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PURPOSE: To validate the Barcelona magnetic resonance imaging predictive model (BCN-MRI PM) in men with pre-biopsy multiparametric MRI (mpMRI) reported with the Prostate Imaging Reporting and Data System (PI-RADS) v2.1, followed by transrectal and transperineal prostate biopsies. MATERIALS AND METHODS: Prospective analysis of 3,264 men with PSA >3.0 ng/mL and/or abnormal digital rectal examination who were referred to ten participant centers in the csPCa early detection program of Catalonia (Spain), between 2021 and 2023. MpMRI was reported with the PI-RADS v2.1, and 2- to 4-core MRI-transrectal ultrasound (TRUS) fusion-targeted biopsy of suspected lesions and/or 12-core systematic biopsy were conducted. 2,295 (70.3%) individuals were referred to six centers for transrectal prostate biopsies, while 969 (39.7%) were referred to four centers for transperineal prostate biopsies. CsPCa was classified whenever the International Society of Urologic Pathology grade group was 2 or higher. RESULTS: CsPCa was detected in 41% of transrectal prostate biopsies and in 45.9% of transperineal prostate biopsies (p < 0.016). Both BCN-MRI PM calibration curves were within the ideal correlation between predicted and observed csPCa. Areas under the curve and 95% confidence intervals were 0.847 (0.830-0.857) and 0.830 (0.823-0.855), respectively (p = 0.346). Specificities corresponding to 95% sensitivity were 37.6 and 36.8%, respectively (p = 0.387). The Net benefit of the BCN-MRI PM was similar with both biopsy methods. CONCLUSIONS: The BCN-MRI PM has been successfully validated when mpMRI was reported with the PI-RADS v2.1 and prostate biopsies were conducted via the transrectal and transperineal route.
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Biopsia Guiada por Imagen , Imágenes de Resonancia Magnética Multiparamétrica , Próstata , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Estudios Prospectivos , Biopsia Guiada por Imagen/métodos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Anciano , Persona de Mediana Edad , Próstata/patología , Próstata/diagnóstico por imagen , Perineo/diagnóstico por imagen , Perineo/patología , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Imagen por Resonancia Magnética/métodosRESUMEN
The human papillomavirus (HPV) is a non-enveloped DNA virus transmitted through skin-to-skin contact that infects epithelial and mucosal tissue. It has over 200 known genotypes, classified by their pathogenicity as high-risk and low-risk categories. High-risk HPV genotypes are associated with the development of different types of cancers, including cervical cancer, which is a leading cause of mortality in women. In clinical practice and the market, the principal tests used to detect HPV are based on cytology, hybrid detection, and qPCR. However, these methodologies may not be ideal for the required timely diagnosis. Tests have been developed based on isothermal nucleic acid amplification tests (INAATs) as alternatives. These tests offer multiple advantages over the qPCR, such as not requiring specialized laboratories, highly trained personnel, or expensive equipment like thermocyclers. This review analyzes the different INAATs applied for the detection of HPV, considering the specific characteristics of each test, including the HPV genotypes, gene target, the limit of detection (LOD), detection methods, and detection time. Additionally, we discuss the tests available on the market that are approved by the Food and Drug Administration (FDA). Finally, we address the challenges and potential solutions for the large-scale implementation of INAATs, particularly in rural or underserved areas.
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Patients undergoing radical prostatectomy for prostate cancer may experience erectile dysfunction (ED). Age of patients, experience of the surgeons and existence of ED before surgery are factors related to its appearance. The objective of the study was to assess the hemodynamic changes produced in the cavernous arteries in patients undergoing laparoscopic radical prostatectomy (LRP) measured with penile Doppler ultrasound (PDUS). A prospective database of 83 patients undergoing LRP was analysed. PDUS were performed at baseline and twelve months after surgery. International Index of Erectile Function (IIEF) and Erectile Hardness Score (EHS) questionnaires were also evaluated. A 12-month decrease in all hemodynamic parameters of both cavernous arteries was found except for the end diastolic velocity (EDV) on the left cavernous artery. Only changes between baseline and twelve-months mean values of the diameter (0.725 vs. 0.67 mm; p= 0.033) and peak systolic velocity (PSV) of the right cavernous artery (32.6 vs. 27.22 cm/s; p = 0.004) presented significant variations. The rest of the parameters were close to statistical significance, except for EDV of the right cavernous artery (p = 0.887). The erectile function domain of the IIEF showed a significant decrease (median at baseline: 26 vs. post-surgery: 7; p < 0.0001) as well as the EHS test (grade I at baseline: 2.4% vs. 12-months: 31.3%; p < 0.0001). Our study supports the idea that LRP produces local vascular injuries. A decrease in the PSV and in the diameter of both cavernous arteries was observed with PDUS and it may explain the vascular origin of ED.
