Indocyanine green (ICG) fluorescence technology in pediatric robotic surgery.

This study aimed to report our experience in indocyanine green (ICG) fluorescence-guided surgery (FGS) in pediatric robotics. The data of 55 patients (35 boys and 20 girls), who underwent robotic surgery using ICG fluorescence in three institutions over the last 7 years, were retrospectively reviewed. The following robotic procedures were included: pyeloplasty (n = 21), complex Lich-Gregoir ureteral reimplantation (n = 8), varicocelectomy (n = 7), adnexal pathology resection (n = 8), partial nephrectomy (n = 4), nephrectomy (n = 4), renal cyst removal (n = 2), and excision of prostatic utricle (n = 1). The ICG was injected intravenously in all indications except for varicocele where intratesticular injection was done, and prostatic utricle or paraureteral diverticulum where trans-catheter injection was done. The ICG dosage was 0.2-0.3 mg/mL/kg. All the procedures were performed using da Vinci Xi platform. Firefly® allowed to switch form bright light to ICG-NIRF view and vice versa. All the procedures were accomplished in robotics without conversions to laparoscopy or open surgery. No episodes of allergy or anaphylaxis to ICG were recorded. An excellent ICG-NIRF view of target organs was obtained in all procedures. Based on our experience, we believe that application of ICG FGS in pediatric robotics enhances the identification of critical anatomical elements and pathological structures, thereby positively impacting both oncological and functional outcomes. This technique is safe, feasible, and versatile. We advocate the consideration of ICG as the standard of care in certain procedures such as partial nephrectomy, varicocele repair, tumor resection, and ovarian torsion. Nonetheless, further investigations are warranted to explore its potential broader applications in pediatric urology.

Urinary Tract Infection Predictors in Patients Undergoing Retrograde IntraRenal Surgery for Renal Stones: Does the Instrument Make the Difference?

Background: Retrograde intrarenal surgery (RIRS) using flexible ureterorenoscopes is a cornerstone approach for renal stone removal, yet it carries a significant risk of postoperative urinary tract infection (UTI). With the emergence of single-use ureterorenoscopes, there is growing interest in their potential to mitigate this risk. This study aimed to compare the postoperative infection rates between single-use and multi-use ureterorenoscopes in RIRS procedures and to identify predictors of postoperative UTI. Methods: Data were collected from 112 consecutive patients who underwent RIRS for renal stones between March 2022 and September 2023. Peri-operative variables including age, gender, body mass index (BMI), stone size, stone location, type of ureterorenoscope, Hounsfield Units (HU), pre-operative hydronephrosis, laboratory analysis, and operative time were evaluated. Univariate and multivariate logistic regression analyses were performed to assess the predictors of postoperative UTI. Results: Of the cohort, 77 surgeries (68.7%) utilized multi-use ureterorenoscopes, while 35 (31.3%) utilized single-use devices. Stone diameter, number of stones, type of ureterorenoscope, and operative time were significant predictors of postoperative UTI in the univariate analysis. Multivariable logistic regression showed that operative time (OR, 1.3; 95% CI, 0.55-0.99; p = 0.03) and type of ureterorenoscope (multi-use vs. single-use) (OR, 1.14; 95% CI, 1.08-1.2; p < 0.001) were independent predictors of postoperative UTI. Conclusions: In conclusion, this study highlights that multi-use ureterorenoscopes and prolonged operative time are associated with an increased risk of postoperative UTI in RIRS procedures. Careful pre-operative evaluation and meticulous patient selection are essential to minimize the occurrence of postoperative UTIs and optimize patient outcomes in RIRS for renal stones.

Trifecta Outcomes of Robot-Assisted Partial Nephrectomy Using the New Hugo™ RAS System Versus Laparoscopic Partial Nephrectomy.

