Proxalutamide in metastatic castration-resistant prostate cancer: Primary analysis of a multicenter, randomized, open-label, phase 2 trial.

We aim to assess the safety and efficacy of proxalutamide, a novel androgen receptor antagonist, for men with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter, randomized, open-label, phase 2 trial. In our study, the enrolled mCRPC patients were randomized to 100, 200 and 300 mg dose groups at 1:1:1. The primary efficacy endpoint was prostate-specific antigen (PSA) response rate. The secondary endpoints included objective response rate (ORR), disease control rate (DCR) and time to PSA and radiographic progression. Safety and pharmacokinetics were also assessed. Finally, there were 108 patients from 17 centers being enrolled. By week 16, there were 13 (35.1%), 12 (36.4%) and 15 (42.9%) patients with confirmed 50% or greater PSA decline in 100 mg (n = 37), 200 mg (n = 33) and 300 mg (n = 35) groups, respectively. Among the 19 patients with target lesions at study entry, three (15.8%) had a partial response and 12 (63.2%) had stable disease. The ORRs of 20.0%, 22.2%, 0% and DCRs of 80.0%, 88.9%, 60.0% were, respectively, achieved in 100, 200 and 300 mg groups. By the maximum follow-up time of 24 weeks, there were 42.6% and 10.2% of cases experiencing PSA progression and radiographic progression, respectively. Overall, adverse events (AEs) were experienced by 94.4% of patients, most of which were mild or moderate. There were 28 patients experiencing ≥grade 3 AEs. The most common AEs were fatigue (17.6%), anemia (14.8%), elevated AST (14.8%) and ALT (13.0%), decreased appetite (13.0%). These findings preliminarily showed the promising antitumor activity of proxalutamide in patients with mCRPC with a manageable safety profile. The proxalutamide dose of 200 mg daily is recommended for future phase 3 trial (Clinical trial registration no. CTR20170177).

Efficacy and safety of Androgen Deprivation Therapy (ADT) combined with modified docetaxel chemotherapy versus ADT combined with standard docetaxel chemotherapy in patients with metastatic castration-resistant prostate cancer: study protocol for a multicentre prospective randomized controlled trial.

BACKGROUND: Androgen deprivation therapy (ADT) combined with docetaxel chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (mCRPC) patients. However, mCRPC patients are mainly frail elderly men, constantly accompanied by comorbidities and showing poor tolerance to standard docetaxel chemotherapy. Some exploratory studies administering modified chemotherapy regimens have reported noninferior oncologic outcomes with fewer adverse events, yet most are retrospective or small studies, and prospective randomized controlled trials have rarely been conducted. Therefore, we designed this modified docetaxel chemotherapy regimen in patients with mCRPC, aiming to evaluate its efficacy and safety compared with the standard docetaxel chemotherapy regimen. METHODS: This is an open-label, multi-institutional, prospective, randomized non-inferiority trial. A total of 128 patients with mCRPC will be randomized to receive ADT combined with modified docetaxel chemotherapy (experimental group, n=64) or ADT combined with standard docetaxel chemotherapy (control group, n=64). Patients in the experimental group will receive a modified regimen with docetaxel 40 mg/m2 on the 1st day and 35 mg/m2 on the 8th day, repeated every 21 days. The primary endpoint is progression-free survival at 2 years. Secondary endpoints include overall survival, prostate-specific antigen response rate, pain response rate, toxicity and quality of life. DISCUSSION: The expected benefit for the patient in the experimental arm is noninferior efficacy with decreased toxicity and improved quality of life compared with that in the control arm. To the best of our knowledge, this will be the first multicentre prospective randomized study to assess the efficacy and safety of modified docetaxel chemotherapy in patients with mCRPC in China. The results of this trial may provide benefit to mCRPC patients, especially those with poor performance. TRIAL REGISTRATION: chictr.org.cn Identifier: ChiCTR2100046636 (May 24, 2021). Ongoing study.

Extended endocrine therapy in breast cancer: A basket of length-constraint feature selection metaheuristics to balance Type I against Type II errors.