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Disfunción Eréctil , Laparoscopía , Pene , Prostatectomía , Neoplasias de la Próstata , Ultrasonografía Doppler , Humanos , Masculino , Prostatectomía/métodos , Laparoscopía/métodos , Pene/irrigación sanguínea , Pene/diagnóstico por imagen , Persona de Mediana Edad , Ultrasonografía Doppler/métodos , Anciano , Disfunción Eréctil/etiología , Estudios Prospectivos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/diagnóstico por imagen , Hemodinámica/fisiología , Arterias/diagnóstico por imagenRESUMEN
Quality control of programs for detection of significant prostate cancer (sPCa) could be defined by the correlation between observed and reference 95% confidence intervals (CIs) for Prostate Imaging-Reporting and Data System (PI-RADS) categories. We used the area under the receiver operating characteristic curve (AUC) for the Barcelona magnetic resonance imaging (MRI) predictive model to screen the quality of ten participant centers in the sPCa opportunistic early detection program in Catalonia. We set an AUC of <0.8 as the criterion for suboptimal quality. Quality was confirmed in terms of the correlation between actual sPCa detection rates and reference 95% CIs. For a cohort of 2624 men with prostate-specific antigen >3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and two- to four-core targeted biopsies of PI-RADS ≥3 lesions and/or 12-core systematic biopsy, AUC values ranged from 0.527 to 0.914 and were <0.8 in four centers (40%). There was concordance between actual sPCa detection rates and reference 95% CIs for one or two PI-RADS categories when the AUC was <0.8, and for three or four PI-RADS categories when the AUC was ≥0.8. A review of procedures used for sPCa detection should be recommended in centers with suboptimal quality. Patient summary: We tested a method for assessing quality control for centers carrying out screening for early detection of prostate cancer. We found that the method can identify centers that may need to review their procedures for detection of significant prostate cancer.
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BACKGROUND: Metastatic hormone-sensitive prostate cancer (mHSPC) is treatment-resistant and generally considered incurable. The development of prostate-specific membrane antigen positron emission-computed tomography (PSMA PET/CT) has generated immense expectations due to its diagnostic accuracy in prostate cancer (PCa). PSMA expression of the primary tumor, quantified by SUVmax, is a predictor of oncological outcomes. The role of PSMA-PET/CT SUVmax in metachronous mHSPC treated with ADT plus second-generation antiandrogens (ARSI) is unknown. The main aim of this study was to evaluate 68Ga-PSMA-11expression (SUVmax) as a potential prognostic biomarker in patients with metachronous mHSPC treated with ADT and first or second-generation antiandrogens. A second aim was to determine the association between PSMA SUVmax and PSA response to hormone therapy. MATERIAL AND METHODS: Patients diagnosed with metachronous mHSPC between July 2017 and February 2023 who developed biochemical recurrence following radical surgery (with or without salvage radiotherapy and/or ADT) or external radiation therapy (with or without ADT) were included. All patients underwent 68 Ga-PSMA-11 PET/CT imaging and the SUVmax value was determined for all measurable locations. The SUVmax value was used for the semiquantitative analysis. The Wilcoxon method was used to compare responders (PSA reduction ≥ 50%) to non-responders (PSA reduction < 50%). The SUVmax value and hormone therapy were evaluated as independent variables relative to the PSA response rate or PSA reduction using the linear regression method. A mixed-effects model (ANOVA) was used for the comparisons. RESULTS: A total of 82 patients were included. Median follow-up was 11.7 months. On the linear regression analysis, patients with a high SUVmax treated with ADT + ARSI showed a greater PSA response (p = 0.034) than those treated with ADT + first-generation antiandrogens. In the mixed-effects model, SUVmax was significant (p = 0.041). On the univariate analysis, PSA at recurrence (HR, 3.2; 95% CI: 1.07-13.6; p = 0.078) and the number of metastases (HR, 4.77; 95% CI 1.1-26.1: p = 0.002) were associated with the type of hormone therapy administered. CONCLUSIONS: PSMA-PET/CT SUVmax is a prognostic biomarker that can be used to predict a PSA response to ADT + ARSI in patients with metachronous mHSPC. However, these findings need to be confirmed in larger prospective studies.
