Predicting contralateral extraprostatic extension in unilateral high-risk prostate cancer: a multicentric external validation study.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients. METHODS: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes. RESULTS: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision. CONCLUSION: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.

Incidental Prostate Cancer in Patients Treated for Benign Prostatic Hyperplasia: Analysis from a Contemporary National Dataset.

(1) Background: Prostate Cancer (PCa) may be incidentally diagnosed during the microscopic evaluation of resected tissue from BPH surgeries, characterizing the clinical condition known as incidental PCa (iPCa). This study aims to assess the prevalence of iPCa following BPH surgery to evaluate the associated surgical procedures and to scrutinize preoperative and postoperative management. (2) Methods: A retrospective analysis was conducted using the PearlDiver™ Mariner database, containing patient records compiled between 2011 and 2021. International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify the population and outcomes. Our primary objective was to assess the prevalence of iPCa, categorized by the type of procedures, and to evaluate the subsequent treatment strategies. The secondary aim was to assess the impact of prostate biopsy (PB) and prostate MRI on iPCa detection. (3) Results: The overall cohort, accounting for 231,626 patients who underwent BPH surgery, exhibited a 2.2% prevalence rate of iPCa. The highest rate was observed for TURP (2.32%), while the lowest was recorded for RASP (1.18%). Preoperative MRI and PB demonstrated opposing trends over the years. Of the 5090 patients identified with iPCa, nearly 68% did not receive active treatment. The most common treatments were RT and ADT; 34.6% underwent RT, 31.75% received ADT, and 21.75% were treated with RT+ADT. RP was administered to approximately 9% of patients undergoing endoscopic procedures. Multivariate logistic regression analysis revealed age and openSP as additional risk factors for iPCa. Conversely, PB and MRI before surgery were linked to a decreased risk. (4) Conclusions: The contemporary prevalence of iPCa after BPH surgery is <3%. The increase in the use of prostate MRI mirrors a decline in the PB biopsy prior to BPH surgery but without resulting in an increased detection rate of iPCa. In contemporary routine clinical practice, iPCa is mostly managed in a different way when compared to biopsy-detected PCa.

The prognostic role of histomorphological subtyping in nonmetastatic papillary renal cell carcinoma after curative surgery: is subtype really irrelevant? A propensity score matching analysis of a multi-institutional real life data.

BACKGROUND AND AIM: The role of histomorphological subtyping is an issue of debate in papillary renal cell carcinoma (papRCC). This multi-institutional study investigated the prognostic role of histomorphological subtyping in patients undergoing curative surgery for nonmetastatic papRCC. PATIENTS AND METHODS: A total of 1,086 patients undergoing curative surgery were included from a retrospectively collected multi-institutional nonmetastatic papRCC database. The patients were divided into 2 groups based on histomorphological subtyping (type 1, n = 669 and type 2, n = 417). Furthermore, a propensity score-matching (PSM) cohort in 1:1 ratio (n = 317 for each subtype) was created to reduce the effect of potential confounding variables. The primary outcome of the study, the predictive role of histomorphological subtyping on the prognosis (recurrence free survival [RFS], cancer specific survival [CSS] and overall survival [OS]) in nonmetastatic papRCC after curative surgery, was investigated in both overall and PSM cohorts. RESULTS: In overall cohort, type 2 group were older (66 vs. 63 years, P = 0.015) and more frequently underwent radical nephrectomy (37.4% vs. 25.6%, P < 0.001) and lymphadenectomy (22.3% vs. 15.1%, P = 0.003). Tumor size (4.5 vs. 3.8 cm, P < 0.001) was greater, and nuclear grade (P < 0.001), pT stage (P < 0.001), pN stage (P < 0.001), VENUSS score (P < 0.001) and VENUSS high risk (P < 0.001) were significantly higher in type 2 group. 5-year RFS (89.6% vs. 74.2%, P < 0.001), CSS (93.9% vs. 84.2%, P < 0.001) and OS (88.5% vs. 78.5%, P < 0.001) were significantly lower in type 2 group. On multivariable analyses, type 2 was a significant predictor for RFS (HR:1.86 [95%CI:1.33-2.61], P < 0.001) and CSS (HR:1.91 [95%CI:1.20-3.04], P = 0.006), but not for OS (HR:1.27 [95%CI:0.92-1.76], P = 0.150). In PSM cohort balanced with age, gender, symptoms at diagnosis, pT and pN stages, tumor grade, surgical margin status, sarcomatoid features, rhabdoid features, and presence of necrosis, type 2 increased recurrence risk (HR:1.75 [95%CI: 1.16-2.65]; P = 0.008), but not cancer specific mortality (HR: 1.57 [95%CI: 0.91-2.68]; P = 0.102) and overall mortality (HR: 1.01 [95%CI: 0.68-1.48]; P = 0.981) CONCLUSIONS: This multiinstitutional study suggested that type 2 was associated with adverse histopathologic outcomes, and predictor of RFS and CSS after surgical treatment of nonmetastatic papRCC, in overall cohort. In propensity score-matching cohort, type 2 remained the predictor of RFS. Eventhough 5th WHO classification for renal tumors eliminated histomorphological subtyping, these findings suggest that subtyping is relevant from the point of prognostic view.

