Publications by authors named "Rocco Papalia"

191 Publications

Biomarkers for Renal Cell Carcinoma Recurrence: State of the Art.

Curr Urol Rep 2021 Apr 22;22(6):31. Epub 2021 Apr 22.

Department of Urology, Campus Bio-Medico University, Rome, Italy.

Purpose Of Review: We aim to summarize the current state of art about the possible use of biomarkers for predicting renal cell carcinoma (RCC) recurrence after curative treatment. In addition, we aim to provide a snapshot about the clinical implication of biomarkers use for follow-up planification.

Recent Findings: A wide variety of biomarkers have been proposed. RCC biomarkers have been individuated in tumoral tissue, blood, and urine. A variety of molecules, including proteins, DNA, and RNA, warrant a good accuracy for RCC recurrence and progression prediction. Their use in prediction models might warrant a better patients' risk stratification. Future prognostic models will probably include a combination of classical features (tumor grade, stage, etc.) and novel biomarkers. Such models might allow a more accurate treatment and follow-up planification.
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http://dx.doi.org/10.1007/s11934-021-01050-0DOI Listing
April 2021

Trends in hospitalisation of Subtalar Joint Arthroereisis in Italy from 2009 to 2016.

Foot Ankle Surg 2021 Apr 5. Epub 2021 Apr 5.

Department of Orthopedic and Trauma Surgery, Campus Bio-Medico University of Rome, Rome, Italy.

Background: Subtalar Joint Arthroereisis (SJA) is the most used technique for the treatment of flexible flatfoot. Limited data are reported to trends of hospitalisation for SJA. This study aimed to estimate annual admissions and the geographical distribution of SJA in young Italian patients from 2009 to 2016.

Methods: Data of this study were collected from the National Hospital Discharge Reports reported at the Italian Ministry of Health. The yearly number of SJA, sex, age and days of hospitalisation were calculated. Public and Private hospitalisations have been analysed individually.

Results: 1.6762 hospitalisations for SJA were performed in Italy during the study period, and the incidence increased from 8.22 to 117.08 (cases/100,000 inhabitants). Men represented the majority of young patients treated by SJA. The mean length of stay was 1.55 ± 0.818 days.

Conclusions: The prevalence of admissions of young patients for SJA increases from 2009 to 2016. The majority of the procedure was performed in public hospitals, but a shorter length of stay was reported in patients treated in private hospitals (p < 0.001). This study highlighted the limits of ICD-9; in fact, difficulties in procedure codification and heterogeneity in diagnosis and procedures performed were reported.
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http://dx.doi.org/10.1016/j.fas.2021.03.021DOI Listing
April 2021

Bone fragility in patients with diabetes mellitus: A consensus statement from the working group of the Italian Diabetes Society (SID), Italian Society of Endocrinology (SIE), Italian Society of Gerontology and Geriatrics (SIGG), Italian Society of Orthopaedics and Traumatology (SIOT).

Nutr Metab Cardiovasc Dis 2021 Feb 4. Epub 2021 Feb 4.

Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, Italy; Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Milan, Italy.

Bone fragility is one of the possible complications of diabetes, either type 1 (T1D) or type 2 (T2D). Bone fragility can affect patients of different age and with different disease severity depending on type of diabetes, disease duration and the presence of other complications. Fracture risk assessment should be started at different stages in the natural history of the disease depending on the type of diabetes and other risk factors. The risk of fracture in T1D is higher than in T2D, imposing a much earlier screening and therapeutic intervention that should also take into account a patient's life expectancy, diabetes complications etc. The therapeutic armamentarium for T2D has been enriched with drugs that may influence bone metabolism, and clinicians should be aware of these effects. Considering the complexity of diabetes and osteoporosis and the range of variables that influence treatment choices in a given individual, the Working Group on bone fragility in patients with diabetes mellitus has identified and issued recommendations based on the variables that should guide screening of bone fragility and management of diabetes and bone fragility: (A)ge, (B)MD, (C)omplications, (D)uration of disease, & (F)ractures (ABCD&F). Consideration of these parameters may help clinicians identify the best time for screening, the appropriate glycaemic target and anti-osteoporosis drug for patients with diabetes at risk of or with bone fragility.
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http://dx.doi.org/10.1016/j.numecd.2021.01.019DOI Listing
February 2021

A Hyaluronan and Platelet-Rich Plasma Hydrogel for Mesenchymal Stem Cell Delivery in the Intervertebral Disc: An Organ Culture Study.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Laboratory for Regenerative Orthopaedics, Orthopaedic and Trauma Surgery Unit, Departmental Faculty of Medicine and Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.

The purpose of the present pilot study was to evaluate the effect of a hydrogel composed of hyaluronic acid (HA) and platelet-rich plasma (PRP) as a carrier for human mesenchymal stem cells (hMSCs) for intervertebral disc (IVD) regeneration using a disc organ culture model. HA was mixed with batroxobin (BTX) and PRP to form a hydrogel encapsulating 1 × 10 or 2 × 10 hMSCs. Bovine IVDs were nucleotomized and filled with hMSCs suspended in ~200 μL of the PRP/HA/BTX hydrogel. IVDs collected at day 0 and nucleotomized IVDs with no hMSCs and/or hydrogel alone were used as controls. hMSCs encapsulated in the hydrogel were also cultured in well plates to evaluate the effect of the IVD environment on hMSCs. After 1 week, tissue structure, scaffold integration, hMSC viability and gene expression of matrix and nucleus pulposus (NP) cell markers were assessed. Histological analysis showed a better preservation of the viability of the IVD tissue adjacent to the gel in the presence of hMSCs (~70%) compared to the hydrogel without hMSCs. Furthermore, disc morphology was maintained, and the hydrogel showed signs of integration with the surrounding tissues. At the gene expression level, the hydrogel loaded with hMSCs preserved the normal metabolism of the tissue. The IVD environment promoted hMSC differentiation towards a NP cell phenotype by increasing cytokeratin-19 (KRT19) gene expression. This study demonstrated that the hydrogel composed of HA/PRP/BTX represents a valid carrier for hMSCs being able to maintain a good cell viability while stimulating cell activity and NP marker expression.
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http://dx.doi.org/10.3390/ijms22062963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999916PMC
March 2021

2019 Marathon of Rome. Hamstring injuries in long distance runners: influence of age, gender, weight, height, numbers of marathon and impact profile.