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Currently, the global lifespan has increased, resulting in a higher proportion of the population over 65 years. Changes that occur in the lung during aging increase the risk of developing acute and chronic lung diseases, such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and lung cancer. During normal tissue homeostasis, cell proliferation and apoptosis create a dynamic balance that constitutes the physiological cell turnover. In basal conditions, the lungs have a low rate of cell turnover compared to other organs. During aging, changes in the rate of cell turnover in the lung are observed. In this work, we review the literature that evaluates the role of molecules involved in cell proliferation and apoptosis in lung aging and in the development of age-related lung diseases. The list of molecules that regulate cell proliferation, apoptosis, or both processes in lung aging includes TNC, FOXM1, DNA-PKcs, MicroRNAs, BCL-W, BCL-XL, TCF21, p16, NOX4, NRF2, MDM4, RPIA, DHEA, and MMP28. However, despite the studies carried out to date, the complete signaling pathways that regulate cell turnover in lung aging are still unknown. More research is needed to understand the changes that lead to the development of age-related lung diseases.
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Envejecimiento , Apoptosis , Proliferación Celular , Pulmón , Humanos , Envejecimiento/fisiología , Pulmón/metabolismo , Pulmón/patología , Animales , Transducción de Señal , Enfermedades Pulmonares/patología , Enfermedades Pulmonares/metabolismoRESUMEN
Osteonecrosis of the jaw (ONJ) is a relatively rare side effect after prolonged use of bisphosphonates, which are drugs used to treat bone resorption in osteoporosis and certain cancers. This study introduces a novel ONJ model in rats by combining exposure to bisphosphonates, oral surgery, and bacterial inoculation. Potential ONJ preventive effects of polyguanidine (GuaDex) or antibiotics were evaluated. The study consisted of twenty-four male Wistar rats were divided into four groups. Groups 1 to 3 were given weekly doses of i.v. Zoledronic acid (ZA), four weeks before and two weeks after an osteotomy procedure on their left mandibular first molar. Group 4 was a negative control. Streptococcus gordonii bacteria were introduced into the osteotomy pulp chamber and via the food for seven days. On day eight, the rats were given different treatments. Group 1 was given a GuaDex injection into the osteotomy socket, Group 2 was given an intramuscular (i.m.) injection of clindamycin, Group 3 (positive control) was given an i.m. injection of saline, and Group 4 was given an i.m. injection of saline. Blood samples were taken two weeks after the osteotomy procedure, after which the rats were euthanized. Bone healing, bone mineral density, histology, and blood status were analyzed. The results showed that Group 1 (GuaDex) had no ONJ, extensive ongoing bone regeneration, active healing activity, vascularization, and no presence of bacteria. Group 2 (clindamycin) showed early stages of ONJ, avascular areas, and bacteria. Group 3 showed stages of ONJ, inflammatory infiltrates, defective healing, and bacterial presence, and Group 4 had normal healing activity and no bacterial presence. Conclusion: ZA treatment and bacterial inoculation after tooth extraction inhibited bone remodeling/healing and induced ONJ characteristic lesions in the rats. Only GuaDex apparently prevented ONJ development, stimulated bone remodeling, and provided an antimicrobial effect.
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Osteonecrosis de los Maxilares Asociada a Difosfonatos , Ratas Wistar , Animales , Masculino , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Ratas , Difosfonatos/farmacología , Difosfonatos/efectos adversos , Guanidinas/farmacología , Guanidinas/uso terapéuticoRESUMEN
PURPOSE: To validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI). MATERIALS AND METHODS: A population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2. RESULTS: The area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783-0.842) and 0.849 (0.806-0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users. CONCLUSIONS: The BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.
