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Background: Holmium laser enucleation of the prostate (HoLEP) is considered a safe and effective treatment in case of bladder outlet obstruction (BOO). Despite technical execution has evolved over ...

Objectives The Rotterdam Prostate Cancer Risk calculator (RPCRC) has been validated in the past years. Recently a new version including multiparametric magnetic resonance imaging (mpMRI) data has been released. The aim of our study was to analyze the performance of the mpMRI RPCRC app. Methods A series of men undergoing prostate biopsies were enrolled in eleven Italian centers. Indications for prostate biopsy included: abnormal Prostate specific antigen levels (PSA>4 ng/ml), abnormal DRE and abnormal mpMRI. Patients’ characteristics were recorded. Prostate cancer (PCa) risk and high-grade PCa risk were assessed using the RPCRC app. The performance of the mpMRI RPCRC in the prediction of cancer and high-grade PCa was evaluated using receiver operator characteristics, calibration plots and decision curve analysis. Results Overall, 580 patients were enrolled: 404/580 (70%) presented PCa and out of them 224/404 (55%) presented high-grade PCa. In the prediction of cancer, the RC presented good discrimination (AUC = 0.74), poor calibration (p = 0.01) and a clinical net benefit in the range of probabilities between 50 and 90% for the prediction of PCa (Fig. 1). In the prediction of high-grade PCa, the RC presented good discrimination (AUC = 0.79), good calibration (p = 0.48) and a clinical net benefit in the range of probabilities between 20 and 80% (Fig. 1). Conclusions The Rotterdam prostate cancer risk App accurately predicts the risk of PCa and particularly high-grade cancer. The clinical net benefit is wide for high-grade cancer and therefore its implementation in clinical practice should be encouraged. Further studies should assess its definitive role in clinical practice.

Introduction: The role of reservoir position was investigated in this series of patients treated with three-pieces penile prosthesis implantation (PPI). The outcomes and the patients’ reported quality of life after insertion of the balloon in the retropubic space, or the Retzius’s space (SOR), were compared with the outcomes of patients who received an intraperitoneal implantation (IP). The study aimed to analyze how the anatomy of the SOR influenced the long-term results of PPI, especially in patients who have been previously exposed to pelvic surgery or radiotherapy. The SOR has usually been identified as ideal for concealing and protecting the reservoir; nevertheless, an increasing rate of patients that ask for a PPI do not conserve the typical favorable characteristic of the SOR. In these cases, the tissue alteration can cause a higher rate of undesired events and can impair the satisfaction from device use. In the recent literature, few articles focus on the topic of reservoir position and very poor information is available about the results of the IP insertion. Materials: Our cohort of patients was retrospectively inspected; the two different subgroups, according to the reservoir position (SOR or IP) were evaluated considering the pre-operative condition, the post-operative complication, the development of undesired events or uncomfortable sensations during the follow-up. The quality of life after PPI was observed as well, with a questionnaire specifically developed for patients treated with PPI. The surgical technique adopted for the intraperitoneal implantation was described. Results: The results of penile prosthesis functionality and patients’ and partners’ reported quality of life (QoL) showed similar results between the two groups but greater satisfaction in the relational domain of the questionnaires adopted was described in the IP subgroup. Conclusion: According to our observations, the IP reservoir insertion guarantees good functionality and lower rates of undesired events after PPI.

Background Aerobic exercise can greatly assist in reducing collateral effects of metabolic syndrome (MetS). Moreover, aerobic exercise is associated with sympathetic activation and adaptive responses to sustain muscle engagement, changes in the release of Orexin A, a pleiotropic neuropeptide. Aim The aim of this study was to analyze the beneficial effects of aerobic exercise without dietary changes, in a cohort of MetS subjects, focusing on the role of sympathetic and orexinergic activity. Several blood parameters linked to MetS ROS production, heart rate, galvanic skin response, d-ROM test, and Orexin A serum levels were evaluated in ten males with MetS (BMI 30-34.9) before and after a period of 6 months of aerobic exercise compared to ten healthy subjects. Methods Ten male subjects (aged 54 ± 4.16) with MetS (MetS group) and ten healthy males (aged 49.7 ± 2.79, Healthy group) were told about the study protocol and possible risks, signed the informed consent, and voluntarily participated in the study. Several blood parameters were evaluated in the two tested groups and were re-evaluated in the MetS group after 6 months of training (MetS6M group). The training protocol consisted of more than 30 min/day of walking (average speed of 4.5 km/h) and 3 days/week of aerobic activities (jogging under heart rate control - 120-140 bpm for 45 min). Results The results showed that exercise induced a significant increase in GSR and plasma Orexin A but no significant increase in d-ROM values. Significant decreases in the serum ALT enzyme, triglycerides, and total cholesterol were found, while the HDL levels were significantly higher. Finally, a significant reduction of BMI and resting HR were reported. Conclusion The results of this study confirm that physical activity is associated with sympathetic activation, having a pivotal role against adverse effects linked to MetS. Moreover, this study demonstrates that, in patients with MetS, Orexin A is involved in hormonal adaptations to exercise.

Traumatic brain injury (TBI) is the principal cause of invalidity and death in the population under 45 years of age worldwide.:This mini-review aims to systematize the forensic approach in neuropathological studies, highlighting the proper elements to be noted during external, radiological, autoptical, and histological examinations with particular attention paid to immunohistochemistry and molecular biology.:In the light of the results of this mini-review, an accurate forensic approach can be considered mandatory in the examination of suspected TBI with medico-legal importance, in order to gather all the possible evidence to corroborate the diagnosis of a lesion that may have caused, or contributed to, death. From this point of view, only the use of an evidence-based protocol can reach a suitable diagnosis, especially in those cases in which there are other neuropathological conditions (ischemia, neurodegeneration, neuro-inflammation, dementia) that may have played a role in death.:This is even more relevant when corpses, in an advanced state of decomposition, are studied, where the radiological, macroscopic and histological analyses fail to give meaningful answers. In these cases, immune-histochemical and molecular biology diagnostics are of fundamental importance and a forensic neuropathologist has to know them. Particularly, MiRNAs are promising biomarkers for TBI both for brain damage identification and for medico-legal aspects, even if further investigations are required to validate the first experimental studies. In the same way, the genetic substrate should be examined during any forensic examination, considering its importance in the outcome of TBI.

