Green Synthesis of Gold Nanoparticles Using Liquiritin and Other Phenolics from Glycyrrhiza glabra and Their Anti-Inflammatory Activity.

Phenolic compounds are the main phytochemical constituents of many higher plants. They play an important role in synthesizing metal nanoparticles using green technology due to their ability to reduce metal salts and stabilize them through physical interaction/conjugation to the metal surface. Six pure phenolic compounds were isolated from licorice (Glycyrrhiza glabra) and employed in synthesizing gold nanoparticles (AuNPs). The isolated compounds were identified as liquiritin (1), isoliquiritin (2), neoisoliquiritin (3), isoliquiritin apioside (4), liquiritin apioside (5), and glabridin (6). The synthesized AuNPs were characterized using UV, zeta sizer, HRTEM, and IR and tested for their stability in different biological media. The phenolic isolates and their corresponding synthesized NP conjugates were tested for their potential in vitro cytotoxicity. The anti-inflammatory effects were investigated in both normal and inflammation-induced settings, where inflammatory biomarkers were stimulated using lipopolysaccharides (LPSs) in the RAW 264.7 macrophage cell line. LPS, functioning as a mitogen, promotes cell growth by reducing apoptosis, potentially contributing to observed outcomes. Results indicated that all six pure phenolic isolates inhibited cell proliferation. The AuNP conjugates of all the phenolic isolates, except liquiritin apioside (5), inhibited cell viability. LPS initiates inflammatory markers by binding to cell receptors and setting off a cascade of events leading to inflammation. All the pure phenolic isolates, except isoliquiritin, neoisoliquiritin, and isoliquiritin apioside inhibited the inflammatory activity of RAW cells in vitro.

The role of neoadjuvant chemotherapy for patients with variant histology muscle invasive bladder cancer undergoing robotic cystectomy: Data from the International Robotic Cystectomy Consortium.

OBJECTIVE: To assess the role of neoadjuvant chemotherapy (NAC) before robot-assisted radical cystectomy (RARC) for patients with variant histology (VH) muscle-invasive bladder cancer (MIBC). METHODS: Retrospective review of 988 patients who underwent RARC (2004-2023) for MIBC. Primary outcomes included the utilization of NAC among this cohort of patients, frequency of downstaging, and discordance between preoperative and final pathology in terms of the presence of VH. Secondary outcomes included disease-specific (DSS), recurrence-free (RFS), and overall survival (OS). RESULTS: A total of 349 (35%) had VH on transurethral resection or at RARC. The 4 most common VH subgroups were squamous (n = 94), adenocarcinoma (n = 64), micropapillary (n = 34), and sarcomatoid (n = 21). There was no difference in OS (log-rank: P = 0.43 for adenocarcinoma, P = 0.12 for micropapillary, P = 0.55 for sarcomatoid, P = 0.29 for squamous), RFS (log-rank: P = 0.25 for adenocarcinoma, P = 0.35 for micropapillary, P = 0.83 for sarcomatoid, P = 0.79 for squamous), or DSS (log-rank P = 0.91 for adenocarcinoma, P = 0.15 for micropapillary, 0.28 for sarcomatoid, P = 0.92 for squamous) among any of the VH based on receipt of NAC. Patients with squamous histology who received NAC were more likely to be downstaged on final pathology compared to those who did not (P < 0.01). CONCLUSION: Our data showed no significant difference in OS, RFS, or DSS for patients with VH MIBC cancer who received NAC before RARC. Patients with the squamous variant who received NAC had more pathologic downstaging compared to those who did not. The role of NAC among patients with VH is yet to be defined. Results were limited by small number in each individual group and lack of exact proportion of VH.

In vitro antimicrobial and antioxidant activities, essential oil composition, and in silico molecular modeling analysis of secondary metabolites from roots of Verbascum sinaiticum.