Extended endocrine therapy beyond 5 years is of major concern to ER + breast cancer survivors. However, it might be unsuitable to apply routinely used genomic tests designed for early recurrence risks to distant recurrence within 10 years in extended treatment context. These tests initially aim at high sensitivities with Type I errors much higher than Type II. Having lower positive predictive values (PPVs), these tests can bring many false positives who might not need further treatment options to avoid adversely affecting quality of life. Alternatively, we proposed a top-down approach to the raised issues. We built 149 targeted genes from four genomic tests upon 381 ER-positive node-negative patients with either metastasis free beyond 10 years (n = 202) or metastasis within 10 years (n = 179). By a basket of SVM-wrapped length-constraint feature selection (LCFS), we discovered four genomic SVMs that traded off Type I against Type II errors. Two independent cohorts were used to validate disease outcome predictions. A 36-gene SVM balanced sensitivities with PPVs at good levels: 74% vs 76% on 10-fold cross validation (n = 347) and 75% vs 71% on a test set (n = 34). Neither Oncotype DX RS (cutoff = 18, 31, 60.97) nor PAM50 ROR-S (cutoff = 29, 53, 61.18) could. Independent cohorts showed the 36-gene SVM predicted disease free survival (n = 136, HR = 2.59; 95% CI, 1.4-4.8) and disease specific survival (n = 127, HR = 4.06; 95% CI, 1.63-10.11) better than RS (DFS, HR = 2.15; DSS, HR = 3.86) and ROR-S (DFS, HR = 2.29; DSS, HR = 2.76). The case study demonstrated how we identified a genomic test to balance Type I against Type II errors for risk stratification. The top-down approach centered around the LCFS-metaheuristics basket is a generic methodology for clinical decision-making and quality of life using targeted profiling data where the number of dimensions (p) is smaller than the number of samples (n).

Diagnostic performance of prostate cancer antigen 3 and the Prostate Health Index in detecting overall and clinically significant prostate cancer in men at first biopsy: A meta-analysis.

OBJECTIVE: To evaluate the diagnostic value of prostate cancer antigen 3 and the Prostate Health Index for the detection of overall and clinically significant prostate cancer at initial biopsy. METHODS: A search was conducted in the online databases PubMed, Embase and the Cochrane database, and relevant articles published up to 23 February 2020 were extracted. RESULTS: Twenty studies including 10 376 patients were included in the meta-analysis. The pooled sensitivity and specificity were 0.55 (95% confidence interval 0.53-0.57) and 0.74 (95% confidence interval 0.72-0.75) for prostate cancer antigen 3 and 0.88 (95% confidence interval 0.86-0.90) and 0.36 (95% confidence interval 0.34-0.38) for the Prostate Health Index. The area under the curve was 0.72 for prostate cancer antigen 3 and 0.76 for the Prostate Health Index. The combination of prostate cancer antigen 3 and the Prostate Health Index had a higher area under the curve (0.79) and diagnostic odds ratio (5.83) than the use of Prostate Health Index (area under the curve 0.75, diagnostic odds ratio 4.69) or prostate cancer antigen 3 (area under the curve 0.77, diagnostic odds ratio 4.84) alone. For clinically significant prostate cancer detection, the pooled sensitivity and specificity were 0.80 (95% confidence interval 0.76-0.84) and 0.53 (95% confidence interval 0.50-0.55), respectively, for prostate cancer antigen 3, and 0.77 (95% confidence interval 0.71-0.82) and 0.64 (95% confidence interval 0.61-0.67), respectively, for the Prostate Health Index. The area under the curve was 0.71 for prostate cancer antigen 3 and 0.77 for the Prostate Health Index. CONCLUSION: Both the Prostate Health Index and prostate cancer antigen 3 showed acceptable and similar results for the detection of overall and clinically significant prostate cancer at first biopsy. A combination of these two diagnostic tests may be more helpful than the use of either test alone in prostate cancer management.

Intratumoral heterogeneity and genetic characteristics of prostate cancer.