Greinacher et al.1 and Schultz et al.2 were the first to independently report the main clinical and laboratory features of 11 and five respective patients from Germany, Austria and Norway who developed life-threatening thrombohemorrhagic complications 5 to 16 days after the administration of the first dose of the chimpanzee adenoviral vector vaccine ChAdOx1nCoV-19 against SARS-CoV-2 and COVID-19. Subsequently Scully et al.3 reported similar findings in 23 patients treated with the same vaccine in the United Kingdom. More recently, See et al.4 reported a case series of 12 patients from the USA with cerebral venous sinus thrombosis following the vaccination with Ad26.CoV2.S employing a human adenoviral vector. The main post-vaccination features common to the case series were the occurrence of venous thromboembolism mainly in unusual sites (cerebral and abdominal veins) and the concomitant presence of bleeding symptoms associated with severe thrombocytopenia, often accompanied by laboratory signs of consumption coagulopathy with low plasma fibrinogen and hugely increased levels of D-dimer. The majority of reported patients reacted positively for serum immunoglobulin G (IgG) antibodies to the platelet factor 4 PF4/heparin complex. 1-4 Another common feature was the high mortality rate. The mechanism of this very rare thrombohemorrhagic syndrome was postulated to be a vaccine-triggered autoimmune reaction, with the development of antibodies against a still ill-defined PF4/polyanion complex that causes platelet activation as in heparin-induced thrombocytopenia (HIT),1-4 notwithstanding the fact that no cases were exposed to heparin before the onset of thrombosis and thrombocytopenia. We report herewith the detailed post-mortem macroscopic and microscopic findings in two similar cases that occurred in the Italian region of Sicily.

Background: The impact of warm ischemia time (WIT) on renal functional recovery remains controversial. We examined the length of WIT >30 min. on the long-term renal function following on-clamp partial nephrectomy (PN). Methods: Data from 23 centers for patients undergoing on-clamp PN between 2000 and 2018 were analyzed. We included patients with two kidneys, single tumor, cT1, minimum 1-year followup, and preoperative eGFR ≥60 ml/min/1.73m2. Patients were divided into two groups according to WIT length: group Ⅰ "WIT ≤30 min." and group Ⅱ "WIT >30 min.". A propensity-score matched analysis (1:1 match) was performed to eliminate potential confounding factors between groups. We compared eGFR values, eGFR (%) preservation, eGFR decline, events of chronic kidney disease (CKD) upgrading, and CKD-free progression rates between both groups. Cox regression analysis evaluated WIT impact on upgrading of CKD stages. Results: The primary cohort consisted of 3526 patients: group Ⅰ (n=2868) and group Ⅱ (n=658). After matching the final cohort consisted of 344 patients in each group. At last followup, there were no significant differences in median eGFR values at 1, 3, 5, and 10 years (P>0.05) between the matched groups. In addition, the median eGFR (%) preservation and absolute eGFR change were similar (89% in group Ⅰ vs. 87% in group Ⅱ, p=0.638) and (-10 in group Ⅰ vs. -11 in group Ⅱ, p=0.577), respectively. The 5 years new-onset CKD-free progression rates were comparable in the non-matched groups (79% in group Ⅰ vs. 81% in group Ⅱ, log-rank, p=0.763) and the matched groups (78.8% in group Ⅰ vs. 76.3% in group Ⅱ, log-rank, p=0.905). Univariable Cox regression analysis showed that WIT >30 min. was not a predictor of overall CKD upgrading (HR:0.953, 95%CI 0.829-1.094, p=0.764) nor upgrading into CKD stage ≥Ⅲ (HR:0.972, 95%CI 0.805-1.173, p=0.764). Retrospective design is a limitation of our study. Conclusions: Our analysis based on a large multicenter international cohort study suggests that WIT length during PN has no effect on the long-term renal function outcomes in patients having two kidneys and preoperative eGFR ≥60 ml/min/1.73m2.

Molecular chaperones, many of which are heat shock proteins, play a role in cell stress response and regulate the immune system in various ways, such as in inflammatory/autoimmune reactions. It would be interesting to study the involvement of these molecules in the damage done to COVID-19-infected lungs. In our study, we performed a histological analysis and an immunomorphological evaluation on lung samples from subjects who succumbed to COVID-19 and subjects who died from other causes. We also assessed Hsp60 and Hsp90 distribution in lung samples to determine their location and post-translational modifications. We found histological alterations that could be considered pathognomonic for COVID-19-related lung disease. Hsp60 and Hsp90 immunopositivity was significantly higher in the COVID-19 group compared to the controls, and immunolocalization was in the plasma membrane of the endothelial cells in COVID-19 subjects. The colocalization ratios for Hsp60/3-nitrotyrosine and Hsp60/acetylate-lisine were significantly increased in the COVID-19 group compared to the control group, similar to the colocalization ratio for Hsp90/acetylate-lisine. The histological and immunohistochemical findings led us to hypothesize that Hsp60 and Hsp90 might have a role in the onset of the thromboembolic phenomena that lead to death in a limited number of subjects affected by COVID-19. Further studies on a larger number of samples obtained from autopsies would allow to confirm these data as well as discover new biomarkers useful in the battle against this disease.

Pharmacogenetics analyzes the individual behavior of DNA genes after the administration of a drug. Pharmacogenetic research has been implemented in recent years thanks to the improvement in genome sequencing techniques and molecular genetics. In addition to medical purposes, pharmacogenetics can constitute an important tool for clarifying the interpretation of toxicological data in post-mortem examinations, sometimes crucial for determining the cause and modality of death. The purpose of this systematic literature review is not only to raise awareness among the forensic community concerning pharmacogenetics, but also to provide a workflow for forensic toxicologists to follow in cases of unknown causes of death related to drug use/abuse. The scientific community is called on to work hard in order to supply evidence in forensic practice, demonstrating that this investigation could become an essential tool both in civil and forensic contexts. The following keywords were used for the search engine: (pharmacogenetics) AND (forensic toxicology); (pharmacogenetics) AND (post-mortem); (pharmacogenetics) AND (forensic science); and (pharmacogenetics) AND (autopsy). A total of 125 articles were collected. Of these, 29 articles were included in this systematic review. A total of 75% of the included studies were original articles (n = 21) and 25% were case reports (n = 7). A total of 78% (n = 22) of the studies involved deceased people for whom a complete autopsy was performed, while 22% (n = 6) involved people in good health who were given a drug with a subsequent pharmacogenetic study. The most studied drugs were opioids (codeine, morphine, and methadone), followed by antidepressants (tricyclic antidepressants and venlafaxine). Furthermore, all studies highlighted the importance of a pharmacogenetics study in drug-related deaths, especially in cases of non-overdose of drugs of abuse. This study highlights the importance of forensic pharmacogenetics, a field of toxicology still not fully understood, which is of great help in cases of sudden death, deaths from overdose, deaths after the administration of a drug, and also in cases of complaint of medical malpractice.