J Sports Med Phys Fitness 2021 Feb 15. Epub 2021 Feb 15.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University, Rome, Italy.

Background: Hamstring diseases are one of the most widespread diseases in athletes, especially in runners, sprinters, and endurance athletes. Notwithstanding the importance of the problem, risk factors are still marginally known. This transversal study analyzes the correlation between Hamstring tendinopathy and hamstring strains and age, gender, weight, height, number of marathons, and impact profile in athletes who took part in the 2019 Rome Marathon.

Methods: At the 2019 Marathon of Rome, 700 runners (484 males and 216 females; mean age: 43.6 years, range 17-80 years) filled the VISA-H and FASH questionnaires. An adequately skilled orthopedic surgeon made a diagnosis of Hamstring tendinopathy and Hamstring strain injuries in line with clinical criteria.

Results: A diagnosis of Hamstring tendinopathy was made in 537 participants while in 624 of hamstring strains. There was evidence of a positive correlation statistically significant between age, weight and impact profile with Hamstring strain injuries, while there was no association between sex and number of marathons and the Hamstring strains. No statistically significant positive correlation was found between all of the parameters analyzed and VISA-H. The association between VISA-H score and FASH score has resulted statistically significant.

Conclusions: In marathon athletes, there was not found evidence of a statistically significant correlation between gender, weight, height, number of marathons, impact profile and Hamstring tendinopathy. Nonetheless, age, weight and impact profile were associated with Hamstring strains, while sex and number of marathons had not shown statistically significant positive association with Hamstring strain injuries.
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http://dx.doi.org/10.23736/S0022-4707.21.12027-4DOI Listing
February 2021

Nutritional Therapy for Athletes with Diabetes.

J Funct Morphol Kinesiol 2020 Nov 13;5(4). Epub 2020 Nov 13.

Department of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, 00128 Rome, Italy.

Diabetes is a worldwide disease also affecting the sports field. The two main forms of diabetes, namely type 1 diabetes (T1D) and type 2 diabetes (T2D), differ in both their pathological and pharmacological characteristics and thus require a distinct nutritional treatment. Diet plays an important role in the management of athletes with diabetes and is crucial to achieving their best performance. This review aims to investigate the objectives of nutritional therapy before, during and after training, in order to improve the best composition of macronutrients during meals. In this review, we provide a brief overview of recent studies about nutritional approaches to people with diabetes for performance optimization and for the control of diabetes-related complications. Thereafter, we discuss the differences between macronutrients and dietary intake before, during and after training. It can be concluded that each sport has particular characteristics in terms of endurance and power, hence demanding a specific energy expenditure and consequent nutritional adjustments. Therefore, the management of athletes with diabetes must be personalized and supported by medical professionals, including a diabetologist, physiologist and a nutritionist.
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http://dx.doi.org/10.3390/jfmk5040083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739333PMC
November 2020

Beneficial Effects of Physical Activity in Diabetic Patients.

J Funct Morphol Kinesiol 2020 Sep 4;5(3). Epub 2020 Sep 4.

Department of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy.

One of the main goals of diabetic therapy is to achieve the best metabolic control to prevent the development and progression of potential complications. A multidisciplinary approach characterized by the combination of diet, physical activity (PA) and drug therapy with oral and injectable (non-insulin) pharmacological agents, is desirable to optimize metabolic control. The aim of this review is to explain the contribution of PA and its beneficial effects on patients affected by type 1 (T1D) and type 2 diabetes (T2D). We provide an overview of evidence on the effects of PA for the main two types of diabetes mellitus (DM) to identify the right level of PA to be recommended. We discuss the physiological and clinical role of PA in people with DM. It can be concluded that the objective of antidiabetic therapy should be the achievement and optimization of metabolic control through a multidisciplinary approach involving non-pharmacological therapy such as diet and PA, which has a crucial role.
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http://dx.doi.org/10.3390/jfmk5030070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7739324PMC
September 2020

How Can the COVID-19 Pandemic Lead to Positive Changes in Urology Residency?

Front Surg 2020 24;7:563006. Epub 2020 Nov 24.

Department of Urology, IEO European Institute of Oncology IRCCS, Milan, Italy.

