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OBJECTIVE: To comprehensively assess total and calculated free testosterone levels in a consecutive group of patients with prostate cancer (PCa) and any potential impact on disease aggressiveness and recurrence outcomes. PARTICIPANTS AND METHODS: The study included a single-centre prospective cohort of 882 patients presenting for radical prostatectomy from 2009 to 2018. Data on total testosterone (TT), sex hormone-binding globulin (SHBG), and calculated free testosterone (cFT) were prospectively collected. Stepwise logistic regression models were used to assess correlations of TT and cFT with pathological Gleason Grade Group (GGG), extraprostatic extension (EPE), seminal vesicle invasion (SVI) and biochemical recurrence (BCR). RESULTS: Total testosterone remained nearly constant across decades (40s-80s): 0.09 decrease/year (R = 0.02), while SHBG increased 0.87/year (R = 0.32) and cFT decreased 0.08/year (R = -0.02). Low cFT of <5.5 independently predicted: very-high-risk GGG (odds ratio [OR] 0.435, 95% confidence interval [CI] 0.846-0.994; P = 0.036), EPE (OR 0.557, 95% CI 0.810-0.987; P = 0.011), SVI (OR 0.396, 95% CI 0.798-1.038; P = 0.059), and BCR within 1 year after robot-assisted radical prostatectomy (OR 0.638, 95% CI 0.971-3.512, P = 0.046). TT was not a predictor. CONCLUSION: In contrast to popular belief, testosterone remained stable in men aged 40-80 years, whereas free testosterone decreased by 2-3%/year. Low cFT was an independent predictor of very-high-risk PCa and BCR.
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Neoplasias da Próstata , Humanos , Masculino , Estudos Prospectivos , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , TestosteronaRESUMO
OBJECTIVES: To assess the impact of statin use on overall and time to biochemical failure following primary treatment of localized prostate cancer (PCa). SUBJECTS/PATIENTS AND METHODS: 1581 patients undergoing radical prostatectomy (RP) or radiation therapy (RT) for primary treatment of PCa between July 2007 and January 2020 were evaluated for statin use, demographic/oncologic characteristics, and biochemical outcomes. Rate of biochemical failure (BF) was assessed overall and at 1, 3, and 5 years; time to BF was estimated with Kaplan-Meier. Logistic and linear regression were used to control for treatment modality and disease characteristics. RESULTS: The average age was 63.0 ± 7.5 years and median pre-treatment PSA was 6.55 (IQR 4.94). 1473 (93.2%) and 108 (6.8%) underwent RP and RT, respectively. RP patients were younger, had lower pre-PSA, lower BMI, and lower risk disease. At 3.4 ± 2.7 years follow-up, 323 (20.4%) experienced BF. When stratified by statin use, BF overall and within 1, 3, and 5 years were not different. Time to BF, was lower in patients using statins (1.8 ± 1.9 years vs. 2.4 ± 2.6 years; p = 0.016). These results persisted in multivariate analysis, wherein statin use was not associated with BF but was associated with a shorter time to BF. CONCLUSION: Overall, statin use was not associated with a reduced risk of BF in RP or RT patients. However, for patients with BF, statin use was associated with a decreased time to BF. Future investigations are warranted to further elucidate the impact of statin use on PCa recurrence.