Introduction: Smart drugs are among the most common drugs used by students. It is estimated that they are second in incidence after cannabis. Although they are usually used for diseases such as attention deficit hyperactivity disorder (ADHD) and dementia, in most cases the use of smart drugs is illegal and without a prescription. Methodological issues: A systematic review was conducted according to PRISMA guidelines. SCOPUS, Medline (using PubMed as a search engine), Embase, Web of Sciences, and Google Scholar were used as search engines from January 1, 1980 to June 1, 2021 to evaluate the association between smart drugs and neuro-enhancement. A total of 4715 articles were collected. Of these, 295 duplicates were removed. A total of 4380 articles did not meet the inclusion criteria. In conclusion, 48 articles were included in the present systematic review. Results: Most of the studies were survey studies, 1 was a prospective longitudinal study, 1 was a cross-over study, and 1 was an experimental study in an animal model (rats). The largest group of consumers was school or university students. The most frequent reasons for using smart drugs were: better concentration, neuro enhancement, stress reduction, time optimization, increased wake time, increased free time, and curiosity. There are conflicting opinions, in fact, regarding their actual functioning and benefit, it is not known whether the benefits reported by consumers are due to the drugs, the placebo effect or a combination of these. The real prevalence is underestimated: it is important that the scientific community focus on this issue with further studies on animal models to validate their efficacy.

To date, little is known regarding the transmission risks of SARS-CoV-2 infection for subjects involved in handling, transporting, and examining deceased persons with known or suspected COVID-19 positivity at the time of death. This experimental study aims to define if and/or how long SARS-CoV-2 persists with replication capacity in the tissues of individuals who died with/from COVID-19, thereby generating infectious hazards. Sixteen patients who died with/from COVID-19 who underwent autopsy between April 2020 and April 2021 were included in this study. Based on PMI, all samples were subdivided into two groups: ‘short PMI’ group (eight subjects who were autopsied between 12 to 72 h after death), ‘long PMI’ (eight subjects who were autopsied between 24 to 78 days after death). All patients tested positive for RT-PCR at nasopharyngeal swab both before death and on samples collected during post-mortem investigation. Moreover, a lung specimen was collected and frozen at −80 °C in order to perform viral culture. The result was defined based on the cytopathic effect (subjective reading) combined with the positivity of the RT-PCR test (objective reading) in the supernatant. Only in one sample (PMI 12 h), virus vitality was demonstrated. This study, supported by a literature review, suggests that the risk of cadaveric infection in cases of a person who died from/with COVID-19 is extremely low in the first hours after death, becoming null after 12 h after death, confirming the World Health Organization (WHO) assumed in March 2020 and suggesting that the corpse of a subject who died from/with COVID-19 should be generally considered not infectious.

INTRODUCTION AND OBJECTIVE:Outcomes of 2 dedicated randomized controlled trials (RCTs) comparing on-clamp versus off-clamp robot-assisted (RPN) or pure laparoscopic partial nephrectomy (LPN) (CLOCK...

Purpose: The aim of this study was to evaluate the efficacy of collagenase Clostridium histolyticum (CCH) in patients with Peyronie’s disease (PD) suffering from atypical deformities. Materials and Methods: We retrospectively collected data of patients with atypical penile curvature (PC) secondary to PD. All patients underwent a modified treatment protocol, consisting of 3 intralesional injections of 0.9 mg of CCH performed at 4-week intervals at the point of maximum PC. Patients were instructed to follow a strict routine, involving daily modeling of erect penis and stretching at the urinary toilette time, two minutes each. Success was defined as a decrease in PC of ≥20° from baseline. Results: Sixty-five patients were included in the analysis. Median age was 59.0 years (interquartile range [IQR], 53.0 to 63.0 years), median curvature 40.0° (IQR, 30.0° to 45.0°) median duration of the disease 12.0 years (IQR, 6.5 to 24.0 years). Fiftythree patients (81.54%) had ventral PC, 7 (10.77%) hourglass PC, and 5 (7.69%) shortening PC. Median changes of PC were -20.0 (IQR, -20.0 to -10.0; p

Purpose:We sought to identify predictive factors of the transition from off clamp to on clamp robotic partial nephrectomy following an intraoperative decision.Materials and Methods:In the multicent...

Objectives: To evaluate the feasibility and safety of a proctored step-by-step training program for GreenLight laser anatomic photovaporization (aPVP) of the prostate.Methods: Data from patients undergoing aPVP between January 2019 and December 2020 operated by a single surgeon following a dedicated step-by-step proctored program were prospectively collected. The procedure was divided into five modular steps of increasing complexity. Preoperative patients' data as well as total operative time, energy delivered on the prostate and postoperative data, were recorded. Then, we assessed how the overall amount of energy delivered and the operative times varied during the training program. Surgical steps were analyzed by cumulative summation. Univariable and multivariable regression models were built to assess the predictors of the amount of energy delivered on the prostate.Results: Sixty consecutive patients were included in the analysis. Median prostate volume was 56.5 mL. The training program was succesfully completed with no intraoperative or meaningful post-operative complications. The energy delivered reached the plateau after the 40th case. At multivariable analysis, increasing surgeon experience was associated with lower amounts of energy delivered as well as lower operative times.Conclusions: A step-by-step aPVP training program can be safely performed by surgeons with prior endoscopic experience if mentored by a skilled proctor. Considering the energy delivered as an efficacy surrogate metrics (given its potential impact on persistent postoperative LUTS), 40 cases are needed to reach a plateau for aPVP proficiency. Further studies are needed to assess the safety of our step-by-step training modular program in other clinical contexts.

Objectives: The incidence of prostate cancer in renal transplant recipients (RTRs) is increasing, but few data are available in the literature. In this study, we reviewed the 25-year experience in the management of prostate cancer after kidney transplantation at the Florence Transplant Centre.Methods: We retrospectively reviewed the data from 617 RTR male patients who underwent renal transplantation at our institute between July 1996 and September 2016. Data regarding demographics, renal transplantation, prostate cancer and immunosuppressive treatment were analyzed. The probability of death was estimated by using the Kaplan-Meier method and differences between patients' groups were assessed by the log-rank test.Results: From July 1991 to September 2016, 617 kidney transplantations of male patients were performed at our institute. Among these, 20 patients were subsequently diagnosed with prostate cancer accounting for a cumulative incidence of 3.24%. After a median follow-up of 59 months, 10 patients underwent radical prostatectomy whereas 10 patients underwent primary radiotherapy. A biochemical recurrence was identified in five (25%) patients while a fatal event occurred in 11 (55%) patients. Univariate Cox regression showed that the basal value of PSA >10 ng/ml was the only significant factor negatively affecting the survival of patients.Conclusions: Standard treatments can be proposed to RTR with satisfactory results on both post-operative and oncological outcomes. Further studies are needed to address the issue of prostate cancer screening based on PSA levels and the optimal management of prostate cancer in RTRs.

