Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
Urol Oncol ; 41(12): 484.e1-484.e5, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37977915

RESUMO

OBJECTIVES: Many patients experience pain, anxiety, and discomfort with prostate biopsy, which may discourage enrollment in active surveillance programs or follow-up biopsy. Guided meditation can significantly reduce pain and anxiety during percutaneous biopsy. We sought to evaluate the effectiveness of a brief mind-body intervention on patient-reported outcomes after prostate biopsy. METHODS AND MATERIALS: We performed a clinically-integrated randomized controlled trial of a brief mind-body intervention during biopsy compared to usual care at a single tertiary care center from 2018 to 2022. All patients offered transrectal ultrasound-guided prostate biopsy in the clinic with local anesthesia were eligible for enrollment. This clinically integrated trial was conducted simultaneously with a randomized controlled trial of 1-stage and 2-stage consent. The primary outcome was patient-reported pain, anxiety, discomfort, and tolerability on a visual-analog scale (0-10). A 15% improvement was prespecified as clinically relevant. We compared the proportion of men in each arm reporting a severe score (7-10) on any of the 4 scales using Fisher's exact test and then compared means for each scale separately using ANCOVA with randomization stratum (first vs. prior biopsy) as a covariate. RESULTS: Of 263 eligible patients, 238 enrolled (119 per arm). One hundred seventy-two (72%) enrolled with 2-stage consent. A total of 37/94 (39%) and 38/102 (37%) patients randomized to usual care and intervention, respectively, reported severe scores in any of the 4 domains, a difference of 2.1% (95% confidence interval [CI] -13, 17%, P = 0.8). There was no evidence of a difference in mean postbiopsy anxiety (P = 0.3), discomfort (P = 0.09), pain (P = 0.4) or tolerability scores (P = 0.2). CONCLUSIONS: A clinically meaningful benefit for this brief mind-body intervention during prostate biopsy is unlikely. Robust patient enrollment is feasible using 2-stage consent.


Assuntos
Manejo da Dor , Próstata , Masculino , Humanos , Próstata/patologia , Manejo da Dor/métodos , Dor/etiologia , Dor/prevenção & controle , Dor/patologia , Biópsia por Agulha/métodos , Ansiedade/etiologia , Ansiedade/prevenção & controle , Consentimento Livre e Esclarecido
2.
BMJ Open ; 13(11): e075113, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37949619

RESUMO

BACKGROUND: Training programmes for obstetrics and gynaecology (O&G) and general surgery (GS) vary significantly, but both require proficiency in laparoscopic skills. We sought to determine performance in each specialty. DESIGN: Prospective, observational study. SETTING: Health Education England North-West, UK. PARTICIPANTS: 47 surgical trainees (24 O&G and 23 GS) were subdivided into four groups: 11 junior O&G, 13 senior O&G, 11 junior GS and 12 senior GS trainees. OBJECTIVES: Trainees were tested on four simulated laparoscopic tasks: laparoscopic camera navigation (LCN), hand-eye coordination (HEC), bimanual coordination (BMC) and suturing with intracorporeal knot tying (suturing). RESULTS: O&G trainees completed LCN (p<0.001), HEC (p<0.001) and BMC (p<0.001) significantly slower than GS trainees. Furthermore, O&G found fewer number of targets in LCN (p=0.001) and dropped a greater number of pins than the GS trainees in BMC (p=0.04). In all three tasks, there were significant differences between O&G and GS trainees but no difference between the junior and senior groups within each specialty. Performance in suturing also varied by specialty; senior O&G trainees scored significantly lower than senior GS trainees (O&G 11.4±4.4 vs GS 16.8±2.1, p=0.03). Whilst suturing scores improved with seniority among O&G trainees, there was no difference between the junior and senior GS trainees (senior O&G 11.4±4.4 vs junior O&G 3.6±2.1, p=0.004). DISCUSSION: GS trainees performed better than O&G trainees in core laparoscopic skills, and the structure of O&G training may require modification. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT05116332).