The COVID-19 outbreak, in a few weeks, overloaded Italian hospitals, and the majority of medical procedures were postponed. During the pandemic, with hospital reorganization, clinical and learning activities performed by residents suffered a forced remodulation. The objective of this study is to investigate how urology training in Italy has been affected during the COVID-19 era. In this multi-academic study, we compared residents' training during the highest outbreak level with their previous activity. Overall 387 (67.1%) of the 577 Italian Urology residents participated in a 72-h anonymous online survey with 36 items sent via email. The main outcomes were clinical/surgical activities, social distancing, distance learning, and telemedicine. Clinical and learning activity was significantly reduced for the overall group, and after categorizing residents as those working only in COVID hospitals, both "junior" and "senior" residents, and those working in any of three geographical areas created (Italian regions were clustered in three major zones according to the prevalence of COVID-19). A significant decrease in outpatient activity, invasive diagnostic procedures, and endoscopic and major surgeries was reported. Through multivariate analysis, the specific year of residency has been found to be an independent predictor for all response modification. Being in zone 3 and zone 2 and having "senior" resident status were independent predictors associated with a lower reduction of the clinical and learning activity. Working in a COVID hospital and having "senior" resident status were independent predictors associated with higher reduction of the outpatient activity. Working in zone 3 and having "senior" resident status were independent predictors of lower and higher outpatient surgical activity, respectively. Working in a COVID hospital was an independent predictor associated with robotic surgical activity. The majority of residents reported that distance teaching and multidisciplinary virtual meetings are still not used, and 44.8% reported that their relationships with colleagues decreased. The COVID-19 pandemic presents an unprecedented challenge, including changes in the training and education of urology residents. The COVID era can offer an opportunity to balance and implement innovative solutions that can bridge the educational gap and can be part of future urology training.
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http://dx.doi.org/10.3389/fsurg.2020.563006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732553PMC
November 2020

Single-Dose Intra-Articular Administration of a Hybrid Cooperative Complex of Sodium Hyaluronate and Sodium Chondroitin in the Treatment of Symptomatic Hip Osteoarthritis: A Single-Arm, Open-Label, Pilot Study.

Rheumatol Ther 2021 Mar 27;8(1):151-165. Epub 2020 Nov 27.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

Introduction: Intra-articular (i.a.) hyaluronic acid is an accepted conservative therapy for knee osteoarthritis (OA). This study evaluated the safety and efficacy of a single i.a. injection of an innovative formulation of sodium hyaluronate 2.4% plus sodium chondroitin non-sulphated 1.6% of biotechnological origin (HA-SC) for the treatment of patients with radiographically confirmed symptomatic hip OA and moderate-to-severe pain.

Methods: In this prospective, multicenter, open-label, pilot study, HA-SC was administered using a standard ultrasound-guided procedure. Adverse events, global/local evaluation of tolerability, and use of rescue analgesics were recorded. Efficacy endpoints included visual analogue scale (VAS) measurement of hip pain, changes in Lequesne's algofunctional Index, and assessment of global status.

Results: Treatment was well tolerated; adverse device events of moderate-to-severe intensity, most commonly, injection site pain/localized arthralgia occurred in 20.8% of subjects. Global evaluation of tolerability was rated as excellent or good (75.0%), fair (16.7%), and poor (8.3%) by subjects and 77.1, 14.6, and 8.3%, respectively, by investigators. There was a rapid and significant decrease in hip pain after a single injection; VAS pain score decreased from a mean of 67.5 mm at baseline to 29.3 mm by day 7, with the effects sustained during 6 months of follow-up (P < 0.0001). There were significant improvements in Lequesne's Index for hip OA total scores at all time points during follow-up (P < 0.0001). The majority of subjects reported 'Very much improved' or 'Slightly improved' global improvement at any time point. Use of rescue paracetamol was generally low.

Conclusions: A single i.a. injection of an innovative HA-SC formulation was well tolerated, safe, and effective in the treatment of symptomatic hip OA.
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http://dx.doi.org/10.1007/s40744-020-00255-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7991040PMC
March 2021

The impact of type 2 diabetes on the development of tendinopathy.

Diabetes Metab Res Rev 2020 Oct 27. Epub 2020 Oct 27.

Department of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Rome, Italy.

Tendinopathy is a chronic and often painful condition affecting both professional athletes and sedentary subjects. It is a multi-etiological disorder caused by the interplay among overload, ageing, smoking, obesity (OB) and type 2 diabetes (T2D). Several studies have identified a strong association between tendinopathy and T2D, with increased risk of tendon pain, rupture and worse outcomes after tendon repair in patients with T2D. Moreover, consequent immobilization due to tendon disorder has a strong impact on diabetes management by reducing physical activity and worsening the quality of life. Multiple investigations have been performed to analyse the causal role of the individual metabolic factors occurring in T2D on the development of tendinopathy. Chronic hyperglycaemia, advanced glycation end-products, OB and insulin resistance have been shown to contribute to the development of diabetic tendinopathy. This review aims to explore the relationship between tendinopathy and T2D, in order to define the contribution of metabolic factors involved in the degenerative process and to discuss possible strategies for the clinical management of diabetic tendinopathy.
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http://dx.doi.org/10.1002/dmrr.3417DOI Listing
October 2020

Three-dimensional, Scaffold-Free, Autologous Chondrocyte Transplantation: A Systematic Review.

Orthop J Sports Med 2020 Sep 21;8(9):2325967120951152. Epub 2020 Sep 21.

University Campus Bio-Medico of Rome, Department of Orthopaedic and Trauma Surgery, Rome, Italy.

Background: A 3-dimensional, scaffold-free, and completely autologous form of chondrocyte transplantation (ACT3D) has been developed and applied in clinical practice in the past decade to overcome disadvantages of previous-generation procedures.

Purpose: To document and analyze the available literature on the results of ACT3D in the treatment of articular chondral lesions in the knee and hip joints.

Study Design: Systematic review; Level of evidence, 4.

Methods: All studies published in English addressing ACT3D were identified and included those that fulfilled the following criteria: (1) level 1 through 4 evidence, (2) measures of radiological or functional/clinical outcome, and (3) outcome related to cartilage lesions of the knee and hip joints.