Introduction Retrograde ureteroscopy (URS), intra-renal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) represent routine interventions for the treatment of ureteral and renal stones, although at times associated with serious adverse events. Of note, the evidence on perioperative complications after these procedures remains sparse and controversial. Moreover, there is a lack of standardized reporting of adverse events using uniform systems. The aim of the present study was to systematically review of the available evidence on URS/RIRS and PCNL for the surgical treatment of urinary stone, assessing the incidence of intra- and postoperative events, classified according to the modified Clavien-Dindo scale. Evidence acquisition A systematic review of the literature was performed according to PRISMA recommendations and was conducted on intra- and postoperative complications, as well as on their management, following URS, RIRS and PCNL procedures, particularly focusing on major events. Evidence synthesis Overall, 26 studies (13 on URS/RIRS and 11 on PCNL) met the inclusion criteria and were evaluated. The highest intraoperative complication rate was 11.5% and 8.5% for RIRS and PCNL, respectively. Major complication rate following URS/RIRS and PCNL ranged between 0.3-31.7% and 2-17.1%, respectively. The most frequent adverse events were obstructive pyelonephritis or urinary leakage requiring the placement of a double J stent or a drainage. Among PCNLs series, life-threatening adverse events have also been reported, including bleeding requiring renal angioembolization and urothorax. Conclusions Despite the inclusion of series using a standardized reporting system, the complication rate after URS/RIRS/PCNL remains extensively heterogeneous in the literature; in addition, a non-negligible proportion of studies did not characterize the adverse events nor report the actual management strategy to solve them. Future research is needed to standardize the classification and reporting of surgical complications after endourological procedures (taking into consideration the surgeon's experience and skills), aiming to improve patient counseling and potentially the strategy for their prevention.

The medico-legal term “sudden death (SD)” refers to those deaths that are not preceded by significant symptoms. SD in apparently healthy individuals (newborn through to adults) represents a challenge for medical examiners, law enforcement officers, and society as a whole. This review aims to introduce a useful flowchart that should be applied in all cases of SD. Particularly, this flowchart mixes the data obtained through an up-to-date literature review and a revision of the latest version of guidelines for autopsy investigation of sudden cardiac death (SCD) in order to support medico-legal investigation. In light of this review, following the suggested flowchart step-by-step, the forensic pathologist will be able to apply all the indications of the scientific community to real cases. Moreover, it will be possible to answer all questions relative to SD, such as: death may be attributable to cardiac disease or to other causes, the nature of the cardiac disease (defining whether the mechanism was arrhythmic or mechanical), whether the condition causing SD may be inherited (with subsequent genetic counseling), the assumption of toxic or illicit drugs, traumas, and other unnatural causes.

Objective: To report a case of robot-assisted partial nephrectomy (RAPN) for two highly complex renal tumors in a patient with a Horseshoe kidney (HSK), focusing on the utility of hyperaccuracy three-dimensional (HA3D) virtual models for accurate preoperative and intraoperative planning of the procedure.Methods: A 74-year-old Caucasian male patient was referred to our Unit for incidental detection of two complex renal masses in the left portion of a HSK. The 50 × 55 mm, larger, predominantly exophytic renal mass was located at the middle-lower pole of the left-sided kidney (PADUA score 9). The 16 × 17 mm, smaller, hilar renal mass was located at the middle-higher pole of the left-sided kidney (PADUA score 9). Contrast-enhanced CT scan images in DICOM format were processed using a dedicated software to achieve a HA3D virtual reconstructions. RAPN was performed by a highly experienced surgeon using the da Vinci Si robotic platform with a three-arm configuration. A selective delayed clamping strategy was adopted for resection of the larger renal mass while a clampless strategy was adopted for the smaller renal mass. An enucleative resection strategy was pursued for both tumors.Results: The overall operative time was 150 min, with a warm ischemia time of 21 min. No intraoperative or postoperative complications were recorded. Final resection technique according to the SIB score was pure enucleation for both masses. At histopathological analysis, both renal masses were clear cell renal cell carcinoma (ccRCC) (stage pT1bNxMx and pT3aNxMx for the larger and smaller mass, respectively). At a follow-up of 7 months, there was no evidence of local or systemic recurrence.Conclusions: Surgical management of complex renal masses in patients with HSKs is challenging and decision-making is highly nuanced. To optimize postoperative outcomes, proper surgical experience and careful preoperative planning are key. In this regard, 3D models can play a crucial role to refine patient counseling, surgical decision-making, and pre- and intraoperative planning during RAPN, tailoring surgical strategies and techniques according to the single patient's anatomy.

Background Entero-colovesical fistula is a rare complication of various benign and malignant diseases. The diagnosis is prominently based on clinical symptoms; imaging studies are necessary not only to confirm the presence of the fistula, but more importantly to demonstrate the extent and the nature of the fistula. There is still a lack of consensus regarding the if, when and how to repair the fistula. The aim of the study is to review the different surgical treatment options, focus on surgical indications, and explore cumulative recurrence, morbidity, and mortality rates of entero-vesical and colo-vesical fistula patients. Methods A systematic review of the literature was conducted according to PRISMA guidelines. Random effects meta-analyses of proportions were developed to assess primary and secondary endpoints. I2 statistic and Cochran’s Q test were computed to assess inter-studies’ heterogeneity. Results Twenty-two studies were included in the analysis with a total of 861 patients. Meta-analyses of proportions pointed out 5, 22.2, and 4.9% rates for recurrence, complications, and mortality respectively. A single-stage procedure was performed in 75.5% of the cases, whereas a multi-stage operation in 15.5% of patients. Palliative surgery was performed in 6.2% of the cases. In 2.3% of the cases, the surgical procedure was not specified. Simple and advanced repair of the bladder was performed in 84.3% and 15.6% of the cases respectively. Conclusions Although burdened by a non-negligible rate of complications, surgical repair of entero-colovesical fistula leads to excellent results in terms of primary healing. Our review offers opportunities for significant further research in this field. Level of Evidence Level III according to ELIS (SR/MA with up to two negative criteria).

In the last two decades, three unknown pathogens have caused outbreaks, generating severe global health concerns. In 2003, after nucleic acid genotyping, a new virus was named severe acute respiratory syndrome coronavirus (SARS-CoV). After nine years, another coronavirus emerged in the middle east and was named MERS-CoV (Middle East Respiratory Syndrome—Coronavirus). Finally, in December 2019, a new unknown coronavirus was isolated from a cluster of patients and was named SARS-CoV-2 (COVID-19, coronavirus disease 2019). This review aims to propose a complete overview of autopsy in the three coronaviruses over the past two decades, showing its pivotal role in the management of unknown diseases. A total of 116 studies fulfilled the inclusion criteria: 14 studies were collected concerning SARS-CoV (87 autopsy reports, from Asian and American countries), 2 studies for MERS-CoV (2 autopsy reports, from Middle-East Asian countries), and 100 studies on SARS-CoV-2 (930 autopsy reports). Analyzing the data obtained on COVID-19, based on the country criterion, a large number of post-mortem investigation were performed in European countries (580 reports), followed by American countries (251 reports). It is interesting to note that no data were found from the Oceanic countries, maybe because of the minor involvement of the outbreak. In all cases, autopsy provided much information about each unknown coronavirus. Despite advanced technologies in the diagnostic fields, to date, autopsy remains the gold standard method to understand the biological features and the pathogenesis of unknown infections, especially when awareness of a pathogen is restricted and the impact on the healthcare system is substantial. The knowledge gained through this technique may positively influence therapeutic strategies, ultimately reducing mortality.

