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{ "id": "10709885", "text": "Coeliac disease has emerged as a public health problem. The aim of the present study was to analyse trends in the occurrence of symptomatic coeliac disease in Swedish children from 1973 to 1997, and to explore any temporal relationship to changes in infant dietary patterns. We established a population-based prospective incidence register of coeliac disease in 1991, and, in addition, retrospective data from 1973 were collected. A total of 2151 cases fulfilled the diagnostic criteria. Furthermore. We collected national data on a yearly basis on duration of breastfeeding, intake of gluten-containing cereals and recommendations on when and how to introduce gluten into the diet of infants. From 1985 to 1987 the annual incidence rate in children below 2 y of age increased fourfold to 200-240 cases per 100000 person years, followed from 1995 by a sharp decline to the previous level of 50-60 cases per 100000 person years. This epidemic pattern is quite unique for a chronic disease of immunological pathogenesis, suggesting that prevention could be possible. The ecological observations made in this study are compatible with the epidemic being the result, at least in part, of a change in and an interplay among three factors within the area of infant feeding, i.e. amount of gluten given, age at introduction of gluten, and whether breastfeeding was ongoing or not when gluten was introduced. Other factor(s) may also have contributed, and the search for these should be intensified." }

{ "id": "11080708", "text": "BACKGROUND:\nEvents occurring during fetal life may affect the development of the immune and respiratory systems and increase the risk of asthma and allergic diseases.\n\nOBJECTIVES:\nWe sought to elaborate the relations between the occurrence of pregnancy complications and other pregnancy-related conditions and the risk of bronchial obstruction during the first 2 years of life and the occurrence of asthma and allergic rhinitis by the age of 4 years. Pregnancy complications were considered both as predictors of the health outcomes and as possible effects caused by other prenatal factors.\n\nMETHODS:\nA population-based, 4-year, cohort study was carried out involving 2531 children born in Oslo, Norway. We collected information on maternally related (hyperemesis, hypertension, and preeclampsia) and uterus-related complications in pregnancy (antepartum hemorrhage, preterm contractions, insufficient placenta, and restricted growth of the uterus) and the child's health and environmental exposures at birth and at 6, 12, 18, and 24 months and 4 years of age. The outcomes of interest were bronchial obstruction during the first 2 years and asthma and allergic rhinitis at the age of 4 years.\n\nRESULTS:\nIn a logistic regression analysis adjusting for potential confounders, uterus-related, but not other pregnancy-related, complications increased the risk of bronchial obstruction (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.3-3.4), asthma (OR, 3.0; 95% CI, 1.8-5.4), and allergic rhinitis (OR, 2.9; 95% CI, 1.6-5.2). These relations were similar in children of atopic and nonatopic parents.\n\nCONCLUSIONS:\nUterus-related complications in pregnancy increase the risk of having asthma and allergic rhinitis in childhood." }

{ "id": "11312420", "text": "BACKGROUND:\nOral methoxsalen (psoralen) and ultraviolet A radiation (PUVA) is a highly effective therapy for psoriasis and many other skin conditions. It is carcinogenic. Previously we reported an increased risk of melanoma that first emerged 15 years after first treatment.\n\nOBJECTIVE:\nOur purpose is to present additional data concerning the associations of previous exposure to PUVA, the passage of time, and the risk of malignant melanoma.\n\nMETHODS:\nWe have prospectively studied a cohort of 1380 patients first treated with PUVA in 1975 and 1976. We have documented the occurrence of melanoma and in this report compare the observed and expected incidence of melanoma in this cohort, particularly melanomas developing since our earlier report (ie, after March 1996).\n\nRESULTS:\nSince 1975, 23 patients have developed 26 invasive or in situ cutaneous melanomas. In an average of 2.25 years since our last report, we detected 7 additional invasive melanomas (incidence rate ratio, 8.4; 95% confidence interval, 3.4-17.3).\n\nCONCLUSION:\nBeginning 15 years after first exposure to PUVA, an increased risk of melanoma is observed in our cohort of PUVA-treated patients. This risk is greater in patients exposed to high doses of PUVA, appears to be increasing with the passage of time, and should be considered in determining the risks and benefits of this therapy." }

{ "id": "11522737", "text": "BACKGROUND & AIMS:\nResults concerning an association between cholecystectomy and right-sided colon cancer are inconsistent. Little is known about the relation between cholecystectomy and small bowel cancer. Therefore, we evaluated cholecystectomy and risk of bowel cancer.\n\nMETHODS:\nCholecystectomized patients, identified through the Swedish Inpatient Register, from 1965 through 1997, were followed up for subsequent cancer. The standardized incidence ratio (SIR) estimated relative risk.\n\nRESULTS:\nIn total, 278,460 cholecystectomized patients, contributing 3,519,682 person-years, were followed up for a maximum of 33 years after surgery. Cholecystectomized patients had an increased risk of proximal intestinal adenocarcinoma, which gradually declined with increasing distance from the common bile duct. The risk was significantly increased for adenocarcinoma (SIR, 1.77; 95% confidence interval [CI], 1.37-2.24) and carcinoids of the small bowel (SIR, 1.71; 95% CI, 1.39-2.08), and right-sided colon cancer (SIR, 1.16; 95% CI, 1.08-1.24). No association was found with more distal bowel cancer. The gradient was further pronounced when surgery of the common bile duct was included. The associations remained increased up to 33 years after cholecystectomy. No differences between sexes were found.\n\nCONCLUSIONS:\nCholecystectomy increases the risk of intestinal cancer, a risk that declines with increasing distance from the common bile duct. Changes in the intestinal exposure to bile might be the underlying biological mechanism." }

{ "id": "11976167", "text": "BACKGROUND:\nCeliac disease, or permanent gluten-sensitive enteropathy, is an immunologic disease strictly dependent on exposure to wheat gluten or related proteins in rye and barley.\n\nOBJECTIVE:\nThe aim of this study was to explore whether breast-feeding and the mode of introducing dietary gluten influence the risk of celiac disease in childhood.\n\nDESIGN:\nA population-based incident case-referent study of Swedish children, 627 cases with celiac disease and 1254 referents, was conducted; 78% of the matched sets were included in the final analyses. A questionnaire was used to assess patterns of food introduction to infants. Models were built, based on current epidemiologic and immunologic knowledge of celiac disease, to study the potential influence of dietary patterns on disease risk and were evaluated by conditional logistic regression in multivariate analyses.\n\nRESULTS:\nThe risk of celiac disease was reduced in children aged <2 y if they were still being breast-fed when dietary gluten was introduced [adjusted odds ratio (OR): 0.59; 95% CI: 0.42, 0.83]. This effect was even more pronounced in infants who continued to be breast-fed after dietary gluten was introduced (OR: 0.36; 95% CI: 0.26, 0.51). The risk was greater when gluten was introduced in the diet in large amounts (OR: 1.5; 95% CI: 1.1, 2.1) than when introduced in small or medium amounts. In older children, these risk factors were of no or only minor importance.\n\nCONCLUSIONS:\nThe gradual introduction of gluten-containing foods into the diet of infants while they are still being breast-fed reduces the risk of celiac disease in early childhood and probably also during the subsequent childhood period." }

{ "id": "12093765", "text": "BACKGROUND:\nInterleukin (IL)-18 plays a central role in orchestrating the cytokine cascade and accelerates atherosclerosis and plaque vulnerability in animal models. However, epidemiological data evaluating the role of IL-18 levels in atherosclerosis are lacking.\n\nMETHODS AND RESULTS:\nIn a prospective study of 1229 patients with documented coronary artery disease, we measured baseline serum concentrations of IL-18 and other markers of inflammation. During the follow-up period (median, 3.9 years), 95 patients died of cardiovascular causes. Median serum concentrations of IL-18 were significantly higher among patients who had a fatal cardiovascular event than among those who did not (68.4 versus 58.7 pg/mL; P<0.0001). The hazard risk ratio of future cardiovascular death increased with increasing quartiles of IL-18 (hazard risk ratio, 1.46; 95% CI 1.21 to 1.76; P for trend <0.0001). After adjustment for most potential confounders, including the strong predictor ejection fraction as well as the inflammatory variables IL-6, high-sensitive C-reactive protein, and fibrinogen, this relation remained almost unchanged, such that patients within the highest quartile of IL-18 had a 3.3-fold increase in hazard risk compared with those in the first quartile (95% CI, 1.3 to 8.4, P=0.01). This relation was observed in patients with stable angina and patients with unstable angina at baseline.\n\nCONCLUSIONS:\nSerum IL-18 level was identified as a strong independent predictor of death from cardiovascular causes in patients with coronary artery disease regardless of the clinical status at admission. This result strongly supports recent experimental evidence of IL-18-mediated inflammation leading to acceleration and vulnerability of atherosclerotic plaques." }

{ "id": "14519706", "text": "CONTEXT:\nDietary factors modifying type 1 diabetes mellitus (DM) risk have been proposed, but little is known if they trigger the islet autoimmunity that precedes clinical disease.\n\nOBJECTIVE:\nTo determine whether breastfeeding duration, food supplementation, or age at introduction of gluten-containing foods influences the risk of developing islet autoantibodies.\n\nDESIGN AND SETTING:\nProspective natural history cohort study conducted from 1989 to 2003 in inpatient/outpatient clinics in Germany.\n\nPARTICIPANTS:\nThe BABYDIAB study follows newborn children of parents with type 1 DM. Eligibility requirements were met in 1610 children. Blood samples were obtained at birth, age 9 months, 2, 5, and 8 years. Dropout rate was 14.4% by age 5 years. Breastfeeding data were obtained by prospective questionnaires (91% complete), and food supplementation data were obtained by family interview (72% for food supplementation and 80% for age of gluten introduction).\n\nMAIN OUTCOME MEASURE:\nDevelopment of islet autoantibodies (insulin, glutamic acid decarboxylase, or IA-2 antibodies) in 2 consecutive blood samples.\n\nRESULTS:\nLife-table islet autoantibody frequency was 5.8% (SE, 0.6%) by age 5 years. Reduced total or exclusive breastfeeding duration did not significantly increase the risk of developing islet autoantibodies. Food supplementation with gluten-containing foods before age 3 months, however, was associated with significantly increased islet autoantibody risk (adjusted hazard ratio, 4.0; 95% confidence interval, 1.4-11.5; P =.01 vs children who received only breast milk until age 3 months). Four of 17 children who received gluten foods before age 3 months developed islet autoantibodies (life-table 5-year risk, 24%; SE, 10%). All 4 children had the high-risk DRB1*03/04,DQB1*0302 genotype. Early exposure to gluten did not significantly increase the risk of developing celiac disease-associated autoantibodies. Children who first received gluten foods after age 6 months did not have increased risks for islet or celiac disease autoantibodies.\n\nCONCLUSION:\nEnsuring compliance to infant feeding guidelines is a possible way to reduce the risk of development of type 1 DM autoantibodies." }

{ "id": "15898094", "text": "BACKGROUND:\nExposure to occupational hazards among firefighters may lead to increased mortality from cancer, lung, or heart disease.\n\nMETHODS:\nAge- and gender-adjusted mortality rates of 34,796 male and 2,017 female Florida professional firefighters between 1972 and 1999 were compared with the Florida general population.\n\nRESULTS:\nOne thousand four hundred eleven male and 38 female firefighter deaths with known causes were identified. In male firefighters, mortality due to all causes and most non-malignant diseases was significantly less than expected. There was no excess overall mortality from cancer, but excesses existed for male breast cancer [standardized mortality ratio (SMR = 7.41; 95% confidence interval (CI): 1.99-18.96) and thyroid cancer (SMR = 4.82; 95% CI: 1.30-12.34)]. Mortality from bladder cancer was increased and approached statistical significance (SMR = 1.79; 95% CI: 0.98-3.00). Firefighters certified between 1972 and 1976 had excess mortality from bladder cancer (SMR = 1.95; 95% CI: 1.04-3.33). Female firefighters had similar morality patterns to Florida women except for atherosclerotic heart disease (SMR = 3.85; 95% CI: 1.66-7.58).\n\nCONCLUSIONS:\nExcess mortality risk from bladder cancer may be related to occupational exposure during firefighting. The thyroid cancer and breast cancer risk in males, as well as the excess risk of cardiovascular disease mortality noted in females warrant further investigation." }

{ "id": "16364180", "text": "Recent consensus statements demonstrate the breadth of the chronic rhinosinusitis (CRS) differential diagnosis. However, the classification and mechanisms of different CRS phenotypes remains problematic." }

{ "id": "16434451", "text": "CONTEXT:\nPolycystic ovary syndrome (PCOS) is associated with menstrual and reproductive abnormalities, insulin resistance, and obesity.\n\nOBJECTIVE:\nThe objective of this study was to determine the prevalence of diagnosed PCOS and its association with cardiovascular risk factors.\n\nSETTING:\nThe study is set in an integrated health care delivery system in northern California.\n\nPATIENTS:\nA total of 11,035 women with PCOS were identified by one or more outpatient diagnoses of PCOS using health plan databases. An age-matched sample of women without PCOS was also selected.\n\nOUTCOME MEASURES:\nPrevalence of PCOS and targeted cardiovascular risk factors [hypertension, dyslipidemia, diabetes mellitus, and body mass index (BMI)] were measured.\n\nRESULTS:\nDuring 2002-2004, the prevalence of diagnosed PCOS among female members aged 25-34 yr was 2.6% (95% confidence interval 1.6-1.7%). Women with diagnosed PCOS were more likely than those without PCOS to be obese [BMI > or = 30 mg/m(2); odds ratio (OR) 4.21, 3.96-4.47]. Furthermore, PCOS was associated with diabetes (OR 2.45, confidence interval 2.16-2.79), hypertension (OR 1.41, 1.31-1.51) and known dyslipidemia (OR 1.53, 1.39-1.68), even after adjusting for BMI and known confounders. Among women with PCOS, compared with whites, Blacks and Hispanics were more likely and Asians less likely to be obese; Asians and Hispanics were more likely to have diabetes; and Blacks were more likely and Hispanics less likely to have hypertension.\n\nCONCLUSIONS:\nWithin a large, community-based population receiving health care, diagnosed PCOS was highly prevalent and associated with a much higher frequency of cardiovascular risk factors that varied by race/ethnicity. Our prevalence estimates likely underestimate the true prevalence of PCOS. Further studies are needed to explore racial/ethnic differences and the extent to which PCOS contributes to future cardiovascular risk." }

{ "id": "16495934", "text": "We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case-case-control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (OR(adj) for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (OR(adj) 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (OR(adj) 2.6 for more than 7000 lifelong hours) and BCC (OR(adj) 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (OR(adj) 2.2 for more than 6000 lifelong hours). In the case-case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma." }

{ "id": "16845665", "text": "BACKGROUND:\nThe familial risk of bladder cancer (BC) is not well understood and, to date, little attention has been paid to the joint effect of smoking and family history in modifying the risk of BC. The authors investigated the role of family history in association with the risk of BC.\n\nMETHODS:\nCase and control probands were identified as part of an on-going BC case-control study. The relative risk associated with a family history of BC was estimated.\n\nRESULTS:\nIn total, 713 cases and 658 controls were included. In a case-control analysis, compared with individuals who never smoked and who had no family history of BC, probands who had smoked and who also had a positive family history were at 5.31-fold increased risk of BC (P for interaction = .04). The 713 case probands and the 658 controls reported 5160 and 4816 first-degree relatives, respectively. Compared with never-smoking relatives who had probands diagnosed with BC at an older age (age >65 years), ever-smoking relatives who had probands diagnosed at a younger age (ages 40-65 years) showed a 6.89-fold (95% confidence interval, from 2.25-fold to 21.12-fold) increased risk. Similar results were obtained for the joint effects of family history of BC and smoking. CONCLUSIONS. The current results indicated that a positive family history of BC may have interacted with smoking habits to increase the risk of BC in the study population." }

{ "id": "16864817", "text": "OBJECTIVE:\nTo assess the influence of the body mass index (BMI) on the prevalence and severity of chronic daily headache (CDH) and its most frequent subtypes, transformed migraine (TM) and chronic tension-type headache (CTTH).\n\nMETHODS:\nThe authors gathered information on headache, medical features, height, and weight using a computer-assisted telephone interview. Participants were divided into five categories, based on BMI: underweight (<18.5), normal weight (18.5 to 24.9), overweight (25 to 29.9), obese (30 to 34.9), and morbidly obese (>35). The prevalence and severity of CDH, TM, and CTTH were assessed. Multivariate analyses modeling these diagnoses as a function of BMI were conducted.\n\nRESULTS:\nAmong 30,215 participants, the prevalence of CDH was 4.1%; 1.3% had TM and 2.8% CTTH. In contrast with the normal weight group (3.9%), the prevalence of CDH was higher in obese (5.0% [odds ratio (OR) = 1.3, 95% CI = 1.1-1.6]) and morbidly obese (6.8% [OR = 1.8, 95% CI = 1.4 to 2.2]). BMI had a strong influence on the prevalence of TM, which ranged from 0.9% of the normal weighted to 1.2% of the overweight (OR = 1.4 [1.1 to 1.8]), 1.6% of the obese (OR = 1.7 [1.2 to 2.43]), and 2.5% of the morbidly obese (OR = 2.2 [1.5 to 3.2]). The effects of the BMI on the prevalence of CTTH were just significant in the morbidly obese group. Adjusted analyses showed that obesity was associated with CDH and TM but not CTTH.\n\nCONCLUSIONS:\nChronic daily headache and obesity are associated. Obesity is a stronger risk factor for transformed migraine than for chronic tension-type headache." }

