Uterine carcinosarcoma (UCS) is a high-grade endometrial cancer characterized by two components: Carcinomatous (epithelial) and sarcomatous (stromal tissue) elements. The present study describes a ...clinical case of this type of UCS and also provides a brief literature review of this type of tumor. A 72-year-old female visited the emergency department of the authors' hospital with pain in the hypogastric region, intestinal dysrhythmia since 3 months prior, fever and a palpable abdominal mass. Laboratory test results revealed sepsis and mild anemia and an imaging test revealed a large uterine tumor with wide areas of necrosis and adenopathies. As determined by the multidisciplinary committee, surgery was considered the main treatment option and this was performed with no incidences. Carcinosarcoma is a rare tumor, which most frequently occurs in older women. The diagnosis is based on symptoms and imaging tests, such as ecography and scans. The gold standard of treatment is surgery, although it is possible that other types of therapies, such as chemotherapy and radiotherapy may also be effective, depending on the tumor stage. On the whole, the prognosis of patients with this type of tumor is poor, with a low survival rate, even in earlier stages due to its malignant component and the possibility for metastasis. Surgery is the optimal treatment for this type of tumor, if this is possible, always individualizing patients.
Objective: To prospectively evaluate the safety and efficacy profile of abatacept in patients with rheumatoid arthritis–associated interstitial lung disease (RA-ILD). Methods: We performed a ...prospective observational multicenter study of a cohort of patients with RA-ILD treated with abatacept between 2015 and 2021. Patients were evaluated using high-resolution computed tomography and pulmonary function tests at initiation, 12 months, and the end of follow-up. The effectiveness of abatacept was evaluated based on whether ILD improved, stabilized, progressed, or was fatal. We also evaluated factors such as infection, hospitalization, and inflammatory activity using the 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR). Cox regression analysis was performed to identify factors associated with progression of lung disease. Results: The study population comprised 57 patients with RA-ILD treated with abatacept for a median (IQR) of 27.3 (12.2–42.8) months. Lung disease had progressed before starting abatacept in 45.6% of patients. At the end of follow-up, lung disease had improved or stabilized in 41 patients (71.9%) and worsened in 13 (22.8%); 3 patients (5.3%) died. No significant decreases were observed in forced vital capacity (FVC) or in the diffusing capacity of the lung for carbon monoxide (DLCO).The factors associated with progression of RA-ILD were baseline DAS28-ESR (OR 95% CI, 2.52 1.03–3.12; p = 0.041), FVC (OR 95% CI, 0.82 0.70–0.96; p = 0.019), and DLCO (OR 95% CI, 0.83 0.72–0.96; p = 0.018). Only 10.5% of patients experienced severe adverse effects. Conclusion: Pulmonary function and joint inflammation stabilized in 71% of patients with RA-ILD treated with abatacept. Abatacept had a favorable safety profile.
Transmission of resistance mutations to integrase strand transfer inhibitors (INSTIs) in HIV-infected patients may compromise the efficacy of first-line antiretroviral regimens currently recommended ...worldwide. Continued surveillance of transmitted drug resistance (TDR) is thus warranted.
We evaluated the rates and effects on virological outcomes of TDR in a 96 week prospective multicentre cohort study of ART-naive HIV-1-infected subjects initiating INSTI-based ART in Spain between April 2015 and December 2016.
Pre-ART plasma samples were genotyped for integrase, protease and reverse transcriptase resistance using Sanger population sequencing or MiSeq™ using a ≥ 20% mutant sensitivity cut-off. Those present at 1%-19% of the virus population were considered to be low-frequency variants.
From a total of 214 available samples, 173 (80.8%), 210 (98.1%) and 214 (100.0%) were successfully amplified for integrase, reverse transcriptase and protease genes, respectively. Using a Sanger-like cut-off, the overall prevalence of any TDR, INSTI-, NRTI-, NNRTI- and protease inhibitor (PI)-associated mutations was 13.1%, 1.7%, 3.8%, 7.1% and 0.9%, respectively. Only three (1.7%) subjects had INSTI TDR (R263K, E138K and G163R), while minority variants with integrase TDR were detected in 9.6% of subjects. There were no virological failures during 96 weeks of follow-up in subjects harbouring TDR as majority variants.
Transmitted INSTI resistance remains rare in Spain and, to date, is not associated with virological failure to first-line INSTI-based regimens.
Rationale, aims, and objectives
To externally validate the PREDICT tool in a cohort of women participating in a population‐based breast cancer screening programme who were diagnosed with breast ...cancer between 2000 and 2008 in Spain.
Methods
A total of 535 women were included in the validation study. We calculated predicted 5‐year survival using the beta values from the development of the PREDICT model and predicted and observed events for a given risk groups. Model fit, discrimination, and calibration were evaluated. Seeking to improve the model, we also explored the impact on discrimination of the inclusion of additional variables, not in the PREDICT algorithm.
Results
In patients who were oestrogen receptor (ER) positive (negative), PREDICT overestimated (underestimated) the 5‐year overall survival in all the subgroups studied. Analysis of model performance showed good calibration but modest discrimination (C‐index, 0.697 ER negative and 0.768 ER positive). When updating the model, no additional variables were found to be significant in ER‐negative patients, but for ER‐positive patients, concurrent liver disease was a significant factor, its inclusion improving model discrimination (C‐index, 0.817).
