Publications by authors named "Alberto Martini"

395 Publications

Time for change at PROJ in 2021.

Pediatr Rheumatol Online J 2021 May 1;19(1):65. Epub 2021 May 1.

University of Genova, Genoa, Italy.

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http://dx.doi.org/10.1186/s12969-021-00560-yDOI Listing
May 2021

Reducing the Risk of Postoperative Complications After Robot-assisted Radical Prostatectomy in Prostate Cancer Patients: Results of an Audit and Feedback Intervention Following the Implementation of Prospective Data Collection.

Eur Urol Focus 2021 Apr 17. Epub 2021 Apr 17.

Department of Urology and Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: Prospective data collection for perioperative outcomes might increase awareness of surgical results obtained for patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). This would prompt the implementation of measures aimed at reducing the risk of adverse outcomes.

Objective: To assess the efficacy of an audit and feedback process aimed at identifying the most common complications after RARP and at implementing measures to improve outcomes.

Design, Setting, And Participants: Overall, 415 patients treated with RARP by a high-volume surgeon were included. Perioperative outcomes for 187 patients treated between September 2016 and December 2017 were prospectively collected at 30 d according to the European Association of Urology guideline recommendations (group 1). An audit and feedback process was implemented in January 2018 whereby the most common complication (anastomotic leak) was identified and measures aimed at improving outcomes (changes in the anastomotic technique) were implemented. The outcomes for group 1 were then compared to 228 patients treated after implementation of the modified surgical technique (group 2).

Surgical Procedure: A novel technique for posterior reconstruction and urethrovesical anastomosis was introduced.

Measurements: Perioperative outcomes included blood loss, operative time, length of stay, and 30-d postoperative complications. Logistic regression models tested the effect of the novel surgical technique on anastomotic leaks.

Results And Limitations: Overall, 97 patients (23%) experienced postoperative complications at 30 d. The rate of anastomotic leaks was significantly lower in group 2 compared to group 1 (3.1% vs 9.6%; p < 0.01). Similarly, overall and Clavien-Dindo grade ≥2 complication rates were lower in group 2 versus group 1 (17% vs 31%, and 6% vs 20%; both p ≤ 0.001). In multivariable analyses, treatment after implementation of changes in the anastomotic technique independently predicted a lower risk of complications (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.38-0.89) and of anastomotic leaks (OR 0.43, 95% CI 0.17-0.97). The lack of randomization represents the main limitation.

Conclusions: Implementation of changes in the urethrovesical anastomosis technique arising from increased awareness of surgical outcomes reduced the risk of anastomotic leaks. These findings highlight the importance of audit and feedback processes using a standardized method for reporting surgical morbidity.

Patient Summary: Increased awareness of surgical outcomes prompted us to change our technique for connecting the bladder to the urethra during robot-assisted surgery to remove the prostate in patients with prostate cancer. These changes resulted in significant improvements in surgical outcomes.
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http://dx.doi.org/10.1016/j.euf.2021.03.026DOI Listing
April 2021

Biological classification of childhood arthritis: roadmap to a molecular nomenclature.

Nat Rev Rheumatol 2021 May 17;17(5):257-269. Epub 2021 Mar 17.

IRCCS Istituto Giannina Gaslini, Genova, Italy.

Chronic inflammatory arthritis in childhood is heterogeneous in presentation and course. Most forms exhibit clinical and genetic similarity to arthritis of adult onset, although at least one phenotype might be restricted to children. Nevertheless, paediatric and adult rheumatologists have historically addressed disease classification separately, yielding a juvenile idiopathic arthritis (JIA) nomenclature that exhibits no terminological overlap with adult-onset arthritis. Accumulating clinical, genetic and mechanistic data reveal the critical limitations of this strategy, necessitating a new approach to defining biological categories within JIA. In this Review, we provide an overview of the current evidence for biological subgroups of arthritis in children, delineate forms that seem contiguous with adult-onset arthritis, and consider integrative genetic and bioinformatic strategies to identify discrete entities within inflammatory arthritis across all ages.
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http://dx.doi.org/10.1038/s41584-021-00590-6DOI Listing
May 2021

Metastatic hormone-sensitive prostate cancer: local treatment strategies.

World J Urol 2021 Mar 17. Epub 2021 Mar 17.

Unit of Urology, San Raffaele Scientific Institute, University Vita-Salute, Milan, Italy.

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http://dx.doi.org/10.1007/s00345-021-03605-9DOI Listing
March 2021

Re: Mathieu Rouanne, Dean F. Bajorin, Raquibul Hannan, et al. Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder. Eur Urol Oncol 2020;3:728-38.

Eur Urol Oncol 2021 Apr 2;4(2):336. Epub 2021 Feb 2.

Unit of Urology, University Vita-Salute, San Raffaele Scientific Institute, Milan, Italy; Division of Experimental Oncology, Urological Research Institute, IRCCS San Raffaele Scientific Institute, Milan, Italy.

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http://dx.doi.org/10.1016/j.euo.2021.01.002DOI Listing
April 2021

On the use of the "": application in cost estimation.

Authors:
Alberto Martini

Transl Androl Urol 2021 Jan;10(1):22-23

Unit of Urology, University Vita-Salute, San Raffaele Scientific Institute, Milan, Italy.

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http://dx.doi.org/10.21037/tau-20-1146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844481PMC
January 2021

Predicting toxicity-related docetaxel discontinuation and overall survival in metastatic castration-resistant prostate cancer: a pooled analysis of open phase 3 clinical trial data.

Prostate Cancer Prostatic Dis 2021 Feb 2. Epub 2021 Feb 2.

Division of Hematology/Oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Docetaxel is widely used in metastatic castration-resistant prostate cancer (mCRPC), however its optimal use remains unclear in the current treatment landscape. Biomarkers to predict Docetaxel toxicity may help optimize treatment selection. We aimed to create a predictive model for toxicity-related Docetaxel discontinuation (TRDD).

Methods: Through Project Data Sphere, we accessed individual patient data from the control arms of three frontline mCRPC trials: ASCENT2, VENICE, and MAINSAIL. The inclusion criteria for these trials were all similar and included patients with chemotherapy-naïve mCRPC. The primary outcome was occurrence of TRDD. A competing risks regression (CRR) was used to predict TRDD, after accounting for the occurrence of competing events (death or progression). The output of the model was used as the dependent variable on a classification and regression tree (CART) to identify risk groups for TRDD.

