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Introduction L’emergence de nouvelles souches du SARS-CoV-2, telles que le variant Delta, presentant une replication virale augmentee et la capacite d’echapper a la reponse immune souleve des inquietudes chez les patients immunodeprimes. Cette etude avait pour objectif d’evaluer le taux de seroconversion, de neutralisation de differents variants, et la reponse lymphocytaire T en reponse a la vaccination par le BNT162b2 chez des patients avec maladies auto-immunes en fonction des traitements recus. Patients et methodes Etude prospective monocentrique realisee a l’Hopital Cochin (Paris) incluant des patients avec maladies auto-immunes traites par immunosuppresseurs et/ou immunomodulateurs, et des professionnels de sante comme controles. Les cas et les controles etaient exclus s’ils avaient une serologie Covid-19 positive a l’inclusion. Le critere de jugement principal etait la proportion d’anticorps anti-Spike et les titres de neutralisation croisee contre les variants Alpha et Delta a 3 mois (apres deux doses de vaccin). Les criteres de jugements secondaires etaient la reponse lymphocytaire T specifique, la proportion d’infections a SARS-CoV-2 symptomatiques et la tolerance du vaccin. Resultats Soixante-quatre cas et 32 controles avec un âge median respectif de 56 (39,5-59,5) et 52 (37,8-66,3) ans etaient inclus. Quatre groupes de traitements etaient defini: patients traites par rituximab (n = 22), methotrexate (n = 16), immunosuppresseurs conventionnels hors methotrexate (n = 19), patients recevant des traitements connus pour ne pas avoir d’impact sur la reponse vaccinale (n = 7). L’ensemble des cas avaient une production diminuee et retardee d’IgG et d’IgA anti-spike apres vaccination par le BNT162b2, ceci de facon plus prononcee dans le groupe rituximab. Alors que 2 doses de vaccin induisaient une reponse humorale neutralisante contre les variants Alpha et Delta chez 100 % des controles, un seul patient sous rituximab (5 %) neutralisait Alpha et aucun Delta. Les autres groupes de traitements avaient une activite neutralisante partielle contre Alpha, et significativement diminuee contre Delta. Les reponses lymphocytaires T specifiques etaient similaires entre les controles et les cas, a l’exception des patients sous metrotrexate qui avaient une reponse completement abrogee apres 1 dose et considerablement diminuee apres 2 doses. Apres 3 mois de suivi, 2 patients traites par rituximab presentaient une infection symptomatique peu severe a SARS-CoV-2, 4 a 7 jours apres la seconde dose de vaccin. Quatre patients (6,3 %) presentaient une poussee de leur maladie auto-immune conduisant a une modification therapeutique. Conclusion Le rituximab et le methotrexate impactent de facon differente l’immunogenicite du vaccin BNT162b2, en alterant respectivement les reponses humorales et cellulaires. Le variant Delta echappe completement a la reponse humorale chez les patients traites par rituximab. Ces resultats soulignent la necessite de protocoles vaccinaux particuliers et d’autres traitements preventifs de l’infection dans cette population de patients.

The engineered Fc-nonbinding (crystallizable fragment-nonbinding) CD3 antibody has lower mitogenicity and a precise therapeutic window for disease remission in patients with type 1 diabetes. Before anti-CD3 can be considered for use in transplantation, the most effective timing of treatment relative to transplantation needs to be elucidated. In this study anti-CD3F(ab′) 2 fragments or saline were administered intravenously for 5 consecutive days (early: d1-3 or delayed: d3-7) to mice transplanted with a cardiac allograft (H2b-to-H2k; d0). Survival of allografts was prolonged in mice treated with the early protocol (MST = 48 days), but most were rejected by d100. In contrast, in mice treated with the delayed protocol allografts continued to survive long term. The delayed protocol significantly inhibited donor alloreactivity at d30 as compared to the early protocol. A marked increase in Foxp3+ T cells (50.3 ± 1.6%) infiltrating the allografts in mice treated with the delayed protocol was observed (p < 0.0001 vs. early (24.9 ± 2.1%)) at d10; a finding that was maintained in the accepted cardiac allografts at d100. We conclude that the timing of treatment with anti-CD3 therapy is critical for inducing long-term graft survival. Delaying administration effectively inhibits the alloreactivity and promotes the dominance of intragraft Foxp3+ T cells allowing long-term graft acceptance. © 2013 The Authors. American Journal of Transplantation Published by Wiley Periodicals Inc.

Assessment of donor-specific alloreactive memory/effector T cell responses using an IFN-γ Elispot assay has been suggested to be a novel immune-monitoring tool for evaluating the cellular immune risk in renal transplantation. Here, we report the cross-validation data of the IFN-γ Elispot assay performed within different European laboratories taking part of the EU RISET consortium. For this purpose, development of a standard operating procedure (SOP), comparisons of lectures of IFN-γ plates assessing intra- and interlaboratory assay variability of allogeneic or peptide stimuli in both healthy and kidney transplant individuals have been the main objectives. We show that the use of a same SOP and count-settings of the Elispot bioreader allow low coefficient variation between laboratories. Frozen and shipped samples display slightly lower detectable IFN-γ frequencies than fresh samples. Importantly, a close correlation between different laboratories is obtained when measuring high frequencies of antigen-specific primed/memory T cell alloresponses. Interestingly, significant high donor-specific alloreactive T cell responses can be similarly detected among different laboratories in kidney transplant patients displaying histological patterns of acute T cell mediated rejection. In conclusion, assessment of circulating alloreactive memory/effector T cells using an INF-γ Elispot assay can be accurately achieved using the same SOP, Elispot bioreader and experienced technicians in kidney transplantation.