Simulation and Training in Robot-Assisted Urological Surgery: From Model to Patient.

(1) Background: Simulation-based training has revolutionized surgical education, providing a solution to the changing demands of surgical training and performance. The increasing demand for standardized training in robotic surgery has accelerated the adoption of simulation-based training as a necessary component of modern surgical education. This study examines the existing literature on training approaches employed in robot-assisted urological surgery; (2) Methods: The authors conducted a standardized search of online databases. Upon collecting the articles, the authors assessed their relevance and content before proceeding with the drafting of the text; (3) Results: The use of simulators is supported by convincing evidence that shows an advantage in the acquisition of robotic skills. Urological societies have created detailed training programs for robotic surgery that guide beginners through the entire process of skill acquisition; (4) Conclusions: The future landscape for robotic urology training is likely to involve organized, obligatory, and centralized training, which may be overseen by urologic associations.

Learning curve for intracorporeal robotic Padua ileal bladder: 10-year functional assessment from a high-volume single-centre series.

OBJECTIVES: To assess the impact of the learning curve (LC) on perioperative and long-term functional outcomes of a consecutive single-centre series of robot-assisted radical cystectomy with Padua intracorporeal orthotopic neobladder. PATIENTS AND METHODS: Patients treated between 2013 and 2022 were included, with ≥1 year of follow-up. The entire cohort was divided in tertiles. Categorical and continuous variables were compared. Joinpoint regression analysis was used to identify significant changes over the decade in linear slope of the 1-year day- and night-time continence. Uni- and multivariable Cox regression analyses identified predictors of day- and night-time continence recovery. Day-time continence was defined as 'totally dry' (no pads), night-time continence as pad wetness ≤50 mL (one safety pad). RESULTS: Overall, 200 patients were included. The mean hospital stay (P = 0.002) and 30-day complications (P = 0.04) significantly reduced over time; the LC significantly impacted on Trifecta achievement (P < 0.001). The 1-year day- and night-time continence probabilities displayed a significant improving trend (day-time continence annual average percentage change [AAPC] 11.45%, P < 0.001; night-time continence AAPC 10.05%, P = 0.009). The LC was an independent predictor of day- (hazard ratio [HR] 1.008; P < 0.001) and night-time continence (HR 1.004; P = 0.03) over time. CONCLUSION: Patients at the beginning of the LC had significantly longer hospitalisations, more postoperative complications, and lower Trifecta rates. At the 10-year analyses, we observed a significant improving trend for both the 1-year day- and night-time continence probabilities, highlighting the crucial role of the LC. However, we are unable to assess the case volume needed to achieve a plateau in terms of day- and night-time continence rates.

Tissue-Based Genomic Testing in Prostate Cancer: 10-Year Analysis of National Trends on the Use of Prolaris, Decipher, ProMark, and Oncotype DX.

BACKGROUND: Prostate cancer (PCa) management is moving towards patient-tailored strategies. Advances in molecular and genetic profiling of tumor tissues, integrated with clinical risk assessments, provide deeper insights into disease aggressiveness. This study aims to offer a comprehensive overview of the pivotal genomic tests supporting PCa treatment decisions, analyzing-through real-world data-trends in their use and the growth of supporting literature evidence. METHODS: A retrospective analysis was conducted using the extensive PearlDiver™ Mariner database, which contains de-identified patient records, in compliance with the Health Insurance Portability and Accountability Act (HIPAA). The International Classification of Diseases (ICD) and Current Procedural Terminology (CPT) codes were employed to identify patients diagnosed with PCa during the study period-2011 to 2021. We determined the utilization of primary tissue-based genetic tests (Oncocyte DX®, Prolaris®, Decipher®, and ProMark®) across all patients diagnosed with PCa. Subsequently, within the overall PCa cohort, patients who underwent radical prostatectomy (RP) and received genetic testing postoperatively were identified. The yearly distribution of these tests and the corresponding trends were illustrated with graphs. RESULTS: During the study period, 1,561,203 patients with a PCa diagnosis were recorded. Of these, 20,748 underwent tissue-based genetic testing following diagnosis, representing 1.3% of the total cohort. An increasing trend was observed in the use of all genetic tests. Linear regression analysis showed a statistically significant increase over time in the use of individual tests (all p-values < 0.05). Among the patients who underwent RP, 3076 received genetic analysis following surgery, representing 1.27% of this group. CONCLUSIONS: Our analysis indicates a growing trend in the utilization of tissue-based genomic testing for PCa. Nevertheless, they are utilized in less than 2% of PCa patients, whether at initial diagnosis or after surgical treatment. Although it is anticipated that their use may increase as more scientific evidence becomes available, their role requires further elucidation.

