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1.
Minerva Urol Nephrol ; 76(1): 42-51, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38426421

RESUMO

INTRODUCTION: Patients' treatment preferences (PTP) depend on the complex interaction of numerous patient- and treatment-related factors; their assessment can guide therapy and promote compliance of patients with erectile dysfunction (ED). We aimed to systematically describe the literature evaluating the treatment preferences of patients with ED, published in the last 25 years. EVIDENCE ACQUISITION: A comprehensive bibliographic search of multiple databases was conducted in June, 2023. The literature search was limited to the articles published since 1998. Articles were deemed eligible if they described male patients with ED (P) undergoing treatment for this condition (I) compared with other treatments, placebo or sham therapy (C), and reported PTP (O). Only randomized controlled trials (RCTs) and post-hoc analyses of RCTs were selected (S). The data were presented in a narrative fashion. The risk of bias (RoB) was evaluated using the RoB 2 tool and the Mulhall-Montorsi model. EVIDENCE SYNTHESIS: A total 14 RCTs evaluating 6,841 patients and 4 post-hoc analyses of RCTs were included. All RCTs were considered to be at high RoB. No validated tool was used to investigate PTP. Sildenafil was the most frequently evaluated ED treatment (9 RCTs). Sildenafil was chosen over placebo by 78-100% of subjects and over ICI in 70% of patients due to its easier route of administration. No significant difference in patient preference was recorded between Sildenafil tablets and orodispersible (53% vs. 47%, P>0.05). Tadalafil was preferred over Sildenafil by 66-73% of patients (P<0.05), mainly because it allowed an erection long after taking the drug (55-67%). Tadalafil as-needed was chosen over Tadalafil 3 times/week by 57-59% of the patients (P<0.05). CONCLUSIONS: The available RCTs support the preference of ED patients for Sildenafil over ICI, Tadalafil over Sildenafil, and Tadalafil as-needed over Tadalafil 3 times/week. However, these findings should be considered at high RoB.


Assuntos
Disfunção Erétil , Humanos , Masculino , Disfunção Erétil/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Citrato de Sildenafila/uso terapêutico , Tadalafila/uso terapêutico , Preferência do Paciente
2.
Medicina (Kaunas) ; 60(2)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38399502

RESUMO

Urinary tract infections (UTIs) are the second most frequent type of infection observed in clinical practice. Gram-negative Enterobacteriaceae are common pathogens in UTIs. Excessive antibiotic use in humans and animals, poor infection control, and increased global travel have accelerated the spread of multidrug-resistant strains (MDR). Carbapenem antibiotics are commonly considered the last line of defense against MDR Gram-negative bacteria; however, their efficacy is now threatened by the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE). This comprehensive review aims to explore the biological mechanisms underlying carbapenem resistance and to present a focus on therapeutic alternatives currently available for complicated UTIs (cUTIs). A comprehensive bibliographic search was conducted on the PubMed/MEDLINE, Scopus, and Web of Science databases in December 2023. The best evidence on the topic was selected, described, and discussed. Analyzed with particular interest were the clinical trials pivotal to the introduction of new pharmacological treatments in the management of complicated cUTIs. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. This overview provides a current and comprehensive examination of the treatment options available for CRE infections, offering a valuable resource for understanding this constantly evolving public health challenge.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções Urinárias , Humanos , Infecções Urinárias/microbiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Carbapenêmicos/uso terapêutico , Farmacorresistência Bacteriana Múltipla
3.
Pathol Res Pract ; 253: 155069, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38181581

RESUMO

Mesothelial tumours of the testicular/paratesticular region are uncommon, poorly characterised and difficult-to-diagnose lesions. They encompass entirely benign proliferations (adenomatoid tumour) and malignant, very aggressive tumours (mesothelioma) whose morphological features can be overlapping, highly variable and confounding. Moreover, testicular/paratesticular mesothelial tumours comprise relatively new entities with indolent behaviour (well-differentiated papillary mesothelial tumour) as well as tumours which cannot be correctly included in any of the aforementioned categories and whose classification is still controversial. The molecular profile of such tumours represents an open issue. In fact, despite the recent discoveries about the genomic landscape of mesothelial proliferations at other sites (pleura, peritoneum), testicular/paratesticular mesothelial tumours, and namely mesotheliomas, are too rare to be extensively studied on large case series and they could arguably hide relevant differences in their molecular background when compared to the more common pleural/peritoneal counterparts.The aim of this review is to provide a guide for the pathological assessment of testicular/paratesticular mesothelial tumours. Herein, we describe the most recent updates on this topic according to the latest (year 2022) World Health Organisation Classification of Urinary and Male Genital Tumours (5th edition) and current literature. The diagnostic criteria, the main differentials and the role of ancillary techniques in the diagnosis of mesothelial testicular/paratesticular tumours are discussed.