Results: A total of 10 studies were selected: 2 randomized controlled trials, 1 cohort study, and 7 case series. The studies revealed significant increases in patients' subjective quality of life, satisfaction, pain reduction, and improvement in joint function at short- to medium-term follow-up. Magnetic resonance imaging-assisted examination and second-look arthroscopy showed a hyaline-like repair tissue with a high degree of defect filling and integration.

Conclusion: ACT3D shows promising results in the therapy of articular cartilage defects in the knee as well as in the hip, but well-designed, long-term studies are lacking. ACT3D might have relevant advantages over common matrix-associated autologous chondrocyte transplantation products, but systematic evaluation and randomized controlled studies are crucial to verify the potential of this tissue-engineered approach.
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http://dx.doi.org/10.1177/2325967120951152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509739PMC
September 2020

The Effects of Physical Exercise on Balance and Prevention of Falls in Older People: A Systematic Review and Meta-Analysis.

J Clin Med 2020 Aug 11;9(8). Epub 2020 Aug 11.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, 00128 Rome, Italy.

The aims of this systematic review and meta-analysis were to evaluate the effects of physical exercise on static and dynamic balance in the elderly population, and to analyze the number of falls and fallers. A systematic literature search was conducted using PubMed-Medline, Cochrane Central, and Google Scholar to select randomized clinical trials that analyzed the role of exercise on balance and fall rate in patients aged 65 or older. Sixteen articles were included in this review. Applying the Cochrane risk-of-bias tool, three studies were determined to be at low risk of bias, nine at unclear risk of bias, and four at high risk of bias. The meta-analysis showed improvements in dynamic balance ( = 0.008), static balance ( = 0.01), participants' fear of falling ( = 0.10), balance confidence ( = 0.04), quality of life ( = 0.08), and physical performance ( = 0.30) in patients who underwent physical exercise compared to controls. The analysis of the total numbers of falls showed a decreased likelihood of falls in patients who participated in exercise programs ( = 0.0008). Finally, the number of patients who fell at least once was significantly reduced in the intervention group ( = 0.02). Physical exercise is an effective treatment to improve balance and reduce fall rates in the elderly.
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http://dx.doi.org/10.3390/jcm9082595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466089PMC
August 2020

Sclerostin Regulation, Microarchitecture, and Advanced Glycation End-Products in the Bone of Elderly Women With Type 2 Diabetes.

J Bone Miner Res 2020 12 2;35(12):2415-2422. Epub 2020 Oct 2.

Unit of Endocrinology and Diabetes, Departmental Faculty of Medicine and Surgery, Campus Bio-Medico University of Rome, Rome, Italy.

Increased circulating sclerostin and accumulation of advanced glycation end-products (AGEs) are two potential mechanisms underlying low bone turnover and increased fracture risk in type 2 diabetes (T2D). Whether the expression of the sclerostin-encoding SOST gene is altered in T2D, and whether it is associated with AGEs accumulation or regulation of other bone formation-related genes is unknown. We hypothesized that AGEs accumulate and SOST gene expression is upregulated in bones from subjects with T2D, leading to downregulation of bone forming genes (RUNX2 and osteocalcin) and impaired bone microarchitecture and strength. We obtained bone tissue from femoral heads of 19 T2D postmenopausal women (mean glycated hemoglobin [HbA1c] 6.5%) and 73 age- and BMI-comparable nondiabetic women undergoing hip replacement surgery. Despite similar bone mineral density (BMD) and biomechanical properties, we found a significantly higher SOST (p = .006) and a parallel lower RUNX2 (p = .025) expression in T2D compared with non-diabetic subjects. Osteocalcin gene expression did not differ between T2D and non-diabetic subjects, as well as circulating osteocalcin and sclerostin levels. We found a 1.5-fold increase in total bone AGEs content in T2D compared with non-diabetic women (364.8 ± 78.2 versus 209.9 ± 34.4 μg quinine/g collagen, respectively; p < .001). AGEs bone content correlated with worse bone microarchitecture, including lower volumetric BMD (r = -0.633; p = .02), BV/TV (r = -0.59; p = .033) and increased trabecular separation/spacing (r = 0.624; p = .023). In conclusion, our data show that even in patients with good glycemic control, T2D affects the expression of genes controlling bone formation (SOST and RUNX2). We also found that accumulation of AGEs is associated with impaired bone microarchitecture. We provide novel insights that may help understand the mechanisms underlying bone fragility in T2D. © 2020 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4153DOI Listing
December 2020

Minimally invasive strategies for the treatment of prostate cancer recurrence after radiation therapy: a systematic review.

Minerva Urol Nefrol 2020 Oct 4;72(5):563-578. Epub 2020 Aug 4.

Department of Urology, Campus Bio-Medico University, Rome, Italy.

Introduction: The aim of this review was to conduct a comprehensive analysis of the role of minimally invasive salvage modalities in radio-recurrent prostate cancer and the associated clinical outcomes and toxicity profiles.

Evidence Acquisition: A systematic review of the current literature was conducted through the Medline and NCBI PubMed, Scopus databases in January 2020. All papers published after 2000, concerning studies conducted on humans for radio-recurrent prostate cancer were considered for the review.

Evidence Synthesis: Overall, 545 studies were identified. After duplicate exclusion, initial screening, and eligibility evaluation, a total of 80 studies were included in the qualitative analysis, corresponding to a cohort of 6681 patients. The median age at initial diagnosis ranged from 59 to 75.5. Pre-treatment PSA ranged from 6.2 to 27.4 ng/mL. All patients underwent primary radiotherapy for localized prostate cancer. Cryotherapy, Brachytherapy, EBRT, HIFU were the minimally invasive options mostly used as salvage therapy. They showed to be promising approaches for recurrent prostate cancer (PCa) control, with acceptable toxicities.