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Inhibidores de 5-alfa-Reductasa , Imagen por Resonancia Magnética , Valor Predictivo de las Pruebas , Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Inhibidores de 5-alfa-Reductasa/uso terapéutico , Anciano , Persona de Mediana Edad , Estudios Retrospectivos , España , Imágenes de Resonancia Magnética MultiparamétricaRESUMEN
Microbiome research is now demonstrating a growing number of bacterial strains and genes that affect our health1. Although CRISPR-derived tools have shown great success in editing disease-driving genes in human cells2, we currently lack the tools to achieve comparable success for bacterial targets in situ. Here we engineer a phage-derived particle to deliver a base editor and modify Escherichia coli colonizing the mouse gut. Editing of a ß-lactamase gene in a model E. coli strain resulted in a median editing efficiency of 93% of the target bacterial population with a single dose. Edited bacteria were stably maintained in the mouse gut for at least 42 days following treatment. This was achieved using a non-replicative DNA vector, preventing maintenance and dissemination of the payload. We then leveraged this approach to edit several genes of therapeutic relevance in E. coli and Klebsiella pneumoniae strains in vitro and demonstrate in situ editing of a gene involved in the production of curli in a pathogenic E. coli strain. Our work demonstrates the feasibility of modifying bacteria directly in the gut, offering a new avenue to investigate the function of bacterial genes and opening the door to the design of new microbiome-targeted therapies.
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Escherichia coli , Microbioma Gastrointestinal , Edición Génica , Klebsiella pneumoniae , beta-Lactamasas , Animales , Ratones , Escherichia coli/genética , Edición Génica/métodos , Klebsiella pneumoniae/genética , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Femenino , Bacteriófagos/genética , Sistemas CRISPR-Cas/genética , Masculino , Tracto Gastrointestinal/microbiología , Genes Bacterianos/genética , Vectores Genéticos/genéticaRESUMEN
PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.
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AIM: To evaluate the clinical outcome of early closure of a protective ileostomy and preoperative stimulation of the efferent limb in a cohort of patients with rectal cancer treated surgically, primarily using the laparoscopic approach. METHODS: We performed an observational retrospective cohort study in a prospectively recorded series of patients with rectal cancer who underwent laparoscopic surgery with a protective loop ileostomy between 2017 and 2022. Ileostomy closure was programmed for within 3 months after surgery. All patients underwent stimulation of the efferent limb. Primary outcomes were morbidity and mortality, length of stay (LOS), and re-admission. RESULTS: Between 2017 and 2022, 108 patients underwent resection for rectal cancer and protective ileostomy. The laparoscopic approach was performed in 84.3% of patients (n = 91). Permanent ileostomy was performed in 5 patients (4.6%). Ileostomy closure was thus performed in 95.4% of patients (n = 103). Median time to closure was 74.5 days (range 57-113). In 63.1% (n = 65) of patients, reconstructive surgery was performed within 90 days. Prior to closure, efferent limb stimulation was performed in 77.8% (n = 84) of patients. Global morbidity was 26.2% (n = 27) (85.19%, n = 23 Clavien-Dindo I and 7.41%, n = 2 Clavien-Dindo II). The main causes of morbidity were postoperative ileus (10.7%, n = 11) and rectal bleeding (8.7%, n = 9). Anastomosis leakage occurred in 2 patients. Median hospital stay was 6 days (5-7). Readmission was needed in 6.8% (n = 7) of patients. CONCLUSION: A previous laparoscopic approach, early closure and stimulation of the efferent limb could be a useful strategy to reduce the morbidity and mortality of temporary ileostomy closure.
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Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure (p 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively (p 0.596). IPCa was detected in 37.6 and 62.5%, respectively (p 0.089). The tumor GG distribution based on 5-ARI exposure was similar (p 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.
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Cianoacrilatos , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/patología , Próstata/patología , Imagen por Resonancia Magnética/métodos , Inhibidores de 5-alfa-ReductasaRESUMEN
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes coronavirus disease 2019 (COVID-19). It is estimated that more than half of new infections are transmitted by asymptomatic people; therefore, the isolation of symptomatic people is not enough to control the spread of the disease. Methods: A total of 171 unvaccinated young adults (18-35 years) from Sonora, Mexico, who underwent a structured survey to identify prior COVID-19 infections, were included in this study. A qualitative determination of anti-SARS-CoV-2 antibodies in serum was performed by lateral flow immunoassay (Certum IgG/IgM Rapid Test™ cassette kit) and neutralizing antibodies were also determined (GenScript cPass assay). Results: A total of 36 people reported a history of COVID-19 infection, and 135 reported no history of COVID-19. In contrast, 49.6% (67/135) of individuals who had not reported a previous SARS-CoV-2 infection were seropositive to the rapid anti-SARS-CoV-2 antibody test, and 48.1% (65/135) of them had neutralizing antibodies. Conclusions: These results suggest that in young adults, SARS-CoV-2 infections could be asymptomatic in a high percentage of individuals, which could contribute in part to the slow control of the current pandemic due to the large number of asymptomatic cases that are contagious and that could be a silent spread of the virus.
