How to manage renal masses in kidney transplant recipients? A collaborative review by the EAU-YAU kidney transplantation and renal cancer working groups.

INTRODUCTION: Kidney transplant (KT) recipients have a four-times higher risk of renal malignancies compared to general population. As these patients frequently harbor bilateral or multifocal tumors, the management of renal masses is still under debate. OBJECTIVE: To explore the current management of the native kidney masses in KT patients. ACQUISITION OF EVIDENCE: We performed a literature search on MEDLINE/PubMed database. A number of 34 studies were included in the present review. SYNTHESIS OF EVIDENCE: In frail patients with renal masses below 3 cm, active surveillance is a feasible alternative. Nephron-sparing surgery is not justified for masses in the native kidney. Radical nephrectomy is the standard treatment for post-transplant renal tumors of the native kidneys in KT recipients, with laparoscopic techniques leading to significantly less perioperative complication rates as compared to the open approach. Concurrent bilateral native nephrectomy at the time of transplantation can be considered in patients with renal mass and polycystic kidney disease, especially if no residual urinary output is present. Patients with localized disease and successful radical nephrectomy do not require immunosuppression adjustment. In metastatic cases, mTOR agents can ensure efficient antitumoral response, while maintaining proper immunosuppression in order to protect the graft. CONCLUSIONS: Post-transplant renal cancer of the native kidneys is a frequent occurrence. Radical nephrectomy is most frequently performed for localized renal masses. A standardized and widely-approved screening strategy for malignancies of native renal units is yet to be implemented.

Influence of climatic parameters on the probabilistic design of green roofs.

Green roofs are effective tools for stormwater control in highly urbanized areas since they allow the reduction of peak runoffs and volumes discharged in sewer systems. Their design is quite standardized, except for the thickness of the growing medium layer, which is strictly related to vegetation type and rainfall regime. The paper proposes an analytical probabilistic approach that relates the climatic variables, the growing medium thickness, and the water content in the condition of fulfilled field capacity to the probability that runoff from green roofs exceeds a fixed threshold. The developed equations also consider the possibility of a reduced retention capacity due to previous rainfall events, that strongly influence the performance of these green infrastructures, especially when short dry periods and/or low evapotranspiration rates occur. This feature, neglected by the traditional design storm approach, and only partially considered by previous analytical probabilistic models, represent a great potentiality of the proposed equations that are also more user-friendly and less time-consuming than continuous simulation analysis. The focus of the paper is on the influence of climatic parameters on runoff probability. To this aim to perform the monthly analysis is fundamental, especially when there is a strong variability of the climatic parameters throughout the year. The model was tested in a case study in Milano, Italy. The application presented a good agreement between the results obtained from the proposed equations and those obtained from the continuous simulation of recorded data. The results also highlighted the importance of performing analysis on a monthly scale.

Radical Nephroureterectomy Tetrafecta: A Proposal Reporting Surgical Strategy Quality at Surgery.

Background: Standardized methods for reporting surgical quality have been described for all the major urological procedures apart from radical nephroureterectomy (RNU). Objective: To propose a tetrafecta criterion for assessing the quality of RNU based on a consensus panel within the Young Association of Urology (YAU) Urothelial Group, and to test the impact of this tetrafecta in a multicenter, large contemporary cohort of patients treated with RNU for upper tract urothelial carcinoma (UTUC). Design setting and participants: This was a retrospective analysis of 1765 patients with UTUC treated between 2000 and 2021. Outcome measurements and statistical analysis: We interviewed the YAU Urothelial Group to propose and score a list of items to be included in the "RNU-fecta." A ranking was generated for the criteria with the highest sum score. These criteria were applied to a large multicenter cohort of patients. Kaplan-Meier curves were built to evaluate differences in overall survival (OS) rates between groups, and a multivariable logistic regression model was used to find the predictors of achieving the RNU tetrafecta. Results and limitations: The criteria with the highest score included three surgical items such as negative soft tissue surgical margins, bladder cuff excision, lymph node dissection according to guideline recommendations, and one oncological item defined by the absence of any recurrence in ≤12 mo. These items formed the RNU tetrafecta. Within a median follow-up of 30 mo, 52.6% of patients achieved the RNU tetrafecta. The 5-yr OS rates were significantly higher for patients achieving tetrafecta than for their counterparts (76% vs 51%). Younger age, lower body mass index, and robotic approach were found to be independent predictors of tetrafecta achievement. Conversely, a higher Eastern Cooperative Oncology Group score, higher clinical stage, and bladder cancer history were inversely associated with tetrafecta. Conclusions: Herein, we present a "tetrafecta" composite endpoint that may serve as a potential tool to assess the overall quality of the RNU procedure. Pending external validation, this tool could allow a comparison between surgical series and may be useful for assessing the learning curve of the procedure as well as for evaluating the impact of new technologies in the field. Patient summary: In this study, a tetrafecta criterion was developed for assessing the surgical quality of radical nephroureterectomy in patients with upper tract urothelial carcinoma. Patients who achieved tetrafecta had higher 5-yr overall survival rates than those who did not.

