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OBJECTIVE: The American Medical Association recommends health information to be written at a 6th grade level reading level. Our aim was to determine whether Artificial Intelligence can outperform the existing health information on kidney stone prevention and treatment. METHODS: The top 50 search results for "Kidney Stone Prevention" and "Kidney Stone Treatment" on Google, Bing, and Yahoo were selected. Duplicate webpages, advertisements, pages intended for health professionals such as science articles, links to videos, paid subscription pages, and links nonrelated to kidney stone prevention and/or treatment were excluded. Included pages were categorized into academic, hospital-affiliated, commercial, nonprofit foundations, and other. Quality and readability of webpages were evaluated using validated tools, and the reading level was descriptively compared with ChatGPT generated health information on kidney stone prevention and treatment. RESULTS: 50 webpages on kidney stone prevention and 49 on stone treatment were included in this study. The reading level was determined to equate to that of a 10th to 12th grade student. Quality was measured as "fair" with no pages scoring "excellent" and only 20% receiving a "good" quality. There was no significant difference between pages from academic, hospital-affiliated, commercial, and nonprofit foundation publications. The text generated by ChatGPT was considerably easier to understand with readability levels measured as low as 5th grade. CONCLUSIONS: The language used in existing information on kidney stone disease is of subpar quality and too complex to understand. Machine learning tools could aid in generating information that is comprehensible by the public.
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Inteligência Artificial , Cálculos Renais , Estados Unidos , Humanos , Compreensão , Cálculos Renais/prevenção & controle , InternetRESUMO
PURPOSE: Pain is the leading cause of unplanned emergency department visits and readmissions after ureteroscopy, making postoperative analgesic stewardship a priority given the current opioid epidemic. We conducted a double-blinded, randomized controlled trial, with noninferiority design, comparing nonsteroidal anti-inflammatory drugs to opiates for postoperative pain control in patients undergoing ureteroscopy for urolithiasis. MATERIALS AND METHODS: Patients were randomized and blinded to either oxycodone (5 mg) or ketorolac (10 mg), taken as needed, with 3 nonblinded oxycodone rescue pills for breakthrough pain. Primary study outcome was visual analogue scale pain score on postoperative days 1-5. Secondary outcomes included medication utilization, side effects, and Ureteral Stent Symptom Questionnaire scores. RESULTS: A total of 81 patients were included (43 oxycodone, 38 ketorolac). The 2 groups had comparable patient, stone, and perioperative characteristics. No differences were found in postoperative pain scores, study medication or rescue pill usage, or side effects. Higher maximum pain scores on days 1-5 (p <0.05) and higher questionnaire score (28.1 vs 21.7, p=0.045) correlated with analgesic usage, irrespective of treatment group. Patients receiving ketorolac reported significantly fewer days confined to bed (mean±SD 1.3±1.3 vs 2.3±2.6, p=0.02). There was no difference in unscheduled postoperative physician encounters. CONCLUSIONS: This is the first double-blinded randomized controlled trial comparing nonsteroidal anti-inflammatory drugs and opiates post-ureteroscopy, and demonstrates noninferiority of nonsteroidal anti-inflammatory drugs in pain control with similar efficacy, safety profile, physician contact and notably, earlier convalescence compared to the opioid group. This provides strong evidence against routine opioid use post-ureteroscopy, justifying continued investigation into reducing postoperative opiate prescriptions.