Results: Overall, 1568 patients were considered. Pooled CI of TRDD was 19% after accounting for competing events (death: 474; progression: 59) within 12 months of starting treatment. To build a risk calculator we relied on a CRR that ultimately included age, ECOG performance status, AST, bilirubin, use of analgesics, and presence of diabetes and chronic kidney disease. The CART analysis identified three risk groups that were named: low (model-derived TRDD risk ≤24%), intermediate (25-64%), and high (≥65%) risk group. In each risk group, probability of TRDD during treatment was 14%, 58%, and 79%, and median OS was 24 months, 20 months, and 13 months, respectively (p < 0.001).

Conclusions: Treatment selection in mCRPC remains a challenge. Our model can help clinicians balance Docetaxel toxicity and efficacy. The three risk categories that we identified correlated with OS and this is particularly useful for an optimal shared decision-making process.
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http://dx.doi.org/10.1038/s41391-021-00326-3DOI Listing
February 2021

Subcutaneous dosing regimens of tocilizumab in children with systemic or polyarticular juvenile idiopathic arthritis.

Rheumatology (Oxford) 2021 Jan 28. Epub 2021 Jan 28.

Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.

Objectives: To determine subcutaneous-tocilizumab (SC-TCZ) dosing regimens for systemic juvenile idiopathic arthritis (sJIA) and polyarticular JIA (pJIA).

Methods: In two 52-week phase 1 b trials, SC-TCZ (162 mg/dose) was administered to sJIA patients every week or every 2 weeks (every 10 days before interim analysis) and to pJIA patients every 2 weeks or every 3 weeks with body weight ≥30 kg or < 30 kg, respectively. Primary endpoints were pharmacokinetics, pharmacodynamics and safety; efficacy was exploratory. Comparisons were made to data from phase 3 trials with intravenous-tocilizumab (IV-TCZ) in sJIA and pJIA.

Results: Study participants were 51 sJIA patients and 52 pJIA patients aged 1-17 years who received SC-TCZ. Steady-state minimum TCZ concentration (Ctrough) >5th percentile of that achieved with IV-TCZ was achieved by 49 (96%) sJIA and 52 (100%) pJIA patients. In both populations, pharmacodynamic markers of disease were similar between body weight groups. Improvements in Juvenile Arthritis Disease Activity Score-71 were comparable between SC-TCZ and IV-TCZ. By week 52, 53% of sJIA patients and 31% of pJIA patients achieved clinical remission on treatment. Safety was consistent with that of IV-TCZ except for injection site reactions, reported by 41.2% and 28.8% of sJIA and pJIA patients, respectively. Infections were reported in 78.4% and 69.2% of patients, respectively. Two sJIA patients died; both deaths were considered related to TCZ.

Conclusion: SC-TCZ provides exposure and risk/benefit profiles similar to those of IV-TCZ. Subcutaneous administration provides an alternative administration route that is more convenient for patients and caregivers and that has potential for in-home use.

Trial Registration: ClinicalTrials.gov, NCT01904292 and NCT01904279.
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http://dx.doi.org/10.1093/rheumatology/keab047DOI Listing
January 2021

Open-Label Phase 3 Study of Intravenous Golimumab in Patients With Polyarticular Juvenile Idiopathic Arthritis.

Rheumatology (Oxford) 2021 Jan 25. Epub 2021 Jan 25.

Cincinnati Children's Hospital Medical Center, Division of Rheumatology, University of Cincinnati, Cincinnati, Ohio, United States of America.

Objectives: Assess efficacy, pharmacokinetics (PK), and safety of intravenous (IV) golimumab in patients with polyarticular-course juvenile idiopathic arthritis (pc-JIA).

Methods: Children aged 2 to < 18 years with active pc-JIA despite methotrexate therapy for ≥2 months received 80 mg/m2 golimumab at Weeks 0, 4, then every 8 weeks through week 52 plus methotrexate weekly through week 28. The primary and major secondary endpoints were PK exposure and model-predicted steady-state area under the curve (AUCss) over an 8-week dosing interval at Weeks 28 and 52, respectively. JIA American College of Rheumatology (ACR) response and safety were also assessed.

Results: In total, 127 children were treated with IV golimumab. JIA ACR 30, 50, 70, and 90 response rates were 84%, 80%, 70%, and 47%, respectively, at week 28 and were maintained through week 52. Golimumab serum concentrations and AUCss were 0.40 µg/ml and 399 µg·day/ml at week 28. PK exposure was maintained at week 52. Steady-state trough golimumab concentrations and AUCss were consistent across age categories and comparable to IV golimumab dosed 2 mg/kg in adults with rheumatoid arthritis. Golimumab antibodies and neutralizing antibodies were detected via a highly sensitive drug-tolerant assay in 31% (39/125) and 19% (24/125) of patients, respectively. Median trough golimumab concentration was lower in antibody-positive vs antibody-negative patients. Serious infections were reported in 6% of patients, including 1 death due to septic shock.

Conclusion: Body surface area-based dosing of IV golimumab was well tolerated and provided adequate PK exposure for clinical efficacy in paediatric patients with active pc-JIA.ClinicalTrials.gov number NCT02277444.
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http://dx.doi.org/10.1093/rheumatology/keab021DOI Listing
January 2021

Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis.

J Rheumatol 2021 Jan 15. Epub 2021 Jan 15.