Biological insight into the extracellular vesicles in women with and without gestational diabetes.

PURPOSE: Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy, with increasing prevalence worldwide and still unclear pathogenic mechanisms. Extracellular vesicles (EVs) are emerging as potential biomarkers of disease-specific pathways in metabolic disorders, but their potential role in GDM is not fully understood. Therefore, the main aim of this study was to evaluate the link between EVs and hyperglycaemia during pregnancy. METHODS: We assessed 50 GDM women and 50 controls at the third trimester of pregnancy in whom we collected demographic characteristics and clinical and anthropometric parameters. In addition, the circulating total EVs (tEVs) and their subpopulations were assessed using flow cytometry. RESULTS: The levels of tEVs and EVs subtypes, expressed as median and interquartile range, were not significantly different between two groups; however, adipocyte-derived EVs (aEVs) concentration, expressed as percentage, was higher in controls than in GDM women (p = 0.045). In addition, a significant correlation was observed between aEVs (%) and third trimester total cholesterol (p = 0.022) within the GDM group. Furthermore, a significant correlation between endothelial-derived EVs (eEVs) and platelet-derived EVs (pEVs) within both groups was found, as well as a significant relation between aEVs and pEVs. CONCLUSIONS: These data, although preliminary, represent the starting point for further studies to determine the role of circulating EVs in GDM.

RIRS in the elderly: Is it feasible and safe?

BACKGROUND: The aim of this study was to compare the safety and efficacy of RIRS in men ≥65 years to those <65 years. MATERIALS AND METHODS: Patients who underwent RIRS were prospectively collected from March 2013 to March 2014 in 5 European centers. Perioperative outcomes and complications in elderly men were compared with men <65 years. Univariable and multivariable analyses were performed for factors predicting overall complications. The groups were compared using Mann-Whitney U test. Categorical variables were compared using chi-squared test and the Yates correction or the Fisher's exact test. RESULTS: A total of 399 patients with renal stones were included, 308 (77.19%) were aged <65 years, 91 (22.8%) were aged ≥65 years. Elderly patients were more likely to have higher ASA scores (35.7% vs 92.3%; p < 001), Charlson Comorbidity Index (1.8 vs. 5.2, p < 0.001), hyperlipidemia (10.06% vs. 30.76%; p = 0,0005) and coronary heart disease (5.51% vs. 17.58; p = 0.005) compared to younger cohort. Perioperative outcomes (stone free rate, operative time and re-intervention rate) did not show differences between the two groups (p > 0.05). Surgical and medical complication rates were similar between the cohorts (14.28% vs 9.89%; p = 0.38). Multivariate analysis did not identify any predictive factors of complications among the two groups (p > 0.05). CONCLUSIONS: In this study, elderly RIRS patients had comparable short term efficacy and perioperative complications to younger patients, despite a higher prevalence of comorbidity. Age itself should not be considered as a risk factor for the development of complications in patients undergoing RIRS for renal stone.