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Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Prostatectomia , Neoplasias da Próstata/radioterapia , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Estudos Retrospectivos , Fatores de Tempo , Falha de TratamentoRESUMO
BACKGROUND: A Risk Evaluation and Mitigation Strategy (REMS) is a drug safety program for certain medications with serious safety concerns required by the U.S. Food and Drug Administration (FDA) of manufacturers to implement to help ensure the benefits of the medication outweigh its risks. FDA is encouraging "the research community to develop novel methods for assessing REMS," conveying the unmet need for a standardized evaluation method of these regulatory-mandated healthcare programs. The objective of this research is to evaluate FDA REMS assessment plans using established implementation science frameworks and identify opportunities for strengthening REMS evaluation. METHODS: A content analysis was conducted of publicly available assessment plans for all REMS programs (N = 23) approved 1/1/2014-12/31/2018 for new drug applications (NDAs) and biologics license applications (BLAs) requiring FDA-mandated Elements to Assure Safe Use (ETASU). Blinded reviewers critically appraised REMS assessment measures (n = 674) using three established implementation science frameworks: RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance); PRECEDE-PROCEED (Predisposing, Reinforcing, and Enabling Constructs in Educational/Environmental Diagnosis and Evaluation - Policy, Regulatory, and Organizational Constructs in Educational and Environmental Development); and CFIR (Consolidated Framework for Implementation Research). Framework constructs were mapped to REMS Assessment categories as defined by FDA Guidance for Industry to evaluate congruence. RESULTS: REMS assessment measures demonstrated strong congruence (> 90% mapping rate) with the evaluative constructs of RE-AIM, PRECEDE-PROCEED, and CFIR. Application of the frameworks revealed that REMS assessment measures heavily emphasize implementation and operations, focus less on health outcomes, and do not evaluate program context and design assumptions. CONCLUSIONS: Implementation science frameworks have utility for evaluating FDA-mandated drug safety programs including the selection of primary measures to determine whether REMS goals are being met and of secondary measures to evaluate contextual factors affecting REMS effectiveness in varying organizational settings.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Avaliação de Risco e Mitigação , Humanos , Ciência da Implementação , Medição de Risco , Estados Unidos , United States Food and Drug AdministrationRESUMO
PURPOSE: American Urological Association (AUA) antibiotic prophylaxis recommendations may be insufficient for covering organisms commonly found in penile prosthesis infections. In this study we assess the difference between AUA recommended antibiotic prophylaxis and nonstandard prophylaxis in preventing device infections in penile prosthesis surgery performed in diabetic patients. MATERIALS AND METHODS: A multicenter, retrospective cohort study of diabetic patients undergoing primary penile prosthesis surgery was performed between April 2003 and August 2018. Eighteen institutions from the United States, Europe and Korea contributed. The association between antibiotic prophylaxis type and postoperative penile prosthesis infections, device explantations and revision surgeries was assessed. RESULTS: Standard AUA antibiotic prophylaxis was followed in 48.6% (391) of cases while nonstandard prophylaxis was used in 51.4% (413). Common nonstandard antibiotic prophylaxis included vancomycin-gentamycin-fluoroquinolone, clindamycin-fluoroquinolone, and vancomycin-fluoroquinolone among other combinations. Patients who received AUA prophylaxis had significantly more postoperative device infections (5.6% vs 1.9%, p <0.01) and explantations (8.3% vs 2.0%, p <0.001) compared to those who received nonstandard prophylaxis. Patients who received AUA prophylaxis had significantly higher odds of a postoperative device infection (OR 2.8, 95% CI 1.1-7.3) and explantation (OR 3.6, 95% CI 1.4-9.1) compared to those who received nonstandard prophylaxis. CONCLUSIONS: Diabetic men with erectile dysfunction who received standard AUA prophylaxis for penile prosthesis surgery had significantly greater odds of experiencing a postoperative device infection and device explantation compared to patients who received nonstandard prophylaxis. Our study provides a strong rationale for a prospective investigation to establish the most appropriate prophylaxis strategy in penile prosthesis surgery.
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Antibioticoprofilaxia/normas , Diabetes Mellitus/imunologia , Disfunção Erétil/cirurgia , Prótese de Pênis/efeitos adversos , Guias de Prática Clínica como Assunto , Implantação de Prótese/efeitos adversos , Infecções Relacionadas à Prótese/epidemiologia , Idoso , Antibacterianos/uso terapêutico , Antibioticoprofilaxia/métodos , Antibioticoprofilaxia/estatística & dados numéricos , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Quimioterapia Combinada/estatística & dados numéricos , Europa (Continente)/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Implantação de Prótese/instrumentação , Infecções Relacionadas à Prótese/imunologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/prevenção & controle , Reoperação/estatística & dados numéricos , República da Coreia/epidemiologia , Estudos Retrospectivos , Sociedades Médicas/normas , Resultado do Tratamento , Estados Unidos/epidemiologia , Urologia/normasRESUMO
OBJECTIVE: To evaluate risk of prostate cancer biochemical recurrence (BCR) after radical prostatectomy (RP) in men receiving vs not receiving testosterone replacement therapy (TRT). PATIENTS AND METHODS: A total of 850 patients underwent RP by a single surgeon. All patients had preoperative testosterone and sex hormone-binding globulin levels determined; free testosterone was calculated prospectively. In all, 152 (18%) patients with low preoperative calculated free testosterone (cFT) levels and delayed postoperative sexual function recovery were placed on TRT and proportionately matched to 419 control patients by pathological Gleason Grade Group (GGG) and stage. Rates and time to BCR [two consecutive prostate-specific antigen (PSA) levels of ≥0.2 ng/mL] were compared in univariate and multivariate regression; Cox regression was used to generate a survival function at the mean of covariates. RESULTS: The median follow-up was 3.5 years. There were no statistically significant differences in demographics or general health complications between groups. BCR occurred in 11/152 (7.2%) and 53/419 (12.6%) patients in the TRT and control groups, respectively. In adjusted time-to-event analysis, TRT was an independent predictor of recurrence-free survival. After accounting for GGG, pathological stage, preoperative PSA level, and cFT, patients on TRT were ~54% less likely to recur (hazard ratio 0.54, 95% confidence interval 0.292-0.997). In men destined to recur, TRT delayed time to recurrence by an average of 1.5 years. CONCLUSION: In our experience, TRT after RP significantly reduced BCR and delayed time to BCR. There was no identifiable general health complications associated with TRT. These findings are hypothesis-generating and require confirmation with multi-centred, prospective randomised controlled trials.