Assuntos
Neoplasias dos Genitais Masculinos , Mesotelioma , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/patologia , Neoplasias dos Genitais Masculinos/patologia , Epitélio/patologia , Mesotelioma/patologia
4.
Curr Oncol Rep ; 25(12): 1431-1443, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37910274

RESUMO

PURPOSE OF REVIEW: To systematically review the evidence on prostate cancer (PCa) in transgender women (TGW). RECENT FINDINGS: A total of 25 studies were included. Fourteen articles were case reports or case series describing 21 TGW with PCa; 11 papers focused primarily on assessing the incidence or screening of PCa in TGW. The median (range) age of patients with PCa was 63 (45-78) years. Median (range) PSA at diagnosis was 7.5 (0.4-1710) ng/mL. Prostate biopsy detected ISUP 3-5 in 10 (67%) cases. T3-4 stages were described in 7 (64%) patients. Three (14.3%) cases of nodal involvement and 2 (9.5%) of metastases were reported at diagnosis. First-line therapy included radical prostatectomy or radiotherapy ± androgen deprivation therapy in 14 (74 %) subjects. Median (range) follow-up was 24 (2-120) months. A good response to first-line therapy was recorded in 8 (47.1%) cases. Median (range) incidence of PCa in TGW was 44.1 (4.34-140) cases per 100,000 person-years. PCa was significantly less frequent in TGW than in cisgender males (HR 0.4, 95% CI 0.2-0.9). Risk of death after PCa diagnosis was significantly higher in TGW compared to cisgender males (HR 1.91, 95% CI 1.06-3.45). TGW had lower lifetime PSA rates (48% vs. 64.6%, p = 0.048) than cisgender males. Few cases of PCa in TGW are currently reported. PCa seems significantly less frequent in TGW than in cisgender males; however, some data suggest a possible higher mortality in this cohort. TGW appear to have less access to PSA testing than cisgender men.


Assuntos
Neoplasias da Próstata , Pessoas Transgênero , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Antígeno Prostático Específico , Antagonistas de Androgênios/uso terapêutico , Prostatectomia
5.
Medicina (Kaunas) ; 59(11)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38004082

RESUMO

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.


Assuntos
MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , MicroRNAs/genética , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Recidiva Local de Neoplasia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/genética , Biomarcadores Tumorais/genética
6.
Dig Liver Dis ; 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37880017

RESUMO

BACKGROUND: Inflammatory Bowel Diseases (IBD), Crohn's Disease (CD), and Ulcerative Colitis (UC) may have extraintestinal manifestations, including disorders of the urinary tract. The prevalence of lower urinary tract symptoms (LUTS) in IBD patients remains unclear. AIMS: Assess the prevalence of LUTS in patients with CD or UC, evaluate the variables implicated in any difference in LUTS prevalence between CD or UC, and assess any relationship between disease activity and LUTS METHODS: LUTS were evaluated in 301 IBD patients through standardised questionnaires: Bristol Female Lower Urinary Tract Symptoms (BFLUTS), NIH-Chronic Prostatitis Symptom Index (NIH-CPSI), and International Prostate Symptom Score (IPSS). IBD activity was determined through the Crohn's Disease Activity Index (CDAI), Partial Mayo Score (PMS), and Total Mayo Score (TMS). RESULTS: BFLUTS total score for females was 6 (3-11). Patients with a higher age at diagnosis had worse filling symptoms (p = 0.049) and a worse quality of life (p = 0.005). In males, 67.1% had mild, 28.5% moderate, and 4.4% severe IPSS symptom grades. The overall NIHCPSI prevalence of chronic prostatitis-like symptoms was 26.8%. The questionnaires revealed some significant differences in the subgroups analysed. CONCLUSION: LUTS should be evaluated in IBD patients by urologic-validated questionnaires for prompt diagnosis and early treatment.