Verbascum sinaiticum is locally used to treat wound, stomachache, viral infection, cancer, sunstroke fever, abdominal colic, diarrhea, hemorrhage, anthrax, and hepatitis. The objective of this study was to identify the compounds and to evaluate the antimicrobial and antioxidant activity of the extracts and isolated compounds from V. sinaiticum. The 1H-NMR, 13C-NMR, and DEPT-135 were used to elucidate the structures of isolated compounds. Essential oils were extracted by hydrodistillation method and their chemical analyses were performed by GC-MS. The broth microdilution method was used to evaluate the antimicrobial activity. The radical scavenging activity of the extracts and isolated compounds were evaluated using DPPH method. Silica gel column chromatographic separation of root extracts afforded seven known compounds: 3'-(4''-methoxy phenyl)-3'-oxo-propionyl hexadecanoate (1), harpagoside (2), pulverulentoside I (3), scrophuloside B4 (4), scropolioside A (5), scropolioside-D2 (6), and harpagide 6-O-ß-glucoside (7), which are all reported from this species for the first time. The EO extracts from leaves and roots were the most susceptible to Streptococcus agalactiae, with a 2 mg/mL MIC. The EO from roots was effective against Candida albicans and Trichophyton mentagrophytes, with a MIC of 8 mg/mL. The MeOH and CH2Cl2/CH3OH (1:1) root extracts showed the maximum activity against S. epidermidis with MIC values of 0.25 mg/mL. The strongest antibacterial effects were demonstrated against Staphylococcus epidermidis, which exhibited a 0.0625 mg/mL MIC for compound 1. The strongest radical scavenging activity was exhibited by the methanol extract (IC50 = 3.4 µg/mL), and compounds 4, 6, 5, 3, 7, and 2 with IC50 values of 3.2, 3.38, 3.6, 3.8, 4.2, and 4.7 µg/mL, respectively, in comparison with ascorbic acid (IC50 = 1.3 µg/mL). The results of the molecular docking analysis of compounds revealed minimal binding energies range from -38.5 to -43.1 kJ/mol, -33.1 to -42.7 kJ/mol, -34.7 to -39.3.7 kJ/mol, -25.5 to -37.6 kJ/mol against human myeloperoxidase (PDB ID: 1DNU), murA enzyme (PDB ID: 1UAE), human topoisomerase IIß (PDB ID: 4fm9), S. epidermidis FtsZ (PDB number: 4M8I) proteins, respectively. The docking results and the in vitro antibacterial activity are in good agreement. These findings show that the isolated compounds 2-7 can act as potential antioxidants and strong antibacterials against Staphylococcus aureus and S. epidermidis. As a result, V. sinaiticum root extracts have the potential to be effective in treating diseases caused by bacteria and free radicals, as long as further investigation has been suggested for the ultimate decision of this plant's potential candidate.

Prodigiosin/celecoxib-loaded into zein/sodium caseinate nanoparticles as a potential therapy for triple negative breast cancer.

Nowadays, breast cancer is considered one of the most upsetting malignancies among females. Encapsulation of celecoxib (CXB) and prodigiosin (PDG) into zein/sodium caseinate nanoparticles (NPs) produce homogenous and spherical nanoparticles with good encapsulation efficiencies (EE %) and bioavailability. In vitro cytotoxicity study conducted on human breast cancer MDA-MB-231 cell lines revealed that there was a significant decline in the IC50 for encapsulated drugs when compared to each drug alone or their free combination. In addition, results demonstrated that there is a synergism between CXB and PDG as their combination indices were 0.62251 and 0.15493, respectively. Moreover, results of scratch wound healing assay revealed enhanced antimigratory effect of free drugs and fabricated NPs in comparison to untreated cells. Furthermore, In vitro results manifested that formulated nanoparticles exhibited induction of apoptosis associated with reduced angiogenesis, proliferation, and inflammation. In conclusion, nanoencapsulation of multiple drugs into nanoparticles might be a promising approach to develop new therapies for the managing of triple negative breast cancer.

Approaches for Stereotactic Radiosurgery (SRS)/Stereotactic Radiotherapy (SRT) in brain metastases using different radiotherapy modalities (Feasibility study).

BACKGROUND: SRS and SRT are precise treatments for brain metastases, delivering high doses while minimizing doses to nearby organs. Modern linear accelerators enable the precise delivery of SRS/SRT using different modalities like three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and Rapid Arc (RA). OBJECTIVE: This study aims to compare dosimetric differences and evaluate the effectiveness of 3DCRT, IMRT, and Rapid Arc techniques in SRS/SRT for brain metastases. METHODS: 10 patients with brain metastases, 3 patients assigned for SRT, and 7 patients for SRS. For each patient, 3 treatment plans were generated using the Eclipse treatment planning system using different treatment modalities. RESULTS: No statistically significant differences were observed among the three techniques in the homogeneity index (HI), maximum D2%, and minimum D98% doses for the target, with a p >  0.05. The RA demonstrated a better conformity index of 1.14±0.25 than both IMRT 1.21±0.26 and 3DCRT 1.37±0.31. 3DCRT and IMRT had lower Gradient Index values compared to RA, suggesting that they achieved a better dose gradient than RA. The mean treatment time decreased by 26.2% and 10.3% for 3DCRT and RA, respectively, compared to IMRT. In organs at risk, 3DCRT had lower maximum doses than IMRT and RA, but some differences were not statistically significant. However, in the brain stem and brain tissues, RA exhibited lower maximum doses compared to IMRT and 3DCRT. Additionally, RA and IMRT had lower V15Gy, V12Gy, and V9Gy values compared to 3DCRT. CONCLUSION: While 3D-CRT delivered lower doses to organs at risk, RA and IMRT provided better conformity and target coverage. RA effectively controlled the maximum dose and irradiated volume of normal brain tissue. Overall, these findings indicate that 3DCRT, RA, and IMRT are suitable for treating brain metastases in SRS/SRT due to their improved dose conformity and target coverage while minimizing dose to healthy tissues.