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Terapia de Reposição Hormonal/métodos , Recidiva Local de Neoplasia/prevenção & controle , Prostatectomia/métodos , Neoplasias da Próstata/terapia , Testosterona/uso terapêutico , Androgênios/uso terapêutico , Estudos de Casos e Controles , Intervalo Livre de Doença , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: In recent years, the assessment of erectile dysfunction (ED) has experienced a paradigm shift from objective, quantitative methods to subjective, qualitative patient-reported outcomes. Facilitated by this shift is the ongoing debate on questionnaire selection and need for standardization, particularly among sexual medicine specialists. AIM: To review current literature on assessment of erectile function via patient-reported outcomes and discuss the context, advantages, and limitations of currently available questionnaires. METHODS: A thorough literature search of erectile function questionnaires developed from 1990 through 2019 was carried out using 3 methods: a search of the MedLine databases; hand-search of peer-reviewed urologic, sexual medicine, and health policy journals; and expert review. The following keywords were used: [assessment of], [inventory], [questionnaire], or [validated measure]; in combination with: [sexual function] or [erectile function]. Measures were stratified into one of the following 3 groups: screening, outcome, or disease-specific. 3 screening measures (International Index of Erectile Function, the Male Sexual Health Questionnaire, and Brief Male Sexual Inventory); 5 outcome measures (Sexual Health Inventory for Men, Erection Hardness Score, Erectile Dysfunction Inventory for Treatment and Satisfaction, and Treatment Satisfaction Scale); and 3 categories of disease-specific measures (cancer, Peyronie's disease, and spinal cord injury) were included. OUTCOMES: Strengths, limitations, and valid uses of each erectile function questionnaire. RESULTS: There currently exists a wide variety of screening, outcome, and disease-specific measures for ED diagnosis, assessment, and treatment. Rigor of psychometric validation varies greatly across studies. However, depending on purpose of use, all abovementioned questionnaires have merit for use in clinical practice, are nonredundant, and can complement and supplement one another. CLINICAL IMPLICATIONS: Before choosing a specific measure for ED diagnosis, assessment, or treatment, there must be careful consideration of the questionnaire's psychometric properties, context of validation, and its possible limitations. STRENGTHS & LIMITATIONS: The patient reported outcome measures highlighted in this article complement and supplement one another, as each emphasizes a related yet distinct central theme. During selection for use in clinical practice and research studies, special attention needs to be paid to the context, strengths, and weaknesses of each measure. CONCLUSION: When used conscientiously, patient-reported questionnaires can significantly optimize patient management. Yafi FA, Huynh LM, Ahlering T, et al. What Is a "Validated Questionnaire"? A Critical Review of Erectile Function Assessment. J Sex Med 2020;17:849-860.