Summary Insulin-dependent (type 1) diabetes is a prototypic organ-specific autoimmune disease resulting from the selective destruction of insulin-secreting β cells within pancreatic islets of Langerhans by an immune-mediated inflammation involving autoreactive CD4+ and CD8+ T lymphocytes which infiltrate pancreatic islets. Current treatment is substitutive, i.e. chronic use of exogenous insulin which, in spite of significant advances, is still associated with major constraints (multiple daily injections, risks of hypoglycaemia) and lack of effectiveness over the long term in preventing severe degenerative complications. Finding a cure for autoimmune diabetes by establishing effective immune-based therapies is a real medical health challenge, as the disease incidence increases steadily in industrialized countries. As the disease affects mainly children and young adults, any candidate immune therapy must therefore be safe and avoid a sustained depression of immune responses with the attendant problems of recurrent infection and drug toxicity. Thus, inducing or restoring immune tolerance to target autoantigens, controlling the pathogenic response while preserving the host reactivity to exogenous/unrelated antigens, appears to be the ideal approach. Our objective is to review the major progress accomplished over the last 20 years towards that aim. In addition, we would like to present another interesting possibility to access new preventive strategies based on the ‘hygiene hypothesis’, which proposes a causal link between the increasing incidence of autoimmune diseases, including diabetes, and the decrease of the infectious burden. The underlying rationale is to identify microbial-derived compounds mediating the protective activity of infections which could be developed therapeutically.

Resume Introduction La chimiokine CXCL10 induite par l’interferon γ serait impliquee dans la physiopathologie de la pneumopathie interstitielle diffuse (PID) de la sclerodermie systemique (ScS). L’objectif de cette etude etait d’evaluer les taux seriques de CXCL10 chez des patients ayant une ScS. Methodes CXCL10 a ete dosee par methode Elisa dans le serum de 23 volontaires sains (mediane : 60,0 ans ; 58,0–67,3) et 29 patients atteints de ScS (63,1 ans ; 60,1–69,4). Ces derniers ont egalement eu des explorations fonctionnelles respiratoires, un examen tomodensitometrique du thorax et une echographie cardiaque. Les taux de CXCL10 (mediane et interquartile 25–75 %) ont ete compares entre patients et volontaires sains, et entre patients avec et sans PID. Resultats Les patients avaient un taux serique median de CXCL10 plus eleve que les volontaires sains (110,0 pg/ml ; 60,8–223,8 pg/ml contre 52,0 pg/ml ; 41,3–65,8 ; p Conclusion Ces resultats montrent l’implication de CXCL10 dans la physiopathologie de la ScS et suggerent plus particulierement une relation a la PID rencontree au cours de cette maladie.

Cytokines play a role in alopecia areata. We used immunohistochemical and in situ hybridization studies to demonstrate the persistence of pro-inflammatory as well as apoptotic mechanisms in skin biopsies from patients with chronic alopecia areata. In situ hybridization allows the visualization of the distribution of immunocompetent cells in vivo. We studied skin biopsies from 11 untreated alopecia areata patients and two normal controls. In situ hybridization was performed on frozen sections using 35S-radio-labeled riboprobes, specific for IL-1beta, IL-2, IL-6, INFgamma, and granzyme B mRNA. Immunohistochemistry was carried out using an anti-IL-1beta monoclonal antibody, and a monoclonal antibody directed against the human Fas protein. We demonstrated the presence of cells labeled with IL-1beta, IL-6, INFgamma, and granzyme B antisense probes. Similarly, cells labeled with anti-IL-1beta were found in 10 of 11 cases. The labeled cells were located in the mononuclear peri- and intrafollicular infiltrate. Cells expressing granzyme B were found in close contact with the follicle. Fas positivity was demonstrated in four of four cases at the level of the cytoplasmic membrane of the hair follicle keratinocytes. These results, based on visualizing the labeled cells, demonstrate that pro-inflammatory cytokines are produced by the mononuclear cell infiltrate in close contact with follicles in alopecia areata. Furthermore, they demonstrate for the first time that apoptotic mechanisms involving granzyme B and Fas-Fas ligand pathways may play a major role in the persistence of chronic alopecia areata.