The ability of digital breast tomosynthesis to reduce additional examinations in older women.

Aims: To assess the diagnostic performance of digital breast tomosynthesis (DBT) in older women across varying breast densities and to compare its effectiveness for cancer detection with 2D mammography and ultrasound (U/S) for different breast density categories. Furthermore, our study aimed to predict the potential reduction in unnecessary additional examinations among older women due to DBT. Methods: This study encompassed a cohort of 224 older women. Each participant underwent both 2D mammography and digital breast tomosynthesis examinations. Supplementary views were conducted when necessary, including spot compression and magnification, ultrasound, and recommended biopsies. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) were calculated for 2D mammography, DBT, and ultrasound. The impact of DBT on diminishing the need for supplementary imaging procedures was predicted through binary logistic regression. Results: In dense breast tissue, DBT exhibited notably heightened sensitivity and NPV for lesion detection compared to non-dense breasts (61.9% vs. 49.3%, p < 0.001) and (72.9% vs. 67.9%, p < 0.001), respectively. However, the AUC value of DBT in dense breasts was lower compared with non-dense breasts (0.425 vs. 0.670). Regarding the ability to detect calcifications, DBT demonstrated significantly improved sensitivity and NPV in dense breasts compared to non-dense breasts (100% vs. 99.2%, p < 0.001) and (100% vs. 94.7%, p < 0.001), respectively. On the other hand, the AUC value of DBT was slightly lower in dense breasts compared with non-dense (0.682 vs. 0.711). Regarding lesion detection for all cases between imaging examinations, the highest sensitivity was observed in 2D mammography (91.7%, p < 0.001), followed by DBT (83.7%, p < 0.001), and then ultrasound (60.6%, p < 0.001). In dense breasts, sensitivity for lesion detection was highest in 2D mammography (92.9%, p < 0.001), followed by ultrasound (76.2%, p < 0.001), and the last one was DBT. In non-dense breasts, sensitivities were 91% (p < 0.001) for 2D mammography, 50.7% (p < 0.001) for ultrasound, and 49.3% (p < 0.001) for DBT. In terms of calcification detection, DBT displayed significantly superior sensitivity compared to 2D mammography in both dense and non-dense breasts (100% vs. 91.4%, p < 0.001) and (99.2% vs. 78.5%, p < 0.001), respectively. However, the logistic regression model did not identify any statistically significant relationship (p > 0.05) between DBT and the four dependent variables. Conclusion: Our findings indicate that among older women, DBT does not significantly decrease the requirement for further medical examinations.

The impact of NCCN-compliant multidisciplinary conference on the uptake of active surveillance among eligible patients with localized prostate cancer.

INTRODUCTION: We sought to investigate the impact of National Comprehensive Cancer Network (NCCN)-compliant multidisciplinary conference on the uptake of active surveillance (AS) among eligible patients with prostate cancer. METHODS: Retrospective review of our AS database was performed. Patients who are eligible for AS who sought a second opinion at a comprehensive cancer center (2010-2021) were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Cochrane Armitage test was used to examine trends over time. Multivariable regression models were fit to evaluate variables associated with the receipt of AS. RESULTS: Seven hundred twelve patients were identified (19% NCCN very low risk, 32% low risk, and 49% intermediate favorable risk). 43% were recommended AS as the preferred option by the community compared to 68% by LPCC, and 65% elected AS. Recommending AS significantly increased between 2010 and 2021 by the community (from 26% to 57%) and by LPCC (from 52% to 82%), while the proportion of men who received AS increased from 47% to 80% during the same period (P < 0.0001 for all). More recent LPCC era 2017 to 2021 (OR 12.31, 95% CI, 5.60-27.03, P < 0.0001), African American race (OR 0.42, 95% CI, 0.18-0.96, P = 0.04), positive cores at biopsy (OR 0.96, 95% CI, 0.94-0.97, P < 0.0001), age (OR 1.14, 95% CI, 1.10-1.18, P < 0.0001), NCCN low risk (OR 0.25, 95% CI, 0.08-0.81, P = 0.02) and NCCN intermediate favorable risk (OR 0.03, 95% CI, 0.01-0.09, P < 0.0001) were associated with receipt of AS. CONCLUSION: AS recommendation increased significantly over time by community urologists and to a higher extent by NCCN-compliant multidisciplinary conference. The Uptake of AS significantly increased within the same period. More recent LPCC era 2017 to 2021, African American race, the proportion of positive cores at biopsy, age, and NCCN risk were the main determinants of receipt of AS.

