Summary Purpose:  Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined. Methods:  We analyzed GADA with a radioimmunoassay in sera of 253 well‐characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies. Results:  GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [≥1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA‐positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra‐TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39–4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001). Discussion:  High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.

These results suggest that women who experience spontaneous pregnancy loss are at a substantially higher risk of MI later in life. Recurrent miscarriage and stillbirth are strong sex-specific predictors for MI and thus should be considered as important indicators for cardiovascular risk factors monitoring and preventive measures. Further research is suggested to elucidate underlying risk factors of pregnancy loss that at the same time strongly predispose to cardiovascular disease. Pregnancy loss and risk of cardiovascular disease: a prospective population-based cohort study (EPIC-Heidelberg)Elham Kharazmi, Laure Dossus, Sabine Rohrmann, Rudolf Kaaks ABSTRACT Objectives To examine whether pregnancy loss (miscarriage, abortion or stillbirth) is associated with a higher risk of myocardial infarction (MI) and stroke. Design Population-based prospective cohort study. Setting The European Prospective Investigation into Cancer and Nutrition (EPIC) cohort in Heidelberg, Germany (mean follow-up 10.8 years). Participants All 11 518 women who had ever been pregnant (aged 35e66). Results Out of the participants, 2876 (25%) had at least one miscarriage, 2053 (18%) had at least one abortion and 209 (2%) had at least one stillbirth. During the follow-up, 82 cases of MI and 112 of stroke (confirmed by medical records) occurred in these women. Each stillbirth increased the risk of MI 2.65 times (95% CI for age-adjusted HR 1.37 to 5.12; HR adjusted for age, smoking, alcohol consumption, body mass index, waist to hip ratio, physical activity, education, number of pregnancies, hypertension, hyperlipidaemia and diabetes mellitus: HR 2.32 95% CI 1.19 to 4.50, 95% CI). Recurrent miscarriage (>3) was associated with about nine times higher risk of MI (age-adjusted HR¼8.90, 95% CI 3.18 to 24.90; fully adjusted HR 5.06, 95% CI 1.26 to 20.29). No significant association was found between abortion and MI or between any type of pregnancy loss and stroke. Conclusions These results suggest that women who experience spontaneous pregnancy loss are at a substantially higher risk of MI later in life. Recurrent miscarriage and stillbirth are strong sex-specific predictors for MI and thus should be considered as important indicators for cardiovascular risk factors monitoring and preventive measures. Further research is suggested to elucidate underlying risk factors of pregnancy loss that at the same time strongly predispose to cardiovascular disease.

Previous studies have reported activation of inflammatory cytokines in seizures, but clinical characteristics of epilepsy associated with cytokine activation have not been well established. In this study, serum levels of interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA) were measured, and clinical characteristics of epilepsy were assessed in 86 well-evaluated patients with refractory focal epilepsy and in 5 patients with controlled focal epilepsy. Epilepsy was evaluated based on patient histories, electroclinical findings, and high-resolution brain MRI scans. Sixty-three healthy blood donors served as controls. IL-6 concentrations were chronically increased in epilepsy patients (11%) compared with healthy controls (0%) (P = 0.007). Increased levels of IL-6 were more prevalent in patients with temporal lobe epilepsy (TLE) compared to patients with extra-TLE (P = 0.028). Also the mean and the median serum levels of IL-6 were higher in patients with TLE than in patients with extra-TLE (P = 0.042). Concentrations of IL-1RA were not significantly different in patients compared with controls. Indicated by increased levels of IL-6 in TLE, epilepsy type is important in determining chronic overproduction of cytokines in refractory focal epilepsy. The results may reflect a chronic immunological process in the brain in patients with refractory epilepsy.

IMPORTANCE Breast cancer screening guidelines acknowledge the need for earlier screening for women at increased risk but provide limited guidance for women with a family history of breast cancer. A risk-adapted starting age of screening for relatives of patients with breast cancer may help supplement current screening guidelines. OBJECTIVE To identify the risk-adapted starting age of breast cancer screening on the basis of a woman's detailed family history. DESIGN, SETTING, AND PARTICIPANTS This nationwide cohort study analyzed data recorded in the Swedish family-cancer data sets. All women born from 1932 onward and with at least 1 known first-degree relative (FDR) were included (

