Accurate primary germ cell cancer diagnosis using serum based microRNA detection (ampTSmiR test)

Multiple studies, including various methods and overall limited numbers of mostly heterogeneous cases, indicate that the level of embryonic stem cell microRNAs (miRs) (e.g. 371a-3p, 372-3p, 373-3p, and 367-3p) are increased in serum at primary diagnosis of almost all testicular germ cell cancer (TGCC). Here we determine the status of three of these miRs in serum samples of 250 TGCC patients, collected at time of primary diagnosis, compared with 60 non-TGCC patients and 104 male healthy donors. The levels of miRs were measured by the robust ampTSmiR test, including magnetic bead-based miR isolation and target specific preamplification followed by real-time quantitative PCR (RT-qPCR) detection. Calibration is performed based on the non-human spike-in ath-miR-159a, and normalization on the endogenous control miR-30b-5p. The serum levels of miR-371a-3p, 373-3p, and 367-3p are informative to accurately detect TGCC patients, both seminomas and non-seminomas, at the time of primary diagnosis (p < 0.000). Receiver Operating Characteristic (ROC) analysis demonstrate that the Area Under the Curve (AUC) for miR-371a-3p is 0.951 (being 0.888 for miR-373-3p and 0.861 for miR-367-3p), with a sensitivity of 90%, and a specificity of 86% (positive predictive value of 94% and negative predictive value of 79%). Inclusion of miR-373-3p and 367-3p resulted in a AUC of 0.962, with a 90% sensitivity and 91% specificity. Similar results were obtained using the raw Ct data. Importantly, the results demonstrate that ampTSmiR is not suitable to detect pure teratoma as well as the precursor of TGCC, i.e., Germ Cell Neoplasia In Situ (GCNIS). The largest series evaluated so far, demonstrate that detection of the embryonic stem cell miR-371a-3p, 373-3p and 367-3p is highly informative to diagnose patients with a primary TGCC

Economic evaluations in aggressive non-Hodgkin's lymphoma

Non-Hodgkin's lymphoma (NHL) has the highest incidence rate of all haematological malignancies in the Western world 1 • In the USA, the number of deaths attributable to NHL currently ranks in the top five of cancer related deaths2 In the Netherlands, haematological malignancies rank 8 in the cancer incidence list, and about 2100 inhabitants per year are newly diagnosed with NHL1 . Between 1973 and 1989, the incidence of NHL increased by nearly 60% in the United States, which is one of the largest increases observed in any cancer3 . This rise has not stopped yet: NHL is amongst the small number of malignancies that also have shown markedly increased incidence and mortality rates during the recent past'· 4 During the same years, health care costs in developed countries have risen faster than the general inflation rate, making economic evaluations an integral part of health care decision making5 These developments underline the need for economic evaluations of NHL, and this thesis will therefore focus on this kind of evaluations in the most prevalent subtype of NHL

microRNA-371a-3p as informative biomarker for the follow-up of testicular germ cell cancer patients

Purpose: α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up. Methods: We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers. Results: At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma. Conclusions: The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection o

A Systematic Review of Literatures onFactors Associated with Educational ndAcademic Performance in Attention DeficitHyperactivity Disorder

__Abstract__ Attention Deficit Hyperactivity Disorder (ADHD) has been shown to impair major life activities including educational functioning. However, there is no consensus on the specific cause for the impact on this worse educational outcome. This systematic review aims to identify factors that have been associated with educational and academic underperformance of children and adolescents with ADHD. A literature search was conducted using PubMed and the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The study focused on articles presenting results of data-based analyses related to ADHD and keywords related to education. The search resulted in 376 records that were screened by title. Of these, 185 articles were screened by abstract and 35 met the eligibility criteria for inclusion in the review. These 35 articles were related to seven domains: educational training, educational environment, pharmacological treatment, ADHD symptoms, associations of ADHD with academic outcomes, self-concept, and specific skills. The main source of educational challenges seems to be related to the inattentive symptoms (or subtype) of ADHD. This outcome is different than expected, since hyperactive symptoms are pronounced more prominently and often refer children to clinical practice. Inattentive symptoms amongst others refer to difficulties in organization skills and can lead to decreased self-efficacy and development of depressive symptoms. This decreased self-efficacy and the depressive symptoms were also found to be related to influence the relation between ADHD and academic performance. Educational outcomes were shown to be improved using small group work, learning via a computer-based service and as a result of coaching and pharmacological treatment. To help children and adults achieve educational goals that now are out of reach, more attention should be spent to the inattentive symptoms of ADHD and possibilities to overcome experienced problems