Prognostic significance of residual tumor at restaging transurethral bladder resection in high-risk non-muscle-invasive bladder cancer.

PURPOSE: To assess prognostic significance of residual tumor at repeat transurethral resection (reTUR) in contemporary non-muscle-invasive bladder cancer (NMIBC) patients. METHODS: Patients were identified retrospectively from eight referral centers in France, Italy and Spain. The cohort included consecutive patients with high or very-high risk NMIBC who underwent reTUR and subsequent adjuvant BCG therapy. RESULTS: A total of 440 high-risk NMIBC patients were screened, 29 (6%) were upstaged ≥ T2 at reTUR and 411 were analyzed (T1 stage: n = 275, 67%). Residual tumor was found in 191 cases (46%). In patients with T1 tumor on initial TURBT, persistent T1 tumor was found in 18% of reTUR (n = 49/275). In patients with high-grade Ta tumor on initial TURBT, T1 tumor was found in 6% of reTUR (n = 9/136). In multivariable logistic regression analysis, we found no statistical association between the use of photodynamic diagnosis (PDD, p = 0.4) or type of resection (conventional vs. en bloc, p = 0.6) and the risk of residual tumor. The estimated 5-yr recurrence and progression-free survival were 56% and 94%, respectively. Residual tumor was significantly associated with a higher risk of recurrence (p < 0.001) but not progression (p = 0.11). Only residual T1 tumor was associated with a higher risk of progression (p < 0.001) with an estimated 5-yr progression-free survival rate of 76%. CONCLUSIONS: ReTUR should remain a standard for T1 tumors, irrespective of the use of en bloc resection or PDD and could be safely omitted in high-grade Ta tumors. Persistent T1 tumor at reTUR should not exclude these patients from conservative management, and further studies are needed to explore the benefit of a third resection in this subgroup.

Telemedicine in Italy: Healthcare authorization profiles in the modern medico-legal reading.

BACKGROUND: The ruling n. 38485, 20 June 2019, of the Italian Supreme Court, III criminal section, addressed by the perspective of the law the very sensitive and new issue of telemedicine. OBJECTIVE: This commentary deals with the issue of authorization of telemedicine activities by the health authority, starting from the Italian Court of Criminal Cassation, III section, decision n. 38485/2019. The case law explored the authorization of a health point, which carries out telemedicine services. METHODS: Starting from the perspective discussed by Italian health regulations, the paper examines how the health act could be defined, with the possibilities offered by telecommunications, and how it now relates legally to the physical place where it takes place. RESULTS: Even if telemedicine opens the way to virtual spaces of health practice, the Ministry of Health Italian Guidelines pose functional and logistical issues to guarantee users' safety and health care system accountability. Then, functional requirements for health legitimate practice, and their continuous monitoring, together with the responsibilities of the service centers, health professionals and health facilities, are discussed. CONCLUSION: The questioning of States' health law, in a broad health system such as that of the Europe, characterized by autonomous health regulations, is extremely important for cross-border health policy with telemedicine, as overall regulatory compliance in health care is the ground criterion for risk prevention and patient safety, to be properly verified.

Investigation of stereochemical stability of 2-, 3- and 4-chloromethcathinones in various biological matrixes.

The stereochemical stability of the popular drugs of abuse 2-, 3- and 4-chloromethcathinone was studied in the mobile phase used for the isolation of their enantiomers by high-performance liquid chromatography, as well as in various biological matrixes such as whole blood, saliva and urine. For 2-, 3-, and 4-chloromethcathinones the rate constants and half-lives of their first order racemization reaction was assessed. It was found that at 25 °C the racemization rate constant decreases in the order 2-CMC > 3-CMC > 4-CMC while their stereochemical stability in biological matrixes decreases in the order urine > saliva > whole blood. This information must be considered for the adequate storage of purified enantiomers in the collected fractions, as well as in the studies focused on their enantioselective transformation in the human body.

Surface Plasmon Resonance Allows to Correlate Molecular Properties with Diffusion Coefficients of Linear Chain Alcohols.