Does the urinary microbiome profile change after treatment of bladder cancer?

INTRODUCTION: We sought to investigate the change in the urinary microbiome profile after transurethral resection of bladder tumor (TURBT). METHODS: Urine specimens were collected from consecutive patients with bladder cancer. Patients were divided into those with bladder tumors ("Tumor group": de novo tumors or recurrent/progressed after TURBT ± intravesical therapy) versus those without evidence of recurrence after treatment "No Recurrent Tumor group". Samples were analyzed using 16S rRNA sequencing. Alteration in the urinary microbiome was described in terms of alpha (diversity within a sample measured by Observed, Chao, Shannon, and Simpson indices), beta diversities (diversity among different samples measured by Brady Curtis Diversity index), and differential abundance of bacteria at the genus level. Analyses were adjusted for gender, method of preservation (frozen vs preservative), and method of collection (mid-stream vs. catheter). RESULTS: Sixty-eight samples were analyzed (42 in "Tumor" vs 26 in "No Recurrent Tumor" groups). The median age was 70 years (IQR 64-74) and 85% were males. All patients in the "No Recurrent Tumor" group had non-muscle invasive bladder cancer and 85% received BCG compared to 69% and 43% for the "Tumor" group, respectively. There was no significant difference in alpha diversity (p > 0.05). Beta diversity was significantly different (p = 0.04). Veillonella and Bifidobacterium were more abundant in the "Tumor" group (> 2FC, p = 0.0002), while Escherichia-Shigella (> 2FC, p = 0.0002) and Helococcus (> 2FC, p = 0.0008) were more abundant in the "No Recurrent Tumor" group. CONCLUSION: Bladder cancer patients with no recurrence and/or progression exhibited a different urinary microbiome profile compared to those with tumors.

The Molluscicidal Activity of Green Synthesized Copper Oxide-Based Annona squamosa Seed Extract Nanoparticles on the Feeding Behavior, Biochemical, Molecular, and Immunohistochemical Alterations of Biomphalaria alexandrina Snails.

Because of their low ecological impact, plant molluscicides have garnered much attention. The work aimed to find out if Annona squamosa (AS) seed extract has a molluscicidal impact on Biomphalaria alexandrina snails and enhances this extract by adding CuO nanoparticles (NPs). Using a scanning electron microscope (SEM), transmission electron microscope (TEM), and PANalytical X'Pert PRO X-ray diffractometer (XRD), the presence of the green A. squamosa-based CuO NPs (AS-CuO NPs) was confirmed. After 24 h of exposure, the half-lethal concentration (LC50) of AS-CuO NPs was more toxic to mature B. alexandrina than the aqueous extract of AS seeds (LC50: 119.25 mg/L vs. 169.03 mg/L). The results show that snails exposed to sublethal doses of AS-CuO NPs at LC10 or LC25 (95.4 or 106.7 mg/L, respectively) had much higher glucose levels and alkaline phosphatase activity than those not exposed. Nevertheless, there was no discernible change in the protein content in general or glycogen phosphorylase production. Histological and immunohistochemical analysis showed that snails exposed to A. squamosa-derived CuO NPs LC10 had shrinking digestive tubules and degeneration as well as vacuolation of many digestive, secretory, ova, and sperm cells, with PCNA expressing positively in the hermaphrodite gland and digestive tubule cells. The toxic profile of green CuO NPs produced by A. squamosa may damage the biological activity of B. alexandrina snails; thus, this compound could be used as a molluscicidal base. Furthermore, B. alexandrina proved to be a useful biomarker of nanomaterial contamination.