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Analgésicos Opioides/uso terapêutico , Cetorolaco/uso terapêutico , Dor Pós-Operatória/prevenção & controle , Ureteroscopia , Anti-Inflamatórios não Esteroides/uso terapêutico , Convalescença , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxicodona/uso terapêutico , Estudos Prospectivos , Escala Visual AnalógicaRESUMO
PURPOSE: Electronic patient portals can be beneficial in providing direct engagement and clarity to avoid unnecessary extra provider encounters. In this study we assessed whether portal usage among endourology patients affected telephone call frequency, unscheduled physician visits, emergency department presentations and complication rates. MATERIALS AND METHODS: We conducted a retrospective chart review of patients undergoing elective endourology procedures by a single surgeon at a tertiary urology center from July 2017 to July 2018. Patient demographics, operative details, patient portal (MyChart) registration, patient initiated MyChart messages, telephone encounters, unscheduled physician visits and emergency department presentations during a 1-month period before and after the procedure were identified. Logistic regression analysis assessed relationships between MyChart use and study outcomes. RESULTS: We identified 313 patients (200 MyChart users, 113 nonusers) who underwent 374 procedures. MyChart users were younger (age 56 vs 61, p=0.0011) and more likely to be married (69.5% vs 48.7%, p=0.0004). MyChart users made fewer telephone calls before (1.1 vs 1.2, p=0.005) and after procedure (0.9 vs 1.3, p=0.029), and had fewer emergency department visits (8 vs 18, p=0.0005) than nonusers. On multivariable analysis MyChart nonusers were 4.55 (95% CI 1.92-11.11) times more likely to have an unscheduled clinic visit (p=0.0006), 1.92 (95% CI 1.075-3.333) times more likely to have an emergency department visit (p=0.028) and 2.7 (95% CI 1.43-5.26) times more likely to have a postoperative complication (p=0.0026). CONCLUSIONS: Patients undergoing endourology procedures who use MyChart make fewer telephone calls and are significantly less likely to have an unscheduled clinic/emergency department visit or a complication.
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Portais do Paciente , Doenças Urológicas/cirurgia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portais do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Most biomarkers in prostate cancer have only been evaluated in surgical cohorts. The value of these biomarkers in a different therapy context remains unclear. Our objective was to test a panel of surgical biomarkers for prognostic value in men treated by external beam radiotherapy (EBRT) and primary androgen deprivation therapy (PADT). METHODS: The Fluidigm® PCR array was used for multi-transcript profiling of laser microdissected tumours from archival formalin-fixed diagnostic biopsies of patients treated by EBRT or PADT. Cases were matched for disease characteristics and had known 5 year biochemical relapse outcomes (n = 60). Results were validated by immunohistochemistry in a custom needle biopsy tissue microarray. Six biomarkers previously tested only in surgical cohorts were analysed (PTEN, E-Cadherin, EGFR, EZH2, PSMA, MSMB). Transcript and protein expression was correlated with clinical outcome analysed using Kruskal Wallis, Fisher's test and Cox proportional hazard model. RESULTS: Altered expression of E-Cadherin (p = 0.008) was associated with early relapse after EBRT. In PADT treated men however only altered MSMB transcript was prognostic for early relapse (p = 0.001). The remaining biomarkers however did not demonstrate prognostic ability in either cohort. In a separate tissue array we validated altered E-Cadherin protein as a predictor of early relapse after EBRT (n = 47) (HR 0.34, CI p = 0.02) but not in PADT treated men (n = 63). CONCLUSION: We demonstrate proof of principle of multiple transcript profiling in archival diagnostic biopsies of non-surgically treated men for biomarker discovery. We identify a role for E-Cadherin as a novel biomarker of early relapse following EBRT.