(1) Background: Laparoscopic partial nephrectomy (LPN) is still performed in many referred urological institutions, representing a valid alternative to robot-assisted partial nephrectomy (RAPN). We aimed to compare trifecta outcomes of LPN and RAPN with the Hugo™ RAS System. (2) Methods: Between October 2022 and September 2023, eighty-nine patients underwent minimally invasive partial nephrectomy (group A, RAPN = 27; group B, Laparoscopic PN = 62) for localized renal tumors at our Institution. Continuous variables were presented as median and IQR and compared by means of the Mann-Whitney U test, while categorical variables were presented as frequencies (%) and compared by means of the χ2 test. (3) Results: Group A showed a higher rate of male patients (81.5% vs. 59.7%, p = 0.04) and a higher trend towards larger clinical tumor size (34 vs. 29 mm, p = 0.14). All the other baseline variables were comparable between the two groups (all p > 0.05). Regarding post-operative data, group A displayed a lower operative time (92 vs. 149.5 min, p = 0.005) and a shorter hospital stay (3 vs. 5, p = 0.002). A higher rate of malignant pathology was evidenced in group A (77.8% vs. 58.1%, p = 0.07) as well as a lower trend towards positive surgical margins (3.7% vs. 4.8%, p = 0.82), even if not statistically significant. (4) Conclusions: The rate of trifecta achievement was 92.6% and 82.3% for group A and B (p = 0.10), respectively. In terms of trifecta outcomes, RAPN using the Hugo™ RAS System showed comparable results to LPN performed by the same experienced surgeon.

Skill Transfer from Laparoscopic Partial Nephrectomy to the Hugo™ RAS System: A Novel Proficiency Score to Assess Surgical Quality during the Learning Curve.

Background/Objectives: The absence of validated tools to assess the skill transfer from laparoscopy to robotic surgery remains an unsolved issue in the context of robot-assisted partial nephrectomy (RAPN). We aimed to describe and validate a novel proficiency score to critically evaluate the surgical quality of RAPN with the Hugo™ RAS System (Medtronic, Minneapolis, MN, USA). Methods: Between October 2022 and September 2023, 27 consecutive patients underwent off-clamp RAPN for localized renal tumors at our institution. To analyze the learning curve (LC), the cohort was chronologically divided into two phases of 6 months each. Proficiency was defined as the achievement of trifecta while maintaining a comparable intraoperative time in the interquartile range of laparoscopic partial nephrectomy performed by the same surgeon. A logistic binary regression model was built to identify predictors of proficiency achievement. Results: A proficiency score was achieved in 14 patients (74.1%). At univariable analysis, number of consecutive procedures > 12 (OR 13.7; 95%CI 2.05-21.1, p = 0.007), pathological tumor size (OR 0.92; 95%CI 0.89-0.99, p = 0.04) and essential blood hypertension (OR 0.16; 95%CI 0.03-0.82, p = 0.02) were found to be predictors of proficiency score. At multivariable analysis, after adjusting for potential confounding factors, number of consecutive procedures > 12 (OR 8.1; 95%CI 1.44-14.6, p = 0.03) was the only independent predictor of proficiency score achievement. Conclusions: Our results showed that the skills of an experienced laparoscopic surgeon are transferrable to the novel Hugo™ RAS System in the context of nephron-sparing surgery. Improved surgical quality may be expected after completing the first 12 consecutive procedures.

Low-cost, versatile, and highly reproducible microfabrication pipeline to generate 3D-printed customised cell culture devices with complex designs.