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Disfunção Erétil , Induração Peniana , Disfunção Erétil/diagnóstico , Humanos , Masculino , Ereção Peniana , Comportamento Sexual , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Modern-day penile prostheses use infection retardant coating to decrease rates of postoperative infection, subsequently reducing explantation and revision rates as well. The Coloplast Titan models are dipped into antimicrobial solutions right before implantation, and the components used for dipping can be tailored toward the patient. AIM: To compare infection, explantation, and revision rates among different dipping solutions used before implantation for patients with diabetes receiving a Coloplast Titan implant. METHODS: We systematically reviewed 932 patients with diabetes receiving a primary penile implant across 18 different centers from the period April 2003 to August 2018. Of those patients, 473 received a Coloplast device, whereas 459 received an AMS device. Data regarding the type of antimicrobial solution used before implantation were recorded for 468 patients receiving a Coloplast Titan, including whether or not they suffered a postoperative infection and if they underwent explantation and/or revision. Outcome rates were compared using Fisher's exact and Pearson's chi-square tests, and logistic regression modeling was performed to account for covariates. OUTCOMES: The main outcome measures of this study were postoperative infection, explantation, and revision rates. RESULTS: Of the total 932 patients reviewed, 33 suffered a postoperative infection. Of 468 patients receiving Coloplast implants, there was a 3.4% infection rate. The most commonly used antibiotic combination before dipping was vancomycin + gentamicin (59.0%). There was a significantly lower rate of postoperative infection, explantation, and revision when vancomycin + gentamicin was used than those associated with the use of all other dipping solutions ([1.4% vs 6.4%; P = .004], [1.1% vs 8.3%; P < .001], and [2.5% vs 12.5; P < .001], respectively). After adjusting for age, body mass index, preoperative blood glucose level, and hemoglobin A1c, the use of other dips was an independent predictor of postoperative infection (odds ratio: 0.191; P = .049). The inclusion of rifampin in the dipping solution trended toward being a significant risk factor for infection (P = .057). Including antifungals in the dipping solution did not affect infection (P = .414), explantation (P = .421), or revision (P = .328) rates. CLINICAL IMPLICATIONS: Vancomycin + gentamicin was the most efficacious combination of antibiotics used for dipping in terms of preventing postoperative infection and subsequent explantation and revision. STRENGTHS AND LIMITATIONS: Data were sampled across multiple institutions providing a large sample that may be more representative of the population of interest. A key limitation of the study was its retrospective nature, which prevented us from controlling certain variables. CONCLUSION: The use of rifampin did not provide the same type of protection, possibly representing a shift in resistance patterns of common bacteria responsible for device infection. Towe M, Huynh LM, Osman MM, et al. Impact of Antimicrobial Dipping Solutions on Postoperative Infection Rates in Patients With Diabetes Undergoing Primary Insertion of a Coloplast Titan Inflatable Penile Prosthesis. J Sex Med 2020;17:2077-2083.
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Diabetes Mellitus , Implante Peniano , Prótese de Pênis , Diabetes Mellitus/tratamento farmacológico , Gentamicinas/uso terapêutico , Humanos , Masculino , Estudos RetrospectivosRESUMO
In the original publication, part of funding information was missed.
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An important function of immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors is cross-regulation of heterologous receptor signaling, but mechanisms of cross-inhibition are poorly understood. We show that high-avidity ligation of ITAM-coupled beta2 integrins and FcgammaRs in macrophages inhibited type I interferon receptor and Toll-like receptor (TLR) signaling and induced expression of interleukin-10 (IL-10); signaling inhibitors SOCS3, ABIN-3, and A20; and repressors of cytokine gene transcription STAT3 and Hes1. Induction of inhibitors was dependent on a pathway composed of signaling molecules DAP12, Syk, and Pyk2 that coupled to downstream kinases p38 and MSKs and required integration of IL-10-dependent and -independent signals. ITAM-induced inhibitors abrogated TLR responses by cooperatively targeting distinct steps in TLR signaling. Inhibitory signaling was suppressed by IFN-gamma and attenuated in inflammatory arthritis synovial macrophages. These results provide an indirect mechanism of cross-inhibition of TLRs and delineate a signaling pathway important for deactivation of macrophages.
