The impact of inter-laboratory glucose bias on the diagnosis of gestational diabetes mellitus: Comparison of common automated central laboratory methods.

BACKGROUND AND AIMS: The diagnosis of gestational diabetes mellitus (GDM) is based exclusively on glucose measurements, which are highly influenced by pre-analytical and analytical factors. Therefore, poor agreement across laboratories may affect the prevalence of GDM. We aimed to determine the inter-laboratory bias of glucose measurements and the impact on GDM prevalence. MATERIAL AND METHODS: A prospective cohort study of women (n = 110) referred for second-trimester GDM diagnostics using a 75 g oral glucose tolerance test. Maternal glucose was assessed from venous plasma at fasting, 1 h and 2 h. Venous blood were collected in Fluoride Citrate tubes and frozen. Samples were analyzed at five central laboratories using four different automated glucose Hexokinase methods and GDM prevalence was evaluated according to WHO2013 diagnostic criteria. RESULTS: Maximum inter-laboratory bias was 0.19, 0.30 and 0.27 mmol/L in fasting, 1 h and 2 h samples, respectively. GDM prevalence ranged 30.0-41.1% across laboratories. CONCLUSION: Inter-laboratory bias for mean venous glucose was low and within desirable limits. Nonetheless, the impact on GDM prevalence was considerable, which may inappropriately affect clinical practice.

First trimester serum apolipoproteins in the prediction of late-onset preeclampsia.

Late-onset preeclampsia occurring after 34 weeks of gestation is the most common form of preeclampsia, but little is known about either etiology or prevention. Current detection methods for preeclampsia in early pregnancy have not shown promising results in detecting late-onset preeclampsia. The aim of this study was to assess whether apolipoproteins in combination with maternal medical history and biophysical factors can be used as an early detection method for late-onset preeclampsia. This nested case-cohort study was based at Odense University Hospital, Denmark. Women attending their first trimester scan were invited to participate if they understood Danish or English, were above the age of 18, and had singleton pregnancies. Blood pressure, maternal medical history, uterine artery pulsatility indices, and blood samples were collected at inclusion. Outcome data were collected from participants' medical files postpartum, and cases were selected when preeclampsia diagnostics were present. Serum samples were analyzed by targeted mass spectrometry using a biomarker panel consisting of 12 apolipoproteins. Logistic regression analyses were performed and finally receiver operating curves were completed. The cohort consisted of 27 cases and 194 normotensive controls, randomized from 340 eligible participants. Significant differences were found between the two groups' baseline characteristics but none of the apolipoproteins showed significant difference (p < 0.05). The ROC-curve combining maternal characteristics, mean arterial pressure and two apolipoproteins showed the best sensitivity of 55.5% at a 10% false-positive rate and an area under the curve of 0.873. In conclusion, apolipoproteins did not improve the detection of late-onset preeclampsia in a combined screening model.

Managing antithrombotic treatment in a patient with atrial fibrillation and coronary stent with transient neurological symptoms in cerebral amyloid angiopathy.

We present the antithrombotic dilemma in a case with atrial fibrillation and a coronary stent and suspected transient ischemic attacks after diagnosed as a probable cerebral amyloid angiopathy and discuss plausible treatment options for the patient based on the available evidence.

Risk factors for development of lymphopenia in dimethyl fumarate-treated patients with multiple sclerosis.