Assuntos
Cirurgia Geral , Ginecologia , Laparoscopia , Humanos , Ginecologia/educação , Estudos Prospectivos , Competência Clínica , Inglaterra , Educação em Saúde , Laparoscopia/educação , Técnicas de Sutura , Cirurgia Geral/educação
3.
Urol Oncol ; 41(10): 433.e19-433.e24, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37640571

RESUMO

BACKGROUND: There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. METHODS: In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). RESULTS: Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. CONCLUSIONS: Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Estudos Retrospectivos , Estudos Prospectivos , Estudos de Viabilidade , Genômica
4.
Cancer ; 129(23): 3790-3796, 2023 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-37584213

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI)-targeted prostate biopsy (MRI-biopsy) detects high-Grade Group (GG) prostate cancers not identified by systematic biopsy (S-biopsy). However, questions have been raised whether cancers detected by MRI-biopsy and S-biopsy, grade-for-grade, are of equivalent oncologic risk. The authors evaluated the relative oncologic risk of GG diagnosed by S-biopsy and MRI-biopsy. METHODS: This was a retrospective analysis of all patients who had both MRI-biopsy and S-biopsy and underwent with prostatectomy (2014-2022) at Memorial Sloan Kettering Cancer Center. Three logistic regression models were used with adverse pathology as the primary outcome (primary pattern 4, any pattern 5, seminal vesicle invasion, or lymph node involvement). The first model included the presurgery prostate-specific antigen level, the number of positive and negative S-biopsy cores, S-biopsy GG, and MRI-biopsy GG. The second model excluded MRI-biopsy GG to obtain the average risk based on S-biopsy GG. The third model excluded S-biopsy GG to obtain the risk based on MRI-biopsy GG. A secondary analysis using Cox regression evaluated the 12-month risk of biochemical recurrence. RESULTS: In total, 991 patients were identified, including 359 (36%) who had adverse pathology. MRI-biopsy GG influenced oncologic risk compared with S-biopsy GG alone (p < .001). However, if grade was discordant between biopsies, then the risk was intermediate between grades. For example, the average risk of advanced pathology for patients who had GG2 and GG3 on S-biopsy was 19% and 66%, respectively, but the average risk was 47% for patients who had GG2 on S-biopsy and patients who had GG3 on MRI-biopsy. The equivalent estimates for 12-month biochemical recurrence were 5.8%, 15%, and 10%, respectively. CONCLUSIONS: The current findings cast doubt on the practice of defining risk group based on the highest GG. Because treatment algorithms depend fundamentally on GG, further research is urgently required to assess the oncologic risk of prostate tumors depending on detection technique. PLAIN LANGUAGE SUMMARY: Using magnetic resonance imaging (MRI) to help diagnose prostate cancer can help identify more high-grade cancers than using a systematic template biopsy alone. However, we do not know if high-grade cancers diagnosed with the help of an MRI are as dangerous to the patient as high-grade cancers diagnosed with a systematic biopsy. We examined all of our patients who had an MRI biopsy and a systematic biopsy and then had their prostates removed to find out if these patients had risk factors and signs of aggressive cancer (cancer that spread outside the prostate or was very high grade). We found that, if there was a difference in grade between the systematic biopsy and the MRI-targeted biopsy, the risk of aggressive cancer was between the two grades.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/diagnóstico por imagem , Próstata/cirurgia , Próstata/patologia , Glândulas Seminais/patologia , Estudos Retrospectivos , Gradação de Tumores , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Prostatectomia , Imageamento por Ressonância Magnética/métodos , Biópsia Guiada por Imagem/métodos
5.
Clin Trials ; 20(6): 642-648, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37403311

RESUMO

BACKGROUND/AIMS: It has been proposed that informed consent for randomized trials should be split into two stages, with the purported advantage of decreased information overload and patient anxiety. We compared patient understanding, anxiety and decisional quality between two-stage and traditional one-stage consent. METHODS: We approached patients at an academic cancer center for a low-stakes trial of a mind-body intervention for procedural distress during prostate biopsy. Patients were randomized to hear about the trial by either one- or two-stage consent (n = 66 vs n = 59). Patient-reported outcomes included Quality of Informed Consent (0-100); general and consent-specific anxiety and decisional conflict, burden, and regret. RESULTS: Quality of Informed Consent scores were non-significantly superior for two-stage consent, by 0.9 points (95% confidence interval = -2.3, 4.2, p = 0.6) for objective and 1.1 points (95% CI = -4.8, 7.0, p = 0.7) for subjective understanding. Differences between groups for anxiety and decisional outcomes were similarly small. In a post hoc analysis, consent-related anxiety was lower among two-stage control patients, likely because scores were measured close to the time of biopsy in the two-stage patients receiving the experimental intervention. CONCLUSION: Two-stage consent maintains patient understanding of randomized trials, with some evidence of lowered patient anxiety. Further research is warranted on two-stage consent in higher-stakes settings.