Transperineal or Transrectal Magnetic Resonance Imaging-targeted Biopsy for Prostate Cancer Detection.

BACKGROUND AND OBJECTIVE: A notable paradigm shift has emerged in the choice of prostate biopsy approach, with a transition from transrectal biopsy (TRBx) to transperineal biopsy (TPBx) driven by the lower risk of severe urinary tract infections. The impact of this change on detection of clinically significant prostate cancer (csPCa) remains a subject of debate. Our aim was to compare the csPCa detection rate of TRBx and TPBx. METHODS: Patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for clinically localized PCa at 15 European referral centers from 2016 to 2023 were included. A propensity score matching (PSM) analysis was performed to minimize selection biases. Logistic regression models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). KEY FINDINGS AND LIMITATIONS: Of 3949 patients who met the study criteria, 2187 underwent TRBx and 1762 underwent TPBx. PSM resulted in 1301 matched pairs for analysis. Patient demographics and tumor characteristics were comparable in the matched cohorts. TPBx versus TRBx was associated with greater detection of csPCa, whether defined as International Society of Urological Pathology grade group ≥2 (51% vs 45%; OR 1.37, 95% CI 1.15-1.63; p = 0.001) or grade group ≥3 (29% vs 23%; OR 1.38, 95% CI 1.13-1.67; p = 0.001). Similar results were found when considering MRI-targeted biopsy alone and after stratifying patients according to tumor location, Prostate Imaging-Reporting and Data System score, and clinical features. Limitations include the retrospective nature of the study and the absence of centralized MRI review. CONCLUSIONS: Our findings bolster existing understanding of the additional advantages offered by TPBx. Further randomized trials to fully validate these findings are awaited. PATIENT SUMMARY: We compared the rate of detection of clinically significant prostate cancer with magnetic resonance imaging (MRI)-guided biopsies in which the sample needle is passed through the perineum or the rectum. Our results suggest that the perineal approach is associated with better detection of aggressive prostate cancer.

Does Overgrading on Targeted Biopsy of Magnetic Resonance Imaging-visible Lesions in Prostate Cancer Lead to Overtreatment?

BACKGROUND AND OBJECTIVE: Targeted biopsy of the index prostate cancer (PCa) lesion on multiparametric magnetic resonance imaging (MRI) is effective in reducing the risk of overdiagnosis of indolent PCa. However, it remains to be determined whether MRI-targeted biopsy can lead to a stage shift via overgrading of the index lesion by focusing only on the highest-grade component, and to a subsequent risk of overtreatment. Our aim was to assess whether overgrading on MRI-targeted biopsy may lead to overtreatment, using radical prostatectomy (RP) specimens as the reference standard. METHODS: Patients with clinically localized PCa who had positive MRI findings (Prostate Imaging-Reporting and Data System [PI-RADS] score ≥3) and Gleason grade group (GG) ≥2 disease detected on MRI-targeted biopsy were retrospectively identified from a prospectively maintained database that records all RP procedures from eight referral centers. Biopsy grade was defined as the highest grade detected. Downgrading was defined as lower GG for the RP specimen than for MRI-targeted biopsy. Overtreatment was defined as downgrading to RP GG 1 for cases with GG ≥2 on biopsy, or to RP low-burden GG 2 for cases with GG ≥3 on biopsy. KEY FINDINGS AND LIMITATIONS: We included 1020 consecutive biopsy-naïve patients with GG ≥2 PCa on MRI-targeted biopsy in the study. Pathological analysis of RP specimens showed downgrading in 178 patients (17%). The transperineal biopsy route was significantly associated with a lower risk of downgrading (odds ratio 0.364, 95% confidence interval 0.142-0.814; p = 0.022). Among 555 patients with GG 2 on targeted biopsy, only 18 (3.2%) were downgraded to GG 1 on RP. Among 465 patients with GG ≥3 on targeted biopsy, three (0.6%) were downgraded to GG 1 and seven were downgraded to low-burden GG 2 on RP. The overall risk of overtreatment due to targeted biopsy was 2.7% (28/1020). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our multicenter study revealed no strong evidence that targeted biopsy results could lead to a high risk of overtreatment. PATIENT SUMMARY: In the diagnosis pathway for prostate cancer, results for targeted biopsies guided by magnetic resonance imaging (MRI) scans lead to a negligible proportion of overtreatment.