Conclusions: Minimally invasive therapeutic options offer promising results in terms of biochemical control in the local recurrence setting. Unfortunately, the absence of high quality and comparative studies makes it difficult to establish which method is the best in terms of oncological and safety outcomes.
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http://dx.doi.org/10.23736/S0393-2249.20.03783-2DOI Listing
October 2020

Management of erectile dysfunction following robot-assisted radical prostatectomy: a systematic review.

Minerva Urol Nefrol 2020 Oct 4;72(5):543-554. Epub 2020 Aug 4.

European Associations of Urology-European Society of Residents in Urology (EAU-ESRU).

Introduction: We aimed to summarize evidences about the efficacy of available treatments for erectile disfunction after robotic assisted radical prostatectomy (RARP).

Evidence Acquisition: A systematic literature review searching on PubMed (Medline), Scopus, and Web of Science databases was performed in December 2019. PRISMA guidelines were followed. Population consisted of patients with erectile disfunction after RARP (P), conservative and surgical intervention were considered of interest (I). No comparator was considered mandatory (C). Outcomes of interest were the recovery of erectile function after conservative treatments and sexual function after surgical treatments (O).

Evidence Synthesis: Eleven studies were included. Seven studies focused on the use of phosphodiesterase-5 inhibitors (PDE5i) alone (five studies) or associated with other treatments (two studies). All the studies confirmed the efficacy of PDE5i, while the most promising association is with vacuum pump erectile devices. Two studies investigated topical treatments, namely low intensity extracorporeal shock wave therapy and alprostadil. Low intensity extracorporeal shock wave therapy may be a promising option in patients in whom nerve-sparing surgery was performed. The use of alprostadil could be an effective alternative to intracorporeal injection in those who underwent non-nerve-sparing surgery. One study focused and confirmed the efficacy of penile implants. Furthermore, one study reported the efficacy of a multi-modal treatment with preoperative medication, showing the benefits of a multimodal approach.

Conclusions: Penile rehabilitation with PDE5i is effective after nerve sparing RARP. The association of PDE5i with vacuum devices could led to a faster recovery. A multimodal approach with preoperative specific care seems to be effective to fasten erectile function recovery.
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http://dx.doi.org/10.23736/S0393-2249.20.03780-7DOI Listing
October 2020

Triggers for delayed intervention in patients with small renal masses undergoing active surveillance: a systematic review.

Minerva Urol Nefrol 2020 Aug;72(4):389-407

European Society of Residents in Urology (ESRU), Arnhem, the Netherlands.

Introduction: Patients with small renal masses (SRM) can be exposed to overdiagnosis and overtreatment. As such, active surveillance (AS) is recommended by all Guidelines for selected patients. However, it remains underutilized. One key reason is the lack of consensus on the factors prompting delayed intervention (DI). Herein we provide an updated overview of the triggers for DI in patients with SRMs initially undergoing AS.

Evidence Acquisition: A systematic review of the English-language literature was performed according to the PRISMA statement recommendations using the MEDLINE, Cochrane Central Register of Controlled Trials and Web of Science databases.

Evidence Synthesis: Overall, 10 prospective studies including 1870 patients were included. Median patient age ranged between 64 and 75 years, while median tumor size between 1.7 cm to 2.3 cm. The proportion of cystic SRMs ranged from 0% to 30%. Baseline renal tumor biopsy was performed in 7-45.2% of patients. Among these, malignant histology was found in 28.5%-83.3% of cases. Overall, the median growth rate of SRMs ranged between 0.10 and 0.27 cm/year. The proportion of patients undergoing DI ranged between 7% and 44%, after a median AS period of 12-27 months. The most commonly performed type of DI was surgery. Of resected SRMs, 0% to 30% were benign. The actual triggers for DI were either tumor-related (renal mass growth, stage progression, development of local complications/symptoms) or patient-related (patient preference, improved medical conditions, or qualification for other surgical procedures). At a median follow-up of 21.7 - 57-6 months, the proportion of patients experiencing metastatic disease, cancer-specific and other-cause mortality was 0-3.1%, 0-4% and 0-45.6%, respectively.

Conclusions: The available evidence shows that both tumor-related and patient-related factors are ultimate triggers for DI in patients with SRMs undergoing AS. However, the level of evidence is still low and further research is needed to individualize AS strategies according to both tumor biology and patient-related characteristics and values.
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http://dx.doi.org/10.23736/S0393-2249.20.03870-9DOI Listing
August 2020

Implementation and strategies to ensure adequate coordination within a Urology Department during the COVID-19 pandemic.

Int Braz J Urol 2020 07;46(suppl.1):170-180

Department of Urology, Campus Bio-Medico University of Rome, Rome, Italy.

Purpose: to provide an update on the management of a Urology Department during the COVID-19 outbreak, suggesting strategies to optimize assistance to the patients, to implement telemedicine and triage protocols, to define pathways for hospital access, to reduce risk of contagious inside the hospital and to determine the role of residents during the pandemic.

Materials And Methods: In May the 6th 2020 we performed a review of the literature through online search engines (PubMed, Web of Science and Science Direct). We looked at recommendations provided by the EAU and ERUS regarding the management of urological patients during the COVID-19 pandemic. The main aspects of interest were: the definition of deferrable and non-deferrable procedures, Personal Protective Equipment (PPE) and hospital protocols for health care providers, triage, hospitalization and surgery, post-operative care training and residents' activity. A narrative summary of guidelines and current literature for each point of interest was performed.

