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Contains fulltext : 294430.pdf (Publisher’s version ) (Open Access) BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p

Item does not contain fulltext BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.

The COVID-19 pandemic has led to severe consequences for people’s mental health. The pandemic has also influenced our language use, shaping our word formation habits. The overuse of new metaphorical meanings has received particular attention from the media. Here, we wanted to investigate whether these metaphors have led to the formation of new semantic associations in memory. A sample of 120 university students was asked to decide whether a target word was or was not related to a prime stimulus. Responses for pandemic pairs in which the target referred to the newly acquired metaphorical meaning of the prime (i.e., “trench”—“hospital”) were compared to pre-existing semantically related pairs (i.e., “trench”—“soldier”) and neutral pairs (i.e., “trench”—“response”). Results revealed greater accuracy and faster response times for pandemic pairs than for semantic pairs and for semantic pairs compared to neutral ones. These findings suggest that the newly learned pandemic associations have created stronger semantic links in our memory compared to the pre-existing ones. Thus, this work confirms the adaptive nature of human language, and it underlines how the overuse of metaphors evoking dramatic images has been, in part, responsible for many psychological disorders still reported among people nowadays.

The COVID-19 pandemic severely affected people’s mental health all over the world. This review aims to present a comprehensive overview of the literature related to the effects of COVID-19 lockdown measures and COVID-19 infection on cognitive functioning in both healthy people and people with neurological conditions by considering only standardized tests. We performed a narrative review of the literature via two databases, PUBMED and SCOPUS, from December 2019 to December 2022. In total, 62 out of 1356 articles were selected and organized into three time periods: short-term (1–4 months), medium-term (5–8 months), and long-term (9–12 months), according to the time in which the tests were performed. Regardless of the time period, most studies showed a general worsening in cognitive performance in people with neurological conditions due to COVID-19 lockdown measures and in healthy individuals recovered from COVID-19 infection. Our review is the first to highlight the importance of considering standardized tests as reliable measures to quantify the presence of cognitive deficits due to COVID-19. Indeed, we believe that they provide an objective measure of the cognitive difficulties encountered in the different populations, while allowing clinicians to plan rehabilitation treatments that can be of great help to many patients who still, nowadays, experience post-COVID-19 symptoms.

Context Carcinoma in situ (CIS) of the bladder is defined as a high-grade flat lesion confined to the mucosa. Intravesical treatment with bacillus Calmette–Guerin (BCG) is commonly used to reduce the risk of recurrence and progression; however, CIS of the bladder exhibits a heterogeneous clinical behavior and a significant proportion of patients do not show a primary response. Objective To evaluate the available evidence concerning diagnosis, treatment strategies, follow-up, prognosis, and oncological outcomes in patients with CIS of the bladder. Evidence acquisition A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The search was conducted using the databases PubMed/MEDLINE and Embase. We included randomized controlled trials, systematic reviews, meta-analyses, and observational studies. Outcomes of interest were: (1) diagnostic strategies, (2) first- and second-line treatments, (3) follow-up strategies, and (4) prognosis and oncological outcomes. Evidence synthesis Overall 62 articles met the inclusion criteria. Most articles concerned retrospective studies and presented mixed data with other non–muscle-invasive bladder cancer categories. The evidence shows that new optical imaging modalities significantly increase the detection rate of CIS. BCG immunotherapy remains the first-line therapy in patients with CIS of the bladder; however, after treatment, adequate follow-up is necessary. Clinicopathological factors remain the main indicators of response to BCG, recurrence, and progression. Conclusions New optical imaging modalities are superior to white light cystoscopy in the detection of CIS of the bladder. There are no robust data that justify consideration of other agents as an alternative to BCG immunotherapy. Despite efforts to identify relevant biomarkers, clinicopathological factors remain the most important prognostic factors. Patient summary New optical techniques have improved the detection of carcinoma in situ (CIS) of the bladder. Bladder preservation using bacillus Calmette-Guerin immunotherapy remains the cornerstone of the treatment of CIS of the bladder.