Robot-assisted Radical Cystectomy with Totally Intracorporeal Urinary Diversion Versus Open Radical Cystectomy: 3-Year Outcomes from a Randomised Controlled Trial.

BACKGROUND AND OBJECTIVE: Randomised controlled trials (RCTs) comparing open radical cystectomy (ORC) and robot-assisted RC (RARC) have involved an extracorporeal approach for urinary diversion (UD), undermining the potential benefits of a totally robotic procedure. Our objective was to compare 3-yr outcomes from a RCT comparing ORC to RARC with totally intracorporeal UD (iUD). METHODS: Patients with cT2-4 N0 M0 or bacillus Calmette-Guérin-failed high-grade non-muscle-invasive urothelial carcinoma who were candidates for RC without absolute contraindications to robotic surgery were included. A covariate adaptive randomisation process based on body mass index, American Society of Anesthesiologists score, preoperative haemoglobin, type of UD, neoadjuvant chemotherapy, and cT stage was used. The primary endpoint was to investigate the superiority of RARC with iUD in terms of a 50% reduction in transfusion rate. Secondary outcomes included adherence to an early recovery after surgery protocol, perioperative and postoperative outcomes, readmission and complication rates, a cost analysis, and functional, oncological, and health-related quality-of-life outcomes. KEY FINDINGS AND LIMITATIONS: Overall, 116 patients were enrolled. The primary endpoint was confirmed, as the overall perioperative transfusion rate was significantly lower in the RARC cohort, with an absolute risk reduction of 19% (95% confidence interval 2-36%; p = 0.046). No differences in perioperative and postoperative complications and 3-yr oncological outcomes were observed between the groups. Despite the superiority of ORC on quantitative analysis of night-time pad use, there were no differences in the probabilities of recovery of daytime and night-time continence. Body image was significantly better in the RARC cohort. Cost analysis confirmed that RARC is a more expensive surgical procedure. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our findings support RARC with iUD as a safe surgical option; the transfusion rate was reduced by 50% and the complication rates and 3-yr oncological outcomes were comparable to those with ORC. The minimally invasive nature of RARC was reflected in better body image perception in this cohort. The probabilities of daytime and night-time continence recovery were comparable between the groups. Higher costs remain a drawback of robotic surgery. PATIENT SUMMARY: This RCT demonstrated a 50% transfusions rate's reduction compared to ORC. We confirmed safety and feasibility of RARC with i-UD providing comparable peri- and postoperative complication rates, as well as, 3yr oncologic outcomes to those of ORC. Patients receiving either RARC-iUD or ORC had comparable probabilities of urinary continence recovery after surgery.

In-label, off-label prescription, efficacy and tolerability of dalbavancin: report from a National Registry.

PURPOSE: Although dalbavancin is currently approved for the treatment of ABSSIs, several studies suggest its efficacy and tolerance as long-term therapy for other off-label indications requiring prolonged intravenous antibiotic administration. METHODS: We conducted a prospective nationwide study of dalbavancin use in real-life settings for both approved and off-label indications analysing for each case the clinical and microbiological characteristics of infection the efficacy and safety of treatments. RESULTS: During the study period (from December 2018 to July 2021), the ID specialists from 14 different centres enrolled 223 patients treated with dalbavancin [141 males (63%) and 82 females (37%); male/female ratio 1.72; mean age 59 (SD 17.2) years, (range 15-96). Most patients in the study population (136/223; 61.0%) came from community rather than health care facilities and most of them were visited in Infectious Diseases wards (93/223; 41.7%) and clinics (55/223; 24.7%) even though some patients were cured in other settings, such as surgery wards (18/223; 8.1%), orthopaedic wards (11/223; 4.9%), Emergency Rooms (7/223; 3.1%) and non-surgical other than ID wards (6/223; 2.7%). The most common ID diagnoses were osteomyelitis (44 cases/223; 19.7%; of which 29 acute and 15 chronic osteomyelitis), cellulitis (28/223; 12.5%), cutaneous abscess (23/223; 10.3%), orthopaedic prosthesis-associated infection (22/223; 9.9%), surgical site infection (20/223; 9.0%) and septic arthritis (15/223; 6.7%). CONCLUSION: In conclusion, by virtue of its PK/PD properties, dalbavancin represents a valuable option to daily in-hospital intravenous or outpatient antimicrobial regimens also for off-label indications requiring a long-term treatment of Gram-positive infections.

