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Objectives: Martini et al. developed a nomogram to predict significant (>25%) renal function loss after robot‐assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini's nomogram on a large, national, multi‐institutional data set including open, laparoscopic, and robot‐assisted partial nephrectomy. Methods: Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini's nomogram were applied to each approach predicting renal function loss at all the specific timeframes. Results: Multivariable models showed high area under the curve for robot‐assisted partial nephrectomy at 6‐ and 12‐month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot‐assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was <70% at 48 months of follow‐up. Conclusions: Martini's nomogram is a valid tool for predicting the decline in renal function at 6 and 12 months after robot‐assisted partial nephrectomy and laparoscopic partial nephrectomy, whereas it showed a lower performance at longer follow‐up and in patients treated with open approach at all these time cutoffs. [ABSTRACT FROM AUTHOR]

Background: Aim of this study was to evaluate and compare perioperative outcomes of transperitoneal (TP) and retroperitoneal (TR) approaches in a multi-institutional cohort of minimally invasive partial nephrectomy (MI-PN). Material and methods: All consecutive patients undergone MI-PN for clinical T1 renal tumors at 26 Italian centers (RECORd2 project) between 01/2013 and 12/2016 were evaluated, collecting the pre-, intra-, and postoperative data. The patients were then stratified according to the surgical approach, TP or RP. A 1:1 propensity score (PS) matching was performed to obtain homogeneous cohorts, considering the age, gender, baseline eGFR, surgical indication, clinical diameter, and PADUA score. Results: 1669 patients treated with MI-PN were included in the study, 1256 and 413 undergoing TP and RP, respectively. After 1:1 PS matching according to the surgical access, 413 patients were selected from TP group to be compared with the 413 RP patients. Concerning intraoperative variables, no differences were found between the two groups in terms of surgical approach (lap/robot), extirpative technique (enucleation vs standard PN), hilar clamping, and ischemia time. Conversely, the TP group recorded a shorter median operative time in comparison with the RP group (115 vs 150 min), with a higher occurrence of intraoperative overall, 21 (5.0%) vs 9 (2.1%); p = 0.03, and surgical complications, 18 (4.3%) vs 7 (1.7%); p = 0.04. Concerning postoperative variables, the two groups resulted comparable in terms of complications, positive surgical margins and renal function, even if the RP group recorded a shorter median drainage duration and hospital length of stay (3 vs 2 for both variables), p < 0.0001. Conclusions: The results of this study suggest that both TP and RP are feasible approaches when performing MI-PN, irrespectively from tumor location or surgical complexity. Notwithstanding longer operative times, RP seems to have a slighter intraoperative complication rate with earlier postoperative recovery when compared with TP. [ABSTRACT FROM AUTHOR]

Background: Aim of the study was to present the surgical techniques and the postoperative outcomes in women treated with robotic excision for deep endometriosis involving the urinary tract.Materials and Methods: We retrospectively reviewed the prospectively recorded clinical data of women consecutively undergoing minimally invasive treatment for complex endometriosis involving urinary tract in our center between January 2012 and June 2018. All the patients received a preoperative multidisciplinary evaluation with the general surgeon, the gynecologist and the urologist due to the frequent concomitant involvement of bowel and genital system. Patients undergoing robotic surgery were treated with the Si or Xi da Vinci surgical system.Results: A total of 74 consecutive patients were enrolled. Twenty-eight (37.8%) patients underwent conventional laparoscopy and 46 (62.2%) robotic surgery. Only patients treated with robotic approach were considered for the final analyses. Overall, 17 (36.9%) patients were treated with partial cystectomy, 13 (28.3%) with ureteral reimplantation, 10 (21.7%) patients were treated with ureteral lysis, 4 (8.7%) with removal of bladder endometrial node without opening the mucosa layer and 2 (4.3%) with ureteral end-to-end anastomosis. Concomitant involvement of bowel and genital system was registered in 14 (30.4%) and 32 (69.5%) patients, respectively. No conversions to laparotomy were recorded. Overall, 5 (10.9%) patients experienced postoperative complications, of which only one was a major complication (Clavien 3b). At a median follow-up of 31.3 (IQR 17.6-43.3) months, 4 (8.7%) patients experienced disease recurrence at the level of urinary tract.Conclusions: Robotic excision of urological endometriosis represents a safe and effective treatment option, since a limited rate of surgical complications was recorded even in cases of multi-organ disease. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of oral supplementation with Serenoa repens (SR) and bovine colostrum (BC) plus tamsulosin (TAM) versus TAM alone over 12 months in men suffering from lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Methods: Between February 2018 and February 2019, men with symptomatic BPH (IPSS ≥10) were prospectively recruited. This prospective, open-label, 12-month study included two different protocols: (1) group A, SR 320 mg/day + BC 30 mg/day + TAM 0.4 mg/day, and (2) group B, TAM 0.4 mg/day only. Results: Overall, 148 patients entered the study, 76 in group A and 72 in group B. At 12 months, the total IPSS had decreased by 5.5 with TAM + SR + BC and by 5.1 with TAM only (p = 0.21). However, when the total IPSS was divided into storage and voiding subscores, at 6 months the storage symptoms had improved significantly more with TAM + SR + BC (–1.6 vs. –0.9 with TAM only, p = 0.02), with the benefit persisting also at the 1-year evaluation (–1.8 vs. –0.8, p = 0.02). Moreover, the improvement in LUTS-related quality of life (QoL) was significantly different between the groups, with a mean decrease in IPSS QoL subscore of –2.5 ± 0.2 for TAM + SR + BC versus –1.8 ± 0.3 for TAM at 6 months (p = 0.04), and of –2.9 ± 0.4 for TAM + SR + BC versus –2.1 ± 0.4 for TAM at 12 months (p = 0.04). Conversely, no significant differences were found in maximal urinary flow rate (p = 0.38), postvoid residual volume (p = 0.12), prostate-specific antigen (p = 0.41), and prostate volume (p = 0.16). Conclusion: Combination treatment with SR and BC plus TAM was shown to be more effective than treatment with TAM only in improving IPSS storage and QoL subscores in BPH patients after 6 months and up to 12 months of treatment. [ABSTRACT FROM AUTHOR]

We consider the problem of correctly classifying a given quantum two-level system (qubit) which is known to be in one of two equally probable quantum states. We assume that this task should be performed by a quantum machine which does not have at its disposal a complete classical description of the two template states, but can only have partial prior information about their level of purity and mutual overlap. Moreover, similarly to the classical supervised learning paradigm, we assume that the machine can be trained by $n$ qubits prepared in the first template state and by $n$ more qubits prepared in the second template state. In this situation, we are interested in the optimal process which correctly classifies the input qubit with the largest probability allowed by quantum mechanics. The problem is studied in its full generality for a number of different prior information scenarios and for an arbitrary size $n$ of the training data. Finite size corrections around the asymptotic limit $n\rightarrow \infty $ are derived. When the states are assumed to be pure, with known overlap, the problem is also solved in the case of d-level systems. [ABSTRACT FROM AUTHOR]

In non-muscle invasive bladder cancer, Bacillus Calmette–Guérin (BCG) responders benefit from strong Th1-type inflammatory and T cell responses mediating tumor rejection. However, the corresponding lack of anti-inflammatory Th2-type immunity impairs tissue repair in the bladder wall and facilitates the development of cystitis, causing urinary pain, urgency, incontinence, and frequency. Mechanistically, the leakage of the glycosaminoglycan (GAG) layer enables an influx of potassium ions, bacteria, and urine solutes towards the underlying bladder tissue, promoting chronic inflammation. Treatments directed towards re-establishing this mucopolysaccharide-based protective barrier are urgently needed. We discuss the pathomechanisms, as well as the therapeutic rationale of how chondroitin and hyaluronic acid instillations can reduce or prevent BCG-induced irritative bladder symptoms. Moreover, we present a case series of five patients with refractory BCG-induced cystitis successfully treated with combined chondroitin and hyaluronic acid instillations. [ABSTRACT FROM AUTHOR]

