OBJECTIVE:To perform a systematic review and meta-analysis to assess the relationship between intraprostatic maximum standardised uptake value (SUVmax) of the dominant prostatic lesion as measured on preoperative prostate-specific membrane antigen (PSMA) positron emission tomography (PET) with radical prostatectomy International Society of Urological Pathology (ISUP) Grade Group, pathological tumour (pT) staging, and biochemical recurrence (BCR). METHODS:Prostate-specific membrane antigen PET may offer non-invasive assessment of histopathological and oncological outcomes before definitive treatment. SUVmax of the dominant lesion has been explored as a prognostic biomarker. Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we performed reviews of digital libraries and databases and retrieved studies reporting SUVmax quantified on PSMA PET computed tomography or magnetic resonance imaging and subsequent radical prostatectomy ISUP Grade Group, pT stage, and BCR. Quality assessment was performed using Quality Assessment of Diagnostic Accuracy Studies-2 and Prediction model Risk of Bias Assessment tools. Random effects meta-analysis and meta-regression by ISUP Grade Group and pT2 vs pT3/4 stage was performed. This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023408170). EVIDENCE SYNTHESIS:After removing duplicates, 23 studies were included for review. Pooled SUVmax (95% confidence interval [CI]) increased monotonically with advancing ISUP Grade Group, with ISUP 1: 5.8 (95% CI 3.9-7.7), through to ISUP 5: 17.3 (95% CI 13.1-21.5). For pT2 disease, pooled SUVmax: 9.7 (95% CI 7.8-11.5) increasing to 13.8 (95% CI 10.9-16.7) for pT3/4 disease. Substantial inconsistency was noted (I2 >50%) for all subgroups. This was not attenuated by restricting analysis only to studies using [68Ga]Ga-PSMA-11. Narrative synthesis of six papers reporting BCR showed increasing SUVmax was associated with reduced time to BCR. CONCLUSION:Preoperative intraprostatic PSMA SUVmax increases monotonically with higher ISUP Grade Group and pathological tumour stage. Higher SUVmax is associated with reduced BCR-free survival. However, the use of single SUVmax thresholds for clinical decision making is not recommended as variability between studies is high.

Isobaric labeling is a commonly used technique in proteomics. In bottom-up proteomics, protein abundance estimation requires combining reporter ion intensities from the corresponding peptide-spectrum matches (PSMs), a process referred to as aggregation. It is usually assumed that PSMs in this step represent protein abundance equally, but the differences in ionizability and propensity for isolation interference result in different levels of quantitative accuracy for PSMs. This work developed an attribute-weighted aggregation (AWA) method that considers PSM attributes with reporter ion intensities to provide a more accurate estimate of protein abundance. A random forest model was trained on the characteristics of PSMs using three spike-in data sets and used to predict the quantitative inaccuracy of PSMs to be aggregated based on their attributes. These PSMs were aggregated to the protein level based on the predicted inaccuracy. AWA was evaluated using the three spike-in data sets and applied to two large cancer cohorts. The results showed that applying AWA to different data sets can lead to better recall in differential expression analyses while maintaining high precision. To facilitate the application of AWA, an R package AWAggregator was developed, which also offers functions to retrain the random forest model for additional or alternative spike-in data sets.

Oats are a rich source of plant-based proteins owing to their nutritional value, diverse functions, and high abundance. However, traditional methods for extracting oat proteins (OPs), such as alkali solution acid precipitation (ASAP), can cause environmental pollution and potentially protein denaturation. In this work, we studied the use of deep eutectic solvents (DESs) and deep eutectic system (DESys)-based methods for OP extraction. The DES are composed of ionic liquids (ILs) and choline chloride (ChCl) as hydrogen bond acceptors (HBAs), and polyols as hydrogen bond donors (HBDs) for OP extraction. By systematically investigating the extraction conditions, it was found that using ChCl as an HBA in the DESys-based method allowed for a significant increase in protein recovery yield compared to the ASAP and DES-based methods. Furthermore, the physicochemical properties of OPs extracted using the ASAP, DES, and DESys-based methods exhibited some differences, particularly in their molecular structure, amino acid composition, and thermal properties, suggesting that the properties of OP could be potentially adjusted by DESys- and DES-based methods. When considering both toxicity and protein recovery yield, the DESys-based extraction method using ChCl as the HBA is more suitable for OP extraction. This study demonstrated a green and efficient method for OP extraction that minimizes environmental impact, potentially bridging the gap between ILs and DES, and offering insights for designing new DES- or DESys-based extraction strategies for biological molecules.