Prostate cancer is a heterogeneous disease and optimum gene targeting treatment is often impermissible. We aim to determine the intratumoral genomic heterogeneity of prostate cancer and explore candidate genes for targeted therapy. Exome sequencing was performed on 37 samples from 16 patients with prostate cancer. Somatic variant analysis, copy number variant (CNV) analysis, clonal evolution analysis and variant spectrum analysis were used to study the intratumoral genomic heterogeneity and genetic characteristics of metastatic prostate cancer. Our study confirmed the high intratumoral genetic heterogeneity of prostate cancer in many aspects, including number of shared variants, tumor mutation burden (TMB), variant genes, CNV burden, weighted genome instability index (wGII), CNV profiles, clonal evolutionary process, variant spectrum and mutational signatures. Moreover, we identified several common genetic characteristics of prostate cancer. Alterations of DNA damage repair genes, RTK/RAS pathway associated gene RASGRF1 and autophagy gene EPG5 may be involved in tumorigenesis in prostate cancer. CNV burden and DNA damage repair (DDR) genes may be associated with metastasis of prostate cancer.

The status and characteristics of urinary stone composition in China.

OBJECTIVES: To explore characteristics of urinary stone composition in China, and determine the effects of gender, age, body mass index (BMI), stone location, and geographical region on stone composition. PATIENTS AND METHODS: We prospectively used Fourier-transform infrared spectroscopy to analyse stones from consecutive patients presenting with new-onset urolithiasis at 46 hospitals in seven geographical areas of China, between 1 June 2010 and 31 May 2015. Chi-squared tests and logistic regression analyses were used to determine associations between stone composition and gender, age, BMI, stone location, and geographical region. RESULTS: The most common stone constituents were: calcium oxalate (CaOx; 65.9%), carbapatite (15.6%), urate (12.4%), struvite (2.7%), and brushite (1.7%). CaOx and urate stones occurred more frequently in males, whereas carbapatite and struvite were more common in females (P < 0.01). CaOx and carbapatite were more common in those aged 30-50 and 20-40 years than in other groups. Brushite and struvite were most common amongst those aged <20 and >70 years. The detection rate of urate increased with age, whilst cystine decreased with age. Obese patients were more likely to have urate stones than carbapatite or brushite stones (P < 0.01). CaOx, carbapatite, brushite, and cystine stones were more frequently found in the kidney than other types, whereas urate and struvite were more frequent in the bladder (P < 0.01). Stone composition varied by geographical region. CONCLUSIONS: The most common stone composition was CaOx, followed by carbapatite, urate, struvite, and brushite. Stone composition differed significantly in patients grouped by gender, age, BMI, stone location, and geographical region.

The clinicopathological characteristics and prognostic value of squamous differentiation in patients with bladder urothelial carcinoma: a meta-analysis.

PURPOSE: Urothelial carcinoma with squamous differentiation (UCSD) is the most common histologic variant in bladder cancer (BCa). Previously, some studies have linked the presence of UCSD with the risk of worse survival outcomes in BCa patients. However, such association is still controversial. In this study, we performed a meta-analysis to clarify the clinicopathological characteristics and to further investigate the prognostic value of UCSD in BCa. METHODS: A systematic literature search was performed in electronic databases including PubMed, Embase, Chinese National Knowledge Infrastructure and Wanfang Data until October 2018. Subgroup analyses were performed according to different treatments and study outcomes. RESULTS: Total of 13,284 patients were enrolled in 19 studies which were included in this meta-analysis. The percentage of female patients with UCSD was significantly higher than those with pure urothelial carcinoma. UCSD was correlated with tumor stage T3/T4, tumor grade 3, positive surgical margin, and lymph node involvement. Moreover, the recurrence rate was higher in patients with UCSD after surgery. UCSD was associated with poorer disease-free survival (DFS). No significant difference of cancer-specific survival (CSS) or overall survival (OS) was found on multivariable analysis between the two groups. CONCLUSIONS: Our study demonstrated that UCSD in BCa was associated not only with unfavorable clinicopathological features, but also with high risk of recurrence and poorer prognosis for DFS. However, UCSD is not independently significant for CSS and OS. Well-designed randomized study with larger sample size is warranted to verify the findings and to further explore the role of UCSD in BCa.