Assuntos
Ansiedade , Emoções , Masculino , Humanos , Consentimento Livre e Esclarecido
6.
Langenbecks Arch Surg ; 408(1): 239, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337084

RESUMO

BACKGROUND: Enhanced recovery programmes are associated with improved short-term outcomes following liver surgery. The impact of enhanced recovery programmes on medium- and long-term outcomes is incompletely understood. This study aimed to assess the impact of an enhanced recovery programme on long-term survival in patients undergoing surgery for colorectal liver metastases. METHODS: At a tertiary hepatobiliary centre, we analysed short-, medium- and long-term outcomes in consecutive patients undergoing liver resection for colorectal liver metastases. A five-year retrospective review was carried out comparing the enhanced recovery programme to standard care. RESULTS: A total of 172 patients were included in the analysis: 87 on standard care and 85 on an enhanced recovery programme. Open surgery was performed in 122 patients: 74 (85.1%) and 48 (56.5%) patients in the standard care and enhanced recovery programme, respectively (p < 0.001). There was a significant reduction in the median (IQR) length of hospital stay in the enhanced recovery programme compared with standard care (7 (5) days vs. 8 (3) days, p = 0.0009). There was no significant difference in survival between standard care and the Enhanced Recovery Programme at one (p = 0.818), three (p = 0.203), and five years (p = 0.247). CONCLUSION: An enhanced recovery programme was associated with a reduced length of hospital stay. There was no effect on the one-, three- and five-year survival.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Hepatectomia , Estudos Retrospectivos , Tempo de Internação , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia
7.
Urology ; 179: 106-111, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37328009

RESUMO

OBJECTIVE: To investigate the utilization of holmium laser enucleation of the prostate (HoLEP) using a large real-world cohort. We compare the safety, readmission, and retreatment rates of HoLEP to other widely used endoscopic surgical interventions for benign prostatic hyperplasia (BPH) including transurethral resection of the prostate (TURP), photoselective vaporization of the prostate, and prostatic urethral lift. METHODS: Men who underwent endoscopic treatments for BPH from 2000 to 2019 were identified in the Premier Healthcare Database (n = 218,793). We compared the relative proportion of each procedure performed and annual physician volume data to identify trends in adoption and utilization. Readmission and retreatment rates were determined at both 30- and 90-days postoperation. Multivariable logistic regression was used to assess the association between procedure type and outcomes. RESULTS: HoLEP accounted for 3.2% (n = 6967) of all the BPH procedures performed between 2000 and 2019 and increased from 1.1% of the procedures in 2008 to 4% in 2019. Patients undergoing HoLEP had lower odds of 90-days readmission compared to TURP (Odds ratio (OR) 0.87, p = 0.025). HoLEP had similar odds of retreatment compared to TURP at both 1-year (OR 0.96, p = 0.7) and 2-years (OR 0.98, p = 0.9), while patients undergoing photoselective vaporization of the prostate and prostatic urethral lift were more likely to retreat within 2-years (OR 1.20, P < 0.001; OR 1.87, P < 0.001). CONCLUSION: HoLEP is a safe therapy for BPH with lower readmission and comparable retreatment rates to the gold standard TURP. Despite this, the utilization of HoLEP has lagged behind other endoscopic procedures and remains low.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Estados Unidos , Próstata , Ressecção Transuretral da Próstata/métodos , Hiperplasia Prostática/cirurgia , Lasers de Estado Sólido/uso terapêutico , Terapia a Laser/métodos , Resultado do Tratamento , Hólmio
8.
Ann Surg Open ; 4(2): e284, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37342254

RESUMO

Introduction: Surgeons are among the most at-risk professionals for work-related musculoskeletal decline and experience high mental demands. This study examined the electromyographic (EMG) and electroencephalographic (EEG) activities of surgeons during surgery. Methods: Surgeons who performed live laparoscopic (LS) and robotic (RS) surgeries underwent EMG and EEG measurements. Wireless EMG was used to measure muscle activation in four muscle groups bilaterally (biceps brachii, deltoid, upper trapezius, and latissimus dorsi), and an 8-channel wireless EEG device was used to measure cognitive demand. EMG and EEG recordings were completed simultaneously during (i) noncritical bowel dissection, (ii) critical vessel dissection, and (iii) dissection after vessel control. Robust ANOVA was used to compare the %MVCRMS and alpha power between LS and RS. Results: Thirteen male surgeons performed 26 laparoscopic surgeries (LS) and 28 robotic surgeries (RS). Muscle activation was significantly higher in the right deltoid (p = 0.006), upper trapezius (left, p = 0.041; right, p = 0.032), and latissimus dorsi (left, p = 0.003; right, p = 0.014) muscles in the LS group. There was greater muscle activation in the right biceps than in the left biceps in both surgical modalities (both p = 0.0001). There was a significant effect of the time of surgery on the EEG activity (p <0.0001). A significantly greater cognitive demand was observed in the RS than in the LS with alpha, beta, theta, delta, and gamma (p = 0.002 - p <0.0001). Conclusion: These data suggest greater muscle demands in laparoscopic surgery, but greater cognitive demands in robotic surgery.