815 Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) or chemoradiation (CRT) is the standard of care for patients (pts) with muscle invasive bladder cancer (MIBC). Mutations in DNA damage repair genes enrich for pathologic downstaging after NAC. In RETAIN-1, a risk-adapted approach was employed to identify patients for cystectomy-sparing active surveillance (AS) following NAC, reporting a 73% 2-year MFS rate. RETAIN-2 employs a similar approach but incorporates neoadjuvant chemoimmunotherapy. Methods: This is a phase II, multi-institutional trial in which pts with cT2-T3N0M0 MIBC, ECOG PS 0-1 and CrCl≥50 mL/min received neoadjuvant accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (AMVAC) with nivolumab. Pre-NAC transurethral bladder resection (TURBT) specimens were sequenced for mutations (pathogenic or VUS) in ATM , ERCC2 or RB1 . Pts with >1 mutation and clinical complete response (cCR) post-NAC (based on restaging TUR, urine cytology and CT imaging) initiated active surveillance (AS). Remaining pts underwent bladder-directed therapy: intravesical therapy (< cT2 post-NAC), CRT or RC. The primary endpoint is 2-year metastasis-free survival (MFS) for ITT pts which is not mature. This interim analysis reports clinically meaningful secondary endpoint outcomes. Results: A total of 80 pts were treated over 40 months at four academic centers and 71 were evaluable per protocol. The median age was 69 years (range: 66-86), 77% were male, 80% had ECOG PS 0 and 87% were cT2. Of 80 treated pts, 60 (75%) completed 3 cycles of AMVAC with nivolumab; 7 tolerated only 1 cycle, and 2 died shortly after completing 3 cycles from treatment-related adverse events and were not evaluable for the primary endpoint. Grade 3-4 TRAEs occurred in 19% of all treated pts. Of 71 evaluable ITT pts, 31 (44%) had a mutation of interest and the cCR rate in those pts was 71%; 35 pts proceeded directly to RC, 10 received CRT, 3 received intravesical therapy and 23 pts started per protocol AS. Of 23 AS pts, 4 did not have mutation. Similarly, 3 pts with tumor mutation and cCR chose RC. In pts who underwent RC, pT0 rate was 46%,

BACKGROUND AND OBJECTIVE:The PRESERVE study (NCT04972097) assessed the safety and effectiveness of irreversible electroporation (IRE) with the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). METHODS:This prospective, nonrandomized, single-arm pivotal trial included patients in the USA who met the key inclusion criteria: age >50 yr with organ-confined, grade group 2 or 3 PCa, clinical stage ≤T2c, prostate-specific antigen (PSA) ≤15 ng/ml, or PSA density <0.15 ng/ml2. The primary endpoints were the rate of local pathological complete response (negative in-field biopsy) and the incidence, type, and severity of adverse events by 12 mo. The secondary endpoints included PSA kinetics, changes in prostate volume, retreatment, and urinary/sexual function. KEY FINDINGS AND LIMITATIONS:Of the 121 patients treated with IRE, the negative in-field biopsy rate at 12 mo was 71% (95% confidence interval [CI]: 62%, 79%). The secondary endpoint of negative in-field biopsy rate defined by the Delphi consensus criterion was 84% (95% CI: 76%, 90%). The time to median PSA nadir was 3.5 mo, and the median percent reduction in PSA at 6 mo was 68.2%. Urinary function outcomes had a mean change from baseline to 12 mo of 3 in the University of California Los Angeles Expanded Prostate Cancer Index Composite urinary domain total score and a mean change of -2 in the International Prostate Symptom Score total symptom score. At 12 mo, 84% of patients with good baseline sexual function maintained erections sufficient for penetration. Fourteen (12%) patients experienced Common Terminology Criteria for Adverse Events grade ≥3 and three experienced procedure-related grade 3 adverse events. CONCLUSIONS AND CLINICAL IMPLICATIONS:IRE with the NanoKnife System is safe and effective for prostate tissue ablation.