Background: Papillary urothelial neoplasm of low malignant potential (PUN-LMP) was introduced as a noninvasive, noncancerous lesion and a separate grade category in 1998. Subsequently, PUN-LMP was reconfirmed by World Health Organization (WHO) 2004 and WHO 2016 classifications for urothelial bladder tumors. Objectives: To analyze the proportion of PUN-LMP diagnosis over time and to determine its prognostic value compared to Ta-LG (low-grade) and Ta-HG (high-grade) carcinomas. To assess the intraobserver variability of an experienced uropathologist assigning (WHO) 2004/2016 grades at 2 time points. Materials and methods: Individual patient data of 3,311 primary Ta bladder tumors from 17 hospitals in Europe and Canada were available. Transurethral resection of the tumor was performed between 1990 and 2018. Time to recurrence and progression were analyzed with cumulative incidence functions, log-rank tests and multivariable Cox-regression stratified by institution. Intraobserver variability was assessed by examining the same 314 transurethral resection of the tumorslides twice, in 2004 and again in 2018. Results: PUN-LMP represented 3.8% (127/3,311) of Ta tumors. The same pathologist found 71/314 (22.6%) PUN-LMPs in 2004 and only 20/314 (6.4%) in 2018. Overall, the proportion of PUN-LMP diagnosis substantially decreased over time from 31.3% (1990-2000) to 3.2% (2000-2010) and to 1.1% (2010-2018). We found no difference in time to recurrence between the three WHO 2004/2016 Ta-grade categories (log-rank, P = 0.381), nor for LG vs. PUN-LMP (log-rank, P = 0.238). Time to progression was different for all grade categories (log-rank, P < 0.001), but not between LG and PUN-LMP (log-rank, P = 0.096). Multivariable analyses on recurrence and progression showed similar results for all 3 grade categories and for LG vs. PUN-LMP. Conclusions: The proportion of PUN-LMP has decreased to very low levels in the last decade. Contrary to its reconfirmation in the WHO 2016 classification, our results do not support the continued use of PUN-LMP as a separate grade category in Ta tumors because of the similar prognosis for PUN-LMP and Ta-LG carcinomas. (C) 2019 Elsevier Inc. All rights reserved.

The best predictors of response to intravesical immunotherapy are tumor grade and stage, tumor recurrence pattern, nomograms, panels of urinary cytokines, and fluorescent in situ hybridization patterns of urine cytology examinations. Future investigations on predictors of Bacillus Calmette-Guerin efficacy are needed to better select those patients who will really benefit from a conservative treatment. Hardly any of the proposed nomograms were designed to precisely predict the outcome of Bacillus Calmette-Guerin immunotherapy. A new nomogram for NMIBC recurrence and progression based on all non-muscle-invasive bladder cancer subgroups would include factors already proven in cancer prognosis and prediction.

This article describes the conversational therapy approach for the treatment of persons with aphasia (PWAs). Around 1970s, this approach was inspired by a series of pragmatic principles and techniques to aphasia rehabilitation whose main objective was to set up a condition of communicative exchange with the PWA using his/her own available communicative resources. Indeed, although language represents the most powerful behavior that humans use for communicating, within the conversational approach any intentional action (i.e., gestures, body movements, facial expression, drawing) can be used to communicate. For this reason, its application is particularly suitable for severe PWAs whose damage has compromised all the modalities of language (i.e., production, comprehension, reading, and writing). In this perspective, the speech-language pathologist's (SLP's) goal is not necessarily focused on restoring the damaged linguistic functions, still today pursued by the cognitive approach, but to ameliorate the use of language by teaching the PWA compensatory, productive strategies, and strengthening his/her residual communicative abilities. In this review, the fundamental principles of the conversational approach together with its modalities of treatment, which emphasize the importance of an active interaction between the SLP and the PWA, are reported. A brief summary of recent experimental evidence which combines conversational therapy with a noninvasive brain stimulation technique, transcranial direct current stimulation, is also included.

Peyronie’s disease is a chronic inflammatory disease involving the formation of plaque in the tunica albuginea of the corpora cavernosa, resulting in penis deformity. It is often associated with penile pain, especially in younger patients, but it is not rare for pain to be absent; the disease is also associated with erectile dysfunction and a depressive state in a large percentage of cases. Objective: Aim of our study was to explore the basic knowledge base and diagnostic and therapeutic practice patterns in Peyronie's disease (PD) of a large number of physicians belonging to the Italian Andrology Society (SIA). Methods: Our survey is based on two questionnaires which were e-mailed to the members of the SIA. The first questionnaire explored diagnostic and therapeutic practice patterns of SIA physicians, while the second questionnaire focused on their knowledge of the disease, as well as their training and level of experience in the specific field. We then planned to compare our outcomes with similar PD surveys from other countries. Results: The first questionnaire was answered by 142 SIA physicians. The second questionnaire was answered by 83 SIA physicians. Most respondents (74.6%) chose penile ultrasonography as first-line diagnostic approach and 47.1% prefer to perform a color Doppler ultrasound after pharmaco-induced erection. Concerning the therapeutic practice patterns in active stage of the disease, most respondents (99.29%) prefer conservative medical therapy. Additionally, most respondents (64.78%), when failure of conservative treatment had been established, considered surgical treatment necessary, specifically corporoplasty, which may be associated with other techniques. Conclusions: The results of our survey show that, in comparison to their foreign counterparts, Italian SIA uro-andrologists have a more proactive diagnostic approach right from when patients first present. When PD is still in its active stage, SIA uro-andrologists mostly opt for medical therapy. In advanced disease or if conservative treatment fails, our survey indicates a greater preference for surgical treatment. Answers to the theoretical knowledge questions showed that SIA physicians have a good understanding of the disease’s etiology, epidemiology, and clinical picture, and of the appropriate indications for treatment.