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Perfilação da Expressão Gênica , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Idoso , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Biomarcadores , Biópsia por Agulha , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias da Próstata/terapia , Terapia com Prótons , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Objective: National guidelines recommend periprocedural antibiotics before percutaneous nephrolithotomy (PCNL), yet it is not clear which is superior. We conducted a randomized trial to compare two guideline-recommended antibiotics: ciprofloxacin (cipro) vs cefazolin, on PCNL outcomes, focusing on the development of systemic inflammatory response syndrome (SIRS) criteria. Methods: Adult patients who were not considered high risk for surgical or infectious complications and undergoing PCNL were randomized to receive either cipro or cefazolin perioperatively. All had negative preoperative urine cultures. Demographic and perioperative data were collected, including SIRS criteria, intraoperative urine culture, duration of hospitalization, and need for intensive care. SIRS is defined by ≥2 of the following: body temperature <96.8°F or >100.4°F, heart rate >90 bpm, respiratory rate >20 per minute, and white blood cell count <4000 or >12,000 cells/mm3. Results: One hundred forty-seven patients were enrolled and randomized (79 cefazolin and 68 cipro). All preoperative characteristics were similar (p > 0.05), except for mean age, which was higher in the cipro group (64 vs 57 years, p = 0.03). Intra- and postoperative findings were similar, with no difference between groups (p > 0.05), except a longer mean hospital stay in the cefazolin group (2 hours longer, p = 0.02). There was no difference between SIRS episodes in both univariate and multivariate analyses. Conclusions: Despite the relatively broader coverage for urinary tract pathogens with ciprofloxacin, this prospective randomized trial did not show superiority over cefazolin. Our findings therefore support two appropriate options for perioperative antibiotic prophylaxis in patients undergoing PCNL who are nonhigh risk for infectious complications.
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Antibacterianos , Cálculos Renais , Nefrolitotomia Percutânea , Complicações Pós-Operatórias , Adulto , Humanos , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Cefazolina/uso terapêutico , Ciprofloxacina/uso terapêutico , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos Prospectivos , Método Simples-Cego , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Síndrome de Resposta Inflamatória Sistêmica/etiologiaRESUMO
Introduction: Ureteral stents can cause significant patient discomfort, yet the temporal dynamics and impact on activities remain poorly characterized. We employed an automated tool to collect daily ecological momentary assessments (EMAs) regarding pain and the ability to work following ureteroscopy with stenting. Our aims were to assess feasibility and better characterize the postoperative patient experience. Materials and Methods: As an exploratory endpoint within an ongoing clinical trial, patients undergoing ureteroscopy with stenting were asked to complete daily EMAs for 10 days postoperatively or until the stent was removed. Questionnaires were distributed through text messages and included a pain scale (0-10) and a single item from the validated Patient-Reported Outcomes Measurement Information System Ability to Participate in Social Roles and Activities instrument, as well as days missed from work or school. Results: Among the first 65 trial participants, 59 completed at least 1 EMA (overall response rate 91%). Response rates were >85% for each time point through postoperative day (POD)10. Median respondent age was 58 years (interquartile range [IQR] 50-67), and 56% were female. Stones were 54% renal and 46% ureteral, with a median diameter of 9 mm (IQR 7-10). Median stent dwell time was 7 days (IQR 6-8). Pain scores were highest on POD1 (median score 4) and declined on each subsequent day, reaching a median score of 2 on POD5. Sixty-three percent of patients on POD1 reported that they had trouble performing their usual work at least sometimes, but by POD5, this was <50% of patients. Patients who work or attend school reported a median of 1 day missed (IQR 0-2). Conclusions: An automated daily EMA system for capturing patient-reported outcomes was demonstrated to be feasible with sustained excellent engagement. Patients with stents reported the worst pain and interference with work on POD1, with steady improvements thereafter, and by POD5, the majority of patients had minimal pain or trouble performing their usual work. This work is associated with a registered clinical trial [NCT05026710].
