119 research outputs found

    Evaluation einer PSMA-PET-basierten, seitengetrennten Nierenfunktionsbestimmung

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    Die MAG3-Szintigraphie mit Bestimmung der seitengetrennten Nierenfunktion (SRF) ist ein Standardverfahren bei Patienten mit metastasiertem kastrationsresistentem Prostatakarzinom (mCRPC), die sich einer PSMA-Radioligandentherapie (PSMA- RLT) unterziehen. Diese Patienten erhalten auch häufige PSMA-PET/CT- Untersuchungen zum Staging und zur Verlaufskontrolle. PSMA wird nicht nur in Epithelzellen der Prostata und des Prostatakarzinoms exprimiert, sondern physiologisch auch in den proximalen Tubuluszellen der Niere. Diese Arbeit untersucht den Nutzen der PSMA-gezielten Bildgebung zur Bestimmung der relativen, also seitengetrennten Nierenfunktion. Methodik: N = 97 mCRPC-Patienten, die ein 68Ga-PSMA11-PET/CT und eine 99mTc- MAG3-Szintigraphie in engem zeitlichem Zusammenhang erhalten haben wurden in diese retrospektive Studie aufgenommen. Der PSMA-PET-basierten SRF, entsprechend dem bilateralen renalen PSMA-Gehalt (Gesamt-PSMA der Niere = SUVmean x Volumen), wurde die MAG3-basierte SRF, unter Verwendung der üblichen Standard-Integralmethode der renalen Sekretionsphase, gegenübergestellt. Die Übereinstimmung von SRFPSMA und SRFMAG3 wurde mittels Pearson-Korrelation und Bland-Altman-Analyse statistisch geprüft. Ergebnisse: Die Korrelation zwischen beiden SRF-Bewertungsmethoden war mit r = 0,91 hoch signifikant (p < 0,001). Die Bland-Altman-Analyse bestätigte die Übereinstimmung der Messungen. Eine hohe Korrelation und Übereinstimmung wurde auch in den Subgruppenanalysen von Patienten mit normaler und reduzierter Nierenfunktion beobachtet (r = 0,81, p < 0,001 und r = 0,98, p < 0,001). Schlussfolgerung: Die renale tubuläre PSMA-Expression ermöglicht die Beurteilung der seitengetrennten Nierenfunktion mittels 68Ga-PSMA-PET/CT-Bildgebung. Eine zusätzliche MAG3-Szintigraphie zum Zweck der Quantifizierung SRF kann in Fällen, in denen ein PSMA-PET durchgeführt wird, eingespart werden; diese Erkenntnis kann Zeit und überflüssige Untersuchungen mitsamt Strahlenbelastung einsparen. MAG3 scintigraphy with determination of split renal function (SRF) is a standard procedure in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PSMA-RLT). These patients also receive frequent PSMA PET/CT examinations for staging and follow-up. PSMA is expressed not only in epithelial cells of the prostate and prostate carcinoma, but also physiologically in proximal tubule cells of the kidney. This work investigates the utility of PSMA-targeted imaging to determine relative, or split, renal function. Methods: N = 97 mCRPC patients who had received 68Ga-PSMA11 PET/CT and 99mTc-MAG3 scintigraphy in close temporal relation were enrolled in this retrospective study. PSMA-PET-based SRF, corresponding to bilateral renal PSMA uptake (total renal PSMA = SUVmean x volume), was contrasted with MAG3-based SRF, using the usual standard integral method of renal secretory phase. Agreement between SRFPSMA and SRFMAG3 was statistically tested using Pearson correlation and Bland-Altman analysis. Results: The correlation between both SRF assessment methods was highly significant at r = 0.91 (p < 0.001). Bland-Altman analysis confirmed the agreement between the measurements. High correlation and agreement were also observed in subgroup analyses of patients with normal and reduced renal function (r = 0.81, p < 0.001 and r = 0.98, p < 0.001). Conclusion: Renal tubular PSMA expression allows assessment of split renal function by 68Ga-PSMA PET/CT imaging. Additional MAG3 scintigraphy for the purpose of quantifying SRF may not be necessary in cases where PSMA-PET is performed; this finding may save time and unnecessary examinations along with radiation exposure.MAG3 scintigraphy with determination of split renal function (SRF) is a standard procedure in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing PSMA radioligand therapy (PSMA-RLT). These patients also receive frequent PSMA PET/CT examinations for staging and follow-up. PSMA is expressed not only in epithelial cells of the prostate and prostate carcinoma, but also physiologically in proximal tubule cells of the kidney. This work investigates the utility of PSMA-targeted imaging to determine relative, or split, renal function. Methods: N = 97 mCRPC patients who had received 68Ga-PSMA11 PET/CT and 99mTc-MAG3 scintigraphy in close temporal relation were enrolled in this retrospective study. PSMA-PET-based SRF, corresponding to bilateral renal PSMA uptake (total renal PSMA = SUVmean x volume), was contrasted with MAG3-based SRF, using the usual standard integral method of renal secretory phase. Agreement between SRFPSMA and SRFMAG3 was statistically tested using Pearson correlation and Bland-Altman analysis. Results: The correlation between both SRF assessment methods was highly significant at r = 0.91 (p < 0.001). Bland-Altman analysis confirmed the agreement between the measurements. High correlation and agreement were also observed in subgroup analyses of patients with normal and reduced renal function (r = 0.81, p < 0.001 and r = 0.98, p < 0.001). Conclusion: Renal tubular PSMA expression allows assessment of split renal function by 68Ga-PSMA PET/CT imaging. Additional MAG3 scintigraphy for the purpose of quantifying SRF may not be necessary in cases where PSMA-PET is performed; this finding may save time and unnecessary examinations along with radiation exposure