The objective of this study was to assess the association between alcohol drinking before and during pregnancy and the risk of spontaneous abortion using data from a case-control study conducted in Milan, Italy. A total of 462 women (median age 30 years) were admitted for spontaneous abortion (within the 12th week of gestation) to a network of obstetrics departments in the greater Milan area. Of these, 148 (32%) were between the fourth and the eighth week of gestation and 314 (68%) between the ninth and the 12th week. A control group was made up of 814 women (median age 29 years) who gave birth at term (> 37 weeks gestation) to healthy infants (Apgar 5th minute > or = 8, weight > or = 3000 g) on randomly selected days at the same hospitals where cases had been identified. A total of 212 cases (46%) and 355 controls (47%) reported alcohol drinking before conception. Considering non-drinkers as the reference category, the relative risks (RR) of spontaneous abortion were 1.2 [95% confidence interval (CI), 0.9-1.6] and 0.8 (95% CI, 0.6-1.1), respectively, in drinkers of one to seven and more than seven drinks per week before conception. No association emerged between the duration of alcohol drinking and the risk of spontaneous abortion. A total of 166 cases (35.9%) and 263 (32.3%) controls reported any alcohol drinking during the first trimester of pregnancy. The corresponding relative risk was 1.1 (95% CI, 0.9-1.4) and no relationship emerged between the number of drinks per week and the risk of abortion.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to analyse the efficacy of resection/ablation of minimal/mild endometriotic lesions for improving fertility, we conducted a randomized clinical trial. Eligible patients were women aged ≤ 36 years who were trying to conceive and had a laparoscopically confirmed diagnosis of minimal/mild endometriosis (stage I or II of the revised American Fertility Society classification) and otherwise unexplained infertility for ≥ 2 years. Eligible women were randomly assigned to resection or ablation of visible endometriosis (54 patients) or diagnostic laparoscopy only (47 patients). After laparoscopy women tried to conceive spontaneously for 1 year (follow-up period). A total of five women withdrew from the study: three for personal reasons, and two were lost to follow-up. Considering 51 women in the resection/ablation and 45 in the no-treatment group who ended the follow-up period, 12 (24%) in the resection/ablation group and 13 (29%) in the no treatment group conceived; the difference was not significant. Two spontaneous abortions were observed in the resection/ablation group and three in the no-treatment one. Thus the 1 year birth rate was 10 out of 51 women (19.6%) in the resection/ablation group and 10 out of 45 women (22.2%) in the no-treatment group. In conclusion, the results of this study do not support the hypothesis that ablation of endometriotic lesions markedly improves fertility rates.

CD3-specific monoclonal antibodies were the first rodent monoclonals introduced in clinical practice in the mid 1980s as approved immunosuppressants to prevent and treat organ allograft rejection. Since then compelling evidence has been accumulated to suggest that in addition to their immunosuppressive properties, CD3-specific antibodies can also afford inducing immune tolerance especially in the context of ongoing immune responses. Thus, they are highly effective at restoring self-tolerance in overt autoimmunity, a capacity first demonstrated in the experimental setting, which was recently transferred to the clinic with success.

Objective: To investigate the relation between wine drinking and intake of selected indicator foods, which may vary in various populations. Design: Cross-sectional analysis of the comparison group of a case- control study. Setting: A network of teaching and general hospitals from six Italian areas. Subjects: 5642 control subjects (3261 females and 2381 males) aged 20‐74 y (median age 58 y), admitted for acute, non-neoplastic conditions unrelated to alcohol consumption. Participation rate was over 95%. Intervention: Trained interviewers collected information using a structured and validated questionnaire. The average intakes of selected food items were computed, together with the multivariate odds ratios (OR) of eating above the median of each food. Results: No appreciable difference in either sex for any food indicator considered (fruit, raw vegetables, cooked vegetables, salad and fish) was observed between abstainers, wine, and other alcoholic beverage drinkers. If anything, female wine drinkers reported less frequently high consumption of salad (ORa 0.8) and raw vegetables (ORa 0.8), both estimates being of borderline significance. Conclusions: In no instance did wine drinkers or mixed drinkers (who include a large proportion of wine drinkers, too) show an association with indicators of healthy diet. Sponsorship: Italian Association for Cancer Research, Milan, Italy. Descriptors: drinking patterns; wine intake; dietary habits; alcoholic beverages; alcohol intake; cross-sectional study; diet European Journal of Clinical Nutrition (2000) 54, 177‐179

Hepatitis B virus (HBV) DNA sequences have been detected in leucocytes from HBV-infected individuals. The aim of this study was to assess the specificity of HBV for a special leucocyte subset in nine healthy chronic HBV carriers, nine HBs antigen-positive patients with chronic active hepatitis, 16 HBs antigen-negative haemophiliacs with HBc and/or HBs antibodies, and 10 patients with HBV-related systemic necrotizing vasculitis. HBV-DNA sequences were found by Southern blot hybridization in the leucocytes of 15 out of the 44 (34%) patients. The prevalence was not significantly different between the four groups. HBV-DNA was found in the CD4+ cells (9/11) as well as in the CD8+ cells (4/11), B cells (4/12) and monocytes (2/12). In conclusion, leucocytes, and particularly CD4+ lymphocytes, are frequently infected by HBV in patients with HBV serum markers.

EDITOR—Owen et al report that the prevalence of smoking in pregnancy and the rates of stopping did not change in England between 1992 and 1995, remaining at around 25%.1They also reported that the prevalence of smoking in pregnancy is higher in young women, unemployed women, and manual workers. We analysed the characteristics of women who gave up or continued smoking during pregnancy in Italy, using the comparison group of a case-control …

Dans les pays industrialises, les maladies auto-immunes (polyarthrite rhumatoide, lupus erythemateux dissemine, sclerose en plaques, diabete juvenile) occupent le troisieme rang apres les maladies cardiovasculaires et le cancer. On comprend donc que leur diagnostic precoce et leur traitement demeurent des enjeux d'envergure. Au cours des dernieres annees, de nouvelles strategies d'immunotherapie des maladies auto-immunes ont ete proposees, dont le but est de restaurer de maniere specifique et durable la tolerance vis-a-vis du ou des autoantigene(s) pathogene(s). L'autoantigene pathogene, qui serait l'outil therapeutique de choix, demeure tres mal caracterise dans la grande majorite des maladies auto-immunes humaines et ne peut donc etre administre. L'utilisation transitoire de certains anticorps monoclonaux antilymphocytes, et plus particulierement des anticorps anti-CD3, testee dans un modele experimental murin de diabete insulinodependant, a permis d'induire une remission totale et durable de l'atteinte auto-immune; une voie therapeutique nouvelle semble ainsi ouverte.