This study was funded by Bristol Myers Squibb. Professional medical writing and editorial assistance was provided by Lola Parfitt, MRes, at Caudex and was funded by Bristol Myers Squibb. The study was designed jointly by academic authors and Bristol Myers Squibb, with data collected by PRINTO/ PRCSG investigators. Consistency in reporting the study data to healthcare authorities and institutional review boards was ensured by Bristol Myers Squibb. All authors attest to the completeness and veracity of data and data analyses. All authors had full access to study data, reviewed and revised the manuscript, and approved the final version to be published. N. Ruperto, MD, MPH, IRCCS Istituto G Gaslini, Clinica Pediatrica e Reumatologia-UOSID Centro Trial, Genoa, Italy; H.I. Brunner, MD, MSc, MBA, D.J. Lovell, MD, MPH, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA; N. Tzaribachev, MD, Pediatric Rheumatology Research Institute, Bad Bramstedt, Germany; G. Vega-Cornejo, MD, CREA Hospital México Americano, Guadalajara, Jalisco, Mexico; I. Louw, MMED, MBChB, Panorama Medical Centre, Cape Town, South Africa; R. Cimaz, MD, University Hospital Meyer, Florence, Italy and Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy; J. Dare, MD, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; G. Espada, MD, Hospital de Niños Dr Ricardo Gutiérrez, Buenos Aires, Argentina; E. Faugier, MD, Hospital Infantil de México Federico Gómez, Mexico City, Mexico; M. Ferrandiz, MD, Instituto Nacional de Salúd del Niño, Breña, Peru; V. Gerloni, MD, Istituto Ortopedico Gaetano Pini, Milan, Italy; P. Quartier, MD, Université de Paris, IMAGINE Institute, RAISE reference centre for rare diseases, Necker-Enfants Malades hospital, AP-HP, Paris, France; C.A. Silva, MD, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil; L. Wagner-Weiner, MD, MS, University of Chicago, Chicago, Illinois, USA; Y. Gandhi, PhD, R. Wong, MD, Bristol Myers Squibb, Princeton, New Jersey, USA; J. Passarell, MA, Cognigen Corporation, Buffalo, New York, USA; M. Nys, MSc, Bristol Myers Squibb, Braine-L'Alleud, Belgium; A. Martini, MD, IRCCS Istituto G Gaslini, Clinica Pediatrica e Reumatologia, Genoa, Italy and Università di Genova, Genoa, Italy. N. Ruperto and H.I. Brunner contributed equally to the manuscript. NR has received honoraria for consultancy or speakers' bureaus from AbbVie, Ablynx, AstraZeneca, Biogen Idec, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, EMD Serono, F. Hoffman-La Roche, GlaxoSmithKline, Janssen, Novartis, Pfizer, R-Pharm, Sanofi, Sinergie, Sobi, and Takeda. The Gaslini Hospital has received contributions from the following companies: Bristol Myers Squibb, F. Hoffman-La Roche, Janssen, Novartis, Pfizer, and Sobi. This money has been reinvested for the research activities of the hospital in a fully independent manner besides any commitment with third parties. HIB has served on speakers bureaus for Genentech, GlaxoSmithKline, and Novartis. The Cincinnati Children's Hospital Medical Center has received consulting fees from AbbVie, AstraZeneca, Bristol Myers Squibb, Centocor, Eli Lilly, F. Hoffman La-Roche, Genentech, Novartis, Pfizer, Regeneron, UBC, and Xoma for the work of HIB. NT has nothing to declare. GVC has received consulting fees from AbbVie, Bayer, Bristol Myers Squibb, Janssen, Sanofi, and UCB. IL has received consulting fees from Amgen, Janssen, Novartis, Pfizer, and Roche. RC has received consulting fees from or participated on speakers bureaus for AbbVie, Novartis, Sanofi, and Sobi. JD has received support for clinical trials/registries from AbbVie, AstraZeneca, Bristol Myers Squibb, Horizon Pharma, Medac, Pfizer, Roche, and UCB. GE has nothing to declare. EF has nothing to declare. MF has nothing to declare. VG has nothing to declare. PQ has received consulting fees from AbbVie, Bristol Myers Squibb, Eli Lilly, Novartis, Novimmune, Pfizer, Roche, and Sobi; has served on speakers bureaus for AbbVie, Bristol Myers Squibb, MedImmune, Novartis, Pfizer, Roche, and Sobi; has served on a safety monitoring board for Sanofi; has acted as a trial investigator for AbbVie, Bristol Myers Squibb, Eli Lilly, Novartis, Novimmune, Pfizer, Roche, and Sanofi; and has received congress financial support from AbbVie, Bristol Myers Squibb, Novartis, Pfizer, and Sobi. CAS has nothing to declare. LWW has nothing to declare. YG, MN, and RW are employees and shareholders of Bristol Myers Squibb. JP is an employee of Cognigen Corporation. AM has received consulting fees from Janssen, Novartis, and Pfizer; Istituto G Gaslini, Clinica Pediatrica e Reumatologia has received consulting fees from AbbVie, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, EMD Serono, Janssen, Novartis, Pfizer, and R-Pharm for the work of AM. DJL has served on speakers bureaus for Bristol Myers Squibb and Genentech; and has served on Data and Safety Monitoring Boards for Forest Research and the National Institutes of Health's National Institute of Arthritis and Musculoskeletal and Skin Diseases. Cincinnati Children's Hospital Medical Center has received consulting fees from AbbVie, AstraZeneca, Bristol Myers Squibb, Centocor, F. Hoffman La-Roche, Genentech, Novartis, Pfizer, Regeneron, UBC, and Xoma for the work of DJL. Address correspondence to Dr. N. Ruperto, Istituto G. Gaslini Clinica Pediatria e Reumatologia-UOSID Centro Trial, PRINTO, EULAR Centre of Excellence in Rheumatology 2008-2023, Via Gaslini, 5, 16147 Genova, Italy. Email: Accepted for publication December 18, 2020.

Objective: To assess the relationship between infection risk and abatacept (ABA) exposure levels in patients with polyarticular-course juvenile idiopathic arthritis (pJIA) following treatment with subcutaneous (SC) and intravenous (IV) ABA.

Methods: Data from 2 published studies (ClinicalTrials.gov: NCT01844518, NCT00095173) of ABA treatment in pediatric patients were analyzed. One study treated patients aged 2-17 years with SC ABA and the other treated patients aged 6-17 years with IV ABA. Association between serum ABA exposure measures and infection was evaluated using Kaplan-Meier plots of probability of first infection vs time on treatment by ABA exposure quartiles and log-rank tests. Number of infections by ABA exposure quartiles was investigated.