Objective: To identify meaningful predictors and to develop a nomogram of postoperative surgical complications in patients treated with partial nephrectomy (PN). Patients and Methods: We prospectively evaluated 4308 consecutive patients who had surgical treatment for renal tumours, between 2013 and 2016, at 26 Italian urological centres (RECORd 2 project). A multivariable logistic regression for surgical complications was performed. A nomogram was created from the multivariable model. Internal validation processes were performed using bootstrapping with 1000 repetitions. Results: Overall, 2584 patients who underwent PN were evaluated for the final analyses. The median (interquartile [IQR]) American Society of Anesthesiologists (ASA) score was 2 (2–3). In all, 72.4% of patients had clinical T1a (cT1a) stage tumours. The median (IQR) Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 7 (6–8). Overall, 34.3%, 27.7%, 38% of patients underwent open PN (OPN), laparoscopic PN (LPN), and robot‐assisted PN (RAPN). Overall and major postoperative surgical complications were recorded in 10.2% and 2.5% of patients, respectively. At multivariable analysis, age, ASA score, cT2 vs cT1a stage, PADUA score, preoperative anaemia, OPN and LPN vs RAPN, were significant predictive factors of postoperative surgical complications. We used these variables to construct a nomogram for predicting the risk of postoperative surgical complications. At decision curve analysis, the nomogram led to superior outcomes for any decision associated with a threshold probability of >5%. Conclusion: Several clinical predictors have been associated with postoperative surgical complications after PN. We used this information to develop and internally validate a nomogram to predict such risk. [ABSTRACT FROM AUTHOR]

The aim of the present review was to assess the prognostic impact of lymphovascular invasion (LVI) in transurethral resection (TUR) of bladder cancer (BCa) specimens on clinical outcomes. A systematic review and meta‐analysis of the available literature from the past 10 years was performed using MEDLINE, EMBASE and Cochrane library in August 2017. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42018084876) and is available in full on the University of York website. Overall, 33 studies (including 6194 patients) evaluating the presence of LVI at TUR were retrieved. LVI was detected in 17.3% of TUR specimens. In 19 studies, including 2941 patients with ≤cT1 stage only, LVI was detected in 15% of specimens. In patients with ≤cT1 stage, LVI at TUR of the bladder tumour (TURBT) was a significant prognostic factor for disease recurrence (pooled hazard ratio [HR] 1.97, 95% CI: 1.47–2.62) and progression (pooled HR 2.95, 95% CI: 2.11–4.13), without heterogeneity (I2 = 0.0%, P = 0.84 and I2 = 0.0%, P = 0.93, respectively). For patients with cT1–2 disease, LVI was significantly associated with upstaging at time of radical cystectomy (pooled odds ratio 2.39, 95% CI: 1.45–3.96), with heterogeneity among studies (I2 = 53.6%, P = 0.044). LVI at TURBT is a robust prognostic factor of disease recurrence and progression in non‐muscle invasive BCa. Furthermore, LVI has a strong impact on upstaging in patients with organ‐confined disease. The assessment of LVI should be standardized, reported, and considered for inclusion in the TNM classification system, helping clinicians in decision‐making and patient counselling. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized sarcopenia as predictive factor as a response to upfront chemotherapy of muscle-invasive urothelial bladder cancer (MIBC). Methods: We retrospectively studied 30 patients who received upfront cisplatin-based chemotherapy for MIBC (pT2–4 N0/+ M0) before planned radical cystectomy. Skeletal muscle index (SMI) was calculated by CT at study baseline and following completion of chemotherapy. Patients were stratified according to the presence of sarcopenia. Endpoints included clinical and pathological response. Results: Sixteen of the 30 patients (53.3%) had sarcopenia at baseline. The median SMI was 51.2 cm2/m2 (IQR 45.6–57.9). Throughout the course of chemotherapy, 22 patients (73.3%) experienced a decline in SMI, which ranged from 1 to 20% (median decline 3%, p < 0.01). All 16 patients with baseline sarcopenia persisted, while 5 of 14 patients (35.7%) without baseline sarcopenia became sarcopenic (p = 0.06). None of the clinical variables were predictive of clinical or pathological response, including SMI (p = 0.78 and p = 0.59), sarcopenia (p = 0.65 and p = 0.16) and SMI kinetics (p = 0.54 and p = 0.77). Conclusion: Sarcopenia is present in a considerable proportion of patients with MIBC undergoing upfront cisplatin-based chemotherapy before planned RC. SMI decreases during treatment, but neither baseline SMI nor its kinetics is associated with response to chemotherapy. [ABSTRACT FROM AUTHOR]

Aims: To investigate the physiological mechanisms leading to rapid improvement in diabetes after Roux‐en‐Y gastric bypass (RYGB) and specifically the contribution of the concurrent peri‐operative dietary restrictions, which may also alter glucose metabolism. Materials and methods: In order to assess the differential contributions of diet and surgery to the mechanisms leading to the rapid improvement in diabetes after RYGB we enrolled 10 patients with type 2 diabetes scheduled to undergo RYGB. All patients underwent a 10‐day inpatient supervised dietary intervention equivalent to the peri‐operative diet (diet‐only period), followed by, after a re‐equilibration (washout) period, an identical period of pair‐matched diet in conjunction with RYGB (diet and RYGB period). We conducted extensive metabolic assessments during a 6‐hour mixed‐meal challenge test, with stable isotope glucose tracer infusion performed before and after each intervention. Results: Similar improvements in glucose levels, β‐cell function, insulin sensitivity and post‐meal hepatic insulin resistance were observed with both interventions. Both interventions led to significant reductions in fasting and postprandial acyl ghrelin. The diet‐only intervention induced greater improvements in basal hepatic glucose output and post‐meal gastric inhibitory polypeptide (GIP) secretion. The diet and RYGB intervention induced significantly greater increases in post‐meal glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY) and glucagon levels. Conclusions: Strict peri‐operative dietary restriction is a main contributor to the rapid improvement in glucose metabolism after RYGB. The RYGB‐induced changes in the incretin hormones GLP‐1 and PYY probably play a major role in long‐term compliance with such major dietary restrictions through central and peripheral mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: Lymphovascular invasion (LVI) is an important step in bladder cancer cell dissemination. We aimed to perform a systematic review and meta-analysis of the literature to assess the prognostic value of LVI in radical cystectomy (RC) specimens.Patients and Methods: A systematic review and meta-analysis of the last 10 years was performed using the MEDLINE, EMBASE, and the Cochrane libraries in July 2017. The analyses were performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement.Results: We retrieved 65 studies (including 78,107 patients) evaluating the effect of LVI on oncologic outcomes in patients treated with RC. LVI was reported in 35.4% of patients. LVI was associated with disease recurrence (pooled hazard ratio [HR] = 1.57; 95% CI: 1.45-1.70) and cancer-specific mortality (CSM) (pooled HR = 1.59; 95% CI: 1.48-1.73) in all studies regardless of tumor stage and node status (pT1-4 pN0-2). LVI was associated with recurrence and CSM in patients with node-negative bladder cancer (BC). In patients with node-negative BC, LVI rate increased and was associated with worse oncologic outcome. LVI had a lower but still significant association with disease recurrence and CSM in node-positive BC.Conclusions: LVI is a strong prognostic factor of worse prognosis in patients treated with RC for bladder cancer. This association is strongest in node-negative BC, but it is also in node-positive BC. LVI should be part of all pathological reporting and could provide additional information for treatment-decision making regarding adjuvant therapy after RC. [ABSTRACT FROM AUTHOR]