Prognostic value of pretreatment neutrophil-to-lymphocyte ratio in renal cell carcinoma: a systematic review and meta-analysis.

BACKGROUND: Numerous studies show that the pretreatment neutrophil-to-lymphocyte ratio (NLR) is associated with the prognosis of patients with RCC. However, their findings are inconsistent, urging us to explore the prognostic value of NLR in RCC patients. METHODS: This study was pre-registered in PROSPERO (CRD42020167131). Two reviewers independently performed a systematical search of PubMed, Web of Science, EMBASE, and Cochrane Library databases for prospective or retrospective cohort studies investigating the prognostic value of pretreatment NLR. Hazard ratios with 95% confidence intervals for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), cancer-specific survival (CSS), and other useful clinicopathological features were extracted and analyzed with fixed or random-effect models by using Review Manager 5.3 and Stata 12.0 software. Heterogeneity was estimated on the basis of Cochran's Q test and I2 value. Sensitivity analyses and subgroup analyses were also performed to explore the potential sources of heterogeneity. Publication bias was assessed with funnel plots and precisely assessed by Egger's tests. The quality of the evidence was evaluated in accordance with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS: Overall, 6461 RCC patients from 24 retrospective studies and 1 prospective study were included. In overall population, elevated pretreatment NLR was associated with poorer OS (pooled HR = 1.90, 95% CI = 1.56-2.30, p < 0.001; I2 = 87%), DFS/PFS (pooled HR = 2.09, 95% CI: 1.49-2.94, p < 0.001; I2 = 99%), and CSS (pooled HR = 2.31, 95% CI: 1.61-3.33, p < 0.001; I2 = 14%). Furthermore, this negative association was further confirmed in patients with nonmetastatic and metastatic RCC patients, respectively. We also investigated the predictive role of NLR in metastatic RCC patients treated with immune checkpoint inhibitors (ICIs). The results indicated that the level of NLR was significantly associated with OS (pooled HR = 3.92, 95% CI: 2.00-7.69, p < 0.001; I2 = 0%) and PFS (pooled HR = 2.20, 95% CI: 95% CI: 1.61-3.01, p < 0.001; I2 = 20%). CONCLUSIONS: This study demonstrated that elevated pretreatment NLR was significantly associated with poor prognosis of RCC patients. NLR could be helpful as a potential prognostic biomarker to guide clinical decision-making and select individualized treatment strategies for RCC patients.

Prognostic value of preoperative lymphocyte-related systemic inflammatory biomarkers in upper tract urothelial carcinoma patients treated with radical nephroureterectomy: a systematic review and meta-analysis.

BACKGROUND: Growing evidence shows that the preoperative lymphocyte-related systemic inflammatory biomarkers are associated with the prognosis of patients with upper tract urothelial carcinoma (UTUC). These markers include neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR). However, these findings are inconsistent, and the prognostic significance of these biomarkers is unclear. Moreover, the currently available prognostic indicators do not precisely predict the outcome of UTUC patients. This motivated us to investigate the prognostic values of NLR, PLR, and MLR in UTUC patients treated with radical nephroureterectomy (RNU). METHODS: We prospectively registered this in PROSPERO (CRD42020186531). We performed a comprehensive literature search of the PubMed, Web of Science, EMBASE, and Cochrane Library databases to identify the eligible studies evaluating the prognostic values of preoperative NLR, PLR, and MLR. Hazard ratios with 95% confidence intervals of overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), recurrence-free survival (RFS), metastasis-free survival (MFS), and progression-free survival (PFS) were extracted from the multivariate analyses and analyzed with fixed or random effects models when applicable. Heterogeneity among the studies was evaluated using Cochran's Q test and I2 statistic. Sensitivity and subgroup analyses were conducted to explore the origin of heterogeneity. The Newcastle-Ottawa Scale (NOS) was applied to assess the quality of each enrolled study. Publication bias was determined using funnel plots together with Egger's tests. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the quality of the evidence. RESULTS: Overall, we included 10,339 UTUC patients from twenty-five retrospective studies. The results indicated that elevated preoperative NLR, PLR, and MLR were significantly associated with worse OS, CSS, DFS/RFS/MFS, and PFS in the UTUC patients undergoing RNU. Furthermore, the results of sensitivity and subgroup analyses demonstrated the rationality and reliability of the results. CONCLUSIONS: The present meta-analysis demonstrated a significant association between elevated preoperative NLR, PLR, and MLR and poor prognosis in patients with surgically treated UTUC. Hence, lymphocyte-related systemic inflammatory biomarkers, in conjunction with clinicopathological factors, molecular markers, and other prognostic indicators, could be helpful to determine the primary treatment strategies and to design individualized follow-up plans for UTUC patients.