The severe acute respiratory syndrome (SARS)-CoV-2 was identified for the first time in China, in December 2019. Confirmed cases of COVID-19 have been reported around the world; indeed, this infection has been declared a pandemic. Consequently, the scientific community is working hard to gain useful information about the history of this virus, its transmission, diagnosis, clinical features, radiological findings, research and development of candidate therapeutics as well as vaccines. This review aims to analyze the diagnostic techniques used to ascertain the COVID-19 infection, critically reviewing positive points and criticism for forensic implications, obviously including autopsy. Finally, this review proposes a practical workflow to be applied in the management of corpses during this outbreak of the COVID-19 infection, which could be useful in cases of future infectious disease emergencies. Analyzing the diagnostic methods, to date, virus nucleic acid RT-PCR represents the standard method used to ascertain the COVID-19 infection in living subjects and corpses, even if this technique has several criticisms: mainly, the staff should be highly specialized, working in high-throughput settings, able to handle high workloads and aware of health risks and the importance of the results. Thus, IgG/IgM serological tests have been developed, overcoming RT-qPCR duration, costs, and management, not requiring highly trained personnel. Nevertheless, serological tests present problems; the WHO recommends the use of these new point-of-care immunodiagnostic tests only in research settings. Furthermore, nothing has yet been published regarding the possibility of applying these methods during post-mortem investigations. In light of this scenario, in this review, we suggest a flow chart for the pathologist called on to ascertain the cause of death of a subject with historical and clinical findings of COVID-19 status or without any anamnestic, diagnostic, or exposure information. Indeed, the literature data confirmed the analytical vulnerabilities of the kits used for laboratory diagnosis of COVID-19, particularly during postmortem examinations. For these reasons, autopsy remains the gold standard method to ascertain the exact cause of death (from or with COVID-19 infection, or other causes), to consequently provide real data for statistical evaluations and to take necessary measures to contain the risks of the infection. Moreover, performing autopsies could provide information on the pathogenesis of the COVID-19 infection with obvious therapeutic implications.

At the end of 2019, a new coronavirus (COVID-19) appeared on the world scene, which mainly affects the respiratory system, causing pneumonia and multi-organ failure, and, although it starts with common symptoms such as shortness of breath and fever, in about 2–3% of cases it leads to death. Unfortunately, to date, no specific treatments have been found for the cure of this virus and, therefore, it is advisable to implement all possible strategies in order to prevent infection. In this context, it is important to better define the role of all behaviors, in particular nutrition, in order to establish whether these can both prevent infection and improve the outcome of the disease in patients with COVID-19. In the literature, it is widely shown that states of malnutrition, overweight, and obesity negatively affect the immune system, leading to viral infections, and several studies have shown that nutritional interventions can act as immunostimulators, helping to prevent viral infections. Even if several measures, such as the assumption of a specific diet regimen, the use of dietary supplements, and other similar interventions, are promising for the prevention, management, and recovery of COVID-19 patients, it is important to highlight that strong data from randomized clinical trials are needed to support any such assumption. Considering this particular scenario, we present a literature review addressing several important aspects related to diet and SARS-CoV-2 infection, in order to highlight the importance of diet and supplementation in prevention and management of, as well as recovery from COVID-19.

To date, there is poor evidence on the transmission of infection in individuals handling the bodies of deceased persons infected with SARS-CoV-2 and in particular, during autopsies. The aim of this study was to demonstrate that when appropriate strategies are adopted autopsy is a safe procedure with a minimal infection risk for all subjects involved (pathologists, technical personnel, and others) when proper strategies are adopted. We performed 16 autopsies on cadavers of persons who had died with confirmed COVID-19 with different post-mortem intervals (PMI). To confirm the presence of SARS-CoV-2 RNA, for each autopsy, 2 swabs were sampled from lungs, while to evaluate environmental contamination, 11 swabs were taken at three different times: T0 (before autopsy), T1 (at the end of the autopsy, without removing the corpse), and T2 (after cleaning and disinfecting the autopsy room). Specifically, 2 swabs were sampled on face shields used by each pathologist, and 4 swabs were collected on the autopsy table, 4 swabs were also collected from walls and 1 from floor. Lung swabs confirmed the presence of SARS-CoV-2 RNA in all cases. Environmental swabs, collected at T0 and T2 were all negative, while swabs sampled at T1 were shown to be positive. Interestingly, no association was shown between PMI length and environmental contamination. Infection control strategies for safe management of clinical forensic autopsies of bodies with suspected or confirmed COVID-19 are also described.

Glycophorins are an important group of red blood cell (RBC) transmembrane proteins. Monoclonal antibodies against GPA are employed in immunohistochemical staining during post-mortem examination: Through this method, it is possible to point out the RBC presence in tissues. This experimental study aims to investigate anti-GPA immunohistochemical staining in order to evaluate the vitality of the lesion from corpses in different decomposition state. Six cases were selected, analyzing autopsies’ documentation performed by the Institute of Legal Medicine of Rome in 2010–2018: four samples of fractured bones and three samples of soft tissues. For the control case, the fracture region of the femur was sampled. The results of the present study confirm the preliminary results of other studies, remarking the importance of the GPA immunohistochemical staining to highlight signs of survival. Moreover, this study suggests that the use of this technique should be routinely applied in cases of corpses with advanced putrefaction phenomena, even when the radiological investigation is performed, the macroscopic investigation is inconclusive, the H&amp, E staining is not reliable. This experimental application demonstrated that the use of monoclonal antibody anti-human GPA on bone fractures and soft tissues could be important to verify whether the lesion is vital or not.