7.
Cancer Biomark ; 38(3): 343-353, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37661873

RESUMO

BACKGROUND: Testis-specific genes encoding for long non-coding RNA (lncRNA) have been detected in several cancers; many produce proteins with restricted or aberrant expression patterns in normal or cancer tissues. OBJECTIVE: To characterize new lncRNA involved in normal and/or pathological differentiation of testicular cells. METHODS: Using bioinformatics analysis, we found that lncRNA LOC100130460 (CAND1.11) is expressed in normal and tumor testis; its expression was assessed in several human cell lines by qRT-PCR. CAND1.11 protein, produced by a single nucleotide mutation, was studied by western blot and immunofluorescence analysis on normal, classic seminoma, and Leydig cell tumor testicular tissues. RESULTS: CAND1.11 gene is primate-specific; its expression was low in SH-SY5Y cells and increased when differentiated with retinoic acid treatment. CAND1.11 expression in PC3 cells was higher than in PNT2 cells. CAND1.11 protein is present in the human testis and overexpressed in testicular cancer tissues. CONCLUSIONS: This report is one of the few providing evidence that a lncRNA produces a protein expressed in normal human tissues and overexpressed in several testicular cancers, suggesting its involvement in regulating cell proliferation and differentiation. Although further studies are needed to validate the results, our data indicate that CAND1.11 could be a potential new prognostic biomarker to use in proliferation and cancer.


Assuntos
Neuroblastoma , RNA Longo não Codificante , Neoplasias Testiculares , Animais , Humanos , Masculino , Proliferação de Células/genética , Neuroblastoma/genética , Neuroblastoma/metabolismo , RNA Longo não Codificante/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patologia , Fatores de Transcrição , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo
8.
Int J Antimicrob Agents ; 62(5): 106974, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37739241

RESUMO

OBJECTIVES: To report the resistance rate against fosfomycin trometamol among outpatient women with symptoms related to urinary tract infections over a 6-year period in a multicentre, cross-sectional study. METHODS: Urinary samples were collected from three high-volume laboratories from January 2015 to December 2020. The pattern of resistance to fosfomycin was analysed by using the Vitek II automated system. RESULTS: A total of 7289 urinary samples were collected and 8321 strains were analysed during the study period. The most commonly isolated uropathogen was Escherichia coli (n = 6583, 79.1%). The mean resistance rate against fosfomycin was 9.7% (range 7.1-11.3). No statistically significant difference was found between the three laboratories (P = 0.53). There was no significant increase in resistance rate during the study period. The mean resistance rate against fosfomycin was higher among extended-spectrum ß-lactamase (ESBL)-producing bacteria when compared with non-ESBL-producing strains (10.8% vs. 7.9%; P < 0.001). CONCLUSION: Uropathogens isolated from women affected by cystitis remained highly susceptible to fosfomycin. These findings confirm recommendations in international guidelines that advocate fosfomycin trometamol for empirical treatment of uncomplicated cystitis in women.


Assuntos
Cistite , Fosfomicina , Infecções Urinárias , Feminino , Humanos , Fosfomicina/farmacologia , Fosfomicina/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Trometamina , Pacientes Ambulatoriais , Estudos Transversais , Testes de Sensibilidade Microbiana , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Cistite/tratamento farmacológico , Escherichia coli , Resistência Microbiana a Medicamentos
9.
Medicina (Kaunas) ; 59(6)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37374369