The Impact of Physical Activity on the Outcomes of Active Surveillance in Prostate Cancer Patients: A Scoping Review.

INTRODUCTION: Active surveillance has emerged as a valid therapeutic option in patients with low-risk prostate cancer, allowing for the deferral of definitive treatment until the time of possible disease progression. Although it is known that physical activity plays a protective role in the onset and progression of this tumor, its impact on patients with low-risk disease who are managed with active surveillance remains unclear. Our scoping review aims to summarize the existing evidence on this subject. EVIDENCE ACQUISITION: On 9 April 2023, a systematic search was conducted using the PubMed and Scopus databases. The search employed the combination of the following terms: ("prostate cancer" OR "prostate tumor") AND ("active surveillance") AND ("physical activity" OR "physical exercise" OR "physical intensive activity" OR "intensive exercise") AND ("lifestyle"). Out of the 506 identified articles, 9 were used for the present scoping review, and their results were reported according to the PRISMA-ScR statement. EVIDENCE SYNTHESIS: We discovered a lack of uniformity in the assessment of PA and its stratification by intensity. There was no consensus regarding what constitutes cancer progression in patients choosing expectant management. In terms of the impact of PA on AS outcomes, conflicting results were reported: some authors found no correlation, while others (six of total studies included) revealed that active men experience smaller increases in PSA levels compared to their sedentary counterparts. Additionally, higher levels of exercise were associated with a significantly reduced risk of PCa reclassification. CONCLUSION: Due to the heterogeneity of the methodologies used in the available studies and the conflicting results reported, it is not possible to draw definitive conclusions concerning the role physical activity may play in the risk of prostate cancer progression in men managed with active surveillance.

Adrenalectomy for Metastasis: The Impact of Primary Histology on Survival Outcome.

Adrenalectomy is commonly considered a curative treatment in case of adrenal gland as site of metastasis. In the present study, we evaluated the impact of primary tumor histology on survival outcomes after a minimally invasive adrenal mastectomy for a solitary metachronous metastasis. From May 2004 to August 2020, we prospectively collected data on minimally invasive adrenalectomies whose pathological examination showed a metastasis. All patients only received metastasectomies that were performed with curative intent, or to achieve non-evidence of disease status. Adjuvant systemic therapy was not administered in any case. Cancer-specific survival (CSS) was assessed using the Kaplan-Meier method. Univariable and multivariable Cox regression analyses were applied to identify independent predictors of CSS. Out of 235 laparoscopic and robotic adrenalectomies, the pathologic report showed metastases in 60 cases. The primary histologies included 36 (60%) renal cell carcinoma (RCC), 9 (15%) lung cancer, 6 (10%) colon cancer, 4 (6.7%) sarcoma, 3 (5%) melanoma and 2 (3.3%) bladder cancer. RCC displayed significantly longer survival rates with a 5-year CSS of 55.9%, versus 22.8% for other histologies (log-rank p = 0.01). At univariable analysis, disease-free interval (defined as the time from adrenalectomy to evidence of disease progression) < 12 months and histology were predictors of CSS (p = 0.003 and p < 0.001, respectively). At multivariable Cox analysis, the only independent predictor of CSS was primary tumor histology (p = 0.005); patients with adrenal metastasis from colon cancer and bladder cancer showed a 5.3- and 75.5-fold increased risk of cancer death, respectively, compared to patients who had RCC as primary tumor histology. Oncological outcomes of adrenal metastasectomies are strongly influenced by primary tumor histology. A proper discussion of the role of surgery in a multidisciplinary context could provide optimal treatment strategies.

Impacts of Neoadjuvant Chemotherapy on Perioperative Outcomes in Patients with Bladder Cancer Treated with Radical Cystectomy: A Single High-Volume Center Experience.

(1) Background: Less than 30% of patients with muscle-invasive bladder cancer (MIBC) receive neoadjuvant chemotherapy (NAC), and reasons for underuse remain unclear. One potential explanation is the concern for the increased risk of perioperative morbidity and mortality. The aim of this study is to investigate the impact of NAC on the risk of detrimental perioperative outcomes in patients with MIBC treated with radical cystectomy (RC). (2) Methods: We identified patients receiving RC for MIBC (T2-4a N0 M0) from 2016 to 2022. Moreover, 1:1 propensity score matching (PSM) was applied between RC alone versus RC plus NAC, and our analysis tested the association between NAC status and peri-operative outcomes. (3) Results: Among the 317 patients treated with RC for identified MIBC, 98 (31%) received NAC. Patients treated with NAC were younger (median yr. 64 vs. 71; p < 0.001), with a lower Charlson Comorbidity Index (3 vs. 4; p > 0.001), and received more frequently continent urinary diversion (61 vs. 32%, p < 0.001). About 43% of patients in each group were treated with robot-assisted radical cystectomy (RARC) with totally intracorporeal urinary diversion (ICUD). After PSM, no differences were detected for the outcomes considered. (4) Conclusions: NAC is not associated with a higher rate of perioperative complications, including patients who received RARC with ICUD.