Every biological and physicochemical process occurring in a fluid phase depends on the diffusion coefficient (D) of the species in solution. In the present work, a model to describe and fit the behaviour of D as a function of structure and extensive thermodynamics parameters in binary solutions of linear chain organic molecules is developed. Supporting experimental and computational evidences for this model are obtained by measuring D for a series of n-alcohols through a novel surface plasmon resonance method and molecular dynamics simulations. This allows to propose a kind of combined analysis to explain the dependence of D on various thermodynamic and structural parameters. The results suggest that for small linear systems in the range from 0 to 200 g mol-1 and under the assumption that the diffusive activation energy is a linear function of mass, D is strictly dependent on the molecular shape and on the relative strength of the solute-solvent intermolecular forces represented by a parameter named R. The newly proposed approach can be utilized to characterize and monitor progressive changes in physicochemical properties for any investigated species upon increasing the dimension of the aggregate/molecule along a certain direction.

Challenges and innovations in the surgical treatment of advanced Dupuytren disease by percutaneous needle fasciotomy: indications, limitations, and medico-legal implications.

BACKGROUND: Dupuytren disease, a chronic thickening and retraction of the palmar aponeurosis of the hands, may result in permanent and progressive flexion of one or more fingers. Percutaneous needle fasciotomy is a simple method that uses a hypodermic needle usually performed under local anaesthesia. The study aim was to report the postoperative results and complications using a percutaneous approach to treat Dupuytren contracture in a consecutive series of patients with advanced Dupuytren disease, also considering the relevant medico-legal implications. METHODS: Retrospective multicentre study of all patients with Tubiana stage 3-4 Dupuytren contracture treated with percutaneous needle aponeurotomy, with no ultrasound assistance, from 2012 to 2022. Patient demographics, disease severity, treatment-related complications, and the incidence of recurrence were identified. An overview of therapeutic treatment options has accounted for 52 relevant sources spanning the 2007-2023 time period. RESULTS: Overall, 41.7% (N = 200) of patients were females, the mean age was 72 years (60-89), the right hand was treated in 54.2% (N = 260) of patients. The little finger was involved in 50% of the patients. The 12 months mean PED was 9°, the mean quickDASH was 8, the mean URAM 6. Minor complications were reported in 18.7% (N = 90) of patients, typically skin lacerations (83.3%) with no clinical sequelae, and no major complications were reported. Recurrence occurred in 30% (N = 144) of patients. CONCLUSIONS: Percutaneous needle fasciotomy is safe and reliable even in patients with advanced Dupuytren disease, resulting in predictably acceptable outcome with low risk of complications.

Robotic assisted vs open radical cystectomy: an updated systematic review and meta-analysis.

Several randomized control trials (RCTs) have been published comparing open (ORC) with robot-assisted radical cystectomy (RARC). However, uncertainty persists regarding this issue, as evidences and recommendations on RARC are still lacking. In this systematic review and metaanalysis, we summarized evidence in this context. A literature search was conducted according to PRISMA criteria, using PubMed/Medline, Web Of Science and Embase, up to March 2024. Only randomized controlled trials (RCTs) were selected. The primary endpoint was to investigate health-related quality of life (QoL) both at 3 and 6 months after surgery. Secondary endpoints include pathological and perioperative outcomes, postoperative complications and oncological outcomes. Furthermore, we conducted a cost evaluation based on the available evidence. Eight RCTs were included, encompassing 1024 patients (515 RARC versus 509 ORC). QoL appeared similar among the two groups both after 3 and 6 months. No significant differences in overall and major complications at 30 days (p = 0.11 and p > 0.9, respectively) and 90 days (p = 0.28 and p = 0.57, respectively) were observed, as well as in oncological, pathological and perioperative outcomes, excepting from operative time, which was longer in RARC (MD 92.34 min, 95% CI 83.83-100.84, p < 0.001) and transfusion rate, which was lower in RARC (OR 0.43, 95% CI 0.30-0.61, p < 0.001). Both ORC and RARC are viable options for bladder cancer, having comparable complication rates and oncological outcomes. RARC provides transfusion rate advantages, however, it has longer operative time and higher costs. QoL outcomes appear similar between the two groups, both after 3 and 6 months.

Cutting Periprosthetic Infection Rate: Staphylococcus aureus Decolonization as a Mandatory Procedure in Preoperative Knee and Hip Replacement Care-Insights from a Systematic Review and Meta-Analysis of More Than 50,000 Patients.

