How is the quality of the available evidence on molar-incisor hypomineralization treatment? An overview of systematic reviews

Clinical Oral Investigations - This overview analyzed the quality of the systematic reviews (SRs) available on treatments for molar-incisor hypomineralization (MIH). Six electronic databases were...     

Calendario de vacunaciones de la Asociación Española de Pediatría: recomendaciones 2021

The CAV-AEP annually publishes the immunisation schedule considered optimal for all children and adolescent resident in Spain, taking into account the available evidence.The 2 + 1 schedule is recommended (2, 4, and 11 months) with hexavalent vaccines (DTPa-VPI-Hib-HB) and with 13-valent pneumococcal conjugate.A 6-year booster is recommended, preferably with DTPa (if available), with a dose of polio for those who received 2 + 1 schemes, as well as vaccination with Tdpa in adolescents and in each pregnancy, preferably between 27 and 32 weeks.Rotavirus vaccine should be systematic for all infants.Meningococcal B vaccine, with a 2 + 1 schedule, should be included in routine calendar.In addition to the inclusion of the conjugated tetravalent meningococcal vaccine (MenACWY) at 12 years of age with catch up to 18 years, inclusive, the CAV recommends this vaccine to be also included at 12 months of age, replacing MenC. Likewise, it is recommended in those over 6 weeks of age with risk factors or who travel to countries with a high incidence of these serogroups.Two-dose schedules for triple viral (12 months and 3-4 years) and varicella (15 months and 3-4 years) will be used. The second dose could be applied as a tetraviral vaccine.Universal systematic vaccination against HPV is recommended, regardless of gender, preferably at 12 years, and greater effort should be made to improve coverage. The 9 genotype extends coverage for both genders.     

Sensitivity of the Montreal Cognitive Assessment in screening for cognitive impairment in patients with newly diagnosed high-grade glioma

Journal of Neuro-Oncology - Cognitive impairment is frequent in patients with high-grade glioma and requires cognitive follow-up. Cognitive screening tools such as the Montreal Cognitive Assessment...     

Re-interpretation of PAM50 gene expression as quantitative tumor dimensions shows utility for clinical trials: application to prognosis and response to paclitaxel in breast cancer

Background

We recently showed PAM50 gene expression data can be represented by five quantitative, orthogonal, multi-gene breast tumor traits. These novel tumor ‘dimensions’ were superior to categorical intrinsic subtypes for clustering in high-risk breast cancer pedigrees, indicating potential to represent underlying genetic susceptibilities and biological pathways. Here we explore the prognostic and predictive utility of these dimensions in a sub-study of GEICAM/9906, a Phase III randomized prospective clinical trial of paclitaxel in breast cancer.

Methods

Tumor dimensions, PC1–PC5, were calculated using pre-defined coefficients. Univariable and multivariable Cox proportional hazards (PH) models for disease-free survival (DFS) were used to identify associations between quantitative dimensions and prognosis or response to the addition of paclitaxel. Results were illustrated using Kaplan–Meier curves.

Results

Dimensions PC1 and PC5 were associated with DFS (Cox PH p = 6.7 \(\times\) 10⁻⁷ and p = 0.036), remaining significant after correction for standard clinical–pathological prognostic characteristics. Both dimensions were selected in the optimal multivariable model, together with nodal status and tumor size (Cox PH p = 1.4 \(\times\) 10⁻¹²). Interactions with treatment were identified for PC3 and PC4. Response to paclitaxel was restricted to tumors with low PC3 and PC4 (log-rank p = 0.0021). Women with tumors high for PC3 or PC4 showed no survival advantage.

Conclusions

Our proof-of-concept application of quantitative dimensions illustrated novel findings and clinical utility beyond standard clinical–pathological characteristics and categorical intrinsic subtypes for prognosis and predicting chemotherapy response. Consideration of expression data as quantitative tumor dimensions offers new potential to identify clinically important patient subsets in clinical trials and advance precision medicine.

     

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks: The GR@ACE project

IntroductionLarge variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways.MethodsGenome Research at Fundacio ACE ([email protected]) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, [email protected] series were meta-analyzed with additional genome-wide association study data sets.ResultsWe classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444.DiscussionThe regulation of vasculature is a prominent causal component of probable AD. [email protected] meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series.