Objective: To provide a step-by-step overview of the University of Florence technique for robotic living donor nephrectomy (LDN), focusing on its technical nuances and perioperative outcomes.Methods: A dedicated robotic LDN program at our Institution was codified in 2012. Data from patients undergoing robotic LDN from 2012 to 2019 were prospectively collected. All robotic LDNs were performed by a highly experienced surgeon, using the da Vinci Si robotic platform in a three-arm configuration. In this report we provide a detailed overview of our surgical technique for robotic LDN. The main objective of the study was to evaluate the technical feasibility and safety of the technique, including perioperative surgical complications rate and mid-term functional outcomes.Results: Overall, 36 patients undergoing robotic LDNs were included in the study. Of these, 28 (78%) were left LDNs. Median (IQR) donor pre-operative eGFR was 88 (75.6–90) ml/min/1.73 m2. In all cases, robotic LDN was completed without need of conversion. The median (IQR) overall operative time was 230 (195–258) min, while the median console time was 133 (IQR 117-166) min. The median (IQR) warm ischemia time was 175 (140–255) s. No intraoperative adverse events or 90-d major surgical complications were recorded. At a median (IQR) follow-up of 24 months (IQR 11-46), median (IQR) eGFR patients undergoing in living donor nephrectomy was 57.4 (47.9; 63.9) ml/min/1.73 m2.Conclusions: In our experience, robotic LDN is technically feasible and safe. The use of robotic surgery for LDN may provide distinct advantages for surgeons while ensuring optimal donors' perioperative and functional outcomes.

Anaphylaxis is a life-threatening or fatal clinical emergency characterized by rapid onset, and death may be sudden. The margin of certainty about the diagnosis of anaphylactic death is not well established. The application of immunohistochemical techniques combined with the evaluation of blood tryptase concentrations opened up a new field of investigation into anaphylactic death. The present study investigated eleven autopsy cases of anaphylactic death, carried out between 2005 and 2017, by the Departments of Forensic Pathology of the Universities of Foggia and Catania (Italy). An analysis of the medical records was carried out in all autopsies. Seven autopsies were carried out on males and four on females. Of the eleven cases, one showed a history of asthma, one of food ingestion, two of oral administration of medications, six did not refer any allergy history, and one subject was unknown. All cases (100%) showed pulmonary congestion and edema, 7/11 (64%) of the cases had pharyngeal/laryngeal edema and mucus plugging in the airway, only one case (9%) had a skin reaction that was found during external examination. Serum tryptase concentration was measured in ten cases, and the mean value was 133.5 &micro, g/L &plusmn, 177.9. The immunohistochemical examination using an anti-tryptase antibody on samples from the lungs, pharynx/larynx, and skin site of medication injection showed that all cases (100%) were strongly immunopositive for anti-tryptase antibody staining on lung samples, three cases (30%) were strongly immunopositive for anti-tryptase antibody staining on pharyngeal/laryngeal samples, and eight cases (80%) were strongly immunopositive for anti-tryptase antibody staining on skin samples. We conclude that a typical clinical history, blood tryptase level &gt, 40 &micro, g/L, and strongly positive anti-tryptase antibody staining in the immunohistochemical investigation may represent reliable parameters in the determination of anaphylactic death with the accuracy needed for forensic purposes.

This chapter focuses on the analysis and identification of human remains, in particular those that are skeletonised. Forensic identification of human remains is a legal duty based on the scientific compatibility of information on missing persons with unidentified human remains. When human skeletal remains are presented, the most important methods for establishing identity include DNA analysis, odontology, comparative X-ray analysis, and skull–photo comparison. Moreover, when human skeletal remains are found, it is mandatory to medically examine them in order to pronounce death and establish, if possible, time, manner, and cause of death where attainable. Once the skeletal remains have been identified as being human, subsequently, the identification of the victim’s characteristics, and cause and manner of death from the skeleton takes place. The identification of human remains is important for both legal and humanitarian reasons. Moreover, a multidisciplinary approach is very important in the case of the recovery of human skeletal remains.

The application of molecular genetics technologies to the forensic field is becoming very important, demonstrating a pivotal role in cases that have to do with civil and criminal law, family law, as well as in cases of catastrophes with numerous victims. This chapter aims to analyze the molecular techniques applied to the human and nonhuman forensic scenario, considering the scientific progress from the past 30–40years which has highlighted and continues to highlight the role of the important tool to solve forensic casework. The molecular techniques meet the human forensic fields in several criminal investigations, with completely different tasks. Considering that the drug assumption has direct consequences both for metabolism responses and by the target organs, emerging genetic tools, like epigenetic applications, could be very useful in the forensic sciences. Pharmacogenetics is the study of inherited genetic differences in drug metabolic pathways, which can affect individual responses to drugs, both in terms of therapeutic effect and in terms of adverse effects.

To assess the safety and efficacy of contrast-enhanced ultrasound (CEUS) imaging for monitoring small (

Objective: To report the University of Florence technique for robot-assisted kidney transplantation (RAKT) from living donor (LD) and deceased donor (DD), highlighting the evolution of surgical indications and technical nuances in light of a single surgeon's learning curve.Materials and Methods: A dedicated program for RAKT from LDs was developed at our Institution in 2017 and implemented later with a specific framework for DDs. All RAKTs were performed by a single highly experienced surgeon. Data from patients undergoing RAKT between January 2017 and December 2019 were prospectively collected in a dedicated web-based data platform. In this report we provide a comprehensive step-by-step overview of our technique for RAKT, focusing on the potential differences in peri-operative and mid-term functional outcomes between LDs vs. DDs.Results: Overall, 160 KTs were performed in our center during the study period. Of these, 39 (24%) were performed with a robot-assisted laparoscopic technique, both from LDs (n = 18/39 [46%]) and from DDs (n = 21/39 [54%]). Eleven (11/39 [18%]), 13(13/39 [26%]), and 15 (15/39 [30%]) RAKTs were performed in 2017, 2018, and 2019, respectively, highlighting an increasing adoption of robotics for KT over time at our Institution. Median time for arterial (19 min for LD and 18 min for DD groups), venous (21 min for LD, 20 min for DD) and uretero–vesical (18 min for LD and 15 for DD) anastomosis were comparable between the two groups (all p > 0.05), as the median rewarming time (59 min vs. 56 min, p = 0.4). The rate of postoperative surgical complications according to Clavien–Dindo classification did not differ between the two study groups, except for Clavien–Dindo grade II complications (higher among patients undergoing RAKT from DDs, 76 vs. 44%, p = 0.042). Overall, 7/39 (18%) patients (all recipients from DDs) experienced DGF; two of them were on dialysis at last FU.Conclusions: Our experience confirms the feasibility, safety, and favorable mid-term outcomes of RAKT from both LDs and DDs in appropriately selected recipients, highlighting the opportunity to tailor the technique to specific recipient- and/or graft-characteristics. Further research is needed to refine the technique for RAKT and to evaluate the benefits and harms of robotics for kidney transplantation from DDs.