RESUMO

Background and Objectives: Patients undergoing cystoscopy can experience discomfort or pain during the procedure. In some cases, a urinary tract infection (UTI) with storage lower urinary tract symptoms (LUTS) may occur in the days following the procedure. This study aimed to assess the efficacy of D-mannose plus Saccharomyces boulardii in the prevention of UTIs and discomfort in patients undergoing cystoscopy. Materials and Methods: A single-center prospective randomized pilot study was conducted between April 2019 and June 2020. Patients undergoing cystoscopy for suspected bladder cancer (BCa) or in the follow-up for BCa were enrolled. Patients were randomized into two groups: D-Mannose plus Saccharomyces boulardii (Group A) vs. no treatment (Group B). A urine culture was prescribed regardless of symptoms 7 days before and 7 days after cystoscopy. The International Prostatic Symptoms Score (IPSS), 0-10 numeric rating scale (NRS) for local pain/discomfort, and EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) were administered before cystoscopy and 7 days after. Results: A total of 32 patients (16 per group) were enrolled. No urine culture was positive in Group A 7 days after cystoscopy, while 3 patients (18.8%) in Group B had a positive control urine culture (p = 0.044). All patients with positive control urine culture reported the onset or worsening of urinary symptoms, excluding the diagnosis of asymptomatic bacteriuria. At 7 days after cystoscopy, the median IPSS of Group A was significantly lower than that of Group B (10.5 vs. 16.5 points; p = 0.021), and at 7 days, the median NRS for local discomfort/pain of Group A was significantly lower than that for Group B (1.5 vs. 4.0 points; p = 0.012). No statistically significant difference (p > 0.05) in the median IPSS-QoL and EORTC QLQ-C30 was found between groups. Conclusions: D-Mannose plus Saccharomyces boulardii administered after cystoscopy seem to significantly reduce the incidence of UTI, the severity of LUTS, and the intensity of local discomfort.


Assuntos
Saccharomyces boulardii , Infecções Urinárias , Humanos , Cistoscopia/efeitos adversos , Cistoscopia/métodos , Qualidade de Vida , Manose/efeitos adversos , Projetos Piloto , Estudos Prospectivos , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Infecções Urinárias/epidemiologia
10.
Arch Ital Urol Androl ; 95(2): 11337, 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37254930

RESUMO

INTRODUCTION: Sexual dysfunctions (SD) are frequently encountered in patients with rheumatologic diseases. In this scenario, a multidisciplinary approach to rheumatologic diseases is often mandatory. The aim of this survey was to assess whether Italian rheumatologists routinely explore sexual health of their patients, their knowledge on the topic, and the barriers to discussing SD in clinical practice. METHODS: A 32-items anonymous questionnaire was mailed to members of the Italian Society of Rheumatology (rheumatologists and residents in rheumatology training) in February 2023. The questionnaire aimed to determine attitudes, knowledge, and practice patterns regarding the discussion of SD with rheumatologic patients. A descriptive analysis of responses was performed. RESULTS: A total of 162 responses were received. Overall, 50.0% of respondents occasionally asked patients about SD related to their rheumatologic pathologies, while 37.1% never did so. Respondents declared that patients occasionally (82.3%) or never (16.1%) reported SD related to rheumatologic diseases. The main barriers to discussing sexual health were lack of time during medical examination (46.6%), patients' discomfort (44.8%), and lack of knowledge/experience (39.7%). Overall, 41.9% and 33.9% of respondents respectively totally and partially agreed that rheumatologists should routinely investigate patients' sexual health. Most of the respondents (79.0%) thought that discussing sexual health problems could help patients cope with their rheumatologic diseases. Of all respondents, 74.2% felt the need to broaden their personal knowledge about SD. Finally, 45.9% and 34.4% of respondents respectively partially and totally agreed that training courses for rheumatologists could be helpful in the management of sexual health in rheumatological patients. CONCLUSIONS: SD was not routinely discussed in rheumatology practice, still remaining a neglected issue. The most frequent explanations for the lack of attention toward SD were lack of time, patients' discomfort, and lack of knowledge/experience. Most of the respondents expressed the possible usefulness of attending SD courses to improve knowledge about these conditions.


Assuntos
Artrite Reumatoide , Doenças Reumáticas , Reumatologia , Disfunções Sexuais Fisiológicas , Humanos , Reumatologia/métodos , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Inquéritos e Questionários , Doenças Reumáticas/complicações
11.
Artigo em Inglês | MEDLINE | ID: mdl-37244971