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Avaliação Momentânea Ecológica , Dor Pós-Operatória , Stents , Ureteroscopia , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Ureteroscopia/métodos , Idoso , Dor Pós-Operatória/etiologia , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Cannabis use is increasing across the United States, yet its short- and long-term effects on sexual function remain controversial. Currently, there is a paucity of studies exploring the relationship between cannabis and men's health. OBJECTIVES: To summarize the available literature on cannabis and men's health and provide insight into lay perceptions of this topic. METHODS: We performed a qualitative PubMed review of the existing literature on cannabis and men's health according to the PRISMA guidelines. Separately, we analyzed relevant themes in online men's health forums. We utilized a Google cloud-based platform (BigQuery) to extract relevant posts from 5 men's health Reddit forums from August 2018 to August 2019. We conducted a qualitative thematic analysis of the posts and quantitatively analyzed them using natural language processing and a meaning extraction method with principal component analysis. RESULTS: Our literature review revealed a mix of animal and human studies demonstrating the negative effects of cannabis on semen parameters and varying effects on erectile function and hormone levels. In our analysis of 372 686 Reddit posts, 1190 (0.3%) included relevant discussion on cannabis and men's health. An overall 272 posts were manually analyzed, showing that online discussions revolve around seeking answers and sharing the effects of cannabis on various aspects of sexual health and quality of life, often with conflicting experiences. Quantitative analysis revealed 1 thematic cluster related to cannabis, insecurity, and mental/physical health. CONCLUSIONS: There is a limited number of quality human studies investigating the effects of cannabis on men's health. Men online are uncertain about how cannabis affects their sexual health and seek more information. As the prevalence of cannabis use increases, so does the need for research in this area.
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Cannabis , Saúde Sexual , Humanos , Masculino , Estados Unidos , Cannabis/efeitos adversos , Qualidade de Vida , Saúde do Homem , InternetRESUMO
INTRODUCTION: Despite AUA guidelines providing criteria for ureteral stent omission after ureteroscopy for nephrolithiasis, stenting rates in practice remain high. Because pre-stenting may be associated with improved patient outcomes, we assessed the impact of stent omission vs placement in pre-stented and non-pre-stented patients undergoing ureteroscopy on postoperative health care utilization in Michigan. METHODS: Using the MUSIC (Michigan Urological Surgery Improvement Collaborative) registry (2016-2019), we identified pre-stented and non-pre-stented patients with low comorbidity undergoing single-stage ureteroscopy for ≤1.5 cm stones with no intraoperative complications. We assessed variation in stent omission for practices/urologists with ≥5 cases. Using multivariable logistic regression, we evaluated whether stent placement in pre-stented patients was associated with emergency department visits and hospitalizations within 30 days of ureteroscopy. RESULTS: We identified 6,266 ureteroscopies from 33 practices and 209 urologists, of which 2,244 (35.8%) were pre-stented. Pre-stented cases had higher rates of stent omission vs non-pre-stented cases (47.3% vs 26.3%). Among the 17 urology practices with ≥5 cases, stent omission rates in pre-stented patients varied widely (0%-77.8%). Among the 156 urologists with ≥5 cases, stent omission rates in pre-stented patients varied substantially (0%-100%); 34/152 (22.4%) never performed stent omission. Adjusting for risk factors, stent placement in pre-stented patients was associated with increased emergency department visits (OR 2.24, 95% CI:1.42-3.55) and hospitalizations (OR 2.19, 95% CI:1.12-4.26). CONCLUSIONS: Pre-stented patients undergoing stent omission after ureteroscopy have lower unplanned health care utilization. Stent omission is underutilized in these patients, making them an ideal group for quality improvement efforts to avoid routine stent placement after ureteroscopy.
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Cálculos Renais , Ureter , Humanos , Ureteroscopia/efeitos adversos , Ureter/cirurgia , Cálculos Renais/etiologia , Aceitação pelo Paciente de Cuidados de Saúde , Stents/efeitos adversosRESUMO
Fictional portrayals of medical conditions on television have been shown to significantly shape understanding and management expectations of the viewing public. Given the high prevalence of kidney stone disease, we aimed to assess the frequency of its portrayal on US television and assess whether its depiction was reflective of the current epidemiology or management of urolithiasis in the US. A detailed search was conducted for English language depictions of kidney stones in fictional television using internet, movie and television database search engines. Television episodes with characters depicting a kidney stone occurrence were independently reviewed by two reviewers and analyzed for genre, initial air date on US television, character age, gender, race and management strategy. Seventeen episodes from 13 different television series portrayed a character with a symptomatic kidney stone. The majority were male (88%). Surgical intervention was performed in 7/17 cases (shockwave lithotripsy n = 1, ureteroscopy n = 2, nephrectomy n = 1, transurethral removal n = 1, unknown n = 2), spontaneous passage or medical expulsive therapy in 7/17 cases and no treatment or resolution portrayed in 3/17 cases. The only surgical complication shown was ureteral avulsion during ureteroscopy. Inpatient management was seen in 9/14 (64%) cases with event resolution. This study identified a number of kidney stone depictions that may be misleading or misrepresent the presentation and management of this condition. Although likely portrayed for plot development and dramatic effect, this could potentially reinforce inaccurate beliefs or misconceptions and future depictions should be mindful of this.