Nutraceuticals and phytoceuticals in the treatment of schizophrenia: a systematic review and network meta-analysis.

Background: Sub-optimal response in schizophrenia is frequent, warranting augmentation strategies over treatment-as-usual (TAU). Methods: We assessed nutraceuticals/phytoceutical augmentation strategies via network meta-analysis. Randomized controlled trials in schizophrenia/schizoaffective disorder were identified via the following databases: PubMed, MEDLINE, EMBASE, Scopus, PsycINFO, CENTRAL, and ClinicalTrials.gov. Change (Standardized Mean Difference=SMD) in total symptomatology and acceptability (Risk Ratio=RR) were co-primary outcomes. Secondary outcomes were positive, negative, cognitive, and depressive symptom changes, general psychopathology, tolerability, and response rates. We conducted subset analyses by disease phase and sensitivity analyses by risk of bias and assessed global/local inconsistency, publication bias, risk of bias, and confidence in the evidence. Results: The systematic review included 49 records documenting 50 studies (n=2,384) documenting 22 interventions. Citicoline (SMD=-1.05,95%CI=-1.85; -.24), L-lysine (SMD=-1.04,95%CI=-1.84;-.25), N-acetylcysteine (SMD=-.87,95%CI=-1.27;-.47) and sarcosine (SMD=-.5,95%CI=-.87-.13) outperformed placebo for total symptomatology. High heterogeneity (tau2=.10, I2=55.9%) and global inconsistency (Q=40.79, df=18, p=.002) emerged without publication bias (Egger's test, p=.42). Sarcosine improved negative symptoms (SMD=-.65, 95%CI=-1.10; -.19). N-acetylcysteine improved negative symptoms (SMD=-.90, 95%CI=-1.42; -.39)/general psychopathology (SMD=-.76, 95%CI=-1.39; -.13). No compound improved total symptomatology within acute phase studies (k=7, n=422). Sarcosine (SMD=-1.26,95%CI=-1.91; -.60), citicoline (SMD=-1.05,95%CI=-1.65;-.44), and N-acetylcysteine (SMD=-.55,95%CI=-.92,-.19) outperformed placebo augmentation in clinically stable participants. Sensitivity analyses removing high-risk-of-bias studies confirmed overall findings in all phases and clinically stable samples. In contrast, the acute phase analysis restricted to low risk-of-bias studies showed a superior effect vs. placebo for N-acetylcysteine (SMD=-1.10,95%CI=-1.75,-.45), L-lysine (SMD=-1.05,95%CI=-1.55,-.19), omega-3 fatty acids (SMD=-.83,95%CI=-1.31,-.34) and withania somnifera (SMD=-.71,95%CI=-1.21,-.22). Citicoline (SMD=-1.05,95%CI=-1.86,-.23), L-lysine (SMD=-1.04,95%CI=-1.84,-.24), N-acetylcysteine (SMD=-.89,95%CI=-1.35,-.43) and sarcosine (SMD=-.61,95%CI=-1.02,-.21) outperformed placebo augmentation of TAU ("any phase"). Drop-out due to any cause or adverse events did not differ between nutraceutical/phytoceutical vs. placebo+TAU. Conclusions: Sarcosine, citicoline, and N-acetylcysteine are promising augmentation interventions in stable patients with schizophrenia, yet the quality of evidence is low to very low. Further high-quality trials in acute phases/specific outcomes/difficult-to-treat schizophrenia are warranted.

The Added Value of Side-specific Systematic Biopsy in Patients Diagnosed by Magnetic Resonance Imaging-targeted Prostate Biopsy.