Methoxylated Flavonols and ent-Kaurane Diterpenes from the South African Helichrysum rutilans and Their Cosmetic Potential.

Chromatographic fractionation of a methanol extract of Helichrysum rutilans afforded seven known compounds. The isolated compounds were identified as 5,7,8-trihydroxy-3,6-dimethoxyflavone-8-O-2-methyl-2-butanoate (C-1), 5,7-dihydroxy-3,6,8-trimethoxyflavone (C-2), 5-hydroxy-3,6,7,8-tetramethoxyflavone (C-3), 5-hydroxy-3,6,7-trimethoxyflavone (C-4), ent-kaurenoic acid (C-5), ent-kauran-18-al (C-6), and 15-α-hydroxy-(-)-ent-kaur-16-en-19-oic acid (C-7). Compounds C-1-C-4 demonstrated high antioxidant capacities on ORAC hydroxyl radical (2.114 ± 4.01; 2.413 ± 6.20; 1.924 ± 16.40; 1.917 ± 3.91) × 106; ORAC peroxyl radical (3.523 ± 3.22; 2.935 ± 0.13; 2.431 ± 8.63; 2.814 ± 5.20) × 103 µMTE/g; and FRAP (1251.45 ± 4.18; 1402.62 ± 5.77) µMAAE/g, respectively. Moderate inhibitory activities against Fe2+-induced lipid peroxidation were observed for C-1-C-4 as IC50 values of 13.123 ± 0.34, 16.421 ± 0.92, 11.64 ± 1.72, 14.90 ± 0.06 µg/mL, respectively, while their respective anti-tyrosinase activities with IC50 values of 25.735 ± 9.62, 24.062 ± 0.61, 39.03 ± 13.12, 37.67 ± 0.98 µg/mL were also observed. All compounds demonstrated TEAC values within the range of 1105-1424 µMTE/g. The result is an indication that a methanol extract of H. rutilans might possibly be a good source of natural antioxidants against ailments caused by cellular oxidative stress and as inhibitors against skin depigmentation, as well as possible raw materials needed for slowing down perishable agricultural products. This is the first report on the phytochemical and biological evaluation of H. rutilans.

Does testosterone replacement therapy increase the risk of conversion to treatment in patients with prostate cancer on active surveillance?

PURPOSE: We aimed to evaluate the impact of testosterone replacement therapy (TRT) in patients with localized prostate cancer (CaP) who elected active surveillance (AS). METHODS: A retrospective review of our CaP database was performed. Patients who received TRT while on AS were identified and were matched to a cohort of patient on AS while not on TRT (1:3) using propensity score matching. Treatment-free survival (TFS) was computed using Kaplan Meier method. Multivariable Cox regression model was used to evaluate variables associated with treatment. RESULTS: Twenty-four patients in the TRT group were matched to 72 patients without TRT. Median follow-up was 5.82 years (IQR 3.27-9.30). There was no significant difference in conversion to treatment (24% vs. 21%, P = 1.00) There was no significant difference in TFS (log rank P = 0.87). Prostate specific antigen (PSA) density was the only variable associated TFS (HR 1.08, 95%CI 1.03-1.13, P = 0.001). CONCLUSION: TRT was not associated with conversion to treatment in this matched analysis among patients with localized prostate cancer on AS.

Green-Synthesized Silver Nanoparticles: Antifungal and Cytotoxic Potential for Further Dental Applications.

Fungal infections caused by Candida albicans (C. albicans) are one of the most prevalent types of oral disorders in the elderly. It has been reported that drug resistance to fungal pathogens poses a severe risk to global healthcare systems and public health. Therefore, the goal of this work is to investigate the cytotoxic and antifungal properties of silver nanoparticles (AgNPs) produced using three different natural extracts: Berzelia lanuginose, Helichrysum cymosum, and Searsia crenata. According to the UV-Vis results, the synthesized AgNPs via B. lanuginose, H. cymosum, and S. crenata show surface plasmonic resonance (SPR) peaks at 430, 440, and 428 nm, respectively. HR-TEM revealed different shapes for the nanoparticles within the size ranges of 16-20, 31-60, and 57-72 nm for B. lanuginose, H. cymosum, and S. crenata, respectively. Using a human oral fibroblast cell line, the cytotoxicity of both AgNPs and plant extracts was tested at concentrations of 0.007, 0.012, 0.025, and 0.062 mg/mL (buccal mucosa fibroblasts). The antifungal activity showed growth inhibition zones of approximately 18 mm, 18.67 mm, and 18.33 mm for the AgNPs conjugated with B. lanuginose, H. cymosum, and S. crenata, respectively. For the studied samples, the minimum inhibitory concentration (MIC50) was less than 0.015 mg/mL. The AgNPs exhibited antifungal activity that was concentration- and size-dependent. The results of this study offer new insights into the cytotoxicity and antifungal activity of the green-synthesized AgNPs.