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PURPOSE: To analyze the reduction in multiparametric magnetic resonance imaging (mpMRI) demand and prostate biopsies after the hypothetical implementation of the Barcelona risk-stratified pathway (BCN-RSP) in a population of the clinically significant prostate cancer (csCaP) early detection program in Catalonia. MATERIALS AND METHODS: A retrospective comparation between the hypothetical application of the BCN-RSP and the current pathway, which relied on pre-biopsy mpMRI and targeted and/or systematic biopsies, was conducted. The BCN-RSP stratify men with suspected CaP based on a prostate specific antigen (PSA) level >10 ng/ml and a suspicious rectal examination (DRE), and the Barcelona-risk calculator 1 (BCN-RC1) to avoid mpMRI scans. Subsequently, candidates for prostate biopsy following mpMRI are selected based on the BCN-RC2. This comparison involved 3,557 men with serum PSA levels > 3.0 ng/ml and/or suspicious DRE. The population was recruited prospectively in 10 centers from January 2021 and December 2022. CsCaP was defined when grade group ≥ 2. RESULTS: CsCaP was detected in 1,249 men (35.1%) and insignificant CaP was overdeteced in 498 (14%). The BCN-RSP would have avoid 705 mpMRI scans (19.8%), and 697 prostate biopsies (19.6%), while 61 csCaP (4.9%) would have been undetected. The overdetection of insignificant CaP would have decrease in 130 cases (26.1%), and the performance of prostate biopsy for csCaP detection would have increase to 41.5%. CONCLUSION: The application of the BCN-RSP would reduce the demand for mpMRI scans and prostate biopsies by one fifth while less than 5% of csCaP would remain undetected. The overdetection of insignificant CaP would decrease by more than one quarter and the performance of prostate biopsy for csCaP detection would increase to higher than 40%.
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Próstata , Neoplasias de la Próstata , Masculino , Humanos , Próstata/diagnóstico por imagen , Próstata/patología , Antígeno Prostático Específico , Estudios Retrospectivos , España , Neoplasias de la Próstata/diagnóstico por imagen , Biopsia , Imagen por Resonancia Magnética/métodos , Biopsia Guiada por Imagen/métodosRESUMEN
BACKGROUND: [18F]flortaucipir (FTP) tau PET quantification is known to be affected by non-specific binding in off-target regions. Although partial volume correction (PVC) techniques partially account for this effect, their inclusion may also introduce noise and variability into the quantification process. While the impact of these effects has been studied in cross-sectional designs, the benefits and drawbacks of PVC on longitudinal FTP studies is still under scrutiny. The aim of this work was to study the performance of the most common PVC techniques for longitudinal FTP imaging. METHODS: A cohort of 247 individuals from the Alzheimer's Disease Neuroimaging Initiative with concurrent baseline FTP-PET, amyloid-beta (Aß) PET and structural MRI, as well as with follow-up FTP-PET and MRI were included in the study. FTP-PET scans were corrected for partial volume effects using Meltzer's, a simple and popular analytical PVC, and both the region-based voxel-wise (RBV) and the iterative Yang (iY) corrections. FTP SUVR values and their longitudinal rates of change were calculated for regions of interest (ROI) corresponding to Braak Areas I-VI, for a temporal meta-ROI and for regions typically displaying off-target FTP binding (caudate, putamen, pallidum, thalamus, choroid plexus, hemispheric white matter, cerebellar white matter, and cerebrospinal fluid). The longitudinal correlation between binding in off-target and target ROIs was analysed for the different PVCs. Additionally, group differences in longitudinal FTP SUVR rates of change between Aß-negative (A-) and Aß-positive (A+), and between cognitively unimpaired (CU) and cognitively impaired (CI) individuals, were studied. Finally, we compared the ability of different partial-volume-corrected baseline FTP SUVRs to predict longitudinal brain atrophy and cognitive decline. RESULTS: Among off-target ROIs, hemispheric white matter showed the highest correlation with longitudinal FTP SUVR rates from cortical target ROIs (R2=0.28-0.82), with CSF coming in second (R2=0.28-0.42). Application of voxel-wise PVC techniques minimized this correlation, with RBV performing best (R2=0.00-0.07 for hemispheric white matter). PVC also increased group differences between CU and CI individuals in FTP SUVR rates of change across all target regions, with RBV again