{ "id": "17040332", "text": "Review of epidemiological and clinical studies suggests that sleep disorders are disproportionately observed in specific headache diagnoses (eg, migraine, tension-type, cluster) and other nonspecific headache patterns (ie, chronic daily headache, \"awakening\" or morning headache). Interestingly, the sleep disorders associated with headache are of varied types, including obstructive sleep apnea (OSA), periodic limb movement disorder, circadian rhythm disorder, insomnia, and hypersomnia. Headache, particularly morning headache and chronic headache, may be consequent to, or aggravated by, a sleep disorder, and management of the sleep disorder may improve or resolve the headache. Sleep-disordered breathing is the best example of this relationship. Insomnia is the sleep disorder most often cited by clinical headache populations. Depression and anxiety are comorbid with both headache and sleep disorders (especially insomnia) and consideration of the full headache-sleep-affective symptom constellation may yield opportunities to maximize treatment. This paper reviews the comorbidity of headache and sleep disorders (including coexisting psychiatric symptoms where available). Clinical implications for headache evaluation are presented. Sleep screening strategies conducive to headache practice are described. Consideration of the spectrum of sleep-disordered breathing is encouraged in the headache population, including awareness of potential upper airway resistance syndrome in headache patients lacking traditional risk factors for OSA. Pharmacologic and behavioral sleep regulation strategies are offered that are also compatible with treatment of primary headache." }

{ "id": "17164760", "text": "In a prospective cohort study, a close to two-fold elevated risk of bladder cancer was found among men reporting a history of gonorrhoea (relative risk=1.92, 95% CI=1.10-3.33). Our finding warrants further examination of the role of gonorrhoea in bladder carcinogenesis." }

{ "id": "17311987", "text": "Perforin is a cytolytic protein expressed mainly in activated cytotoxic lymphocytes and natural killer cells. Inherited perforin mutations account for 20% to 40% of familial hemophagocytic lymphohistiocytosis, a fatal disease of early childhood characterized by the absence of functional perforin. Aplastic anemia, the paradigm of immune-mediated bone marrow failure syndromes, is characterized by hematopoietic stem cell destruction by activated T cells and Th1 cytokines. We examined whether mutations in the perforin gene occurred in acquired aplastic anemia. Three nonsynonymous PRF1 mutations among 5 unrelated patients were observed. Four of 5 patients with the mutations showed some hemophagocytosis in the bone marrow at diagnosis. Perforin protein levels in these patients were very low or absent, and perforin granules were completely absent. Natural killer (NK) cell cytotoxicity from these patients was significantly decreased. Our data suggest that PRF1 genetic alterations help explain the aberrant proliferation and activation of cytotoxic T cells and may represent genetic risk factors for bone marrow failure." }

{ "id": "17427485", "text": "Clinically silent adrenal masses (incidentaloma) are incidentally discovered lesions when noninvasive imaging methods (ultrasonography--USG, computer tomography--CT, magnetic resonance imaging--MRI) are performed for the reason other than known or suspected adrenal disease. Most of studies report the prevalence of adrenal incidentaloma range between 1 and 10% in radiological series." }

{ "id": "17634245", "text": "OBJECTIVES:\nAir pollution has been associated with an increased risk for lung cancer. We examined whether long-term air pollution is associated with bladder cancer risk.\n\nMETHODS:\nInformation from a case-control study in Spain that included 1219 incident cases and 1271 hospital controls was used. Information on residential history including several indicators of exposure to air pollution and other potential risk factors was collected in a face-to-face computerised personal interview. Odds ratios (OR) and 95% confidence intervals (95% CI) were adjusted for age, gender, region, smoking, occupation, water contaminants and diet.\n\nRESULTS:\nLiving more than 40 years in a city with a population of more than 100 000 was associated with an increased risk for bladder cancer overall (OR 1.30, 95% CI 1.04 to 1.63). Emissions of polycyclic aromatic hydrocarbons and diesel from industries near the residence, as evaluated by experts, were associated with an increased risk (OR 1.29, 95% CI 0.85 to 1.98), while lower or no excess risks were observed for other pollution-related variables. Odds ratios among never smokers tended to be higher than among smokers.\n\nCONCLUSIONS:\nThe small to moderate positive associations found for several indices of air pollution and bladder cancer, while suggestive of excess risk, require further evaluation in other settings." }

{ "id": "17646581", "text": "BACKGROUND:\nConsumption of soft drinks has been linked to obesity in children and adolescents, but it is unclear whether it increases metabolic risk in middle-aged individuals.\n\nMETHODS AND RESULTS:\nWe related the incidence of metabolic syndrome and its components to soft drink consumption in participants in the Framingham Heart Study (6039 person-observations, 3470 in women; mean age 52.9 years) who were free of baseline metabolic syndrome. Metabolic syndrome was defined as the presence of > or = 3 of the following: waist circumference > or = 35 inches (women) or > or = 40 inches (men); fasting blood glucose > or = 100 mg/dL; serum triglycerides > or = 150 mg/dL; blood pressure > or = 135/85 mm Hg; and high-density lipoprotein cholesterol < 40 mg/dL (men) or < 50 mg/dL (women). Multivariable models included adjustments for age, sex, physical activity, smoking, dietary intake of saturated fat, trans fat, fiber, magnesium, total calories, and glycemic index. Cross-sectionally, individuals consuming > or = 1 soft drink per day had a higher prevalence of metabolic syndrome (odds ratio [OR], 1.48; 95% CI, 1.30 to 1.69) than those consuming < 1 drink per day. On follow-up (mean of 4 years), new-onset metabolic syndrome developed in 717 of 4033 participants (17.8%) consuming < 1 drink/day and in 433 of 2006 persons (21.6%) [corrected] consuming > or = 1 soft drink/day [corrected] Consumption of > or = 1 soft drink per day was associated with increased odds of developing metabolic syndrome (OR, 1.44; 95% CI, 1.20 to 1.74), obesity (OR, 1.31; 95% CI, 1.02 to 1.68), increased waist circumference (OR, 1.30; 95% CI, 1.09 to 1.56), impaired fasting glucose (OR, 1.25; 95% CI, 1.05 to 1.48), higher blood pressure (OR, 1.18; 95% CI, 0.96 to 1.44), hypertriglyceridemia (OR, 1.25; 95% CI, 1.04 to 1.51), and low high-density lipoprotein cholesterol (OR, 1.32; 95% CI 1.06 to 1.64).\n\nCONCLUSIONS:\nIn middle-aged adults, soft drink consumption is associated with a higher prevalence and incidence of multiple metabolic risk factors." }

{ "id": "17671226", "text": "Cigarette smoking is a major risk factor for bladder cancer and a prominent point source of 4-aminobiphenyl (4-ABP), a recognized human bladder carcinogen. 4-ABP-hemoglobin (Hb) adducts are established biomarkers of 4-ABP exposure in humans. The role of environmental tobacco smoke (ETS) in the etiology of bladder cancer is largely unknown. As part of a large population-based bladder cancer study in Los Angeles County, California, lifetime exposure to ETS was ascertained for 148 cases and 292 control subjects who had never used any tobacco products over their lifetime. 4-ABP-Hb adducts were quantitatively measured on 230 control subjects. Female lifelong nonsmokers living with two or more smokers during childhood were significantly related to risk of bladder cancer [odds ratio (OR), 3.08; 95% confidence interval (95% CI), 1.16-8.22]. During adulthood, approximately 2-fold risks were seen among women living with a spouse/domestic partner who smoked for > or =10 years or having a coworker who smoked in an indoor environment for > or =10 years. When all sources of ETS exposure were combined, a statistically significant, dose-dependent association (P for trend = 0.03) was noted in women, with the OR for the highest category of ETS exposure being 5.48 (95% CI, 1.06-28.36). Levels of 4-ABP-Hb adducts varied by ETS exposure status among female control subjects. Mean level was lowest in women never exposed to ETS (16.4 pg/g Hb) and highest in those with current ETS exposure (23.6 pg/g Hb). ETS exposure was associated with neither bladder cancer risk nor 4-ABP-Hb adduct levels in male lifelong nonsmokers. In conclusion, ETS is a risk factor for bladder cancer in women who were lifelong nonusers of any tobacco products." }

{ "id": "17684133", "text": "The relationship between family history of cancer in first-degree relatives and risk of bladder cancer was examined in the Spanish Bladder Cancer Study. Information on family history of cancer was obtained for 1,158 newly diagnosed bladder cancer cases and 1,244 controls included in 18 hospitals between 1998 and 2001. A total of 464 (40.1%) cases and 436 (35.1%) controls reported a family history of cancer in >/=1 relative [odds ratio (OR), 1.32; 95% confidence interval (95% CI), 1.11-1.59]; the OR was 1.23 (95% CI, 1.01-1.50) among those with only one relative affected and 1.67 (95% CI, 1.23-2.29) among those with >/=2 affected relatives (P(trend) = 0.0004). A greater risk of bladder cancer was observed among those diagnosed at age </=45 years (OR, 2.67; 95% CI, 1.10-6.50) compared with those diagnosed over age 45 years (OR, 1.27; 95% CI, 1.06-1.52). The OR of bladder cancer among subjects reporting a family history of cancer of the bladder was 2.34 (95% CI, 0.95-5.77). Statistically significant associations emerged between bladder cancer risk and family history of cancer of the esophagus, lung, prostate, and brain. The OR of bladder cancer for those reporting family history of bladder cancer was 4.76 (95% CI, 1.25-18.09) among NAT2-slow acetylators and 1.17 (95% CI, 0.17-7.86) among NAT2-rapid/intermediate acetylators (P(interaction) = 0.609). Among individuals with GSTM1 null and present genotypes, the corresponding ORs were 2.91 (95% CI, 0.44-19.09) and 4.21 (95% CI, 1.26-14.14), respectively (P(interaction) = 0.712). Limitations of our study are small sample size in subgroup analyses, reliability of family history data, and possible residual confounding by shared environmental exposures. Overall, our findings support the hypothesis that genetic factors play a role in bladder cancer etiology. Whether these correspond to low-penetrance cancer-predisposing polymorphisms acting together and/or interacting with environmental factors warrants further research." }

{ "id": "17891891", "text": "Using the fixed-effect model, the author quantitatively estimated the risks of cancers of the colon, bladder, kidneys, and brain as well as non-Hodgkin's lymphoma and leukemia among firefighters. The risk of these six cancers was not markedly elevated when cohort mortality studies were considered. When all mortality studies were considered, however, there was a mild increase in risk for kidney cancer and non-Hodgkin's lymphoma, with a summary relative risk (sumRR) of 1.22 (95% confidence interval [CI] = 1.02-1.43) and 1.40 (95% CI = 1.20-1.60), respectively. A subcohort analysis based on duration of employment revealed that firefighters with 30 or more years of employment had a significantly increased mortality risk for colon cancer, sumRR of 1.51 (95% CI = 1.05-2.11); kidney cancer, sumRR of 6.25 (95% CI = 1.70-16.00); brain cancer, sumRR of 2.53 (95% CI = 1.27 7.07); and leukemia, sumRR of 2.87 (95% CI = 1.43-5.14). After firefighters had 40 or more years of employment, their risk of mortality was significantly increased for colon cancer, sumRR of 4.71 (95% CI = 2.03-9.27); kidney cancer, sumRR of 36.12 (95% CI = 4.03-120.42); and bladder cancer, sumRR of 5.7 (95% CI = 1.56-14.63). The risk for non-Hodgkin's lymphoma was elevated but not significantly so among firefighters with 20 or more years of employment, with sumRR of 1.72 (95% CI = 0.90-3.31). Kidney cancer risk was significantly elevated as early as the second decade of employment." }

{ "id": "17932376", "text": "RATIONALE:\nRisk factors for asthma among farm women are understudied.\n\nOBJECTIVES:\nWe evaluated pesticide and other occupational exposures as risk factors for adult-onset asthma.\n\nMETHODS:\nStudying 25,814 farm women in the Agricultural Health Study, we used self-reported history of doctor-diagnosed asthma with or without eczema and/or hay fever to create two case groups: patients with atopic asthma and those with nonatopic asthma. We assessed disease-exposure associations with polytomous logistic regression.\n\nMEASUREMENTS AND MAIN RESULTS:\nAt enrollment (1993-1997), 702 women (2.7%) reported a doctor's diagnosis of asthma after age 19 years (282 atopic, 420 nonatopic). Growing up on a farm (61% of all farm women) was protective for atopic asthma (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.43-0.70) and, to a lesser extent, for nonatopic asthma (OR, 0.83; 95%CI, 0.68-1.02; P value for difference = 0.008). Pesticide use was almost exclusively associated with atopic asthma. Any use of pesticides on the farm was associated only with atopic asthma (OR, 1.46; 95% CI, 1.14-1.87). This association with pesticides was strongest among women who had grown up on a farm. Women who grew up on farms and did not apply pesticides had the lowest overall risk of atopic asthma (OR, 0.41; 95% CI, 0.27-0.62) compared with women who neither grew up on farms nor applied pesticides. A total of 7 of 16 insecticides, 2 of 11 herbicides, and 1 of 4 fungicides were significantly associated with atopic asthma; only permethrin use on crops was associated with nonatopic asthma.\n\nCONCLUSIONS:\nThese findings suggest that pesticides may contribute to atopic asthma, but not nonatopic asthma, among farm women." }

{ "id": "18311140", "text": "Our genome-wide association study of celiac disease previously identified risk variants in the IL2-IL21 region. To identify additional risk variants, we genotyped 1,020 of the most strongly associated non-HLA markers in an additional 1,643 cases and 3,406 controls. Through joint analysis including the genome-wide association study data (767 cases, 1,422 controls), we identified seven previously unknown risk regions (P < 5 x 10(-7)). Six regions harbor genes controlling immune responses, including CCR3, IL12A, IL18RAP, RGS1, SH2B3 (nsSNP rs3184504) and TAGAP. Whole-blood IL18RAP mRNA expression correlated with IL18RAP genotype. Type 1 diabetes and celiac disease share HLA-DQ, IL2-IL21, CCR3 and SH2B3 risk regions. Thus, this extensive genome-wide association follow-up study has identified additional celiac disease risk variants in relevant biological pathways." }

{ "id": "1833349", "text": "Case-control studies of Alzheimer's disease were re-analysed to examine the association of Alzheimer's disease with family history in first degree relatives of dementia, Down's syndrome and Parkinson's disease. Overall, the relative risk of Alzheimer's disease for those with at least one first degree relative with dementia was 3.5 (95% confidence interval 2.6-4.6). Stratification according to age of onset of Alzheimer's disease showed that the relative risk decreased with increasing onset age. However, among patients with an onset of disease after 80 years, there were still significantly more subjects with one or more first degree relatives with dementia as compared to controls (relative risk 2.6; 95% confidence interval 1.3-5.2). The relative risk of Alzheimer's disease was significantly lower in patients who had one first degree relative with dementia (relative risk 2.6; 95% confidence interval 2.0-3.5) as compared to those who had two or more affected relatives (relative risk 7.5; 95% confidence interval 3.3-16.7). Furthermore, the re-analysis showed a significant association between Alzheimer's disease and family history of Down's syndrome (relative risk 2.7; 95% confidence interval 1.2-5.7), which was strongest in those patients who had a positive family history of dementia. The relative risk of Alzheimer's disease for those with a positive family history of Parkinson's disease was 2.4 (95% confidence interval 1.0-5.8)." }

{ "id": "18591432", "text": "BACKGROUND:\nPrediction of coronary heart disease (CHD) and cerebrovascular disease (CeVD) can aid healthcare providers and prevention programs. Previous reports have focused on traditional cardiovascular risk factors; less information has been available on the role of overweight and obesity.\n\nMETHODS AND RESULTS:\nBaseline data from 4780 Framingham Offspring Study adults with up to 24 years of follow-up were used to assess risk for a first CHD event (angina pectoris, myocardial infarction, or cardiac death) alone, first CeVD event (acute brain infarction, transient ischemic attack, and stroke-related death) alone, and CHD and CeVD events combined. Accelerated failure time models were developed for the time of first event to age, sex, cholesterol, high-density lipoprotein cholesterol, diabetes mellitus (DM), systolic blood pressure, smoking status, and body mass index (BMI). Likelihood-ratio tests of statistical significance were used to identify the best-fitting predictive functions. Age, sex, smoking status, systolic blood pressure, ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were highly related (P<0.01 for all) to the development of first CHD events, and all of the above except sex and DM were highly related to the first CeVD event. BMI also significantly predicted the occurrence of CHD (P=0.05) and CeVD (P=0.03) in multivariable models adjusting for traditional risk factors. The magnitude of the BMI effect was reduced but remained statistically significant when traditional variables were included in the prediction models.\n\nCONCLUSIONS:\nGreater BMI, higher systolic blood pressure, higher ratio of cholesterol to high-density lipoprotein cholesterol, and presence of DM were all predictive of first CHD events, and all but the presence of DM were predictive of first CeVD events. These results suggest that common pathophysiological mechanisms underlie the roles of BMI, DM, and systolic blood pressure as predictors for first CHD and CeVD events." }

