arachidonic acid, could be viewed as candidate biomarker for a state of risk of relapse in children with idiopathic nephrotic syndrome.