performing best (No PVC: Cohen's d = 0.26-0.66; RBV: Cohen's d = 0.43-0.74). These improvements were not observed for differentiating A- from A+ groups. Additionally, voxel-wise PVC techniques strengthened the correlation between baseline FTP SUVR and longitudinal grey matter atrophy and cognitive decline. CONCLUSION: Quantification of longitudinal FTP SUVR rates of change is affected by signal from off-target regions, especially the hemispheric white matter and the CSF. Voxel-wise PVC techniques significantly reduce this effect. PVC provided a significant but modest benefit for tasks involving the measurement of group-level longitudinal differences. These findings are particularly relevant for the estimations of sample sizes and analysis methodologies of longitudinal group studies.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Encéfalo/metabolismo , Estudios Transversales , Enfermedad de Alzheimer/metabolismo , Estudios Longitudinales , Péptidos beta-Amiloides/metabolismo , Disfunción Cognitiva/patología , Tomografía de Emisión de Positrones/métodos , Atrofia/patología , Proteínas tau/metabolismoRESUMEN
PURPOSE: To relate the prostate volume category (PVC) assessed with digital rectal examination (DRE)-small, median, and large-and the prostate volumes (PVs) assessed with magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). To compare the clinically significant prostate cancer (csPCa) discrimination ability of two predictive models based on DRE-PVC and MRI-PV. MATERIALS AND METHODS: A prospective trial of 2,090 men with prostate-specific antigen >3 ng/mL and/or PCa suspicious DRE were prospectively recruited in 10 centers from Catalonia (Spain), between 2021 and 2022, in whom DRE-PVC was assessed. Pre-biopsy MRI, and 12-core TRUS-random biopsy was always performed after 2- to 6-core TRUS-fusion targeted biopsy of prostate imaging-report and data system >3 lesions. In 370 men (17.7%) the DRE-PVC was unconclusive. Among the 1,720 men finally analyzed the csPCa (grade group >2) detection was 42.4%. RESULTS: The median (interquartile range) of TRUS and MRI-PVs of small prostates were 33 mL (19-37 mL) and 35 mL (23-30 mL), p=0.410; in median prostates they were 51 mL (38-58 mL) and 55 mL (48-63 mL) respectively, p<0.001; in large prostates 80 mL (60-100 mL) and 95 mL (75-118 mL) respectively, p<0.001. The predictive models sharing the MRI-PV and DRE-PVC showed areas under the curves of 0.832 (95% confidence interval [CI], 0.813-0.851) and 0.828 (95% CI, 0.809-0.848) respectively, p=0.632, as well as similar net benefit and clinical utility. CONCLUSIONS: PVC was unconclusive in 17% of DREs. MRI-PV overestimated the TRUS-PV in median and large prostates. The predictive models based on MRI-PV and DRE-PVC showed similar efficacy to predict csPCa. PVC assessed with DRE is helpful to predict the csPCa risk before MRI.
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OBJECTIVES: To examine the prevalence of extra-musculoskeletal manifestations (EMM) and the association between diagnostic delay and their incidence in AS and PsA. METHODS: This was a retrospective, cohort study comprising two single centre cohorts in Europe and one multicentre cohort in Latin America (RESPONDIA). Crude prevalence of EMMs (uveitis, IBD and psoriasis) was calculated across geographic area and adjusted by direct standardization. Cox proportional hazard analysis was performed to assess the association between diagnostic delay and EMM incidence. RESULTS: Of 3553 patients, 2097 had AS and 1456 had PsA. The overall prevalence of uveitis was 22.9% (95% CI: 21.1, 24.8) in AS and 3.8% (95% CI: 2.9, 5.0) in PsA; 8.1% (95% CI: 7.0, 9.4) and 2.1% (1.3, 2.9), respectively, for IBD; and 11.0% (95% CI: 9.7, 12.4) and 94.6% (93.0, 95.9), respectively, for psoriasis. The EMM often presented before the arthritis (uveitis 45.1% and 33.3%, and IBD 37.4% and 70%, in AS and PsA, respectively). In the multivariable model, longer diagnostic delay (≥5 years) associated with more uveitis (hazard ratio [HR] 4.01; 95% CI: 3.23, 4.07) and IBD events (HR 1.85; 95% CI: 1.28, 2.67) in AS. Diagnostic delay was not significantly associated with uveitis (HR 1.57; 95% CI: 0.69, 3.59) or IBD events (HR 1.59; 95% CI: 0.39, 6.37) in PsA. CONCLUSION: EMMs are more prevalent in AS than PsA and often present before the onset of the articular disease. A longer diagnostic delay is associated with the 'de novo' appearance of uveitis and IBD in AS, highlighting the need to enhance diagnostic strategies to shorten the time from first symptom to diagnosis in SpA.