{ "id": "19240061", "text": "OBJECTIVE:\nOur previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts.\n\nDESIGN:\n458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p<1 x 10(-04) and were then genotyped in an independent Italian coeliac cohort (538 cases and 593 controls).\n\nRESULTS:\nWe identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p = 1.3 x 10(-08), and rs842647 p = 5.2 x 10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression.\n\nCONCLUSIONS:\nBoth TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappaB) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain approximately 40% of the heritability of coeliac disease." }

{ "id": "19244173", "text": "BACKGROUND:\nWith the exception of breast cancer, little is known about the effect of moderate intakes of alcohol, or of particular types of alcohol, on cancer risk in women.\n\nMETHODS:\nA total of 1,280,296 middle-aged women in the United Kingdom enrolled in the Million Women Study were routinely followed for incident cancer. Cox regression models were used to calculate adjusted relative risks and 95% confidence intervals (CIs) for 21 site-specific cancers according to amount and type of alcoholic beverage consumed. All statistical tests were two-sided.\n\nRESULTS:\nA quarter of the cohort reported drinking no alcohol; 98% of drinkers consumed fewer than 21 drinks per week, with drinkers consuming an average of 10 g alcohol (1 drink) per day. During an average 7.2 years of follow-up per woman 68,775 invasive cancers occurred. Increasing alcohol consumption was associated with increased risks of cancers of the oral cavity and pharynx (increase per 10 g/d = 29%, 95% CI = 14% to 45%, Ptrend < .001), esophagus (22%, 95% CI = 8% to 38%, Ptrend = .002), larynx (44%, 95% CI = 10% to 88%, Ptrend = .008), rectum (10%, 95% CI = 2% to 18%, Ptrend = .02), liver (24%, 95% CI = 2% to 51%, Ptrend = .03), breast (12%, 95% CI = 9% to 14%, Ptrend < .001), and total cancer (6%, 95% CI = 4% to 7%, Ptrend < .001). The trends were similar in women who drank wine exclusively and other consumers of alcohol. For cancers of the upper aerodigestive tract, the alcohol-associated risk was confined to current smokers, with little or no effect of alcohol among never and past smokers (P(heterogeneity) < .001). Increasing levels of alcohol consumption were associated with a decreased risk of thyroid cancer (Ptrend = .005), non-Hodgkin lymphoma (Ptrend = .001), and renal cell carcinoma (Ptrend = .03).\n\nCONCLUSIONS:\nLow to moderate alcohol consumption in women increases the risk of certain cancers. For every additional drink regularly consumed per day, the increase in incidence up to age 75 years per 1000 for women in developed countries is estimated to be about 11 for breast cancer, 1 for cancers of the oral cavity and pharynx, 1 for cancer of the rectum, and 0.7 each for cancers of the esophagus, larynx and liver, giving a total excess of about 15 cancers per 1000 women up to age 75." }

{ "id": "19454285", "text": "BACKGROUND & AIMS:\nCeliac disease (CD) is a common chronic disorder of the small intestine, resulting from aberrant cellular responses to gluten peptides, and often remains undiagnosed. It is a complex genetic disorder, although 95% of the patients carry the risk heterodimer human leukocyte antigen (HLA)-DQ2. Genome-wide association studies on CD have identified 9 non-HLA loci that also contribute to CD risk, most of which are shared with other immune-related diseases. Our aim is to predict the genetic risk for CD using HLA and non-HLA risk alleles.\n\nMETHODS:\nWe selected 10 independent polymorphisms in 2,308 cases and 4,585 controls from Dutch, UK, and Irish populations and categorized the individuals into 3 risk groups, based on their HLA-DQ2 genotype. We used the summed number of non-HLA risk alleles per individual to analyze their cumulative effect on CD risk, adjusting for gender and population group in logistic regression analysis. We validated our findings in 436 Italian cases and 532 controls.\n\nRESULTS:\nCD cases carried more non-HLA risk alleles than controls: individuals carrying > or = 13 risk alleles had a higher CD risk (odds ratio, 6.2; 95% confidence interval, 4.1-9.3) compared with those carrying 0-5 risk alleles. Combining HLA and non-HLA risk genotypes in one model increases sensitivity by 6.2% compared with using only HLA for identification of high-risk individuals with slight decrease in specificity.\n\nCONCLUSIONS:\nWe can use non-HLA risk factors for CD to improve identification of high-risk individuals. Our risk model is a first step toward better diagnosis and prognosis in high-risk families and population-based screening." }

{ "id": "19500688", "text": "BACKGROUND & AIMS:\nSusceptibility to celiac disease (CD) is related to HLA-DQ2 and DQ8 alleles and the heterodimers they encode. The objective of this study was to stratify risk for CD on the basis of HLA-DQ genotype.\n\nMETHODS:\nDNA from 10,191 subjects who are at risk for CD was analyzed for HLA-DQ haplotypes. Individuals with CD were identified as those who tested positive for anti-endomysial immunoglobulin A (EMA+) in an immunofluorescence assay.\n\nRESULTS:\nSamples homozygous for DQ2.5 (HLA-DQA1 05-DQB1 02) or DQ2.2/DQ2.5 (HLA-DQA1 05-DQB1 02 and HLA-DQA1 0201-DQB1 02) comprised 5.38% of the total; 28.28% of these were EMA+ (95% confidence interval [CI], 24.55-32.26). Of the samples that were DQ2.5 heterozygous (HLA-DQA1 05-DQB1 02); 9.09% were EMA+ (95% CI, 7.82-10.51). Among samples in which HLA-DQ8 (HLA-DQA1 03-DQB1 0302) was detected, 8.42% of homozygotes (95% CI, 3.71-15.92) and 2.11% of heterozygotes (95% CI, 1.43-3.00) were EMA+. Samples with DQ2.2/DQ8 or DQ2.5/DQ8 comprised 5.08% of the total, and 11.78% of these were EMA+ (95% CI, 9.13-14.87). HLA-DQ2 and HLA-DQ8 were absent in 4283 samples (42.03% of the total); 0.16% of these samples were EMA+ (95% CI, 0.07-0.34).\n\nCONCLUSIONS:\nHigh-resolution, sequence-specific oligonucleotide probe typing with 35 DQA1-specific and 37 DQB1-specific probes of DNA from more than 10,000 subjects was used to stratify risk of CD in an at-risk U.S. population. DQ2 homozygosity (DQ2.5/DQ2.2+2.5) increased risk for CD, estimated by the rate of EMA positivity, compared with the entire sample population and other DQ genotypes. These data suggest a quantitative relationship between the type/proportion of DQ heterodimers and the risk of CD and identify potential immunotherapeutic targets." }

{ "id": "19515369", "text": "Familial LCAT deficiency (FLD) is a disease characterized by a defect in the enzyme lecithin:cholesterol acyltransferase (LCAT) resulting in low HDL-C, premature corneal opacities, anemia as well as proteinuria and renal failure. We have identified the first French Canadian kindred with familial LCAT deficiency. Two brothers, presenting classical signs of FLD, were shown to be homozygous for a novel LCAT mutation. This c.102delG mutation occurs at the codon for His35 and causes a frameshift that stops transcription at codon 61 abolishing LCAT enzymatic activity both in vivo and in vitro. It has a dramatic effect on the lipoprotein profile, with an important reduction of HDL-C in both heterozygotes (22%) and homozygotes (88%) and a significant decrease in LDL-C in heterozygotes (35%) as well as homozygotes (58%). Furthermore, the lipoprotein profile differs markedly between the two affected brothers who had different APOE genotypes. We propose that APOE could be an important modifier gene explaining heterogeneity in lipoprotein profiles observed among FLD patients. Our results suggest that a LCAT-/- genotype associated with an APOE epsilon2 allele could be a novel mechanism leading to dysbetalipoproteinemia." }

{ "id": "19789839", "text": "Although the risk for most cancers appears to be relatively low in patients with Parkinson's disease (PD), skin cancers and melanomas occur more frequently in the PD population as compared to controls. This article summarizes the findings of cohort studies on skin cancer in Parkinson's disease. Given that melanoma may precede use of L-dopa, the increased risk of melanoma for PD patients cannot be attributed to L-dopa. On the basis of these observations it may be reasonable to recommend that all patients with PD, whether treated with L-dopa or not, should undergo regular dermatological screening for neoplastic or pre-neoplastic skin lesions, especially melanoma." }

{ "id": "20212233", "text": "OBJECTIVE:\nTo evaluate the possible association of Parkinson disease (PD) and melanoma in North America.\n\nDESIGN, SETTING, AND PATIENTS:\nThirty-one centers enrolled patients with idiopathic PD. At visit 1, a neurologist obtained a medical history. At visit 2, a dermatologist recorded melanoma risk factors, performed a whole-body examination, and performed a biopsy of lesions suggestive of melanoma for evaluation by a central dermatopathology laboratory. We compared overall prevalence of melanoma with prevalence calculated from the US Surveillance Epidemiology and End Results (SEER) cancer database and the American Academy of Dermatology skin cancer screening programs.\n\nRESULTS:\nA total of 2106 patients (mean [SD] age, 68.6 [10.6] years; duration of PD, 7.1 [5.7] years) completed the study. Most (84.8%) had received levodopa. Dermatology examinations revealed 346 pigmented lesions; dermatopathological findings confirmed 20 in situ melanomas (0.9%) and 4 invasive melanomas (0.2%). In addition, histories revealed 68 prior melanomas (3.2%). Prevalence (5-year limited duration) of invasive malignant melanoma in the US cohort of patients with PD (n = 1692) was 2.24-fold higher (95% confidence interval, 1.21-4.17) than expected in age- and sex-matched populations in the US SEER database. Age- or sex-adjusted relative risk of any melanoma for US patients was more than 7 times that expected from confirmed cases in American Academy of Dermatology skin cancer screening programs.\n\nCONCLUSIONS:\nMelanoma prevalence appears to be higher in patients with PD than in the general population. Despite difficulties in comparing other databases with this study population, the study supports increased melanoma screening in patients with PD." }

{ "id": "20231496", "text": "OBJECTIVE:\nTo quantify the risk of subsequent primary cancers among patients with primary cutaneous malignant melanoma.\n\nDESIGN:\nPopulation-based registry study.\n\nSETTING:\nWe evaluated data from 9 cancer registries of the Surveillance, Epidemiology, and End Results program from 1973-2006.\n\nPARTICIPANTS:\nWe included 89 515 patients who survived at least 2 months after their initial melanoma diagnosis.\n\nRESULTS:\nOf the patients with melanoma, 10 857 (12.1%) developed 1 or more subsequent primary cancers. The overall risk of a subsequent primary cancer increased by 28% (observed to expected [O:E] ratio = 1.28). One quarter of the cancers were subsequent primary melanomas (O:E = 8.61). Women with head and neck melanoma and patients younger than 30 had markedly increased risks (O:E = 13.22 and 13.40, respectively) of developing a subsequent melanoma. Second melanomas were more likely to be thin than were the first of multiple primary melanomas (thickness at diagnosis <1.00 mm, 77.9% vs 70.3%, respectively; P < .001). Melanoma survivors had increased risk of developing several cancers; the most common cancers with elevated risks were breast, prostate, and non-Hodgkin lymphoma (O:E = 1.10, 1.15, and 1.25, respectively).\n\nCONCLUSIONS:\nMelanoma survivors have an approximately 9-fold increased risk of developing subsequent melanoma compared with the general population. The risk remains elevated more than 20 years after the initial melanoma diagnosis. This increased risk may be owing to behavioral factors, genetic susceptibility, or medical surveillance. Although the percentage of subsequent primary melanomas thicker than 1 mm is lower than for the first of multiple primary melanomas, it is still substantial. Melanoma survivors should remain under surveillance not only for recurrence but also for future primary melanomas and other cancers." }

{ "id": "20548022", "text": "We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure." }

{ "id": "20798970", "text": "Patients with longstanding extensive colitis, both ulcerative colitis and Crohn's colitis, have an increased risk of developing colorectal cancer. Because of this risk, colonoscopic surveillance for neoplasia is recommended by most authorities. Although there has been no randomised controlled trial to demonstrate surveillance effectiveness, there are several retrospective comparative studies, which suggest that surveillance reduces colorectal cancer mortality. Over the past decade there have been a number of developments in our understanding of colitis cancer. We have discovered that the severity of colorectal inflammation is an important risk factor, in addition to other known risk factors such as the extent and duration of colitis, primary sclerosing cholangitis and a family history of colorectal cancer. Endoscopic techniques have also improved and evidence now demonstrates that pancolonic chromoendoscopy yields significantly more intraepithelial neoplasia than random biopsies. Endoscopic resection of well-circumscribed lesions is now also recognised as being an appropriate strategy, potentially reducing the number of patients requiring colectomy. It is hoped that such developments will further improve the effectiveness of colitis surveillance." }

{ "id": "21447005", "text": "Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis. It is characterized by non-malignant lymphoproliferation autoimmunity mostly directed toward blood cells and increased risk of lymphoma. Majority of patients with ALPS harbor heterozygous germline mutations in the gene for the TNF receptor-family member Fas (CD 95, Apo-1) which are inherited in an autosomal dominant fashion. Somatic Fas mutations are the second most common genetic etiology of ALPS. Additionally mutations in the genes encoding Fas-ligand (FASLG), caspase 10 (CASP10) and caspase 8 (CASP8), NRAS and KRAS have been identified in a small number of patients with ALPS and related disorders. Approximately one-third of patients with ALPS have yet unidentified defect. ALPS was initially thought to be a very rare disease, but recent studies have shown that it may be more common than previously thought. Testing for ALPS should therefore be considered in patients with unexplained lymphadenopathy, cytopenias, and hepatosplenomegaly. There have been significant advances in the understanding of the pathophysiology of ALPS in last few years which has resulted in the development of new diagnostic criteria and a number of targeted therapies. This review describes the clinical and laboratory manifestations found in patients with ALPS, as well as the molecular basis for the disease and new advances in treatment." }

{ "id": "22294430", "text": "Evidence concerning the role of Helicobacter pylori infection in the development of colorectal cancer remains controversial. The authors assessed the association of H. pylori seroprevalence with risk of colorectal cancer in a large population-based case-control study from Germany in 2003-2007. Serum antibodies to H. pylori in general and the cytotoxin-associated gene A protein (CagA) were measured in 1,712 incident colorectal cancer cases and 1,669 controls. The association between H. pylori seroprevalence and colorectal cancer risk was estimated by logistic regression, with adjustment for potential confounders and stratification by age group, sex, anatomic subsites, and cancer stage. Overall, H. pylori seroprevalence was higher in cases (46.1%) than in controls (40.1%), resulting in an age- and sex-adjusted odds ratio of 1.30 (95% confidence interval (CI): 1.14, 1.50). Adjustment for established colorectal cancer risk factors decreased the odds ratio to 1.26 (95% CI: 1.09, 1.47), with a further reduction to 1.18 (95% CI: 1.01, 1.38) after additional adjustment for previous colorectal endoscopy. Stratified analyses showed risk elevation to be essentially confined to left-sided colorectal cancer, with an odds ratio of 1.22 (95% CI: 1.02, 1.45), suggesting that H. pylori infection may be associated with a small yet relevant risk increase in the left colorectum." }

{ "id": "22833605", "text": "OBJECTIVE:\nTo estimate the burden of melanoma resulting from sunbed use in western Europe.\n\nDESIGN:\nSystematic review and meta-analysis.\n\nDATA SOURCES:\nPubMed, ISI Web of Science (Science Citation Index Expanded), Embase, Pascal, Cochrane Library, LILACS, and MedCarib, along with published surveys reporting prevalence of sunbed use at national level in Europe.\n\nSTUDY SELECTION:\nObservational studies reporting a measure of risk for skin cancer (cutaneous melanoma, squamous cell carcinoma, basal cell carcinoma) associated with ever use of sunbeds.\n\nRESULTS:\nBased on 27 studies ever use of sunbeds was associated with a summary relative risk of 1.20 (95% confidence interval 1.08 to 1.34). Publication bias was not evident. Restricting the analysis to cohorts and population based studies, the summary relative risk was 1.25 (1.09 to 1.43). Calculations for dose-response showed a 1.8% (95% confidence interval 0% to 3.8%) increase in risk of melanoma for each additional session of sunbed use per year. Based on 13 informative studies, first use of sunbeds before age 35 years was associated with a summary relative risk of 1.87 (1.41 to 2.48), with no indication of heterogeneity between studies. By using prevalence data from surveys and data from GLOBOCAN 2008, in 2008 in the 15 original member countries of the European Community plus three countries that were members of the European Free Trade Association, an estimated 3438 cases of melanoma could be attributable to sunbed use, most (n=2341) occurring among women.\n\nCONCLUSIONS:\nSunbed use is associated with a significant increase in risk of melanoma. This risk increases with number of sunbed sessions and with initial usage at a young age (<35 years). The cancerous damage associated with sunbed use is substantial and could be avoided by strict regulations." }