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Antígenos CD18/imunologia , Interferon Tipo I/imunologia , Receptores Imunológicos/imunologia , Receptores Toll-Like/imunologia , Proteínas Adaptadoras de Transdução de Sinal/deficiência , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Células Cultivadas , Quinase 2 de Adesão Focal/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Tirosina Quinases/metabolismo , Transdução de Sinais , Quinase Syk , Receptores Toll-Like/metabolismoRESUMO
BACKGROUND: In May 2012, the US Preventive Services Task Force issued a grade D recommendation against PSA-based prostate cancer screening. Epidemiologists have concerns that an unintended consequence is a problematic increase in high-risk disease and subsequent prostate cancer-specific mortality. MATERIALS AND METHODS: To assess the effect of decreased PSA screening on the presentation of high-risk prostate cancer post-radical prostatectomy (RP). Nine high-volume referral centers throughout the United States (n = 19,602) from October 2008 through September 2016 were assessed and absolute number of men presenting with GS ≥ 8, seminal vesicle and lymph node invasion were compared with propensity score matching. RESULTS: Compared to the 4-year average pre-(Oct. 2008-Sept. 2012) versus post-(Oct. 2012-Sept. 2016) recommendation, a 22.6% reduction in surgical volume and increases in median PSA (5.1-5.8 ng/mL) and mean age (60.8-62.0 years) were observed. The proportion of low-grade GS 3 + 3 cancers decreased significantly (30.2-17.1%) while high-grade GS 8 + cancers increased (8.4-13.5%). There was a 24% increase in absolute numbers of GS 8+ cancers. One-year biochemical recurrence rose from 6.2 to 17.5%. To discern whether increases in high-risk disease were due to referral patterns, propensity score matching was performed. Forest plots of odds ratios adjusted for age and PSA showed significant increases in pathologic stage, grade, and lymph node involvement. CONCLUSIONS: All centers experienced consistent decreases of low-grade disease and absolute increases in intermediate and high-risk cancer. For any given age and PSA, propensity matching demonstrates more aggressive disease in the post-recommendation era.
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Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Idoso , Detecção Precoce de Câncer , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores/tendências , Estadiamento de Neoplasias/tendências , Razão de Chances , Guias de Prática Clínica como Assunto , Pontuação de Propensão , Prostatectomia , Neoplasias da Próstata/sangue , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/patologia , Glândulas Seminais/patologiaRESUMO
OBJECTIVE: To introduce a patient-reported erection fullness scale (%fullness) after robot-assisted radical prostatectomy (RARP) as a qualitative adjunct to the five-item version of the International Index of Erectile Function (IIEF-5) and as a 90-day predictor of 2-year potency outcomes. PATIENTS AND METHODS: Prospective data were collected from 540 men with preoperative IIEF-5 scores of 22-25 who underwent RARP by a single surgeon, and of whom 299 had complete data at all time points up to 2 years. In addition to standard assessment tools (IIEF-5 and erections sufficient for intercourse [ESI]), the men were asked to 'indicate the fullness you are able to achieve in erections compared to before surgery?' (range: 0-100%). The primary outcome was prediction of potency (defined as ESI) at 24 months, based on 90-day %fullness tertile (0-24%, 25-74% and 75-100%). RESULTS: A total of 299 men with complete follow-up were included in the study. Significant predictors of 24-month potency included age, body mass index, pathological stage, nerve-sparing status and %fullness tertiles. When the men (preoperative IIEF-5 score 22-25) were assessed at 90 days after RARP, 181/299 (61%) had erections inadequate for intercourse. If IIEF-5 scores of 1-6 were used, 142/181 men (78%) would be targeted for early intervention. By contrast, if 0-24% fullness was used, 88/181 men (49%) would be targeted. If both the IIEF-5 score and %fullness were used, this would be reduced to 77/181 men (43%). CONCLUSIONS: We introduce %fullness as a qualitative adjunct to the IIEF-5 score, and separately as a 90-day predictor of 2-year potency recovery. This initial report is hypothesis-generating, such that the use of %fullness enables the identification of men who are most likely to benefit from early, secondary intervention.