Retrolaparoscopic adrenalectomy assisted by three-dimensional reconstructed digital model in a patient with situs inversus totalis.

BACKGROUND: Situs inversus totalis is a relatively rare congenital anomaly. Performing the retrolaparoscopic adrenalectomy for the patient with situs inversus totalis is a skill-demanding and challenging surgical task, which has been even more rarely reported. CASE PRESENTATION: We present a case with a large right adrenal mass (10.2 × 9.4 × 7.9 cm) complicated by situs inversus totalis. This 59-year-old female patient underwent the retrolaparoscopic adrenalectomy in our department. In order to facilitate the surgical orientation and improve the manipulating accuracy, the data from computed tomography images was extracted and the three-dimensional digital model was reconstructed. Under the assistance of preoperative planning and intraoperative navigation by the three-dimensional digital model, the retrolaparoscopic adrenalectomy was technically precise and successful. The targeted adrenal tumor was excised completely with final pathological diagnosis of adrenocortical adenoma. CONCLUSIONS: Retrolaparoscopic adrenalectomy can be performed safely in patients with situs inversus totalis. The assistance of preoperative planning and intraoperative navigation by the reconstructed three-dimensional digital model can facilitate the operation and lead to more precise vessel manipulation and accurate excision of tumor that is both effective and safe.

The effect of mast cells on the biological characteristics of prostate cancer cells.

AIM OF THE STUDY: To investigate the effects of mast cells on the proliferation, invasion, and metastasis of prostate cancer cells. MATERIAL AND METHODS: The mast cell P815 and prostate cancer LNCaP cells were chosen using a Transwell chamber to construct a two-cell cocultured in vitro model to observe the migration of mast cells to prostate cancer cells. RESULTS: In the migration experiment, the migration rate of mast cells from the experimental group (%) was 10.167 ±0.833, the mast cell migration rate (%) of the control group was 0.833 ±0.208, and the difference was statistically significant (p < 0.05). The MTT test showed that the OD value of cells in each group over time increased gradually, and 24 h after LNCaP cells were cocultured with different concentrations of mast cells, the OD value was significantly higher than that of the control group (p < 0.05). QRT-PCR and western blot results showed that, compared with the control group, E-cad expression from the experimental group was significantly weakened; N-cad and vimentin expression increased (p < 0.05), and c-kit and SCF expression from experimental group were significantly higher than that of the control group (p < 0.05). After the addition of c-kit neutralising antibodies, compared with the control group, the mast cell migration rate of experimental group decreased significantly and prostate cancer cell proliferation significantly decreased (p < 0.05). CONCLUSIONS: Mast cells could promote the proliferation of prostate cancer cells and the occurrence of epithelial mesenchymal transition (EMT), which could promote the invasion and metastasis of prostate cancer cells.

Endoplasmic reticulum stress is involved in apoptosis of detrusor muscle in streptozocin-induced diabetic rats.