Background In December 2006, the region of Tuscany (Italy) authorized the free-of-charge provision of phosphodiesterase type 5 inhibitors (PDE5I) for all patients with Tuscan citizenship who undergo nerve-sparing radical prostatectomy (NSRP). Objective To compare sexual rehabilitation outcomes in patients with low risk of erectile dysfunction and minimal comorbidities who received PDE5Is free of charge (PDE5I-F) with those who paid for PDE5Is (PDE5I-P) after bilateral NSRP. Methods We reviewed prospectively recorded clinical data of 2,368 patients with Tuscan (PDE5I-F) and non-Tuscan (PDE5I-P) citizenship treated with NSRP at 3 different institutions in Tuscany from 2008 to 2013. Inclusion criteria for the final analysis were open or robot-assisted bilateral NSRP; low risk of postoperative erectile dysfunction according to the Briganti risk stratification tool; no smoking and no drug and alcohol abuse; no cardiovascular risk factors; no major surgery before and after NSRP; no neoadjuvant or adjuvant treatment; and no biochemical relapse. Dropout was defined as an interruption longer than 40 days of the treatment protocol indicated in the inclusion criteria. Treatment compliance was defined as more than 90% consumption of the prescribed PDE5I. Outcomes The Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) and the Italian version of the University of California–Los Angeles Prostate Cancer Index sexual function (UCLA-PCI-s) questionnaires were administered to assess patients' satisfaction with PDE5I treatment and sexual function. Results Overall, 648 patients in the PDE5I-F group and 182 in the PDE5I-P group met the inclusion criteria and were eligible for the study. Patients had comparable preoperative and surgical characteristics. The PDE5I-F group had a significantly higher early rehabilitation onset ( P < .001), lower treatment dropout at 12, 24, and 36 months ( P < .001 for all comparisons), and higher compliance to the treatment protocol at 6 and 12 months ( P = .01 and P < .001, respectively). At multivariable analysis, the PDE5I-F protocol was an independent predictor of an EDITS score higher than 50 (hazard ratio = 1.54, P = .03) and a UCLA-PCI-s score higher than 50 (hazard ratio = 3.12, P = .01) after adjusting for the effects of several clinical features. Clinical Implications The free-of-charge protocol has a significant impact on patients' satisfaction with PDE5I treatment. Strengths and Limitations To our knowledge, this is the first study comparing free vs paid access to a sexual rehabilitation protocol. Major limitations are the observational nature of the study and the different population sizes of the 2 groups. Conclusions In a selected cohort of patients after NSRP, free-of-charge access to a sexual rehabilitation protocol was significantly associated with higher early rehabilitation onset, major compliance to the protocol, minor treatment dropout, and higher satisfaction rate of patients. Siena G, Mari A, Canale A, et al. Sexual Rehabilitation After Nerve-Sparing Radical Prostatectomy: Free-of-Charge Phosphodiesterase Type 5 Inhibitor Administration Improves Compliance to Treatment. J Sex Med 2018;15:120–123. [ABSTRACT FROM AUTHOR]

Purpose: To review the currently available literature reporting the patterns of recurrence and their predictive factors after open radical cystectomy (RC) for bladder cancer.Methods: A review of the literature was performed using the MEDLINE, Scopus and Web of Sciences databases from January 1997 to May 2017. The PRISMA guidelines were followed for the conduct of the study.Results: Local recurrence rate ranges between 30 and 54%. Distant recurrence is not often standardized and is reported in up to 50% of cases. The overall 5-year recurrence-free survival rates from 58 to 81%. The mean follow-up of studies included in the analysis ranged from 18 to 350 months. Details on the most important demographic and epidemiological, clinical, histologic and pathologic predictors of recurrence after radical cystectomy are provided through an evidence-based approach. The impact of the extension of lymph node dissection on recurrence after RC is investigated.Conclusions: A correct prognostic assessment is essential for patients undergoing radical cystectomy for bladder cancer, thereby potentially improving their oncologic outcomes. [ABSTRACT FROM AUTHOR]

References 1 Erdogan B, Berg S, Noldus J, Müller G. Early continence after ileal neobladder: objective data from inpatient rehabilitation. Authors retrospectively reviewed data from 283 male patients treated with a three-week inpatient rehabilitation after radical cystectomy (RC) and orthotopic neobladder (ONB) for bladder cancer, concluding that a dedicated rehabilitation program with a special multimodal continence therapy might improve early continence. Of course, optimizing nerve sparing procedure might be beneficial also for continence rates, since autonomic nerve fibers within neurovascular bundles innervate the striated urethral sphincter or pass through the sphincter to innervate the smooth muscle sphincter component of the membranous urethra [[4]]. [Extracted from the article]

Objective: To evaluate perioperative results of open (OPN), laparoscopic (LPN), and robot-assisted partial nephrectomies (RAPN) and to identify predictive factors of Trifecta achievement for clinical T1b renal tumors in a multicenter prospective dataset.Methods: Data of 285 patients who had OPN (133), LPN (57), or RAPN (95) for cT1b renal tumors were extracted from the RECORd Project. High-volume centers were defined as ≥50 overall cases of partial nephrectomy per year. Trifecta was defined as simultaneous absence of perioperative complications, negative surgical margins, and ischemia time <25 minutes.Results: The 3 groups had comparable body mass index, preoperative hemoglobin, creatinine and estimated glomerular filtration rate, tumor clinical diameter, and growth pattern. LPN and RAPN were more frequently exclusive of high-volume centers. RAPN showed significantly lower median estimated blood loss compared with OPN and LPN. Trifecta was achieved in 62.4%, 63.2%, and 69.5% of OPN, LPN, and RAPN (P = NS) cases. Median warm ischemia time (WIT) was significantly shorter during OPN than during LPN and RAPN. RAPN had significantly shorter WIT compared with LPN. RAPN was significantly less morbid than OPN regarding intraoperative and postoperative complications. LPN (1.9%) and RAPN (2.5%) showed a lower rate of positive margins compared with OPN (6.8%) (P = NS). At multivariable analysis, exophytic tumor growth pattern, estimated blood loss, and high-volume centers were significant predictive factors for Trifecta achievement.Conclusion: Clinically, T1b renal tumors suitable for NSS can be safely treated by LPN or RAPN in high-volume centers. RAPN allows for significantly lower WIT and estimated blood loss with higher rate of Trifecta achievement compared with LPN. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this paper is to present evidence regarding the associations between smoking and the following urologic cancers: prostate, bladder, renal, and upper tract urothelial cancer (UTUC). Methods: This is a narrative review. PubMed was queried for evidence-based analyses and trials regarding the associations between smoking and prostate, bladder, renal, and UTUC tumors from inception to September 1, 2022. Emphasis was placed on articles referenced in national guidelines and protocols. Results: Prostate—multiple studies associate smoking with higher Gleason score, higher tumor stage, and extracapsular invasion. Though smoking has not yet been linked to tumorigenesis, there is evidence that it plays a role in biochemical recurrence and cancer-specific mortality. Bladder—smoking is strongly associated with bladder cancer, likely due to DNA damage from the release of carcinogenic compounds. Additionally, smoking has been linked to increased cancer-specific mortality and higher risk of tumor recurrence. Renal—smoking tobacco has been associated with tumorigenesis, higher tumor grade and stage, poorer mortality rates, and a greater risk of tumor recurrence. UTUC—tumorigenesis has been associated with smoking tobacco. Additionally, more advanced disease, higher stage, lymph node metastases, poorer survival outcomes, and tumor recurrence have been linked to smoking. Conclusion: Smoking has been shown to significantly affect most urologic cancers and has been associated with more aggressive disease, poorer outcomes, and tumor recurrence. The role of smoking cessation is still unclear, but appears to provide some protective effect. Urologists have an opportunity to engage in primary prevention by encouraging cessation practices. [ABSTRACT FROM AUTHOR]