9.
Eur Urol Focus ; 9(4): 575-578, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37028984

RESUMO

Bladder cancer at an individual level is likely to be the consequence of repeated, long-term exposure to one or more known bladder carcinogens, some of which are endemic or unavoidable in daily life, in addition to host factors. This Mini-Review highlights exposures that are associated with higher risk of bladder cancer, summarizes the evidence for each association, and suggests strategies to decrease risk at both individual and population levels. PATIENT SUMMARY: Tobacco smoking, exposure to certain chemicals in your diet, environment, or workplace, urinary infections, and certain medications can increase your risk of bladder cancer.


Assuntos
Carcinógenos , Neoplasias da Bexiga Urinária , Humanos , Carcinógenos/toxicidade , Fumar/efeitos adversos , Fumar/epidemiologia , Neoplasias da Bexiga Urinária/induzido quimicamente , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/prevenção & controle , Bexiga Urinária , Comportamento de Redução do Risco
11.
Eur Urol Focus ; 9(4): 660-661, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36604237

RESUMO

Thermal partial-gland ablation (TPGA) is a promising treatment option for patients with prostate cancer (PCa) that has an excellent side-effect profile. However, the literature on TPGA in high-risk PCa is not robust enough to discount the risk of undertreatment and understaging in this population. Future studies, especially with incorporation of advanced imaging to better select patients, are necessary to understand the safety and efficacy of TPGA in high-risk disease.


Assuntos
Próstata , Neoplasias da Próstata , Masculino , Humanos , Próstata/cirurgia , Neoplasias da Próstata/cirurgia
12.
Urol Oncol ; 40(6): 271.e1-271.e7, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35490048

RESUMO

PURPOSE: Biobanking tissue of high quality and fidelity is imperative for cancer genomics research. Since it is a challenging process, we sought to develop a protocol that improves the fidelity and quantity of biobanked primary prostate cancer (CaP) tissue. MATERIALS AND METHODS: We conducted a pilot study evaluating pathologic concordance of biobanked tissue and the radical prostatectomy specimen using either standard protocol (SP) vs. next-generation protocol (NGP). RESULTS: There were no significant differences in clinical and pathologic characteristics (age, BMI, preoperative PSA, prostate weight, race, final prostatectomy Gleason score, or pathologic tumor and nodal stages) between the two protocol arms. Utilization of the NGP compared to the standard protocol resulted in a significantly higher rate of pathologic concordance between the biobanked and RP specimens (61.8% vs. 37.9%, P = 0.0231) as well as a nearly two-fold increase in the amount of biobanked tumor tissue (330 mm3 vs. 174 mm3, P < 0.001). When looking at relevant clinical and pathologic characteristics, NGP was associated with pathologic concordance on both univariate [OR 2.65 (95% CI 1.13-6.21), P = 0.025] and multivariate analysis [OR 3.11 (95% CI 1.09-8.88), P = 0.034]. CONCLUSIONS: Our study validates the NGP as a multidisciplinary approach for improving the fidelity and amount of biobanked primary CaP tissue for future studies. Given the challenges to banking tissue from primary CaP as tumors are often difficult to visualize grossly and are frequently multifocal, optimizing the fidelity and volume of biobanked tissue is an important step forward to improve the generalizability of genomic data as we move towards precision medicine.