Conclusion: In the actual Covid-19 scenario, while the number of positive patients globally keep on rising, it is fundamental to embrace a new way to deliver healthcare and to overcome challenges of physical distancing and self-isolation. The use of appropriate PPE, definite pathways to access the hospital, the implementation of telemedicine protocols can represent effective strategies to carry on delivering healthcare.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.S122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719985PMC
July 2020

How Targeted Therapy Influence Renal Surgery for Renal Cell Carcinoma.

Curr Drug Targets 2020 ;21(15):1550-1557

Department of Urology, Campus Biomedico, University of Rome, Rome, Italy

Between the end of 2005 and the beginning of 2006, several new target therapies have been introduced for the treatment of renal cell carcinoma. In this review, we aimed to explore and summarize the main findings of the use of systemic treatment and its effect on surgery in patients with renal cell carcinoma. We identified three different settings: neoadjuvant and adjuvant settings as well as the association of systemic therapy with surgery in the metastatic renal cell carcinoma patients. Neoadjuvant target therapy with tyrosine kinase inhibitor may facilitate the tumor resection and reduce the overall tumor diameter and its complexity. However, most of the evidence is from small phase I or II clinical trials and results are often conflicting without determining a relevant change in the main parameters investigated, such as tumor complexity. In the adjuvant setting, results from pivotal trials investigating the use of tyrosine kinase inhibitors for patients with non-metastatic RCC treated with surgery discourage this practice. Indeed, most of the evidence from single clinical trials and pooled results from meta-analysis failed to find a survival advantage with the use of adjuvant systemic treatment. To date, an improvement of clinical outcomes after systemic targeted therapies could be only found in the setting of cytoreductive nephrectomy. However, the CARMENA and SURTIME trials recently confirmed the evidence against a surgical treatment in patients with mRCC and poor prognosis. In the near future, significant changes may be introduced by the use of immunotherapies.
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http://dx.doi.org/10.2174/1389450121666200704150933DOI Listing
January 2020

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering.

Stem Cells Int 2019 10;2019:2376172. Epub 2019 Sep 10.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.

Low back pain (LBP) in one of the most disabling symptoms affecting nearly 80% of the population worldwide. Its primary cause seems to be intervertebral disc degeneration (IDD): a chronic and progressive process characterized by loss of viable cells and extracellular matrix (ECM) breakdown within the intervertebral disc (IVD) especially in its inner region, the nucleus pulposus (NP). Over the last decades, innovative biological treatments have been investigated in order to restore the original healthy IVD environment and achieve disc regeneration. Mesenchymal stem cells (MSCs) have been widely exploited in regenerative medicine for their capacity to be easily harvested and be able to differentiate along the osteogenic, chondrogenic, and adipogenic lineages and to secrete a wide range of trophic factors that promote tissue homeostasis along with immunomodulation and anti-inflammation. Several and preclinical studies have demonstrated that MSCs are able to acquire a NP cell-like phenotype and to synthesize structural components of the ECM as well as trophic and anti-inflammatory mediators that may support resident cell activity. However, due to its unique anatomical location and function, the IVD presents distinctive features: avascularity, hypoxia, low glucose concentration, low pH, hyperosmolarity, and mechanical loading. Such conditions establish a hostile microenvironment for both resident and exogenously administered cells, which limited the efficacy of intradiscal cell therapy in diverse investigations. This review is aimed at describing the characteristics of the healthy and degenerated IVD microenvironment and how such features influence both resident cells and MSC viability and biological activity. Furthermore, we focused on how recent research has tried to overcome the obstacles coming from the IVD microenvironment by developing innovative cell therapies and functionalized bioscaffolds.
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http://dx.doi.org/10.1155/2019/2376172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294366PMC
September 2019

What is the role of residents during a pandemic?

Minerva Urol Nefrol 2020 06;72(3):387-388

Department of Urology, Campus Bio-Medico, University of Rome, Rome, Italy.

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http://dx.doi.org/10.23736/S0393-2249.20.03903-XDOI Listing
June 2020

Urologic surgery in a safe hospital during the COVID-19 pandemic scenario.

Minerva Urol Nefrol 2020 Jun 22. Epub 2020 Jun 22.

Department of Urology, Campus Bio-medico, University of Rome, Rome, Italy -

The COVID-19 pandemic induced a global emergency that overwhelmed most hospitals around the world. Access to Hospitals has been restricted to selective oncological and urgent patients to minimize surgeries requiring Intensive Care Unit care. All other kind of non- urgent and benign surgeries have been rescheduled. The burden of oncological and urgent cases on the healthcare system has increased. We have been asked to become the referral center for major oncological and urgent urological surgeries, increasing our surgical volume. Through meticulous hospital protocols on PPE, use of nasopharyngeal swabs, controlled hospital access and the prompt management of suspected/positive cases, we were able to perform 31% more urological surgical procedures during the COVID-19 pandemic compared to the same period in 2019. We observed a 72% increase in oncological surgical procedures and 150% in urgent procedures. Our experience shows how the management of oncological and urgent cases can be maintained during unexpected, global emergencies, such as COVID-19.
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http://dx.doi.org/10.23736/S0393-2249.20.03923-5DOI Listing
June 2020

Endourology (Lithiasis). Management, surgical considerations and follow-up of patients in the COVID-19 era.

Int Braz J Urol 2020 07;46(suppl.1):39-49

Department of Urology, Campus Biomédico, University of Rome, Rome, Italy.

Purpose: To provide recommendations on the endourological management of lithiasis in the scenario of the COVID-19 pandemic.