Background: No consensus in the literature has been found about the necessity of implementing a decolonization screening protocol for Staphylococcus aureus in patients who undergo prosthesis implantation of the knee (TKA) or of the hip (THA), with the aim of reducing periprosthetic infections (PJIs). Methods: A systematic literature search was conducted using PubMed, Web of Science, and Embase in April 2024. Studies conducted on patients who underwent a TKA or THA and who followed a screening and decolonization protocol from S. aureus were included. The benefits of implementing this protocol were evaluated through the number of infections overall caused by S. aureus and other pathogens. The risk of bias and quality of evidence were assessed using Cochrane guidelines. Results: A total of 922 articles were evaluated, and of these, 12 were included in the study for a total of 56,930 patients. The results of the meta-analysis showed a reduced risk of overall PJI (p = 0.002), PJI caused by S. aureus (p < 0.0001), and PJI caused by MRSA (p < 0.0001) and highlighted no differences between the two groups in the onset of a PJI caused by other bacteria (p = 0.50). Conclusions: This study showed that the screening and decolonization of S. aureus in patients undergoing THA or THA procedures reduced the risk of a PJI. The screening and decolonization protocol for this kind of patient represents an important procedure for the safety of the patient and in social-economic and medico-legal terms.

The legally charged issue of cross-border surrogacy: Current regulatory challenges and future prospects.

The article aims to shed a light on the unique complexities inherent in surrogacy and the legal-ethical challenges that currently exists even in many advanced democracies, which frequently result in uneven and ill-defined standards and processes. The recent proposal of making surrogacy a "universal crime", meant to prevent cross-border surrogacy, i.e. travels by citizens from countries where it is illegal to countries where it is legal, has also been weighed, by exploring the current legislative state of affairs, trends and future horizons. Recent case-law has been analyzed and interpreted, with a close focus on Italian Supreme Court ruling n. 38162, issued on 30th December 2022 and European Court of Human Rights (ECtHR) rulings issued over the past decade. Uncertainty and ill-defined norms and court rulings risk harming the rights of children, surrogate mothers and intended parents. So far, court decisions have somehow filled the legal vacuum, considering that cross-border surrogacy is not specifically regulated in many countries and the status of children born abroad is still controversial. The views and judgments of supranational courts on the issue need to be accounted for when drafting new specific legislation. It is of utmost importance to uphold the rights of children born through surrogacy abroad, whose best interests risk being damaged. Legislative harmonization at the international level is essential to prevent the cross-border surrogacy trend. The "universal crime" draft bills appear to be difficult to enforce and too vague to be credible at the moment.

In Vitro and In Vivo Human Metabolism of Ostarine, a Selective Androgen Receptor Modulator and Doping Agent.

Ostarine (enobasarm) is a selective androgen receptor modulator with great therapeutic potential. However, it is also used by athletes to promote muscle growth and enhance performances without the typical adverse effects of anabolic steroids. Ostarine popularity increased in recent years, and it is currently the most abused "other anabolic agent" (subclass S1.2. of the "anabolic agents" class S1) from the World Anti-Doping Agency's (WADA) prohibited list. Several cases of liver toxicity were recently reported in regular users. Detecting ostarine or markers of intake in biological matrices is essential to document ostarine use in doping. Therefore, we sought to investigate ostarine metabolism to identify optimal markers of consumption. The substance was incubated with human hepatocytes, and urine samples from six ostarine-positive cases were screened. Analyses were performed via liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) and software-assisted data mining, with in silico metabolite predictions. Ten metabolites were identified with hydroxylation, ether cleavage, dealkylation, O-glucuronidation, and/or sulfation. The production of cyanophenol-sulfate might participate in the mechanism of ostarine liver toxicity. We suggest ostarine-glucuronide (C25H22O9N3F3, diagnostic fragments at m/z 118, 185, and 269) and hydroxybenzonitrile-ostarine-glucuronide (C25H22O10N3F3, diagnostic fragments at m/z 134, 185, and 269) in non-hydrolyzed urine and ostarine and hydroxybenzonitrile-ostarine (C19H14O4N3F3, diagnostic fragments at m/z 134, 185, and 269) in hydrolyzed urine as markers to document ostarine intake in doping.