RESUMO

BACKGROUND: Outcomes of radical prostatectomy (RP) in men with history of lower urinary tract symptoms related to benign prostatic enlargement (LUTS/BPE) surgery represents a controversial issue. We performed an updated systematic review and meta- analysis evaluating oncological and functional outcomes of RP in this subset of patients. METHODS: Eligible studies were identified from MEDLINE, Web of Science and the Scopus databases. The following outcomes were evaluated: incidence of positive surgical margins (PSM), incidence of biochemical recurrence (BCR), 3-mo and 1-year urinary continence (UC) rates, incidence of nerve-sparing (NS) procedures, 1-year erectile function (EF) recovery rates. We estimated pooled Odds ratios (OR) and 95% confidence intervals (CI) using random effects models. Sub-analyses were performed according to the type of RP and LUTS/BPE surgery. RESULTS: Twenty-five retrospective studies including 11,101 patients undergoing RP were included in the analysis (2113 with history of LUTS/BPE surgery, and 8898 controls). PSM rate was significantly higher in patients with history of LUTS/BPE surgery (OR 1.39, 95% CI 1.18-1.63, p < 0.001). No statistically significant difference in terms of BCR emerged between patients with or without history of LUTS/BPE surgery (OR 1.46, 95% CI 0.97-2.18, p = 0.066). Three-months and 1-year UC rates were significantly lower in patients with previous LUTS/BPE surgery (OR 0.48, 95% CI 0.34-0.68, p < 0.001 and OR 0.44, 95% CI 0.31-0.62, p < 0.001; respectively). Although not statistically significant differences between the two groups emerged in terms of adoption of NS procedures (OR 0.59, 95% CI 0.32-1.12, p = 0.107), 1-year EF recovery was significantly lower in patients with history of LUTS/BPE procedures (OR 0.60, 95% CI 0.40-0.89, p = 0.010). CONCLUSIONS: In conclusions, RP in patients with history of previous LUTS/BPE surgery is associated with increased incidence of PSM, lower UC rates at both 3-months and 1-year follow-up as well as lower rates of EF recovery at 1-year follow-up.

12.
Diagnostics (Basel) ; 13(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37238229

RESUMO

Bladder cancer (BC) is the tenth most common cancer, with urothelial carcinoma representing about 90% of all BC, including neoplasms and carcinomas of different grades of malignancy. Urinary cytology has a significant role in BC screening and surveillance, although it has a low detection rate and high dependence on the pathologist's experience. The currently available biomarkers are not implemented into routine clinical practice due to high costs or low sensitivity. In recent years, the role of lncRNAs in BC has emerged, even though it is still poorly explored. We have previously shown that the lncRNAs Metallophosphoesterase Domain-Containing 2 Antisense RNA 1 (MPPED2-AS1), Rhabdomyosarcoma-2 Associated Transcript (RMST), Kelch-like protein 14 antisense (Klhl14AS) and Prader Willi/Angelman region RNA 5 (PAR5) are involved in the progression of different types of cancers. Here, we investigated the expression of these molecules in BC, first by interrogating the GEPIA database and observing a different distribution of expression levels between normal and cancer specimens. We then measured them in a cohort of neoplastic bladder lesions, either benign or malignant, from patients with suspicion of BC undergoing transurethral resection of bladder tumor (TURBT). The total RNA from biopsies was analyzed using qRT-PCR for the expression of the four lncRNA genes, showing differential expression of the investigated lncRNAs between normal tissue, benign lesions and cancers. In conclusion, the data reported here highlight the involvement of novel lncRNAs in BC development, whose altered expression could potentially affect the regulatory circuits in which these molecules are involved. Our study paves the way for testing lncRNA genes as markers for BC diagnosis and/or follow-up.