Magnetic resonance spectroscopic imaging 3T and postate cáncer: correlation with transperineal ultrasound guided prostate biopsy

OBJETIVO: El objetivo de este estudio era correlacionar los resultados obtenidos con la resonancia magnética por espectroscopia 3T (RMNE3T) con los obtenidos por la evaluación histológica de las muestras de biopsia de próstata transperineal guiada por ecografía. MÉTODOS: 34 Pacientes fueron incluidos en el estudio. Todos los pacientes tenían la sospecha de cáncer de próstata por elevación del PSA y/o tacto rectal anormal. Los pacientes fueron sometidos a RMNE 3T y posteriormente biopsia transperineal guiada por ecografía. RESULTADOS: De los 22 pacientes (22/34) que presentaban anomalías en la RMNE 3T, 9 tuvieron el diagnóstico histológico de adenocarcinoma. De los 13 restantes, 6 fueron diagnosticados de hiperplasia benigna de próstata y 7 de inflamación intersticial crónica o PIN de alto grado. De 12 pacientes (12/34) que no presentaban alteraciones periféricas en la próstata en la RMNE 3T, ninguno tenía adenocarcinoma o inflamación en la histología. La sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo fueron del 100%, 48%, 40% y 100% respectivamente. DISCUSIÓN: En este estudio correlacionamos los valores obtenidos por RMNE 3T con los resultados del examen histológico de las biopsias de próstata. Nuestro trabajo muestra que el 72% de los voxeles en los que había un cambio en el cociente de Cit/(Cho+ Cr) correspondían con áreas de enfermedad del tejido prostático. De éstas, el 73,2% eran positivas para adenocarcinoma y el 26% para inflamación intersticial crónica o PIN de alto grado. En la literatura, se observa que el cáncer de próstata se puede distinguir de áreas de tejido benigno en la zona periférica, en base a los valores de la ratio Cit/(Cho+cr) (17), aunque algunas condiciones benignas, tales cómo la prostatitis o el PIN de alto grado, pueden alterar estos valores (18-19). CONCLUSIONES: En conclusión, el uso de la RMNE 3T antes de la realización de biopsias de próstata puede representar una ayuda válida para el urólogo en el diagnóstico de CaP, permitiéndole evitar biopsias de próstata innecesarias que pudieran ser negativas. Además, también sería posible reducir el número total de biopsias, disminuyendo así la exposición del paciente a riesgos innecesarios asociados con la biopsia

OBJECTIVES: The aim of our study was to correlate the results obtained by 3T Magnetic Resonance Spectroscopic Imaging (MRSI3T) with those obtained by histological examination of samples of the trans-perineal ultrasound-guided prostate biopsy (TPUS-B). METHODS: 34 patients were enrolled in the study. All patients had a clinical suspicion of cancer due to increased PSA and/or positive digital rectal examination. Patients were subjected to an MRSI 3T examination and subsequently to TPUS-B. RESULTS: Of the 22 (22/34) patients who presented abnormalities MRSI at 3T, 9 had a histological diagnosis of Prostate adenocarcinoma. Of the remaining 13 patients, 6 were found to be histologically positive for Benign Prostatic Hypertrophy and 7 Chronic Interstitial Inflammation or High Grade Prostatic Intraepithelial Neoplasia. 12 (12/34) patients found to have no peripheral alterations in their prostate on 3T MRSI, none were positive for ADK or inflammation on histology. The sensitivity, specificity, positive predictive value and negative predictive value were 100%, 48%, 40% and 100% respectively. DISCUSSION: In this study, we correlated the values obtained from 3T MRSI with the results of histologically examined prostate biopsies. Our work shows that 72.8% of the voxels in which there was a change in ratio of Cit/(Cho + Cr), corresponded to areas of prostate tissue disease. Of these, 73.2% were positive for ADK and 26.8% for CII or HG PIN. In literature, it is noted that PCa can be distinguished from areas of benign tissue, in the peripheral zone, on the basis of the values of the ratio Cit/(Cho + Cr) (17), although some benign conditions, such as prostatitis or PINHG, can alter these values (18-19). CONCLUSIONS In conclusion, the use of MRSI 3T before performing prostate biopsies may represent a valid aid for the urologist in the diagnosis of PCa, allowing them to avoid unnecessary prostate biopsies that may be negative. Furthermore, it would also be possible to reduce the total number of biopsies, thus decreasing patient ex posure to the unnecessary risks associated with biopsy

[Questionnaires for occupational disability evaluation in patients with chronic respiratory diseases]. / Questionari per la valutazione della disabilità occupazionale in pazienti con malattie respiratorie croniche.