Summary Histiocytosis X cells were demonstrated to react with T 6 antigen as well as with the M 1 and I 1 markers of monocytes using immuno-electron microscopy and double labeling immunofluorescence technique. The data confirm the close relationship existing between histiocytic X cells, Langerhans cells and dendritic cells, and suggest to consider the T 6 antigen either as an early differentiation marker of thymocytes or as a functional marker of Mononuclear Phagocyte System subpopulations.

The authors examined the immune status at the cellular and humoral levels of 16 untreated schizophrenic patients. No abnormality in the distribution of T cell subsets (CD4+, CD8+) was detected. The proliferative response to the T cell mitogen phytohemagglutinin was normal. No increase in the number of T cells showing activation markers, such as human leukocyte antigens and interleukin-2 receptors, was noted. Conversely, function studies revealed a clear deficiency in interleukin-2 production by purified T cells. This lower production was probably intrinsic to the patients' T cells, since interleukin-2 production showed normal sensitivity to prostaglandin E2-mediated down-regulation by autologous monocytes.

Sixteen proteins were demonstrated by crossed immunoelectrophoresis (CIE) of Triton X-100 solubilized megakaryoblasts against a rabbit antiserum. One of these reacted with a recently developed monoclonal antibody (SA-1) prepared by immunization with cells from a patient with megakaryoblastic leukemia. Leukemic cells from 8/15 patients with AML stained brightly for this antigen by indirect immunofluorescence. The antiserum also stained a minor subpopulation of myelo-monocytic cells in blood and bone-marrow of healthy individuals, but not lymphoblasts from 5 patients with ALL or cells from 5 CLL patients and 4 non-Hodgkin lymphomas. The protein was shown to be amphiphilic (integral) by charge-shift CIE and hydrophobic interaction CIE with phenyl-Sepharose. It was shown not to be glycosylated by Lentil lectin affinity CIE and by Sodiumborohydride labelling. SDS-polyacrylamide gel electrophoresis of 125I (Bolton-Hunter) labelled, immunoprecipitated material demonstrated 2 bands of molecular weight 34.000 and 46.000 under reducing and non-reducing conditions.

It is generally admitted that human idiopathic glomerulonephritides are due to the pathogenetic effect of immune complexes. The formation of the immune complexes implies that an antigen has induced the formation of antibodies in adequate amount and with a certain (yet undefined) quality. The participation of cell-mediated immunity has also been recently suggested (2, 5).

Cyclosporin 5-10 mg/kg daily was given for 2-8 months to twelve recently diagnosed type 1 diabetics from a mean of 49 +/- SE 14 days after the start of insulin therapy, which was regulated to give near-normal blood glucose and haemoglobin A1c values. Mean insulin dosage dropped from 46 +/- 5 U/day before cyclosporin treatment to 16 +/- 4 U/day by the 7th month. Four patients had a complete remission and the insulin needs of four more were cut by half. The remaining four did not have remissions. Initial basal and glucagon-stimulated C peptide concentrations were higher in those who went into remission than in those who did not; they rose during cyclosporin treatment in the former but not in the latter. OKT4+ lymphocyte functions were suppressed in all patients and OKT4/OKT8 ratios declined. Anti-beta-cell autoimmunity, as indicated by lymphocyte-induced inhibition of insulin release from mouse islet cells, declined in all patients who went into remission. No consistent trend was observed for anti-islet cell antibodies. In forty-four similar, but non-randomised, recently diagnosed diabetics treated with insulin alone, the incidence of remission was 6%.

Background The goals are to estimate time trends (1986‐1994) of major coronary risk factors in an industrialized low CHD incidence population and to assess education class (EC) differences in risk factor prevalence and in time trends. Methods Three population surveys were conducted in 1986‐1987, 1989‐1990 and 1993‐ 1994 on independent and two-stage age- and gender-stratified random samples (1906 men and 1941 women) of 35‐64 year old residents of Brianza, an affluent region of northern Italy. The protocol for data collection, clinical measurements and biochemical determinations adhered to the WHO MONICA manual and underwent repeated quality control assessments. EC were identified according to gender- and 5-year birth-cohort specific tertiles. Results In the initial, middle and final surveys 1258, 1259 and 1330 subjects were enrolled, corresponding to participation rates of 70.1%, 70.3% and 74.3%, respectively. Over the 8-year period, in men systolic blood pressure and smoking habits declined, body mass index and serum total cholesterol increased. In women systolic blood pressure showed a constant reduction, total cholesterol and BMI increased and the prevalence of smokers remained stable. Overall inverse associations with EC were found for body mass index, for prevalence of cigarette smokers in men and for systolic blood pressure in women. Decreases in blood pressure were more evident in the lowest EC. Cigarette smoking was on the decline in the higher EC in men. BMI and total cholesterol increased in all EC with the notable exception of the ‘low’ EC in women. Conclusions Favourable changes of the risk factor profile in the low socio-economic classes may have contributed to reduce CHD rates in this population. Specific policies oriented to lowest socio-economic classes are needed to continue to combat the smoking epidemic.