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Cálculos Renais , Litotripsia , Feminino , Humanos , Cálculos Renais/etiologia , Cálculos Renais/terapia , Masculino , Filmes Cinematográficos , Televisão , UreteroscopiaRESUMO
Individuals with urinary stone disease (USD) exhibit dysbiosis in the urinary tract and the loss of Lactobacillus that promote urinary tract health. However, the microbial metabolic functions that differentiate individuals with USD from healthy individuals are unknown. The objective of the current study was to determine the microbial functions across prokaryotic, viral, fungal, and protozoan domains that are associated with calcium oxalate (CaOx) stone formers through comparative shotgun metagenomics of midstream, voided urine samples for a small number of patients (n = 5 CaOx stone formers, n = 5 healthy controls). Results revealed that CaOx stone formers had reduced levels of genes associated with oxalate metabolism, as well as transmembrane transport, proteolysis, and oxidation-reduction processes. From 17 draft genomes extracted from the data and > 42,000 full length reference genomes, genes enriched in the Control group mapped overwhelming to Lactobacillus crispatus and those associated with CaOx mapped to Pseudomonas aeruginosa and Burkholderia sp. The microbial functions that differentiated the clinical cohorts are associated with known mechanisms of stone formation. While the prokaryotes most differentiated the CaOx and Control groups, a diverse, trans-domain microbiome was apparent. While our sample numbers were small, results corroborate previous studies and suggest specific microbial metabolic pathways in the urinary tract that modulate stone formation. Future studies that target these metabolic pathways as well as the influence of viruses, fungi, and protozoa on urinary tract physiology is warranted.
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Cálculos Renais , Microbiota , Cálculos Urinários , Sistema Urinário , Urolitíase , Cálcio/urina , Oxalato de Cálcio/metabolismo , Feminino , Humanos , Masculino , Cálculos Urinários/urina , Sistema Urinário/química , Sistema Urinário/metabolismo , Urolitíase/urinaRESUMO
OBJECTIVE: To assess the effects of different surgeon positions and ureteroscope types on muscle activation as measured by surface electromyography (sEMG) during simulated ureteroscopy in an endourology box-trainer model and the kidney phantom. METHODS: For this exploratory study, sEMG was used to quantify muscle activation of 3 endourology fellows during various ureteroscopic tasks. Electrodes were placed on the ureteroscope-holding side of the following muscles: thenar, forearm flexor, forearm extensor, biceps, triceps, deltoid, and trapezius. Subjects wore fitted lead aprons in an operating room and used a cystoscopy table with surgical drapes and an endoscopic video tower. Trials were completed with a disposable and reusable ureteroscope, both in the standing and sitting positions. Each subject performed an identical set of tasks in a phantom silicone kidney and ureteroscopy box trainer to recreate the procedural components of basketing, navigating a renal collecting system, and dusting. Raw EMG data for each task was processed and normalized as a percent of each subject's maximum voluntary contraction to allow comparison. RESULTS: The forearm extensor was the most heavily utilized muscle. The trapezius and deltoid muscles were activated more during sitting whereas the forearm flexors had increased activity during standing. The heavier reusable ureteroscope had increased forearm extensor activation compared to the disposable ureteroscope. CONCLUSION: Preliminary data show measurable differences in muscle activation based on both surgical posture and type of ureteroscope used. This highlights the need for more extensive EMG studies to identify techniques and equipment to optimize ergonomics and potentially minimize injury during flexible ureteroscopy.