Chronic Obstructive Pulmonary Disease (COPD) represents a model of respiratory degenerative chronic disabling disorder. In Pulmonary Rehabilitation (PR), occupational approach is aimed at restoring patient's abilities at best in the social, familiar and working scenarios, and it is an essential part of a good PR Programme. To evaluate first occupational disability and then the occupational outcome of a PR programme, we need appropriate tools. London Chest Activity of Daily Living (LCADL) ed il Manchester Respiratory Activities of Daily Living (MRADL) are two questionnaires with such characteristics available in the literature. Our aim was to translate into Italian and adapt to the Italian social reality these two questionnaires. This may be a preliminary albeit necessary step to obtain reliable data on the occupational outcome of PR programmes in Italy.

The interplay between the master transcription factor PU.1 and miR-424 regulates human monocyte/macrophage differentiation.

We describe a pathway by which the master transcription factor PU.1 regulates human monocyte/macrophage differentiation. This includes miR-424 and the transcriptional factor NFI-A. We show that PU.1 and these two components are interlinked in a finely tuned temporal and regulatory circuitry: PU.1 activates the transcription of miR-424, and this up-regulation is involved in stimulating monocyte differentiation through miR-424-dependent translational repression of NFI-A. In turn, the decrease in NFI-A levels is important for the activation of differentiation-specific genes such as M-CSFr. In line with these data, both RNAi against NFI-A and ectopic expression of miR-424 in precursor cells enhance monocytic differentiation, whereas the ectopic expression of NFI-A has an opposite effect. The interplay among these three components was demonstrated in myeloid cell lines as well as in human CD34+ differentiation. These data point to the important role of miR-424 and NFI-A in controlling the monocyte/macrophage differentiation program.

[Function recovery in patients with knee arthroplasty: role of proprioceptive rehabilitation]. / Il recupero funzionale del ginocchio artroprotesizzato: ruolo dell'allenamento propriocettivo.

This study evaluates the outcome of proprioceptive rehabilitation in 18 patients who underwent knee joint prosthetic replacement using the dynamic electronic plate Pro-kin_machine. The proprioceptive performance was determined by having the patients trace a set of three outlines (horizontal, vertical and circular) using the foot of the operated limb. The measures of outcome parameters were: 1) time taken to do the test; 2) score of accuracy of the test measured in percentage. Tests were performed on admission, half way through rehabilitation and on discharge. Each patient had 15 sittings of physiotherapy. Our results demonstrate a significant improvement of both parameters at the end of the treatment. After prosthetic knee joint replacement, not only is it important to re-establish mechanical stability but also dynamic stability. The latter can be achieved through active virtual taping by the stabilizer muscles. Prompt management of instability of the joint in the rehabilitation phase is extremely important in the re-activating of the control mechanisms that are compromised by the surgical operation.

[Assessment of function recovery in patients with total knee prosthesis]. / Valutazione della ripresa funzionale nei pazienti sottoposti ad intervento di protesi totale di ginocchio.

The aim of this study was to analyse the evolution of motor performance in a group of patients who underwent surgical knee replacement. We also assessed patient satisfaction at 3 and 9 months after the operation. Sixty-two patients (40 women, 22 men, mean age 72.4 years) underwent isokinetic evaluation associated with surface EMG. All the patients had undergone a total prosthetic knee joint replacement for arthrosis, and had followed a standardised 30-day rehabilitation program at our centre for recovery of knee joint function, strengthening of the flexor-extensor muscles and restoration of ambulation as best as possible. Each of these patients underwent isokinetic evaluations 3 months and 9-10 months after their operation. The isokinetic test consisted of carrying out 5 flexion-extensions of the knee at an angular velocity of 60 degrees/second, followed by an endurance test of 30 repetitions of flexion-extension of the knee at 120 degrees/second. This isokinetic test provided data on extensor strength and flexor strength; furthermore, specifically designed software allowed simultaneous visualisation of the surface EMG tracing, torque and joint excursion. The first analysis showed a macroscopic decrease in the strength of the flexor-extensor muscles of the knee. This muscle weakness was clearly evident 3 months after the operation and was particularly pronounced for the extensor muscles of the operated limb compared with the muscles of contralateral, unoperated limb. Muscle weakness was still present 9 months after the operation although there had been a considerable improvement compared with 6 months previously; the imbalance in the flexor/extensor ratio, which differed from that in the contralateral, unoperated limb, was noted to be still present. The surface EMG demonstrated persistent myoelectrical activity in the flexors even when the extensor activity was predominant: this is an expression of imbalance between agonists-antagonists. A questionnaire administered to the patients about their satisfaction with the operation revealed that 9 months after the surgery 23 patients still complained of continuous joint pain with increased loads, 27 complained of frequent pain with load-bearing and only 12 no longer complained of any disturbance, manifesting full satisfaction with the operation. Total knee replacement is thus a valid treatment in those cases in which degenerative joint disease necessitates a radical solution. Nevertheless, dissatisfaction with the operation is common, and may be due to persistence of joint pain and incomplete joint recovery of joint function or muscle strength. In our series of patients, we found that although there was progressive recovery of strength of both the flexor and extensor muscles, a considerable imbalance remained between the operated and unoperated limbs; this finding was also confirmed by the surface EMG investigation.