AIMS: Endoplasmic reticulum stress (ERS) has been proven to be associated with apoptosis and plays a critical role in the development of many diabetic complications. In the pathogenesis of diabetic cystopathy (DCP), the role of ERS is still unclear. Our study is aimed at the investigation of the involvement of ERS-associated detrusor muscle apoptosis in streptozocin (STZ)-induced diabetic rats. METHODS: At different timepoints (4, 8, 12, and 16 weeks after induction of type 1 diabetic rat models), hematoxylin & eosin (H&E) staining was performed to assess the histological changes of the diabetic detrusor; the sub-cellular ultrastructure, especially the zone of endoplasmic reticulum (ER), was observed by transmission electron microscopy (TEM), and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labeling (TUNEL) staining was used to identify the enhanced apoptosis. Moreover, the expression of three hallmarks of ERS-associated apoptosis, including glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and caspase12, was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. RESULTS: Light microscopic impairments of histology, including progressive loosely packed muscle bundles and increased fibrous tissue, can be seen; the ultrastructural changes featuring the swollen and fused cisternaes in ER zone and deformed nucleus were also observed in the detrusor smooth muscle (DSM). Increased apoptosis and elevated expression of GRP78, CHOP, and caspase12 at both protein and mRNA levels in a time-dependent fashion were detected. CONCLUSIONS: The occurrence of ERS-associated apoptosis may be involved in the development of DCP and may contribute to the diabetic detrusor impairment. Neurourol. Urodynam. 36:65-72, 2017. © 2015 Wiley Periodicals, Inc.

Combination of α-blocker and 5α-reductase inhibitor for treatment of benign prostatic hyperplasia.

PURPOSE: This study compared the efficacy of an α-blocker monotherapy alone with a combination of α-blocker plus 5α-reductase in treatment of benign prostatic hyperplasia (BPH). METHODS: Medline (PubMed), EMBASE, CENTRAL (Cochrane databases) and Google Scholar were searched until May 2015 using the following search terms: ([α-blocker] AND 5α-reductase inhibitor) AND benign prostatic hyperplasia; and benign prostatic hyperplasia AND (adrenergic alpha blockers OR 5 alpha reductase inhibitor). Randomized controlled trials (RCTs) that included men with a clinical diagnosis of BPH were included. Eligible studies had to have an intervention group that received combination therapy (5α reductase inhibitor plus α-blocker) and a control group that received only α-blocker. Quality assessment and sensitivity analysis were performed. RESULTS: Six studies were included. Combination therapy was found to significantly reduce urinary retention incidence rate (OR=0.286, 95%CI: 0.199 - 0.412, P.

[Diagnosis and treatment of ovotesticular disorder of sex development: A report of 2 cases].

OBJECTIVE: To investigate the characteristics, diagnosis, and treatment of ovotesticular disorder of sex development (OT-DSD). METHODS: We retrospectively analyzed 2 cases of OT-DSD treated in our hospital. The patients were 19 and 15 years old, respectively, and both received systematic physical examination and examinations of the karyotype, sex hormone, adrenocorticotropic hormone (ACTH), color Doppler ultrasonography, urethrocystoscopy, and human chorionic gonadotropin (HCG) test. Under the laparoscope, we performed surgical gonad exploration, gonadectomy, and vulvar orthopedics. Intraoperative exploration and pathology confirmed true hermaphroditism in both cases, with sex selection as female. One underwent laparoscopic resection of the ovotestis, and the other removal of the testis with the ovarian tissue reserved. RESULTS: The patients were followed up for 12 months postoperatively, which found no abnormality in either the vulvas or the genital glands. CONCLUSION: Surgical exploration of the gonad is the only method for the diagnosis of OT-DSD and sex selection is the key to treatment. Laparoscopic surgical exploration of the gonad and vulvar orthopedics are the first treatment options.

Evaluation of an Enhanced Role-Based Access Control model to manage information access in collaborative processes for a statewide clinical education program.

BACKGROUND: Managing information access in collaborative processes is a critical requirement to team-based biomedical research, clinical education, and patient care. We have previously developed a computation model, Enhanced Role-Based Access Control (EnhancedRBAC), and applied it to coordinate information access in the combined context of team collaboration and workflow for the New York State HIV Clinical Education Initiative (CEI) program. We report in this paper an evaluation study to assess the effectiveness of the EnhancedRBAC model for information access management in collaborative processes when applied to CEI. METHODS: We designed a cross-sectional study and performed two sets of measurement: (1) degree of agreement between EnhancedRBAC and a control system CEIAdmin based on 9152 study cases, and (2) effectiveness of EnhancedRBAC in terms of sensitivity, specificity, and accuracy based on a gold-standard with 512 sample cases developed by a human expert panel. We applied stratified random sampling, partial factorial design, and blocked randomization to ensure a representative case sample and a high-quality gold-standard. RESULTS: With the kappa statistics of four comparisons in the range of 0.80-0.89, EnhancedRBAC has demonstrated a high level of agreement with CEIAdmin. When evaluated against the gold-standard, EnhancedRBAC has achieved sensitivities in the range of 97-100%, specificities at the level of 100%, and accuracies in the range of 98-100%. CONCLUSIONS: The initial results have shown that the EnhancedRBAC model can be effectively used to manage information access in the combined context of team collaboration and workflow for coordination of clinical education programs. Future research is required to perform longitudinal evaluation studies and to assess the effectiveness of EnhancedRBAC in other applications.