Despite safety recommendations for the management of corpses with COVID-19 infection and the high number of deaths worldwide, the post-mortem investigation rate is extremely low as well as the scientific contributions describing the pathological features. The first results of post-mortem investigations provided interesting findings and contributed to promoting unexplored therapeutic approaches and new frontiers of research. A systematic review is provided with the aim of summarizing all autopsy studies up to February 2020 in which a complete post-mortem investigation in patients with COVID-19 disease was performed, focusing on histopathological features. We included case reports, case series, retrospective and prospective studies, letters to the editor, and reviews. A total of 28 studies fulfilled the inclusion criteria, producing a pooled dataset of 407 full autopsies. Analyzing the medical history data, only 12 subjects had died without any comorbidities (for 15 cases the data were not available). The post-mortem investigation highlighted that acute respiratory distress syndrome (ARDS) and multiple organ failure represent the main clinical features of COVID-19 disease, often leading to pulmonary thromboembolism and superimposed bronchopneumonia. The discussed data showed a strict relationship among the inflammatory processes, diffuse alveolar, and endothelial damage. In light of these results, the full autopsy can be considered as the gold standard to investigate unknown infections or pathogens resulting in death.

INTRODUCTION Transurethral resection of the prostate (TURP) remains the gold standard for treatment of benign prostatic hyperplasia (BPH). Yet, the introduction of lasers for the treatment of LUTS due to BPO has dramatically changed the surgical landscape of benign prostatic obstruction (BPO) treatment. Recently, "en-bloc" techniques have shown to prove advantageous in terms of better visualization, more prompt identification of the surgical capsule and the correct plane to dissect. Herein we provide a comprehensive overview of available series of en-bloc enucleation of the prostate, focusing on surgical techniques, perioperative and functional outcomes. EVIDENCE ACQUISITION A systematic review of the literature was performed according to PRISMA recommendations and was conducted on surgical techniques and perioperative outcomes of minimally invasive en-bloc surgery for prostate adenoma detachment. EVIDENCE SYNTHESIS Overall, 16 studies with 2750 patients between 2003 and 2019 were included. Specific technical nuances have been described to maximize perioperative outcomes of en-bloc prostatic enucleation, including early apical release, horse-shape incisions, inverted U-shape tractions and low power. Overall, regardless of the energy employed, en-bloc prostatic enucleation achieved favorable outcomes including low risk of major complications and quality of life improvement. However, a great heterogeneity of study design, patients' inclusion criteria, prostate volume and en-bloc surgical strategy was found. CONCLUSIONS En-bloc endoscopic enucleation of the prostate has been shown to be technically feasible and safe, with potential technical advantages over the classic three-lobe technique. Larger comparative studies are needed to evaluate the ultimate impact of the en-bloc approach on postoperative outcomes, in light of the surgeon's learning curve.

Pediatrics, among all the branches of medicine, is a sector not particularly affected by a high number of claims. Nevertheless, the economic value of the compensation is significantly high, for example in cases of children who suffered multiple disabilities following perinatal lesions with a long-life expectancy. In Italy, the most of the claims for compensation concern surgical pathologies and infections. Among this latter, the dominant role is taken by respiratory tract infections. In this context, the purpose of this manuscript is to present a case series of infant deaths in different emergency-related facilities (ambulances, emergency rooms), denounced by relatives. Following these complaints, the autopsy was performed and subsequent histological examinations revealed the presence of typical and pathognomic histological findings of acute viral bronchiolitis, whose morphological appearance is poorly reported in the literature. The analysis of these cases made it possible to highlight the following conclusions: the main problems in diagnosing sudden death causes, especially in childhood, are the rapidity of death and the scarce correlation between the preexistent diseases and of the cause of death itself. For all these reasons, the autopsy, either clinical or medico-legal, is mandatory in cases of sudden unexpected infant death to manage claim requests, because only the histological examinations performed on samples collected during the autopsy can reveal the real cause of death.

Context The unprecedented health care scenario caused by the coronavirus disease 2019 (COVID-19) pandemic has revolutionized urology practice worldwide. Objective To review the recommendations by the international and European national urological associations/societies (UASs) on prioritization strategies for both oncological and nononcological procedures released during the current emergency scenario. Evidence acquisition Each UAS official website was searched between April 8 and 18, 2020, to retrieve any document, publication, or position paper on prioritization strategies regarding both diagnostic and therapeutic urological procedures, and any recommendations on the use of telemedicine and minimally invasive surgery. We collected detailed information on all urological procedures, stratified by disease, priority (higher vs lower), and patient setting (outpatient vs inpatient). Then, we critically discussed the implications of such recommendations for urology practice in both the forthcoming “adaptive” and the future “chronic” phase of the COVID-19 pandemic. Evidence synthesis Overall, we analyzed the recommendations from 13 UASs, of which four were international (American Urological Association, Confederation Americana de Urologia, European Association of Urology, and Urological Society of Australia and New Zealand) and nine national (from Belgium, France, Germany, Italy, Poland, Portugal, The Netherlands, and the UK). In the outpatient setting, the procedures that are likely to impact the future burden of urologists’ workload most are prostate biopsies and elective procedures for benign conditions. In the inpatient setting, the most relevant contributors to this burden are represented by elective surgeries for lower-risk prostate and renal cancers, nonobstructing stone disease, and benign prostatic hyperplasia. Finally, some UASs recommended special precautions to perform minimally invasive surgery, while others outlined the potential role of telemedicine to optimize resources in the current and future scenarios. Conclusions The expected changes will put significant strain on urological units worldwide regarding the overall workload of urologists, internal logistics, inflow of surgical patients, and waiting lists. In light of these predictions, urologists should strive to leverage this emergency period to reshape their role in the future. Patient summary Overall, there was a large consensus among different urological associations/societies regarding the prioritization of most urological procedures, including those in the outpatient setting, urological emergencies, and many inpatient surgeries for both oncological and nononcological conditions. On the contrary, some differences were found regarding specific cancer surgeries (ie, radical cystectomy for higher-risk bladder cancer and nephrectomy for larger organ-confined renal masses), potentially due to different prioritization criteria and/or health care contexts. In the future, the outpatient procedures that are likely to impact the burden of urologists’ workload most are prostate biopsies and elective procedures for benign conditions. In the inpatient setting, the most relevant contributors to this burden are represented by elective surgeries for lower-risk prostate and renal cancers, nonobstructing stone disease, and benign prostatic hyperplasia., Take Home Message There was a large consensus among the different urological associations/societies regarding the prioritization of most urological procedures. However, some differences were found regarding specific cancer surgeries (ie, radical cystectomy for higher-risk bladder cancer and nephrectomy for larger organ-confined renal masses). In the future, the procedures that are likely to impact the burden of urologists’ workload most are prostate biopsies, elective procedures for benign conditions, elective surgeries for lower-risk prostate and renal cancers, nonobstructing stone disease, and benign prostatic hyperplasia.