BACKGROUND: Systematic biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted biopsy is still recommended considering the risk of missing clinically significant prostate cancer (csPCa). OBJECTIVE: To evaluate the added value in csPCa detection on side-specific SB relative to MRI lesion and to externally validate the Noujeim risk stratification model that predicts the risk of csPCa on distant SB cores relative to the index MRI lesion. DESIGN, SETTING, AND PARTICIPANTS: Overall, 4841 consecutive patients diagnosed by MRI-targeted biopsy and SB for Prostate Imaging Reporting and Data System score ≥3 lesions were identified from a prospectively maintained database between January 2016 and April 2023 at 15 European referral centers. A total of 2387 patients met the inclusion criteria and were included in the analysis. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: McNemar's test was used to compare the csPCa detection rate between several biopsy strategies including MRI-targeted biopsy, side-specific SB, and a combination of both. Model performance was evaluated in terms of discrimination using area under the receiver operation characteristic curve (AUC), calibration plots, and decision curve analysis. Clinically significant prostate cancer was defined as International Society of Urological Pathology grade group ≥2. RESULTS AND LIMITATIONS: Overall, the csPCa detection rate was 49%. Considering MRI-targeted biopsy as reference, the added values in terms of csPCa detection were 5.8% (relative increase of 13%), 4.2% (relative increase of 9.8%), and 2.8% (relative increase of 6.1%) for SB, ipsilateral SB, and contralateral SB, respectively. Only 35 patients (1.5%) exclusively had csPCa on contralateral SB (p < 0.001). Considering patients with csPCa on MRI-targeted biopsy and ipsilateral SB, the upgrading rate was 2% (20/961) using contralateral SB (p < 0.001). The Noujeim model exhibited modest performance (AUC of 0.63) when tested using our validation set. CONCLUSIONS: The added value of contralateral SB was negligible in terms of cancer detection and upgrading rates. The Noujeim model could be included in the decision-making process regarding the appropriate prostate biopsy strategy. PATIENT SUMMARY: In the present study, we collected a set of patients who underwent magnetic resonance imaging (MRI)-targeted and systematic biopsies for the detection of prostate cancer. We found that biopsies taken at the opposite side of the MRI suspicious lesion have a negligible impact on cancer detection. We also validate a risk stratification model that predicts the risk of cancer on biopsies beyond 10 mm from the initial lesion, which could be used in daily practice to improve the personalization of the prostate biopsy.

MRI for risk stratification of muscle invasion by upper tract urothelial carcinoma: a feasibility study.

BACKGROUND: Magnetic resonance imaging (MRI) is recommended in patients with upper tract urothelial carcinoma (UTUC) only when computed tomography (CT) is contraindicated. However, CT does not allow distinguishing ureter wall layers, making impossible to assess muscle invasion, a factor contributing to differentiate high- from low-risk UTUCs, which require different therapeutic approaches. We investigated the feasibility of MRI assessment of UTUC muscle invasion. METHODS: From June 2022 to March 2023, we prospectively enrolled patients suspected of UTUC, i.e., with positive urinary tract ultrasound and/or ureteroscopy, or positive urinary cytology and/or hematuria but negative cystoscopy and bladder ultrasound at two Italian centers. They underwent CT followed by MRI (≤ 24 h apart), independently reported by two experienced radiologists, blinded from histopathology results. After imaging confirmation, they all underwent nephroureterectomy and histopathology analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic curve (AUC) were calculated. RESULTS: Thirty-nine lesions were detected in 30 patients on both CT and MRI. Muscle-invasive UTUC prevalence was 81% (21/26) among patients with MRI suspicion and 8% (1/13) among those without MRI suspicion (p < 0.001). Considering the assessment of muscle-layer invasion, the more experienced reader achieved 95% sensitivity (95% confidence interval 82-100), 71% specificity (47-88), 81% PPV (63-93), 92% NPV (70-100), 85% accuracy (67-96), and 0.84 AUC (0.70-0.98). Inter-reader agreement was substantial (κ = 0.73). CONCLUSIONS: MRI showed a promising diagnostic performance for the assessment of UTUC risk of muscle invasion. RELEVANCE STATEMENT: Resulting feasible both in technical and clinical terms, MRI could be helpful for upper tract urothelial carcinomas pre-operative risk stratification, to allow a personalized patients' management. These results play in favor of promoting preoperative MRI for UTUC, as already proven for bladder cancer. KEY POINTS: • Muscle invasion is a crucial information for tailored treatments of upper tract urothelial carcinomas. • CT does not distinguish ureter wall layers, making muscle invasion risk assessment not feasible. • MRI was shown to reliably diagnose muscle-layer invasion by upper tract urothelial carcinomas (sensitivity 95%, specificity 71%).

Insomnia and related mental health conditions: Essential neurobiological underpinnings towards reduced polypharmacy utilization rates.