High-risk non-muscle-invasive bladder cancer (NMIBC) is a common and heterogeneous entity and it often represents a clinical dilemma for urologists due to need to balance the risk of recurrence and progression with the risk of overtreatment (i.e., early radical cystectomy).1 Transurethral resection of bladder tumor (TURBT) is the standard diagnostic and therapeutic approach to NMIBC. Bladder cancer prospective cohort study on high-risk non-muscle invasive bladder cancer after photodynamic diagnosis-assisted transurethral resection of the bladder tumor (BRIGHT study). Editorial Comment from Dr Tellini et al. to Bladder cancer prospective cohort study on high-risk non-muscle invasive bladder cancer after photodynamic diagnosis-assisted transurethral resection of the bladder tumor (BRIGHT study). [Extracted from the article]

In this paper, we explore the set of linear maps sending the set of quantum Gaussian states into itself. These maps are in general not positive, a feature which can be exploited as a test to check whether a given quantum state belongs to the convex hull of Gaussian states (if one of the considered maps sends it into a non-positive operator, the above state is certified not to belong to the set). Generalizing a result known to be valid under the assumption of complete positivity, we provide a characterization of these Gaussian-to-Gaussian (not necessarily positive) superoperators in terms of their action on the characteristic function of the inputs. For the special case of one-mode mappings, we also show that any Gaussianto- Gaussian superoperator can be expressed as a concatenation of a phase-space dilatation, followed by the action of a completely positive Gaussian channel, possibly composed with a transposition. While a similar decomposition is shown to fail in the multi-mode scenario, we prove that it still holds at least under the further hypothesis of homogeneous action on the covariance matrix. [ABSTRACT FROM AUTHOR]

Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-βCGS to the 2-h hyperglycemic clamp-βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia. [ABSTRACT FROM AUTHOR]

Although GLP-1 has been suggested as a major factor for the marked improvement of glucose tolerance commonly seen after sleeve gastrectomy (SG), several observations challenge this hypothesis. To better understand the role of GLP-1 in the remission of type 2 diabetes mellitus (T2DM) long term after SG in humans, we conducted two separate cross-sectional studies: 1) the GLP-1 response to a standardized mixed liquid meal (SMLM) was compared in subjects with T2DM antedating SG but with different long-term (>2 years) T2DM outcomes (remission, relapse, or lack of remission) (study 1) and 2) the effect of GLP-1 receptor blockade with exendin (9-39) on glucose tolerance was examined in subjects with T2DM antedating surgery, who had undergone SG and presented with long-term T2DM remission (study 2). In study 1, we observed a comparable GLP-1 response to the SMLM regardless of the post-SG outcome of T2DM. In study 2, the blockade of GLP-1 action resulted in impaired insulin secretion but limited deterioration of glucose tolerance. Thus, our data suggest the enhanced GLP-1 secretion observed long term after SG is neither sufficient nor critical to maintain normal glucose tolerance in subjects with T2DM antedating the surgery. [ABSTRACT FROM AUTHOR]

The incretin effect on insulin secretion was investigated in 8 subjects with type 2 diabetes (T2D) and 8 with normal glucose tolerance (NGT), using 25, 75, and 125 g oral glucose tolerance tests (OGTT) and isoglycemic intravenous glucose infusions (IIGI). The ß-cell response was evaluated using a model embedding a dose-response (slope = glucose sensitivity), an early response (rate sensitivity), and potentiation (time-related secretion increase). The incretin effect, as OGTT/IIGI ratio, was calculated for each parameter. In NGT, the incretin effect on total secretion increased with dose (1.3±0.1, 1.7±0.2, 2.2±0.2 fold of IIGI, P<0.0001), mediated by a dose-dependent increase of the incretin effect on glucose sensitivity (1.9±0.4, 2.4±0.4, 3.1±0.4, P = 0.005), and a dose-independent enhancement of the incretin effect on rate sensitivity (894 [1145], 454 [516], 783 [1259] pmol m−2 L mmol−1 above IIGI; median [interquartile range], P<0.0001). The incretin effect on potentiation also increased (0.97±0.06, 1.45±0.20, 1.24±0.16, P<0.0001). In T2D, the incretin effect on total secretion (1.0±0.1, 1.1±0.1, 1.3±0.1, P = 0.004) and glucose sensitivity (1.2±0.2, 1.3±0.2, 2.0±0.2, P = 0.005) were impaired vs NGT; however, the incretin effect on rate sensitivity increased already at 25 g (269 [169], 284 [301], 193 [465] pmol m−2 L mmol−1 above IIGI; negligible IIGI rate sensitivity in T2D prevented the calculation of the fold increment). OGTT did not stimulate potentiation above IIGI (0.94±0.04, 0.89±0.06, 1.06±0.09; P<0.01 vs NGT). In the whole group, the incretin effect was inversely associated with total secretion during IIGI, although systematically lower in T2D. In conclusion, 1) In NGT, glucose sensitivity and potentiation mediate the dose-dependent incretin effect increase; 2) In T2D, the incretin effect is blunted vs NGT, but rate sensitivity is enhanced at all loads; 3) Relatively lower incretin effect in NGT is associated with higher secretion during IIGI, suggesting that the reduced incretin effect does not result from ß-cell dysfunction. [ABSTRACT FROM AUTHOR]

The increase in malnutrition due to excess supports the need to reassess the role of food environments in the well-being and food security of the population. The objective of this bibliographic review is to carry out a descriptive search of food environments and how these condition states of malnutrition due to excess and the food security of the population. Through a narrative investigation in search engines and databases (Medline, Scielo, Scopus, Virtual Health Library, Medes and Google Scholar), original articles or reviews in Spanish and English published between 2017 and 2021 were identified, served the purposes of the study. 56 articles were included, which allowed to study in more detail the five theoretical categories: institutional and organizational food environment, restoration, public thoroughfare, supply and home; as well as in the way in which these environments enhance malnutrition due to excess and put pressure on the food security of the population. The different environments or food environments direct the lifestyles and well-being of people and communities, in addition to influencing the etiology and maintenance of malnutrition due to excess and the food security of the population. [ABSTRACT FROM AUTHOR]