Results: Overall, 343 patients were included in this analysis: 219 patients received SC ABA and 124 patients received IV ABA. Overall, 237/343 (69.1%) patients had ≥ 1 infection over 24 months. No significant difference in time to first infection across 4 quartiles of ABA exposure levels was observed in the pooled ( = 0.45), SC (2-5 yrs: = 0.93; 6-17 yrs: = 0.48), or IV ( = 0.50) analyses. Concomitant use of methotrexate and glucocorticoids (at baseline and throughout) with ABA did not increase infection risk across the ABA exposure quartiles. There was no evidence of association between number of infections and ABA exposure quartiles. No opportunistic infections related to ABA were reported.

Conclusion: In patients aged 2-17 years with pJIA, no evidence of association between higher levels of exposure to IV ABA or SC ABA and incidence of infection was observed.
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http://dx.doi.org/10.3899/jrheum.200154DOI Listing
January 2021

Neoadjuvant and adjuvant immunotherapy in renal cell carcinoma.

World J Urol 2021 Jan 1. Epub 2021 Jan 1.

Unit of Urology, University Vita-Salute, San Raffaele Scientific Institute, Milan, Italy.

Objective: The treatment landscape for renal cell carcinoma (RCC) is rapidly evolving. The aim of this review is to summarize the randomized-controlled trials evaluating the role of immunotherapy in neoadjuvant or adjuvant setting.

Materials And Methods: We searched PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies including neoadjuvant or adjuvant immunotherapy, and provided a brief overview of the pharmacodynamics of immunotherapy for RCC.

Results: Several drugs are currently under investigation. In the neoadjuvant setting, four studies are evaluating the role of single-agent immunotherapy, one of dual-agent immunotherapy, and four studies the role of immunotherapy in combination with tyrosine kinase inhibitors or anti-interleukin-1 beta. In the adjuvant setting, two studies are evaluating the role of single-agent immunotherapy and two of dual-agent immunotherapy.

Conclusions: The approval of immune checkpoint inhibition as a front-line therapeutic strategy for advanced RCC has also ultimately led to the investigation of these agents first in the adjuvant and then in the neoadjuvant setting. Currently, there are nine studies aimed to evaluate the role of immunotherapy in the neoadjuvant setting and four studies in the adjuvant setting.
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http://dx.doi.org/10.1007/s00345-020-03550-zDOI Listing
January 2021

RE: Validating the Martini Staging System for Rectourethral Fistula: A Meta-analysis of Postoperative Outcomes.

Urology 2021 Jan 19;147:323. Epub 2020 Nov 19.

Department of Urology, University Vita Salute, San Raffaele Hospital, Milan, Italy.

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http://dx.doi.org/10.1016/j.urology.2020.10.049DOI Listing
January 2021

The effect of tumor location on overall survival for pT2-4 bladder and upper tract urothelial carcinoma following radical surgery.

Can Urol Assoc J 2021 May;15(5):E248-E255

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Introduction: Historically, staging and treatment for upper tract urothelial carcinoma were extrapolated from bladder urothelial carcinoma literature. However, embryological, genetic, and anatomical differences exist between them. We sought to explore the relationship between location of urothelial cancer and overall survival (OS).

Methods: Data was culled from the National Cancer Database from 2004-2015. Patients with pT2-pT4 treated with definitive surgery were included; those with metastatic disease or who received neoadjuvant or adjuvant treatment were excluded. Patients were stratified by tumor location and pathological stage. The primary outcome was OS. Secondary outcomes were predictors of mortality in each pT stage stratum.

Results: A total of 11 330 patients with bladder, 954 patients with ureteral, and 1943 patients with renal pelvis urothelial carcinoma were analyzed. Mean followup was 43.3, 39.4, and 41.4 months for bladder, ureteral, and renal pelvis, respectively. On univariable analysis, ureteral pT2 was associated with worse OS compared to both bladder (61.3 vs. 80.4 months, p=0.007) and renal pelvis (61.3 vs. 80.5 months, p=0.014). Renal pelvis pT3 was associated with improved OS compared to both bladder (42.5 vs. 28.6 months, p=0.003) and ureteral (42.5 vs. 25.7 months, p<0.001). Renal pelvis pT4 had decreased survival compared to bladder (11.4 vs. 17.7 months, p<0.001). On multivariable Cox regression, only renal pelvis pT3 was associated with a 20% decreased risk of mortality compared to bladder pT3 (hazard ratio 0.80, 95% confidence interval 0.72-0.88, p<0.001).

Conclusions: Renal pelvis pT3 is associated with lower mortality. Mutational and embryological differences may play a role in this disparity.
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http://dx.doi.org/10.5489/cuaj.6698DOI Listing
May 2021

Hood Technique for Robotic Radical Prostatectomy-Preserving Periurethral Anatomical Structures in the Space of Retzius and Sparing the Pouch of Douglas, Enabling Early Return of Continence Without Compromising Surgical Margin Rates.

Eur Urol 2020 Oct 13. Epub 2020 Oct 13.

Department of Urology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.

Background: A common side effect following radical prostatectomy is urinary incontinence. Here, we describe a novel surgical technique to reduce postoperative urinary incontinence and facilitate early return of continence.

Objective: To describe the novel "hood technique" for robotic-assisted radical prostatectomy (RARP).

Design, Setting, And Participants: This is an institutional review board-approved prospective study of 300 patients (median age 64 yr) with localized prostate cancer treated with the RARP hood technique at a major urban hospital between April 2018 and March 2019. The exclusion criteria were as follows: patients with anterior tumor location based on biopsy or multiparametric magnetic resonance imaging. All but one patient participated in follow-up over 12 mo after the procedure.

Surgical Procedure: The RARP "hood technique" was performed to preserve the detrusor apron, puboprostatic ligament complex, arcus tendineus, endopelvic fascia, and pouch of Douglas.

Measurements: Clinical data collected included pre- and intraoperative variables, and postoperative functional and oncological outcomes and complications. Descriptive statistical analysis was performed.

Results And Limitations: Continence rates at 1, 2, 4, 6 12, 24, and 48 wk after catheter removal were 21%, 36%, 83%, 88%, 91%, 94%, and 95%, respectively. Positive surgical margin rate was 6%. Thirty patients (9.7%) experienced complications after RARP: 17 (5.7%), 11 (3.6%), and one (0.4%) had Clavien-Dindo grade I, II, and III complications, respectively. This study was conducted within a single health system and may not be generalizable. The study lacked randomization and a comparative arm.