Until the past century, mortality trends from coronary heart disease (CHD) and cerebrovascular disease (CVD) were less favorable in Latin than in North America. We calculated age-standardized mortality rates using data from the World Health Organization database over the period 1980 to 2013. To identify significant changes in trends, we performed joinpoint analysis. Since the early 2000's, CHD mortality rates decreased by about 35% in the USA and Canada in both genders; similar decreases were observed in some Latin American countries (i.e., Ecuador, Puerto Rico, and Chile), whereas the decreases were smaller in the other countries. In 2011 to 2013, the highest rates were in Venezuela (114.4/100,000 men) and Colombia (86.1/100,000 men) and the lowest ones (apart from Ecuador) in Panama, Chile, and Argentina (from 41 to 46/100,000 men and 18 to 19/100,000 women). For CVD mortality, a decrease by about 30% was observed in Argentina, Panama, and Uruguay plus Colombia for women, in addition to the USA and Canada. Smaller declines were observed in the other Latin American countries (from 23% in Colombian men to 5% in Venezuelan men). Throughout the period, rates in Latin America remained appreciably higher than those in North America. The highest CVD rates were observed in Brazil (51.6/100,000 men) and the lowest ones in Canada (12.9/100,000 women). In conclusion, trends in CHD and CVD mortality continue to be less favorable in Latin America than in Canada and the USA. The marked excess of CVD mortality is partly or largely attributable to inadequate control of dyslipidemia and hypertension.

We updated trends in breast cancer mortality in Europe up to the late 2000's. In the EU, age-adjusted (world standard population) breast cancer mortality rates declined by 6.9% between 2002 and 2006. from 17.9 to 16.7/100,000. The largest falls were in northern European countries, but more recent declines were also observed in central and eastern Europe. In 2007, all major European countries had overall breast cancer rates between 15 and 19/100,000. In relative terms, the declines in mortality were larger at younger age (-11.6% at age 20-49 years between 2002 and 2007 in the EU), and became smaller with advancing age (-6.6% at age 50-69, 5.0% at age 70-79 years). The present report confirms and further quantifies the persisting steady fall in breast cancer mortality in Europe over the last 25-30 years, which is mainly due to advancements in the therapy. (C) 2011 Published by Elsevier Ltd.

Scanty information, limited to selected areas of the country, is available on cancer mortality in Brazil. Age-standardized (world population) mortality rates between 1980 and 2004, derived from the WHO database, were computed for all cancers and 24 major cancer sites in Brazil. Joinpoint regression analyses were used to identify the significant changes in trends and estimate annual percent change (APC) in rates. Total cancer mortality rates increased over the last decade in men (APC = 0.5) to reach 101.2/100 000, and in women (APC = 0.3) to reach 71.3/100 000. In men, upward trends were observed for cancers of the oral cavity and pharynx with a rate of 5.9/100 000 in 2000-2004, intestines (whose rate, however was low, i.e. 7.6), prostate (12.2), and leukemias (3.4). Male lung cancer increased until 1993 (APC = 1.39) and decreased thereafter (APC = -0.29), with a relatively low rate of 16.2/100 000 in 2000-2004. In women, there were steady upward trends for cancers of the lung (APC = 2.3), reaching 6.2/100 000 in 2000-2004, and leukemias (2.5). Breast cancer mortality leveled off at around 10/100 000 in the last decade, whereas declines were observed for cancers of the uterus, whose rate (8.3) however, remained comparatively high. Declines were observed for stomach cancer in both sexes, with rates of 11.1 in men and 4.6 in women. In conclusion, the key issues of cancer mortality in Brazil are the high rates of head and neck cancers in men and (cervix) uterine cancer in women, that is, in principle cancers that are largely avoidable through prevention, screening, and early diagnosis.

Until the mid-1990s, gastric cancer has been the first cause of cancer death worldwide, although rates had been declining for several decades and gastric cancer has become a relatively rare cancer in North America and in most Northern and Western Europe, but not in Eastern Europe, Russia and selected areas of Central and South America or East Asia. We analyzed gastric cancer mortality in Europe and other areas of the world from 1980 to 2005 using joinpoint regression analysis, and provided updated site-specific incidence rates from 51 selected registries. Over the last decade, the annual percent change (APC) in mortality rate was around -3, -4% for the major European countries. The APC were similar for the Republic of Korea (APC = -4.3%), Australia (-3.7%), the USA (-3.6%), Japan (-3.5%), Ukraine (-3%) and the Russian Federation (-2.8%). In Latin America, the decline was less marked, but constant with APC around -1.6% in Chile and Brazil, -2.3% in Argentina and Mexico and -2.6% in Colombia. Cancers in the fundus and pylorus are more common in high incidence and mortality areas and have been declining more than cardia gastric cancer. Steady downward trends persist in gastric cancer mortality worldwide even in middle aged population, and hence further appreciable declines are likely in the near future. (C) 2609 UICC