To characterize the defects in β-cell function in subjects with impaired fasting glucose (IFG) and compare the results to impaired glucose tolerance (IGT) and normal glucose tolerance (NGT) subjects, β-cell glucose sensitivity and rate sensitivity during the oral glucose tolerance test were measured with the model by Mari in 172 Mexican Americans. A subgroup (n = 70) received a 2-h hyperglycemic clamp (+125 mg/dL), and first- and second-phase insulin secretion were quantitated. Compared with NGT, subjects with IFG and IGT manifested a decrease in b-cell glucose sensitivity; IFG subjects, but not IGT subjects, had decreased β-cell rate sensitivity. In IFG subjects, the defect in β-cell glucose sensitivity was time dependent, began to improve after 60 min, and was comparable to NGT after 90 min. The incremental area under the plasma C-peptide concentration curve during the first 12 min of the hyperglycemic clamp (ΔC-pep [AUC]0-12) was inversely related with the increase in FPG concentration (r = 236, r = 0.001), whereas ΔC-pep[AUC]15-120 positively correlated with FPG concentration (r = 0.29, r , 0.05). When adjusted for the prevailing level of insulin resistance, first-phase insulin secretion was markedly decreased in both IFG and IGT, whereas second-phase insulin secretion was decreased only in IGT. These results demonstrate distinct defects in β-cell function in IFG and IGT. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT) and whether they contribute to dysglycemia in impaired glucose regulation (IGR). RESEARCH DESIGN AND METHODS--Insulin sensitivity (by euglycemic clamp), insulin-induced secretory response at isoglycemia (IISR) (as C-peptide percent change from basal during the clamp), glucose-induced secretory response (GISR) to an intravenous glucose bolus, and β-cell glucose sensitivity (β-GS) (by oral glucose tolerance test [OGTT] modeling) were measured in 1,151 NGT and 163 IGR subjects from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study. RESULTS--In NGT, IISR was related to both insulin sensitivity and antecedent insulin exposure; GISR was related to insulin exposure. IISR was positively, if weakly, related to β-GS (r = 0.16, P < 0.0001). Both IISR (-23 [39] vs. 29 [2]%, median [interquartile range], P < 0.03) and β-GS (69 [47] vs. 118 [83] pmol x min--1 x m--2 x mmol--1 x L, P < 0.0001) were decreased in IGR compared with NGT. Insulin sensitivity and β-GS were the major determinants of mean OGTT glucose in both NGT and IGR, with a minor role for IISR. In a multivariate logistic model, IGR was predicted by β-GS (odds ratio 4.84 [95% CI 2.89--8.09]) and insulin sensitivity (3.06 [2.19--4.27]) but not by IISR (1.11 [0.77--1.61]). CONCLUSIONS--Pre-exposure to physiological hyperinsulinemia stimulates insulin secretion to a degree that depends on insulin sensitivity. However, this phenomenon has limited impact on β-cell dysfunction and dysglycemia. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To quantitate the separate impact of obesity and hyperlycemia on the incretin effect (i.e., the gain in β-cell function after oral glucose versus intravenous glucose). RESEARCH DESIGN AND METHODS--Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51 subjects (24 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT], and 10 with type 2 diabetes) with a wide range of BMI (20-61 kg/m[sup 2]). C-peptide deconvolution was used to reconstruct insulin secretion rates, and β-cell glucose sensitivity (slope of the insulin secretion/glucose concentration doseresponse curve) was determined by mathematical modeling. The incretin effect was defined as the oral-to-intravenous ratio of responses. In 8 subjects with NGT and 10 with diabetes, oral glucose appearance was measured by the double-tracer technique. RESULTS--The incretin effect on total insulin secretion and β-cell glucose sensitivity and the GLP-1 response to oral glucose were significantly reduced in diabetes compared with NGT or IGT (P ≤ 0.05). The results were similar when subjects were stratified by BMI tertile (P ≤ 0.05). In the whole dataset, each manifestation of the incretin effect was inversely related to both glucose tolerance (2-h plasma glucose levels) and BMI (partial r = 0.27-0.59, P ≤ 0.05) in an independent, additive manner. Oral glucose appearance did not differ between diabetes and NGT and was positively related to the GLP-1 response (r = 0.53, P < 0.01). Glucagon suppression during the oral glucose tolerance test was blunted in diabetic patients. CONCLUSIONS--Potentiation of insulin secretion, glucose sensing, glucagon-like peptide-1 release, and glucagon suppression are physiological manifestations of the incretin effect. Glucose tolerance and obesity impair the incretin effect independently of one another. Diabetes 57:1340-1348, 2008 [ABSTRACT FROM AUTHOR]

OBJECTIVE -- We studied the effects of the oral insulin secretagogue nateglinide on insulin secretion using a modeling approach to obtain β-cell function parameters from a meal test and examined the impact of the β-cell improvement on glucose tolerance. RESEARCH DESIGN AND METHODS -- Mild type 2 diabetic men and women (n = 108; fasting glucose 7.0-8.3 mmol/l) on diet treatment alone randomly received 30, 60, or 120 mg nateglinide or placebo for 24 weeks. β-Cell function parameters were derived by modeling (based on C-peptide deconvolution) from a standardized meal test at baseline and after 24 weeks of treatment. RESULTS -- The baseline demographic and metabolic characteristics of the four groups were similar. Nateglinide treatment resulted in dose-dependent reductions in the mean postprandial glucose response and at the 120-mg dose in fasting glucose. Fasting or total insulin secretion during the meal were not different. In contrast, we found differences in the model parameters. Rate sensitivity (expressing early insulin secretion when glucose is rising) was significantly enhanced at 24 weeks with the lowest nateglinide dose, with no further stimulation at higher doses. Early potentiation (expressing an initial insulin secretion enhancement), glucose sensitivity (the slope of the glucose-insulin secretion relationship), and insulin secretion at a fixed-reference 7-mmol/l glucose concentration all showed a trend toward increasing, with increasing nateglinide dose, and were significantly greater than placebo at the 120-mg dose. In multiple regression analyses, changes in rate sensitivity, glucose sensitivity, and potentiation all contributed to the observed glucose changes. CONCLUSIONS -- The model-derived parameters are sensitive measures of β-cell function, showing improvements after nateglinide treatment and predicting changes in glucose tolerance. [ABSTRACT FROM AUTHOR]

This study presents a circulatory model of glucose kinetics for application to non-steady-state conditions, examines its ability to predict glucose appearance rates from a simulated oral glucose load, and compares its performance with compartmental models. A glucose tracer bolus was injected intravenously in rats to determine parameters of the circulatory and two-compartment models. A simulated oral glucose tolerance test was performed in another group of rats by infusing intravenously labeled glucose at variable rates. A primed continuous intravenous infusion of a second tracer was given to determine glucose clearance. The circulatory model gave the best estimate of glucose appearance, closely followed by the two-compartment model and a modified Steele one-compartment model with a larger total glucose volume. The standard one-compartment model provided the worst estimate. The average relative errors on the rate of glucose appearance were: circulatory, 10%; two-compartment, 13%; modified one-compartment, 11%; standard one-compartment, 16%. Recovery of the infused glucose dose was 93±2, 94±2, 92±2 and 85±2%, respectively. These results show that the circulatory model is an appropriate model for assessing glucose turnover during an oral glucose load. [Copyright &y& Elsevier]

We investigated β-cell function and its relationship to insulin sensitivity in 17 normal volunteers. For insulin secretion (derived by C-peptide deconvolution), a mathematical model was applied to 24-h triple-meal tests (MT) as well as oral glucose tolerance tests (OGTT); insulin sensitivity was assessed by the euglycemic insulin clamp technique. The β-cell model featured a glucose concentration-insulin secretion dose response (characterized by secretion at 5 mM glucose and slope), a secretion component proportional to the glucose concentration derivative, and a time-dependent potentiation factor (modulating the dose response and accounting for effects of sustained hyperglycemia and incretins). The β-cell dose-response functions estimated from the whole 24-h MT, the first 2 h of the MT, and the OGTT differed systematically, because a different potentiation factor was involved. In fact, potentiation was higher than average during meals (1.6 ± 0.1-fold during the first meal) and had a different time course in the MT and OGTT. However, if potentiation was accounted for, the 24and 2-h MT and the OGTT yielded similar dose responses, and most β-cell function parameters were intercorrelated (r = 0.50-0.86, P ≤ 0.05). The potentiation factor was found to be related to plasma glucose-dependent insulin-releasing polypeptide concentrations (r = 0.49, P < 0.0001). Among β-cell function parameters, only insulin secretion at 5 mM glucose from MT correlated inversely with insulin sensitivity (24-h MT: r = -0.74, P < 0.001; 2-h MT: r = -0.52, P < 0.05), whereas the dose-response slope and the OGTT parameters did not. In nine other subjects, reproducibility of model parameters was evaluated from repeated MTs. Coefficients of variation were generally ∼20%, but the derivative component was less reproducible. We conclude that our model for the multiple MT yields useful information on β-cell function, particularly with regard to the role... [ABSTRACT FROM AUTHOR]