13.
J Exp Clin Cancer Res ; 42(1): 134, 2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37231503

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. Large-scale metabolomic data have associated metabolic alterations with the pathogenesis and progression of renal carcinoma and have correlated mitochondrial activity with poor survival in a subset of patients. The aim of this study was to determine whether targeting mitochondria-lysosome interaction could be a novel therapeutic approach using patient-derived organoids as avatar for drug response. METHODS: RNAseq data analysis and immunohistochemistry were used to show overexpression of Purinergic receptor 4 (P2XR4) in clear cell carcinomas. Seahorse experiments, immunofluorescence and fluorescence cell sorting were used to demonstrate that P2XR4 regulates mitochondrial activity and the balance of radical oxygen species. Pharmacological inhibitors and genetic silencing promoted lysosomal damage, calcium overload in mitochondria and cell death via both necrosis and apoptosis. Finally, we established patient-derived organoids and murine xenograft models to investigate the antitumor effect of P2XR4 inhibition using imaging drug screening, viability assay and immunohistochemistry. RESULTS: Our data suggest that oxo-phosphorylation is the main source of tumor-derived ATP in a subset of ccRCC cells expressing P2XR4, which exerts a critical impact on tumor energy metabolism and mitochondrial activity. Prolonged mitochondrial failure induced by pharmacological inhibition or P2XR4 silencing was associated with increased oxygen radical species, changes in mitochondrial permeability (i.e., opening of the transition pore complex, dissipation of membrane potential, and calcium overload). Interestingly, higher mitochondrial activity in patient derived organoids was associated with greater sensitivity to P2XR4 inhibition and tumor reduction in a xenograft model. CONCLUSION: Overall, our results suggest that the perturbed balance between lysosomal integrity and mitochondrial activity induced by P2XR4 inhibition may represent a new therapeutic strategy for a subset of patients with renal carcinoma and that individualized organoids may be help to predict drug efficacy.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Animais , Camundongos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Receptores Purinérgicos P2X4/metabolismo , Cálcio/metabolismo , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Mitocôndrias/metabolismo , Linhagem Celular Tumoral
14.
Medicina (Kaunas) ; 59(4)2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37109725

RESUMO

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Sunitinibe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/cirurgia , Estudos Prospectivos , Procedimentos Cirúrgicos de Citorredução , Nefrectomia , Estudos Retrospectivos
15.
Arch Ital Urol Androl ; 95(1): 11076, 2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36924375

RESUMO

INTRODUCTION: Mobile health applications (MHAs) represent an interesting issue to assist and improve the quality of life of patients affected by Kidney Stone Disease (KSD). Despite this, their scientific quality and adherence to guidelines are not yet addressed. MATERIAL AND METHODS: On 2 November 2022, we conducted an observational cross-sectional descriptive study of all MHAs on KSD. A search in the Apple App Store and Google Play Store was performed. We reviewed all mobile apps from Apple App Store and Google Play Store for KSD and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. RESULTS: In total 13 MHA were included in the final analysis. All MHAs, 4 (30.8%) from the Apple App Store and 9 (69.2%) from the Google Play Store are geared towards the patient. Engagement ranged from 1.73 to 4.06; Functionality ranged from 3.17 to 4.75; Aesthetics ranged from 1.9 to 4.12; Information ranged from 2.25 to 4.27, and Subjective quality ranged from 1.58 to 3.23. MHAs reported low and medium adherence to EAU guidelines. CONCLUSIONS: MHAs provide a very useful assistance in several medical fields, including KSD. Despite MHAs development is constantly increasing, the scientific validation, content, and quality are not yet solved. Future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.


Assuntos
Cálculos Renais , Aplicativos Móveis , Telemedicina , Humanos , Estudos Transversais , Cálculos Renais/terapia , Qualidade de Vida
16.
Int J Impot Res ; 2023 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-36788352

RESUMO

The aim of this paper was to describe the long-term outcomes of extracorporeal shock wave therapy (ESWT) in patients with acute Peyronie'disease (PD). An observational retrospective study was conducted in men with acute PD who underwent ESWT between 2009-2013 at a single institution. ESWT protocol consisted of 1 session (3000 shock waves, 0.10-0.25 mJ/mm^2, 4-6 Hz) per week for 4 weeks. Penile pain was chosen as the primary outcome. Penile curvature angle, erectile function, and satisfaction with ESWT were selected as secondary long-term outcomes. A total of 194 patients were included. The mean follow-up duration after ESWT was 125.6 months. Mean penile curvature worsened significantly at 3 months (18.3 vs. 21.5 degrees; p = 0.023) and 12 months (21.5 vs. 28.6 degrees; p = 0.001) and stabilized over the long-term (28.6 vs. 28.8 degrees; p = 0.335). Mean penile pain improved significantly at 3 months (6.5 vs. 3.1 points; p < 0.001) and 12 months (3.1 vs. 1.0 points; p = 0.001), remaining stable over time (1.0 vs. 1.0 points; p = 0.074). The mean five-item version of the International Index of Erectile Function (IIEF-5) increased significantly at 3 months (14.5 vs. 17.9 points; p = 0.001), remaining stable at 12 months (17.9 vs. 18.5 points; p = 0.082), and deteriorating in the long-term (18.5 vs. 15.8 points; p = 0.003). A high satisfaction rate with ESWT was recorded at 3 months (92.3%), remaining similar at 12 months (91.2%) and over the long-term (90.2%). No new acute phase and low rate of PD surgery (4.1%) were recorded in the long-term analysis. In patients with acute PD, ESWT seems to be associated with early and persistent relief of penile pain, transient improvement in erectile function, no significant effect on penile curvature, and a high rate of patient satisfaction constant over time.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36767978