Purpose of review To review the current literature concerning the intravesical treatment of nonmuscle invasive bladder cancer. Recent findings Bladder cancer is a high prevalent disease. Despite the recognized efficacy of traditional intravesical therapies, the best treatment strategy still needs to be found. Improvement in bladder cancer research lead to develop new intravesical agents and drug delivery systems for nonmuscle invasive bladder cancer tumours. Moreover, the emerging knowledge of bladder cancer immune profile strongly improves and provides new available treatment strategies. Summary The future of nonmuscle invasive bladder cancer therapy will be influenced by the development of immunotherapy and new technologies for device-assisted treatment. Moreover, nanotechnology and delivery systems present promising results.

Resumen Introduccion y objetivos Existen varios estudios con el objetivo de validar las tablas del Club Urologico Espanol de Tratamiento Oncologico (CUETO). Sin embargo, ninguno de estos estudios se ha centrado en el cancer de vejiga de alto y muy alto riesgo. El objetivo del presente estudio fue validar externamente el modelo CUETO para predecir la recidiva y la progresion de la enfermedad en el grupo de tumores T1G3 tratados con bacilo Calmette-Guerin (BCG). Pacientes o materiales y metodos Se analizaron los datos de 414 pacientes con cancer de vejiga T1G3 primario. Para evaluar la discriminacion del modelo se usaron modelos de riesgos proporcionales de Cox y se calcularon los indices de concordancia. Resultados La mediana de seguimiento fue de 68 meses. Se observo recidiva en 212 (51,2%) y 64 pacientes (15,5%) experimentaron mas de un episodio de recurrencia durante el periodo de seguimiento. La progresion del cancer se observo en 106 pacientes (25,6%), 115 pacientes (27,8%) fueron tratados con cistectomia radical, y hubo 64 (15,5%) muertes por tumor. Para la probabilidad de recidiva y progresion, el indice de concordancia de los modelos CUETO fue de 0,633 y 0,697, respectivamente. Las tablas de CUETO subestimaron significativamente el riesgo de recidiva y marginalmente el riesgo de progresion en el primer ano de observacion. Durante los 5 anos de observacion, la tendencia de la recidiva fue mucho menos clara. Por el contrario, hubo una ligera sobreestimacion en el riesgo de progresion. El estudio esta limitado por su naturaleza retrospectiva. Conclusiones Se demostro que las tablas de riesgo del grupo CUETO logran una discriminacion correcta, tanto para la recidiva de la enfermedad como para la progresion, en pacientes con T1G3 tratados con BCG. El modelo de puntuacion (CUETO) subestima el riesgo de recidiva del tumor, pero acierta al predecir el riesgo de progresion.

Purpose Nodal recurrent prostate cancer (PCa) after primary radical treatment represents a heterogeneous entity with many treatment options. In some cases, surgical removal of metastatic nodes seems to improve cancer control and delay systemic treatments. The objectives of this study were to analyze the available literature on salvage lymphadenectomy for the treatment of nodal recurrent PCa and to elucidate the real oncological benefit deriving from this procedure. Methods A PubMed search was performed using the following terms: prostate cancer, metastatic, oligometastatic, salvage lymphadenectomy, salvage lymph node dissection, salvage lymph node excision, and cytoreductive surgery. We included in the study all papers on salvage lymphadenectomy in nodal recurrent PCa, with no temporal limits. In addition, several papers addressing cytoreductive surgery and the biology of oligometastatic disease, published in different medical and basic research journals, were included. Results Salvage lymphadenectomy is still characterized by a lack of standardization in patient selection and surgical template. Its primary objectives are to prolong progression-free survival and to delay the need for systemic therapy. The improvements in preoperative imaging techniques in conjunction with the wide use of minimally invasive surgery have generated growing interest in this procedure. Conclusion Salvage lymphadenectomy is a promising treatment approach; however, its real oncological benefit is still far from proven. Prospective randomized trials need to be designed to improve understanding of this issue.