An Investigation into the Acute and Subacute Toxicity of Extracts of Cassipourea flanaganii Stem Bark In Vivo.

The conventional use of medicinal plants is in part based on the widespread belief that plant crude extracts are non-toxic. In South Africa, traditional preparations of Cassipourea flanaganii used to treat hypermelanosis have accordingly been regarded by many as non-toxic. Whether that is so impacts on the potential of bark extracts to be developed as a commercial drug to treathypermelanosis, given their documented capacity to inhibit tyrosinase activity. Our study investigated the acute and subacute toxicity of the methanol extract of C. flanaganii bark in rats. Wistar rats were randomly assigned into different treatment groups. The rats received a daily oral gavage of crude extract for acute and subacute toxicity tests. Haematological, biomechanical, clinical and histopathology examinations were carried out to evaluate the possible toxicity of C. flanaganii. The results were subjected to the Student's t-test and ANOVA. For both acute and subacute toxicity, there was no statistical difference between the groups. There were no clinical or behavioral signs of toxicity observed in the rats. No treatment-related gross pathology lesions and no histopathology were observed. The findings of this study demonstrate the absence of acute or subacute toxicity after oral treatment with C. flanaganii stem bark extracts in Wistar rats at the levels administered. Chemical profiling of the total extract using LC-MS tentatively identified eleven (11) compounds as the major chemical constituents.

Carbon dots labeled Lactiplantibacillus plantarum: a fluorescent multifunctional biocarrier for anticancer drug delivery.

A carbon dots (CDs)-biolabeled heat-inactivated Lactiplantibacillus plantarum (HILP) hybrid was investigated as a multifunctional probiotic drug carrier with bioimaging properties using prodigiosin (PG) as anticancer agent. HILP, CDs and PG were prepared and characterized using standard methods. CDs-labeled HILP (CDs/HILP) and PG loaded CDs/HILP were characterized by transmission electron microscopy (TEM), laser scanning confocal microscopy (LSCM) and for entrapment efficiency (EE%) of CDs and PG, respectively. PG-CDs/HILP was examined for stability and PG release. the anticancer activity of PG-CDs/HILP was assessed using different methods. CDs imparted green fluorescence to HILP cells and induced their aggregation. HILP internalized CDs via membrane proteins, forming a biostructure with retained fluorescence in PBS for 3 months at 4°C. Loading PG into CDs/HILP generated a stable green/red bicolor fluorescent combination permitting tracking of both drug carrier and cargo. Cytotoxicity assay using Caco-2 and A549 cells revealed enhanced PG activity by CDs/HILP. LCSM imaging of PG-CDs/HILP-treated Caco-2 cells demonstrated improved cytoplasmic and nuclear distribution of PG and nuclear delivery of CDs. CDs/HILP promoted PG-induced late apoptosis of Caco-2 cells and reduced their migratory ability as affirmed by flow cytometry and scratch assay, respectively. Molecular docking indicated PG interaction with mitogenic molecules involved in cell proliferation and growth regulation. Thus, CDs/HILP offers great promise as an innovative multifunctional nanobiotechnological biocarrier for anticancer drug delivery. This hybrid delivery vehicle merges the physiological activity, cytocompatibility, biotargetability and sustainability of probiotics and the bioimaging and therapeutic potential of CDs.

Development and validation of nomogram to improve the specificity of multiparametric MRI for clinically significant prostate cancer.