Conclusions: Results indicate that the hood technique spares musculofascial structures anterior to the urethral sphincter complex with early return of continence after surgery, without compromising positive surgical margin rates. Exclusion of anterior tumor location contributed to a reduction in positive surgical margins.

Patient Summary: By better preservation of anatomical structures around the urethra, we were able to achieve early return of urinary continence without a negative impact on complications and cancer outcomes.
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http://dx.doi.org/10.1016/j.eururo.2020.09.044DOI Listing
October 2020

Fused Omics Data Models Reveal Gut Microbiome Signatures Specific of Inactive Stage of Juvenile Idiopathic Arthritis in Pediatric Patients.

Microorganisms 2020 Oct 6;8(10). Epub 2020 Oct 6.

Department of Laboratories, Unit of Parasitology and Area of Genetics and Rare Diseases, Unit of Human Microbiome, Bambino Gesù Children's Hospital, IRCCS, 00165 Rome, Italy.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. Herein, we evaluated the relationship between the gut microbiome (GM) and disease phenotype by an integrated omics fused approach. In a multicenter, observational cohort study, stools from Italian JIA patients were collected at baseline, active, and inactive disease stages, and their GM compared to healthy controls (CTRLs). The microbiota metabolome was analyzed to detect volatile- and non-volatile organic compounds (VOCs); the data were fused with operational taxonomic units (OTUs) from 16S RNA targeted-metagenomics and classified by chemometric models. Non-VOCs did not characterize JIA patients nor JIA activity stages compared to CTRLs. The core of VOCs, (Ethanol, Methyl-isobutyl-ketone, 2,6-Dimethyl-4-heptanone and Phenol) characterized patients at baseline and inactive disease stages, while the OTUs represented by Ruminococcaceae, Lachnospiraceae and Clostridiacea discriminated between JIA inactive stage and CTRLs. No differences were highlighted amongst JIA activity stages. Finally, the fused data discriminated inactive and baseline stages versus CTRLs, based on the contribution of the invariant core of VOCs while Ruminococcaceae concurred for the inactive stage versus CTRLs comparison. In conclusion, the GM signatures enabled to distinguish the inactive disease stage from CTRLs.
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http://dx.doi.org/10.3390/microorganisms8101540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650812PMC
October 2020

Abatacept: A Review of the Treatment of Polyarticular-Course Juvenile Idiopathic Arthritis.

Paediatr Drugs 2020 Dec 8;22(6):653-672. Epub 2020 Oct 8.

IRCCS Istituto Giannina Gaslini, Clinica Pediatrica E Reumatologia-PRINTO, Genoa, Italy.

Juvenile idiopathic arthritis (JIA) encompasses several forms of chronic inflammatory arthritis of unknown etiology presenting in children < 16 years of age, with a minimum symptom duration of 6 weeks. Approximately half of affected children have polyarticular-course JIA (pJIA), a functional concept related to several clinically and genetically heterogeneous JIA categories (systemic, extended oligoarthritis, polyarticular rheumatoid factor-positive or rheumatoid factor-negative, enthesitis-related arthritis, and psoriatic arthritis), which has as its defining feature the involvement of five or more joints during the disease course. Chronic inflammation and joint damage lead to the manifestations of JIA such as pain, limitation of motion, and loss of physical function, all of which negatively impact patients' quality of life. The American College of Rheumatology recommends initial treatment with a conventional synthetic disease-modifying antirheumatic drug (csDMARD), such as methotrexate (MTX) and, in patients with pJIA who have an inadequate response or intolerance to MTX, the use of a biologic DMARD (bDMARD) such as a tumor necrosis factor inhibitor, abatacept, or tocilizumab. Abatacept selectively modulates the CD80/CD86:CD28 co-stimulatory signal required for full T cell activation, and thus has a distinct mechanism of action upstream of that of other currently available bDMARD treatments for rheumatic diseases. To enable physicians to make informed treatment decisions, it is important to review available data for the existing therapeutic agents. Here, we summarize the current evidence from phase III pivotal trials of intravenous (IV) and subcutaneous (SC) abatacept and from an ongoing registry of patients with JIA treated with abatacept. In the pivotal trials for IV and SC abatacept, either with or without MTX, both formulations demonstrated clinical efficacy, with a high proportion of patients achieving stringent clinical responses, as well as improvements in patient-reported outcomes and a favorable safety profile, particularly with regard to infections.
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http://dx.doi.org/10.1007/s40272-020-00422-2DOI Listing
December 2020

Prediction of the Need for an Extended Lymphadenectomy at the Time of Radical Cystectomy in Patients with Bladder Cancer.

Eur Urol Focus 2020 Oct 2. Epub 2020 Oct 2.

Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy.

Background: A prospective randomized trial (LEA AUO AB 25/02) found no survival benefit in extended compared with limited pelvic lymph node dissection (PLND) templates in bladder cancer (BCa) patients treated with radical cystectomy (RC). However, the rate of lymph node invasion (LNI) in the standard and extended templates was lower than estimated.

Objective: To assess the accuracy of preoperative clinical and pathological parameters to predict LNI and to develop a model to preoperatively select candidates for the extended PLND templates.

Design, Setting, And Participants: A total of 903 BCa patients treated at a single institution were retrospectively identified. The primary outcome was to identify preoperatively the risk of LNI to tailor the type of PLND. The extended PLND templates consisted in the removal of pelvic lymph nodes together with the common iliac, presacral, para-aortocaval, interaortocaval, and paracaval sites up to the inferior mesenteric artery.

Intervention: A total of 903 BCa patients were treated with RC and bilateral extended PLND templates.

Outcome Measurements And Statistical Analysis: Several models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses. A nomogram predicting LNI in the extended pattern was developed and validated internally.

Results And Limitations: Overall, 55 patients (6.1%) had LNI in the extended PLND templates at RC. The median number of nodes removed was 19 (interquartile range: 13-26). A model including age, clinical T stage, clinical node stage, lymphovascular invasion, and presence of carcinoma in situ at the last transurethral resection before RC was developed. The AUC of this model is 73%. Using a cutoff of 3%, 108 extended PLNDs (12%) would be spared and only two LNIs (3%) would be missed. The main limitations of our model are the retrospective nature of the data, lack of external validation, and low rate of LNI.