Assuntos
Neoplasias da Próstata , Bancos de Espécimes Biológicos , Humanos , Masculino , Estadiamento de Neoplasias , Projetos Piloto , Próstata/patologia , Próstata/cirurgia , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia
13.
J Gastrointest Surg ; 26(7): 1520-1530, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35426034

RESUMO

BACKGROUND: Surgeons are among the most at risk of work-related musculoskeletal health decline because of the physical demands of surgery, which is also associated with cognitive fatigue. Minimally invasive surgery offers excellent benefits to patients but the impact of robotic or laparoscopic surgery on surgeon well-being is less well understood. This work examined the musculoskeletal and cognitive demands of robot-assisted versus standard laparoscopic surgery. METHODS: Medline, Embase and Cochrane databases were systematically searched for 'Muscle strain' AND 'musculoskeletal fatigue' AND 'occupational diseases' OR 'cognitive fatigue' AND 'mental fatigue' OR 'standard laparoscopic surgery' AND 'robot-assisted laparoscopic surgery'. Primary outcomes measured were electromyographic (EMG) activity for musculoskeletal fatigue and questionnaires (NASA-TLX, SMEQ, or Borg CR-10) for cognitive fatigue. A systematic review was conducted in accordance with the Synthesis Without Meta-analysis (SWiM) Guidelines. The study was preregistered on Prospero ID: CRD42020184881. RESULTS: Two hundred and ninety-eight original titles were identified. Ten studies that were all observational studies were included in the systematic review. EMG activity was consistently lower in robotic than in laparoscopic surgery in the erector spinae and flexor digitorum muscles but higher in the trapezius muscle. This was associated with significantly lower cognitive load in robotic than laparoscopic surgery in 7 of 10 studies. CONCLUSIONS: Evidence suggests a reduction in musculoskeletal demands during robotic surgery in muscles excluding the trapezius, and this is associated with most studies reporting a reduced cognitive load. Robotic surgery appears to have less negative cognitive and musculoskeletal impact on surgeons compared to laparoscopic surgery.


Assuntos
Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Cognição , Humanos , Laparoscopia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos
14.
J Alzheimers Dis ; 86(3): 1201-1220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35180123

RESUMO

BACKGROUND: The Alzheimer's disease (AD)-associated amyloid-beta protein precursor (AßPP) can be cleaved by ß-site AßPP cleaving enzyme 1 (BACE1) and the γ-secretase complex to yield neurotoxic amyloid-ß (Aß) peptides. However, AßPP can also be cleaved in a 'non-amyloidogenic' manner either by α-secretase to produce soluble AßPP alpha (sAßPPα) (a fragment with neuroprotective/neurogenic functions) or through alternative BACE1-mediated 'beta prime' activity yielding soluble AßPP beta prime (sAßPPß'). OBJECTIVE: To determine whether sAßPPα depletion, as opposed to Aß peptide accumulation, contributes to cytotoxicity in AD-relevant SH-SY5Y neuroblastoma cell models. METHODS: AßPP proteolysis was characterized by immunoblotting in mock-, wild-type AßPP (wtAßPP)-, BACE1-, and Swedish mutant AßPP (SweAßPP)-transfected cells. AßPP beta prime cleavage was confirmed through secretase inhibitor studies and C-terminal fragment analysis. The roles of sAßPPα and sAßPPß' in cell viability were confirmed by overexpression studies. RESULTS: Despite producing enhanced Aß peptide levels, wtAßPP- and SweAßPP-transfected cells did not exhibit reduced viability whereas BACE1-transfected cells did. sAßPPα generation in SH-SY5Y-BACE1 cells was virtually ablated in lieu of BACE1-mediated sAßPPß' production. sAßPPα overexpression in SH-SY5Y-BACE1 cells restored viability whereas sAßPPß' overexpression decreased viability further. The anti-AßPP 6E10 antibody was shown to cross-react with sAßPPß'. CONCLUSION: sAßPPα depletion and/or sAßPPß' accumulation, but not elevated Aß peptide levels, represent the cytotoxic mechanism following BACE1 overexpression in SH-SY5Y cells. These data support the novel concept that competitive sAßPPα depletion by BACE1 beta prime activity might contribute to AD. The cross-reactivity of 6E10 with AßPPß'also questions whether previous studies assessing sAßPPα as a biomarker using this antibody should be revisited.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Peptídeos beta-Amiloides , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Sobrevivência Celular , Humanos
18.
Int Urol Nephrol ; 53(12): 2453-2458, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34661823