We developed a mathematical model of the glucose control of insulin secretion capable of quantifying beta-cell function from a physiological meal test. The model includes a static control, i.e., a secretion component that is a function of plasma glucose concentration (the dose-response function), and a dynamic control, i.e., a secretion component that is proportional to the positive values of the glucose concentration derivative. Furthermore, the dose-response function is assumed to be modulated by a time-varying potentiation factor. To test the model, nine nondiabetic control subjects and nine type 2 diabetic patients received three standardized mixed meals over a period of 14-15 h. Blood samples were drawn for the measurement of glucose, insulin, and C-peptide concentration. The dose-response function, the parameter of the dynamic control, and the potentiation factor were determined by fitting the model to glucose and C-peptide concentrations. In diabetic patients, the dose-response function was shifted to the right (glucose concentration at a reference insulin secretion of 300 pmol.min(-1).m(-2) was 11.7 +/- 1.1 vs. 7.2 +/- 0.7 mmol/l; P < 0.05), and decreased in slope (53 +/- 15 vs. 148 +/- 38 pmol.min(-1).m(-2).mmol(-1).l; P < 0.05) and the parameter of the dynamic control was decreased (220 +/- 67 vs. 908 +/- 276 pmol.m(-2).mmol(-1).l; P < 0.05) compared with the nondiabetic control subjects. Furthermore, potentiation was markedly blunted and delayed: maximum potentiation was observed at the first meal in normal subjects and at the second meal (about 4 h later) in diabetic subjects; the mean time for the potentiation factor was higher (7.1 +/- 0.2 vs. 5.9 +/- 0.2 h; P < 0.01), and the size of potentiation was reduced (2.6 +/- 0.5 vs. 7.2 +/- 1.5 fold increase; P < 0.005). In conclusion, our model of insulin secretion extracts multiple indexes of beta-cell function from a physiological meal test. Use of the model in patients with type 2 diabetes retrieves known defects in insulin secretion but also uncovers new facets of beta-cell dysfunction. [ABSTRACT FROM AUTHOR]

Objective: Available insulin sensitivity (IS) methods based on the oral glucose tolerance test (OGTT) are empirical. We used a glucose-insulin model to derive an OGTT-based IS (oral glucose insulin sensitivity [OGIS]) index, which predicts glucose clearance in a glucose clamp. We validated OGIS against clamp data.Research Design and Methods: OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0, 2, and 3 h (3-h OGTT) or at 0, 1.5, and 2 h (2-h OGTT). The formula includes six constants optimized to match the clamp results. For this purpose, 15 lean nondiabetic subjects (BMI < 25 kg/m2), 38 obese nondiabetic subjects (BMI > 25 kg/m2), and 38 subjects with type 2 diabetes randomly underwent an OGTT and a 120 mU x min(-1) x m(-2) insulin infusion euglycemic clamp. Glucose clearance (Cl CLAMP), calculated as the ratio of glucose infusion to concentration during the last hour of the clamp, was compared with OGIS. OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance (IGT).Results: OGIS and Cl CLAMP were correlated in the whole group (R = 0.77, P < 0.0001), in the subgroups (lean: R = 0.59; obese: R = 0.73; type 2 diabetes: R = 0.49; P < 0.02), and in the independent IGT group (R = 0.65, P < 0.02). Reproducibility of OGIS and Cl CLAMP were similar (coefficients of variation: OGIS 7.1%, Cl CLAMP 6.4%). OGIS was as effective as Cl CLAMP in discriminating between groups (for OGIS, lean vs. obese: 440 +/- 16 vs. 362 +/- 11 ml x min(-1) x m(-2), p < 0.001; lean vs. type 2 diabetes: 440 +/- 16 vs. 239 +/- 7, P < 0.0001; obese vs. type 2 diabetes: 362 +/- 11 vs. 239 +/- 7, P < 0.0001; results were similar for Cl CLAMP). The relationships between IS and BMI, fasting plasma insulin, and insulin secretion (calculated from the OGTT insulin concentration) were examined. OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles. The performance of the index for the 3-h and 2-h OGTT was similar.Conclusions: OGIS is an index of IS in good agreement with the clamp. Because of its simplicity (only three blood samples required), this method has potential use for clinical investigation including large-scale epidemiological studies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node‐positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. Patients and Methods: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose‐dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1–3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni‐ and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer‐specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. Results: Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles (P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2‐year OS estimates were 63% (95% confidence interval [CI] 0.53–0.74) and 63% (95% CI 0.58–0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni‐ or multivariable Cox regression analyses. Conclusion: Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation. [ABSTRACT FROM AUTHOR]

Pancreatic β cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here, we report that succinate receptor 1 (SUCNR1) is expressed in β cells and is upregulated in hyperglycemic states in mice and humans. We found that succinate acted as a hormone-like metabolite and stimulated insulin secretion via a SUCNR1-GqPKC–dependent mechanism in human β cells. Mice with β cell–specific Sucnr1 deficiency exhibited impaired glucose tolerance and insulin secretion on a high-fat diet, indicating that SUCNR1 is essential for preserving insulin secretion in diet-induced insulin resistance. Patients with impaired glucose tolerance showed an enhanced nutrition-related succinate response, which correlates with the potentiation of insulin secretion during intravenous glucose administration. These data demonstrate that the succinate/SUCNR1 axis is activated by high glucose and identify a GPCR-mediated amplifying pathway for insulin secretion relevant to the hyperinsulinemia of prediabetic states. [ABSTRACT FROM AUTHOR]

Background: Follow-up after radical cystectomy (RC) for bladder cancer can be divided into oncological and functional surveillance. It remains unclear how follow-up after RC should ideally be scheduled. The aim of this report was to gain insight into the organization of follow-up after RC in Europe, for which we conducted a roundtable inventory within the EAU Young Academic Urologists Urothelial Cancer working group. Methods: An inventory semi-structured survey was performed among urologists of the EAU Young Academic Urologists Urothelial Cancer working group to describe the organization of follow-up. The surveys were analyzed using a deductive approach. Similarities and differences in follow-up after RC for bladder cancer were described. Results: The survey included 11 urologists from six different European countries. An institutional follow-up scheme was used by six (55%); three (27%) used a national or international guideline, and two (18%) indicated that there was no defined follow-up scheme. Major divergent aspects included the time points of follow-up, the frequency, and the end of follow-up. Six centers (55%) adopted a risk-adapted follow-up approach tailored to (varying) patient and tumor characteristics. Laboratory tests and CT scans were used in all cases; however, the intensity and frequency varied. Functional follow-up overlapped with oncological follow-up in terms of frequency and duration. Patient-reported outcome measures were only used by two (18%) urologists. Conclusions: Substantial variability exists across European centers regarding the follow-up after RC for bladder cancer. This highlights the need for an international analysis focusing on its organization and content as well as on opportunities to improve patients' needs during follow-up after RC. [ABSTRACT FROM AUTHOR]

Assesses insulin sensitivity with a minimal model and the role of the model assumptions. Model used to assess insulin sensitivity; What was used to ascertain validity of approach; Selection of reference data used in study; Detailed information of study; Results of study; Equations used in study.

Examines the role of model assumptions on assessment of insulin sensitivity using minimal model (MM). Basic definitions; MM expression of glucose logarithmic slope; Adequacy of MM expression of glucose logarithmic slope; Physiological determinants of glucose logarithmic slope; Role of glucose production and hepatic insulin sensitivity.