Conclusions: This is the first proposed model to predict LNI in the extended PLND templates. This model might help urologists identify which patients might benefit from an extended PLND at the time of RC, reserving a standard PLND for all the others.

Patient Summary: We developed the first nomogram to predict lymph node invasion (LNI) in the extended pelvic lymph node dissection templates in bladder cancer patients treated with radical cystectomy. The adoption of our model to identify candidates for the extended pelvic lymph node dissection templates could avoid up to 12% of these procedures at the cost of missing only 3% of patients with LNI.
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http://dx.doi.org/10.1016/j.euf.2020.09.009DOI Listing
October 2020

Using biomarkers in patients with positive multiparametric magnetic resonance imaging: 4Kscore predicts the presence of cancer outside the index lesion.

Int J Urol 2021 Jan 27;28(1):47-52. Epub 2020 Sep 27.

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Objectives: To evaluate if the blood biomarker, 4Kscore, in addition to multiparametric magnetic resonance imaging information could identify patients who would benefit from undergoing only a targeted biopsy.

Methods: We retrospectively analyzed a population of 256 men with positive multiparametric magnetic resonance imaging who underwent standard + targeted biopsy at Mount Sinai Hospital, New York, NY, USA. 4Kscore (OPKO Health, Miami, FL, USA) was sampled from all patients before biopsy. Uni- and multivariable binary logistic regression analyses were carried out to predict clinically significant prostate cancer, defined as International Society of Urological Pathology grade group ≥2, in standard biopsy cores. The model with the best area under the curve was selected and internal validation was carried out using the leave-one-out cross-validation.

Results: The developed model showed an area under the curve of 0.86. Carrying out only targeted biopsy in patients with a model-derived probability <12.5% resulted in 39.5% (n = 101) fewer standard biopsies and a 33.9% (n = 20) reduction of detecting grade group 1 disease, while missing grade group ≥2 in 5.2% (n = 4) using standard biopsy only and 1.1% (n = 1) using standard biopsy + targeted biopsy.

Conclusions: 4Kscore in combination with multiparametric magnetic resonance imaging can help to reduce unnecessary standard biopsy and decrease detection of clinically insignificant prostate cancer.
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http://dx.doi.org/10.1111/iju.14385DOI Listing
January 2021

Combined Use of Prostate-specific Antigen Density and Magnetic Resonance Imaging for Prostate Biopsy Decision Planning: A Retrospective Multi-institutional Study Using the Prostate Magnetic Resonance Imaging Outcome Database (PROMOD).

Eur Urol Oncol 2020 Sep 21. Epub 2020 Sep 21.

Department of Urology and Organ Transplantation, University of Foggia, Foggia, Italy.

Background: Previous studies suggested that prostate-specific antigen (PSA) density (PSAd) combined with magnetic resonance imaging (MRI) may help avoid unnecessary prostate biopsy (PB) with a limited risk of missing clinically significant prostate cancer (csPCa; Gleason grade group [GGG] >1).

Objective: To define optimal diagnostic strategies based on the combined use of PSAd and MRI in patients at risk of prostate cancer (PCa).

Design, Setting, And Participants: A retrospective analysis of the international multicenter Prostate MRI Outcome Database (PROMOD), including 2512 men having undergone PSAd and prostate MRI before PB between 2013 and 2019, was performed.

Outcome Measurements And Statistical Analysis: Rates of avoided PB, missed GGG 1, and csPCa according to 10 strategies based on PSAd values and MRI reporting scores (Prostate Imaging Reporting and Data System [PI-RADS]/Likert/IMPROD biparametric prostate MRI Likert). Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. Combined systematic and targeted biopsies were used for reference.

Results And Limitations: According to DCA, the best strategy in biopsy-naive patients was #7 (PI-RADS/Likert 4-5 or PI-RADS/Likert 3 if PSAd >0.2), which avoided 41.2% PBs while missed 44% of GGG 1 and 10.9% of csPCa cases. From a clinical standpoint, however, strategies with a lower risk of missing csPCa included #10 (PI-RADS/Likert 4-5 or PI-RADS 3 if PSAd >0.10 or PSAd >0.2), which avoided 27% PBs while missing 24.4% GGG 1 and 4% csPCa cases, or #5 (PI-RADS/Likert 3-5 or PSAd>0.15), which avoided 14.7% PBs while missing 9.3% GGG 1 and 1.7% csPCa cases. Similar results were found in patients with a previous negative biopsy. This study is limited by its retrospective nature, and no central review of MRI and histopathological findings.

Conclusions: Combined PSAd and MRI findings allows individualization of the decision to perform PB on the basis of the risk of missing PCa that both patients and clinicians are ready to accept to avoid this procedure.

Patient Summary: We compared several biopsy strategies based on a combination of prostate magnetic resonance imaging findings and prostate-specific antigen density, providing a readily available tool for each center and practicing urologist to counsel patients about their individual risk of significant prostate cancer.
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http://dx.doi.org/10.1016/j.euo.2020.08.014DOI Listing
September 2020

Quantitative Polymerase Chain Reaction Detection of Microchimerism in Female Transplant Renal Recipients.

Urol Int 2020 21;104(11-12):865-870. Epub 2020 Sep 21.

Molecular and Clinical Biochemistry Unit, Department of Experimental and Clinical Biomedical Sciences "Mario Serio," Careggi Hospital, University of Florence, Florence, Italy.

Introduction: Microchimerism (MC) is the presence of a small amount of foreign cells or DNA within a person's circulation or tissues. It has been identified also in recipients of solid organ transplants where it seems to be critical for the development and maintenance of immunological tolerance. Nevertheless, natural and/or iatrogenic MC can be acquired prior to transplantation, through pregnancy and/or blood transfusion.

Objective: The aim of this study was to detect the presence of MC in women after renal transplantation from male cadaveric donors and its relationship with graft outcomes.

Methods: We studied by qPCR the presence of the DYS14 gene sequence of the Y chromosome in 12 females who received a kidney graft from a male donor before transplantation (T0), after 15 days (T1) and 1 year of transplantation (T2). We found the sequence in all recipients after renal transplantation.

