Background
Electrical isolation of pulmonary veins (PV) with high-power short-duration (HPSD) radiofrequency application (RFa) may reduce the duration of atrial fibrillation (AF) ablation, without ...compromising the procedural efficacy and safety in comparison with the conventional approach. This hypothesis has been generated in several observational studies; the POWER FAST III will test it in a randomized multicenter clinical trial.
Methods
It is a multicenter randomized, open-label and non-inferiority clinical trial with two parallel groups. AF ablation using 70 W and 9–10 s RFa is compared with the conventional technique using 25–40 W RFa guided by numerical lesion indexes. The main efficacy objective is the incidence of atrial arrhythmia recurrences electrocardiographically documented during 1-year follow-up. The main safety objective is the incidence of endoscopically detected esophageal thermal lesions (EDEL). This trial includes a substudy of incidence of asymptomatic cerebral lesions detected by magnetic resonance imaging (MRI) after ablation
.
Results
A randomized clinical trial compares for the first time high-power short-duration and conventional ablation in order to obtain data about the efficacy and safety of the high-power technique in an adequate methodological context.
Conclusions
The results of the POWER FAST III could support the use of the high-power short-duration ablation in clinical practice.
Registration
: ClinicalTrials.gov: NTC04153747.
Graphical Abstract
Multiple myeloma (MM) arises following malignant proliferation of plasma cells in the bone marrow, that secrete high amounts of specific monoclonal immunoglobulins or light chains, resulting in the ...massive production of unfolded or misfolded proteins. Autophagy can have a dual role in tumorigenesis, by eliminating these abnormal proteins to avoid cancer development, but also ensuring MM cell survival and promoting resistance to treatments. To date no studies have determined the impact of genetic variation in autophagy-related genes on MM risk. We performed meta-analysis of germline genetic data on 234 autophagy-related genes from three independent study populations including 13,387 subjects of European ancestry (6863 MM patients and 6524 controls) and examined correlations of statistically significant single nucleotide polymorphisms (SNPs;
< 1 × 10
) with immune responses in whole blood, peripheral blood mononuclear cells (PBMCs), and monocyte-derived macrophages (MDM) from a large population of healthy donors from the Human Functional Genomic Project (HFGP). We identified SNPs in six loci,
,
,
,
,
, and
associated with MM risk (
= 4.47 × 10
-5.79 × 10
). Mechanistically, we found that the
SNP correlated with circulating concentrations of vitamin D3 (
= 4.0 × 10
), whereas the
SNP correlated with the number of transitional CD24
CD38
B cells (
= 4.8 × 10
) and circulating serum concentrations of Monocyte Chemoattractant Protein (MCP)-2 (
= 3.6 × 10
). We also found that the
SNP correlated with numbers of CD19
B cells, CD19
CD3
B cells, CD5
IgD
cells, IgM
cells, IgD
IgM
cells, and CD4
CD8
PBMCs (
= 4.9 × 10
-8.6 × 10
) and circulating concentrations of interleukin (IL)-20 (
= 0.00082). Finally, we observed that the
SNP correlated with levels of CD4
EMCD45RO
CD27
cells (
= 9.3 × 10
). These results suggest that genetic variants within these six loci influence MM risk through the modulation of specific subsets of immune cells, as well as vitamin D3
, MCP-2
, and IL20-dependent pathways.
Breast cancer (BC) is a disease with different clinical, histological and molecular characteristics, frequently presenting mutated tumour-suppressing genes and oncogenes. P53 is a known tumour ...suppressor that is often mutated in BC; several mutations in p53 inhibit its role as a transcriptional repressor of several oncogenes. Topoisomerase 2α (TOP2α) is a gene target of p53, and it is also a known target for anthracyclines. The aim of the present study, was to analyse the genetic alterations of p53 and TOP2α genes and their levels of protein expression, as well as their association with survival in Mexican women with BC. A total of 102 biopsies were collected (tumour and adjacent tissues) from patients with BC. To identify point mutations and deletions in the p53 gene, the Sanger sequencing method was carried out. Deletions or amplifications for TOP2α gene were determined using quantitative polymerase chain reaction (qPCR). In addition, the expression of the TOP2α and p53 proteins was evaluated by western blotting. Furthermore, p53 protein expression was analysed by proximity ligation assay (PLA)-qPCR. Only 28.5% of the patients were found to have triple-negative breast cancer (TNBC); the average age at the time of diagnosis of these patients was 50 years, and Scarff-Bloom-Richardson (SBR) histological grade III (p=0.0089). No differences in point mutations or deletions in p53, and deletions or amplifications as well as protein expression level of TOP2α were observed between patients with TNBC and non-TNBC patients. However, patients with TNBC showed p53 protein overexpression as determined by PLA-qPCR and western blotting (p<0.0001). Furthermore, we found an association between TOP2α amplification and overexpression of its protein in patients with TNBC (p<0.0001). Concerning p53, overexpression resulted in a lower survival in patients with BC.