Cell culture devices, such as microwells and microfluidic chips, are designed to increase the complexity of cell-based models while retaining control over culture conditions and have become indispensable platforms for biological systems modelling. From microtopography, microwells, plating devices, and microfluidic systems to larger constructs such as live imaging chamber slides, a wide variety of culture devices with different geometries have become indispensable in biology laboratories. However, while their application in biological projects is increasing exponentially, due to a combination of the techniques, equipment and tools required for their manufacture, and the expertise necessary, biological and biomedical labs tend more often to rely on already made devices. Indeed, commercially developed devices are available for a variety of applications but are often costly and, importantly, lack the potential for customisation by each individual lab. The last point is quite crucial, as often experiments in wet labs are adapted to whichever design is already available rather than designing and fabricating custom systems that perfectly fit the biological question. This combination of factors still restricts widespread application of microfabricated custom devices in most biological wet labs. Capitalising on recent advances in bioengineering and microfabrication aimed at solving these issues, and taking advantage of low-cost, high-resolution desktop resin 3D printers combined with PDMS soft lithography, we have developed an optimised a low-cost and highly reproducible microfabrication pipeline. This is thought specifically for biomedical and biological wet labs with not prior experience in the field, which will enable them to generate a wide variety of customisable devices for cell culture and tissue engineering in an easy, fast reproducible way for a fraction of the cost of conventional microfabrication or commercial alternatives. This protocol is designed specifically to be a resource for biological labs with limited expertise in those techniques and enables the manufacture of complex devices across the µm to cm scale. We provide a ready-to-go pipeline for the efficient treatment of resin-based 3D-printed constructs for PDMS curing, using a combination of polymerisation steps, washes, and surface treatments. Together with the extensive characterisation of the fabrication pipeline, we show the utilisation of this system to a variety of applications and use cases relevant to biological experiments, ranging from micro topographies for cell alignments to complex multipart hydrogel culturing systems. This methodology can be easily adopted by any wet lab, irrespective of prior expertise or resource availability and will enable the wide adoption of tailored microfabricated devices across many fields of biology.

Antiphospholipid syndrome pathogenesis in 2023: an update of new mechanisms or just a reconsideration of the old ones?

Antibodies against phospholipid (aPL)-binding proteins, in particular, beta 2 glycoprotein I (ß2GPI), are diagnostic/classification and pathogenic antibodies in antiphospholipid syndrome (APS). ß2GPI-aPL recognize their target on endothelium and trigger a pro-thrombotic phenotype which is amplified by circulating monocytes, platelets and neutrophils. Complement activation is required as supported by the lack of aPL-mediated effects in animal models when the complement cascade is blocked. The final result is a localized clot. A strong generalized inflammatory response is associated with catastrophic APS, the clinical variant characterized by systemic thrombotic microangiopathy. A two-hit hypothesis was suggested to explain why persistent aPL are associated with acute events only when a second hit allows antibody/complement binding by modulating ß2GPI tissue presentation. ß2GPI/ß2GPI-aPL are also responsible for obstetric APS, being the molecule physiologically present in placental/decidual tissues. Additional mechanisms mediated by aPL with different characteristics have been reported, but their diagnostic/prognostic value is still a matter of research.

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.

Laparoscopic versus Ultrasound-Guided Transversus Abdominis Plane Block for Postoperative Analgesia Management after Radical Prostatectomy: Results from a Single Center Study.

(1) Background: Regional anesthesia, achieved through nerve blocks, has gained widespread acceptance as an effective pain management approach. This research aimed to evaluate the efficacy of laparoscopic (LAP) transversus abdominis plane (TAP) block in patients undergoing laparoscopic radical prostatectomy. (2) Methods: From January 2023 to July 2023, 60 consecutive patients undergoing minimally invasive radical prostatectomy were selected. Patients were split into two groups receiving ultrasound-guided (US) or laparoscopic-guided TAP block. The primary outcome was a pain score expressed by a 0-10 visual analog scale (VAS) during the first 72 h after surgery. (3) Results: Both LAP-TAP and US-TAP block groups were associated with lower pain scores postoperatively. No statistically significant differences were observed between the two groups in surgery time, blood loss, time to ambulation, length of stay, and pain after surgery (all p > 0.2). In the LAP-TAP block group, the overall operating room time was significantly shorter than in the US-TAP block group (140 vs. 152 min, p = 0.04). (4) Conclusions: The laparoscopic approach, compared to the US-TAP block, was equally safe and not inferior in reducing analgesic drug use postoperatively. Moreover, the intraoperative LAP-TAP block seems to be a time-sparing procedure that could be recommended when patient-controlled analgesia cannot be delivered.