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Artritis Psoriásica , Enfermedades Inflamatorias del Intestino , Psoriasis , Uveítis , Humanos , Diagnóstico Tardío/efectos adversos , Estudios Retrospectivos , Estudios de Cohortes , Artritis Psoriásica/complicaciones , Uveítis/diagnóstico , Uveítis/epidemiología , Uveítis/etiología , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/epidemiología , Psoriasis/epidemiología , PrevalenciaRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of apalutamide prostate cancer compared to the pivotal trials patients and to identify the first subsequent therapy in a real-world setting. METHODS: The study is prospective and observational based on real-world evidence, performed by different medical disciplines and eight academics centres around Barcelona, Spain. It included all patients with metastatic hormone-sensitive prostate cancer (mHSPC) and high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treated with apalutamide from June 2018 to December 2022. RESULTS: Of 227 patients treated with apalutamide, 10% had ECOG-PS 2, and 41% were diagnosed with new-generation imaging. In the mHSPC group (209 patients), 75 years was the median age, 53% had synchronous metastases, and 22% were M1a. In the nmCRPC (18 patients), 82 years was the median age, and 81% ≤6 months had PSA doubling time. Patients achieved PSA90 in 92% of mHSPC and 50% of nmCRPC and PSA ≤0.2 in 71% of mHSPC and 39% of nmCRPC. Treatment-related adverse events occurred in 40.1% of mHSPC and 44.4% of nmCRPC. After discontinuation of apalutamide due to disease progression, 54.5% in mHSPC and 75% in nmCRPC started chemotherapy, while after discontinuation because of adverse events, 73.3% in mHSPC and 100% in nmCRPC continued with other hormonal-therapies. CONCLUSIONS: The efficacy and safety of apalutamide were similar to that described in the pivotal trials, despite including an older and more comorbid population. Usually, subsequent therapies after apalutamide differed depending on the reason for discontinuation: by disease progression started chemotherapy and by adverse events hormonal sequencing.
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Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Antígeno Prostático Específico , Estudios Prospectivos , Progresión de la Enfermedad , Antagonistas de Andrógenos/efectos adversosRESUMEN
Glutamate and GABA signaling systems are necessary to maintain proper function of the central nervous system through excitation/inhibition (E/I) balance. Alteration of this balance in the medial prefrontal cortex (mPFC), as an effect of early-life stress, may lead to the development of anxiety and depressive disorders. Few studies exist in the infralimbic division of the mPFC to understand the effect of early-life stress at different ages, which is the purpose of the present work. Newborn Sprague Dawley male rats were subjected to maternal separation (MS) for two weeks. First, tests measuring anxiety- and depression-like behaviors were performed on adolescent and adult rats subjected to MS (MS-rats). Then, to establish a relationship with behavioral results, electrophysiological recordings were performed in neurons of the infralimbic cortex in acute brain slices of infant, adolescent, and adult rats. In the behavioral tests, there were no significant differences in MS-rats compared to control rats at any age. Moreover, MS had no effect on the passive membrane properties nor neuronal excitability in the infralimbic cortex, whereas spontaneous synaptic activity in infralimbic neurons was altered. The frequency of spontaneous glutamatergic synaptic events increased in infant MS-rats, whereas in adolescent MS-rats both the frequency and the amplitude of spontaneous GABAergic events increased without any effect on glutamatergic synaptic responses. In adult MS-rats, these two parameters decreased in spontaneous GABAergic synaptic events, whereas only the frequency of glutamatergic events decreased. These data suggest that rats subjected to MS did not exhibit behavioral changes and presented an age-dependent E/I imbalance in the infralimbic cortex, possibly due to differential changes in neurotransmitter release and/or receptor expression.