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Disfunção Erétil/etiologia , Tratamentos com Preservação do Órgão/métodos , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Gradação de Tumores , Satisfação do Paciente , Ereção Peniana/fisiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Curva ROC , Traumatismos do Sistema Nervoso/prevenção & controleRESUMO
INTRODUCTION AND OBJECTIVES: Medical expulsive therapy is based on pharmacologic ureteral relaxation. We hypothesized this concept may facilitate the deployment of the large 16 French (F) ureteral access sheath (UAS) when patients are intentionally pre-treated with oral tamsulosin, i.e., medical impulsive therapy. METHODS: We retrospectively analyzed our experience with UAS deployment during endoscopic-guided percutaneous nephrolithotomy in prone position in patients pre-treated for 1 week with oral tamsulosin with a contemporary untreated cohort. Between January 2015 and September 2016, seventy-seven patients without a pre-existing ureteral stent met inclusion criteria. Demographic data, tamsulosin usage, UAS size, deployment failure, ureteral injuries, stone-free rates, and complications were recorded. Univariate and multivariate analysis was conducted to assess the impact of tamsulosin on deployment of the 16F UAS. RESULTS: There was no statistical difference between the tamsulosin (n = 40) group and non-tamsulosin (n = 37) group in regard to demographic data. The tamsulosin group had a significantly higher percentage of 16F UAS deployment, 87 vs. 43% (p < 0.001), and no significant difference in ureteral injuries (p = 0.228). Univariate and multivariate analysis revealed that tamsulosin significantly increased the odds ratio (9.3 and 19.4, respectively) for successful passage of a 16F UAS. Despite a larger stone volume, there was no significant difference in computed tomography scan complete stone-free rates (29 vs. 42%; p = 0.277) at median post-operative time of only 3 days. CONCLUSIONS: In this retrospective study, 1 week of preoperative tamsulosin was associated with an increase in the deployment of a 16F UAS in patients without preoperative ureteral stent placement.
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Antagonistas de Receptores Adrenérgicos alfa 1/uso terapêutico , Nefrolitotomia Percutânea/métodos , Cuidados Pré-Operatórios/métodos , Stents , Tansulosina/uso terapêutico , Cálculos Ureterais/cirurgia , Cateterismo Urinário/métodos , Cateteres Urinários , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Posicionamento do Paciente , Decúbito Ventral , Estudos RetrospectivosRESUMO
Preoperative nomograms offer systematic and quantitative methods to assess patient- and stone-related characteristics and their impact on successful treatment and potential risk of complication. Discrepancies in the correlation of perioperative variables to patient outcomes have led to the individual development, validation, and application of four independent scoring systems for the percutaneous nephrolithotomy: Guy's stone score, S.T.O.N.E. nephrolithometry, Clinical Research Office of the Endourology Society nomogram, and Seoul National University Renal Stone Complexity. The optimal nomogram should have high predictive ability, be practically integrated into clinical use, and be widely applicable to urinary stone disease. Herein, we seek to provide a contemporary evaluation of the advantages, disadvantages, and commonalities of each scoring system. While the current data is insufficient to conclude which scoring system is destined to become the gold standard, it is crucial that a nephrolithometric scoring system be incorporated into common practice to improve surgical planning, patient counseling, and outcome assessment.
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Cálculos Renais/diagnóstico por imagem , Cálculos Renais/cirurgia , Nefrolitotomia Percutânea/métodos , Humanos , Nomogramas , Medição de Risco , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
ITAM-coupled receptors play an essential role in regulating macrophage activation and function by cross-regulating signaling from heterologous receptors. We investigated mechanisms by which ITAM-associated receptors inhibit type I IFN (IFN-α/ß) signaling in primary human macrophages and tested the effects of simultaneous ligation of ITAM-associated receptors and TLR4 on TLR4-induced Jak-STAT signaling that is mediated by autocrine IFN-ß. Preligation of ITAM-coupled ß2 integrins and FcγRs inhibited proximal signaling by the type I IFN receptor IFNAR. Cross-inhibition of IFNAR signaling by ß2 integrins resulted in decreased Jak1 activation and was mediated by partial downregulation of the IFNAR1 subunit and MAPK-dependent induction of USP18, which blocks the association of Jak1 with IFNAR2. Simultaneous engagement of ITAM-coupled ß2 integrins or Dectin-1 with TLR4 did not affect TLR4-induced direct activation of inflammatory target genes such as TNF or IL6 but abrogated subsequent induction of IFN response genes that is mediated by autocrine IFN-ß signaling. Type I IFNs promote macrophage death postinfection by Listeria monocytogenes. Consequently, attenuation of IFN responses by ß2 integrins protected primary human macrophages from L. monocytogenes-induced apoptosis. These results provide a mechanism for cross-inhibition of type I IFN signaling by ITAM-coupled ß2 integrins and demonstrate that ITAM signaling qualitatively modulates macrophage responses to pathogen-associated molecular patterns and pathogens by selectively suppressing IFN responses.