Robotic Medtronic Hugo™ RAS System Is Now Reality: Introduction to a New Simulation Platform for Training Residents.

The use of robotic surgery (RS) in urology has grown exponentially in the last decade, but RS training has lagged behind. The launch of new robotic platforms has paved the way for the creation of innovative robotics training systems. The aim of our study is to test the new training system from Hugo™ RAS System-Medtronic. Between July 2020 and September 2022, a total of 44 residents from urology, gynaecology and general surgery at our institution participated in advanced robotic simulation training using the Hugo™ RAS simulator. Information about sex, age, year of residency, hours spent playing video games, laparoscopic or robotic exposure and interest in robotics (90.9% declared an interest in robotics) was collected. The training program involved three robotic exercises, and the residents performed these exercises under the guidance of a robotics tutor. The residents' performance was assessed based on five parameters: timing, range of motion, panoramic view, conflict of instruments and exercise completion. Their performance was evaluated according to an objective Hugo system form and a subjective assessment by the tutor. After completing the training, the residents completed a Likert scale questionnaire to gauge their overall satisfaction. The rate of the residents' improvement in almost all parameters of the three exercises between the first and the last attempts was statistically significant (p < 0.02), indicating significant progress in the residents' robotic surgical skills during the training. The mean overall satisfaction score ± standard deviation (SD) was 9.4 ± 1.2, signifying a high level of satisfaction among the residents with the training program. In conclusion, these findings suggest that the training program utilizing the Hugo™ RAS System is effective in enhancing robotic surgical skills among residents and holds promise for the development of standardized robotics training programs in various surgical specialties.

Robot-Assisted Renal Surgery with the New Hugo Ras System: Trocar Placement and Docking Settings.

The current literature relating to the novel HugoTM RAS System lacks consistent data concerning the bedside features of robot-assisted partial nephrectomy (RAPN). To describe the trocar placement and docking settings for RAPN with a three-arm configuration to streamline the procedure with HugoTM RAS, between October 2022 and April 2023, twenty-five consecutive off-clamp RAPNs for renal tumors with the HugoTM RAS System were performed. We conceived a trouble-free three-arm setting to ease and standardize RAPN trocar placement and docking settings with HugoTM RAS. Perioperative data were collected. Post-operative complications were reported according to the Clavien-Dindo classification. The eGFR was calculated according to the CKD-EPI formula. Continuous variables were presented as the median and IQR, while frequencies were reported as categorical variables. Off-clamp RAPNs were successfully performed in all cases without the need for conversion or additional port placement. The median age and BMI were 69 years (IQR, 60-73) and 27.3 kg/m2 (IQR, 25.7-28.1), respectively. The median tumor size and R.E.N.A.L. score were 32.5 mm (IQR, 26-43.7) and 6 (IQR, 5-7), respectively. Two patients were affected by cT2 renal tumors. The median docking and console time were 5 (IQR, 5-6) and 90 min (IQR, 68-135.75 min), respectively, with slightly progressive improvements in the docking time achieved. No intraoperative complications occurred alongside clashes between instruments or with the bed assistant. In experienced hands, this simplified three-instrument configuration of the HugoTM RAS System for off-clamp RAPN resulted in feasible and safe practice, providing patient-tailored trocar placement and docking with non-inferior peri-perioperative outcomes to other robotic platforms.

Predictors of mid-term functional outcomes for robot-assisted Madigan simple prostatectomy: results of a multicentric series according to the BPH-6 achievement.