Background Epidemiological data on infant feeding practices and allergic diseases are controversial. The purpose of this study was to explore the association of early weaning with the occurrence of atopic dermatitis (AD). Methods We conducted a matched case–control study on incident physician-diagnosed AD in early childhood including 451 cases and 451 controls. Data on several factors, including feeding practices, were collected through an interviewer-administered questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were estimated through logistic regression models, conditioned on study center, age, sex, and period of interview, and adjusted for potential confounders. Results Early weaning, defined as the introduction of solid foods at 4 or 5 months of age, was inversely related to the risk of AD, with children weaned at 4 months having lower AD risk (OR = 0.41, 95% CI, 0.20–0.87) compared to those exclusively breastfed. Similar results were observed for weaning started at 5 months of age (OR = 0.39, 95% CI, 0.18–0.83). This association persisted when children with and without family history of allergy were considered separately. Prolonged partial breastfeeding (breastmilk plus milk formulas) was not associated with AD. Consistently, the introduction of a high number of different solid foods reduced the risk of AD (P trend = 0.02 at 4 months of age and P trend = 0.04 at 5 months). Conclusion Our data provide evidence against the preventing role of prolonged exclusive (but not partial) breastfeeding in AD occurrence and confirm recent results indicating a beneficial role of early weaning in AD.

BACKGROUND: After a peak in the late 1980s, cancer mortality in Europe has declined by ∼10% in both sexes up to the early 2000s. We provide an up-to-date picture of patterns and trends in mortality from major cancers in Europe. METHODS: We analyzed cancer mortality data from the World Health Organization for 25 cancer sites and 34 European countries (plus the European Union, EU) in 2005-2009. We computed age-standardized rates (per 100 000 person-years) using the world standard population and provided an overview of trends since 1980 for major European countries, using joinpoint regression. RESULTS: Cancer mortality in the EU steadily declined since the late 1980s, with reductions by 1.6% per year in 2002-2009 in men and 1% per year in 1993-2009 in women. In western Europe, rates steadily declined over the last two decades for stomach and colorectal cancer, Hodgkin lymphoma, and leukemias in both sexes, breast and (cervix) uterine cancer in women, and testicular cancer in men. In central/eastern Europe, mortality from major cancer sites has been increasing up to the late 1990s/early 2000s. In most Europe, rates have been increasing for lung cancer in women and for pancreatic cancer and soft tissue sarcomas in both sexes, while they have started to decline over recent years for multiple myeloma. In 2005-2009, there was still an over twofold difference between the highest male cancer mortality in Hungary (235.2/100 000) and the lowest one in Sweden (112.9/100 000), and a 1.7-fold one in women (from 124.4 in Denmark to 71.0/100 000 in Spain). CONCLUSIONS: With the major exceptions of female lung cancer and pancreatic cancer in both sexes, in the last quinquennium, cancer mortality has moderately but steadily declined across Europe. However, substantial differences across countries persist, requiring targeted interventions on risk factor control, early diagnosis, and improved management and pharmacological treatment for selected cancer sites.

We considered trends in mortality from leukemia in Europe over the period 1970-2009 using data from the World Health Organization. We computed age-standardized (world population) mortality rates, at all ages and in selected age groups, in 11 selected European countries, the European Union (EU) and, for comparative purposes, in the USA and Japan. For the EU, we also provided projections of the mortality to 2012. Over the period considered, mortality from leukemia steadily declined in most European countries in children and young adults, as well as in western and southern Europe at middle-age (45-69 years); in central/eastern Europe, reductions at ages 45-69 started since the mid-late 1990s. In the EU, annual percent changes were -3.7% in males and -3.8% in females at age 0-14, -2% in both sexes at age 15-44, and -0.6% in males and -1% in females at middle-age and overall. No decline was observed at age 70 or more. Between 1997 and 2007, overall EU rates decreased from 5.4 to 4.8/100,000 males and from 3.4 to 2.9/100,000 females. Declines were from 6.2 to 5.5/100,000 males and from 3.7 to 3.2/100,000 females in the USA and from 3.9 to 3.5/100,000 males and from 2.5 to 2.0/100,000 females in Japan. Projected overall rates in the EU at 2012 are 4.3/100,000 males (-11% compared to 2007) and 2.6/100,000 females (-12%). Copyright

Lung cancer mortality in men from the European Union (EU) peaked in the late 1980s at an age-standardised (world standard population) rate over 53/100,000 and declined subsequently to reach 44/100,000 in the early 2000s. To provide a comprehensive picture of recent trends in male lung cancer mortality in Europe, we analyzed available data from the World Health Organization up to 2009 and predicted future rates to 2015. Lung cancer mortality rates in EU men continued to fall over recent years, to reach a value of 41.1/100,000 in 2005-2009. The fall was similar at all-ages and in middle-aged men (less than 2% per year over most recent years), but was appreciably larger in young men (aged 20-44 years, over 5% per year). A favourable trend is thus likely to be maintained in the foreseeable future, although the predicted overall EU rate in 2015 is still over 35/100,000, i.e., higher than the US rate in 2007 (33.7/100,000). Over most recent calendar years, overall male lung cancer rates were around 35-40/100,000 in western Europe, as compared to over 50/100,000 in central and eastern Europe. Within western Europe, lung cancer rates were lower in northern countries such as Sweden, but also Finland and the UK (below 30/100,000), where the tobacco-related epidemic started earlier and rates have long been declining, whereas mortality was high in Belgium (51.6), France (42.3), the Netherlands and Spain (around 43.0), where the epidemic started later but is persisting. Widespread measures for smoking control and cessation in middle-aged European men, i.e., in the generations where smoking prevalence used to be high, would lead to appreciable reductions in male lung cancer mortality in the near future. This is particularly urgent in central and eastern European countries.