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Antígenos CD18/imunologia , Interferon Tipo I/antagonistas & inibidores , Listeria monocytogenes/imunologia , Macrófagos/imunologia , Receptor de Interferon alfa e beta/antagonistas & inibidores , Receptores Imunológicos/imunologia , Transdução de Sinais/imunologia , Receptor 4 Toll-Like/imunologia , Motivos de Aminoácidos , Apoptose , Comunicação Autócrina , Células Cultivadas/imunologia , Citocinas/biossíntese , Citocinas/genética , Humanos , Interferon Tipo I/imunologia , Janus Quinases/fisiologia , Sistema de Sinalização das MAP Quinases , Monócitos/imunologia , Interferência de RNA , Receptor de Interferon alfa e beta/imunologia , Receptores Imunológicos/química , Fatores de Transcrição STAT/fisiologiaRESUMO
The clinical integration of prostate membrane specific antigen (PSMA) positron emission tomography and computed tomography (PET/CT) scans represents potential for advanced data analysis techniques in prostate cancer (PC) prognostication. Among these tools is the use of radiomics, a computer-based method of extracting and quantitatively analyzing subvisual features in medical imaging. Within this context, the present review seeks to summarize the current literature on the use of PSMA PET/CT-derived radiomics in PC risk stratification. A stepwise literature search of publications from 2017 to 2023 was performed. Of 23 articles on PSMA PET/CT-derived prostate radiomics, PC diagnosis, prediction of biopsy Gleason score (GS), prediction of adverse pathology, and treatment outcomes were the primary endpoints of 4 (17.4%), 5 (21.7%), 7 (30.4%), and 7 (30.4%) studies, respectively. In predicting PC diagnosis, PSMA PET/CT-derived models performed well, with receiver operator characteristic curve area under the curve (ROC-AUC) values of 0.85-0.925. Similarly, in the prediction of biopsy and surgical pathology results, ROC-AUC values had ranges of 0.719-0.84 and 0.84-0.95, respectively. Finally, prediction of recurrence, progression, or survival following treatment was explored in nine studies, with ROC-AUC ranging 0.698-0.90. Of the 23 studies included in this review, 2 (8.7%) included external validation. While explorations of PSMA PET/CT-derived radiomic models are immature in follow-up and experience, these results represent great potential for future investigation and exploration. Prior to consideration for clinical use, however, rigorous validation in feature reproducibility and biologic validation of radiomic signatures must be prioritized.
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PURPOSE: To assess the diagnostic performance and utility of the ExoDx IntelliScore and an OPKO4K score to predict prostate cancer in men presenting with elevated PSA-both as independent predictors and in combination with clinical/MRI characteristics. METHODS: Patients with elevated PSA were retrospectively reviewed. Abnormal tests were defined as an OPKO4K score ≥ 7.5% and an ExoDx IntelliScore ≥ 15.6. Four regression models and ROC curves were generated based on: (1) age, PSA, and DRE, (2) model 1 + OPKO4K 4Kscore ≥ 7.5%, (3) model 2 + ExoDx IntelliScore ≥ 15.6, and (4) model 3 + MRI PIRADS 4-5. RESULTS: 359 men received an OPKO4K test, 307 had MRI and 113 had ExoDx tests. 163 men proceeded to prostate biopsy and 196 (55%) were saved from biopsy. Mean age was 65.0 ± 8.7 years and mean PSA was 7.1 ± 6.1 ng/mL. Positive biopsies were found in 84 (51.5%) men. The sensitivity and negative predictive value of an OPKO4K score were 86.7% and 72.3%; values for an ExoDx test were 76.5% and 77.1%, respectively. On regression analysis, clinical markers (Age, PSA, DRE) generated an AUC of 0.559. The addition of an OPKO4K score raised the AUC to 0.653. The stepwise addition of an ExoDx score raised the AUC to 0.766. The combined use of both biomarkers, patient characteristics, and MRI yielded an AUC of 0.825. CONCLUSION: This analysis demonstrates the high negative predictive value of both the OPKO4K score and ExoDX IntelliScore independently while demonstrating that the combination of an OPKO4K score, an ExoDX IntelliScore, and MRI increases predictive capability for biopsy confirmed prostate cancer.