To assess the repeatability, intersession and interobserver reproducibility, and agreement of central corneal thickness (CCT) measurements obtained by scanning-slit topography (SST) and noncontact ...specular microscopy (NCSM) after advanced surface ablation (ASA).
To analyze repeatability, one examiner measured 63 post-myopic ASA eyes five times successively using both techniques randomly. To calculate interobserver reproducibility a second examiner obtained another CCT measurement in a random fashion. To study intersession reproducibility, the first operator obtained CCT measurements from another 24 eyes during two sessions 1 week apart.
With regard to intrasession repeatability, SST and NCSM within-subject standard deviation (S(w)) and intraclass correlation coefficient (ICC) were 7.35 and 3.81 μm, and 0.97 and 0.99, respectively. For interobserver reproducibility, SST measurement variability showed correlation with CCT magnitude (r(s) = -0.38; P = 0.002), whereas NCSM did not. NCSM S(w) and ICC were 3.83 μm and 0.99, respectively. For intersession reproducibility, no difference in CCT measurements was found for any technique; S(w) and ICC estimates for SST and NCSM were 12.2 and 8.37 μm, and 0.94 and 0.95, respectively. We found a tendency for the difference (mean SST-NCSM = 13.39 μm) to increase in thicker corneas (r(s) = 0.45, P = 0.001).
Both noncontact pachymetry techniques provided highly repeatable and quite reproducible CCT measurements in post-ASA patients having no clinically significant corneal haze, except for SST interobserver reproducibility, which decreased in thinner corneas. However, the techniques were not interchangeable. The estimates provided should help clinicians differentiate real CCT change from noncontact pachymetry measurement variability after ASA.
To evaluate whether positron-emission tomography/computed tomography with
Ga-PSMA (
Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer (PCa).
...Although
Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent
Ga-PSMA PET/CT imaging.
All patients (n = 27) with a histological diagnosis of PCa who underwent
Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017-2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the
Ga-PSMA PET/CT were available.
Most patients (n = 26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent
Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall,
Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests-MRI, CT, or bone scans-performed prior to the
Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the
Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study.
Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.
To evaluate whether positron-emission tomography/computed tomography with 68Ga-PSMA (68Ga-PSMA PET/CT) influences the therapeutic management of patients with primary or recurrent prostate cancer ...(PCa).
Although 68Ga-PSMA PET/CT is one of the best options for staging or restaging patients with PCa, its availability is still very limited in Spain. The present study reports the results of the first group of patients in Spain who underwent 68Ga-PSMA PET/CT imaging.
All patients (n = 27) with a histological diagnosis of PCa who underwent 68Ga-PSMA PET/CT prior to the definitive treatment decision at the only centre with this technology in Spain during 2017–2018 were included. Two nuclear medicine physicians and a radiologist reviewed the imaging studies. The clinical impact was assessed from a theoretical perspective, based on the treatment that would have been applied if no data from the 68Ga-PSMA PET/CT were available.
Most patients (n = 26; 96%) had persistent disease or biochemical recurrence after radical prostatectomy, radiotherapy, or combined treatment. One patient underwent 68Ga-PSMA PET/CT imaging to stage high-risk PCa. Overall, 68Ga-PSMA PET/CT was positive in 19 patients (70.4%). In 68.75% of these patients, none of the other imaging tests—MRI, CT, or bone scans—performed prior to the 68Ga-PSMA PET/CT were able to detect the presence of cancerous lesions. Overall, the findings of the 68Ga-PSMA PET/CT led to a modification of the therapeutic approach in 62.96% of the patients in the study.
68Ga-PSMA PET/CT alters the therapeutic approach in a substantial proportion of patients with PCa.
This study aimed to determine the effectiveness of photodynamic therapy (PDT), using δ‐aminolevulinic acid (5‐ALA), in the elimination of premalignant cervical lesions in Mexican patients with human ...papillomavirus (HPV) infection and/or cervical intraepithelial neoplasia (CIN). Thirty women diagnosed with CIN I and/or positive for HPV participated in the study. Topical 6% 5‐ALA in gel form was applied to the uterine cervix; after 4 h, the lesion area was irradiated with a light dose of 200 J cm−2 at 635 nm. This procedure was performed three times at 48‐h intervals. Clinical follow‐up was performed at 3, 6, and 12 months after the initial PDT administration, by colposcopy, cervical cytology, histopathological analysis, polymerase chain reaction, and hybrid capture. Of HPV‐infected patients without evidence of CIN I, 80% cleared the infection, while HPV associated with CIN I was eliminated in 83% of patients (P < 0.05). At 12 months, CIN I had regressed in 57% of patients, although this response was not statistically significant. PDT using 6% 5‐ALA is concluded to be effective in eliminating HPV infection associated or not with CIN I.
We investigated the effectiveness of photodynamic therapy using δ‐aminolevulinic acid in eliminating premalignant cervical lesions in patients with HPV infection and/or cervical intraepithelial neoplasia (CIN). Topical 6% 5‐ALA gel was applied to the uterine cervix; 4 h later, the lesion was irradiated with a dose of 200 J cm−2 (635 nm). This procedure was repeated 3× at 48‐h intervals. Clinical follow‐up showed that in HPV‐infected patients without CIN I, 80% cleared the infection, while HPV associated with CIN I was eliminated in 83% of patients (P < 0.05). At 12 months, CIN I had regressed in 57% of patients, although not statistically significantly.