BACKGROUND: BPH-6 achievement remains an objective far to be evaluated for every technique currently available for the surgical management of bladder outlet obstruction (BOO) with the goal of preserving ejaculatory function. The aim of this study was to evaluate predictors of BPH-6 achievement of urethral-sparing robot assisted simple prostatectomy (us-RASP) on a large series performed at two tertiary-care centers. METHODS: Two institutional us-RASP datasets were merged, considering eligible all patients with a follow-up >12 months. Baseline, perioperative and functional data according to BPH-6 endpoint were assessed. Descriptive analysis was used. Frequencies and proportions were reported for categorical variables while medians and interquartile ranges (IQRs) were reported for continuously coded variables. A logistic regression model was built to identify predictors of BPH-6 achievement. For all statistical analyses, a two-sided P<0.05 was considered significant. RESULTS: Study cohort consisted of 94 eligible patients. The median follow-up was 40.7 months (IQR 31.3-54.2). Overall BPH-6 achievement was 54.7%. Compared to baseline, reduction of ≥30% in IPSS was observed in 93.6% of patients, reduction of <6 points for SHIM in 95.7% and response to MSHQ-EjD question 3 indicating emission of semen in 72.6%, respectively. On multivariable analysis, prostate volume between 110-180 mL (OR 0.09; 95% CI 0.01-0.92; P=0.043) and higher preoperative SHIM score (OR 1.18; 95% CI 1.05-1.32; P<0.01) were independent predictors of BPH-6 metric achievement. CONCLUSIONS: us-RASP may provide a complete resolution of BOO and preservation of ejaculatory function in sexually active men with a prostate volume ranging 110-180 mL.

Robotic Surgery in Urology: History from PROBOT® to HUGOTM.

The advent of robotic surgical systems had a significant impact on every surgical area, especially urology, gynecology, and general and cardiac surgery. The aim of this article is to delineate robotic surgery, particularly focusing on its historical background, its evolution, its present status, and its future perspectives. A comprehensive literature review was conducted upon PubMed/MEDLINE, using the keywords "robotic surgical system", "robotic surgical device", "robotics AND urology". Additionally, the retrieved articles' reference lists were investigated. Analysis concentrated on urological surgical systems for laparoscopic surgery that have been given regulatory approval for use on humans. From the late 1980s, before daVinci® Era in 2000s, ancestor platform as Probot® and PUMA 560 were described to outline historical perspective. Thus, new robotic competitors of Intuitive Surgical such as Senhance®, Revo-I®, Versius®, Avatera®, Hinotori®, and HugoTM RAS were illustrated. Although daVinci® had high level competitiveness, and for many years represented the most plausible option for robotic procedures, several modern platforms are emerging in the surgical market. Growing competition through unique features of the new robotic technologies might extend applications fields, improve diffusion, and increase cost-effectiveness procedures. More experiences are needed to identify the role of these new advancements in surgical branches and in healthcare systems.

State of the Art in Robotic Surgery with Hugo RAS System: Feasibility, Safety and Clinical Applications.

Since its introduction in the early 2000s, robotic surgery has represented a significative innovation within a minimally invasive surgery approach. A variety of robotic platforms have been made available throughout the years, and the outcomes related to those platforms have been described in the literature for many types of surgeries. Medtronic's HugoTM RAS system is one of the newest robotic generations launched, but because of its recent placing on the field, comprehensive clinical data are still lacking. The aim of the present state of the art is to address the current literature concerning the use of the HugoTM RAS robot in order to report its feasibility, safety and clinical applications in different surgical branches. Two reviewers independently conducted a search on the "PubMed" electronic database, using the keywords "Hugo" and "Hugo RAS". After the initial screening of 35 results, a total of 15 articles concerning the Hugo RAS system were selected for the review, including both oncological and benign surgery. Patients' demographic and baseline data were compared including, when available, docking system times, complications and oncological outcomes in the fields of urologic, gynecologic and general surgery. With reference to urological procedures, a total of 156 robot-assisted radical prostatectomies, 10 robot-assisted partial nephrectomies, and 5 robot-assisted adrenalectomies were performed, involving a total of 171 patients. The surgical branch in which the Hugo system found its major application was urology, which was followed by gynecology and general surgery. The Hugo RAS system by Medtronic represents an innovative and safe surgical platform, with excellent perspective for the future and different clinical applications in many surgical branches. More studies are needed to validate the safety and results from this new robotic platform.