OBJECTIVE: To develop and validate a nomogram to improve the specificity of prostate imaging reporting and data system (PI-RADS) on multiparametric magnetic resonance imaging (MRI) for clinically significant prostate cancer on targeted fusion biopsy. METHODS: A retrospective review of patients who underwent fusion biopsy for PI-RADS 3-5 lesions using UroNav and Artemis systems between 2016 and 2022 was performed. Patients were divided into those with CS disease on fusion biopsy (Gleason grade group ≥2) versus those without. Multivariable analysis was used to identify variables associated with CS disease. A 100-point nomogram was constructed, and ROC curve was generated. RESULTS: 1485 lesions (1032 patients) were identified, 510 (34%) were PI-RADS 3, 586 (40%) were PI-RADS 4, and 389 (26%) were PI-RADS 5. Of these, 11% of PI-RADS 3, 39% of PI-RADS 4, and 61% of PI-RADS 5 showed CS disease. CS disease was associated with older age (OR 1.04, 95% CI 1.02-1.06, p < 0.01), previous negative biopsy (OR 0.52, 95% CI 0.36-0.74, p < 0.01), presence of multiple PI-RADS 3-5 lesions (OR 0.61, 95% CI 0.45-0.83, p < 0.01), peripheral zone location (OR 1.88, 95% CI 1.30-2.70, p < 0.01), PSA density (OR 1.48 per 0.1 unit, 95% CI 1.33-1.64, p < 0.01), PI-RADS score 4 (OR 3.28, 95% CI 2.21-4.87, p < 0.01), and PI-RADS score 5 (OR 7.65, 95% CI 4.93-11.85, p < 0.01). Area under ROC curve was 82% for nomogram compared to 75% for PI-RADS score alone. CONCLUSION: We report a nomogram that combines PI-RADS score with other clinical parameters. The nomogram outperforms PI-RADS score for the detection of CS prostate cancer.

Impact of an NCCN-Compliant Multidisciplinary Conference on Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: We sought to investigate the impact of an NCCN-compliant multidisciplinary conference on treatment decisions of patients with localized prostate cancer. METHODS: A retrospective review of our quality assurance localized prostate cancer database was performed. All patients with localized prostate cancer who sought a second opinion at Roswell Park Comprehensive Cancer Center between 2009 and 2019 were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Multivariable regression models were fit to evaluate variables associated with concordance between community recommendations, LPCC recommendations, and treatment received by patients. RESULTS: A total of 1,164 patients were identified, of whom 26% had NCCN very low-/low-risk, 27% had favorable intermediate-risk, 25% had unfavorable intermediate-risk, and 22% had high-/very high-risk prostate cancer. Pathology changed in 11% of patients after genitourinary pathologist review, which caused disease reclassification in 9%. Concordance between community and LPCC recommendations occurred in 78%, with lowest concordance for androgen deprivation therapy (21%) and radiotherapy (53%). Concordance between community recommendations and treatment received occurred in 65%, with lowest concordance for androgen deprivation therapy and radiotherapy; among those who were recommended radiotherapy as the only option by their community urologist, only 26% received it. Concordance between LPCC recommendations and treatment received occurred in 92%. CONCLUSIONS: Community recommendations differed from the multidisciplinary NCCN-compliant recommendations in 22% of patients, primarily for radiotherapy. Multidisciplinary recommendations matched the treatment received in 92% of patients compared with 65% for community recommendations.

The Urinary Microbiome and Bladder Cancer.

Bladder cancer is the 10th most common cancer worldwide. Approximately 75% of patients with bladder cancer will present with non-muscle invasive disease. Patients are usually treated with transurethral resection of bladder tumor (TURBT), in addition to adjuvant intravesical therapy (chemotherapy or anti-cancer immunotherapy with Bacillus Calmette Guerin- BCG) for those at intermediate-risk and high-risk of recurrence and progression. For many years, urine has been thought to be "sterile"; however, advanced microbiological and molecular techniques, including 16S ribosomal RNA (16S rRNA) sequencing, have negated that previous paradigm and confirmed the presence of a urinary microbiome. The urinary microbiome has been associated with several urological diseases, including interstitial cystitis, urgency urinary incontinence, neurogenic bladder dysfunction, and others. More recently, many reports are emerging about the role of the urinary microbiome in urothelial carcinogenesis, including gender disparity in bladder cancer and responses to treatments. The urinary microbiome may serve as a biomarker that can help with risk stratification as well as prediction of the response to intravesical therapies. However, the microbiome literature has been hampered by the lack of a unified standardized methodology for sample collection, type, preservation, processing, as well as bioinformatics analysis. Herein we describe and critique the literature on the association between urinary microbiome and bladder cancer and highlight some of the future directions.

Development of a predictive model for recurrence-free survival in pTa low-grade bladder cancer.