Simultaneous chemo- and enantio-separation of 2-, 3- and 4-chloro-methcatinones by high-performance liquid chromatography-tandem mass spectrometry and its application to oral fluid samples.

A method of analysis was developed for the simultaneous chemo- and enantioseparation of 2-, 3-, and 4-chloromethcathinones by high-performance liquid chromatography tandem mass-spectrometry. The fast method enables the reliable identification of positional isomers of chloromethcathinones in biological samples. In addition, the same method can be used for the enantioselective quantitative determination of one of these compounds and its major phase-1 metabolites in biological fluids. The developed method was applied to oral fluid samples collected by police during routine random traffic control in Belgium from January to November, 2023. It was found that 3-CMC was more frequently abused compared to 4-CMC. Although some differences were observed between the concentrations of enantiomers in OF, most likely the drugs were abused in the racemic form. No abuse of 2-CMC was detected at the timepoint of sample collection.

Oncological and Functional Outcomes of Penile Shaft Sparing Surgery for Localised Penile Cancer: A Systematic Review.

CONTEXT: Penile shaft sparing (PSS) surgery for localised penile cancer (PeCa) aims to balance oncological and functional outcomes. OBJECTIVE: To summarise the published evidence on different PSS approaches. EVIDENCE ACQUISITION: We performed a systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The systematic search was performed on PubMed, EMBASE, and Scopus databases up to February 14, 2023. The inclusion criteria encompassed retrospective or prospective studies including patients ≥18 yr of age with localised PeCa treated with different PSS approaches, classified as laser ablation, circumcision, wide local excision, glansectomy with or without split skin graft, glans resurfacing, and mixed technique excision. The risk of bias was assessed using the Newcastle-Ottawa scale. A quantitative synthesis was not performed due to anticipated data heterogeneity and a lack of comparative studies. EVIDENCE SYNTHESIS: Out of 4343 articles identified, 47 met our inclusion criteria, including 10 847 patients. The year of publication ranged between 1983 and 2021. Nine studies were prospective case series, while the remaining studies were retrospective. No comparative studies were identified. Most of the cases included in these studies were Ta and T1. The oncological outcomes were good for all the approaches, with cancer-specific mortality ranging between 0% and 18%. Sexual and cosmetic outcomes, despite being under-reported, were good for all the approaches, with almost all patients being satisfied with their quality of life after surgery. The Newcastle and Ottawa scale revealed a high or severely high risk of bias in all the included studies. CONCLUSIONS: PSS approaches were safe and had good functional outcomes, considering however the overall low quality of the studies on this issue. PATIENT SUMMARY: The perioperative, function, and oncological outcomes of penile shaft sparing approaches are good. However, high-quality studies are needed to determine whether these approaches benefit patients with localised penile cancer.

A green analytical method for the simultaneous determination of 17 perfluoroalkyl substances (PFAS) in human serum and semen by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

The ubiquity of perfluoroalkyl substances has raised concerns about the unintended consequences of PFAS exposure on human health. In the present study, an eco-friendly ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed for the simultaneous determination of 17 PFAS in human serum and semen samples. QuEChERS salts MgSO4:NaCl 4:1 (w/w) were used for the extraction. The separation of analytes was performed on an ACQUITY BEH C18 column (100 × 2.1 mm, 1.7 µm), using water:methanol 95:5 and methanol as mobile phases A and B, respectively, both containing 2 mM ammonium acetate. Multiple reaction monitoring (MRM) in negative ion mode was used, selecting two transitions for each analyte, except for perfluorobutanoic acid (PFBA) and perfluoropentanoic acid (PFPeA). The analytical method was validated according to the Organization of Scientific Area Committees (OSAC) for Forensic Sciences guidelines and AGREE approach software was used to evaluate the greenness of the method. The developed procedure was applied to the analysis of 10 paired human serum and semen samples, proving the suitability in high throughput laboratories due to the easy preparation and the reduced volume of toxic solvents. Moreover, it allows to perform further investigation on the correlation between serum and semen PFAS concentration, focusing on male reproductive system correlated pathologies, such as male infertility.

Use of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) PET/CT for lymph node assessment before radical cystectomy in bladder cancer patients.