RESUMO

PURPOSE: To assess the impact of microsurgical varicocelectomy technique on clinical outcomes. METHODS: Men diagnosed with varicocele between 2017 and 2020 were reviewed. We included men who underwent microsurgical varicocelectomy by two high-volume surgeons who differed in surgical technique: Method (1) testicular delivery with gubernacular vein ligation, and ligation of vasal veins > 2.5 mm; Method (2) no delivery and ligation of dilated vasal veins in cases of recurrence. Post-operative changes for semen parameters, DNA fragmentation, and serum testosterone were evaluated for each technique and compared. RESULTS: 313 patients were included; 162 with Method 1 and 151 with Method 2. The cohorts were of similar age (median 35 years, interquartile range (IQR) 28-43; 34, IQR 28-39, respectively), and BMI (25 kg/m2, IQR 23-27; 25, IQR 23-28, respectively). For Method 1, 84 (51.9%) had bilateral surgery, and 78 (48.1%) had unilateral surgery. For Method 2, 63 (41.7%) had bilateral surgery, and 88 (58.3%) unilateral surgery. In patients with sperm concentration > 5 M/mL, both techniques resulted in an improvement (p < 0.01), but there was no difference between the methods (p = 0.18). Both methods were associated with an improvement in total motile count (p < 0.05) and the amount of DNA fragmentation (p < 0.05), although no differences were apparent between the techniques (p = 0.09, p = 0.81, respectively). Finally, testosterone levels improved with Method 1, but the post-operative difference was not different than Method 2 (p = 0.06). CONCLUSION: Delivery of the testis and ligation of dilated vasal veins compared to not performing those steps do not impact semen parameters, but are associated with improvement in testosterone levels.


Assuntos
Microcirurgia/métodos , Testículo/irrigação sanguínea , Varicocele/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Humanos , Ligadura , Masculino , Veias/cirurgia
19.
Cell Rep ; 36(10): 109625, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34496233

RESUMO

The normal androgen receptor (AR) cistrome and transcriptional program are fundamentally altered in prostate cancer (PCa). Here, we profile the chromatin landscape and AR-directed transcriptional program in normal prostate cells and show the impact of SPOP mutations, an early event in prostate tumorigenesis. In genetically normal mouse prostate organoids, SPOP mutation results in accessibility and AR binding patterns similar to that of human PCa. Consistent with dependence on AR signaling, castration of SPOP mutant mouse models results in the loss of neoplastic phenotypes, and human SPOP mutant PCa shows a favorable response to AR-targeted therapies. Together, these data validate mouse prostate organoids as a robust model for studying epigenomic and transcriptional alterations in normal prostate, provide valuable datasets for further studies, and show that a single genomic alteration may be sufficient to reprogram the chromatin of normal prostate cells toward oncogenic phenotypes, with potential therapeutic implications for AR-targeting therapies.


Assuntos
Cromatina/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Próstata/metabolismo , Neoplasias da Próstata/metabolismo , Androgênios/imunologia , Animais , Carcinogênese/genética , Masculino , Camundongos Transgênicos , Neoplasias da Próstata/genética , Receptores Androgênicos/metabolismo , Proteínas Repressoras/metabolismo , Transdução de Sinais/fisiologia
20.
J Vasc Interv Radiol ; 32(9): 1328-1340.e11, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34256123

RESUMO

PURPOSE: To review and compare the outcomes of prostatic artery embolization (PAE) with 3 other minimally invasive surgical treatments for benign prostatic hyperplasia, including photoselective vaporization (PVP), prostatic urethral lift (PUL), and water vapor thermal therapy (WV). METHODS: A literature review was used to identify 35 publications, which included 2,653 patients (studies, patients): PVP (13, 949), PUL (9, 577), WV (3, 330), and PAE (10, 728). The international prostate symptom score (IPSS) and the international index of erectile function (IIEF-5) and quality of life (QOL) scores were recorded at baseline, 6 months, and 12 months. Meta-analyses, pooling the standardized mean difference between scores recorded before and after treatment, were conducted for each modality and time point to assess the magnitude of a therapy's effect to yield pooled effect sizes. A negative score indicates IPSS and QOL improvement. A positive score indicates IIEF-5 improvement. RESULTS: At 6 and 12 months, the IPSS and QOL were most improved after PVP, followed by that after PAE, PUL, and, lastly, WV (measured only at 12 months). Between 6 and 12 months, the IPSS and QOL improved with PAE and worsened with PVP and PUL. Only PAE demonstrated statistical improvement in the IIEF-5, which improved from 6 to 12 months. CONCLUSIONS: PVP and PAE resulted in the largest improvements in the IPSS and QOL. Only PAE resulted in improvement of the IIEF-5.


Assuntos
Embolização Terapêutica , Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Humanos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Masculino , Hiperplasia Prostática/complicações , Hiperplasia Prostática/terapia , Qualidade de Vida , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA