Immunological mechanisms of fecal microbiota transplantation in recurrent Clostridioides difficile infection

Fecal microbiota transplantation (FMT) is a successful method for treating recurrent Clostridioides difficile (C. difficile) infection (rCDI) with around 90% efficacy. Due to the relative simplicity of this approach, it is being widely used and currently, thousands of patients have been treated with FMT worldwide. Nonetheless, the mechanisms underlying its effects are just beginning to be understood. Data indicate that FMT effectiveness is due to a combination of microbiological direct mechanisms against C. difficile, but also through indirect mechanisms including the production of microbiota-derived metabolites as secondary bile acids and short chain fatty acids. Moreover, the modulation of the strong inflammatory response triggered by C. difficile after FMT seems to rely on a pivotal role of regulatory T cells, which would be responsible for the reduction of several cells and soluble inflammatory mediators, ensuing normalization of the intestinal mucosal immune system. In this minireview, we analyze recent advances in these immunological aspects associated with the efficacy of FMT.     

Computer-Aided Diagnosis of Vertebral Compression Fractures Using Convolutional Neural Networks and Radiomics

Journal of Digital Imaging - Vertebral Compression Fracture (VCF) occurs when the vertebral body partially collapses under the action of compressive forces. Non-traumatic VCFs can be secondary to...     

Desarrollo y validación de la versión abreviada del Transsexual Voice Questionnaire for Male-to-Female Transsexuals en español

ObjectiveThe aim of this study was to create and validate an abbreviated version of the Spanish Transsexual Voice Questionnaire for Male-to-Female Transsexuals (SvTVQ^MtF).SettingThe study was conducted by two referral hospitals for voice feminization surgery and by a university department of psychology and speech therapy, all in Spain.Subjects and methodsWe prospectively studied 51 male-to-female transsexuals who underwent voice feminization surgery between January 2017 and December 2018. The SvTVQ^MtF was completed before and after surgery, and the 10 items with the greatest variation were selected by clinical consensus of an expert panel to develop the short version of the SvTVQ^MtF (SvTVQ^MtF-10). The correlation between the total score and the score for each item on the SvTVQ^MtF and the SvTVQMtF-10 was studied. The internal consistency of the SvTVQ^MtF-10 was analysed.ResultsGood correlation (Pearson coefficient above .90) was found between the two questionnaires. A significant correlation was found between the total SvTVQ^MtF-10 score and the score for each item. A significant negative correlation was found between the SvTVQ^MtF and fundamental frequency after voice feminization surgery. Cronbach's α was .79.ConclusionThe SvTVQ^MtF-10 is a valid short version of the SvTVQ^MtF and can be used to quantify voice-related quality of life in MtF transsexuals.     

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.     

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.

     

Placental metal concentrations and birth outcomes: The Environment and Childhood (INMA) project

Objective

To examine the association of placental levels of arsenic (As), cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and chromium (Cr) with birth outcomes (birth weight, length, and head circumference, low birth weight [LBW], gestational age, preterm delivery, and small for gestational age [SGA]) in mother-child pairs from the Environment and Childhood (INMA) Project in Spain.