A systematic review and meta-analysis combined with bioinformatic analysis on the predictive value of E-cadherin in patients with renal cell carcinoma.

OBJECTIVES: Renal cell carcinoma (RCC) is the most common cancer of the kidney. This study aims to evaluate the potential predictive value of E-cadherin, a marker of the epithelial mesenchymal transit (EMT) process that has been associated with tumor metastasis. METHODS: We searched PubMed, Embase, and Cochrane Library to identify prospective studies. Hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were summarized to validate the relationship between E-cadherin and survival and clinical characteristics. The quality of the included studies was assessed using the NOS table. Then, we analyzed genetic data and clinical characteristics from The Cancer Genome Atlas Program (TCGA) database using R language with the dplyr package for validation. RESULTS: Including 21 articles. The analysis revealed a strong link between high E-cadherin expression and favorable prognosis (for OS, HR = 0.35, 95% CI: 0.19-0.62; for PFS, HR = 0.19, 95% CI: 0.03-0.53; for DSS, HR = 0.25, 95% CI: 0.08-0.76; for RFS, HR = 0.71, 95% CI: 0.44-1.16; for DFS, HR = 0.28, 95% CI: 0.13-0.61; for T stage, OR = 0.21, 95% CI: 0.11-0.41; for N stage, OR = 0.07, 95%CI: 0.02-0.25; for M stage, OR = 0.12, 95% CI: 0.02-0.60; for clinical stage, OR = 0.29, 95% CI: 0.18-0.47; for nuclear grade, OR = 0.23, 95% CI: 0.13-0.41; for tumor size, OR = 0.49, 95% CI: 0.26-0.92). The findings were supported by bioinformatic analysis which used TCGA RCC patient's cohort (P < 0.01). CONCLUSION: Based on the current data, E-cadherin may predict a better prognosis in RCC patients.

Evaluation of a Patient Decision Aid for Refractive Eye Surgery.

BACKGROUND: We developed a prototype patient decision aid, EyeChoose, to assist college-aged students in selecting a refractive surgery. EyeChoose can educate patients on refractive errors and surgeries, generate evidence-based recommendations based on a user's medical history and personal preferences, and refer patients to local refractive surgeons. OBJECTIVES: We conducted an evaluative study on EyeChoose to assess the alignment of surgical modality recommendations with a user's medical history and personal preferences, and to examine the tool's usefulness and usability. METHODS: We designed a mixed methods study on EyeChoose through simulations of test cases to provide a quantitative measure of the customized recommendations, an online survey to evaluate the usefulness and usability, and a focus group interview to obtain an in-depth understanding of user experience and feedback. RESULTS: We used stratified random sampling to generate 245 test cases. Simulated execution indicated EyeChoose's recommendations aligned with the reference standard in 243 (99%). A survey of 55 participants with 16 questions on usefulness, usability, and general impression showed that 14 questions recorded more than 80% positive responses. A follow-up focus group with 10 participants confirmed EyeChoose's useful features of patient education, decision assistance, surgeon referral, as well as good usability with multimedia resources, visual comparison among the surgical modalities, and the overall aesthetically pleasing design. Potential areas for improvement included offering nuances in soliciting user preferences, providing additional details on pricing, effectiveness, and reversibility of surgeries, expanding the function of surgeon referral, and fixing specific usability issues. CONCLUSION: The initial evaluation of EyeChoose suggests that it could provide effective patient education, generate appropriate recommendations, connect to local refractive surgeons, and demonstrate good system usability in a test environment. Future research is required to enhance the system functions, fully implement and evaluate the tool in naturalistic settings, and examine the findings' generalizability to other populations.