    Cirugía robótica en patología quirúrgica benigna y maligna: urología, cirugía general y digestiva, cirugía cardiotorácica, ginecología, endocrinología, oftalmología y cirugía de cabeza y cuello. Capítulo II: cirugía urológica, ginecológica, general y digestiva

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    Cirurgia robòtica; Tècniques quirúrgiques; InnovacióCirugía robótica; Técnicas quirúrgicas; InnovaciónRobotic surgery; Surgical techniques; InnovationS'ha avaluat, de manera específica, l’eficàcia o l’efectivitat, la seguretat i l’eficiència de la cirurgia assistida per robot en comparació amb la cirurgia oberta o la cirurgia laparoscòpica en un grup d’indicacions de patologia benigna o maligna en les especialitats de cirurgia urològica, ginecològica i general i digestiva. De manera addicional, s’ha analitzat l’activitat de la cirurgia robòtica a Espanya per a les indicacions ginecològiques en els últims cinc anys.Se ha evaluado, de forma específica, la eficacia o la efectividad, la seguridad y la eficiencia de la cirugía asistida por robot en comparación con la cirugía abierta o la cirugía laparoscópica en un grupo de indicaciones de patología benigna o maligna en las especialidades de cirugía urológica, ginecológica y general y digestiva. De forma adicional, se ha analizado la actividad de la cirugía robótica en España para las indicaciones ginecológicas en los últimos cinco años.The aim of the study is to determine whether robot-assisted surgery has sufficient evidence to be included in the common portfolio of the UK NHS healthcare services. To this end, the efficacy or effectiveness, safety and efficiency of robot-assisted surgery compared to open surgery or laparoscopic surgery in a group of indications of benign or malignant pathology in the specialities of urological, gynaecological and general and digestive surgery has been specifically evaluated. In addition, the activity of robotic surgery in Spain for gynaecological indications in the last five years has been analysed.Este documento ha sido realizado por la Agència de Qualitat i Avaluació Sanitàries de Catalunya en el marco de la financiación del Ministerio de Sanidad para el desarrollo de las actividades del Plan anual de Trabajo de la Red Española de Agencias de Evaluación de Tecnologías Sanitarias y Prestaciones del SNS, aprobado en el Pleno del Consejo Interterritorial del SNS de 28 de octubre de 2020 (conforme al Acuerdo del Consejo de Ministros de 9 de diciembre de 2020)

    Genetic Variants in ARHGEF6 Cause Congenital Anomalies of the Kidneys and Urinary Tract in Humans, Mice, and Frogs