OBJECTIVE: To assess the diagnostic performance of 18F-fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomograpy (PET)/computed tomography (CT) in nodal staging before radical cystectomy (RC) and pelvic lymph node dissection (PLND) for bladder cancer (BCa). MATERIALS AND METHODS: This analysis was based on a cohort of 199 BCa patients undergoing RC and bilateral PLND between 2015 and 2022. Neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) was administered after oncological evaluation. All patients received preoperative 18F-FDG PET/CT to assess extravesical disease. Point estimates for true negative, false negative, false positive, true positive, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of conventional imaging and PET/CT were calculated. Subgroup analysis in patients receiving neoadjuvant treatment was performed. RESULTS: At preoperative evaluation, 30 patients (15.1%) had 48 suspicious nodal spots on 18F-FDG PET/CT. At RC and bilateral PLND, a total of 4871 lymph nodes (LNs) were removed with 237 node metastases corresponding to 126 different regions. Pathological node metastases were found in 17/30 (57%) vs 39/169 patients (23%) with suspicious vs negative preoperative 18F-FDG PET/CT, respectively (sensitivity = 0.30, specificity = 0.91, PPV = 0.57, NPV = 0.77, accuracy = 0.74). On per-region analysis including 1367 nodal regions, LN involvement was found in 19/48 (39%) vs 105/1319 (8%) suspicious vs negative regions at PET/CT, respectively (sensitivity = 0.15, specificity = 0.98, PPV = 0.40, NPV = 0.92, ACC = 0.90). Similar results were observed for patients receiving NAC (n = 44, 32.1%) and NAI (n = 93, 67.9% [per-patient: sensitivity = 0.36, specificity = 0.91, PPV = 0.59, NPV = 0.80, accuracy = 0.77; per-region: sensitivity = 0.12, specificity = 0.98, PPV = 0.32, NPV = 0.93, ACC = 0.91]). Study limitations include its retrospective design and limited patient numbers. CONCLUSIONS: In eight out of 10 patients with negative preoperative 18F-FDG PET/CT, pN0 disease was confirmed at final pathology. No differences were found based on NAC vs NAI treatment. These findings suggest that 18F-FDG PET/CT could play a role in the preoperative evaluation of nodal metastases in BCa patients, although its cost-effectiveness is uncertain.

Peri- and post-operative outcomes of robot-assisted radical cystectomy after the implementation of the EAU guidelines recommendations for collecting and reporting complications at a high-volume referral center.

PURPOSE: No studies relied on a standardized methodology to collect postoperative complications after robot-assisted radical cystectomy (RARC). The aim of our study was to evaluate peri- and post-operative outcomes of patients undergoing RARC adhering to the European Association of Urology (EAU) recommendations for reporting surgical outcomes and using a long postoperative follow-up. MATERIALS AND METHODS: 246 patients who underwent RARC with intracorporal urinary diversion at a single tertiary referral center with a postoperative follow-up ≥ 1 year for survivors. Postoperative outcomes were collected prospectively by interviews done by medical doctors. Complications were scored using the Clavien-Dindo classification (CD), grouped by type and severity (severe: CD score ≥ 3). We described peri- and post-operative outcomes and complication chronological distribution. RESULTS: Overall, 16 (6.5%) and 225 patients (91%) experienced intraoperative and postoperative complications, respectively. Moreover, 139 (57%) experienced severe complications. The most common any-grade and severe complications were infectious (72%) and genitourinary (35%), respectively. Overall, 52% of complications (358/682) occurred within 10 days from surgery, and 51% of severe complications (106/207) occurred within 35 days. However, 13% of complications (90/682) and 28% of severe complications (59/207) occurred 3 months after surgery. The earliest complications were fever of unknown origins and paralytic ileus (median time-to-complication [mTTC]: 4 days), the latest complications were urinary tract infection (mTTC: 40 days) and hydronephrosis/ureteral obstruction (mTTC: 70 days). CONCLUSIONS: The rate of postoperative complications after RARC is > 90% when a standardized collection method and a long follow-up is implemented. These results should be used to identify potential areas of improvement and for preoperative patient counseling.

Magnetic Resonance Imaging in Prostate Cancer Screening: A Systematic Review and Meta-Analysis.