{ "id": "22905651", "text": "BACKGROUND:\nPREVENTCD, Prevent Coeliac Disease, is an international project investigating the hypothesis of possible induction of tolerance to gluten in genetically predisposed children through introducing small quantities of gluten during the period of breastfeeding.\n\nAIM:\nTo summarise current knowledge on the possible relationship between early feeding practices and the risk of coeliac disease (CD).\n\nMETHODS:\nThe Cochrane Library, MEDLINE, and EMBASE databases were searched in May 2011, and the search was updated in January 2012, and again in July 2012.\n\nRESULTS:\nBreastfeeding (BF) and CD: some studies show a protective effect of BF, while others show no effect. No studies have shown a long-term preventive effect. BF at the time of gluten introduction and CD: Results from a meta-analysis of five observational case-control studies suggest that BF at gluten introduction is associated with a lower risk of CD compared with formula feeding. It is unclear whether BF provides a permanent protection or only delays the onset of CD. Timing of gluten introduction: The data suggest that both early (≤4 months) and late (≥7 months) introduction of gluten may increase the risk of CD. Amount of gluten at weaning (and later) and CD: One incident case-referent study documented that the introduction of gluten in large amounts compared with small or medium amounts increased the risk of CD.\n\nCONCLUSIONS:\nIn the absence of clear evidence, in order to decrease the risk of later coeliac disease, it is reasonable to avoid both early (<4 months) and late (≥7 months) introduction of gluten, and to introduce gluten while the infant is still being breastfed. Future studies may clarify the remaining uncertainties." }

{ "id": "23155333", "text": "Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either \"typical\" or \"atypical\". In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture." }

{ "id": "23204143", "text": "A growing body of evidence demonstrates an association between vascular risk factors and Alzheimer's disease. This study investigated the frequency and severity of atherosclerotic plaques in the circle of Willis in Alzheimer's disease and multiple other neurodegenerative diseases. Semi-quantitative data from gross and microscopic neuropathological examinations in 1000 cases were analysed, including 410 with a primary diagnosis of Alzheimer's disease, 230 with synucleinopathies, 157 with TDP-43 proteinopathies, 144 with tauopathies and 59 with normal ageing. More than 77% of subjects with Alzheimer's disease had grossly apparent circle of Willis atherosclerosis, a percentage that was significantly higher than normal (47%), or other neurodegenerative diseases (43-67%). Age- and sex-adjusted atherosclerosis ratings were highly correlated with neuritic plaque, paired helical filaments tau neurofibrillary tangle and cerebral amyloid angiopathy ratings in the whole sample and within individual groups. We found no associations between atherosclerosis ratings and α-synuclein or TDP-43 lesion ratings. The association between age-adjusted circle of Willis atherosclerosis and Alzheimer's disease-type pathology was more robust for female subjects than male subjects. These results provide further confirmation and specificity that vascular disease and Alzheimer's disease are interrelated and suggest that common aetiologic or reciprocally synergistic pathophysiological mechanisms promote both vascular pathology and plaque and tangle pathology." }

{ "id": "23531950", "text": "Alveolar soft-part sarcoma (ASPS) is a translocation-associated sarcoma that occurs most commonly in the lower extremities and rarely in orbit. Only 34 orbital cases have been reported in the literature, and it is often misdiagnosed due to its rare occurrence and nonspecific clinical findings." }

{ "id": "23569324", "text": "PURPOSE:\nSite-specific risk of colorectal cancer (CRC) among survivors of endometrial cancer (EC) is not known. The objective of the present study was to assess the risk of CRC (overall and subsite specific) among EC survivors.\n\nMETHODS:\nA historical cohort study was performed by linking the Manitoba Cancer Registry and the Manitoba Health administrative databases. Each subject diagnosed with EC as her first cancer between 1987 and 2008 was age matched with up to five women with no history of invasive cancer on the index date (date of EC diagnosis). All subjects were followed up to the date of diagnosis of CRC or another cancer, death, migration, or study end point (December 31, 2009). Competing-risk proportional hazards models were used to compare the CRC incidence rates with adjustment for age, history of lower gastrointestinal endoscopy, and socioeconomic status. There were three mutually exclusive (and competing) outcomes: CRC, another primary cancer, and death.\n\nRESULTS:\nA total of 3,115 women with EC and 15,084 without EC were followed up for a total of 145,502 person-years. Women diagnosed with EC at age ≤ 50 years had an increased risk of being diagnosed with CRC (all CRC: hazard ratio [HR] = 4.41; 95% CI, 1.47 to 13.26; right-sided CRC: HR = 7.48; 95% CI, 1.29 to 43.28). There was no increased risk of all CRC among women 51 to 65 years of age or those older than 65 years at the time of EC diagnosis. However, women 51 to 65 years of age at EC diagnosis had an increased risk of right-sided CRC (HR = 2.30; 95% CI, 1.05 to 5.01).\n\nCONCLUSION:\nThis study suggests young women (age ≤ 50 years) with EC are at increased risk of CRC; risk of right-sided CRC is also increased in women 51 to 65 years old at EC diagnosis." }

{ "id": "23620537", "text": "BACKGROUND:\nHyperuricemia is known to be a risk factor for incident type 2 diabetes mellitus, but the absolute magnitude of the association is not known. We aimed to evaluate the strength of association between hyperuricemia and the risk of developing diabetes among the US veterans with gout.\n\nMETHODS:\nPatients (age ≥ 18 years) with ≥2 clinical encounters with gout diagnoses, no history of inflammatory diseases or diabetes and two serum urate (sUA) measurements between 1 January 2002 and 1 January 2011 were selected. Diabetes was identified using International Classification of Disease-9-Clinical Modification codes, use of anti-diabetic medications or HbA1c ≥6.5%. sUA levels were assessed at 6-month cycles (hyperuricemia: sUA >7 mg/dl). Accumulated hazard curves for time to first diabetes diagnosis were derived from Kaplan-Meier (KM) analysis. Risk of diabetes associated with hyperuricemia was estimated using a Cox proportional hazards model. Population attributable fraction (AF) of new-onset diabetes within 1 year was estimated using logistic regression.\n\nRESULTS:\nAmong 1923 patients, average age was 62.9 years, body mass index was 30.6 kg/m(2), and follow-up time was 80 months. Diabetes rates from KM were 19% for sUA ≤ 7 mg/dl, 23% for 7 mg/dl < sUA ≤ 9 mg/dl and 27% for sUA > 9 mg/dl at the end of follow-up period (P < 0.001). Hyperuricemia was associated with a significantly higher risk of developing diabetes, after adjusting for confounding factors (hazard ratio: 1.19, 95% confidence interval: [1.01-1.41]). Approximately, 8.7% of all new cases of diabetes were statistically attributed to hyperuricemia.\n\nCONCLUSIONS:\nAmong veterans, hyperuricemia was associated with excess risk for developing diabetes. Approximately, 1 in 11 new cases of diabetes were statistically attributed to hyperuricemia." }

{ "id": "24101761", "text": "OBJECTIVES:\nTiming of gluten introduction has been associated with the risk of celiac disease (CD) in children, but the optimal time window is unknown. We aimed to study the effect of age of gluten introduction on the risk of CD, adjusting for continued breastfeeding.\n\nMETHODS:\nIn The Norwegian Mother and Child Cohort Study, a prospective birth cohort including 107,000 children, CD was identified by questionnaires and by linkage to the Norwegian Patient Register. Gluten introduction was reported monthly from 0 to 6 months of age, and breastfeeding from 0 to 18 months.\n\nRESULTS:\nAfter exclusion of cases with insufficient information, 324 children with CD in a cohort of 82,167 were used in the analyses. Gluten was introduced before or at 4 months in 8.0%, 5 to 6 months in 45.3%, and after 6 months in 46.6%, whereas continued breastfeeding was stable at ≈ 78% at 6 months age. CD was diagnosed in 3.68/1000 of the infants with gluten introduction at 5 to 6 months compared with 4.15/1000 with late and 4.24/1000 with early gluten introduction. After adjustment for the child's age and gender, breastfeeding, and maternal CD, delayed gluten introduction was associated with an increased risk of CD (adjusted odds ratio, 1.27 [95% confidence interval, 1.01-1.65], P = .045). Breastfeeding >12 months was also associated with increased risk (adjusted odds ratio, 1.49 [95% confidence interval, 1.01-2.21], P = .046).\n\nCONCLUSIONS:\nWe found an increased risk of CD in children introduced to gluten after 6 months and a higher risk in children breastfed after 12 months age." }

{ "id": "24164287", "text": "BACKGROUND:\nRecent studies reported increased risks for the development of asthma in children after prenatal exposure to acid-suppressive drugs. As a result of common pathogenesis, associations could also be present for other allergic diseases.\n\nMETHODS:\nUsing the prescription database IADB.nl, we conducted a cohort study amongst 33 536 children in the Netherlands, with a maximum follow-up of 8 years. Maternal exposure was defined as ≥1 dispensed prescription for proton pump inhibitors (PPIs) and/or Histamine 2-antagonists (H2As) during pregnancy. Children were considered to have a drug-treated allergic disease if they received either ≥2 prescriptions for dermal (atopic dermatitis), inhaled (asthma) or nasal (allergic rhinitis) steroids within a 12-month period. Clustered Cox proportional hazard regression was used to estimate crude and adjusted hazard ratios (aHR) with 95% confidence intervals (95% CI).\n\nRESULTS:\nThe aHR for the development of any allergic disease was 1.37 (95% CI: 1.14-1.66) for children exposed to PPIs or H2As. Prenatal exposure to PPIs and/or H2As was associated with atopic dermatitis, asthma and allergic rhinitis with aHRs of 1.32 (95% CI 1.06-1.64), 1.57 (95% CI 1.20-2.05) and 2.40 (95% CI 1.42-4.04), respectively. The aHR for the development of two or more (aHR 2.13 95% CI: 1.43-3.19) and three allergic diseases (aHR 5.18 95% CI: 2.16-12.42) were even more elevated after prenatal exposure to PPIs or H2As.\n\nCONCLUSION:\nPrenatal exposure to PPIs and H2As appeared associated with an increased risk for the development of atopic dermatitis, asthma and allergic rhinitis in the offspring, especially with the development of multiple allergic diseases. Because our study has limitations inherent to observational studies, prospective studies are now warranted to confirm our findings." }

{ "id": "24190118", "text": "PURPOSE:\nSteroid hormones, particularly androgens, play a major role in prostatic carcinogenesis. Personal history of severe acne, a surrogate for higher androgen activity, has been associated with an increased risk of prostate cancer (PCa), and one recent study indicated that severe teenage acne was a novel risk factor for melanoma. These findings suggest a possible relationship between PCa and risk of melanoma. We prospectively evaluated this association among US men.\n\nMETHODS:\nA total of 42,372 participants in the Health Professionals' Follow-Up Study (HPFS; 1986 to 2010) were included. Biennially self-reported PCa diagnosis was confirmed using pathology reports. Diagnosis of melanoma and nonmelanoma skin cancer (NMSC) was self-reported biennially, and diagnosis of melanoma was pathologically confirmed. We sought to confirm the association in 18,603 participants from the Physicians' Health Study (PHS; 1982 to 1998).\n\nRESULTS:\nWe identified 539 melanomas in the HPFS. Personal history of PCa was associated with an increased risk of melanoma (multivariate-adjusted hazard ratio [HR], 1.83; 95% CI, 1.32 to 2.54). Although we also detected a marginally increased risk of NMSC associated with PCa (HR, 1.08; 95% CI, 0.995 to 1.16), the difference in the magnitude of the association between melanoma and NMSC was significant (P for heterogeneity = .002). We did not find an altered risk of melanoma associated with personal history of other cancers. The association between PCa and risk of incident melanoma was confirmed in the PHS (HR, 2.17; 95% CI, 1.12 to 4.21).\n\nCONCLUSION:\nPersonal history of PCa is associated with an increased risk of melanoma, which may not be entirely a result of greater medical scrutiny." }

{ "id": "24444654", "text": "We studied 2332 individuals with monoallelic mutations in MUTYH among 9504 relatives of 264 colorectal cancer (CRC) cases with a MUTYH mutation. We estimated CRC risks through 70 years of age of 7.2% for male carriers of monoallelic mutations (95% confidence interval [CI], 4.6%-11.3%) and 5.6% for female carriers of monoallelic mutations (95% CI, 3.6%-8.8%), irrespective of family history. For monoallelic MUTYH mutation carriers with a first-degree relative with CRC diagnosed by 50 years of age who does not have the MUTYH mutation, risks of CRC were 12.5% for men (95% CI, 8.6%-17.7%) and 10% for women (95% CI, 6.7%-14.4%). Risks of CRC for carriers of monoallelic mutations in MUTYH with a first-degree relative with CRC are sufficiently high to warrant more intensive screening than for the general population." }

{ "id": "24876226", "text": "BACKGROUND:\nFew prospective studies have examined the relationship between sun exposure, other potential risk factors, and risk of different skin cancers [including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma] simultaneously.\n\nMETHODS:\nWe evaluated the association between a number of potential risk factors and skin cancer risk in a cohort of 108,916 US women, the Nurses' Health Study II (1989-2009).\n\nRESULTS:\nDuring 2.05 million years of follow-up, we identified 6,955, 880, and 779 diagnoses of BCC, SCC, and melanoma, respectively. Compared with participants in the lowest quintile of cumulative ultraviolet flux in adulthood, participants in the highest quintile had multivariable-adjusted relative risks (RR) of 2.35 (Ptrend < 0.0001) for BCC, 2.53 (Ptrend = 0.009) for SCC, and 0.68 (Ptrend = 0.38) for melanoma. In contrast, the RRs were 1.68 (95% CI, 1.55-1.82) for BCC, 1.68 (95% CI, 1.34-2.11) for SCC, and 1.80 (95% CI, 1.42-2.28) for melanoma for participants with ≥5 blistering sunburns when compared with participants without sunburn between ages 15 and 20 years. We found significant interactions between family history of melanoma, number of blistering sunburns between ages 15 and 20 years and BCC risk, and between sunburn reaction as a child/adolescent and SCC risk (all Pinteraction < 0.05).\n\nCONCLUSION:\nIn a cohort of U.S. women, we found that sun exposures in both early life and adulthood were predictive of BCC and SCC risks, whereas melanoma risk was predominantly associated with sun exposure in early life.\n\nIMPACT:\nOur results may have potential implications for the prevention of skin cancers. Cancer Epidemiol Biomarkers Prev; 23(6); 1080-9. ©2014 AACR." }

{ "id": "24881994", "text": "BACKGROUND:\nThe associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.\n\nMETHODS:\nWe used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371.\n\nFINDINGS:\nDuring 5·2 years median follow-up, we recorded 83,098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90-114 mm Hg and diastolic blood pressure of 60-74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32-1·58]), subarachnoid haemorrhage (1·43 [1·25-1·63]), and stable angina (1·41 [1·36-1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00-1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86-0·98]) and strongest for peripheral arterial disease (1·23 [1·20-1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9-63·8) compared with 46·1% (45·5-46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8-5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years.\n\nINTERPRETATION:\nThe widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them.\n\nFUNDING:\nMedical Research Council, National Institute for Health Research, and Wellcome Trust." }

{ "id": "25104173", "text": "BACKGROUND:\nPosttraumatic stress disorder (PTSD) is associated with endocrine and immune abnormalities that could increase risk for autoimmune disorders. However, little is known about the risk for autoimmune disorders among individuals with PTSD.\n\nMETHODS:\nWe conducted a retrospective cohort study of 666,269 Iraq and Afghanistan veterans under age 55 who were enrolled in the Department of Veterans Affairs health care system between October 7, 2001, and March 31, 2011. Generalized linear models were used to examine if PTSD, other psychiatric disorders, and military sexual trauma exposure increased risk for autoimmune disorders, including thyroiditis, inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and lupus erythematosus, adjusting for age, gender, race, and primary care visits.\n\nRESULTS:\nPTSD was diagnosed in 203,766 veterans (30.6%), and psychiatric disorders other than PTSD were diagnosed in an additional 129,704 veterans (19.5%). Veterans diagnosed with PTSD had significantly higher adjusted relative risk (ARR) for diagnosis with any of the autoimmune disorders alone or in combination compared with veterans with no psychiatric diagnoses (ARR = 2.00; 95% confidence interval, 1.91-2.09) and compared with veterans diagnosed with psychiatric disorders other than PTSD (ARR = 1.51; 95% confidence interval, 1.43-1.59; p < .001). The magnitude of the PTSD-related increase in risk for autoimmune disorders was similar in women and men, and military sexual trauma exposure was independently associated with increased risk in both women and men.\n\nCONCLUSIONS:\nTrauma exposure and PTSD may increase risk for autoimmune disorders. Altered immune function, lifestyle factors, or shared etiology may underlie this association." }