Results: All the women were negative for this sequence prior to transplantation (T0). Mean (SD) Y-related DNA quantity was 0.80 (0.69) ng/mL plasma and 0.15 (0.26) ng/mL plasma at T1 and T2, respectively. No acute rejection was observed, and mean (SD) estimated Cr clearance was 68.8 (16.9) mL/min within 1 year from transplantation.

Conclusions: Presence of MC was associated with good kidney graft outcomes after 1 year of transplantation, but further studies will be needed to investigate the relationship between clinical outcomes and the development of MC in renal transplant recipient.
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http://dx.doi.org/10.1159/000508796DOI Listing
September 2020

Can anesthetics affect bladder cancer recurrence? Total intravenous versus volatile anesthesia in patients undergoing robot-assisted radical cystectomy: A single institution retrospective analysis.

Urol Oncol 2021 Apr 18;39(4):233.e1-233.e8. Epub 2020 Sep 18.

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY.

Background: Radical cystectomy is standard of care and part of a multidisciplinary approach for long-term survival in patients with muscle-invasive bladder cancer (MIBC) or high-grade non-MIBC. Recent data have suggested that anesthetic technique can affect long-term survival and recurrence in patients undergoing cancer related surgery.

Methods: The records of all patients who underwent robot-assisted radical cystectomy for high-risk non-MIBC or MIBC at a single academic institution from 2014 to 2020 were retrospectively reviewed. Patients were grouped according to whether they received total intravenous (TIVA) or volatile inhalation anesthesia (VIA). Univariable and multivariable cox proportional hazards models were used to compare hazard ratios for distant recurrence. Kaplan-Meier recurrence-free survival curves were constructed from the date of surgery to recurrence.

Results: A total of 231 patients were included, of which 126 (55%) received TIVA and 105 (45%) received VIA. Distant recurrence occurred in 8.7% and 26.7% of patients who received TIVA and VIA, respectively (P < 0.001). Kaplan-Meier analysis demonstrated significant improvement in distant recurrence-free survival with TIVA (log-rank P < 0.001). Multivariable analysis revealed a significant increase in recurrence risk with VIA (HR: 3.4, 95%CI: 1.5-7.7, P < 0.01) and increasing tumor pathological stage (pT2, pT3, pT4, all P < 0.05).

Conclusions: The use of volatile inhalation anesthetics during robot-assisted radical cystectomy may be associated with an increased risk of distant recurrence. Further studies will be necessary to validate these findings.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.024DOI Listing
April 2021

Efficacy and Safety of Tocilizumab for Polyarticular-Course Juvenile Idiopathic Arthritis in the Open-Label Two-Year Extension of a Phase III Trial.

Arthritis Rheumatol 2021 03 9;73(3):530-541. Epub 2021 Feb 9.

IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy.

Objective: To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA).

Methods: Patients ages 2-17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA-American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA-ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure.

Results: Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years.

Conclusion: Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.
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http://dx.doi.org/10.1002/art.41528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986602PMC
March 2021

Black race may be associated with worse overall survival in renal cell carcinoma patients.

Urol Oncol 2020 12 17;38(12):938.e9-938.e17. Epub 2020 Sep 17.

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address:

Objective: To examine socio-demographic and treatment variables in an attempt to identify factors associated with survival differences between black and white patients with renal cell carcinoma (RCC).

Patients And Methods: We identified 79,618 white and 10,604 black patients diagnosed with RCC in the National Cancer Database. We compared the distribution of socio-demographic, presentation and treatment variables between Blacks and Whites and then utilized a multivariable cox proportion hazards regression model to evaluate the contribution of differences in these variables to disparities in overall survival (OS).

Results: Black patients were younger (60 vs. 63 years, P< 0.001) and with a lower stage (12.0% vs. 18.8% Stage III-IV P< 0.001). Blacks presented with a higher Charlson-Deyo score (P< 0.001), lower income (P< 0.001), lower education (P< 0.001) and were less likely to receive radical nephrectomy and systemic therapy for stage IV RCC (29.9% vs. 38.8%, P< 0.001). Unadjusted OS was lower for Whites (5-year survival 79% for Blacks and 77% for Whites). However, OS was lower for Blacks when adjusted for all variables (5-year survival 89% for Blacks and 93% for Whites). On multivariable analysis, black race was independently associated with worse OS, HR: 1.09 (95% confidence interval: 1.03, 1.14, P= 0.002). A sensitivity analysis including patients with complete data on tumor grade confirmed our results.

Conclusion: Our study indicates that black patients present at a younger age and with lower stage RCC, but have worse OS. Blacks experienced disparities in socio-demographic characteristics, clinical presentation, treatment-related factors, and had an independently increased hazard of death.
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http://dx.doi.org/10.1016/j.urolonc.2020.08.034DOI Listing
December 2020

Expanding Active Surveillance Inclusion Criteria: A Novel Nomogram Including Preoperative Clinical Parameters and Magnetic Resonance Imaging Findings.

Eur Urol Oncol 2020 Sep 2. Epub 2020 Sep 2.

Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Background: Current European Association of Urology, American Urological Association, and National Comprehensive Cancer Network guidelines recommend active surveillance (AS) for selected intermediate-risk prostate cancer (PCa) patients. However, limited evidence exists regarding which men can be selected safely.

Objective: To externally validate the Gandaglia risk calculator (Gandaglia-RC), designed to predict adverse pathology (AP) at radical prostatectomy (RP) and thus able to improve selection of intermediate-risk PCa patients suitable for AS, and to assess whether addition of magnetic resonance imaging (MRI) findings (MAP model) improves the predictive ability of Gandaglia-RC.

Design, Setting, And Participants: This is a retrospective analysis of a single-center cohort of 1284 consecutive men with low- and intermediate-risk PCa treated with RP between 2013 and 2019.

Outcome Measurements And Statistical Analysis: AP was defined as non-organ-confined disease and/or lymph node invasion and/or pathological grade group≥3 at RP. Logistic regression was used to calculate the predictors of AP; calculated coefficients were used to develop a risk score. Receiver operating characteristic curve analysis and decision curve analysis were performed to evaluate the net benefit within models.