Evidence that childbearing is associated with future development of diabetes remains conflicting and the role of pregnancy loss in this association has not been investigated. We aimed to examine whether pregnancy and/or pregnancy loss (miscarriage, abortion, or stillbirth) are associated with maternal higher risk of diabetes later in life, using a population-based prospective cohort study (mean follow-up = 10.7 years), including 13,612 women (aged 35-65 at baseline). We found pregnancy per se did not change the risk of diabetes after considering the effect of education, smoking, alcohol consumption, physical activity, BMI, waist/hip ratio, hypertension, and hyperlipidemia (fully-adjusted OR: 1.04, 95 % CI: 0.82-1.31). Having more than four live births was associated with around two times higher risk of diabetes later in life (fully-adjusted OR: 1.77, 95 % CI: 1.12-2.80). Having more than two miscarriages was associated with about two-fold higher risk of diabetes (fully-adjusted Odd ratio (OR): 1.85, 95 % CI: 1.17-2.93). After further adjustment for parity, the higher risk of diabetes in those who had history of more than two miscarriages did not change substantially (OR: 1.82; 95 % CI: 1.15-2.88), but the association between more than four live births and diabetes disappeared when the role of pregnancy loss was considered (fully-adjusted HR: 1.06; 95 % CI: 0.54-2.08). No significant association was found between abortion, stillbirth and risk of maternal diabetes. Pregnancy per se did not increase risk of diabetes. Women who experience more than two miscarriages are at around two times higher risk of diabetes later in life. The association between high parity and diabetes is mediated by history of miscarriages and known risk factors of diabetes. The underlying reason for association between miscarriage and diabetes needs further investigation.

Objective To determine whether familial risk of cancer is limited to early onset cases.

Key Points• We provide clinically relevant familial risk estimates for classical HL patients by relationship, histology, age at diagnosis, and sex.We aimed to provide the familial risk of classical Hodgkin lymphoma (HL) by relationship, histology, age at diagnosis, and sex. A cohort of 57 475 first-degree relatives of 13 922 HL patients diagnosed between 1955 and 2009 in 5 European countries was observed for HL incidence. The overall lifetime cumulative risk (CR) of HL in first-degree relatives of a patient with HL was 0.6%, which represents a threefold (standardized incidence ratio [SIR], 3.3; 95% confidence interval [CI], 2.8-3.9) increased risk over the general population risk. The risk in siblings (6.0-fold; 95% CI, 4.8-to 7.4-fold) was significantly higher than in parents and/or children (2.1-fold; 95% CI, 1.6-to 2.6-fold). Very high lifetime risk of HL was found for those with multiple affected first-degree relatives (13-fold; 95% CI, 2.8-to 39-fold) and for same-sex twins (57-fold; 95% CI, 21-to 125-fold). We found high familial risks between some concordant histologic subtypes of HL such as lymphocyte-rich (81-fold; 95% CI, 30-to 177-fold) and nodular sclerosis (4.6-fold; 95% CI, 2.9-to 7.0-fold) and also between some discordant subtypes. The familial risk in sisters (9.4-fold; 95% CI, 5.9-to 14-fold) was higher than in brothers (4.5-fold; 95% CI, 2.9-to 6.7-fold) or unlike-sex siblings (5.9-fold; 95% CI, 4.3-to 8.1-fold). The lifetime risk of HL was higher when first-degree relatives were diagnosed at early ages (before age 30 years). This study provides tangible absolute risk estimates for relatives of HL patients, which can be used as a sex-, age-, and family history-based risk calculator for classical HL by oncologists and genetic counselors.

In a nationally representative sample (the Health 2000 Survey) comprising 3,937 Finnish women aged 30-99 years, we examined the association of miscarriage (assessed by questionnaire) with risk of cardiovascular disease (assessed by physician's examination and linkages to hospital discharge and drug reimbursement registers). We considered age, smoking, body mass index, waist/hip ratio, physical activity, education, number of previous pregnancies, blood pressure, and fasting blood glucose and cholesterol as potentially confounding factors in the analysis. In women 50-74 years of age who had experienced pregnancy, history of miscarriage tended to be associated with a higher risk of myocardial infarction (age-adjusted odds ratio (OR): 2.1, 95% confidence interval (CI): 1.0-4.3), and the risk increased significantly with the number of miscarriages (age-adjusted OR per miscarriage: 1.4, 95% CI: 1.1-1.8). These results suggest that women who experience repeated miscarriages may be at an increased risk of cardiovascular disease later in life.