Intellectual disability (ID) compromises intellectual and adaptive functioning. People with an ID show difficulty with procedural skills, with loss of autonomy in daily life. From an embodiment perspective, observation of action promotes motor skill learning. Among promising technologies, virtual reality (VR) offers the possibility of engaging the sensorimotor system, thus, improving cognitive functions and adaptive capacities. Indeed, VR can be used as sensorimotor feedback, which enhances procedural learning. In the present study, fourteen subjects with an ID underwent progressive steps training combined with VR aimed at learning gardening procedures. All participants were trained twice a week for fourteen weeks (total 28 sessions). Participants were first recorded while sowing zucchini, then they were asked to observe a virtual video which showed the correct procedure. Next, they were presented with their previous recordings, and they were asked to pay attention and to comment on the errors made. At the end of the treatment, the results showed that all participants were able to correctly garden in a real environment. Interestingly, action observation facilitated, not only procedural skills, but also specific cognitive abilities. This evidence emphasizes, for the first time, that action observation combined with VR improves procedural learning in ID.

Background: In the current European Association of Urology (EAU) non-muscle invasive bladder cancer (NMIBC) guideline, two classification systems for grade are advocated: WHO1973 and WHO2004/2016. Objective: To compare the prognostic value of these WHO systems. Design, setting, and participants: Individual patient data for 5145 primary Ta/T1 NMIBC patients from 17 centers were collected between 1990 and 2019. The median follow-up was 3.9 yr. Outcome measurements and statistical analysis: Univariate and multivariable analyses of WHO1973 and WHO2004/2016 stratified by center were performed for time to recurrence, progression (primary endpoint), cystectomy, and duration of survival, taking into account age, concomitant carcinoma in situ, gender, multiplicity, tumor size, initial treatment, and tumor stage. Harrell's concordance (C-index) was used for prognostic accuracy of classification systems. Results and limitations: The median age was 68 yr; 3292 (64%) patients had Ta tumors. Neither classification system was prognostic for recurrence. For a four-tier combination of both WHO systems, progression at 5-yr follow-up was 1.4% in lowgrade (LG)/G1, 3.8% in LG/G2, 7.7% in high grade (HG)/G2, and 18.8% in HG/G3 (log rank, p < 0.001). In multivariable analyses with WHO1973 and WHO2004/2016 as independent variables, WHO1973 was a significant prognosticator of progression (p < 0.001), whereas WHO2004/2016 was not anymore (p = 0.067). C-indices for WHO1973, WHO2004, and the WHO systems combined for progression were 0.71, 0.67, and 0.73, respectively. Prognostic analyses for cystectomy and survival showed results similar to those for progression. Conclusions: In this large prognostic factor study, both classification systems were prognostic for progression but not for recurrence. For progression, the prognostic value of WHO1973 was higher than that of WHO 2004/2016. The four-tier combination (LG/G1, LG/G2, HG/G2, and HG/G3) of both WHO systems proved to be superior, as it divides G2 patients into two subgroups (LG and HG) with different prognoses. Hence, the current EAU-NMIBC guideline recommendation to use both WHO classification systems remains correct. Patient summary: At present, two classification systems are used in parallel to grade non-muscle-invasive bladder tumors. Our data on a large number of patients showed that the older classification system (WHO1973) performed better in terms of assessing progression than the more recent (WHO2004/2016) one. Nevertheless, we conclude that the current guideline recommendation for the use of both classification systems remains correct, since this has the advantage of dividing the large group of WHO1973 G2 patients into two subgroups (low and high grade) with different prognoses. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Background: The European Association of Urology (EAU) prognostic factor risk groups for non–muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. Objective: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. Design, setting, and participants: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. Intervention: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. Outcome measurements and statistical analysis: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. Results and limitations: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004–2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from 40%. Limitations include the retrospective collection of data and the lack of central pathology review. Conclusions: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. Patient summary: The newly updated European Association of Urology prognostic factor risk groups for non–muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule. The updated European Association of Urology prognostic factor risk groups for patients with non–muscle-invasive bladder cancer provide urologists with information that they should take into account when choosing a patient's treatment and scheduling follow-up.