667 Background: A critical need persists to develop treatments for BCG-unresponsive (BCG-U) non-muscle invasive bladder cancer (NMIBC) patients (pts). The intravesical gemcitabine plus docetaxel (Gem/Doc) doublet and intravenous agents targeting the PD-(L)1 immune checkpoint have both demonstrated complete responses (CRs) in BCG-U NMIBC investigations. With this knowledge, we aimed to assess the clinical efficacy and safety of durvalumab (D) in combination with intravesical Gem/Doc. Methods: The multi-arm, multi-stage ADAPT-BLADDER trial design has been previously described (Hahn NM et al, Eur Urol 2023). Here, we report outcomes from the D + Gem/Doc (cohort 4) phase 1 and phase 2 expansion arms. In phase 1, BCG-U NMIBC patients were enrolled in a 6 + 3 + 3 fashion to establish safety. In phase 2, additional patients were enrolled to evaluate the primary endpoint of CR rate in the total study population and to provide a CR rate estimate within the subset of patients with CIS. Per protocol, phase 1 and 2 efficacy analyses were combined. Enrollment of pure papillary patients was capped to ensure at least 20 patients with CIS. Patients received D 1500 mg iv on day 1 of each 4-week cycle for up to 6 cycles. In addition, they received intravesical Gem 1000 mg + Doc 37.5 mg weekly for the first 6 weeks. Patients achieving a CR were encouraged, but not required, to receive Gem/Doc monthly maintenance therapy. Cystoscopic and urine cytology assessments were performed every three months in year one with a mandatory biopsy at 12-months in responding patients. Toxicity rates were reported per CTCAE v5.0. Results: Between 1/2022-10/2024, 40 pts enrolled (12 phase 1, 28 phase 2) from 6 sites. The study completed its full planned accrual. Demographics included: median age 69 years; 83% male; CIS (8 pts), high-grade (HG) T1 + CIS (7 pts), HG Ta + CIS (6 pts), HG Ta (13 pts) and HG T1 (6 pts). No dose limiting toxicities were observed in the phase 1 portion. Among 27 patients (15 CIS, 12 papillary) evaluable for response at the August 2024 data lock, a CR was observed in 24 patients (89%) (CIS – 13/15 (87%); Papillary – 11/12 (92%)). Evaluation of pts still receiving study treatment for CR and durability of response is ongoing. One pt (4%) progressed to muscle invasion on study treatment. Highest grade treatment-related adverse events observed were grade 1 – 12 (36%) pts, grade 2 – 11 (33%) pts, grade 3 – 2 (6%) pts (sepsis n=1, pneumonitis n=1), and grade 4 – 1 (3%) pt (cough n=1) respectively. One on-study death due to retroperitoneal bleed unrelated to study therapy was observed. Conclusions: Combination treatment with durvalumab plus intravesical gemcitabine and docetaxel demonstrates promising clinical efficacy with a high complete response rate. Observed adverse event type, frequency, and severity were consistent with prior durvalumab trial experiences. Clinical trial information: NCT03317158 .

Synthetic dye production and the consequent generation of dye-rich wastewater are major concerns of water quality in many countries. We developed a sustainable approach with deep eutectic solvent (DES) treatment to enhance the efficiency of mixed cellulose ester (MCE) membrane-based dye removal material. The DES composition and treatment conditions were optimized, and the treated membranes were comprehensively characterized. DES-treated membranes exhibited improved morphology, surface properties, and superior dye adsorption capabilities. Our study revealed that the adsorption process was chemically controlled and driven by electrostatic and hydrogen bond interactions. Thermodynamic analysis confirmed the endothermic and spontaneous nature of the adsorption process. Moreover, the treated membranes exhibited good separation performance for dye/salt mixtures. Additionally, we demonstrated selective adsorption of cationic dyes over anionic dyes using these treated membranes. This selectivity enabled the development of a membrane solid-phase extraction (MSPE) method for quantification of trace amount of dyes. Compared with other methods, DES-treated MCE membranes present a promising solution for efficient dye quantification and removal, offering a green and effective strategy to address water pollution stemming from synthetic dyes. Additionally, this study provides a novel strategy for green chemistry modification of cellulose-based materials.