Background: In recent decades, there have been substantial changes in mortality from urologic cancers in Europe. Objective: To provide updated information, we analyzed trends in mortality from cancer of the prostate, testis, bladder, and kidney in Europe from 1970 to 2008. Design, setting, and participants: We derived data for 33 European countries from the World Health Organization database. Measurements: We computed world-standardized mortality rates and used join-point regression to identify significant changes in trends. Results and limitations: Mortality from prostate cancer has leveled off since the 1990 s in countries of western and northern Europe, particularly over the last few years while it was still rising in Bulgaria, Romania, and Russia. In the European Union (EU), it reached a peak in 1995 at 15.0 per 100 000 men and declined to 12.5 per 100 000 in 2006. Mortality from testicular cancer has steadily declined in most countries in western and northern Europe since the 1970 s. The declines were later and appreciably lower in central/eastern Europe. In EU, rates declined from 0.75 in 1980 to 0.32 per 100 000 men in 2006, with stronger declines up to the late 1990 s and an apparent leveling off in rates thereafter. Over the last 15 years, mortality from bladder cancer has declined in most European countries in both sexes. The major exceptions were Bulgaria, Poland, and Romania. In the EU, bladder cancer mortality was stable until 1992 and declined thereafter from 7.3 to 5.5 per 100 000 men and from 1.5 to 1.2 per 100 000 women in 2006. Mortality from kidney cancer increased throughout Europe until the early 1990 s and leveled off thereafter in many countries, except in a few central and eastern ones. Between 1994 and 2006, rates declined from 4.9 to 4.3 per 100 000 in EU men and from 2.1 to 1.8 per 100 000 in EU women. Conclusions: Over the last two decades, trends in urologic cancer mortality were favorable in Europe, with the exception of a few central and eastern countries. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Background: Over the last two decades, mortality from coronary heart disease (CHD) and cerebrovascular disease (CVD) declined by about 30% in the European Union (EU). Design: We analyzed trends in CHD (X ICD codes: 120-125) and CVD (X ICD codes: 160-169) mortality in young adults (age 35-44 years) in the EU as a whole and in 12 selected European countries, over the period 1980-2007. Methods: Data were derived from the World Health Organization mortality database. With joinpoint regression analysis, we identified significant changes in trends and estimated average annual percent changes (AAPC). Results: CHD mortality rates at ages 35-44 years have decreased in both sexes since the 1980s for most countries, except for Russia (130/100,000 men and 24/100,000 women, in 2005-7). The lowest rates (around 9/100,000 men, 2/100,000 women) were in France, Italy and Sweden. In men, the steepest declines in mortality were in the Czech Republic (AAPC = -6.1%), the Netherlands (-5.2%), Poland (-4.5%), and England and Wales (-4.5%). Patterns were similar in women, though with appreciably lower rates. The AAPC in the EU was -3.3% for men (rate = 16.6/100,000 in 2005-7) and -2.1% for women (rate = 3.5/100,000). For CVD, Russian rates in 2005-7 were 40/100,000 men and 16/100,000 women, 5 to 10-fold higher than in most western European countries. The steepest declines were in the Czech Republic and Italy for men, in Sweden and the Czech Republic for women. The AAPC in the EU was -2.5% in both sexes, with steeper declines after the mid-late 1990s (rates = 6.4/100,000 men and 4.3/100,000 women in 2005-7). Conclusions: CHD and CVD mortality steadily declined in Europe, except in Russia, whose rates were 10 to 15-fold higher than those of France, Italy or Sweden. Hungary and Poland, and also Scotland, where CHD trends were less favourable than in other western European countries, also emerge as priorities for preventive interventions.

The objective of this study was to provide information on recent trends in cancer mortality in Mexico. We analyzed data provided by the World Health Organization, using joinpoint analysis to detect changes in trends between 1981 and 2007. For most cancers, mortality was upward but started to decline in the late 1980's/early 1990's for both sexes. Overall cancer mortality was 75.53/100 000 men, world standard, and 69.2/100 000 women in 2005-2007. Mortality from uterine cancer declined by approximately 2.5% per year in the 1990s, and by approximately 5% per year in the last decade, but its rates remained exceedingly high (9.7/100 000 in 2005-2007). Other major declines over recent years were those of stomach cancer (approximately 2.5% per year, with rates of 6.6/100 000 in men and 4.9/100 000 in women in 2005-2007) and lung cancer (2-2.5% per year, 11.0/100 000 in men and 4.5/100 000 in women in 2005-2007). Mortality leveled off only since the early 1990s for breast and prostate, and since the late 1990s for colorectal cancer. Death rates from cancer in Mexico remained low on a worldwide scale and showed favorable trends over more recent calendar years. Mortality from (cervix) uterine cancer still represents a major public health priority in this country. European Journal of Cancer Prevention 20:355-363 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Aims and Background This report provides data and statistics for cancer mortality in Italy in 2003, updating previous work on the issue. Methods Cancer death certification numbers by cause and estimates of the resident population in 2003, stratified by sex and quinquennium of age, were obtained from the World Health Organization database. In 2003, cause of death encoding was changed from the 9th to the 10th Revision of the International Classification of Diseases (ICD). All cancers and groups of cancers, classified according to the 10th revision of the ICD, were grouped into 30 categories, besides other and unspecified sites. Mortality rates were age-standardized on the world standard population in five-year age groups up to 80-84 years and 85+. Results The total number of cancer deaths in Italy was 167,144 in 2003 (96,127 men and 71,017 women), with age-standardized death rates of 160.63 and 89.32 per 100,000 inhabitants, respectively. Lung cancer mortality in men confirmed the favorable trend, with rates of 43.72/100,000 and 51.68/100,000 in the all ages and truncated groups, respectively. Most other tobacco-related cancers were also declining in men but not in women. Cancers of the female breast and uterus (cervix and corpus) continue to decrease, with overall rates of 17.11/100,000 and 3.71/100,000. Declines were also observed in stomach and testis cancers. A few cancer sites such as prostate and multiple myeloma appeared to rise, but these trends were mainly due to the ICD change and the stricter age-standardization categories (80-84 and 85+ instead of 80+). Conclusions Trends in cancer mortality remained favorable for most major cancer sites, mainly in men for tobacco-related cancers. Due to the classification changes brought about by the change of ICD and the stricter age standardization, the present mortality rates should only be compared to previous ones with due caution.