Importance: Prostate magnetic resonance imaging (MRI) is increasingly integrated within the prostate cancer (PCa) early detection pathway. Objective: To systematically evaluate the existing evidence regarding screening pathways incorporating MRI with targeted biopsy and assess their diagnostic value compared with prostate-specific antigen (PSA)-based screening with systematic biopsy strategies. Data Sources: PubMed/MEDLINE, Embase, Cochrane/Central, Scopus, and Web of Science (through May 2023). Study Selection: Randomized clinical trials and prospective cohort studies were eligible if they reported data on the diagnostic utility of prostate MRI in the setting of PCa screening. Data Extraction: Number of screened individuals, biopsy indications, biopsies performed, clinically significant PCa (csPCa) defined as International Society of Urological Pathology (ISUP) grade 2 or higher, and insignificant (ISUP1) PCas detected were extracted. Main Outcomes and Measures: The primary outcome was csPCa detection rate. Secondary outcomes included clinical insignificant PCa detection rate, biopsy indication rates, and the positive predictive value for the detection of csPCa. Data Synthesis: The generalized mixed-effect approach with pooled odds ratios (ORs) and random-effect models was used to compare the MRI-based and PSA-only screening strategies. Separate analyses were performed based on the timing of MRI (primary/sequential after a PSA test) and cutoff (Prostate Imaging Reporting and Data System [PI-RADS] score ≥3 or ≥4) for biopsy indication. Results: Data were synthesized from 80 114 men from 12 studies. Compared with standard PSA-based screening, the MRI pathway (sequential screening, PI-RADS score ≥3 cutoff for biopsy) was associated with higher odds of csPCa when tests results were positive (OR, 4.15; 95% CI, 2.93-5.88; P ≤ .001), decreased odds of biopsies (OR, 0.28; 95% CI, 0.22-0.36; P ≤ .001), and insignificant cancers detected (OR, 0.34; 95% CI, 0.23-0.49; P = .002) without significant differences in the detection of csPCa (OR, 1.02; 95% CI, 0.75-1.37; P = .86). Implementing a PI-RADS score of 4 or greater threshold for biopsy selection was associated with a further reduction in the odds of detecting insignificant PCa (OR, 0.23; 95% CI, 0.05-0.97; P = .048) and biopsies performed (OR, 0.19; 95% CI, 0.09-0.38; P = .01) without differences in csPCa detection (OR, 0.85; 95% CI, 0.49-1.45; P = .22). Conclusion and relevance: The results of this systematic review and meta-analysis suggest that integrating MRI in PCa screening pathways is associated with a reduced number of unnecessary biopsies and overdiagnosis of insignificant PCa while maintaining csPCa detection as compared with PSA-only screening.

Human metabolism of four synthetic benzimidazole opioids: isotonitazene, metonitazene, etodesnitazene, and metodesnitazene.

Following isotonitazene scheduling in 2019, the availability of alternative 2-benzylbenzimidazole opioids (nitazenes) on the global drug market increased, resulting in many fatalities worldwide. Nitazenes are potent µ-opioid receptor agonists with strong narcotic/analgesic effects, and their concentrations in biological matrices are low, making the detection of metabolite biomarkers of consumption crucial to document use in clinical and forensic settings. However, there is little to no data on the metabolism of the most recently available nitazenes, especially desnitro-analogues. The aim of the research was to assess isotonitazene, metonitazene, etodesnitazene, and metodesnitazene human metabolism and identify specific metabolite biomarkers of consumption. The four analogues were incubated with 10-donor-pooled human hepatocytes, and the incubates were analyzed by liquid chromatography-high-resolution tandem mass spectrometry and data mining with Compound Discoverer (Thermo Scientific); the analysis was supported by in silico metabolite predictions with GLORYx open-access software. Metabolites were identified in postmortem blood and/or urine samples from two metonitazene-positive and three etodesnitazene-positive cases following the same workflow, with and without glucuronide hydrolysis in urine, to confirm in vitro results. Twelve, nine, twenty-two, and ten metabolites were identified for isotonitazene, metonitazene, etodesnitazene, and metodesnitazene, respectively. The main transformations were N-deethylation at the N,N-diethylethanamine side chain, O-dealkylation, and further O-glucuronidation. In vitro and autopsy results were consistent, demonstrating the efficacy of the 10-donor-pooled human hepatocyte model to predict human metabolism. We suggest the parent and the corresponding O-dealkyl- and N-deethyl-O-dealkyl metabolites as biomarkers of exposure in urine after glucuronide hydrolysis, and the corresponding N-deethyl metabolite as additional biomarker in blood.