OBJECTIVE:To evaluate the efficacy of risk-based, protocol-driven management versus usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSCs). BACKGROUND:Major cancer surgery is associated with significant perioperative risks, which result in worse long-term outcomes. METHODS:Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and comanagement versus usual management. The primary study outcome was a 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free survival and overall survival. RESULTS:Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the intervention arm and 732 patients in the control arm were eligible for analysis. Thirty-day rate of DSC with the intervention was 15.0% (95% CI: 12.5%-17.6%) versus 14.1%, (95% CI: 11.6%-16.6%) with usual management ( P = 0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room), postoperative length of stay, rate of discharge to home, or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of antineoplastic therapy between the study arms. At a median follow-up of 48 months, overall survival ( P = 0.57) and disease-free survival ( P = 0.91) were similar. CONCLUSIONS:Risk-based, protocol-driven management did not reduce the 30-day rate of DSC after elective major cancer surgery compared with usual management, nor did it improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery.

Advancements in food technology have increased the need for thorough analysis to ensure food safety, quality, and compliance with regulatory requirements. Capillary electrophoresis-mass spectrometry (CE-MS) has emerged as a powerful tool in food analysis due to its high separation efficiency, low sample consumption, and ability to handle complex matrices. However, challenges such as the use of volatile running buffers and maintaining the stability of the electrical circuit connecting the CE and MS systems have been addressed through advancements in interface designs, such as sheathless systems and optimized sheath-liquid compositions. Online and offline preconcentration techniques have significantly enhanced CE-MS sensitivity (up to 1000-fold) through stacking methods such as large volume sample stacking (LVSS) and dynamic pH junction stacking. Meanwhile, offline sample preparation techniques, such as solid-phase extraction (SPE) and liquid-based methods, are essential for removing matrix interferences and preconcentrating targeted analytes. This review explores both online and offline preconcentration methods and emphasizes the importance of CE-MS in helping researchers develop effective strategies for selecting the best preconcentration methods for food analysis.

Magnetic aromatic polyamide (MAPA) composites were synthesized using a green mechanochemical ball milling process and used for magnetic solid-phase extraction (MSPE) and detection of trace level fluoroquinolone antibiotics (FQs) from water samples. The formation of MAPAs was facilitated by deep eutectic systems (DESys) created from magnetic beads and organic monomers during ball milling. A comprehensive study was conducted to investigate the kinetics, thermodynamics, and mechanisms of MAPA adsorption of ciprofloxacin hydrochloride (CIP) and ofloxacin (OFL) from water. The maximum adsorption capacities for CIP and OFL were found to be 151.5 mg/g and 164.1 mg/g, respectively. Additionally, the recyclability and selective adsorption capabilities of MAPAs were evaluated. MAPAs were subsequently used for MSPE of CIP and OFL in water samples. Both UV-Vis spectrometry and HPLC methods can be used for analysis, the MSPE-HPLC method showed superior linearity for CIP (0.06-1500 μg/L) and OFL (1-1200 μg/L), with R² values of 0.9995 and 0.9999, and limit of detection (LOD) as low as 0.006 μg/L and 0.02 μg/L, respectively. Both analytical methods are highly effective and practical for use with real water samples. MAPA used for MSPE offer a promising green approach for detecting antibiotic contamination in aquatic ecosystems.