{ "id": "25208536", "text": "OBJECTIVES:\nTo investigate the relation between the risk of Alzheimer's disease and exposure to benzodiazepines started at least five years before, considering both the dose-response relation and prodromes (anxiety, depression, insomnia) possibly linked with treatment.\n\nDESIGN:\nCase-control study.\n\nSETTING:\nThe Quebec health insurance program database (RAMQ).\n\nPARTICIPANTS:\n1796 people with a first diagnosis of Alzheimer's disease and followed up for at least six years before were matched with 7184 controls on sex, age group, and duration of follow-up. Both groups were randomly sampled from older people (age >66) living in the community in 2000-09.\n\nMAIN OUTCOME MEASURE:\nThe association between Alzheimer's disease and benzodiazepine use started at least five years before diagnosis was assessed by using multivariable conditional logistic regression. Ever exposure to benzodiazepines was first considered and then categorised according to the cumulative dose expressed as prescribed daily doses (1-90, 91-180, >180) and the drug elimination half life.\n\nRESULTS:\nBenzodiazepine ever use was associated with an increased risk of Alzheimer's disease (adjusted odds ratio 1.51, 95% confidence interval 1.36 to 1.69; further adjustment on anxiety, depression, and insomnia did not markedly alter this result: 1.43, 1.28 to 1.60). No association was found for a cumulative dose <91 prescribed daily doses. The strength of association increased with exposure density (1.32 (1.01 to 1.74) for 91-180 prescribed daily doses and 1.84 (1.62 to 2.08) for >180 prescribed daily doses) and with the drug half life (1.43 (1.27 to 1.61) for short acting drugs and 1.70 (1.46 to 1.98) for long acting ones).\n\nCONCLUSION:\nBenzodiazepine use is associated with an increased risk of Alzheimer's disease. The stronger association observed for long term exposures reinforces the suspicion of a possible direct association, even if benzodiazepine use might also be an early marker of a condition associated with an increased risk of dementia. Unwarranted long term use of these drugs should be considered as a public health concern." }

{ "id": "25422909", "text": "BACKGROUND:\nAlcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial.\n\nMETHODS:\nWe investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity.\n\nRESULTS:\nA total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated.\n\nCONCLUSIONS:\nAlcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma." }

{ "id": "25623697", "text": "OBJECTIVE:\nTo investigate the association of cannabis use and tobacco smoking on the incidence of bladder cancer within the California Men's Health Study cohort.\n\nMETHODS:\nWe evaluated the records of 84,170 participants in a multiethnic cohort of men aged 45-69 years. Information on demographic and lifestyle factors including smoking history and cannabis use was collected using mailed questionnaires between 2002 and 2003. We linked the study data with clinical records including cancer data from electronic health records.\n\nRESULTS:\nOverall 34,000 (41%) cohort members reported cannabis use, 47,092 (57%) reported tobacco use, 22,500 (27%) reported using both, and 23,467 (29%) used neither. Men were followed over an 11-year period and 279 (0.3%) developed incident bladder tumors. Among cannabis users, 89 (0.3%) developed bladder cancer in comparison to 190 (0.4%) men who did not report cannabis use (P < .001). After adjusting for age, race or ethnicity, and body mass index, using tobacco only was associated with an increased risk of bladder cancer (hazard regression [HR], 1.52; 95% confidence interval [CI], 1.12-2.07), whereas cannabis use only was associated with a 45% reduction in bladder cancer incidence (HR, 0.55; 95% CI, 0.31-1.00). Using both cannabis and tobacco was associated with an HR of 1.28 (95% CI, 0.91-1.80).\n\nCONCLUSION:\nAlthough a cause and effect relationship has not been established, cannabis use may be inversely associated with bladder cancer risk in this population." }

{ "id": "25671687", "text": "IMPORTANCE:\nThe risk of next melanoma in patients with 2 or more previous melanomas stratified by familial and sporadic cases separately has not yet been reported, although a few population-based studies have assessed the risk of second melanoma.\n\nOBJECTIVE:\nTo assess the risk of next melanoma in patients with multiple primary melanomas by number of previous melanomas, stratified by demographic and melanoma characteristics.\n\nDESIGN, SETTING, AND PARTICIPANTS:\nProspective population-based cohort study with follow-up from 1958 to 2010 using the Swedish Family-Cancer Database with information on cancer cases retrieved from the Swedish Cancer Registry. A total of 65,429 patients with invasive or in situ melanoma who received a diagnosis during 1958 through 2010 were observed for next melanoma incidence.\n\nMAIN OUTCOMES AND MEASURES:\nStandardized incidence ratios (SIRs) expressing risk of next melanoma by calculating the incidence of next (second, third, fourth, and fifth) melanoma in melanoma patients who had received a diagnosis of 1, 2, 3, and 4, respectively, previous melanomas, compared with the risk of first melanoma in the Swedish population.\n\nRESULTS:\nFor patients with either familial or sporadic melanoma, we observed a stable 2- to 3-times elevated risk by increasing number of previous melanomas; for example, for 2 previous melanomas, the SIR was 2.8 (95% CI, 2.3-3.4) for patients with familial melanoma and 2.5 (95% CI, 2.3-2.7) for patients with sporadic melanoma. Overall risk of second melanoma was higher in patients with familial melanoma who received a diagnosis at younger than 40 years (SIR, 4.7 [95% CI, 3.9-5.6]), and we found a notable risk in young patients with familial melanoma during the first 5-year follow-up after first melanoma: SIR of 6.1 (95% CI, 4.0-9.0) for interval up to 1 year, 6.2 (95% CI, 3.2-11) for 2 to 3 years, and 19 (95% CI, 10-31) for 4 to 5 years. Risk was notable in young (<40 years) patients with sporadic melanoma within the first year of follow-up (SIR, 5.3 [95% CI, 4.3-6.4]) and afterward remained steadily elevated by 2 to 3 times.\n\nCONCLUSIONS AND RELEVANCE:\nWe found a stable 2- to 3-times elevated risk by number of previous melanomas for patients with either familial or sporadic melanoma. Notable risk in young patients with familial melanoma during first 5-year follow-up after first melanoma may suggest that it is important to refer these patients for clinical genetic testing." }

{ "id": "26103029", "text": "IMPORTANCE:\nThe target for the oral erectile dysfunction drugs, phosphodiesterase type 5 (PDE5) inhibitors, is part of a pathway implicated in the development of malignant melanoma. An increased risk of melanoma in sildenafil users was recently reported.\n\nOBJECTIVE:\nTo examine the association between use of PDE5 inhibitors and melanoma risk, including data on specific PDE5 inhibitors, number of prescriptions, and melanoma stage.\n\nDESIGN, SETTING, AND PARTICIPANTS:\nNationwide, population-based, nested case-control study in the Swedish Prescribed Drug Register, the Swedish Melanoma Register, and other health care registers and demographic databases in Sweden, including 4065 melanoma cases diagnosed from 2006 through 2012 and 5 randomly selected controls per case with matching year of birth.\n\nEXPOSURES:\nNumber of filled prescriptions for the PDE5 inhibitors sildenafil and vardenafil or tadalafil.\n\nMAIN OUTCOMES AND MEASURES:\nRisk of melanoma; overall and by stage and risk of basal cell carcinoma in multivariable logistic regression analyses.\n\nRESULTS:\nOf 4065 melanoma cases, 435 men (11%) had filled prescriptions for PDE5 inhibitors, as did 1713 men of 20,325 controls (8%). In multivariable analysis, there was an increased risk of melanoma in men taking PDE5 inhibitors (OR, 1.21 [95% CI, 1.08-1.36]). The most pronounced increase in risk was observed in men who had filled a single prescription (OR, 1.32 [95% CI, 1.10-1.59]; exposure rate, 4% for cases vs 3% for controls), but was not significant among men with multiple filled prescriptions (for 2-5 prescriptions: OR, 1.14 [95% CI, 0.95-1.37], 4% for cases and 3% for controls; for ≥6 prescriptions: OR, 1.17 [95% CI, 0.95-1.44], 3% for cases vs 2% for controls). PDE5 inhibitors were significantly associated with melanoma stage 0 (OR, 1.49 [95% CI, 1.22-1.83], 13% for cases vs 8% for controls) and stage I (OR, 1.21 [95% CI, 1.02-1.43], 12% for cases vs 10% for controls), but not stage II through IV (OR, 0.83 [95% CI, 0.63-1.09], 6% for cases vs 7% for controls). The risk estimates were similar for sildenafil and vardenafil or tadalafil. PDE5 inhibitor use was also associated with an increased risk of basal cell carcinoma (OR, 1.19 [95% CI, 1.14-1.25], 9% for cases vs 8% for controls). Men taking PDE5 inhibitors had a higher educational level and annual income, factors that were also significantly associated with melanoma risk.\n\nCONCLUSIONS AND RELEVANCE:\nIn a Swedish cohort of men, the use of PDE5 inhibitors was associated with a modest but statistically significant increased risk of malignant melanoma. However, the pattern of association (eg, the lack of association with multiple filled prescriptions) raises questions about whether this association is causal." }

{ "id": "26124488", "text": "PURPOSE:\nCitrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption.\n\nMETHODS:\nA total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records.\n\nRESULTS:\nOver 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001).\n\nCONCLUSION:\nCitrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications." }

{ "id": "26416192", "text": "OBJECTIVES:\nFirst-degree relatives (FDRs) of patients with celiac disease (CD) are at high risk for CD and prevalence among them varies from 1.6 to 38%. The risk of having CD among FDRs if the FDR is sister, brother, mother, father, son, or daughter of index patient with CD is not known. We conducted a meta-analysis and calculated pooled prevalence of CD among FDRs, second-degree relatives (SDRs), and specific relations with index patient.\n\nMETHODS:\nOn search of literature, 2,259 articles appeared of which 54 articles were included in this meta-analysis. Diagnosis of CD was based on standard criteria.\n\nRESULTS:\nPooled prevalence of CD was 7.5% (95% confidence interval (CI) 6.3%, 8.8%) in 10,252 FDRs and 2.3% (95% CI 1.3%, 3.8%) in 642 SDRs. Pooled prevalence of CD was highest in siblings (8.9%), followed by offsprings (7.9%) and parents (3.0%). Female FDRs had higher prevalence than male FDRs (8.4% vs. 5.2%, P=0.047). While sisters and daughters of index patient had the highest risk of having CD (1 in 7 and 1 in 8, respectively), the risk was 1 in 13 in sons, 1 in 16 in brothers, 1 in 32 in mothers, and 1 in 33 in fathers. There were also differences in the pooled prevalence of CD in FDRs according to their geographic location.\n\nCONCLUSIONS:\nPooled prevalence of CD among FDRs is 7.5% and varies considerably with their relationship with the index patient. The risk of CD in FDRs also varies according to gender and geographical location." }

{ "id": "26426533", "text": "BACKGROUND:\nThe risk of periodontitis (PD) is increased in the patient group of rheumatoid arthritis (RA). RA and PD also shared some pathological mechanism. The aim of this study is to investigate the risk of RA associated with PD exposure.\n\nMETHODS AND FINDINGS:\nThis study identified 3 mutually exclusive cohorts using the 1999-2010 Taiwanese National Health Insurance Research Database (NHIRD) to investigate the association between PD and the risk of incident RA. All patients with PD in 2000 were identified from the database of all enrollees as the PD cohort. From the representative database of 1,000,000 enrollees randomly selected in 2010 (LHID2010), individuals without any periodontal disease (PO) during 1999-2010 were selected as the non-PO cohort. Individuals who were not included in the non-PO cohort and received dental scaling (DS) no more than two times per year during 1999-2010 were selected as the DS cohort from LHID2010. Using cox proportional regression analysis, hazard ratios (HRs) with 95% confidence intervals (Cis) were calculated to quantify the association between PD exposure and RA development. In the three-group comparison using the non-PO cohort as reference, we found that the risk of RA was higher in the PD and DS cohorts (HRs, 1.89 and 1.43; 95% CIs, 1.56-2.29 and 1.09-1.87, respectively). For comparisons between two cohorts, the PD cohort had a higher risk of RA than the non-PO and DS cohorts (HRs, 1.91 and 1.35; 95% CIs, 1.57-2.30 and 1.09-1.67, respectively).\n\nCONCLUSION:\nPD was associated with an increased risk of RA development." }

{ "id": "26453630", "text": "There are conflicting data regarding the magnitude and determinants of chronic obstructive pulmonary disease (COPD) risk in farmers.In a cross-sectional study of 917 nonfarming working controls and 3787 farmers aged 40-75 years, we assessed respiratory symptoms, tobacco exposure, job history (without direct exposure measurement) and lung function. COPD was defined by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criterion (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.70) and by the Quanjer reference equation (post-bronchodilator FEV1/FVC <lower limit of normal (LLN)).The prevalence (95% CI) of COPD according to the GOLD criterion was 5.1% (4.4-5.8%) and 2.9% (1.8-4.0%) in farmers and controls, respectively (p=0.005), and 3.1% (2.5-3.6%) and 1.5% (0.7-2.3%), respectively, for the LLN criterion (p<0.01). For both COPD criteria after adjustment for age, sex and smoking status, COPD prevalence was similar in controls and crop farmers. Compared to controls, four job categories had a higher prevalence of COPD according to the GOLD criterion, namely, cattle breeders, swine breeders, poultry breeders and breeders of two or more livestock types. Among cattle breeders, only those from Franche-Comté had higher prevalence of COPD according to both GOLD and LLN criteria.The prevalence of COPD in farmers is higher than in nonfarming working controls, and depends on the farming activity, the region and the criterion used to define COPD." }

{ "id": "26541532", "text": "Recent studies suggest that males with chronic obstructive pulmonary disease (COPD) have more emphysema than females. It is not known if these differences persist across degrees of COPD severity. Our aim was to identify sex-specific differences in quantitative emphysema within COPD subgroups based on COPD severity.We included non-Hispanic white and African-American subjects from the COPDGene study with at least 10 pack-years of smoking and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry grade II or greater. We examined sex-specific differences in log-transformed emphysema (log per cent low-attenuation area (%LAA)) by GOLD spirometry grade among subjects with early-onset COPD (<55 years old) and advanced emphysema (>25% emphysema).Compared with females, males had higher log %LAA: overall (1.97±1.4 versus 1.69±1.6, β=0.32 (0.04), p=1.34×10(-14)), and among non-Hispanic white (p=8.37×10(-14)) and African-American subjects (p=0.002). Females with early-onset COPD, severe emphysema and GOLD grade IV COPD had similar emphysema as males, but markedly fewer pack-years smoking (early-onset, p=0.01; severe emphysema and GOLD grade IV, p<0.001).This study identifies subsets of female smokers with COPD who are particularly susceptible to parenchymal destruction." }

{ "id": "26586037", "text": "BACKGROUND:\nPrevious studies investigating the relationship between Mycoplasma pneumoniae and incident asthma in the general population have been inconclusive.\n\nOBJECTIVE:\nWe conducted a nationwide cohort study to clarify this relationship.\n\nMETHODS:\nUsing the National Health Insurance Research Database of Taiwan, we identified 1591 patients with M pneumoniae infection (International Classification of Diseases, Ninth Revision, Clinical Modification code 4830) given diagnoses between 2000 and 2008. We then frequency matched 6364 patients without M pneumoniae infection from the general population according to age, sex, and index year. Cox proportional hazards regression analysis was performed to determine the adjusted hazard ratio (aHR) of the occurrence of asthma in the M pneumoniae cohort compared with that in the non-M pneumoniae cohort.\n\nRESULTS:\nRegardless of comorbidities and the use of antibiotic or steroid therapies, patients with M pneumonia infection had a higher risk of incident asthma than those without it. The aHR of asthma was 3.35 (95% CI, 2.71-4.15) for the M pneumoniae cohort, with a significantly higher risk when patients were stratified by age, sex, follow-up time, and comorbidities, including allergic rhinitis, atopic dermatitis, or allergic conjunctivitis. Patients with M pneumoniae infection had a higher risk of having early-onset (age, <12 years; aHR, 2.87) and late-onset (age, ≥12 years; aHR, 3.95) asthma. The aHR was also higher within the less than 2-year follow-up in the M pneumoniae cohort (aHR, 4.41; 95% CI, 3.40-5.74) than in the cohort without the infection.\n\nCONCLUSION:\nThis study found that incident cases of early-onset and late-onset asthma are closely related to M pneumoniae infection, even in nonatopic patients." }

{ "id": "26815017", "text": "BACKGROUND:\nThe European Society for Paediatric Gastroenterology, Hepatology and Nutrition recommended in 2008, based on observational data, to avoid both early (<4 months) and late (≥7 months) introduction of gluten and to introduce gluten while the infant is still being breast-fed. New evidence prompted ESPGHAN to revise these recommendations.\n\nOBJECTIVE:\nTo provide updated recommendations regarding gluten introduction in infants and the risk of developing coeliac disease (CD) during childhood.\n\nSUMMARY:\nThe risk of inducing CD through a gluten-containing diet exclusively applies to persons carrying at least one of the CD risk alleles. Because genetic risk alleles are generally not known in an infant at the time of solid food introduction, the following recommendations apply to all infants, although they are derived from studying families with first-degree relatives with CD. Although breast-feeding should be promoted for its other well-established health benefits, neither any breast-feeding nor breast-feeding during gluten introduction has been shown to reduce the risk of CD. Gluten may be introduced into the infant's diet anytime between 4 and 12 completed months of age. In children at high risk for CD, earlier introduction of gluten (4 vs 6 months or 6 vs 12 months) is associated with earlier development of CD autoimmunity (defined as positive serology) and CD, but the cumulative incidence of each in later childhood is similar. Based on observational data pointing to the association between the amount of gluten intake and risk of CD, consumption of large quantities of gluten should be avoided during the first weeks after gluten introduction and during infancy. The optimal amounts of gluten to be introduced at weaning, however, have not been established." }