Negative regulation of axis formation and Wnt signaling in Xenopus embryos by the F-box/WD40 protein beta TrCP.

Screening a maternal Xenopus expression library for activities that synergize with low levels of injected beta-catenin, we have isolated a clone encoding the C-terminal end of x-beta TrCP-2, a highly conserved protein belonging to the F-box/WD40 family of ubiquitin-ligase specificity factors. We show that x-beta TrCP-2 expression reduces dorsal axis formation in Xenopus embryos. A dominant negative mutant lacking the F-box triggers the opposite effect, inducing secondary axes and activating the expression of Wnt responsive genes in ectodermal explants. In light of the existence of beta TrCP transcripts associated with the vegetal cortex, we propose that beta TrCP plays a fundamental role in the establishment of the dorsal determinants during cortical rotation in Xenopus.

Cloning, expression and functional role of XrpFI alpha and beta subunits in Xenopus laevis oocyte.

The cDNAs coding for the alpha and beta components of XrpFI, an activator of ribosomal protein genes transcription, were isolated. RNA analysis showed that transcripts of the beta genes are present at constant level throughout Xenopus development unlike the beta proteins which are undetectable in the early stages of embryogenesis when transcription is silent. On the contrary, alpha transcripts and proteins were found in all the embryo stages examined. The role of the XrpFI alpha and beta subunits in rp-gene transcription has been studied by mRNA microinjection into X.laevis oocytes. The presence of the beta subunit appears to be critical for the proper rp-gene promoter function.

XrpFI, an amphibian transcription factor composed of multiple polypeptides immunologically related to the GA-binding protein alpha and beta subunits, is differentially expressed during Xenopus laevis development.

XrpFI, first identified in the extract of Xenopus laevis oocyte nuclei, binds to a proximal sequence of the L14 ribosomal protein gene promoter. Its target sequence, 5'-TAACCGGAAGTTTGT-3', is required to fully activate the promoter, and the two G's of the central motif are essential for factor binding and transcriptional activation; our data also suggest that XrpFI may play a role in cap site positioning. The binding site of XrpFI is homologous to the sequence recognized by the family of ets genes. Antibodies specific for Ets-1 and Ets-2 proteins did not react with XrpFI, but those raised against the rat alpha and beta GA-binding proteins both supershifted the retarded bands formed by XrpFI. The Xenopus polypeptides related to GA-binding protein alpha interact with DNA both as monomers and as heterodimers associated with beta-related proteins. Oocyte nuclei contain multiple forms of alpha- and beta-related proteins: the alpha-like proteins remain throughout development, while the pattern of the beta species changes in the embryonic stages examined. beta-like proteins are undetectable in the cleavage period up to the neurula stage, but at later stages, when ribosomal protein genes are actively transcribed, two beta-related polypeptides reappear.

Clinical physiological data on the bronchodilator effect of Duovent versus salbutamol in chronic obstructive lung disease.

We studied the bronchodilator effect of a combination of fenoterol (100 micrograms) and ipratropium bromide (40 micrograms) (Duovent) versus salbutamol and placebo in 16 patients with chronic obstructive lung disease (COLD). FEV1 and the side-effects (palpitations, tremors, excitation) were measured at 0, 30, 60, 120, 240, 360 and 420 min after administration. The drugs were administered in aerosol form following a randomization schedule. The bronchodilator effect of Duovent was greater than that of salbutamol; moreover, Duovent had a lasting efficacy and few side-effects. Duovent is thus a useful drug therapeutically.