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1.
Cell Mol Life Sci ; 81(1): 132, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38472446

ABSTRACT

P2Y11 is a G protein-coupled ATP receptor that activates IL-1 receptor (IL-1R) in a cyclic AMP dependent manner. In human macrophages, P2Y11/IL-1R crosstalk with CCL20 as a prime target is controlled by phosphodiesterase 4 (PDE4), which mediates breakdown of cyclic AMP. Here, we used gene expression analysis to identify activation of CXCR4 and CXCR7 as a hallmark of P2Y11 signaling. We found that PDE4 inhibition with rolipram boosts P2Y11/IL-1R-induced upregulation of CXCR7 expression and CCL20 production in an epidermal growth factor receptor dependent manner. Using an astrocytoma cell line, naturally expressing CXCR7 but lacking CXCR4, P2Y11/IL-1R activation effectively induced and CXCR7 agonist TC14012 enhanced CCL20 production even in the absence of PDE4 inhibition. Moreover, CXCR7 depletion by RNA interference suppressed CCL20 production. In macrophages, the simultaneous activation of P2Y11 and CXCR7 by their respective agonists was sufficient to induce CCL20 production with no need of PDE4 inhibition, as CXCR7 activation increased its own and eliminated CXCR4 expression. Finally, analysis of multiple CCL chemokines in the macrophage secretome revealed that CXCR4 inactivation and CXCR7 activation selectively enhanced P2Y11/IL-1R-mediated secretion of CCL20. Altogether, our data establish CXCR7 as an integral component of the P2Y11/IL-1R-initiated signaling cascade and CXCR4-associated PDE4 as a regulatory checkpoint.


Subject(s)
Receptors, CXCR4 , Signal Transduction , Humans , Cell Line , Chemokine CXCL12/genetics , Chemokine CXCL12/metabolism , Chemokine CXCL12/pharmacology , Cyclic AMP/metabolism , Macrophages/metabolism , Receptors, CXCR4/genetics , Receptors, Purinergic/metabolism
2.
Int J Mol Sci ; 24(3)2023 Jan 19.
Article in English | MEDLINE | ID: mdl-36768312

ABSTRACT

Mitochondrial diseases (MDs) are inherited genetic conditions characterized by pathogenic mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA). Current therapies are still far from being fully effective and from covering the broad spectrum of mutations in mtDNA. For example, unlike heteroplasmic conditions, MDs caused by homoplasmic mtDNA mutations do not yet benefit from advances in molecular approaches. An attractive method of providing dysfunctional cells and/or tissues with healthy mitochondria is mitochondrial transplantation. In this review, we discuss what is known about intercellular transfer of mitochondria and the methods used to transfer mitochondria both in vitro and in vivo, and we provide an outlook on future therapeutic applications. Overall, the transfer of healthy mitochondria containing wild-type mtDNA copies could induce a heteroplasmic shift even when homoplasmic mtDNA variants are present, with the aim of attenuating or preventing the progression of pathological clinical phenotypes. In summary, mitochondrial transplantation is a challenging but potentially ground-breaking option for the treatment of various mitochondrial pathologies, although several questions remain to be addressed before its application in mitochondrial medicine.


Subject(s)
Mitochondria , Mitochondrial Diseases , Humans , Mitochondria/genetics , Mitochondria/pathology , DNA, Mitochondrial/genetics , Mitochondrial Diseases/genetics , Mitochondrial Diseases/therapy , Mitochondrial Diseases/pathology , Mutation , Phenotype
3.
BJU Int ; 130(4): 528-535, 2022 10.
Article in English | MEDLINE | ID: mdl-37382230

ABSTRACT

OBJECTIVE: To determine whether proficiency-based progression (PBP) training leads to better robotic surgical performance compared to traditional training (TT), given that the value of PBP training for learning robotic surgical skills is unclear. MATERIALS AND METHODS: The PROVESA trial is a multicentric, prospective, randomized and blinded clinical study comparing PBP training with TT for robotic suturing and knot-tying anastomosis skills. A total of 36 robotic surgery-naïve junior residents were recruited from 16 training sites and 12 residency training programmes. Participants were randomly allocated to metric-based PBP training or the current standard of care TT, and compared at the end of training. The primary outcome was percentage of participants reaching the predefined proficiency benchmark. Secondary outcomes were the numbers of procedure steps and errors made. RESULTS: Of the group that received TT, 3/18 reached the proficiency benchmark versus 12/18 of the PBP group (i.e. the PBP group were ~10 times as likely to demonstrate proficiency [P = 0.006]). The PBP group demonstrated a 51% reduction in number of performance errors from baseline to the final assessment (18.3 vs 8.9). The TT group demonstrated a marginal improvement (15.94 vs 15.44) in errors made. CONCLUSIONS: The PROVESA trial is the first prospective randomized controlled trial on basic skills training in robotic surgery. Implementation of a PBP training methodology resulted in superior surgical performance for robotic suturing and knot-tying anastomosis performance. Compared to TT, better surgical quality could be obtained by implementing PBP training for basic skills in robotic surgery.


Subject(s)
Robotic Surgical Procedures , Robotics , Humans , Prospective Studies , Anastomosis, Surgical , Benchmarking
4.
J Surg Res ; 277: 224-234, 2022 09.
Article in English | MEDLINE | ID: mdl-35504150

ABSTRACT

INTRODUCTION: The introduction of robot-assisted surgical devices requires the application of objective performance metrics to verify performance levels. OBJECTIVE: To develop and validate (face, content, response process, and construct) the performance metrics for a robotic dissection task using a chicken model. METHODS: In a procedure characterization, we developed the performance metrics (i.e., procedure steps, errors, and critical errors) for a robotic dissection task, using a chicken model. In a modified Delphi panel, 14 experts from four European Union countries agreed on the steps, errors, and critical errors (CEs) of the task. Six experienced surgeons and eight novice urology surgeons performed the robotic dissection task twice on the chicken model. In the Delphi meeting, 100% consensus was reached on five procedure steps, 15 errors and two CEs. Novice surgeons took 20 min to complete the task on trial 1 and 14 min during trial two, whereas experts took 8.2 min and 6.5 min. On average, the Expert Group completed the task 56% faster than the Novice Group and made 46% fewer performance errors. RESULTS: Sensitivity and specificity for procedure errors and time were excellent to good (i.e., 1.0-0.91) but poor (i.e., 0.5) for step metrics. The mean interrater reliability for the assessments by two robotic surgeons was 0.91 (Expert Group inter-rater reliability = 0.92 and Novice Group = 0.9). CONCLUSIONS: We report evidence which supports the demonstration of face, content, and construct validity for a standard and replicable basic robotic dissection task on the chicken model.


Subject(s)
Robotic Surgical Procedures , Robotics , Surgeons , Clinical Competence , Humans , Reproducibility of Results
5.
Ann Surg ; 274(2): 281-289, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33630473

ABSTRACT

OBJECTIVE: To analyze all published prospective, randomized, and blinded clinical studies on the proficiency-based progression (PBP) training using objective performance metrics. BACKGROUND: The benefit of PBP methodology to learning clinical skills in comparison to conventional training is not settled. METHODS: Search of PubMed, Cochrane library's Central, EMBASE, MEDLINE, and Scopus databases, from inception to 1st March 2020. Two independent reviewers extracted the data. The Medical Education Research Study Quality Instrument (MERSQI) was used to assess the methodological quality of included studies. Results were pooled using biased corrected standardized mean difference and ratio-of-means. Summary effects were evaluated using a series of fixed and random effects models. The primary outcome was the number of procedural errors performed comparing PBP and non-PBP-based training pathways. Secondary outcomes were the number of procedural steps completed and the time to complete the task/procedure. RESULTS: From the initial pool of 468 studies, 12 randomized clinical studies with a total of 239 participants were included in the analysis. In comparison to the non-PBP training, ratio-of-means results showed that PBP training reduced the number of performance errors by 60% (P < 0.001) and procedural time by 15% (P = 0.003) and increased the number of steps performed by 47% (P < 0.001). CONCLUSIONS AND RELEVANCE: Our systematic review and meta-analysis confirms that PBP training in comparison to conventional or quality assured training improved trainees' performances, by decreasing procedural errors and procedural time, while increasing the number of correct steps taken when compared to standard simulation-based training.


Subject(s)
Clinical Competence , Education, Medical/methods , General Surgery/education , Simulation Training/methods , Feedback , Humans
6.
World J Urol ; 39(9): 3465-3471, 2021 Sep.
Article in English | MEDLINE | ID: mdl-33538866

ABSTRACT

INTRODUCTION: Telementoring is one of the applications of telemedicine capable of bringing highly experienced surgeons to areas lacking expertise. In the current study, we aimed to assess a novel telementoring application during the learning curve of transurethral enucleation of the prostate using bipolar energy (TUEB). MATERIAL AND METHODS: A telementoring system was developed by our engineering department. This application was used to mentor ten prospective cases of TUEB performed by an expert endourologist (novice to the TUEB). A questionnaire was filled by the operating surgeon and the mentor to provide subjective evaluation of the telementoring system. Finally, the outcomes of these patients were compared to a control group consisting of ten consecutive patients performed by the mentor. RESULTS: Ten consecutive TUEB were performed using this telementoring application. Delayed and interrupted connection were experienced in two and one patients, respectively; however, their effect was minor, and they did not compromise the safety of the procedure. None of the patients required conversion to conventional transurethral resection of the prostate. Only one patient in our series experienced grade IIIb complication. CONCLUSION: The telementoring application for TUEB is promising. It is a simple and low-cost tool that could be a feasible option to ensure patients' safety during the initial phase of the learning curve without time and locations constraints for both the mentor and the trainee; However, it should be mentioned that telementoring cannot yet replace the traditional surgical training with the mentor and trainee being in the operative room. Further studies are required to confirm the current results.


Subject(s)
Education, Distance , Electrosurgery , Mentoring/methods , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/education , Aged , Aged, 80 and over , Feasibility Studies , Humans , Learning Curve , Male , Middle Aged , Pilot Projects , Prospective Studies
7.
Surg Endosc ; 35(8): 4285-4294, 2021 08.
Article in English | MEDLINE | ID: mdl-32857241

ABSTRACT

BACKGROUND: To improve patient safety, there is an imperative to develop objective performance metrics for basic surgical skills training in robotic surgery. OBJECTIVE: To develop and validate (face, content, and construct) the performance metrics for robotic suturing and knot tying, using a chicken anastomotic model. DESIGN, SETTING AND PARTICIPANTS: Study 1: In a procedure characterization, we developed the performance metrics (i.e., procedure steps, errors, and critical errors) for robotic suturing and knot tying, using a chicken anastomotic model. In a modified Delphi panel of 13 experts from four EU countries, we achieved 100% consensus on the five steps, 18 errors and four critical errors (CE) of the task. Study 2: Ten experienced surgeons and nine novice urology surgeons performed the robotic suturing and knot tying chicken anastomotic task. The mean inter-rater reliability for the assessments by two experienced robotic surgeons was 0.92 (95% CI, 0.9-0.95). Novices took 18.5 min to complete the task and experts took 8.2 min. (p = 0.00001) and made 74% more objectively assessed performance errors than the experts (p = 0.000343). CONCLUSIONS: We demonstrated face, content, and construct validity for a standard and replicable basic anastomotic robotic suturing and knot tying task on a chicken model. Validated, objective, and transparent performance metrics of a robotic surgical suturing and knot tying tasks are imperative for effective and quality assured surgical training.


Subject(s)
Chickens , Robotic Surgical Procedures , Animals , Clinical Competence , Humans , Reproducibility of Results , Suture Techniques
8.
BJU Int ; 125(6): E7-E14, 2020 06.
Article in English | MEDLINE | ID: mdl-32249538

ABSTRACT

OBJECTIVE: To discuss the impact of COVID-19 on global health, particularly on urological practice and to review some of the available recommendations reported in the literature. MATERIAL AND METHODS: In the current narrative review the PubMed database was searched to identify all the related reports discussing the impact of COVID-19 on the urological field. RESULTS: The COVID-19 pandemic is the latest and biggest global health threat. Medical and surgical priorities have changed dramatically to cope with the current challenge. These changes include postponements of all elective outpatient visits and surgical procedures to save facilities and resources for urgent cases and patients with COVID-19 patients. This review discuss some of the related changes in urology. CONCLUSIONS: Over the coming weeks, healthcare workers including urologists will be facing increasingly difficult challenges, and consequently, they should adopt triage strategy to avoid wasting of medical resources and they should endorse sufficient protection policies to guard against infection when dealing with COVID-19 patients.


Subject(s)
Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Urologic Surgical Procedures , Betacoronavirus/physiology , COVID-19 , Elective Surgical Procedures , Global Health , Humans , SARS-CoV-2 , Triage , Urinary Tract/microbiology
9.
Gynecol Endocrinol ; 34(8): 704-708, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29385860

ABSTRACT

MicroRNAs can be used as very efficient circulating biomarkers. The role of microRNAs in polycystic ovary syndrome (PCOS) and the effects of antiandrogen therapy on microRNA expression is still not fully understood. A panel of serum microRNAs were retrotranscribed via looped reverse primer transcription specific for each miRNA and quantified via probe specific RT-PCR in 16 Caucasian hyperandrogenic PCOS women selected according to the Rotterdam criteria and in a subset of seven patients after four months of sequential reverse antiandrogenic therapy. All women recruited underwent an oral glucose tolerance test (OGTT) and a baseline total cholesterol, high density lipoproteins cholesterol, triglycerides, AST and ALT dosage. In the follicular phase women were evaluated for total testosterone, Δ4-androstenedione, DHEAS, 17OHpg, FSH, LH, and 17-ß-E2. The AUC2hglucose, ISI Matsuda, oral disposition index (DIo) and visceral adipose index (VAI) were also calculated. We suggest that miR-155 might have a role as biomarker in hyperandrogenic PCOS patients to monitor the effect of antiandrogen therapy.


Subject(s)
MicroRNAs/blood , Polycystic Ovary Syndrome/blood , Androgen Antagonists/therapeutic use , Biomarkers/blood , Female , Humans , Polycystic Ovary Syndrome/drug therapy
10.
Clin Exp Nephrol ; 20(3): 433-42, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26453483

ABSTRACT

BACKGROUND: The beneficial effects of dietary restriction of proteins in chronic kidney disease are widely recognized; however, poor compliance to prescribed low-protein diets (LPD) may limit their effectiveness. To help patients to adhere to the dietary prescriptions, interventions as education programmes and dietary counselling are critical, but it is also important to develop simple and attractive approaches to the LPD, especially when dietitians are not available. Therefore, we elaborated a simplified and easy to manage dietary approach consisting of 6 tips (6-tip diet, 6-TD) which could replace the standard, non-individualized LPD in Nephrology Units where dietary counselling is not available; hence, our working hypothesis was to evaluate the effects of such diet vs a standard moderately protein-restricted diet on metabolic parameters and patients' adherence. METHODS: In this randomized trial, 57 CKD patients stage 3b-5 were randomly assigned (1:1) to receive the 6-TD (Group 6-TD) or a LPD containing 0.8 g/kg/day of proteins (Group LPD) for 6 months. The primary endpoint was to evaluate the effects of the two different diets on the main "metabolic" parameters and on patients' adherence (registration number NCT01865526). RESULTS: Both dietary regimens were associated with a progressive reduction in protein intake and urinary urea excretion compared to baseline, although the decrease was more pronounced in Group 6-TD. Effects on serum levels of urea nitrogen and urinary phosphate excretion were greater in Group 6-TD. Plasma levels of phosphate, bicarbonate and PTH, and urinary NaCl excretion remained stable in both groups throughout the study. 44 % of LPD patients were adherent to the dietary prescription vs 70 % of Group 6-TD. CONCLUSIONS: A simplified diet, consisting of 6 clear points easily managed by CKD patients, produced beneficial effects either on the metabolic profile of renal disease and on patients' adherence to the dietary plan, when compared to a standard LPD.


Subject(s)
Diet, Healthy , Diet, Protein-Restricted , Patient Compliance , Renal Insufficiency, Chronic/diet therapy , Adult , Aged , Biomarkers/blood , Biomarkers/urine , Blood Urea Nitrogen , Diet, Carbohydrate-Restricted , Diet, Sodium-Restricted , Feeding Behavior , Female , Fruit , Humans , Italy , Male , Middle Aged , Nutritional Status , Phosphates/blood , Phosphates/urine , Portion Size , Prospective Studies , Recommended Dietary Allowances , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/urine , Severity of Illness Index , Sodium/urine , Time Factors , Treatment Outcome , Urea/urine , Vegetables
12.
Transfus Med Rev ; 38(2): 150826, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38581862

ABSTRACT

Hemoglobin levels are commonly assessed to prevent causing or worsening of anemia in prospective blood donors. We compared head-to-head the accuracy of different technologies for measuring hemoglobin suitable for use in mobile donation units. We included 144 persons donating platelets at the Central Institute for Blood Transfusion and Immunology in Innsbruck, Austria. Hemoglobin levels were measured in venous blood using the portable hemoglobinometer HemoCue Hb-801 and noninvasively using OrSense NBM-200, and compared to values obtained with the Sysmex XN-430, an automated hematology analyzer employing the sodium lauryl sulphate method, which is broadly used as reference method in everyday clinical practice. Mean age of participants was 34.2 years (SD 13.0); 34.0% were female. Hemoglobin values measured with HemoCue were more strongly correlated with the Sysmex XN-430 (r = 0.90 [95% CI: 0.87-0.93]) than measured with OrSense (r = 0.49 [0.35-0.60]). On average, HemoCue overestimated hemoglobin by 0.40 g/dL (0.31-0.48) and OrSense by 0.75 g/dL (95% CI: 0.54-0.96). When using OrSense, we found evidence for higher overestimation at higher hemoglobin levels (proportional bias) specifically in females but not in males (Pdifference = .003). Sensitivity and specificity for classifying donors according to the hemoglobin donation thresholds were 99.2% (95% CI: 95.3%-100.0%) and 43.8% (23.1%-66.8%) for HemoCue vs 95.3% (89.9%-98.0%) and 12.5% (2.2%-37.3%) for OrSense. Areas under the receiver operating characteristic curves were higher using HemoCue vs OrSense both in females (0.933 vs 0.547; P = .044) and males (0.948 vs 0.628; P < .001). HemoCue Hb-801 measures hemoglobin more accurately than OrSense NBM-200 in the setting of mobile blood donation units. Our findings are particularly relevant for females, having in mind that anemia is more prevalent in females than in males.


Subject(s)
Blood Donors , Hemoglobins , Humans , Female , Blood Donors/statistics & numerical data , Male , Hemoglobins/analysis , Adult , Middle Aged , Hemoglobinometry/methods , Hemoglobinometry/instrumentation , Hemoglobinometry/standards , Anemia/blood , Anemia/diagnosis , Young Adult , Austria
13.
Eur Urol Open Sci ; 61: 18-28, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38384440

ABSTRACT

Background: Currently, the landscape of surgical training is undergoing rapid evolution, marked by the initial implementation of standardized surgical training programs, which are further facilitated by the emergence of new technologies. However, this proliferation is uneven across various countries and hospitals. Objective: To offer a comprehensive overview of the existing surgical training programs throughout Europe, with a specific focus on the accessibility of simulation resources and standardized surgical programs. Design setting and participants: A dedicated survey was designed and spread in May 2022 via the European Association of Urology (EAU) mail list, to Young Urologist Office (YUO), Junior membership, European Urology Residents Education Program participants between 2014 and 2022, and other urologists under 40 yr, and via the EAU Newsletter. Intervention: A 64-item, online-based survey in accordance with the Checklist for Reporting Results of Internet E-Surveys (CHERRIES) using the platform of Survey Monkey (Portland, OR, USA) was realized. Outcome measurements and statistical analysis: The study involved an assessment of the demographic characteristics. Additionally, it explored the type of center, availability of various surgical approaches, presence of training infrastructure, participation in courses, organization of training, and participants' satisfaction with the training program. The level of satisfaction was evaluated using a Likert-5 scale. The subsequent sections delved into surgical training within the realms of open, laparoscopic, robotic, and endoscopic surgery, each explored separately. Finally, the investigation encompassed the presence of a structured training course and the availability of a duly validated final evaluation process. Results and limitations: There were 375 responders with a completion rate of 82%. Among them, 75% were identified as male, 50.6% were young urologists, 31.7% were senior residents, and 17.6% were junior residents. A significant majority of participants (69.6%) were affiliated with academic centers. Regarding the presence of dry lab training facilities, only 50.3% of respondents indicated its availability. Among these centers, 46.7% were primarily focused on laparoscopy training. The availability of virtual and wet lab training centers was even more limited, with rates of 31.5% and 16.2%, respectively. Direct patient involvement was reported in 80.5% of cases for open surgery, 58.8% for laparoscopy, 25.0% for robotics, and 78.6% for endourology. It is worth noting that in <25% of instances, training followed a well-defined standardized program comprising both preclinical and clinical modular phases. Finally, the analysis of participant feedback showed that 49.7% of respondents expressed a satisfaction rating of either 4 or 5 points with respect to the training program. The limitations of our study include the low response rate, predominance of participants from academic centers, and absence of responses from individuals not affiliated with the EAU network. Conclusions: The current distribution of surgical training centers falls short of ensuring widespread access to standardized training programs. Although dry lab facilities are relatively well spread, the availability of wet lab resources remains restricted. Additionally, it appears that many trainees' initial exposure to surgery occurs directly with patients. There is a pressing need for continued endeavors to establish uniform training routes and assessment techniques across various surgical methodologies. Patient summary: Nowadays, the surgical training landscape is heterogeneous across different countries. The implementation of a standardized training methodology to enhance the overall quality of surgical training and thereby improving patient outcomes is needed.

14.
Ann Clin Transl Neurol ; 11(6): 1615-1629, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38750253

ABSTRACT

OBJECTIVE: COASY, the gene encoding the bifunctional enzyme CoA synthase, which catalyzes the last two reactions of cellular de novo coenzyme A (CoA) biosynthesis, has been linked to two exceedingly rare autosomal recessive disorders, such as COASY protein-associated neurodegeneration (CoPAN), a form of neurodegeneration with brain iron accumulation (NBIA), and pontocerebellar hypoplasia type 12 (PCH12). We aimed to expand the phenotypic spectrum and gain insights into the pathogenesis of COASY-related disorders. METHODS: Patients were identified through targeted or exome sequencing. To unravel the molecular mechanisms of disease, RNA sequencing, bioenergetic analysis, and quantification of critical proteins were performed on fibroblasts. RESULTS: We identified five new individuals harboring novel COASY variants. While one case exhibited classical CoPAN features, the others displayed atypical symptoms such as deafness, language and autism spectrum disorders, brain atrophy, and microcephaly. All patients experienced epilepsy, highlighting its potential frequency in COASY-related disorders. Fibroblast transcriptomic profiling unveiled dysregulated expression in genes associated with mitochondrial respiration, responses to oxidative stress, transmembrane transport, various cellular signaling pathways, and protein translation, modification, and trafficking. Bioenergetic analysis revealed impaired mitochondrial oxygen consumption in COASY fibroblasts. Despite comparable total CoA levels to control cells, the amounts of mitochondrial 4'-phosphopantetheinylated proteins were significantly reduced in COASY patients. INTERPRETATION: These results not only extend the clinical phenotype associated with COASY variants but also suggest a continuum between CoPAN and PCH12. The intricate interplay of altered cellular processes and signaling pathways provides valuable insights for further research into the pathogenesis of COASY-associated diseases.


Subject(s)
Phenotype , Transcriptome , Humans , Male , Female , Child , Child, Preschool , Epilepsy/genetics , Fibroblasts/metabolism , Adolescent , Autism Spectrum Disorder/genetics , Adult , Transferases
15.
Clin Endocrinol (Oxf) ; 79(6): 845-52, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23506485

ABSTRACT

OBJECTIVE: Currently available studies that fully analyse the metabolic parameters in patients with prolactinoma are scarce and discordant. The aim of this study was to evaluate the metabolic effects of cabergoline (CAB) treatment in patients with newly diagnosed prolactinoma in relation to disease control and CAB dosage. DESIGN: This is a retrospective clinical-based therapy analysis. PATIENTS: Forty-three patients with prolactinoma (eight men, 35 women), aged 33·65 ± 11·23 years, were evaluated metabolically at baseline and after 12 months of CAB treatment. MEASUREMENTS: Body mass index (BMI), systolic and diastolic blood pressure, waist circumference (WC), lipid profile, haemoglobinA1c (HbA1c), glucose and insulin levels (and their areas under the curve, AUC) after an oral glucose tolerance test, homoeostasis model assessment of insulin resistance (Homa-IR) index, insulin sensitivity index (ISI) Matsuda, oral disposition index (DIo) and visceral adiposity index (VAI) were measured at baseline and after 12 months of treatment. RESULTS: Twelve months of CAB reduced WC (P < 0·001), total (P = 0·001) and low-density lipoprotein \terol (P < 0·001), triglycerides (P = 0·024), fasting insulin (P < 0·001), AUCINSULIN (P < 0·001), HbA1c (P = 0·022), Homa-IR (P < 0·001) and VAI (P < 0·001), with a concomitant increase in high-density lipoprotein cholesterol (P < 0·001) and in ISI Matsuda (P < 0·001), regardless of the degree of reduction in prolactin levels. The patients receiving higher doses (>0·50 mg/week) of CAB showed lower BMI (P = 0·009), fasting insulin (P = 0·001), Homa-IR (P < 0·001) and VAI (P = 0·018) and higher ISI Matsuda (P = 0·002) and DIo (P = 0·011), compared with those on lower doses. CONCLUSIONS: A significant metabolic improvement was observed in patients with prolactinoma after 12 months of CAB treatment, especially when higher doses were used, highlighting the importance of considering the metabolic profile in these patients and the role of active treatment with high CAB doses.


Subject(s)
Dopamine Agonists/administration & dosage , Ergolines/administration & dosage , Pituitary Neoplasms/blood , Pituitary Neoplasms/drug therapy , Prolactin/blood , Prolactinoma/blood , Prolactinoma/drug therapy , Adiposity/drug effects , Adult , Blood Glucose/metabolism , Body Mass Index , Cabergoline , Dose-Response Relationship, Drug , Female , Humans , Insulin Resistance , Lipids/blood , Male , Metabolome/drug effects , Pituitary Neoplasms/pathology , Prolactinoma/pathology , Retrospective Studies , Waist Circumference/drug effects , Young Adult
16.
J Robot Surg ; 17(3): 1143-1150, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36380261

ABSTRACT

Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) for non-metastatic bladder cancer (BCa) are limited. The purpose of this study is to describe long-term oncologic outcomes of patients receiving robotic radical cystectomy at a high-volume European Institution. We analyzed data of 107 patients treated with RARC between 2003 and 2012 at a high-volume robotic center. Clinical, pathologic, and survival data at the latest follow-up were collected. Clinical recurrence (CR)-free survival, cancer-specific mortality (CSM)-free survival, and overall survival (OS) were plotted using Kaplan-Meier survival curves. Cox proportional hazard models investigated predictors of CR and CSM. Competing-risk regressions were utilized to depict cumulative incidences of death from BCa and death from other causes after RARC at long term. Pathologic nonorgan-confined BCa was found in 40% of patients, and 7 (7%) patients had positive soft tissue surgical margins. Median (interquartile range [IQR]) number of nodes removed was 11 (6, 14), and 26% of patients had pN + disease. Median (IQR) follow-up for survivors was 123 (117, 149) months. The 12-year CR-free, CSM-free and overall survival were 55% (95% confidence interval [CI] 44%, 65%), 62% (95% CI 50%, 72%), and 34% (95% CI 24%, 44%), respectively. Nodal involvement on final pathology was associated with poor prognosis on multivariable competing risk analysis. The cumulative incidence of non-cancer death exceeded that of death from BCa after approximately ten years after RARC. We provided relevant data on oncologic outcomes of RARC at a high-volume robotic center, with acceptable rates of clinical recurrence and cancer-specific survival at long-term. In patients treated with RARC, the cumulative incidence of death from causes other than BCa is non-negligible, and should be taken into consideration for post-operative follow-up.


Subject(s)
Robotic Surgical Procedures , Robotics , Urinary Bladder Neoplasms , Humans , Cystectomy/adverse effects , Robotic Surgical Procedures/methods , Follow-Up Studies , Urinary Bladder Neoplasms/pathology , Treatment Outcome , Risk Factors , Margins of Excision , Retrospective Studies
17.
Ann Surg Open ; 4(3): e307, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37746611

ABSTRACT

Objective: To compare binary metrics and Global Evaluative Assessment of Robotic Skills (GEARS) evaluations of training outcome assessments for reliability, sensitivity, and specificity. Background: GEARS-Likert-scale skills assessment are a widely accepted tool for robotic surgical training outcome evaluations. Proficiency-based progression (PBP) training is another methodology but uses binary performance metrics for evaluations. Methods: In a prospective, randomized, and blinded study, we compared conventional with PBP training for a robotic suturing, knot-tying anastomosis task. Thirty-six surgical residents from 16 Belgium residency programs were randomized. In the skills laboratory, the PBP group trained until they demonstrated a quantitatively defined proficiency benchmark. The conventional group were yoked to the same training time but without the proficiency requirement. The final trial was video recorded and assessed with binary metrics and GEARS by robotic surgeons blinded to individual, group, and residency program. Sensitivity and specificity of the two assessment methods were evaluated with area under the curve (AUC) and receiver operating characteristics (ROC) curves. Results: The PBP group made 42% fewer objectively assessed performance errors than the conventional group (P < 0.001) and scored 15% better on the GEARS assessment (P = 0.033). The mean interrater reliability for binary metrics and GEARS was 0.87 and 0.38, respectively. Binary total error metrics AUC was 97% and for GEARS 85%. With a sensitivity threshold of 0.8, false positives rates were 3% and 25% for, respectively, the binary and GEARS assessments. Conclusions: Binary metrics for scoring a robotic VUA task demonstrated better psychometric properties than the GEARS assessment.

18.
Pituitary ; 15(4): 539-51, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22116639

ABSTRACT

To evaluate the metabolic effects of first-line somatostatin analogues or surgery in acromegaly. Retrospective, comparative, 12-month follow-up. Two hundred and thirty one patients (123 men, age 47.32 ± 14.63 years) with active acromegaly, first line treatments were somatostatin analogues in 151 (65.4%) and surgery in 80 (34.6%). Metabolic syndrome (MS) parameters, glucose, insulin and GH during oral glucose tolerance test, stimulated insulin sensitivity by insulin sensitivity index (ISI Matsuda), early and total insulin-secretion rate by insulinogenic index and AUC(INS), visceral adiposity function, expressed by visceral adipose index (VAI). Somatostatin analogues treatment improved all MS parameters and significantly reduced fasting glucose (P < 0.001), HbA1c (P = 0.014) and the prevalence of DM (P = 0.003) when disease control was achieved. Both somatostatin analogues and surgery improved ISI Matsuda (P < 0.001) and reduced AUC(INS) (P < 0.001) and VAI (P < 0.001 and P = 0.003, respectively). Only in controlled somatostatin analogues-treated patients a significant reduction in insulinogenic index (P = 0.010) was observed. ISI Matsuda showed a significant independent correlation with IGF-1 levels (ß = -0.258; P = 0.001) and VAI score (ß = -0.430; P < 0.001). VAI was independently correlated with IGF-1 (ß = 0.183; P = 0.004). Both somatostatin analogues and surgery can safely be used as first-line therapy in acromegaly, without any untoward effects on glucose tolerance. The control of acromegaly is the main determinant of beneficial effects on general features of insulin sensitivity. VAI could represent an additional link between disease control and insulin sensitivity.


Subject(s)
Acromegaly/drug therapy , Acromegaly/surgery , Somatostatin/analogs & derivatives , Somatostatin/therapeutic use , Acromegaly/metabolism , Adult , Aged , Aged, 80 and over , Blood Glucose/metabolism , Female , Human Growth Hormone/metabolism , Humans , Insulin-Like Growth Factor I/metabolism , Male , Middle Aged , Retrospective Studies , Young Adult
19.
J Robot Surg ; 16(3): 677-685, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34383208

ABSTRACT

The evolution of robotic technology and its diffusion does not seem to have been adequately accompanied by the development and implementation of surgeon training programs that ensure skilled and safe device use at the start of the learning curve. The objective of the study is to develop and validate performance metrics for vessel dissection, vessel loop positioning, clip applying and bipolar coagulation using an avian model. Three robotic surgeons and a behavioral scientist characterized the performance metrics of the task according to the proficiency-based progression methodology. Fourteen experienced robotic surgeons from different European countries participated in a modified online Delphi consensus. Eight experienced surgeons and eight novices performed the robotic task twice. In the Delphi meeting, 100% consensus was reached on the performance metrics. Novice surgeons took 26 min to complete the entire task on trial 1 and 20 min on trial 2. Experts took 10.1 min and 9.5 min. On average the Expert Group completed the task 137% faster than the Novice Group. The amount of time to reach the vessel part of the task was also calculated. Novice surgeons took 26 min on trial 1 and 20 min on trial 2. Experts took 5.5 min and 4.8 min. On average the experts reached the vessel 200% faster than the novices. The Expert Group made 155% fewer performance errors than the Novice Group. The mean IRR of video-recorded performance assessments for all metrics was 0.96 (95% confidence intervals (CI) lower = 0.94-upper = 0.98). We report the development and validation for a standard and replicable basic robotic vessel dissection, vessel loop positioning, clip applying and bipolar coagulation task on an avian model. The development of objective performance metrics, based on a transparent and fair methodology (i.e., PBP), is the first fundamental step toward quality assured training. This task developed on the avian model proved to have good results in the validation study.


Subject(s)
Robotic Surgical Procedures , Robotics , Clinical Competence , Humans , Learning Curve , Robotic Surgical Procedures/methods , Surgical Instruments
20.
Eur Urol Focus ; 8(2): 506-513, 2022 03.
Article in English | MEDLINE | ID: mdl-33775611

ABSTRACT

BACKGROUND: Despite efforts aimed at preserving renal function, the functional decline after robot-assisted partial nephrectomy (RAPN) is not negligible. To address the risk of intraparenchymal vessel injuries during renorrhaphy, with consequent loss of functional renal parenchyma, we introduced a new surgical technique for RAPN. OBJECTIVE: To compare perioperative patient outcomes between selective-suturing or sutureless RAPN (suRAPN) and standard RAPN (stRAPN). DESIGN, SETTING, AND PARTICIPANTS: Ninety-two consecutive patients undergoing RAPN for a renal mass performed by a high-volume surgeon at a European tertiary center were included. Propensity-score matching was used to account for baseline differences between suRAPN and stRAPN patients. INTERVENTION: RAPN using a selective-suturing or sutureless technique versus standard RAPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Perioperative outcomes included operative time, blood loss, length of stay, and intraoperative and 30-d postoperative complications. We also evaluated trifecta achievement (warm ischemia time ≤25 min, negative surgical margins, and no perioperative complications) and the incidence of postoperative acute kidney injury (AKI). We applied χ2 tests, t tests, and Kruskal-Wallis tests to assess differences in perioperative outcomes between suRAPN and stRAPN. RESULTS AND LIMITATIONS: Overall, 29 patients (31%) were treated with suRAPN. Only one suRAPN patient experienced intraoperative complications (p = 0.9). Two suRAPN patients (6.9%) and four stRAPN patients (13.8%) experienced 30-d postoperative complications (p = 0.3). Operative time (110 vs 150 min; p < 0.01) and length of stay (2 vs 3 d; p = 0.02) were shorter for suRAPN than for stRAPN. The trifecta outcome was achieved in 25 suRAPN patients (86%) and 20 stRAPN patients (70%; p = 0.1). Only one suRAPN patient (3.4%) versus five stRAPN patients (17%) experienced postoperative AKI (p = 0.2). Finally, the decrease in the estimated glomerular filtration rate at 6-mo follow-up was lower in the suRAPN (-5.2%) than in the stRAPN group (-9.1%; p < 0.01). Lack of randomization represents the main study limitation. CONCLUSIONS: A selective-suturing or sutureless technique in RAPN is feasible and safe. Moreover, suRAPN is a lower-impact surgical procedure. We obtained promising results for trifecta and functional outcomes, but prospective randomized trials are needed to validate the impact of selective suturing or a sutureless technique on long-term functional outcomes. PATIENT SUMMARY: We assessed a new technique in robotic surgery to remove part of the kidney because of kidney cancer. Our new technique involves selective suturing or no suturing of the area from where the tumor is removed. We found that the rate of complications did not increase and the operating time and length of hospital stay were shorter using this new technique.


Subject(s)
Acute Kidney Injury , Robotic Surgical Procedures , Robotics , Acute Kidney Injury/epidemiology , Acute Kidney Injury/etiology , Humans , Nephrectomy/methods , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prospective Studies , Robotic Surgical Procedures/methods , Treatment Outcome
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