BACKGROUND: Data on Ta low-grade (LG) non-muscle invasive bladder cancer (NMIBC) have shown that follow-up cystoscopies are normal in 82% and 67% of patients with single and multiple tumors, respectively. OBJECTIVE: To develop a predictive model associated with recurrence-free survival (RFS) at 6, 12, 18 and 24 months in TaLG cases that consider the patients' risk aversion. MATERIALS AND METHODS: Data from a prospectively maintained database of 202 newly diagnosed TaLG NMIBC patients treated at Scandinavian institutions were used for the analysis. To identify risk groups associated with recurrence, we performed a classification tree analysis. Association between risk groups and RFS was evaluated by Kaplan Meier analysis. A Cox proportional hazard model selected significant risk factors associated with RFS using the variables defining the risk groups. The reported C index for the Cox model was 0.7. The model was internally validated and calibrated using 1000 bootstrapped samples. A nomogram to estimate RFS at 6, 12, 18, and 24 months was generated. The performance of our model was compared to EUA/AUA stratification using a decision curve analysis (DCA). RESULTS: The tree classification found that tumor number, tumor size and age were the most relevant variables associated with recurrence. The patients with the worst RFS were those with multifocal or single, ≥ 4cm tumors. All the relevant variables identified by the classification tree were significantly associated with RFS in the Cox proportional hazard model. DCA analysis showed that our model outperformed EUA/AUA stratification and the treat all/none approaches. CONCLUSION: We developed a predictive model to identify TaLG patients that benefit from less frequent follow-up cystoscopy schedule based on the estimated RFS and personal recurrence risk aversion.

Transition from da Vinci to Versius robotic surgical system: initial experience and outcomes of over 100 consecutive procedures.

We sought to describe the development of the robotic urology program at Sindh Institute of Urology and Transplantation (SIUT) and the feasibility of transitioning from the da Vinci to Versius robotic systems. The SIUT robotics program began in 2017 utilizing the da Vinci Si robotic system, transitioning to the Versius system in 2021. Retrospective review of our quality assurance database was performed. All procedures performed utilizing the two systems were identified, analyzed, and compared. Data were described with descriptive statistics. Matched procedures (by type of procedure) performed by the same surgeons utilizing the da Vinci and Versius were compared. All tests were double-sided with statistical significance set at p < 0.05.106 cases were performed by the Versius robotic surgical system in 2021. Median age was 42 years (IQR 26-56), and 69 (65%) were males. Procedures included both benign (83%) and malignant disorders (17%), several upper tract (75%), and pelvic/lower tract (25%). No major intraoperative complications were observed. Conversion to open occurred in six procedures. Malfunction of the robotic arms occurred in two procedures: the erroneous bedside units (BSU) were replaced. Eight patients developed postoperative high-grade complications. Matched analysis of various procedures (pyeloplasty, stone surgery, radical, partial, and simple nephrectomy) showed no significant difference in perioperative outcomes. To our knowledge, this is the first and largest series of urologic procedures performed by the Versius robotic surgical system.

Analysis of Complications After Robot-Assisted Radical Cystectomy Between 2002-2021.

OBJECTIVE: To identify trends in complications following robot-assisted radical cystectomy (RARC) using a multi-institutional database, the International Robotic Cystectomy Consortium (IRCC). METHODS: A retrospective review of the IRCC database was performed (2976 patients, 26 institutions from 11 countries). Postoperative complications were categorized as overall or high grade (≥ Clavien Dindo III) and were further categorized based on type/organ site. Descriptive statistics was used to summarize the data. Multivariate analysis (MVA) was used to identify variables associated with overall and high-grade complications.  Cochran-Armitage trend test was used to describe the trend of complications over time. RESULTS: 1777 (60%) patients developed postoperative complications following RARC, 51% of complications occurred within 30 days of RARC, 19% between 30-90 days, and 30% after 90 days. 835 patients (28%) experienced high-grade complications. Infectious complications (25%) were the most prevalent, while bleeding (1%) was the least. The incidence of complications was stable between 2002-2021. Gastrointestinal and neurologic postoperative complications increased significantly (P < .01, for both) between 2005 and 2020 while thromboembolic (P = .03) and wound complications (P < .01) decreased. On MVA, BMI (OR 1.03, 95%CI 1.01-1.05, P < .01), prior abdominal surgery (OR 1.26, 95%CI 1.03-1.56, P = .03), receipt of neobladder (OR 1.52, 95%CI 1.17-1.99, P < .01), positive nodal disease (OR 1.33, 95%CI 1.05-1.70, P = .02), length of inpatient stay (OR 1.04, 95%CI 1.02-1.05, P < .01) and ICU admission (OR 1.67, 95%CI 1.36-2.06, P < .01) were associated with high-grade complications. CONCLUSION: Overall and high-grade complications after RARC remained stable between 2002-2021. GI and neurologic complications increased, while thromboembolic and wound complications decreased.