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, unconventional rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the principal approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proven to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review reveals an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Aphasia is a highly disabling acquired language disorder, usually caused by left-lateralized brain damage [...]

Aphasia is one of the most socially disabling post-stroke deficits. Although traditional therapies have been shown to induce adequate clinical improvement, aphasic symptoms often persist. Therefore, new rehabilitation techniques which act as a substitute or as an adjunct to traditional approaches are urgently needed. The present review provides an overview of the efficacy and safety of the most innovative approaches which have been proposed over the last twenty years. First, we examined the effectiveness of the pharmacological approach, principally used as an adjunct to language therapy, reporting the mechanism of action of each single drug for the recovery of aphasia. Results are conflicting but promising. Secondly, we discussed the application of Virtual Reality (VR) which has been proved to be useful since it potentiates the ecological validity of the language therapy by using virtual contexts which simulate real-life everyday contexts. Finally, we focused on the use of Transcranial Direct Current Stimulation (tDCS), both discussing its applications at the cortical level and highlighting a new perspective, which considers the possibility to extend the use of tDCS over the motor regions. Although the review revels an extraordinary variability among the different studies, substantial agreement has been reached on some general principles, such as the necessity to consider tDCS only as an adjunct to traditional language therapy.

Since its introduction more than 40 years ago, adjuvant treatment with BCG (Bacillus Calmette-Guérin) for non-muscle invasive bladder cancer (NMIBC) continues to be the treatment recommended in the highrisk group, and one of the most successful immunotherapies for cancer treatment. However, up to 20% of patients will progress to muscle-invasive disease after BCG treatment. On the other hand, we are facing a shortage of BCG supply worldwide. Despite its extensive clinical use, there is no clear certainty of the mechanism of action of BCG, and controversy persists regarding to the most effective dose and strains, as well as their usefulness in combined treatments with other drugs and with devices that could facilitate their action on the bladder. This article historically reviews the impact that has had BCG in the treatment of NMIBC, the current guidelines in terms of doses, strains and treatments combination, and the future that will happen with the results of the ongoing clinical trials with systemic immunotherapy, vaccines and gene therapy.Desde su introducción hace más de 40 años, el tratamiento adyuvante con BCG (Bacilo Calmette-Guérin) para el tumor vesical no-músculo invasivo (TVNMI) sigue siendo el tratamiento de elección en el grupo de alto riesgo, y una de las inmunoterapias para el cáncer de mayor éxito. Sin embargo, hasta el 20% de los pacientes progresarán a enfermedad músculo-invasiv adespués del tratamiento con BCG. Por otra parte,nos encontramos ante una escasez de suministro de BCG a nivel mundial. A pesar de su extenso uso clínico, no existe una clara certeza del mecanismo de acción de la BCG, y todavía persiste controversia en cuanto a las dosis y cepas más eficaces, así como su utilidad en tratamientos combinados con otros fármacos y con dispositivos que podrían facilitan su acción en la vejiga. En este artículo se revisa históricamente el impacto que ha tenido la BCG en el tratamiento del TVNMI, las directrices actuales en cuanto a dosis, cepas y tratamientos de combinación, y el futuro que acontecerá con los resultados de los ensayos clínicos sobre inmunoterapia sistémica, inmuno moduladores, vacunas y terapia génicaen el TVNMI.

Metastatic lymph node dissection (LND) in nodal recurrent PCa after radical treatments has become a feasible salvage approach, and salvage LND (sLND) has been proposed in patients with “node-only” biochemical recurrence (BCR) after definitive treatment of primary PCa. This chapter examines the salvage lymph node dissection.

After primary RT for PCa, treatment failure can be distinguished in biochemical and clinical relapse. According to the available literature, cancer is confined to the prostate and seminal vesicles in over one-third of RT failures, while almost 60% of disease recurrence occurs in the bone, visceral organs, and pelvic and abdominal lymph nodes. This chapter examines salvage re-irradiation therapy after loco-regional failure.