Effect of CHST11, a novel biomarker, on the biological functionalities of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor, and the role of carbohydrate sulfotransferase 11 (CHST11) in this cancer remains unclear. Here, by using bioinformatics methods, we comprehensively analyzed the relationship between CHST11 and clinical significance, immune infiltration, functional enrichment, m6A methylation, and protein-protein interaction networks. We found that CHST11 expression was significantly higher in ccRCC samples than in normal tissues. Additionally, CHST11 levels correlated with the clinicopathological features of ccRCC patients and functioned as a prognostic factor for patient survival. Functional analysis revealed the involvement of CHST11 in metabolic pathways. Immune infiltration and m6A methylation analysis suggested the association of CHST11 with immune cell abundance in the tumor microenvironment and specific methylation patterns in ccRCC. The in vitro analysis of the clinical samples and ccRCC cell lines demonstrated that the overexpression of CHST11 promotes ccRCC cell proliferation, migration, and invasion, while its suppression has the opposite effect. Thus, CHST11 may play a remarkable role in the occurrence and progression of ccRCC. Functionally, CHST11 promotes the aggressiveness of ccRCC cells. These findings provide insights into the role of CHST11 in ccRCC progression.Registry and the Registration No. of the study/trial: No. 2021K034.

Development of a Study Protocol for Evaluation of a Novel Measure to Incorporate Information Freshness into Network Analysis of Online Resources for COVID-19.

We proposed a novel measure, Degree of Connectivity with Integration of Freshness (DCIF), to incorporate information freshness into analysis of online resource networks. We conducted a pilot study to apply this new measure to a dataset of online information resources related to COVID-19 risk assessment. Among the 52 nodes, we recorded statistically significant difference between the numerical values of DCIF and the traditional structural measure Degree of Connectivity (DC). Manual reviews of 18 selected nodes showed that DCIF outperformed DC in 11 of them, suggesting potential promise of the proposed new measure. We finalized the protocol for manual review based on the pilot and started a full-scale study. The proposed new measure has the potential to provide quantitative assessment on information freshness for timely and effective dissemination of clinical evidence. Further research is required to address the limitations of this pilot study and to examine the generalization of the findings.

The impact of positive surgical margin parameters and pathological stage on biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis.

BACKGROUND: To systematically review and perform a meta-analysis on the predictive value of the primary Gleason grade (PGG) at the positive surgical margin (PSM), length of PSM, number of PSMs, and pathological stage of the primary tumor on biochemical recurrence (BCR) in patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS: A systematic literature search was performed using electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, from January 1, 2005, to October 1, 2023. The protocol was pre-registered in PROSPERO. Subgroup analyses were performed according to the different treatments and study outcomes. Pooled hazard ratios with 95% confidence intervals were extracted from multivariate analyses, and a fixed or random effect model was used to pool the estimates. Subgroup analyses were performed to explore the reasons for the heterogeneity. RESULTS: Thirty-one studies that included 50,028 patients with PCa were eligible for this meta-analysis. The results showed that, compared to PGG3, PGG4/5 was associated with a significantly increased risk of BCR. Compared with PSM ≤3 mm, PSM ≥3 mm was associated with a significantly increased risk of BCR. Compared with unifocal PSM, multifocal PSM (mF-PSM) was associated with a significantly increased risk of BCR. In addition, pT >2 was associated with a significantly increased risk of BCR compared to pT2. Notably, the findings were found to be reliable based on the sensitivity and subgroup analyses. CONCLUSIONS: PGG at the PSM, length of PSM, number of PSMs, and pathological stage of the primary tumor in patients with PCa were found to be associated with a significantly increased risk of BCR. Thus, patients with these factors should be treated differently in terms of receiving adjunct treatment and more frequent monitoring. Large-scale, well-designed prospective studies with longer follow-up periods are needed to validate the efficacy of these risk factors and their effects on patient responses to adjuvant and salvage therapies and other oncological outcomes.