Insomnia represents a significant public health burden, with a 10% prevalence in the general population. Reduced sleep affects social and working functioning, productivity, and patient's quality of life, leading to a total of $100 billion per year in direct and indirect healthcare costs. Primary insomnia is unrelated to any other mental or medical illness; secondary insomnia co-occurs with other underlying medical, iatrogenic, or mental conditions. Epidemiological studies found a 40-50% comorbidity prevalence between insomnia and psychiatric disorders, suggesting a high relevance of mental health in insomniacs. Sleep disturbances also worsen the outcomes of several psychiatric disorders, leading to more severe psychopathology and incomplete remission, plausibly contributing to treatment-resistant conditions. Insomnia and psychiatric disorder coexistence can lead to polypharmacy, namely, the concurrent use of two or more medications in the same patient, regardless of their purpose or rationale. Polypharmacy increases the risk of using unnecessary drugs, the likelihood of drug interactions and adverse events, and reduces the patient's compliance due to regimen complexity. The workup of insomnia must consider the patient's sleep habits and inquire about any medical and mental concurrent conditions that must be handled to allow insomnia to be remitted adequately. Monotherapy or limited polypharmacy should be preferred, especially in case of multiple comorbidities, promoting multipurpose molecules with sedative properties and with bedtime administration. Also, non-pharmacological interventions for insomnia, such as sleep hygiene, relaxation training and Cognitive Behavioral Therapy may be useful in secondary insomnia to confront behaviors and thoughts contributing to insomnia and help optimizing the pharmacotherapy. However, insomnia therapy should always be patient-tailored, considering drug indications, contraindications, and pharmacokinetics, besides insomnia phenotype, clinical picture, patient preferences, and side effect profile.

Development and internal validation of a nomogram predicting 3-year chronic kidney disease upstaging following robot-assisted partial nephrectomy.

PURPOSE: Aim of the present study was to develop and validate a nomogram to accurately predict the risk of chronic kidney disease (CKD) upstaging at 3 years in patients undergoing robot-assisted partial nephrectomy (RAPN). METHODS: A multi-institutional database was queried to identify patients treated with RAPN for localized renal tumor (cT1-cT2, cN0, cM0). Significant CKD upstaging (sCKD-upstaging) was defined as development of newly onset CKD stage 3a, 3b, and 4/5. Model accuracy was calculated according to Harrell C-index. Subsequently, internal validation using bootstrapping and calibration was performed. Then nomogram was depicted to graphically calculate the 3-year sCKD-upstaging risk. Finally, regression tree analysis identified potential cut-offs in nomogram-derived probability. Based on this cut-off, four risk classes were derived with Kaplan-Meier analysis tested this classification. RESULTS: Overall, 965 patients were identified. At Kaplan-Meier analysis, 3-year sCKD-upstaging rate was 21.4%. The model included baseline (estimated glomerular filtration rate) eGFR, solitary kidney status, multiple lesions, R.E.N.A.L. nephrometry score, clamping technique, and postoperative acute kidney injury (AKI). The model accurately predicted 3-year sCKD-upstaging (C-index 84%). Based on identified nomogram cut-offs (7 vs 16 vs 26%), a statistically significant increase in sCKD-upstaging rates between low vs intermediate favorable vs intermediate unfavorable vs high-risk patients (1.3 vs 9.2 vs 22 vs 54.2%, respectively, p < 0.001) was observed. CONCLUSION: Herein we introduce a novel nomogram that can accurately predict the risk of sCKD-upstaging at 3 years. Based on this nomogram, it is possible to identify four risk categories. If externally validated, this nomogram may represent a useful tool to improve patient counseling and management.

Statins may increase the risk of being diagnosed with prostate cancer.

BACKGROUND: Although statins are known to protect against cardiovascular accidents, their anti-inflammatory features could play a role in preventing tumorigenesis. We investigated the association between statin intake and prostate cancer (PCa) diagnosis and aggressiveness. METHODS: A retrospective analysis was performed. Our dataset on patients undergone systematic prostate biopsy from December 2008 to December 2022 was searched for histopathologic and clinical data. Prognostic Grade Group ≥3 tumors were defined as high-grade (HG). The association between Metabolic Syndrome (MetS), statin use and PCa diagnosis and HG disease was assessed using logistic regression analyses. RESULTS: Data on 1685 patients were collected; MetS affected 344 (20.4%) men and 138 (36.5%) were taking statins at least for 6 months at the time of biopsy. Among the 671 (39.8%) men diagnosed with PCa, 327 (48.7%) presented with a HG disease. Tumor incidence was higher among men taking statins, compared to controls (46.8% vs. 37.8%; P=0.002); also, high grade diseases were more common in the former group, but the difference did not reach statistical significance (49.1% vs. 48.6%; P=0.89). Statin intake (OR 1.44; 95% CI [1.05-1.98]; P=0.02) independently predicted PCa diagnosis but not high-grade disease (P=0.8). CONCLUSIONS: Statin use may be associated with an increased risk of PCa diagnosis.