Background: Recently, a growing body of evidence has shown that, from the early stage of impairment, Alzheimer’s patients (AD) present difficulties on a variety of tasks mostly relying on executive functions. These strongly impact their daily life activities causing a severe loss of independency and autonomy. Objective: To evaluate the efficacy of transpinal direct current stimulation (tsDCS) combined with cognitive trainings for improving attentional and executive function abilities in a group of AD patients. Methods: In a randomized-double blind design, sixteen AD patients underwent different cognitive trainings combined with tsDCS. During the treatment, each subject received tsDCS (20 min, 2 mA) over the thoracic vertebrae (IX-X vertebrae) in two different conditions: 1) anodal, and 2) sham while performing three computerized tasks: alertness, selective attention, and executive functions. Each experimental condition was run in ten consecutive daily sessions over two weeks. Results: After anodal tsDCS, a greater improvement in executive functions compared to sham condition was found. More importantly, the follow-up testing revealed that these effects lasted over 1 month after the intervention and generalized to the different neuropsychological tests administered before, after the treatment and at one month after the end of the intervention. This generalization was present also in the attentional domain. Conclusion: This evidence emphasizes, for the first time, that tsDCS combined with cognitive training results efficacious for AD patients. We hypothesize that enhancing activity into the spinal sensorimotor pathways through stimulation improved cognitive abilities which rely on premotor activity, such as attention and executive functions.

Introduction: Radiotherapy is a valid treatment option for nasopharyngeal carcinoma. However, complications can occur following irradiation of the closest anatomical structures, including brainstem radionecrosis (BRN). The rehabilitation is poorly described in patients with BRN, despite its usefulness in improving functional independence in patients with brain tumors. We aimed at testing the usefulness of intensive, robot-assisted neurorehabilitation program to improve functional independence in a 57-year-old male with BRN. Patient concerns: A 57-year-old male diagnosed with a nasopharyngeal carcinoma, received a radiation total dose of 72 Gy. Owing to the appearance of a severe symptomatology characterized by dysphagia, hearing loss, and left sided hemiparesis, the patient was hospitalized to be provided with intensive pharmacological and neurorehabilitation treatment. Diagnosis: Follow-up brain magnetic resonance imaging disclosed no residual cancer, but some brainstem lesions compatible with BRN areas were appreciable. Intervention: The patient underwent a 2-month conventional, respiratory, and speech therapy. Given that the patient only mildly improved, he was provided with intensive robot-aided upper limb and gait training and virtual reality-based cognitive rehabilitation for other 2 months. Outcomes: The patient reported a significant improvement in functional independence, spasticity, cognitive impairment degree, and balance. Conclusion: Our case suggests the usefulness of neurorobotic intensive rehabilitation in BRN to reduce functional disability. Future studies should investigate whether an earlier, even multidisciplinary rehabilitative treatment could lead to better functional outcome in patients with BRN.

Introduction Traditional physiotherapy is currently the best approach to manage patients with intensive care unit acquired weakness (ICUAW). We report on a patient with ICUAW, who was provided with an intensive, in-patient regimen, that is, conventional plus robot-assisted physiotherapy. Aim of this case study was to assess the efficacy of a combined approach (conventional plus robot-assisted physiotherapy), on muscle strength, overall mobility, and disability burden in a patient with ICUAW in post-ICU intensive rehabilitation setting. Patient concerns A 56-years-old male who was unable to stand and walk independently after hospitalization in an Intensive Care Unit. He initially was provided with daily sessions of conventional physiotherapy for 2 months, with mild results. Diagnosis The patient was affected by ICUAW. Intervention Given that the patient showed a relatively limited improvement after conventional physiotherapy, he was provided with daily sessions of robot-aided training for upper and lower limbs and virtual reality-aided rehabilitation for other 4 months, beyond conventional physiotherapy. Outcomes At the discharge (6 months after the admission), the patient reached the standing station and was able to ambulate with double support. Conclusions Our case suggests that patients with ICUAW should be intensively treated in in-patient regimen with robot-aided physiotherapy. Even though our approach deserves confirmation, the combined rehabilitation strategy may offer some advantage in maximizing functional recovery and containing disability.

Purpose The aim of this study was to analyse the influence of age on the treatment outcome and toxicity in patients with T1HG non-muscle invasive bladder cancers treated with BCG immunotherapy. Methods Data from 637 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in two academic centres were retrospectively reviewed. Median follow-up was 57 months. Patients were divided into two groups: younger (< 70 years old) and older (>= 70 years old). Additional analyses in subgroups of older (> 75 and > 80) patients were performed. Log-rank test, Cox regression analysis, and propensity score matching were performed to compare the groups. Results There were 389 patients below and 248 patients above or equal 70 years old. Recurrence-free, progression-free, and cancer-specific survival rates did not differ significantly between younger and older patients. Recurrence-free survival for younger and older patients were 55.4% vs 52.9%, progression-free survival 75.9% vs 76.6%, and cancer-specific survival were 87.5% vs 89.9% (all p > 0.05). Differences in the oldest subgroups also did not reach statistical significance. In both regression analysis and propensity score matching, no statistically significant associations of age with any of analysed end-points were found. Finally, there were no statistically significant differences between younger and older group in terms of moderate and severe complications occurrence (47.6% vs. 44.5%; p > 0.05) Conclusions It was shown that increasing age was not associated with BCG immunotherapy oncological outcomes, or with BCG toxicity in T1HG non-muscle invasive bladder cancer.