Materials And Methods: A non-systematic review in PubMed and the grey literature, as well as recommendations by a panel of stakeholders was made, regarding management, surgical considerations and follow-up of patients affected by lithiasis in the COVID-19 era.

Results: Under the current outbreak and COVID-19 pandemic scenario, patients affected by lithiasis should be prioritized into low, intermediate and high risk categories, to decide their delay and save resources, healthcare personnel, beds and ventilators. However, patients with potentially serious septic complications need emergency interventions. The possibility of performing or restarting elective activity depends on local conditions, the availability of beds and ventilators, and the implementation of screening protocols in the context of the COVID-19 pandemic. Delaying lithiasis surgery and increasing waiting lists will have consequences and will require considerable additional effort. Teleconsultation may be useful in guiding these patients, reducing visits and unnecessary exposure.

Conclusions: categorization and prioritization of patients affected by lithiasis is crucial for management, surgical selection and follow-up. Protocols, measures and additional efforts should be carried out in the current situation of the COVID-19 pandemic.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.S105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719981PMC
July 2020

COVID-19's Impact on Italian Urology.

Int Braz J Urol 2020 07;46(suppl.1):26-33

Department of Urology, Campus Biomédico, University of Rome, Rome, Italy.

The COVID-19 pandemic has impacted our lives, our habits and our healthcare system. Italy is one of the countries affected first and more aggressively from the outbreak. Our rapidity has been guide for other healthcare systems from around the World. We describe the impact of COVID-19 on Urology, how the Urological scientific community responded to the emergency and our experience in a high-volume Roman University hospital. The aim of our work is to share our experience providing suggestions for other global hospitals on how to manage the COVID-19 emergency.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.S103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719978PMC
July 2020

Irisin Recovers Osteoarthritic Chondrocytes In Vitro.

Cells 2020 06 17;9(6). Epub 2020 Jun 17.

Laboratory of Regenerative Orthopaedics, Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128 Rome, Italy.

Physical exercise favors weight loss and ameliorates articular pain and function in patients suffering from osteoarthritis. Irisin, a myokine released upon muscle contraction, has demonstrated to yield anabolic effects on different cell types. This study aimed to investigate the effect of irisin on human osteoarthritic chondrocytes (hOAC) in vitro. Our hypothesis was that irisin would improve hOAC metabolism and proliferation. Cells were cultured in growing media and then exposed to either phosphate-buffered saline (control group) or human recombinant irisin (experimental group). Cell proliferation, glycosaminoglycan content, type II/X collagen gene expression and protein quantification as well as p38/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK), protein kinase B (Akt), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) involvement were evaluated. Furthermore, gene expression of interleukin (IL)-1 and -6, matrix metalloproteinase (MMP)-1 and -13, inducible nitric oxide synthase (iNOS), and tissue inhibitor of matrix metalloproteinases (TIMP)-1 and -3 were investigated following irisin exposure. Irisin increased hOAC cell content and both type II collagen gene expression and protein levels, while decreased type X collagen gene expression and protein levels. Moreover, irisin decreased IL-1, IL-6, MMP-1, MMP-13 and iNOS gene expression, while increased TIMP-1 and TIMP-3 levels. These effects seemed to be mediated by inhibition of p38, Akt, JNK and NFκB signaling pathways. The present study suggested that irisin may stimulate hOAC proliferation and anabolism inhibiting catabolism through p38, Akt, JNK, and NFκB inactivation in vitro, demonstrating the existence of a cross-talk between muscle and cartilage.
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http://dx.doi.org/10.3390/cells9061478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348865PMC
June 2020

Metastasis-directed therapy and prostate-targeted therapy in oligometastatic prostate cancer: a systematic review.

Minerva Urol Nefrol 2020 Oct 16;72(5):531-542. Epub 2020 Jun 16.

EAU Young Urologist Office (YOU), Arnhem, the Netherlands.

Introduction: The aim of this review was to summarize the available evidence on the role of metastasis-directed therapy (MDT) and/or prostate-targeted therapy (PTT) in the setting of oligometastatic prostate cancer (PCa).

Evidence Acquisition: We searched PubMed, the Web of Science, and the Cochrane Library databases. The following keywords were used: ("prostate cancer" OR "prostate carcinoma" OR "prostate neoplasm" OR "prostate tumor") AND ("oligometastatic" OR "oligometastasis" OR "PSMA") AND ("surgery" OR "prostatectomy" OR "radical prostatectomy" OR "cytoreductive" OR "local treatment" OR "radiotherapy" OR "stereotactic" OR "stereotaxic") AND ("survival" OR "mortality").

Evidence Synthesis: After evaluating the selection criteria, 81 studies were evaluated for our endpoints. We included 22 studies for PTT of synchronous mPCa. There have been no randomized studies on cytoreductive prostatectomy (cRP). Four prospective studies showed that cRP was feasible but did not contribute to a positive effect on overall survival (OS). Regarding PTT-radiotherapy, two randomized controlled phase 3 trials showed that OS was improved in men with a low metastatic burden. Regarding MDT of metachronous lymph node recurrence, we included 29 retrospective studies. For MDT of oligometastases, we included 30 studies. One randomized phase 2 trial showed that androgen deprivation therapy-free survival improved with stereotactic body radiation therapy compared to that with surveillance; however, benefits on OS remain unclear.

Conclusions: We performed a comprehensive overview of the current literature on MDT and PTT. The feasibility of MDT and PTT is supported by several retrospective studies. Nevertheless, there remains a lack of high-quality trials to prove its survival benefits. Results from ongoing prospective trials data are awaited.
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http://dx.doi.org/10.23736/S0393-2249.20.03779-0DOI Listing
October 2020

Bladder Cancer at the time of COVID-19 Outbreak.