Type 2 diabetes (T2D) risk is lower in females than males. It has been reported that females have greater pancreatic 훽‐cell function than males, which may at least in part contribute to the T2D risk in females. 훽‐cell function is influenced by exercise training; however, previous trials comparing 훽‐cell function between the sexes have not included participants matched for training status. Furthermore, the acute effects of different modes of exercise on 훽‐cell function, and whether sex inherently influences these effects, are largely unexamined. Males and females (12/sex) completed a 120‐min oral glucose tolerance test (OGTT) at rest (CON) and following acute bouts of high‐intensity interval exercise (HIIE), moderate intensity continuous (MIC) exercise, and low‐load high‐repetition (LLHR) resistance exercise to assess whether sex inherently influences baseline and/or post‐exercise pancreatic function in the absence of pathology. We found no sex differences in basal pancreatic 훽‐cell function. Females had greater basal insulin clearance following MIC exercise compared to males (p = 0.01) and males tended to have a higher potentiation ratio following HIIE (p = 0.07). Females also had lower glucose sensitivity following MIC exercise compared to HIIE (p = 0.007) and LLHR (p = 0.003). Insulin clearance during the OGTT was greater following HIIE as compared with CON and MIC exercise (p = 0.02). 2‐H oral glucose insulin sensitivity was greater following LLHR compared to CON (p = 0.01). Acute bouts of different modes of exercise do not differentially influence 훽‐cell function but do influence insulin clearance and insulin sensitivity. Therefore, sex and exercise mode interact to differentially influence insulin clearance and glucose sensitivity. [ABSTRACT FROM AUTHOR]

Purpose: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette–Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). Methods: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19–76). The cumulative incidence and Kaplan–Meier curves were applied for CSM and OM, respectively, and compared with the Pepe–Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. Results: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe–Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). Conclusion: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen. [ABSTRACT FROM AUTHOR]

Background: To investigate the perioperative and morbidity outcomes after partial nephrectomy (PN) in patients with short life expectancy (SLE) (≥95% 10-year expected mortality (10y-EM)), to assess the main predictors of outcomes in this population and to compare these results with those of a group at the opposite upper range with long LE (LLE, ≤5% 10y-EM) relying on a multicenter Italian prospective registry of kidney surgery (the RECORD 2 project).Methods: Clinical data of 4,325 patients undergone kidney surgery were collected at 26 urological Italian Centers from 2013 to 2016. SLE was defined as a ≥95% 10y-EM (assessed using the age-adjusted Charlson comorbidity index [CCI]). A multivariable logistic regression for overall postoperative complications, acute kidney injury (AKI), positive surgical margins (SM) and ∆ estimated glomerular filtration rate (eGFR) ≥25% at 2 years from surgery was performed in patients with SLE including clinically relevant variables. Adjusted outcomes reported as mean (SD) of the 2 groups were generated using separate multivariable logistic regression models and compared.Results: Overall, 559 patients with SLE were selected. Patients had an ASA score ≥3 in 58.4% of cases. A clinical T1a, T1b, and T2 stage was found in 412 (74.5%), 124 (22.4%), and 17 (3.1%) patients. The median PADUA score was 7 (6-8). Surgical and medical postoperative complication rates were registered in 14.8% and 6% cases. Postoperative AKI was reported in 27.3% cases, positive surgical margins (PSM) in 9.3% cases. In this subgroup of patients, ASA score, cerebrovascular disease, surgery in low volume centers, and open surgery were independent predictors of overall complications. ASA and PADUA scores, renal clamping, resection technique and lower eGFR at baseline were independent predictors of AKI. PADUA score, open approach and resection technique were independent predictors of PSM. Cardiovascular disease, hilar clamping, and resection technique were independent predictors of eGFR decrease >25% at 2 years from surgery. Patients with SLE were compared with those with LLE (n = 302). All analyzed parameters at baseline were significantly different among the groups with the exception of cancer laterality. After adjusting for several clinical variables, the SLE group had a significantly higher risk rate of adjusted overall postoperative complication rate compared to the LLE group (20.6% ± 0.36 vs. 9.9% ± 0.65, P < 0.0001), while the overall intraoperative complications (4.1% ±0.13 vs. 2.3% ± 0.23), overall postoperative major complications (3.8% ± 0.09 vs. 1.9% ± 0.14) adjusted AKI (24.2% ± 0.37 vs. 22.6% ± 0.92), positive surgical margins (8% ± 0.22 vs. 6.4% ± 0.49), and 2-year RF loss (13.4% ± 0.17 vs. 12.4% ± 0.74).Conclusion: In selected patients with SLE, PN is feasible with an acceptable safety profile that is overall comparable to patients with no LE limitations. While a robotic approach and surgery performed in high volume centers could reduce the risk of complications, an off-clamp approach and a SE surgical technique may decrease the risk of postoperative AKI and of longer term eGFR decrease. [ABSTRACT FROM AUTHOR]

Background: There is a need for effective nonsurgical treatment options in patients with nonmuscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed.Objective: We aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) with NMIBC after BCG failure.Design, Setting, and Participants: A retrospective review of 26 NMIBC patients in whom BCG therapy failed who received BCG/EMDA-MMC between 2013 and 2017 was performed. All but 4 patients fulfilled the FDA criteria for BCG unresponsive disease. Progression and recurrence-free survival (RFS)were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. We used FDA-defined criteria as complete response (CR) for single-arm trials of BCG-unresponsive patients.Results and Limitations: Twenty-six patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26), and pTa HG disease in 11.6% (3/26). Twelve of 26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 58.3% (95% confidence interval [CI] 41.1-82.1) at 1 year and 48.9% (95% CI 48.9) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. RFS was 41.9% (95% CI 25.9-67.8) at 1 year and 27.2% (95% CI 13.6-54.4) at 2 years. CR at 6, 12, and 18 months was observed in 16 (61.5%), 11 (44.0%), and 7 patients (30.4%), respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). Three patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study.Conclusions: EMDA-MMC BCG represents a viable option in patients with BCG unresponsive NMIBC with close to 50% progression-free survival at 2 years. However, these patients have a high risk of death from bladder cancer (15% in our cohort at 2 years) thus warranting extremely close surveillance. [ABSTRACT FROM AUTHOR]

Background: To identify predictors of survival in patients treated with docetaxel chemotherapy for castration-resistant prostate cancer (CRPC).Methods: We retrospectively analyzed clinical data from 186 patients who underwent docetaxel chemotherapy for CRPC from 2005 to 2016 at a single center. Pretreatment baseline variables including demographic and clinicopathological data were reviewed. Disease progression was defined by imaging and/or consecutive prostate-specific antigen (PSA) elevation. The systemic immune-inflammation index (SII), the modified Glasgow Prognostic Score (mGPS), and the neutrophil-lymphocyte ratio (NLR) were calculated. Univariable and multivariable Cox proportional hazards regression analyses reporting hazard ratios assessed the risk for disease progression and overall survival (OS). A survival nomogram was constructed.Results: Most patients (n = 139, 74.7%) completed at least 6 cycles of docetaxel chemotherapy. 156 patients (82.9%) experienced disease progression during the studied period. Only mGPS was independently associated with disease progression in a multivariable model (P < 0.01). During the studied period, 98 patients (52.1%) died. The built survival nomogram included statistically significant variables for OS in univariable analysis: hemoglobin, PSA, alkaline phosphatase (AP), lactate dehydrogenase, SII, neutrophil-lymphocyte ratio, mGPS, and site of metastases; and had a concordance index of 0.703. At decision curve analysis, the nomogram led to superior outcomes for any decision associated with a threshold probability of above 40%. In multivariable analysis, only AP (P = 0.02), hemoglobin and PSA (P < 0.01, respectively) remained associated with OS.Conclusions: PSA, AP, and hemoglobin are independent prognosticators for OS. Although mGPS is a promising marker for tumor progression and SII is a plausible prognostic marker for OS, valid integration of inflammatory indices into a prognostic model requires validation studies. Predictive and prognostic biomarkers are desperately needed to guide physicians in treatment counseling given the heterogeneous nature of CRPC and the plethora of effective therapies. [ABSTRACT FROM AUTHOR]

The article focuses on a study which examines the surgical and postoperative outcomes of consecutive patients treated with robot-assisted pyeloplasty (RAP) for ureteropelvic junction obstruction and absence of drain placement in a tertiary referral health center. Results show that RAP can be considered as a safe minimally invasive treatment approach for ureteropelvic junction obstruction.