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Ureteroscópios , Ureteroscopia , Humanos , Projetos Piloto , Ergonomia , Eletromiografia , Músculo EsqueléticoRESUMO
BACKGROUND: The existing treatment options for men with intermediate- or high-volume low-risk prostate cancer (PCa) are associated with a substantial risk of over- or undertreatment. The development of risk-adjusted therapies is an unmet need for these patients. OBJECTIVE: To describe our novel technique of precision prostatectomy, a form of surgical focal therapy that allows radical excision of the index PCa lesion along with >90% prostatic tissue extirpation while preserving the prostatic capsule and seminal vesicle/vas deferens complex on the side contralateral to the dominant cancer lesion, and to report on medium-term functional and oncologic outcomes in the first 88 consecutive men who underwent this procedure between December 2016 and January 2020. DESIGN, SETTING, AND PARTICIPANTS: Men with (1) prostate-specific antigen (PSA) ≤20 ng/ml, (2) clinical T stage ≤cT2, (3) a dominant unilateral lesion with Gleason ≤ 4 + 3 disease with any number or percentage of cores involved ipsilaterally on prostate biopsy, (4) no primary Gleason ≥4 lesion contralaterally, and (5) a preoperative Sexual Health Inventory of Men (SHIM) score of ≥17 (out of 25) with/without phosphodiesterase type-5 inhibitor use who consented to undergo precision prostatectomy were included in this single-arm, single-center, IDEAL stage 2b prospective development study. INTERVENTION: Robotic precision prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The safety and urinary, sexual, and oncologic outcomes of the precision prostatectomy technique were studied. Descriptive statistics and Kaplan-Meier analyses were used to assess 12-mo urinary continence (0-1 pad), 12-mo sexual potency (SHIM score ≥17), 36-mo freedom from clinically significant PCa (grade group ≥2), secondary treatments, metastatic disease, and mortality. RESULTS AND LIMITATIONS: At study entry, the median age, PSA, and SHIM score were 60.0 yr (interquartile range [IQR] 54.2-65.9), 5.7 ng/ml (IQR 4.2-7.1), and 22 points (IQR 19-24), respectively. The median follow-up was 25 mo (IQR 14-38). At 12 mo, all patients were continent (0-1 pads), with 90.9% of patients using 0 pads. The median time to urinary continence was 1 mo (IQR 1-4). At 12 mo, 85% of all-comers and 90.2% of the preoperatively potent men were potent. The median time to sexual potency was 4 mo (IQR 4-12). From an oncologic standpoint, at 36 mo an estimated 93.4% of the patients were free from clinically significant residual PCa and 91.7% had not undergone any additional treatment. All patients were alive and free of metastatic disease at 36 mo. CONCLUSIONS: Precision prostatectomy is technically safe and reproducible and offers excellent postoperative functional results. At 36-mo follow-up, the oncologic outcomes and secondary treatment rates appear to be superior to existing ablative focal therapy results. Pending long-term data, a risk-stratified surgical approach to PCa may avoid whole-gland therapy and preserve functional quality of life in men with localized PCa. PATIENT SUMMARY: Precision prostatectomy is a new form of focal therapy for intermediate-risk prostate cancer in which a 5-10-mm rim of prostate capsule is left on the opposite side of the gland to where the dominant cancer is located. The technique appears to be safe and efficacious and adds to the growing armamentarium of risk-adapted therapies for treatment of localized prostate cancer that avoid the adverse effects on urinary and erectile function of whole-gland treatments.