La formación de conceptos en Educación Física: ¿Qué saben los alumnos de Educación primaria? Hernández Álvarez, J.L., Velázquez Buendía, R., Garoz Puerta, I., López Crespo, C., López Rodríguez, A., Martínez Gorroño, Mª E., Alonso Curiel, D., Maldonado Rico, A., Moya Morales, J.Mª; Castejón Oliva, F.J.
Revista internacional de medicina y ciencias de la actividad física y del deporte,
12/2006, Letnik:
6, Številka:
24
Journal Article
Odprti dostop
Esta investigación se centró en la exploración del grado de conocimiento de la población escolar española referido a conceptos básicos relacionados conla Educación Físicay la salud. Se ha aplicado un ...cuestionario sobre aprendizaje de conceptos en Educación Física (CACEF) a los alumnos y alumnas de Educación Primaria, elaborado por expertos y por profesores en activo (validez de contenido). Se obtuvo una fiabilidad de Alfa de Cronbach (0.85), así como una correlación test-retest en la prueba piloto de 0.84. La muestra estuvo configurada por 1.397 sujetos (N = 1.397) de 6 provincias españolas. Los resultados muestran diferencias relevantes en función de las diferentes dimensiones de conocimiento exploradas. Con carácter general, es necesario señalar que en algunos conceptos relevantes para el conocimiento y la propia salud, se han obtenido resultados muy bajos que indican la necesidad de reforzar las estrategias encaminadas a elevar la “cultura física” de esta población.
The effect of resveratrol on the in vitro maturation (IVM) of ovine (Ovis aries) oocytes and the development of handmade cloned embryos was evaluated. The nuclear maturation and reactive oxygen ...species (ROS) levels in the oocytes, as well as the early development and morphological cloned embryo quality, were evaluated under different resveratrol concentrations (0, 0.5, 2 and 5 μM). After IVM, no significant difference was observed in the maturation rate of oocytes treated with 0.5 μM (81.3 %) and 2 μM (72 %) resveratrol compared to that of the control group (0 μM) (74.2 %), but the rate significantly decreased at 5 μM (56 %) (p < 0.05). When the oocyte ROS levels were determined, no significant differences among the groups were observed (p > 0.05). For cloned embryo development, the embryos obtained from the oocytes treated with 0.5 μM resveratrol showed higher (p < 0.05) compacted morula rates (10.7 %) compared to the embryos obtained from the oocytes treated with 0, 2 and 5 μM (6.2, 0 and 0 %, respectively). Regarding embryo morphological quality, the embryos from the oocytes treated with 0.5 μM resveratrol showed a lower rate of poor quality morulae (4.7 %) in comparison to those treated with 0, 2 and 5 μM (23.8, 23.3 and 33.3 %, respectively) (p < 0.05). In conclusion, resveratrol showed no significant improvement on the IVM or ROS levels in domestic ovine oocytes. However, treatment with 0.5 μM resveratrol during IVM improved embryo quality and promoted morulae compaction of Ovis aries handmade cloned embryos.Figure 3. Different developmental stages of the HMC sheep embryos cultured in the WOW system. Cleaved embryos (a-d), 8‒16 blastomere embryos (e-h), morulae (i-l) and compact morulae (m-p) (200X).
Chimeric antigen receptor (CAR) T-cell therapy is a promising immunotherapy for the treatment of refractory hematopoietic malignancies. Adverse events are common, and neurotoxicity is one of the most ...important. However, the physiopathology is unknown and neuropathologic information is scarce.
Post-mortem examination of 6 brains from patients that underwent CAR T-cell therapy from 2017 to 2022. In all cases, polymerase chain reaction (PCR) in paraffin blocks for the detection of CAR T cells was performed.
Two patients died of hematologic progression, while the others died of cytokine release syndrome, lung infection, encephalomyelitis, and acute liver failure. Two out of 6 presented neurological symptoms, one with extracranial malignancy progression and the other with encephalomyelitis. The neuropathology of the latter showed severe perivascular and interstitial lymphocytic infiltration, predominantly CD8+, together with a diffuse interstitial histiocytic infiltration, affecting mainly the spinal cord, midbrain, and hippocampus, and a diffuse gliosis of basal ganglia, hippocampus, and brainstem. Microbiological studies were negative for neurotropic viruses, and PCR failed to detect CAR T -cells. Another case without detectable neurological signs showed cortical and subcortical gliosis due to acute hypoxic-ischemic damage. The remaining 4 cases only showed a mild patchy gliosis and microglial activation, and CAR T cells were detected by PCR only in one of them.
In this series of patients that died after CAR T-cell therapy, we predominantly found non-specific or minimal neuropathological changes. CAR T-cell related toxicity may not be the only cause of neurological symptoms, and the autopsy could detect additional pathological findings.
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