The article offers information on the incretin effect (IE) and its role in regulating β cell functional response and insulin secretion dynamics. Topics include the impact of IE reduction in type 2 diabetes, a study using surgical removal of β cell mass as a model for diabetes development, and findings suggesting that preexisting defects in β cell response to incretins predict the risk of developing impairments in glucose tolerance after β cell mass reduction.

Objective: To determine the oncological impact of extended pelvic lymph node dissection (ePLND) vs standard PLND (sPLND) during radical cystectomy (RC) in clinically lymph node‐positive (cN+) bladder cancer (BCa). Patients and Methods: In this retrospective, multicentre study we included 969 patients who underwent RC with sPLND (internal/external iliac and obturator lymph nodes) or ePLND (sPLND plus common iliac and presacral nodes) with or without platin‐based peri‐operative chemotherapy for cTany N1‐3 M0 BCa between 1991 and 2022. We assessed the impact of ePLND on recurrence‐free survival (RFS) and the distribution of recurrences (locoregional and distant recurrences). The secondary endpoint was overall survival (OS). We performed propensity‐score matching using covariates associated with the extent of PLND in univariable logistic regression analysis. The association of the extent of PLND with RFS and OS was investigated using Cox regression models. Results: Of 969 cN+ patients, 510 were 1:1 matched on propensity scores. The median (interquartile range [IQR]) time to recurrence was 8 (4–16) months, and median (IQR) follow‐up of alive patients was 30 (13–51) months. Disease recurrence was observed in 104 patients in the ePLND and 107 in the sPLND group. Of these, 136 (27%), 47 (9.2%) and 19 patients (3.7%) experienced distant, locoregional, or both distant and locoregional disease recurrence, respectively. When stratified by the extent of PLND, we did not find a difference in recurrence patterns (P > 0.05). ePLND improved neither RFS (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.70–1.19; P = 0.5) nor OS (HR 0.78, 95% CI 0.60–1.01; P = 0.06) compared to sPLND. Stratification by induction chemotherapy did not change outcomes. Conclusion: Performing an ePLND at the time of RC in cN+ patients improved neither RFS nor OS compared to sPLND, regardless of induction chemotherapy status. Pretreatment risk stratification is paramount to identify ideal candidates for RC with ePLND as part of a multimodal treatment approach. [ABSTRACT FROM AUTHOR]

Simple Summary: This study provides a thorough review of robot-assisted partial nephrectomy (RAPN) in managing renal hilar masses. It focuses on the evaluation of RAPN's effectiveness and the exploration of varied surgical methods for these complex tumors. The research underscores the reliability of RAPN and emerging surgical techniques in addressing these challenges with a manageable risk of complications. The findings are poised to significantly contribute to the medical community's understanding and management of renal hilar masses, especially in terms of effectively balancing treatment efficacy and complication risks. Background: Robot-assisted partial nephrectomy (RAPN) is increasingly being employed in the management of renal cell carcinoma (RCC) and it is expanding in the field of complex renal tumors. The aim of this systematic review was to consolidate and assess the results of RAPN when dealing with entirely central hilar masses and to examine the various methods used to address the surgical difficulties associated with them. Methods: A thorough literature search in September 2023 across various databases focused on RAPN for renal hilar masses, adhering to PRISMA guidelines. The primary goal was to evaluate RAPN's surgical and functional outcomes, with a secondary aim of examining different surgical techniques. Out of 1250 records, 13 full-text manuscripts were reviewed. Results: Evidence is growing in favor of RAPN for renal hilar masses. Despite a predominance of retrospective studies and a lack of long-term data, RAPN shows positive surgical outcomes and preserves renal function without compromising cancer treatment effectiveness. Innovative suturing and clamping methods are emerging in surgical management. Conclusions: RAPN is a promising technique for managing renal hilar masses in RCC, offering effective surgical outcomes and renal function preservation. The study highlights the need for more long-term data and prospective studies to further validate these findings. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the associations among mannose, indexes of insulin resistance (IR) and secretion, and long-term cardiovascular outcomes. RESEARCH DESIGN AND METHODS: Fasting mannose was assayed in 1,403 participants, one-half of which had a first myocardial infarction (MI) with either normal glucose tolerance (n = 1,045) or newly detected dysglycemia (i.e., impaired glucose tolerance or type 2 diabetes; n = 358). Regression models were used to explore mannose associations with surrogate indexes of IR/insulin secretion. Multivariate Cox models were used to investigate the independent association between high (higher quartile) versus low (lower three quartiles) mannose and major adverse cardiac events (MACE) (n = 163) during the 10-year follow-up. RESULTS: Mannose was independently associated with IR indexes (all P ≤ 0.001). High versus low mannose was independently associated with MACE (hazard ratio 1.54, 95% CI 1.07–2.20) in the overall population. CONCLUSIONS: Mannose might represent a new biomarker able to track early, potentially detrimental glucometabolic alterations independently of glycemic state. [ABSTRACT FROM AUTHOR]

In this multicenter observational study, we evaluated different tumor diameters for identifying ≥ pT2 upper tract urothelial carcinoma at radical nephroureterectomy. In preoperative predictive models including 932 patients, the > 2-cm cutoff (odds ratio, 2.38; 95% confidence interval, 1.70-3.32; P < .001) was independently associated. This tumor size threshold could help to best select patients for kidney-sparing surgery. Introduction: The objective of this study was to evaluate the performance of different tumor diameters for identifying ≥ pT2 upper tract urothelial carcinoma (UTUC) at radical nephroureterectomy. Patients and Methods: This was a multi-institutional retrospective study that included 932 patients who underwent radical nephroureterectomy for nonmetastatic UTUC between 2000 and 2016. Tumor sizes were pathologically assessed and categorized into 4 groups: ≤ 1 cm, 1.1 to 2 cm, 2.1 to 3 cm, and > 3 cm. We performed logistic regression and decision-curve analyses. Results: Overall, 45 (4.8%) patients had a tumor size ≤ 1 cm, 141 (15.1%) between 1.1 and 2 cm, 247 (26.5%) between 2.1 and 3 cm, and 499 (53.5%) > 3 cm. In preoperative predictive models that were adjusted for the effects of standard clinicopathologic features, tumor diameters > 2 cm (odds ratio, 2.38; 95% confidence interval, 1.70-3.32; P < .001) and > 3 cm (odds ratio, 1.81; 95% confidence interval, 1.38-2.38; P < .001) were independently associated with ≥ pT2 pathologic staging. The addition of the > 2-cm diameter cutoff improved the area under the curve of the model from 58.8% to 63.0%. Decision-curve analyses demonstrated a clinical net benefit of 0.09 and a net reduction of 8 per 100 patients. Conclusion: The 2-cm cutoff appears to be most useful in identifying patients at risk of harboring ≥ pT2 UTUC. This confirms the current European Association of Urology guideline's risk stratification. Tumor size alone is not sufficient for optimal risk stratification, rather a constellation of features is needed to select the best candidate for kidney-sparing surgery. [ABSTRACT FROM AUTHOR]