Results And Limitations: At multivariable analysis, age at surgery, prostate-specific antigen, systematic and targeted biopsy Gleason grade group, MRI prostate volume, Prostate Imaging Reporting and Data System score, and MRI extraprostatic extension were significantly associated with AP. The model significantly improved the ability of Gandaglia-RC to predict AP (area under the curve 0.71 vs 0.63 [p<0.0001]). Using a 30% threshold, the proportions of men eligible for AS were 45% and 77% and the risks of AP were 16% and 17%, for Gandaglia-RC and MAP model, respectively.

Conclusions: Compared with Gandaglia-RC, the MAP model significantly increased the number of patients eligible for AS without significantly increasing the risk of AP at RP.

Patient Summary: In this report, we have developed a risk prediction tool to select men for conservative treatment of prostate cancer. Using the novel tool, more men could safely be allocated to conservative treatment rather than surgery or radiation.
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http://dx.doi.org/10.1016/j.euo.2020.08.001DOI Listing
September 2020

RHAPSODY: Rationale for and design of a pivotal Phase 3 trial to assess efficacy and safety of rilonacept, an interleukin-1α and interleukin-1β trap, in patients with recurrent pericarditis.

Am Heart J 2020 10 14;228:81-90. Epub 2020 Jul 14.

Kiniksa Pharmaceuticals Corp., Lexington, MA.

Recurrent pericarditis (RP) occurs in 15% to 30% of patients following a first episode, despite standard treatment with nonsteroidal anti-inflammatory drugs, colchicine, and corticosteroids; many patients become dependent on corticosteroids. Rilonacept (KPL-914), an interleukin-1α and β inhibitor, is in development for the treatment of RP. RHAPSODY, a double-blind, placebo-controlled, randomized-withdrawal (RW) pivotal Phase 3 trial (NCT03737110), enrolls patients 12 years or older presenting with at least a third pericarditis episode, pericarditis pain score ≥4 (11-point numeric rating scale [NRS]), and C-reactive protein ≥1 mg/dL at screening. After a subcutaneous loading dose (adults, 320 mg; children, 4.4 mg/kg), all patients receive blinded weekly subcutaneous rilonacept (adults, 160 mg; children, 2.2 mg/kg) during the run-in period. Patients must taper and discontinue concomitant pericarditis medications during the blinded run-in period and achieve clinical response (C-reactive protein ≤0.5 mg/dL and weekly average NRS ≤2.0 during the 7 days prior to and including the day of randomization) by end of the run-in (while on rilonacept monotherapy) to be randomized to either continued rilonacept or placebo in the RW period. Primary efficacy end point was time to adjudicated pericarditis recurrence during the RW period; secondary efficacy end points were proportion of patients maintaining clinical response, percentage of days with NRS ≤2, and percentage of patients with no-to-minimal pericarditis symptoms at week 16 of the RW period. Safety evaluations include adverse event monitoring, physical examinations, and laboratory tests. The RHAPSODY trial will evaluate the efficacy and safety of rilonacept in the treatment of RP to improve outcomes and patient health-related quality of life.
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http://dx.doi.org/10.1016/j.ahj.2020.07.004DOI Listing
October 2020

Prognostic Implications of Multiparametric Magnetic Resonance Imaging and Concomitant Systematic Biopsy in Predicting Biochemical Recurrence After Radical Prostatectomy in Prostate Cancer Patients Diagnosed with Magnetic Resonance Imaging-targeted Biopsy.

Eur Urol Oncol 2020 12 23;3(6):739-747. Epub 2020 Aug 23.

Unit of Urology/Division of Oncology, URI, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Background: The prognostic role of multiparametric magnetic resonance imaging (mpMRI) and systematic biopsy in predicting biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer (PCa) patients has not been addressed yet.

Objective: To develop a risk tool predicting BCR after RP in patients diagnosed with magnetic resonance imaging (MRI)-targeted biopsy.

Design, Setting, And Participants: A total of 804 patients with a clinical suspicion of PCa and positive mpMRI diagnosed with MRI-targeted plus concomitant systematic biopsy treated with RP were identified.

Outcome Measurements And Statistical Analyses: The outcome was represented by BCR defined as two prostate-specific antigen (PSA) values ≥0.2ng/ml after surgery. Multivariable Cox regression analyses assessed the predictors of BCR. A risk tool model based on imaging and biopsy parameters was developed and validated internally. The c-index, calibration plot, and decision curve analyses were used to assess discrimination, calibration, and the net benefit associated with its use in predicting BCR at 36 mo.

Results And Limitations: Median (interquartile range) follow-up was 28 (25-29) mo, and 89 patients experienced BCR. The 36-mo BCR-free survival rate was 89%. The maximum diameter of the index lesion and seminal vesicle invasion (SVI) at mpMRI as well as the presence of clinically significant PCa at systematic biopsy (defined as a grade group of >2) were associated with BCR (all p≤0.03). A model based on PSA, Prostate Imaging Reporting and Data System score, SVI at mpMRI, diameter of the index lesion, grade group at MRI-targeted biopsy, and clinically significant PCa at systematic biopsy achieved the highest discrimination (77%) among all clinical models, as well as the European Association of Urology risk groups (62%) and the Cancer of the Prostate Risk Assessment (CAPRA) score (60%). This tool was characterized by excellent calibration at internal validation and the highest net benefit when predicting BCR for the threshold risk between 0% and 30%.

Conclusions: The adoption of predictive models accounting for mpMRI and MRI-targeted biopsy-derived variables and concomitant systematic biopsy would improve clinicians' ability to identify patients at a higher risk of early recurrence after surgery.

Patient Summary: The use of information obtained at multiparametric magnetic resonance imaging (mpMRI), and MRI-targeted and concomitant systematic biopsy would improve clinicians' ability to identify prostate cancer patients at a higher risk of experiencing early biochemical recurrence after surgery.
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http://dx.doi.org/10.1016/j.euo.2020.07.008DOI Listing
December 2020

Tapering Canakinumab Monotherapy in Patients With Systemic Juvenile Idiopathic Arthritis in Clinical Remission: Results From a Phase IIIb/IV Open-Label, Randomized Study.

Arthritis Rheumatol 2021 02 11;73(2):336-346. Epub 2020 Dec 11.

Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, United States.

Objective: To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA).

Methods: The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study.

Results: In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified.

Conclusion: Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin-1 inhibition appears necessary to maintain this response.
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http://dx.doi.org/10.1002/art.41488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898684PMC
February 2021