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Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Estudos Prospectivos , Antígeno Prostático Específico/análise , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Neoplasias da Próstata/patologia , Qualidade de Vida , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: FGF receptor substrates (FRS2 and FRS3) are key adaptor proteins that mediate FGF-FGFR signalling in benign as well as malignant tissue. Here we investigated FRS2 and FRS3 as a means of disrupting global FGF signalling in prostate cancer. METHODS: FRS2 and FRS3 manipulation was investigated in vitro using over-expression, knockdown and functional assays. FRS2 and FRS3 expression was profiled in cell lines and clinical tumors of different grades. RESULTS: In a panel of cell lines we observed ubiquitous FRS2 and FRS3 transcript and protein expression in both benign and malignant cells. We next tested functional redundancy of FRS2 and FRS3 in prostate cancer cells. In DU145 cells, specific FRS2 suppression inhibited FGF induced signalling. This effect was not apparent in cells stably over-expressing FRS3. Indeed FRS3 over-expression resulted in enhanced proliferation (p = 0.005) compared to control cells. Given this functional redundancy, we tested the therapeutic principle of dual targeting of FRS2 and FRS3 in prostate cancer. Co-suppression of FRS2 and FRS3 significantly inhibited ERK activation with a concomitant reduction in cell proliferation (p < 0.05), migration and invasion (p < 0.05). Synchronous knockdown of FRS2 and FRS3 with exposure to cytotoxic irradiation resulted in a significant reduction in prostate cancer cell survival compared to irradiation alone (p < 0.05). Importantly, this synergistic effect was not observed in benign cells. Finally, we investigated expression of FRS2 and FRS3 transcript in a cohort of micro-dissected tumors of different grades as well as by immunohistochemistry in clinical biopsies. Here, we did not observe any difference in expression between benign and malignant biopsies. CONCLUSIONS: These results suggest functional overlap of FRS2 and FRS3 in mediating mitogenic FGF signalling in the prostate. FRS2 and FRS3 are not over-expressed in tumours but targeted dual inhibition may selectively adversely affect malignant but not benign prostate cells.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células , Sobrevivência Celular/efeitos da radiação , Estudos de Coortes , Inativação Gênica , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana/genética , Proteínas de Neoplasias/genética , Neoplasias da Próstata/genéticaRESUMO
Introduction: A number of clinical and radiological predictors of either stone impaction or ureteral stone passage (SP) have been proposed. We aimed at identifying the key predictors of successful SP by using readily available CT-based tools/measurements. Methods: Patients presenting to the emergency department from February 2017 to February 2018 with an acute unilateral ureteral stone confirmed on non-contrast CT and managed conservatively were followed for SP. Patients with renal impairment, sepsis or requiring emergent intervention were excluded. Patients were followed at 1 month to confirm SP (stone collection/repeat imaging) or failure of passage. The CT variables analyzed included: Stone factors [location, size, volume, HU density (HUD)], impaction factors [ureteral HUD above and below the stone, maximal ureteral wall thickness (UWT) at the stone site, contralateral UWT, and ureteral diameter above and below the stone]. Binary logistic regression analysis was performed to identify predictors of SP. Results: Forty-nine patients met study inclusion criteria, of whom 32 (65.3%) passed the stone without further intervention. Patients with successful passage were more likely to have smaller, lower volume and less dense stones located in the distal ureter (p < 0.01). Lower ureteral HUD below the stone, lower maximal UWT, and lower ureteral diameter above the stone were associated with successful passage (p < 0.01). On multivariable logistic regression analysis, only maximal UWT at the stone site was a significant independent predictor of SP outcome (p = 0.01). Youden's criterion identified 2.3 mm as the optimal UWT cut-off point, which will accurately predict SP with 82.4% sensitivity and 87.5% specificity. Conclusions: Maximal UWT at the stone site was the most significant predictor of successful passage in acute unilateral ureteral stones, with an optimal cut-off point of 2.3 mm. Further prospective studies are needed to accurately predict spontaneous SP.