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Próstata , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Próstata/patologia , Antígeno Prostático Específico , Biomarcadores Tumorais , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Biópsia , Imageamento por Ressonância MagnéticaRESUMO
Purpose: The aim of this study was to further assess the clinical utility of multiparametric magnetic resonance imaging (MP-MRI) in prostate cancer (PC) staging following 2023 clinical guideline changes, both as an independent predictor of high-stage (>T3a) or high-risk PC and when combined with patient characteristics. Methods and Materials: The present study was a retrospective review of 171 patients from 2008 to 2018 who underwent MP-MRI before radical prostatectomy at a single institution. The accuracy of clinical staging was compared between conventional staging and MP-MRI-based clinical staging. Sensitivity, specificity, positive predictive value, and negative predictive value were compared, and receiver operating characteristic curves were generated. Linear regression analyses were used to calculate concordance (C-statistic). Results: Of the 171 patients, final pathology revealed 95 (55.6%) with T2 disease, 62 (36.3%) with T3a disease, and 14 (8.2%) with T3b disease. Compared with conventional staging, MP-MRI-based staging demonstrated significantly increased accuracy in identifying T3a disease, intermediate risk, and high/very-high-risk PC. When combined with clinical characteristics, MP-MRI-based staging improved the area under the curve from 0.753 to 0.808 (P = .0175), compared with conventional staging. Conclusions: MP-MRI improved the identification of T3a PC, intermediate-risk PC, and high- or very-high-risk PC. Further, when combined with clinical characteristics, MP-MRI-based staging significantly improved risk stratification, compared with conventional staging. These findings represent further evidence to support the integration of MP-MRI into prostate adenocarcinoma clinical staging guidelines.
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The development of precise medical imaging has facilitated the establishment of radiomics, a computer-based method of quantitatively analyzing subvisual imaging characteristics. The present review summarizes the current literature on the use of diagnostic magnetic resonance imaging (MRI)-derived radiomics in prostate cancer (PCa) risk stratification. A stepwise literature search of publications from 2017 to 2022 was performed. Of 218 articles on MRI-derived prostate radiomics, 33 (15.1%) generated models for PCa risk stratification. Prediction of Gleason score (GS), adverse pathology, postsurgical recurrence, and postradiation failure were the primary endpoints in 15 (45.5%), 11 (33.3%), 4 (12.1%), and 3 (9.1%) studies. In predicting GS and adverse pathology, radiomic models differentiated well, with receiver operator characteristic area under the curve (ROC-AUC) values of 0.50-0.92 and 0.60-0.92, respectively. For studies predicting post-treatment recurrence or failure, ROC-AUC for radiomic models ranged from 0.73 to 0.99 in postsurgical and radiation cohorts. Finally, of the 33 studies, 7 (21.2%) included external validation. Overall, most investigations showed good to excellent prediction of GS and adverse pathology with MRI-derived radiomic features. Direct prediction of treatment outcomes, however, is an ongoing investigation. As these studies mature and reach potential for clinical integration, concerted effort to validate these radiomic models must be undertaken.
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Purpose: While erectile dysfunction and urinary incontinence are commonly cited side effects following radical prostatectomy (RP), climacturia and penile length shortening are less explored. The present study seeks to explore the incidence, risk factors, and predictors of recovery associated with climacturia and penile length shortening following robot-assisted radical prostatectomy (RARP). Patients and Methods: From September 2018 to January 2020, 800 patients underwent RARP for primary treatment of localized prostate cancer. A survey was sent to patients following 1-year follow-up assessing outcomes of continence, erectile dysfunction, climacturia, and penile length shortening. Descriptive statistics were utilized to describe incidence and risk factors and logistic regression modeling was used to identify predictors associated with recovery. Results: Of the 800 patients surveyed, 339 (42%) and 369 (46%) patients responded, with 127/339 (37.5%) and 216/369 (58.5%) endorsing climacturia and penile length shortening. In univariate analysis, a lack of bilateral nerve sparing was associated with climacturia; high body mass index (BMI), high prostate weight, lack of nerve-sparing, and high pathologic stage was associated with penile length shortening. In logistic regression modeling, BMI, prostate weight, and p-stage were all significantly correlated with penile length shortening. Recovery from climacturia was associated with a preoperative International Index of Erectile Function-5 score >21. When patients were asked to rank the importance of these outcomes compared to erectile dysfunction and incontinence, <5% of patients ranked either climacturia or penile length shortening as a high priority following RP. Conclusion: While incidence of climacturia and penile length shortening following RP is significant, impact on patient- and partner-related quality of life are low in comparison to risks of erectile dysfunction and urinary incontinence.