In this study, a simple and eco-friendly method was used to treat alkaline lignin with an acidic deep eutectic solvent (DES) to obtain regenerated lignin for the efficient adsorption of pollutant dyes from aqueous environment. Based on the yield and adsorption capacity of the sorbent for these dyes, conditions such as the type and concentration of DES component, solid-to-liquid ratio, reaction time, and temperature were optimized. By characterizing and comparing alkali lignin with regenerated lignin, a series of reactions were demonstrated to occur during the DES treatment process. The performance and mechanism of methylene blue and rhodamine B adsorption on regenerated lignin were studied systematically, and the maximum adsorbed amounts were 348.29 and 551.05 mg/g at 323 K, respectively. This study provides a new strategy for the green preparation of functionalized lignin and its use in the water pollutant treatment.

Direct surface analysis in ambient conditions provides information on the position and chemical composition of an object at the time of investigation. An angled sampling probe is developed in this work for direct analysis in real time (DART) ionization high-resolution mass spectrometry. The DART ion source and the interface were modified for improved surface resolution, increased ion transfer efficiency, as well as enabling two-dimensional surface scanning. The angled probe DART-MS system was used for investigating a variety of food samples including fruit peels, ginseng root, plant leaves and sections of radish. Abundant signals and distinct chemical profiles are obtained in seconds, and spatial distribution of different molecules across the sample surfaces can be observed. In addition, the developed system can quickly identify the chemical changes when the surfaces were treated. The method is capable of directly evaluating food sample surfaces with different shapes, hardness, and conditions, without any sample pretreatments.

The review examines the vital role of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) in the diagnosis, staging, and treatment of prostate cancer (PCa). It focuses on the superior diagnostic abilities of PSMA PET/CT for identifying both nodal and distant PCa, and its potential as a prognostic indicator for biochemical recurrence and overall survival. Additionally, we focused on the variability of PSMA’s expression and its impact on personalised treatment, particularly the use of [177Lu] Lu-PSMA-617 radioligand therapy. This review emphasises the essential role of PSMA PET/CT in enhancing treatment approaches, improving patient outcomes, and reducing unnecessary interventions, positioning it as a key element in personalised PCa management.

ObjectiveTo examine the role of bowel diversion and reconstructive surgeries in managing Fournier's gangrene (FG) to facilitate multidisciplinary collaboration between urologists, colorectal and plastic surgery teams.MethodsA review of the literature was conducted using the databases Medline, Embase, PubMed in June 2023. The review included studies that evaluated the outcomes of FG following reconstructive surgeries or diverting colostomies.ResultsThe existing evidence suggests that bowel diversion and colostomy formation could reduce the need for further debridement, shorten the time to wound healing, and facilitate skin graft or flap uptake in patients with FG. Additionally, the psychological impact of a stoma was shown not to be a major concern for patients. However, stoma carries a risk of perioperative complications and therefore may prolong the length of hospital stay. In reviewing the evidence for reconstruction in FG, large and deep defects seem to benefit from skin grafts or flaps. Noticeably, burial of testicles in thigh pockets has grown out of favour due to concerns regarding the thermoregulation of the testicles and the psychological impact on patients.ConclusionThe use of bowel diversion and reconstructive surgeries in managing FG is case dependent. Therefore, it is important to have close discussions with colorectal and plastic surgery teams when managing FG.

INTRODUCTION:Surgeons use several quality-of-life instruments to track outcomes following abdominal wall reconstruction (AWR); however, there is no universally agreed upon instrument. We review the instruments used in AWR and report their utilization trends within the literature. METHODS:This scoping review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews guidelines using the PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane databases. All published articles in the English language that employed a quality-of-life assessment for abdominal wall hernia repair were included. Studies which focused solely on aesthetic abdominoplasty, autologous breast reconstruction, rectus diastasis, pediatric patients, inguinal hernia, or femoral hernias were excluded. RESULTS:Six hernia-specific tools and six generic health tools were identified. The Hernia-Related Quality-of-Life Survey and Carolinas Comfort Scale are the most common hernia-specific tools, while the Short-Form 36 (SF-36) is the most common generic health tool. Notably, the SF-36 is also the most widely used tool for AWR outcomes overall. Each tool captures a unique set of patient outcomes which ranges from abdominal wall functionality to mental health. CONCLUSIONS:The outcomes of AWR have been widely studied with several different assessments proposed and used over the past few decades. These instruments allow for patient assessment of pain, quality of life, functional status, and mental health. Commonly used tools include the Hernia-Related Quality-of-Life Survey, Carolinas Comfort Scale, and SF-36. Due to the large heterogeneity of available instruments, future work may seek to determine or develop a standardized instrument for characterizing AWR outcomes.