{ "id": "27050141", "text": "IMPORTANCE:\nDespite the unquestioned relationship of UV radiation (UVR) exposure and melanoma development, UVR-independent development of melanoma has only recently been described in mice. These findings in mice highlight the importance of the genetic background of the host and could be relevant for preventive measures in humans.\n\nOBJECTIVE:\nTo study the role of the melanocortin-1 receptor (MC1R) and melanoma risk independently from UVR in a clinical setting.\n\nDESIGN, SETTING, AND PARTICIPANTS:\nHospital-based case-control study, including genetic testing, questionnaires, and physical data (Molecular Markers of Melanoma Study data set) including 991 melanoma patients (cases) and 800 controls.\n\nMAIN OUTCOMES AND MEASURES:\nAssociation of MC1R variants and melanoma risk independent from sun exposure variables.\n\nRESULTS:\nThe 1791 participants included 991 with a diagnosis of melanoma and 800 control patients (mean [SD] age, 59.2 [15.6] years; 50.5% male). Compared with wild-type carriers, carriers of MC1R variants were at higher melanoma risk after statistically adjusting for previous UVR exposure (represented by prior sunburns and signs of actinic skin damage identified by dermatologists), age, and sex compared with wild-type carriers (≥2 variants, OR, 2.13 [95% CI, 1.66-2.75], P < .001; P for trend <.001). After adjustment for sex, age, sunburns in the past, and signs of actinic skin damage, the associations remained significant (OR, 1.65 [95% CI, 1.02-2.67] for R/R, OR, 2.63 [95% CI, 1.82-3.81] for R/r; OR, 1.83 [95% CI, 1.36-2.48] for R/0; and OR, 1.50 [95% CI, 1.01-2.21] for r/r, with P values ranging from <.001 to .04 when adjusted for facial actinic skin damage; OR, 2.36 [95% CI, 1.62-3.43] for R/r; and OR, 1.47 [95% CI, 1.08-1.99] for R/0 with P values ranging from <.001 to .01 when adjusted for dorsal actinic skin damage; and OR, 2.54 [95% CI, 1.76-3.67] for R/r, OR, 1.75 [95% CI, 1.30-2.36] for R/0; and OR, 1.50 [95% CI, 1.02-2.20] for r/r with P values ranging from <.001 to .04 when adjusted for actinic skin damage on the hands).\n\nCONCLUSIONS AND RELEVANCE:\nCarriers of MC1R variants were at increased melanoma risk independent of their sun exposure. Further studies are required to elucidate the causes of melanoma development in these individuals." }

{ "id": "27171547", "text": "BACKGROUND:\nEarly infantile Krabbe disease is rapidly fatal, but hematopoietic stem cell transplantation (HSCT) may improve outcomes if performed soon after birth. New York State began screening all newborns for Krabbe disease in 2006.\n\nMETHODS:\nInfants with abnormal newborn screen results for Krabbe disease were referred to specialty-care centers. Newborns found to be at high risk for Krabbe disease underwent a neurodiagnostic battery to determine the need for emergent HSCT.\n\nRESULTS:\nAlmost 2 million infants were screened. Five infants were diagnosed with early infantile Krabbe disease. Three died, two from HSCT-related complications and one from untreated disease. Two children who received HSCT have moderate to severe developmental delays. Forty-six currently asymptomatic children are considered to be at moderate or high risk for development of later-onset Krabbe disease.\n\nCONCLUSIONS:\nThese results show significant HSCT-associated morbidity and mortality in early infantile Krabbe disease and raise questions about its efficacy when performed in newborns diagnosed through newborn screening. The unanticipated identification of \"at risk\" children introduces unique ethical and medicolegal issues. New York's experience raises questions about the risks, benefits, and practicality of screening newborns for Krabbe disease. It is imperative that objective assessments be made on an ongoing basis as additional states begin screening for this disorder.Genet Med 18 12, 1235-1243." }

{ "id": "27286779", "text": "To summarize the principal findings on risk and protective factors for childhood asthma, we retrieved systematic reviews on these topics in children (aged 1 to 18 years), up to January 2016, through MEDLINE, EMBASE, CINAHL, SCOPUS, and CDSR. A total of 227 studies were searched from databases. Among those, 41 systematic reviews (SRs) were included: 9 focused on prenatal factors, 5 on perinatal factors, and 27 on postnatal factors. Of these 41 SRs, 83% had good methodological quality, as determined by the Assess Systematic Reviews tool. After reviewing all evidence, parental asthma, prenatal environmental tobacco smoke, and prematurity (particularly very preterm birth) are well-established risk factors for childhood asthma. Current findings do suggest mild-to-moderate causal effects of certain modifiable behaviors or exposures during pregnancy (maternal weight gain or obesity, maternal use of antibiotics or paracetamol, and maternal stress), the perinatal period (birth by Caesarean delivery), or postnatal life (severe respiratory syncytial virus infection, overweight or obesity, indoor exposure to mold or fungi, and outdoor air pollution) on childhood asthma, but this suggestive evidence must be confirmed in interventional studies or (if interventions are not feasible) well-designed prospective studies." }

{ "id": "27626972", "text": "RATIONALE:\nPreeclampsia reflects an unusual increase in systemic inflammation during pregnancy.\n\nOBJECTIVES:\nWe studied associations between preeclampsia and asthma, allergy, and eczema in Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) and in national registries.\n\nMETHODS:\nCOPSAC is a high-risk birth cohort of 411 Danish children. Asthma, allergy, and eczema were diagnosed prospectively, and lung function measured at age 1 month and 7 years. Sensitization was evaluated at age 6 months, 18 months, 4 years, and 6 years by skin prick tests and IgE measurements. The register-based cohort included 1.7 million children from Danish national registries in the 35-year period 1977-2012. Children born to mothers with preeclampsia were analyzed regarding risk of asthma, allergy, and eczema.\n\nMEASUREMENTS AND MAIN RESULTS:\nIn the COPSAC cohort, 5.6% (n = 23) were diagnosed with preeclampsia. Preeclampsia was associated with increased risk of treatment with inhaled corticosteroids at age 7 years (adjusted odds ratio, 4.01 [95% confidence interval (CI), 1.11-14.43]; P = 0.0337), increased bronchial responsiveness to methacholine (adjusted β-coefficient log-μmol, -0.80 [95% CI, -1.55 to -0.06]; P = 0.0348), and allergic rhinitis (adjusted odds ratio, 4.83 [95% CI, 1.58-14.78]; P = 0.0057) in the 7-year-old children. Furthermore, the children had an increased risk of sensitization to both aeroallergens and food allergens, and increased amount of total IgE during childhood. In the registry-based cohort, 3.7% (n = 62,728) were born to mothers with preeclampsia. Preeclampsia was associated with increased risk of asthma, eczema, and aeroallergen and food allergy, especially pronounced after a duration of preeclampsia of 14 days or more. Maternal asthma increased the risk of preeclampsia.\n\nCONCLUSIONS:\nPreeclampsia is a shared prenatal risk factor for asthma, eczema, and allergy in childhood pointing toward in utero immune programming of the child." }

{ "id": "27629559", "text": "OBJECTIVES:\nTo evaluate the risk of BlCa developing after radiation for PCa, stratified by ethnicity and follow-up duration.\n\nMETHODS:\nThe 1973-2011 surveillance, epidemiology and end results database was used to determine the observed and expected number of BlCa after PCa radiation. The adjusted relative risks (RRs) of developing BlCa were calculated for the various radiation modalities relative to no radiation, stratified by ethnicity and follow-up duration. BlCa characteristics were compared between patients with a history of prostate radiation and those without PCa.\n\nRESULTS:\nPCa was radiated in 346,429 men, 6401 of whom developed BlCa versus 2464 expected cases [SIR (95 % CI) of 2.60 (2.53-2.66)]. All radiation modalities were found to have an increased RR of developing BlCa after 10 years, with brachytherapy having a significantly higher RR than external beam radiation (EBRT) or combined EBRT and brachytherapy in Caucasian men and a significantly higher RR than EBRT in men of other/unknown ethnicity. Post-radiation BlCa, in particular that after brachytherapy, had higher grade (P = 0.0001) and lower stage (P = 0.0001) versus the general population.\n\nCONCLUSIONS:\nThe increased risk of BlCa after prostate radiation occurs predominantly after 10 years, regardless of ethnicity. The RR of developing BlCa after 10 years is significantly higher following brachytherapy than after EBRT or EBRT and brachytherapy. Bladder cancers after prostate radiation, especially after brachytherapy, are generally lower stage but higher grade than those in patients without PCa." }

{ "id": "28166365", "text": "Perampanel (PER) was used in 12 patients with Unverricht-Lundborg disease (ULD) to evaluate its efficacy against myoclonus and seizures." }

{ "id": "28228423", "text": "We previously found that the introduction of small quantities of gluten at 4-6 mo of age did not reduce the risk of celiac disease (CD) in a group of high-risk children. However, the consumption of high amounts of gluten early in life has been suggested to increase CD risk. The aim of this study was to evaluate this hypothesis by using data from the previous study of the PreventCD trial (www.preventcd.com). Gluten intake was prospectively quantified by using specific food records between 11 and 36 mo of age in 715 children positive for the human leukocyte antigen ()- and/or from 5 European countries. According to the PreventCD protocol, infants received 100 mg immunologically active gluten/d or placebo from 4 to 6 mo of age, with a stepwise and fixed gluten increase until age 10 mo and unrestricted intake thereafter. The primary outcome of the present study was the impact of the amount of gluten consumed from age 10 mo onward on CD development. Mean daily gluten intakes from 10 mo onward were significantly different between countries for children at all ages ( < 0.001) but not between children who developed CD and those who did not within the same country ( > 0.05). The variables country, sex, intervention group, and gluten consumption pattern did not show significant associations with CD development risk (HRs not significant). In addition, the interaction between risk group and gluten consumption pattern showed no significant risk on CD development, except for the DQ2.2/DQ7 haplotype (HR: 5.81; 95% CI: 1.18, 28.74; = 0.031). Gluten consumption patterns as well as the amount of gluten consumed at 11-36 mo of age do not influence CD development for most related genotypes in children with a genetic risk. This study reports the gluten consumption pattern in children at risk of CD from different European countries. This trial was registered at www.controlled-trials.com as ISRCTN74582487." }

{ "id": "28579413", "text": "OBJECTIVE:\nTo study pregnancy chance in adult women with classic galactosemia and primary ovarian insufficiency. Despite dietary treatment, >90% of women with classic galactosemia develop primary ovarian insufficiency, resulting in impaired fertility. For many years, chance of spontaneous conception has not been considered, leading to counseling for infertility. But an increasing number of reports on pregnancies in this group questions whether current counseling approaches are correct.\n\nDESIGN:\nMulticenter retrospective observational study.\n\nSETTING:\nMetabolic centers.\n\nPATIENT(S):\nAdult women (aged >18 y) with confirmed classic galactosemia and primary ovarian insufficiency were included.\n\nINTERVENTION(S):\nParticipants and medical records were consulted to obtain study data in a standardized manner with the use of a questionnaire.\n\nMAIN OUTCOME MEASURE(S):\nConception opportunities, time to pregnancy, pregnancy outcome, hormone replacement therapy use, fertility counseling, and the participants' vision of fertility were evaluated. Potential predictive factors for increased pregnancy chance were explored.\n\nRESULT(S):\nEighty-five women with classic galactosemia and primary ovarian insufficiency participated. Twenty-one women actively attempted to conceive or did not take adequate contraceptive precautions. Of these 21 women, nine became pregnant spontaneously (42.9%). This was higher than reported in primary ovarian insufficiency due to other causes (5%-10%). After a period of 12 months, a cumulative proportion of 27.8% of couples had conceived, which increased to 48.4% after 24 months and 61.3% after 27 months. Predictive factors could not be identified. A considerable miscarriage rate of 30% was observed (6 of 20 pregnancies). Although a substantial proportion of women expressed a child-wish (n = 28/53; 52.8%), the vast majority of participants (n = 43/57; 75.4%) considered conceiving to be highly unlikely, owing to negative counseling in the past.\n\nCONCLUSION(S):\nThe pregnancy rate in women with classic galactosemia and primary ovarian insufficiency was higher than for women with primary ovarian insufficiency of any cause. This shifting paradigm carries significant implications for fertility counseling and potential application of fertility preservation techniques." }

{ "id": "28586371", "text": "OBJECTIVE:\nThe association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis.\n\nMETHODS:\nThe study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3.\n\nRESULTS:\nWe included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05-4.87) and 5.7 (1.9-16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6-7.7).\n\nCONCLUSION:\nThis meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It is therefore expected to be a risk factor for other cancers." }

{ "id": "28746700", "text": "IMPORTANCE:\nMelanoma risk factors and incidence in renal transplant recipients can inform decision making for both patients and clinicians.\n\nOBJECTIVE:\nTo determine risk factors and characteristics of renal transplant recipients who develop melanoma.\n\nDESIGN, SETTING, AND PARTICIPANTS:\nThis cohort study of a large national data registry used a cohort of renal transplant recipients from the United States Renal Data System (USRDS) database from the years 2004 through 2012. Differences in baseline characteristics between those who did and did not develop melanoma were examined, and a survival analysis was performed. Patients with renal transplants who received a diagnosis of melanoma according to any inpatient or outpatient claim associated with a billing code for melanoma were included. A history of pretransplant melanoma, previous kidney transplantation, or transplantation after 2012 or before 2004 were exclusion criteria. The data analysis was conducted from 2015 to 2016.\n\nEXPOSURE:\nReceipt of a renal transplant.\n\nMAIN OUTCOMES AND MEASURES:\nIncidence and risk factors for melanoma.\n\nRESULTS:\nOf 105 174 patients (64 151 [60.7%] male; mean [SD] age, 49.6 [15.3] years) who received kidney transplants between 2004 and 2012, 488 (0.4%) had a record of melanoma after transplantation. Significant risk factors for developing melanoma vs not developing melanoma included older age among recipients (mean [SD] age, 60.5 [10.2] vs 49.7 [15.3] years; P < .001) and donors (42.6 [15.0] vs 39.2 [15.1] years; P < .001), male sex (71.5% vs 60.7%; P < .001), recipient (96.1% vs 66.5%; P < .001) and donor (92.4% vs 82.9%; P < .001) white race, less than 4 HLA mismatches (44.9% vs 37.1%; P = .001), living donors (44.7% vs 33.7%; P < .001), and sirolimus (22.3% vs 13.2%; P < .001) and cyclosporine (4.9% vs 3.2%; P = .04) therapy. Risk factors significant on survival analysis included older recipient age (hazard ratio [HR] per year, 1.06; 95% CI, 1.05-1.06; P < .001), recipient male sex (HR, 1.53; 95% CI, 1.25-1.88; P < .001), recipient white race, living donors (HR, 1.35; 95% CI, 1.11-1.64; P = .002), and sirolimus (HR, 1.54; 95% CI, 1.22-1.94; P < .001) and cyclosporine (HR, 1.93; 95% CI, 1.24-2.99; P = .004) therapy. The age-standardized relative rate of melanoma in USRDS patients compared with Surveillance, Epidemiology, and End Results patients across all years was 4.9. A Kaplan-Meier estimate of the median time to melanoma among those patients who did develop melanoma was 1.45 years (95% CI, 1.31-1.70 years).\n\nCONCLUSIONS AND RELEVANCE:\nRenal transplant recipients had greater risk of developing melanoma than the general population. We believe that the risk factors we identified can guide clinicians in providing adequate care for patients in this vulnerable group." }