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    Background About 40 disease genes have been described to date for isolated congenital anomalies of the kidneys and urinary tract (CAKUT), the most common cause of childhood chronic kidney disease. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in such biologic processes as cell migration and focal adhesion, acts downstream of integrin linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva, leading to CAKUT in mice with this variant. Methods To identify novel genes that, when mutated, result in CAKUT, we performed exome sequencing in an international cohort of 1265 families with CAKUT. We also assessed the effects in vitro of wild-type and mutant ARHGEF6 proteins, as well as the effects of Arhgef6 deficiency in mouse and frog models. Results We detected six different hemizygous variants in the gene ARHGEF6 (which is located on the X chromosome in humans) in eight individuals from six families with CAKUT. In kidney cells, overexpression of wild-type ARHGEF6-but not proband-derived mutant ARHGEF6- increased active levels of CDC42/RAC1, induced lamellipodia formation, and stimulated PARVAdependent cell spreading. ARHGEF6 mutant proteins showed loss of interaction with PARVA. Three-dimensional MDCK cell cultures expressing ARHGEF6 mutant proteins exhibited reduced lumen formation and polarity defects. Arhgef6 deficiency in mouse and frog models recapitulated features of human CAKUT. Conclusions Deleterious variants in ARHGEF6 may cause dysregulation of integrin-parvinRAC1/CDC42 signaling, thereby leading to X-linked CAKUT

    New Advances in Kidney Transplantation

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    This Special Issue in renal transplantation covers a variety of clinical and research areas in kidney transplantation. The recent decade is associated with an ongoing shortage of organs for transplantation with efforts to increase the organ pool with DCDs and extended criteria donors. However, with the increasing success rate of kidney transplants, there is also a growth in the candidate list because of removal of the age barrier and transplantation of high risk patients with other comorbidities. The future seems promising with the development of innovative non-invasive technologies introducing biomarkers for diagnosis of rejection and ischemic reperfusion injury, use of cell therapy for tolerance induction, development of artificial organs, and overcoming immune and non-immune barriers in xenotransplantation. This Special Issue will touch some of these topics that are in the frontiers of the modern era of kidney transplantation

    Evaluation of PD-L1 expression in various formalin-fixed paraffin embedded tumour tissue samples using SP263, SP142 and QR1 antibody clones

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    Background & objectives: Cancer cells can avoid immune destruction through the inhibitory ligand PD-L1. PD-1 is a surface cell receptor, part of the immunoglobulin family. Its ligand PD-L1 is expressed by tumour cells and stromal tumour infltrating lymphocytes (TIL). Methods: Forty-four cancer cases were included in this study (24 triple-negative breast cancers (TNBC), 10 non-small cell lung cancer (NSCLC) and 10 malignant melanoma cases). Three clones of monoclonal primary antibodies were compared: QR1 (Quartett), SP 142 and SP263 (Ventana). For visualization, ultraView Universal DAB Detection Kit from Ventana was used on an automated platform for immunohistochemical staining Ventana BenchMark GX. Results: Comparing the sensitivity of two different clones on same tissue samples from TNBC, we found that the QR1 clone gave higher percentage of positive cells than clone SP142, but there was no statistically significant difference. Comparing the sensitivity of two different clones on same tissue samples from malignant melanoma, the SP263 clone gave higher percentage of positive cells than the QR1 clone, but again the difference was not statistically significant. Comparing the sensitivity of two different clones on same tissue samples from NSCLC, we found higher percentage of positive cells using the QR1 clone in comparison with the SP142 clone, but once again, the difference was not statistically significant. Conclusion: The three different antibody clones from two manufacturers Ventana and Quartett, gave comparable results with no statistically significant difference in staining intensity/ percentage of positive tumour and/or immune cells. Therefore, different PD-L1 clones from different manufacturers can potentially be used to evaluate the PD- L1 status in different tumour tissues. Due to the serious implications of the PD-L1 analysis in further treatment decisions for cancer patients, every antibody clone, staining protocol and evaluation process should be carefully and meticulously validated

    Kidney Inflammation, Injury and Regeneration 2020

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    Acute kidney injury (AKI) is still associated with high morbidity and mortality incidence rates, and also bears an elevated risk of chronic kidney disease in the sequel. Whereas the kidney has a remarkable capacity for regeneration after injury and may recover completely depending on the type of renal lesions, the options for clinical intervention are restricted to fluid management and extracorporeal kidney support. The development of novel therapies to prevent AKI, to improve renal regeneration capacity after AKI, and to preserve renal function—in both the short- and long-term—is urgently needed. This Special Issue includes papers investigating the pathological mechanisms of renal inflammation and AKI and diagnostics using new biomarkers. Furthermore, experimental in vitro and in vivo studies examining potential new approaches to attenuate kidney dysfunction are included, as well as review articles

    Minimally Invasive Detection of Transplant Rejection

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