Although positron emission tomography/computed tomography (PET/CT) underwent rapid growth during the last quarter-century, becoming a new standard-of-care for imaging most cancer types, CT and bone scan remained the gold standard for patients with prostate cancer. This occurred as 2-fluorine-18-fluoro-2-deoxy-d-glucose was perceived to have a limited role owing to low sensitivity in many patients. A resurgence of interest occurred with the use of fluorine-18-sodium-fluoride PET/CT as a replacement for bone scintigraphy, and then choline, fluciclovine, and dihydrotestosterone (DHT) PET/CT as prostate "specific" radiotracers. The last decade, however, has seen a true revolution with the meteoric rise of prostate-specific membrane antigen PET/CT.

Purpose:The summary presented herein covers recommendations on salvage therapy for recurrent prostate cancer intended to facilitate care decisions and aid clinicians in caring for patients who have experienced a recurrence following prior treatment with curative intent. This is Part I of a three-part series focusing on treatment decision-making at the time of suspected biochemical recurrence (BCR) after radical prostatectomy (RP). Please refer to Part II for discussion of treatment delivery for non-metastatic BCR after RP and Part III for discussion of evaluation and management of recurrence after radiotherapy (RT) and focal therapy, regional recurrence, and oligometastasis.Materials and Methods:The systematic review that informs this Guideline was based on searches in Ovid MEDLINE (1946 to July 21, 2022), Cochrane Central Register of Controlled Trials (through August 2022), and Cochrane Database of Systematic Reviews (through August 2022). Update searches were conducted on July 26, 2023. Searches were supplemented by reviewing electronic database reference lists of relevant articles.Results:In a collaborative effort between AUA, ASTRO, and SUO, the Salvage Therapy for Prostate Cancer Panel developed evidence- and consensus-based statements to provide guidance for the care of patients who experience BCR after initial definitive local therapy for clinically localized disease.Conclusions:Advancing work in the area of diagnostic tools (particularly imaging), biomarkers, radiation delivery, and biological manipulation with the evolving armamentarium of therapeutic agents will undoubtedly present new opportunities for patients to experience long-term control of their cancer while minimizing toxicity.

The PRESERVE study (NCT04972097) aims to evaluate the safety and effectiveness of the NanoKnife System to ablate prostate tissue in patients with intermediate-risk prostate cancer (PCa). The NanoKnife uses irreversible electroporation (IRE) to deliver high-voltage electrical pulses to change the permeability of cell membranes, leading to cell death. A total of 121 subjects with organ-confined PCa ≤ T2c, prostate-specific antigens (PSAs) ≤ 15 ng/mL, and a Gleason score of 3 + 4 or 4 + 3 underwent focal ablation of the index lesion. The primary endpoints included negative in-field biopsy and adverse event incidence, type, and severity through 12 months. At the time of analysis, the trial had completed accrual with preliminary follow-up available. Demographics, disease characteristics, procedural details, PSA responses, and adverse events (AEs) are presented. The median (IQR) age at screening was 67.0 (61.0–72.0) years and Gleason distribution 3 + 4 (80.2%) and 4 + 3 (19.8%). At 6 months, all patients with available data (n = 74) experienced a median (IQR) percent reduction in PSA of 67.6% (52.3–82.2%). Only ten subjects (8.3%) experienced a Grade 3 adverse event; five were procedure-related. No Grade ≥ 4 AEs were reported. This study supports prior findings that IRE prostate ablation with the NanoKnife System can be performed safely. Final results are required to fully assess oncological, functional, and safety outcomes.