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Insuficiência Renal , Ureter , Cálculos Ureterais , Humanos , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Cálculos Ureterais/diagnóstico por imagemRESUMO
To determine whether functionally relevant questions associated with the urinary or gut microbiome and urinary stone disease (USD) can be answered from metagenome-wide association studies (MWAS), we performed the most comprehensive meta-analysis of published clinical MWAS in USD to date, using publicly available data published prior to April 2021. Six relevant studies met inclusion criteria. For alpha-diversity, significant differences were noted between USD status, stone composition, sample type, study location, age, diet, and sex. For beta-diversity, significant differences were noted by USD status, stone composition, sample type, study location, antibiotic use (30 days and 12 months before sampling), sex, hypertension, water intake, body habitus, and age. Prevotella and Lactobacillus in the gut and urinary tract, respectively, were associated with healthy individuals, while Enterobacteriaceae was associated with USD in the urine and stones. Paradoxically, other Prevotella strains were also strongly associated with USD in the gut microbiome. When data were analyzed together, USD status, stone composition, age group, and study location were the predominant factors associated with microbiome composition. Meta-analysis showed significant microbiome differences based on USD status, stone composition, age group or study location. However, analyses were limited by a lack of public data from published studies, metadata collected, and differing study protocols. Results highlight the need for field-specific standardization of experimental protocols in terms of sample collection procedures and the anatomical niches to assess, as well as in defining clinically relevant metadata and subphenotypes such as stone composition. IMPORTANCE Studies focused on the microbiome broadly support the hypothesis that the microbiome influences the onset of chronic diseases such as urinary stone disease. However, it is unclear what environmental factors shape the microbiome in ways that increase the risk for chronic disease. In addition, it is unclear how differences in study methodology can impact the results of clinical metagenome-wide association studies. In the current meta-analysis, we show that age, stone composition, and study location are the predominant factors that associate with the microbiome and USD status. Furthermore, we reveal differences in results based on specific analytical protocols, which impacts the interpretation of any microbiome study.
Assuntos
Metagenoma , Microbiota/genética , Cálculos Urinários/química , Urolitíase/microbiologia , Humanos , Masculino , Microbiota/fisiologia , Sistema Urinário/microbiologia , Sistema Urinário/patologiaRESUMO
Background: Pandemic restrictions have changed how patients approach symptomatic kidney stones. We used a mixed-methods digital ethnographic approach to evaluate social media discussions about patient concerns and preferences for urolithiasis care during the COVID-19 pandemic. Materials and Methods: We retrospectively analyzed kidney stone-related discussions on a large social media platform using qualitative analysis and natural language processing-based sentiment analysis. Posts were mined for demographic details, treatments pursued, and health care encounters. Pre-COVID-19 (January 1, 2020-February 29, 2020) and COVID-19 (March 1, 2020-June 1, 2020) posts were extracted from the popular online Reddit discussion board, "r/KidneyStones," which is dedicated to discussions related to urolithiasis. Results: We extracted n = 649 posts (250 pre-COVID-19, 399 COVID-19); 150 from each cohort underwent thematic analysis and data extraction. Quantitative sentiment analysis was performed on 418 posts (179 pre-COVID-19, 239 COVID-19) that described stone-related decision making before intervention. Notable discussion themes during COVID-19 focused on barriers to care and concerns about stone management. Discussants exhibited more negative and anxious tones during COVID-19, based on sentiment analysis (p < 0.01). Patient preferences shifted away from in-person visits and procedures (p < 0.001). Mean reported stone size among those visiting emergency room (ER) increased from 5.1 to 10.5 mm (p < 0.001). The proportion of discussants preferring conservative management with stones ≥10 mm increased (12.5% pre-COVID-19 vs 26% during COVID-19, p = 0.002). Opioid mentions increased from 9% to 27% of posts (p < 0.001) and were most associated with conservative management discussions. Conclusions: Online discussion forums provide contemporaneous insight into patients' experiences during a time when traditional patient-centered research methodologies are limited due to social distancing. During the pandemic, patients with symptomatic kidney stones expressed anxiety regarding outpatient encounters and reluctance toward procedural intervention. Patients opted instead for at-home conservative treatment beyond clinical guidelines and reserved ER visits for larger stones, potentially causing self-harm. Opioid discussions proliferated, an alarming consequence of the pandemic.