{ "id": "28770319", "text": "AIMS/HYPOTHESIS:\nRespiratory infections and onset of islet autoimmunity are reported to correlate positively in two small prospective studies. The Environmental Determinants of Diabetes in the Young (TEDDY) study is the largest prospective international cohort study on the environmental determinants of type 1 diabetes that regularly monitors both clinical infections and islet autoantibodies. The aim was to confirm the influence of reported respiratory infections and to further characterise the temporal relationship with autoantibody seroconversion.\n\nMETHODS:\nDuring the years 2004-2009, 8676 newborn babies with HLA genotypes conferring an increased risk of type 1 diabetes were enrolled at 3 months of age to participate in a 15 year follow-up. In the present study, the association between parent-reported respiratory infections and islet autoantibodies at 3 month intervals up to 4 years of age was evaluated in 7869 children. Time-dependent proportional hazard models were used to assess how the timing of respiratory infections related to persistent confirmed islet autoimmunity, defined as autoantibody positivity against insulin, GAD and/or insulinoma antigen-2, concordant at two reference laboratories on two or more consecutive visits.\n\nRESULTS:\nIn total, 87,327 parent-reported respiratory infectious episodes were recorded while the children were under study surveillance for islet autoimmunity, and 454 children seroconverted. The number of respiratory infections occurring in a 9 month period was associated with the subsequent risk of autoimmunity (p < 0.001). For each 1/year rate increase in infections, the hazard of islet autoimmunity increased by 5.6% (95% CI 2.5%, 8.8%). The risk association was linked primarily to infections occurring in the winter (HR 1.42 [95% CI 1.16, 1.74]; p < 0.001). The types of respiratory infection independently associated with autoimmunity were common cold, influenza-like illness, sinusitis, and laryngitis/tracheitis, with HRs (95% CI) of 1.38 (1.11, 1.71), 2.37 (1.35, 4.15), 2.63 (1.22, 5.67) and 1.76 (1.04, 2.98), respectively.\n\nCONCLUSIONS/INTERPRETATION:\nRecent respiratory infections in young children correlate with an increased risk of islet autoimmunity in the TEDDY study. Further studies to identify the potential causative viruses with pathogen-specific assays should focus especially on the 9 month time window leading to autoantibody seroconversion." }

{ "id": "28832212", "text": "BACKGROUND:\nSoft tissue sarcomas (STS) of the hand are exceedingly rare. The aim of this study was to review our institution's experience with STS of the hand to identify factors affecting outcomes and survivorship.\n\nMETHODS:\nWe retrospectively reviewed the records of 46 hand STS treated with definitive surgery at our institution between 1992 and 2013. Pertinent demographics as well as information regarding the surgical procedure, and disease status at latest follow-up were reviewed. Mean age at diagnosis was 38 years with a mean follow-up of 5 years.\n\nRESULTS:\nThe most common tumor subtypes were epithelioid (n = 10) and synovial sarcoma (n = 8). Sixty-one percent were superficial in location. Thirty-three patients had had a nononcologic resection prior to definitive surgical treatment at our institution. Ultimately, negative margins were obtained in all cases. Local recurrence was observed in 5 patients and distant metastases in 14 patients. Tumor sizes ≥2 cm, American Joint Committee on Cancer (AJCC) grade, and depth of the tumor were found to adversely affect the outcome in terms of disease-free and overall survival. Reexcision of an inadvertently excised tumor at an outside institution did not adversely affect the outcome. The 10-year overall and disease-free survival was 72% and 63%.\n\nCONCLUSIONS:\nLocal recurrence after a wide excision was observed infrequently; however, distant disease was relatively common. Tumors with a size ≥2 cm were associated with a worse disease-free and overall survival, highlighting the aggressive nature of these tumors." }

{ "id": "29055934", "text": "Sitosterolemia is an autosomal recessive metabolic disease caused by mutations in ABCG5 or ABCG8 genes which encode for the (ATP)-binding cassette (ABC) transporters that are responsible for the trafficking of xenosterols. Liver involvement is not a recognized manifestation of this disease, and cirrhosis has been reported only once in the medical literature. We describe a fatal case of a 21-year old South Asian male who presented with decompensated cirrhosis, and biochemical abnormalities consistent with sitosterolemia. Genetic testing showed a homozygous pathogenic mutation in ABCG5, confirming the diagnosis. Sitosterolemia is a rare, but likely under-recognized condition, and a high degree of suspicion is imperative to make the diagnosis. We propose that sitosterolemia should be included in the differential diagnosis for patients with cryptogenic cirrhosis, especially as there are effective oral therapies to treat this condition. Newly diagnosed sitosterolemia patients should undergo a thorough hepatology evaluation and follow-up to evaluate for the presence, development, and progression of any hepatic involvement." }

{ "id": "29128935", "text": "AIMS/HYPOTHESIS:\nWith genetics thought to explain only 40-50% of the total risk of type 1 diabetes, environmental risk factors in early life have been proposed. Previous findings from studies of type 1 diabetes incidence by birthweight and gestational age at birth have been inconsistent. This study aimed to investigate the relationships between birthweight, gestational age at birth and subsequent type 1 diabetes in England.\n\nMETHODS:\nData were obtained from a population-based database comprising linked mother-infant pairs using English national Hospital Episode Statistics from 1998 to 2012. In total, 3,834,405 children, categorised by birthweight and gestational age at birth, were followed up through record linkage to compare their incidence of type 1 diabetes through calculation of multivariable-adjusted HRs.\n\nRESULTS:\nOut of 3,834,405 children, 2969 had a subsequent hospital diagnosis of type 1 diabetes in childhood. Children born preterm (<37 weeks) or early term (37-38 weeks) experienced significantly higher incidence of type 1 diabetes than full term children (39-40 weeks) (HR 1.19 [95% CI 1.03, 1.38] and 1.27 [95% CI 1.16, 1.39], respectively). Children born at higher than average birthweight (3500-3999 g or 4000-5499 g) after controlling for gestational age experienced higher incidence of type 1 diabetes than children born at medium birthweight (3000-3499 g) (HR 1.13 [95% CI 1.03, 1.23] and 1.16 [95% CI 1.02, 1.31], respectively), while children at low birthweight (<2500 g) experienced lower incidence (0.81 [95% CI 0.67, 0.98]), signifying a statistically significant trend (p trend 0.001).\n\nCONCLUSIONS/INTERPRETATION:\nHigh birthweight for gestational age and low gestational age at birth are both independently associated with subsequent type 1 diabetes. These findings help contextualise the debate about the potential role of gestational and early life environmental risk factors in the pathogenesis of type 1 diabetes, including the potential roles of insulin sensitivity and gut microbiota." }

{ "id": "29228305", "text": "BACKGROUND:\nFamily history of bladder cancer confers an increased risk for concordant and discordant cancers in relatives. However, previous studies investigating this relationship lack any correction for smoking status of family members. We conducted a population-based study of cancer risks in relatives of bladder cancer patients and matched controls with exclusion of variant subtypes to improve the understanding of familial cancer clustering.\n\nMETHODS:\nCase subjects with urothelial carcinoma were identified using the Utah Cancer Registry and matched 1:5 to cancer-free controls from the Utah Population Database. Cox regression was used to determine the risk of cancer in first-degree relatives, second-degree relatives, first cousins, and spouses. A total of 229 251 relatives of case subjects and 1 197 552 relatives of matched control subjects were analyzed. To correct for smoking status, we performed a secondary analysis excluding families with elevated rates of smoking-related cancers. All statistical tests were two-sided.\n\nRESULTS:\nFirst- and second-degree relatives of case subjects had an increased risk for any cancer diagnosis (hazard ratio [HR] = 1.06, 95% confidence interval [CI] = 1.03 to 1.09, P < .001; HR = 1.04, 95% CI = 1.02 to 1.07, P = .001) and urothelial cancer (HR = 1.73, 95% CI = 1.50 to 1.99, P < .001; HR = 1.35, 95% CI = 1.21 to 1.51, P < .001). Site-specific analysis found increased risk for bladder (HR = 1.69, 95% CI = 1.47 to 1.95, P < .001), kidney (HR = 1.30, 95% CI = 1.08 to 1.57, P = .006), cervical (HR = 1.25, 95% CI = 1.06 to 1.49, P = .01), and lung cancer (HR = 1.34, 95% CI = 1.19 to 1.51, P < .001) in first-degree relatives. Second-degree relatives had increased risk for bladder (HR = 1.35, 95% CI = 1.2 to 1.5, P < .001) and thyroid cancer (HR = 1.18, 95% CI = 1.03 to 1.35, P = .02). Spouses showed an increased risk for laryngeal (HR = 2.68, 95% CI = 1.02 to 7.05, P = .04) and cervical cancer (HR = 1.57, 95% CI = 1.13 to 2.17, P = .007). These results did not substantively change after correction for suspected smoking behaviors.\n\nCONCLUSION:\nOur results suggest familial urothelial cancer clustering independent of smoking, with increased risk in relatives for both concordant and discordant cancers, suggesting shared genetic or environmental roots. Identifying families with statistically significant risks for non-smoking-related urothelial cancer would be extremely informative for genetic linkage studies." }

{ "id": "29344584", "text": "Leukodystrophies (LD) are devastating inherited disorders leading to rapid neurological deterioration and premature death. Hematopoietic stem cell transplantation (HSCT) can halt disease progression for selected LD. Cord blood is a common donor source for transplantation of these patients because it is rapidly available and can be used without full HLA matching. However, precise recommendations allowing care providers to identify patients who benefit from HSCT are lacking." }

{ "id": "29551552", "text": "The endothelial lining can be viewed as the first line of defense against risk factors of vascular disease. Endothelial dysfunction is regarded as an initial event for atherogenesis since defects in vascular integrity and homeostasis are responsible for lipid infiltration and recruitment of monocytes into the vessel wall. Monocytes-turned-macrophages, which possess astounding inflammatory plasticity, perpetuate chronic inflammation and growth of atherosclerotic plaques and, are therefore central for the pathogenesis of atherosclerosis. Because endothelial cells and macrophages are key players during atherogenesis, it is crucial to understand the regulation of their functions in order to develop strategies to intervene disease progression. Interestingly, non-coding RNAs (ncRNAs), broad class of RNA molecules that do not code for proteins, are capable of reprogramming multiple cell functions and, thus, can be used as target agents. MicroRNAs are small ncRNAs whose roles in the regulation of vascular functions and development of atherosclerosis through post-transcriptional manipulation of gene expression have been widely explored. Recently, other ncRNAs including long noncoding RNAs (lncRNAs) have also emerged as potential regulators of these functions. However, given their poor-genetic conservation between species, much work will be needed to elucidate the specific role of lncRNAs in vascular biology. This review aims to provide a comprehensive perspective of ncRNA, mostly focusing in lncRNAs, mechanism of action and relevance in regulating lipid metabolism-independent endothelial and macrophages functions in the pathogenesis of atherosclerosis." }

{ "id": "29650248", "text": "BACKGROUND:\nAlthough exposure to cigarette smoking and air pollution is common, the current prevalence of chronic obstructive pulmonary disease (COPD) is unknown in the Chinese adult population. We conducted the China Pulmonary Health (CPH) study to assess the prevalence and risk factors of COPD in China.\n\nMETHODS:\nThe CPH study is a cross-sectional study in a nationally representative sample of adults aged 20 years or older from ten provinces, autonomous regions, and municipalities in mainland China. All participants underwent a post-bronchodilator pulmonary function test. COPD was diagnosed according to 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.\n\nFINDINGS:\nBetween June, 2012, and May, 2015, 57 779 individuals were invited to participate, of whom 50 991 (21 446 men and 29 545 women) had reliable post-bronchodilator results and were included in the final analysis. The overall prevalence of spirometry-defined COPD was 8·6% (95% CI 7·5-9·9), accounting for 99·9 (95% CI 76·3-135·7) million people with COPD in China. Prevalence was higher in men (11·9%, 95% CI 10·2-13·8) than in women (5·4%, 4·6-6·2; p<0·0001 for sex difference) and in people aged 40 years or older (13·7%, 12·1-15·5) than in those aged 20-39 years (2·1%, 1·4-3·2; p<0·0001 for age difference). Only 12·0% (95% CI 8·1-17·4) of people with COPD reported a previous pulmonary function test. Risk factors for COPD included smoking exposure of 20 pack-years or more (odds ratio [OR] 1·95, 95% CI 1·53-2·47), exposure to annual mean particulate matter with a diameter less than 2·5 μm of 50-74 μg/m (1·85, 1·23-2·77) or 75 μg/m or higher (2·00, 1·36-2·92), underweight (body-mass index <18·5 kg/m; 1·43, 1·03-1·97), sometimes childhood chronic cough (1·48, 1·14-1·93) or frequent cough (2·57, 2·01-3·29), and parental history of respiratory diseases (1·40, 1·23-1·60). A lower risk of COPD was associated with middle or high school education (OR 0·76, 95% CI 0·64-0·90) and college or higher education (0·47, 0·33-0·66).\n\nINTERPRETATION:\nSpirometry-defined COPD is highly prevalent in the Chinese adult population. Cigarette smoking, ambient air pollution, underweight, childhood chronic cough, parental history of respiratory diseases, and low education are major risk factors for COPD. Prevention and early detection of COPD using spirometry should be a public health priority in China to reduce COPD-related morbidity and mortality.\n\nFUNDING:\nMinistry of Health and Ministry of Science and Technology of China." }

{ "id": "29706374", "text": "BACKGROUND:\nThe management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. Our aim was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis.\n\nMETHODS:\nIn this systematic review and meta-analysis, we searched PubMed, MEDLINE, Google Scholar, Scopus, Embase, and Cochrane databases with no language restrictions for studies published from inception of the databases to Aug 1, 2017, assessing the risk of gastrointestinal cancers in patients with cystic fibrosis. We also searched abstracts from scientific meetings and the bibliographies of identified articles for additional references. Studies were included if they reported the standardised incidence ratio (SIR) or incidence ratio per person-years. No exclusion criteria with regard to patient characteristics (age, sex, comorbidities, cystic fibrosis mutation type), study setting (location and time period), or method of reporting cancer diagnoses were applied. The primary outcome was risk of gastrointestinal cancer and site-specific gastrointestinal cancers in patients with cystic fibrosis compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of gastrointestinal cancer varied according to patient lung transplant status. The study is registered with PROSPERO, number CRD42017075396.\n\nFINDINGS:\nOur search identified 95 681 records, of which six cohort studies including 99 925 patients (544 695 person-years) were eligible for the meta-analysis. The overall risk of gastrointestinal cancer was significantly higher in patients with cystic fibrosis than in the general population (pooled SIR 8·13, 95% CI 6·48-10·21; p<0·0001; log SIR 2·10, 95% CI 1·87-2·32; p<0·0001, I=93·93%). Subgroup analyses showed that the risk of gastrointestinal cancer among patients with cystic fibrosis who had a lung transplant was increased compared with that of patients who did not receive a transplant (pooled SIR 21·13, 95% CI 14·82-30·14; p<0·0001; log SIR 3·05, 95% CI 2·70-3·41; p<0·0001, I=28·52% vs pooled SIR 4·18, 3·10-5·62; p<0·0001; log SIR 1·43, 1·13-1·73; p<0·0001, I=22·66%). The risk for the following site-specific cancers was also significantly increased in patients with cystic fibrosis compared with the general population: small bowel cancer (pooled SIR 18·94, 95% CI 9·37-38·27; p<0·0001; log SIR 2·94, 95% CI 2·24-3·64; p<0·0001, I=38·61%), colon cancer (10·91, 8·42-14·11; p<0·0001; log SIR 2·39, 2·13-2·65; p<0·0001, I=88·09%), biliary tract cancer (17·87, 8·55-37·36; p<0·0001; log SIR 2·88, 2·15-3·62; p<0·0001, I=10·16%), and pancreatic cancer (6·18, 1·31-29·27; p=0·022; log SIR 1·82, 0·27-3·38; p<0·0001, I=62·57%).\n\nINTERPRETATION:\nOur study suggests that patients with cystic fibrosis had a significantly increased risk of gastrointestinal cancer compared with the general population, including small bowel, colon, biliary tract, and pancreatic cancers. These findings highlight the need to develop individualised screening strategies for site-specific gastrointestinal cancers in patients with cystic fibrosis.\n\nFUNDING:\nNone." }

{ "id": "29941778", "text": "Celiac disease is a small intestinal inflammatory disease with autoimmune features that is triggered and maintained by the ingestion of the storage proteins (gluten) of wheat, barley, and rye. Prevalence of celiac disease is increased in patients with mono- and/or polyglandular autoimmunity and their relatives. We have reviewed the current and pertinent literature that addresses the close association between celiac disease and endocrine autoimmunity. The close relationship between celiac disease and glandular autoimmunity can be largely explained by sharing of a common genetic background. Further, between 10 and 30% of patients with celiac disease are thyroid and/or type 1 diabetes antibody positive, while around 5⁻7% of patients with autoimmune thyroid disease, type 1 diabetes, and/or polyglandular autoimmunity are IgA anti-tissue transglutaminase antibody positive. While a gluten free diet does not reverse glandular autoimmunity, its early institution may delay or even prevent its first manifestation. In conclusion, this brief review highlighting the close association between celiac disease and both monoglandular and polyglandular autoimmunity, aims to underline the need for prospective studies to establish whether an early diagnosis of celiac disease and a prompt gluten-free diet may positively impact the evolution and manifestation of glandular autoimmunity." }

{ "id": "29972110", "text": "With the increase in long-term survival of post-transplant children, there is a paradigm shift in the emphasis of post-transplant care." }