Preoperative risk calculator for the probability of completing nephron sparing for kidney cancer.

PURPOSE: In absence of predictive models, preoperative estimation of the probability of completing partial (PN) relative to radical nephrectomy (RN) is invariably inaccurate and subjective. We aimed to develop an evidence-based model to assess objectively the probability of PN completion based on patients' characteristics, tumor's complexity, urologist expertise and surgical approach. DESIGN, SETTING AND PARTICIPANTS: 675 patients treated with PN or RN for cT1-2 cN0 cM0 renal mass by seven surgeons at one single experienced centre from 2000 to 2019. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSES: The outcome of the study was PN completion. We used a multivariable logistic regression (MVA) model to investigate predictors of PN completion. We used SPARE score to assess tumor complexity. We used a bootstrap validation to compute the model's predictive accuracy. We investigated the relationship between the outcomes and specific predictors of interest such as tumor's complexity, approach and experience. RESULTS: Of 675 patients, 360 (53%) were treated with PN vs. 315 (47%) with RN. Smaller tumors [Odds ratio (OR): 0.52, 95%CI 0.44-0.61; P < 0.001], lower SPARE score (OR: 0.67, 95%CI 0.47-0.94; P = 0.02), more experienced surgeons (OR: 1.01, 95%CI 1.00-1.02; P < 0.01), robotic (OR: 10; P < 0.001) and open (OR: 36; P < 0.001) compared to laparoscopic approach resulted associated with higher probability of PN completion. Predictive accuracy of the model was 0.94 (95% CI 0.93-0.95). CONCLUSIONS: The probability of PN completion can be preoperatively assessed, with optimal accuracy relaying on routinely available clinical information. The proposed model might be useful in preoperative decision-making, patient consensus, or during preoperative counselling. PATIENT SUMMARY: In patients with a renal mass the probability of completing a partial nephrectomy varies considerably and without a predictive model is invariably inaccurate and subjective. In this study we build-up a risk calculator based on easily available preoperative variables that can predict with optimal accuracy the probability of not removing the entire kidney.

Orthotopic Robot-assisted Kidney Transplantation: Surgical Technique and Preliminary Results.

BACKGROUND AND OBJECTIVE: Orthotopic kidney transplantation (KT) has been proposed as an option for patients ineligible for heterotopic KT. In this scenario, orthotopic robot-assisted KT (oRAKT) represents a novel, minimally invasive alternative to the open approach. Here we describe the largest oRAKT series of patients, with a focus on the surgical technique, perioperative surgical outcomes, and functional results. METHODS: We queried prospectively maintained databases from three referral centers to identify patients who underwent oRAKT and evaluated surgical and functional outcomes. KEY FINDINGS AND LIMITATIONS: Overall, 16 oRAKT procedures were performed between January 2020 and August 2023. These involved four donors after cardiovascular death, five donors after brain death, and seven living donors. All oRAKT procedures were carried out in the left renal fossa. The indication for oRAKT was extensive calcification of the external iliac vessels (100%), frequently associated with prior KT (31%). The median operative time was 295 min (interquartile range [IQR] 268-360) and the median rewarming time 48 min (IQR 40-54). Conversion to open surgery occurred in two cases (12%), and delayed graft function was observed in two cases (12%). Postoperative complications occurred in 11 patients (69%) and three (18%) experienced Clavien-Dindo grade >II complications. At median follow-up of 9 mo (IQR 7-17), 14 patients had a functioning graft and median creatinine of 1.49 mg/dl (IQR 1.36-1.72). CONCLUSIONS AND CLINICAL IMPLICATIONS: Although oRAKT is a challenging procedure, it represents a feasible option for individuals ineligible for heterotopic KT and yields favorable perioperative and mid-term functional outcomes. PATIENT SUMMARY: We evaluated outcomes of orthotopic robot-assisted kidney transplantation (KT), in which the native kidney is removed and the donor kidney is transplanted into its place, in patients who are not eligible for heterotopic KT, in which the native kidney is left in place and the donor kidney is transplanted into a new location. We found that robot-assisted surgery is a safe and feasible alternative to traditional open surgery for orthotopic KT.