Predictors of Urinary Continence Recovery after Laparoscopic-Assisted Radical Prostatectomy: Is Surgical Urethral Length the Only Key Factor?

Several efforts in recent years have been made to predict urinary continence (UC) recovery after radical prostatectomy. The aim of our study was to investigate the impact of surgical urethral length preservation (SULP) on urinary continence after LARP (laparoscopic-assisted radical prostatectomy). We retrospectively queried our datasets from May 2021 to May 2022. After the application of exclusion criteria, a total of 100 patients who underwent LARP for prostate cancer at our institution were enrolled. Through a sterile ruler inserted by a 12 mm trocar, the length of the membranous urethra spared during LARP was assessed intra-operatively. The baseline and peri- and postoperative data of patients were collected, and UC was defined as 0 or 1 on a safety pad. The median SULP was 20.5 mm (IQR, 14.5-25), and the median intraoperative EBL were 150 mL (IQR, 100-200). The Kaplan-Meier curve showed a significant difference at 20 mm, which was used as the cut-off value for SULP (log-rank test, p < 0.001). Multivariate Cox proportional hazards models showed that SULP and EBL < 250 mL were associated with UC recovery (all p < 0.02). Surgical urethral length preservation seemed to improve early UC recovery after LARP. Further multicentric studies are needed to confirm our findings.

Single-Setting 3D MRI/US-Guided Frozen Sectioning and Cryoablation of the Index Lesion: Mid-Term Oncologic and Functional Outcomes from a Pilot Study.

Our study explored frozen section reliability in prostate cancer (PCa) diagnoses and described surgical steps of a 3D magnetic resonance imaging (MRI)-ultrasound (US)-guided prostate biopsy (PB) and focal cryoablation of the index lesion (IL) in a single-setting procedure. Patients with a suspicious prostatic specific antigen (PSA) value, with a PIRADS 4 or 5 single lesion, were enrolled for trans perineal 3D MRI-US-guided PB and TRUS-guided focal cryoablation. Three cores were taken from the IL, three cores from the surrounding area, while systematic sampling was performed for the rest of the gland. After confirmation of PCa in frozen sections, focal cryoablation was performed. The 1st-year follow-up schedule included a PSA test at a 3-month interval, MRI 3 months and 1 year postoperatively and PB of the treated area at 1 year. Following the follow-up schedule, an involved PSA test at a 3-month interval and yearly MRI were performed. The PCa diagnosis was histologically confirmed in all three patients with frozen sections. At final histology, a single Gleason score upgrade from 6 (3 + 3) to 7 (3 + 4) was observed. All patients were discharged on postoperative day 1. At the 3-month evaluation, mean PSA values decreased from 12.54 (baseline) to 1.73 ng/mL and MRI images showed complete ablation of the IL in all patients. Urinary continence and potency were preserved in all patients. At the 1-year follow-up, one patient had suspicious ipsilateral recurrence on MRI and underwent a new analogous procedure. Post follow-up was uneventful and PSA remained stable in all patients. Three-dimensional MRI-US-guided frozen sectioning and focal cryoablation of the IL is a step forward towards a "patient-tailored" minimally invasive approach to the diagnosis and cure of PCa.

Video Consensus and Radical Prostatectomy: The Way to Chase the Future?