To date, new advances in technology have already shown the effectiveness of non-invasive brain stimulation and, in particular, of transcranial direct current stimulation (tDCS), in enhancing language recovery in post-stroke aphasia. More recently, it has been suggested that the stimulation over the spinal cord improves the production of words associated to sensorimotor schemata, such as action verbs. Here, for the first time, we present evidence that transpinal direct current stimulation (tsDCS) combined with a language training is efficacious for the recovery from speech apraxia, a motor speech disorder which might co-occur with aphasia. In a randomized-double blind experiment, ten aphasics underwent five days of tsDCS with concomitant treatment for their articulatory deficits in two different conditions: anodal and sham. In all patients, language measures were collected before (T0), at the end (T5) and one week after the end of treatment (F/U). Results showed that only after anodal tsDCS patients exhibited a better accuracy in repeating the treated items. Moreover, these effects persisted at F/U and generalized to other oral language tasks (i.e. picture description, noun and verb naming, word repetition and reading). A further analysis, which compared the tsDCS results with those collected in a matched group of patients who underwent the same language treatment but combined with tDCS, revealed no differences between the two groups. Given the persistency and severity of articulatory deficits in aphasia and the ease of use of tsDCS, we believe that spinal stimulation might result a new innovative approach for language rehabilitation.

Salvage radical prostatectomy has historically yielded a poor functional outcome and a high complication rate. However, recent reports of robotic salvage radical prostatectomy have demonstrated improved results. In this study we assessed salvage radical prostatectomy functional outcomes and complications when comparing robotic and open approaches.We retrospectively collected data on salvage radical prostatectomy for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers from 2000 to 2016. The Clavien-Dindo classification was applied to classify complications. Complications and functional outcomes were evaluated by univariable and multivariable analysis.We included 395 salvage radical prostatectomies, of which 186 were open and 209 were robotic. Robotic salvage radical prostatectomy yielded lower blood loss and a shorter hospital stay (each p0.0001). No significant difference emerged in the incidence of major and overall complications (10.1%, p=0.16, and 34.9%, p=0.67), including an overall low risk of rectal injury and fistula (1.58% and 2.02%, respectively). However, anastomotic stricture was more frequent for open salvage radical prostatectomy (16.57% vs 7.66%, p0.01). Overall 24.6% of patients had had severe incontinence, defined as 3 or more pads per day, for 12 or 6 months. On multivariable analysis robotic salvage radical prostatectomy was an independent predictor of continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature of the study and the absence of a standardized surgical technique.In this contemporary series to our knowledge salvage radical prostatectomy showed a low risk of major complications and better functional outcomes than previously reported. Robotic salvage radical prostatectomy may reduce anastomotic stricture, blood loss and hospital stay, and improve continence outcomes.

INTRODUCTION AND OBJECTIVES:CIS has been already identified as one of the most important prognostic risk factors in NMIBC in BCG treated patients. Interestingly, this information mostly derived fro...

INTRODUCTION AND OBJECTIVES:Salvage radical prostatectomy (sRP) has been associated with high complication rates and poor functional outcomes in the past, while latest sRP series have shown a subst...

INTRODUCTION AND OBJECTIVES:A curative option in men with biochemical recurrence (BCR) after primary treatment is represented by salvage radical prostatectomy (sRP). To enhance cancer control and b...