Conclusions
The PREDICT tool does not discriminate well in our population considering only the variables of the original algorithm. More accurate tools are needed to obtain a better discrimination.
The prevention of obesity and improvement of academic achievement in children are concerns of industrialized societies. Obesity has been associated with psychological disorders, including attention ...deficit hyperactivity disorder, whose prevalence has been estimated at 6.8 % in Spanish children and adolescents. It is known that physical activity is positively related to academic achievement and negatively related to the risk of obesity in children. However, studies to test the effectiveness of physical activity interventions in improving academic achievement in preschool children are scarce and have some weaknesses that threaten their validity. Moreover, very few studies have examined their effectiveness in improving symptoms of attention deficit hyperactivity disorder. This paper outlines a two-year multidimensional preschool intervention (Movi-Kids) aimed at preventing obesity and improving academic achievement in children with or without attention deficit hyperactivity disorder.
Twenty-one schools from Ciudad Real and Cuenca, Spain, were randomized to intervention and control groups. In the first academic year, children in the third grade of preschool and the first grade of primary school in the intervention group received the Movi-Kids intervention. In the second academic year, schools were crossed over to the other group. The intervention included children, parents and teachers, and the school environment, and consisted of: (i) three hour-long sessions of recreational non-competitive physical activity after school, weekly, (ii) educational materials for parents and teachers addressing sedentary lifestyle risks and (iii) playground modifications to promote physical activity during breaks. Primary outcome measures of this study were academic achievement (intelligence, cognition, memory, attention and perception), assessed by the Battery of General and Differential Aptitudes, and adiposity measures (body mass index, waist circumference, triceps skinfold thickness and body fat percentage). Secondary outcome measures were: attention deficit hyperactivity disorder risk, motor skills, health-related quality of life and sleep quality. These variables will all be measured in both groups at baseline and at the end of the first and second academic years.
It seems reasonable that an intervention to promote physical activity based on playground games will be useful for simultaneously improving academic achievement and controlling obesity.
ClinicalTrials.gov NCT01971827 .
Transcription factors (TFs) are key regulators of gene expression in all organisms. In eukaryotes, TFs are often represented by functionally redundant members of large gene families. Overexpression ...might prove a means to unveil the biological functions of redundant TFs; however, constitutive overexpression of TFs frequently causes severe developmental defects, preventing their functional characterization. Conditional overexpression strategies help to overcome this problem. Here, we report on the TRANSPLANTA collection of Arabidopsis lines, each expressing one of 949 TFs under the control of a β–estradiol‐inducible promoter. Thus far, 1636 independent homozygous lines, representing an average of 2.6 lines for every TF, have been produced for the inducible expression of 634 TFs. Along with a GUS‐GFP reporter, randomly selected TRANSPLANTA lines were tested and confirmed for conditional transgene expression upon β–estradiol treatment. As a proof of concept for the exploitation of this resource, β–estradiol‐induced proliferation of root hairs, dark‐induced senescence, anthocyanin accumulation and dwarfism were observed in lines conditionally expressing full‐length cDNAs encoding RHD6, WRKY22, MYB123/TT2 and MYB26, respectively, in agreement with previously reported phenotypes conferred by these TFs. Further screening performed with other TRANSPLANTA lines allowed the identification of TFs involved in different plant biological processes, illustrating that the collection is a powerful resource for the functional characterization of TFs. For instance, ANAC058 and a TINY/AP2 TF were identified as modulators of ABA‐mediated germination potential, and RAP2.10/DEAR4 was identified as a regulator of cell death in the hypocotyl–root transition zone. Seeds of TRANSPLANTA lines have been deposited at the Nottingham Arabidopsis Stock Centre for further distribution.
Background
Acute heart failure (AHF) patients with high troponin levels have a worse prognosis. High‐sensitive troponin T (hs‐TnT) has been used as a tool to stratify prognosis in many scales but ...always as a qualitative and not as a quantitative variable.
Objectives
The main objective of this study was to determine the best hs‐TnT cut‐off for prediction of 30‐day all‐cause mortality.
Methods
The EAHFE registry, a prospective follow‐up cohort of patients with AHF, was analysed. We performed a propensity score analysis of the optimal hs‐TnT cut‐off point previously determined by receiver operating characteristic (ROC) curve analysis.
Results
Of the 13 791 patients in the EAHFE cohort, we analysed 3190 patients in whom hs‐TnT determination was available. The area under the ROC curve for 30‐day all‐cause mortality was 0.70 (CI95% 0.68 to 0.71; P < .001), establishing an optimal cut‐off of hs‐TnT of 35 ng/L. The sensitivity and specificity of this cut‐off were 76.2 and 55.5%, respectively, with a negative predictive value (NPV) of 95.3%. A propensity score was made with 34 variables showing differences based on the cut‐off of 35 ng/L for hs‐TnT. In the analysis of the population obtained with the propensity score, patients with hs‐TnT > 35 ng/L showed a greater 30‐day all‐cause mortality, with a HR of 2.95 (CI95% 1.83‐4.75; P < .001). External validation reported similar results.
Conclusions
An hs‐TnT value of 35 ng/L is an adequate cut‐off to evaluate the prediction of 30‐day all‐cause mortality with a NPV of 95.3%.