In the age of information, new platforms are consulted by patients to acquire consciousness about medical treatments. The aim of this study was to assess the level of understanding and feasibility of video consensus (VC) administration in patients scheduled for radical prostatectomy (RP), comparing it with standard informed consensus (SIC). According to the European Association of Urology Patient Information, we set up a video content for RP that was translated in Italian and implemented with information about possible perioperative and postoperative complications, days of hospitalization etc. From 2021 to 2022, all patients undergoing RP at our institution were prospectively included in this study. Patients received an SIC and after that, a VC about RP. After two consensuses were administered, patients received a preformed Likert 10 scale and STAI questionnaires. On the RP dataset, 276 patients were selected and 552 questionnaires for both SIC and VC were evaluated. Out of these, the median age was 62 years (IQR 60-65). Patients reported a higher overall satisfaction for VC (8.8/10) compared to the traditional informed consent (6.9/10). Therefore, VC may play a role in the future of surgery, improving the consciousness and satisfaction of patients and reducing preoperative anxiety.

Impact of Robotic Technologies on Prostate Cancer Patients' Choice for Radical Treatment.

Prostate cancer (PCa) surgery has a strong impact on men's social and sexual lives. For this reason, many patients ask for robotic surgery. To assess the rate of lost patients due to the lack of a robotic platform (RPl) at our center, we retrospectively selected 577 patients who underwent prostate biopsy between 2020 and 2021 who were eligible for radical prostatectomy (RP) (ISUP ≥ 2; age ≤ 70 yr). Patients eligible for surgery who decided to be operated received a phone call interview asking the reason for their choice. Overall, 230 patients (31.7%) underwent laparoscopic-assisted radical prostatectomy (LaRP) at our center, while 494 patients (68.3%) were not treated in our hospital. Finally, 347 patients were included: 87 patients (25.1%) underwent radiotherapy; 59 patients (17%) were already under another urologist's care; 113 patients (32.5%) underwent robotic surgery elsewhere; and 88 patients (25.4%) followed the suggestion of friends or relatives based on their surgical experience. Despite no surgical technique for RP having shown superiority in terms of oncological or functional outcomes, patients eligible for PCa treatment decided to be operated on elsewhere because of the lack of an RPl. Our results show how the presence of an RPl may increase the case volume of RP by 49% at our center.

Generation of an MTM1-mutant iPSC line (CRICKi008-A) from an individual with X-linked myotubular myopathy (XLMTM).

Centronuclear myopathies (CNMs) are a group of inherited rare muscle disorders characterised by the abnormal position of the nucleus in the center of the muscle fiber. One of CNM is the X-Linked Myotubular Myopathy, caused by mutations in the myotubularin (MTM1) gene (XLMTM), characterised by profound muscle hypotonia and weakness, severe bulbar and respiratory involvement. Here, we generated an induced pluripotent stem cell (iPSC) line from a patient with a severe form of XLMTM. Dermal fibroblasts were reprogrammed to pluripotency using a non-integrating mRNA-based protocol. This new MTM1-mutant iPSC line could facilitate disease-modelling and therapy development studies for XLMTM.

3D human induced pluripotent stem cell-derived bioengineered skeletal muscles for tissue, disease and therapy modeling.

Skeletal muscle is a complex tissue composed of multinucleated myofibers responsible for force generation that are supported by multiple cell types. Many severe and lethal disorders affect skeletal muscle; therefore, engineering models to reproduce such cellular complexity and function are instrumental for investigating muscle pathophysiology and developing therapies. Here, we detail the modular 3D bioengineering of multilineage skeletal muscles from human induced pluripotent stem cells, which are first differentiated into myogenic, neural and vascular progenitor cells and then combined within 3D hydrogels under tension to generate an aligned myofiber scaffold containing vascular networks and motor neurons. 3D bioengineered muscles recapitulate morphological and functional features of human skeletal muscle, including establishment of a pool of cells expressing muscle stem cell markers. Importantly, bioengineered muscles provide a high-fidelity platform to study muscle pathology, such as emergence of dysmorphic nuclei in muscular dystrophies caused by mutant lamins. The protocol is easy to follow for operators with cell culture experience and takes between 9 and 30 d, depending on the number of cell lineages in the construct. We also provide examples of applications of this advanced platform for testing gene and cell therapies in vitro, as well as for in vivo studies, providing proof of principle of its potential as a tool to develop next-generation neuromuscular or musculoskeletal therapies.