Introduction and objectives: Various studies tried to validate Club Urologico Espanol de Tratamiento Oncologico (CUETO) tables, yet, none of this papers focused on the high and very high risk bladder cancers. The aim of the study was to externally validate the CUETO model for predicting disease recurrence and progression in group of T1G3 tumors treated with BCG immunotherapy. Patients or materials and methods: Data from 414 patients with primary T1G3 bladder cancer were analysed. To evaluate the model discrimination, Cox proportional hazard regression models were created and concordance indexes were calculated. Results: The median follow-up was 68 months. The recurrence was observed in 212 (51.2%) and 64 patients (15.5%) experienced the recurrence more than once during the study follow-up. Progression of the cancer was observed in 106 patients (25.6%). Radical cystectomy was performed in 115 patients (27.8%) and there were 64 (15.5%) cancer specific deaths. For recurrence and progression probability, the concordance index of the CUETO models was 0.633 and 0.697 respectively. CUETO tables underestimated significantly the risk of recurrence and marginally the risk of progression in the first year of observation. For 5 years of observation, the trend for the recurrence was much less clear. On the contrary, there was slight overestimation in the risk of progression. The study is limited by retrospective nature. Conclusions: It was shown that the CUETO risk tables exhibit a fair discrimination for both disease recurrence and progression in T1G3 patients treated with BCG. CUETO scoring model underestimates the risk of tumor recurrence, but predicts well risk of progression. (C) 2019 AEU. Published by Elsevier Espana, S.L.U. All rights reserved.

Introduction and objectives: The aim of this study was to analyse prognostic impact of tumour histological grade on survival differences between primary G2 and G3 WHO1973 stage T1 tumours which were graded as HG according to WHO2004 grading system. Materials and methods: Data from 481 patients with primary T1HG bladder cancer who were treated between 1986 and 2016 in 2 university centres were retrospectively reviewed. Log-rank test and Cox regression analysis was performed to compare the groups. Results: 95 (19,8%) tumours were classified as G2 and 386 (80,2%) were G3. Median follow-up was 68 months. The recurrence was observed in 228 (47,5%), and progression in 109 patients (22,7%). Radical cystectomy was performed in 114 pts (23,7%) and there were 64 (13,3%) cancer specific deaths. Recurrence-free rates at 5-years follow-up for G2, G3 and all patients were 68,7%, 51,2% and 56,3% and progression-free rates were 89,3%, 73,2% and 78,1% respectively. For total observation period patients with G3 tumours presented also worse recurrence-free, and progression-free survival levels than patients with G2 tumours. In multivariate analysis, after adjustment for clinical features, the risk of recurrence and progression for G3 tumours was 1,65 and 2,42 fold higher than for G2 tumours. Conclusions: It was shown that G3 T1 tumours are characterized by worse recurrence free and progression free survivals when compared to G2 cancers. (C) 2019 AEU. Published by Elsevier Espana, S.L.U. All rights reserved.

Several behavioural and neuroimaging studies have suggested that the language function is not restricted into the left areas but it involves regions not predicted by the classical language model. Accordingly, the Embodied Cognition theory postulates a close interaction between the language and the motor system. Indeed, it has been shown that non-invasive brain stimulation (NIBS) is effective for language recovery also when applied over sensorimotor regions, such as the motor cortex, the cerebellum and the spinal cord. We will review a series of NIBS studies in post-stroke aphasic people aimed to assess the impact of NIBS on verb recovery. We first present results which, following the classical assumption of the Broca's area as the key region for verb processing, have shown that the modulation over this area is efficacious for verb improvement. Then, we will present experiments which, according to Embodied Cognition, have directly investigated through NIBS the role of different sensorimotor regions in enhancing verb production. Since verbs play a crucial role for sentence construction which are most often impaired in the aphasic population, we believe that these results have important clinical implications. Indeed, they address the possibility that different structures might support verb processing.

Background and Objectives: Renal transplant recipients (RTRs) have a 2- to 7-fold risk of developing a neoplasm compared to general population. Bladder urothelial neoplasms in this cohort has an incidence of 0.4–2%. Many reports describe a more aggressive behavior. The objective of this study is to describe oncologic characteristics of bladder urothelial neoplasms in RTRs and to evaluate its recurrence, progression, and survival rates. Methods: A retrospective multicentered study was performed evaluating all de novo bladder urothelial neoplasms cases in RTRs from 1988 to 2014. Descriptive statistical analysis and evaluation of recurrence, progression, and survival rates were performed. Results: A total of 28 de novo bladder transitional cell carcinomas (TCCs) were identified (incidence rate 0.64%). Cancer-specific survival rates were 100, 75, and 70% after 1, 5, and 10 years, respectively. Age at diagnosis superior to 60 years was found to be a statistically significant variable for recurrence risk. Progression rate was 14%. Presence of CIS was significantly associated with progression. All cancer-specific deaths were in the high-risk group and all were progressions from non-muscle invasive to muscle invasive bladder cancer. Conclusions: Bladder urothelial neoplasms following renal transplant is associated with a trend toward worst prognosis. Early aggressive treatments, such as early radical cystectomy, might be advisable to reduce cancer-specific deaths.

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P