RESUMO

The aim of this study was to evaluate the ability of Google Assistant, Alexa, and Siri to recognize and answer questions about male sexual health. Each VA was tested on a smart speaker: Alexa on Amazon Echo Dot 4th Gen., Google Assistant on Google Home Mini, and Siri on Apple HomePod. A pool of patients' frequently asked questions regarding erectile dysfunction (ED), premature ejaculation (PE), Peyronie's disease (PD), male infertility, and other aspects of male sexual health were identified by authors. The recognition of question was evaluated ("yes" or "not"). For each recognized question, the response characteristics (domains) were rated on a scale from 0 to 10 (according to the quality). We chose the recognition rate of the questions as the primary outcome and the quality of the answers as the secondary outcome. Overall, the best VA in recognizing questions was Siri, with a total of 83.3% questions compared with 64.0% for Alexa (p = 0.024) and 74.0% for Google Assistant (p = 0.061). Siri was associated with a significantly higher recognition rate than Alexa for PE (80% vs. 40%; p = 0.002) and PD (66.7% vs. 33.3%; p = 0.010). The quality of the responses was classified as low in 57 out of 105 cases (54.3%), intermediate in 46 cases (43.8%), and high in only 2 cases (1.9%), highlighting an overall intermediate-low quality of the answers. Male infertility was the condition associated with the highest mean scores in "Targeted response to the problem" (7.32 ± 2.57), "Scientific correctness of the answer", (5.9 ± 2.76) "Completeness of the answer" (5.14 ± 2.56), and "Understandability of the response for a patient" (5.3 ± 2.51) domains. Siri was associated with significantly higher scores than Alexa (p < 0.05) in several domains of all conditions evaluated. The question recognition rate of VAs is quite high; however, the quality of the answers is still intermediate-low. Siri seems superior to Alexa in both question recognition and response quality. Male infertility appears to be the sexual dysfunction best addressed by VAs.


Assuntos
Disfunção Erétil , Infertilidade Masculina , Saúde Sexual , Voz , Humanos , Masculino , Consultores
19.
J Basic Clin Physiol Pharmacol ; 34(1): 49-54, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35390245

RESUMO

OBJECTIVES: Stress urinary incontinence is defined by a complaint of any involuntary loss of urine on effort or physical exertion or on sneezing or coughing and represents a major complication after radical prostatectomy. According to surgical technique, incidence of post-prostatectomy incontinence varies from open (7-39.5%), laparoscopic (5-33.3%) or robotic-assisted (4-31%) approaches. The ProACT® device (Uromedica, Inc., MN) is a possible surgical option for the treatment of this condition. METHODS: We retrospectively analyzed surgical records of consecutive patients underwent ProACT® implantation in our department between January 2006 to November 2010. We collected data at 6 and 12 months after surgical approach about the daily pad use, International Prostatic Symptoms Score and its quality of life domain. RESULTS: 42 patients were included in the final analysis. Most patients (92.9%) received minimally invasive surgery for treating prostate cancer. During the follow up after 6 and 12 months, the daily pad, International Prostatic Symptom Score and its quality of life domain significantly improved compared to preoperative outcomes. The logistic regression analysis found that presence of comorbidities was the only predictive factor of low satisfaction rate (PGE-I > 2) in patients who underwent ProACT® implant. CONCLUSIONS: ProACT® implant represents an effective and safe treatment for post-prostatectomy stress urinary incontinence with a high satisfaction degree and a low rate of complications.


Assuntos
Neoplasias da Próstata , Incontinência Urinária por Estresse , Masculino , Humanos , Incontinência Urinária por Estresse/etiologia , Incontinência Urinária por Estresse/cirurgia , Seguimentos , Qualidade de Vida , Estudos Retrospectivos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/complicações , Resultado do Tratamento
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