BACKGROUND: Dimethyl fumarate (DMF, Tecfidera®) is a first-line disease-modifying therapy for relapsing-remitting multiple sclerosis. Lymphopenia is a frequent reason for discontinuation in fumarate-treated patients. Management strategies to minimize risk of lymphopenia are warranted. OBJECTIVE: The aims of this study were to investigate the correlation of body mass index (BMI), baseline absolute lymphocyte count (ALC), age and sex with risk of DMF-induced lymphopenia in MS patients. METHODS: The study was a retrospective cohort study of 452 MS patients who had been prescribed DMF at six clinics in two Danish regions between May 2014 and September 2017. Data on lymphocyte counts, BMI, age, sex, and reason for discontinuation of DMF were collected through the Danish Multiple Sclerosis Registry, with follow- up to two years after treatment start. RESULTS: 28.5% of patients had lymphopenia grade II or higher at some time in the first two years of DMF treatment. Increased risk of lymphopenia was observed in patients with baseline ALC of 1.00-1.49×109 cells/L (odds ratio, OR 5.48, p<0.0001) and 1.50-1.99×109 cells/L (OR 2.08, p = 0.0009). Reduced risk of lymphopenia was observed in patients with ALC of 2.00-2.49×109 cells/L (OR 0.51, p< 0.01) and ≥ 2.50×109 cells/L (0.12, p<0.0001). Patients aged ≥ 56 years had an increased risk of lymphopenia (OR 3.58, p<0.001), and patients with BMI ≥ 30 kg/m2 had a decreased risk of lymphopenia (OR 0.53, p value = 0.03). CONCLUSION: Low baseline ALC and older age were risk factors for DMF-induced lymphopenia, while BMI ≥ 30 kg/m2 and high baseline ALC were protective factors for developing lymphopenia in MS patients treated with DMF.

First trimester serum matrix metalloproteinase-7 is a poor predictor of late-onset preeclampsia.

OBJECTIVES: This study aims to evaluate matrix metalloproteinase-7 as a first trimester biomarker for late-onset preeclampsia, both alone and in combination with mean arterial pressure, uterine artery pulsatility index, and maternal characteristics. STUDY DESIGN: We conducted a nested case-control study from a prospective cohort consisting of 416 pregnant women who attended a routine first trimester scan. Baseline variables were obtained at inclusion and analysed subsequently to formation of case and control groups. The study was designed to detect a mean difference of > 15% in matrix metalloproteinase-7 concentrations between groups with a statistical power of 80%. MAIN OUTCOME MEASURES: The primary outcome was preeclampsia with delivery after 34 weeks of pregnancy. RESULTS: The median matrix metalloproteinase-7 concentration in cases of late-onset preeclampsia (n = 27) was marginally lower compared to normotensive controls but this difference was not statistically significant. Matrix metalloproteinase-7 predicted 14.8% of cases at a 10% false-positive rate. Addition of matrix metalloproteinase-7 to any combination of variables did not significantly improve their performance. CONCLUSIONS: Matrix metalloproteinase-7 is not a useful biomarker for late-onset preeclampsia, neither alone nor in combination with mean arterial pressure, uterine artery pulsatility index, or maternal characteristics.

Characterization of Familial and Sporadic Migraine.

BACKGROUND: It is unknown whether clinical parameters differ between migraineurs with and without first-degree family members with migraine. OBJECTIVES: The present cross-sectional study describes differences between familial and sporadic migraine with a focus on migraine characteristics, migraine severity, comorbidities, and treatment. METHOD: From the Danish Headache Center we recruited 358 patients with familial migraine and 1727 patients with sporadic migraine. Each participant was assessed using a validated semi-structured interview. RESULTS: No differences in age (Mean = 44 and 44 [SD = 12.28 and 12.58] for familial and sporadic migraineurs, respectively; P = .900) or sex (295/358 (82.4%) and 1413/1727 (81.8%) women in familial and sporadic migraineurs, respectively; P = .853) were found. Familial migraineurs had more aphasic aura than sporadic migraineurs (41% vs 27%, P = .001). Sporadic migraineurs had more lifetime attacks ie, >100 attacks (45% vs 70%, P < .001) and prolonged attacks ie, lasting >72 hours (5% vs 12%, P < .001) than familial migraineurs. Further, sporadic migraineurs had a higher incidence of concussions (37% vs 41%, P = .001) compared to familial migraineurs. In agreement with a previous study, there was no difference between familial and sporadic migraine regarding triptan response (84% vs 81%, P = .440). CONCLUSION: Headache characteristics, triptan response, and comorbidities where similar in individulas with and without inherited migraine, suggesting that migraine are to be considered a hmogenoues disease. The difference in the clinical presentation of migraine with aura symptoms among patients with familial migraine should be considered in future studies. Further, more severe migraine among patients with sporadic migraine with aura could suggest that sporadic migraineurs have been exposed to stronger or multiple environmental factors and indicate that an early intervention in migraine treatment could lessen the severity of migraine.