BACKGROUND: Over the last 4 decades, childhood cancer mortality declined in most developed areas of the world. However, scant information is available from middle-income and developing countries. The authors analyzed and compared patterns in childhood cancer mortality in 24 developed and middle-income countries in America, Asia, and Oceania between 1970 and 2007. METHODS: Childhood age-standardized annual mortality rates were derived from the World Health Organization (WHO) database for all neoplasms, bone and kidney cancer, non-Hodgkin lymphoma (NHL), and leukemias. RESULTS: Since 1970, rates for all childhood cancers dropped from approximately 8 per 100,000 boys to 3 per 100,000 boys and from 6 per 100,000 girls to 2 per 100,000 girls in North America and Japan. Latin American countries registered rates of approximately 5 per 100,000 boys and 4 per 100,000 girls for 2005 through 2007, similar to the rates registered in more developed areas in the early 1980s. Similar patterns were observed for leukemias, for which the mortality rates were 0.81 per 100,000 boys and 0.55 per 100,000 girls in North America, 0.86 per 100,000 boys and 0.68 per 100,000 girls in Japan, and 1.98 per 100,000 boys and 1.65 per 100,000 girls in Latin America for 2005 through 2007. Bone cancer rates for 2005 through 2007 were approximately 2-fold higher in Argentina than in the United States. During the same period, Mexico registered the highest rate for kidney cancer and Colombia registered the highest rate for NHL, whereas the lowest rates were registered by Japan for kidney and by Japan and the United States for NHL. CONCLUSIONS: Improvements in the adoption of current integrated treatment protocols in Latin American and other lower- and middle-income countries worldwide would avoid a substantial proportion of childhood cancer deaths. Cancer 2010;. © 2010 American Cancer Society.

To update trends in childhood cancer mortality in Europe, we analysed mortality data derived from the World Health Organization for all childhood neoplasms, bone and kidney cancers, non-Hodgkin's lymphomas (NHL) and leukaemias, in 30 European countries up to 2007. Between 1990-1994 and 2005-2007, mortality from all neoplasms steadily declined in most European countries (from 5.2 to 3.5/100,000 boys and from 4.3 to 2.8/100,000 girls in the European Union, EU). In 2005-2007, however, mortality rates from childhood cancers were still higher in countries from Eastern (4.9/100,000 boys and 3.9/100,000 girls) and Southern (4.0/100,000 boys and 3.1/100,000 girls) Europe than in those from Western (3.1/100,000 boys and 2.5/100,000 girls) and Northern (3.2/100,000 boys and 2.5/100,000 girls) Europe. Similar temporal trends and geographic patterns were observed for leukaemias, with declines from 1.7 to 0.9/100,000 boys and from 1.3 to 0.7/100,000 girls between 1990-1994 and 2005-2007 in the EU. For kidney cancer and NHL mortality rates were low and have been declining in larger European countries over the last 15 years. The pattern of trends was less clear for bone cancer, with no systematic downward trends at age 0-14, though some fall was evident at age 15-19. Thus, mortality from childhood cancer continued to decline over more recent years in most European countries. However, the mortality rates in Eastern - but also Southern - European countries in the mid 2000's were similar to those in the Western and Northern European ones in the early 1990's. Some further improvement in childhood cancer mortality is therefore achievable through more widespread and better adoption of currently available treatments. (C) 2009 Elsevier Ltd. All rights reserved.

We investigated gastric cancer risk in relation to dietary glycemic index (GI) and glycemic load (GL), which represent indirect measures of carbohydrate absorption and consequently of dietary insulin demand, in a case-control study conducted in northern Italy between 1997 and 2007, including 230 patients with the incident, histologically confirmed gastric cancer and 547 frequency matched controls, admitted to the same hospitals as cases with acute non-neoplastic conditions. We used conditional logistic regression models, including terms for major recognised gastric cancer risk factors and non-carbohydrate energy intake. The odds ratios (ORs) in the highest vs lowest quintile were 1.9 (95% CI: 1.0–3.3) for GI and 2.5 (95% CI: 1.3–4.9) for GL. Compared with participants reporting low GL and high fruits/vegetables intake, the OR rose across strata of high GL and low fruits/vegetables, to reach 5.0 (95% CI: 2.2–11.5) for those reporting low fruits/vegetables intake and high GL. Our study may help to explain the direct relation observed in several studies between starchy foods and gastric cancer risk.