{ "id": "30124939", "text": "OBJECTIVES:\nTo investigate the link between smoking status, including childhood and adult passive exposure, and the risk of incident RA.\n\nMETHODS:\nThe French E3N cohort includes 98 995 female volunteers prospectively followed since 1990. Self-administered questionnaires sent every 2-3 years collected medical events, general, lifestyle and environmental characteristics. RA diagnoses were collected in three successive questionnaires and confirmed if women received reimbursement for an RA-specific medication. The risk of incident RA was estimated using an age-adjusted Cox model that considers smoking status as a time-dependent variable.\n\nRESULTS:\nAmong 71 248 women, 371 incident RA cases were confirmed. Ever-smokers not exposed to passive smoking had an increased risk of RA [1.38 (95% CI 1.10, 1.74)]. In never-smokers, passive smoking exposure during childhood was associated with a borderline increased risk of RA in the same range as active smoking in adults, with an hazard ratio (HR) of 1.43 (95% CI 0.97, 2.11). Ever-smokers who also had childhood passive smoking exposure had a higher risk of RA than smokers not exposed during childhood [HR 1.67 (95% CI 1.17, 2.39)], but without a significant difference (P = 0.30). RA began earlier in smokers exposed to childhood passive smoking.\n\nCONCLUSION:\nThis study confirms that active smoking is associated with an increased risk of RA. It suggests for the first time that passive exposure to tobacco during childhood might also increase the risk of RA in future light smokers and probably non-smokers. Our results highlight the importance of avoiding any tobacco environment in children, especially in those with a family history of RA." }

{ "id": "30267597", "text": "OBJECTIVE AND METHODS:\nPediatric-inspired regimens have been adopted by several groups as the treatment strategy for adult patients with acute lymphoblastic leukemia (ALL). Whether subsequent modifications of these protocols have led to an improvement in the outcome of patients is uncertain, especially in T-cell ALL. We analyzed 169 patients with high-risk T-cell ALL included in two consecutive trials of the PETHEMA Group (HR-ALL03 [n = 104] and the more contemporary HR-ALL11 [n = 65]).\n\nRESULTS:\nPatients and disease characteristics were balanced between both groups. Regarding efficacy, we observed a similar complete remission (CR) rate, relapse and disease-free survival (DFS) between both protocols. Patients included in the HR-ALL11 trial had better 2-year overall survival (OS) compared with the HR-ALL03 (65% [95% CI 51%-79%] vs 44% [95% CI 34%-54%], P = 0.026). Regarding toxicity, we observed a better safety profile in the HR-11 protocol. Irrespective of the protocol, patients with good measurable residual disease (MRD) clearance had a promising outcome without allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, with 2-year OS of 67%.\n\nCONCLUSION:\nPatients with T-cell ALL included in the HR-11 trial showed better OS than patients in the HR-03, mostly driven by a reduction of NRM." }

{ "id": "30477003", "text": "IMPORTANCE:\nTwo pathways have been hypothesized for the development of cutaneous melanoma: one typically affects the head and neck, a site with chronic sun damage, and the other affects the trunk, which is less exposed to the sun. However, the possible cause of limb melanomas is less studied under this hypothesis.\n\nOBJECTIVE:\nTo investigate the association between phenotypic characteristics, pattern of UV radiation exposure, and risk of melanoma on different body sites.\n\nDESIGN, SETTING, AND PARTICIPANTS:\nThis study used data on 161 540 women with information on phenotypic characteristics and UV radiation exposure who were part of the Norwegian Women and Cancer study, a population-based prospective study established in 1991 with exposure information collected by questionnaires at baseline and every 4 to 6 years during follow-up through 2015. Data analysis was performed from October 2017 through May 2018.\n\nEXPOSURES:\nParticipants reported hair color, eye color, untanned skin color, number of small symmetric and large asymmetric nevi, and freckling, as well as histories of sunburns, sunbathing vacations, and indoor tanning in childhood, adolescence, and adulthood.\n\nMAIN OUTCOMES AND MEASURES:\nThe Norwegian Women and Cancer study was linked to the Cancer Registry of Norway for data on cancer diagnosis and date of death or emigration. Primary melanoma site was categorized as head and neck, trunk, upper limbs, and lower limbs.\n\nRESULTS:\nDuring follow-up of the 161 540 women in the study (mean age at study entry, 50 years [range, 34-70 years]; mean age at diagnosis, 60 years [range, 34-87 years]), 1374 incident cases of melanoma were diagnosed. Having large asymmetric nevi was a significant risk factor for all sites and was strongest for the lower limbs (relative risk [RR], 3.38; 95% CI, 2.62-4.38) and weakest for the upper limbs (RR, 1.96; 95% CI, 1.22-3.17; P = .02 for heterogeneity). Mean lifetime number of sunbathing vacations was significantly associated with risk of trunk melanomas (RR, 1.14; 95% CI, 1.07-1.22) and lower limb melanomas (RR, 1.12; 95% CI, 1.05-1.19) but not upper limb melanomas (RR, 0.98; 95% CI, 0.88-1.09) and head and neck melanomas (RR, 0.87; 95% CI, 0.73-1.04; P = .006 for heterogeneity). Indoor tanning was associated only with trunk melanomas (RR for the highest tertile, 1.49; 95% CI, 1.16-1.92) and lower limb melanomas (RR for the highest tertile, 1.33; 95% CI, 1.00-1.76; P = .002 for heterogeneity). Skin color, hair color, small symmetric nevi, and history of sunburns were associated with risk of melanoma on all sites.\n\nCONCLUSIONS AND RELEVANCE:\nThese results appear to support the hypothesis of divergent pathways to melanoma and that recreational sun exposure and indoor tanning are associated with melanoma on the lower limbs, the most common site of melanoma in women. These findings appear to have important preventive implications." }

{ "id": "30760441", "text": "OBJECTIVE:\nTo determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease.\n\nDESIGN:\nCase-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and followed to September 2016.\n\nSETTING:\nNorwegian population.\n\nPARTICIPANTS:\nChildren carrying the HLA genotype DR4-DQ8/DR3-DQ2 conferring increased risk of coeliac disease.\n\nEXPOSURES:\nEnterovirus and adenovirus detected using real time polymerase chain reaction in monthly stool samples from age 3 to 36 months.\n\nMAIN OUTCOME MEASURE:\nCoeliac disease diagnosed according to standard criteria. Coeliac disease antibodies were tested in blood samples taken at age 3, 6, 9, and 12 months and then annually. Adjusted odds ratios from mixed effects logistic regression model were used to assess the relation between viral infections before development of coeliac disease antibodies and coeliac disease.\n\nRESULTS:\nAmong 220 children, and after a mean of 9.9 (SD 1.6) years, 25 children were diagnosed as having coeliac disease after screening and were matched to two controls each. Enterovirus was found in 370 (17%) of 2135 samples and was significantly more frequent in samples collected before development of coeliac disease antibodies in cases than in controls (adjusted odds ratio 1.49, 95% confidence interval 1.07 to 2.06; P=0.02). The association was restricted to infections after introduction of gluten. High quantity samples (>100 000 copies/μL) (adjusted odds ratio 2.11, 1.24 to 3.60; P=0.01) and long lasting infections (>2 months) (2.16, 1.16 to 4.04; P=0.02) gave higher risk estimates. Both the commonly detected enterovirus species and were significantly associated with coeliac disease. The association was not found for infections during or after development of coeliac disease antibodies. Adenovirus was not associated with coeliac disease.\n\nCONCLUSIONS:\nIn this longitudinal study, a higher frequency of enterovirus, but not adenovirus, during early childhood was associated with later coeliac disease. The finding adds new information on the role of viral infections in the aetiology of coeliac disease." }

{ "id": "30760605", "text": "OBJECTIVES:\nFarming has been associated with rheumatoid arthritis (RA). Some studies have evaluated the effects of pesticides, but other agricultural exposures may also affect immune response.\n\nMETHODS:\nWe investigated non-pesticide agricultural exposures in relation to RA in licensed pesticide applicators (n=27 175, mostly male farmers) and their spouses (n=22 231) in the Agricultural Health Study (AHS) cohort (1993-1997) who completed at least one follow-up survey through 2015. Incident RA cases (n=229 applicators and 249 spouses) were identified based on self-report confirmed by use of disease-modifying antirheumatic drugs or medical records. Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) were estimated by Cox proportional hazard models adjusting for applicator status, state, smoking, education and specific pesticide use, allowing estimates to vary by median age when hazards assumptions were not met.\n\nRESULTS:\nOverall, RA was associated with regularly applying chemical fertilisers (HR=1.50; 95% CI 1.11 to 2.02), using non-gasoline solvents (HR=1.40; 95% CI 1.09 to 1.80), and painting (HR=1.26; 95% CI 1.00 to 1.59). In older applicators (>62 years), RA was associated with driving combines (HR=2.46; 95% CI 1.05 to 5.78) and milking cows (HR=2.56; 95% CI 1.01 to 6.53). In younger participants (≤62 years), RA was inversely associated with raising animals as well as crops (HR=0.68; 95% CI 0.51 to 0.89 vs crops only). Associations with specific crops varied by age: some (eg, hay) were inversely associated with RA in younger participants, while others (eg, alfalfa) were associated with RA in older participants.\n\nCONCLUSION:\nThese findings suggest several agricultural tasks and exposures may contribute to development of RA." }

{ "id": "30790475", "text": "OBJECTIVE:\nTo investigate the impact and timing of smoking cessation on developing rheumatoid arthritis (RA) and serologic phenotypes.\n\nMETHODS:\nWe investigated smoking cessation and RA risk in the Nurses' Health Study (NHS) (1976-2014) and the NHS II (1989-2015). Smoking exposures and covariates were obtained by biennial questionnaires. Self-reported RA was confirmed by medical record review for American College of Rheumatology/European League Against Rheumatism criteria. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for RA serologic phenotypes (all, seropositive, seronegative) according to smoking status, intensity, pack-years, and years since cessation.\n\nRESULTS:\nAmong 230,732 women, we identified 1,528 incident cases of RA (63.4% of which were seropositive) during 6,037,151 person-years of follow-up. Compared with never smoking, current smoking increased the risk of all RA (multivariable HR 1.47, 95% CI 1.27-1.72) and seropositive RA (HR 1.67, 95% CI 1.38-2.01) but not seronegative RA (HR 1.20, 95% CI 0.93-1.55). An increasing number of smoking pack-years was associated with an increased trend for the risk of all RA (P < 0.0001) and seropositive RA (P < 0.0001). With increasing duration of smoking cessation, a decreased trend for the risk of all RA was observed (P = 0.009) and seropositive RA (P = 0.002). Compared to recent quitters (<5 years), those who quit ≥30 years ago had an HR of 0.63 (95% CI 0.44-0.90) for seropositive RA. However, a modestly increased risk of RA was still detectable 30 years after quitting smoking (for all RA, HR 1.25 [95% CI 1.02-1.53]; for seropositive RA, HR 1.30 [95% CI 1.01-1.68]; reference, never smoking).\n\nCONCLUSION:\nThese results confirm that smoking is a strong risk factor for developing seropositive RA and demonstrate for the first time that a behavior change of sustained smoking cessation could delay or even prevent seropositive RA." }

{ "id": "30792131", "text": "Efforts to quantify the global burden of enteric fever are valuable for understanding the health lost and the large-scale spatial distribution of the disease." }

{ "id": "30922351", "text": "BACKGROUND:\nExtremity myxoid liposarcoma (MLS) is a rare soft tissue sarcoma in adults. We performed this study to define distinctive clinical features of extremity MLS by assessing prognostic factors.\n\nMETHODS:\nBetween 1973 and 2015, 1756 patients with extremity MLS who underwent surgical resection were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute. Both overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method (to obtain OS and CSS curves) and a Cox proportional hazards regression model.\n\nRESULTS:\nOf the 1756 patients with extremity MLS, the mean and median patient age at diagnosis were 47 and 45 years, respectively. More than half (n = 1027, 58.5%) of the patients were male. In terms of location, 10.5% tumors were located in the upper limbs and 89.5% in lower limbs. All patients received local surgery, and about half of the patients (57.2%) received radiation treatment. The 5- and 10-year OS rates of the entire cohort were 86.4% and 75.9%, respectively. The 5- and 10-year CSS rates were 90.5% and 85.2%, respectively. On multivariate analysis, older age, male gender, high tumor grade, and tumor size > 10 cm were found to be independent risk factors of both decreased OS and CSS. Year of diagnosis ≥ year 2000 was significantly associated with an increased CSS. In addition, radiation treatment failed to become an independent risk factor for either OS or CSS.\n\nCONCLUSION:\nWe identified age, gender, tumor grade, year of diagnosis, and tumor size as independent prognostic factors for OS and CSS in patients with extremity MLS." }

{ "id": "31250012", "text": "BACKGROUND:\nThe role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings.\n\nAIMS:\nThis study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study.\n\nMETHODS:\nA total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan's National Health Insurance Research Database. The Kaplan-Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC.\n\nRESULTS:\nThe cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37-2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection.\n\nCONCLUSIONS:\nOur study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies." }

{ "id": "31371090", "text": "Herein it is hypothesized that M2-like macrophages or pre-macrophages of fetal origin might play a central role in development and closure of the neural tube. Early in embryonic development, pre-macrophages arise from the fetal yolk sac and track through the bloodstream to reach diverse embryonic tissues, where they mature." }

{ "id": "31665782", "text": "Analyses of the global spatial and temporal distribution of enteric fever outbreaks worldwide are important factors to consider in estimating the disease burden of enteric fever disease burden." }

{ "id": "31804006", "text": "Adult T-cell acute lymphoblastic leukemia (T-ALL) is a heterogeneous group of acute leukemias that account for about one third of all cases of Philadelphia chromosome (Ph)-negative ALL. Recently, a molecular classifier using the mutational status of NOTCH1, FBXW7, RAS, and PTEN (NFRP) has been shown to distinguish low- vs high-risk groups in adult T-ALL patients treated using the Berlin-Frankfurt-Münster ALL protocol. However, it is unknown if this molecular classifier can stratify adult T-ALL patients treated with hyper-CVAD ± nelarabine. We identified a relatively small cohort of 27 adults with T-ALL who were uniformly treated with hyper-CVAD ± nelarabine with available mutational analysis at time of diagnosis. The most commonly mutated genes in this group were NOTCH1 (52%), NRAS (22%), DNMT3A (19%), KRAS (15%), and TP53 (7%). The NFRP molecular classifier failed to stratify overall survival (OS; P = .84) and relapse-free survival (RFS; P = .18) in this cohort. We developed a new stratification model combining K/NRAS and TP53 mutations as high-risk factors and showed that mutations in these genes predicted poorer OS (P = .03) and RFS (P = .04). While the current study is limited by cohort size, these data suggest that the NFRP molecular classifier might not be applicable to adult T-ALL patients treated with hyper-CVAD ± nelarabine. RAS/TP53 mutation status, however, was useful in risk stratification in adults with T-ALL." }

{ "id": "31939580", "text": "Hereditary spastic paraplegias (HSP) are a group of genetic diseases characterized by lower limb spasticity with or without additional neurological features. Swallowing dysfunction is poorly studied in HSP and its presence can lead to significant respiratory and nutritional complications." }

{ "id": "32210617", "text": "Phosphoinositide 3-kinase (PI3K) and the downstream Akt/mammalian target of rapamycin (mTOR) pathway are central to the control of cell proliferation and survival. Although abnormal activation of this pathway has been well established in a variety of tumours, limited studies are available on synovial sarcoma. The aim of this study was to investigate the expression of several key proteins of those pathways in synovial sarcomas and to correlate the expression of these proteins with clinicopathologic features and prognosis." }

{ "id": "32816888", "text": "BACKGROUND AND OBJECTIVES:\nC3 glomerulopathy is a complement-mediated disease arising from abnormalities in complement genes and/or antibodies against complement components. Previous studies showed that treatment with corticosteroids plus mycophenolate mofetil (MMF) was associated with improved outcomes, although the genetic profile of these patients was not systematically analyzed. This study aims to analyze the main determinants of disease progression and response to this therapeutic regimen.\n\nDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:\nWe conducted a retrospective, multicenter, observational cohort study in 35 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases. Patients diagnosed with C3 glomerulopathy (=81) or dense deposit disease (=16) between January 1995 and March 2018 were enrolled. Multivariable and propensity score matching analyses were used to evaluate the association of clinical and genetic factors with response to treatment with corticosteroids and MMF as measured by proportion of patients with disease remission and kidney survival (status free of kidney failure).\n\nRESULTS:\nThe study group comprised 97 patients (84% C3 glomerulopathy, 16% dense deposit disease). Forty-two patients were treated with corticosteroids plus MMF, and this treatment was associated with a higher rate of remission and lower probability of kidney failure (79% and 14%, respectively) compared with patients treated with other immunosuppressives (24% and 59%, respectively), or ecluzimab (33% and 67%, respectively), or conservative management (18% and 65%, respectively). The therapeutic superiority of corticosteroids plus MMF was observed both in patients with complement abnormalities and with autoantibodies. However, patients with pathogenic variants in complement genes only achieved partial remission, whereas complete remissions were common among patients with autoantibody-mediated forms. The main determinant of no remission was baseline proteinuria. Relapses occurred after treatment discontinuation in 33% of the patients who had achieved remission with corticosteroids plus MMF, and a longer treatment length of MMF was associated with a lower risk of relapse.\n\nCONCLUSIONS:\nThe beneficial response to corticosteroids plus MMF treatment in C3 glomerulopathy appears independent of the pathogenic drivers analyzed in this study." }