Int Braz J Urol 2020 07;46(suppl.1):62-68

Department of Urology, Campus Bio-Medico University of Rome, Rome, Italy.

The COVID-19 outbreak has led to the deferral of a great number of surgeries in an attempt to reduce transmission of infection, free up hospital beds, intensive care and anaesthetists, and limit aerosol-generating procedures. Guidelines and suggestions have been provided to categorize Urological diseases into risk groups and recommendations are available on procedures that can be or cannot be deferred. We aim to summarise updates on diagnosis, treatment and follow up of bladder cancer during the COVID-19 outbreaks.
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http://dx.doi.org/10.1590/S1677-5538.IBJU.2020.S107DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719998PMC
July 2020

Return to Sport Activity in the Elderly Patients after Unicompartmental Knee Arthroplasty: A Systematic Review and Meta-Analysis.

J Clin Med 2020 Jun 5;9(6). Epub 2020 Jun 5.

Deaprtment of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via A. Del Portillo, 21, 00128 Rome, Italy.

In patients with knee osteoarthritis, when only medial or lateral compartment of the knee is involved, unicompartimental knee arthroplasty (UKA) is a reliable option for addressing the symptoms and restore function. The main aim of the present review is to systematically collect the available evidence concerning the return to sport activity in the elderly patients after UKA. An electronic search was carried out on the following databases; Pubmed-Medline, Cochrane central, and Scopus, searching for randomized controlled trials, prospective cohort studies, retrospective case-control studies, and case series. Data concerning the evaluation of the return to sport (RTS) and of functional outcomes in the elderly patients after UKA surgery. MINORS score was used to assess the risk of methodological biases. Odds ratios and raw proportions were used to report the pooled effect of UKA on the return to sport in comparative and non-comparative studies, respectively. Same level RTS in elderly patients was of 86% (pooled return proportion 0.86, 95%CI 0.78, 0.94), showing also better relative RTS and time to RTS of patients undergoing UKA, in comparison to those undergoing TKA. Sport-specific RTS showed that higher return rates were observed for low-impact sports, whereas high-impact sports prevented a full return to activities. UKA is a valid and reliable option for elderly patients to satisfactorily resume their sport practice, especially for low impact activities. The rate of return to sports following UKA is higher than TKA.
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http://dx.doi.org/10.3390/jcm9061756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356230PMC
June 2020

The role of the orthopaedic surgeon in the COVID-19 era: cautions and perspectives.

J Exp Orthop 2020 May 27;7(1):35. Epub 2020 May 27.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 200, 00128, Rome, Italy.

The current coronavirus disease 2019 (COVID-19) pandemic has revolutionized global healthcare in an unprecedented way and with unimaginable repercussions. Resource reallocation, socioeconomic confinement and reorganization of production activities are current challenges being faced both at the national and international levels, in a frame of uncertainty and fear. Hospitals have been restructured to provide the best care to COVID-19 patients while adopting preventive strategies not to spread the infection among healthcare providers and patients affected by other diseases. As a consequence, the concept of urgency and indications for elective treatments have been profoundly reshaped. In addition, several providers have been recruited in COVID-19 departments despite their original occupation, resulting in a profound rearrangement of both inpatient and outpatient care. Orthopaedic daily practice has been significantly affected by the pandemic. Surgical indications have been reformulated, with elective cases being promptly postponed and urgent interventions requiring exceptional attention, especially in suspected or COVID-19 patients. This has made a strong impact on inpatient management, with the need of a dedicated staff, patient isolation and restrictive visiting hour policies. On the other hand, outpatient visits have been limited to reduce contacts between patients and the hospital personnel, with considerable consequences on post-operative quality of care and the human side of medical practice.In this review, we aim to analyze the effect of the COVID-19 pandemic on the orthopaedic practice. Particular attention will be dedicated to opportune surgical indication, perioperative care and safe management of both inpatients and outpatients, also considering repercussions of the pandemic on resident education and ethical implications.
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http://dx.doi.org/10.1186/s40634-020-00255-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250587PMC
May 2020

Return to Sport after Anatomic and Reverse Total Shoulder Arthroplasty in Elderly Patients: A Systematic Review and Meta-Analysis.

J Clin Med 2020 May 22;9(5). Epub 2020 May 22.

Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico University of Rome, 00128 Rome, Italy.

The aim of this systematic review and meta-analysis was to evaluate the rate of return to sport in elderly patients who underwent anatomic (ATSA) and reverse (RTSA) total shoulder arthroplasty, to assess postoperative pain and functional outcomes and to give an overview of postoperative rehabilitation protocols. A systematic search in Pubmed-Medline, Cochrane Library, and Google Scholar was carried out to identify eligible randomized clinical trials, observational studies, or case series that evaluated the rate of return to sport after RTSA or ATSA. Six retrospective studies, five case series, and one prospective cohort study were included in this review. The overall rate of return to sport was 82% (95% CI 0.76-0.88, < 0.01). Patients undergoing ATSA returned at a higher rate (90%) (95% CI 0.80-0.99, < 0.01) compared to RTSA (77%) (95% CI 0.69-0.85, < 0.01). Moreover, the results showed that patients returned to sport at the same or a higher level in 75% of cases. Swimming had the highest rate of return (84%), followed by fitness (77%), golf (77%), and tennis (69%). Thus, RTSA and ATSA are effective to guarantee a significative rate of return to sport in elderly patients. A slightly higher rate was found for the anatomic implant.
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http://dx.doi.org/10.3390/jcm9051576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291255PMC
May 2020