Adipose tissue is a multifunctional organ involved in many physiological and metabolic processes through the production of adipokines and, in particular, adiponectin. Caloric restriction is one of the most important strategies against obesity today. The very low-calorie ketogenic diet (VLCKD) represents a type of caloric restriction with very or extremely low daily food energy consumption. This study aimed to investigate the physiological effects of a VLCKD on anthropometric and biochemical parameters such as adiponectin levels, as well as analyzing oligomeric profiles and cytokine serum levels in obese subjects before and after a VLCKD. Twenty obese subjects were enrolled. At baseline and after eight weeks of intervention, anthropometric and biochemical parameters, such as adiponectin levels, were recorded. Our findings showed a significant change in the anthropometric and biochemical parameters of these obese subjects before and after a VLCKD. We found a negative correlation between adiponectin and lipid profile, visceral adipose tissue (VAT), C-reactive protein (CRP), and pro-inflammatory cytokines such as tumor necrosis factor-&alpha, (TNF-&alpha, ), which confirmed the important involvement of adiponectin in metabolic and inflammatory diseases. We demonstrated the beneficial short-term effects of a VLCKD not only in the treatment of obesity but also in the establishment of obesity-correlated diseases.

Background: The current outbreak of COVID-19 infection, which started in Wuhan, Hubei province, China, in December 2019, is an ongoing challenge and a significant threat to public health requiring surveillance, prompt diagnosis, and research efforts to understand a new, emergent, and unknown pathogen and to develop effective therapies. Despite the increasing number of published studies on COVID-19, in all the examined studies the lack of a well-defined pathophysiology of death among patients who died following COVID-19 infection is evident. Autopsy should be considered mandatory to define the exact cause of death, thus providing useful clinical and epidemiologic information as well as pathophysiological insights to further provide therapeutic tools. Methods: A literature review was performed on PubMed database, using the key terms: “COVID-19”, “nCov 19”, and “Sars Cov 2”. 9709 articles were retrieved; by excluding all duplicated articles, additional criteria were then applied: articles or abstracts in English and articles containing one of the following words: “death”, “died”, “comorbidity”, “cause of death”, “biopsy”, “autopsy”, or “pathological”. Results: A total of 50 articles met the inclusion criteria. However, only 7 of these studies reported autopsy-based data. Discussion: The analysis of the main data from the selected studies concerns the complete analysis of 12,954 patients, of whom 2269 died (with a mortality rate of 17.52%). Laboratory confirmation of COVID-19 infection was obtained in all cases and comorbidities were fully reported in 46 studies. The most common comorbidities were: cardiovascular diseases (hypertension and coronary artery disease), metabolic disorders (diabetes, overweight, or obesity), respiratory disorders (chronic obstructive pulmonary disease), and cancer. The most common reported complications were: acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, liver insufficiency, and septic shock. Only 7 papers reported histological investigations. Nevertheless, only two complete autopsies are described and the cause of death was listed as COVID-19 in only one of them. The lack of postmortem investigation did not allow a definition of the exact cause of death to determine the pathways of this infection. Based on the few histopathological findings reported in the analyzed studies, it seems to be a clear alteration of the coagulation system: frequently prothrombotic activity with consequent thromboembolism was described in COVID-19 patients. As a scientific community, we are called on to face this global threat, and to defeat it with all the available tools necessary. Despite the improvement and reinforcement of any method of study in every field of medicine and science, encouraging the autopsy practice as a tool of investigation could also therefore, help physicians to define an effective treatment to reduce mortality.

Peyronie's disease (PD) is a common condition which results in penile curvature making sexual intercourse difficult or impossible. Collagenase clostridium histolyticum (CCH) is the first licensed drug for the treatment of PD and is indicated in patients with palpable plaque and curvature deformity of at least 30° of curvature. However, only few monocentric studies are available in the current literature and this is the first national multicentric study focusing on this new treatment. In five Italian centres, 135 patients have completed the treatment with three injections of CCH using Ralph's shortened modified protocol. The protocol consisted of three intralesional injections of CCH (0.9 mg) given at 4-weekly intervals in addiction to a combination of home modelling, stretching and a vacuum device on a daily basis. An improvement in the angle of curvature was recorded in 128/135 patients (94.8%) by a mean (range) of 19.1 (0–40)° or 42.9 (0–67)% from baseline (p

none 10 no Anabolic androgenic steroids (AAS) are some of the most common drugs used among athletes, frequently in combination with resistance training, to improve physical performance or for aesthetic purpose. A great number of scientific reports showed the detrimental effects of anabolic androgenic steroids on different organs and tissues. In this literature review, we analyzed the AAS-mediated carcinogenicity, focusing on Leydig cell tumor. AAS-induced carcinogenicity can affect DNA transcription through two pathways. It can act directly via the androgen receptor, by means of dihydrotestosterone (DHT) produced by the action of 5-a-reductase. It can also work through the estrogen receptor, by means of estradiol produced by CYP19 aromatase. In addition, nandrolone and stanazolol can activate the PI3K/AKT and PLC/PKC pathways via IGF-1. This would result in cell proliferation in Leydig cell cancer, or magnify cyclin D1 concentration inducing breast cell proliferation. AAS abuse is becoming a serious public health concern in view of the severe health consequences secondary to AAS abuse. The negative role of AAS in supraphysiological dosage impairs the expression of enzymes involved in testosterone biosynthesis. Abnormal synthesis of testosterone plays has a negative effect on the hormonal changes/regulation, and might be involved in certain carcinogenic mechanisms. At the light of this review, it could become very interesting to perform an information campaign more strengthened in gyms and schools in order to prevent male fertility impairment and other tissues damage. none Salerno, Monica; Cascio, Orazio; Bertozzi, Giuseppe; Sessa, Francesco; Messina, Antonietta; Monda, Vincenzo; Cipolloni, Luigi; Biondi, Antonio; Daniele, Aurora; Pomara, Cristoforo* Salerno, Monica; Cascio, Orazio; Bertozzi, Giuseppe; Sessa, Francesco; Messina, Antonietta; Monda, Vincenzo; Cipolloni, Luigi; Biondi, Antonio; Daniele, Aurora; Pomara, Cristoforo

Cystic nephroma is a benign kidney tumor, which presents as a unilateral cystic mass without solid elements. We presented the first case of cystic nephroma treated with robotic nephron-sparing surgery in a pediatric patient. The procedure adopted was the robot-assisted simple enucleation of the lesion, without arterial clamping.

// Maria Consiglia Trotta 1, * , Monica Salerno 2, * , Anna Lisa Brigida 1 , Vincenzo Monda 3 , Antonietta Messina 3 , Carmela Fiore 2 , Roberto Avola 4 , Renato Bernardini 4 , Francesco Sessa 2 , Gabriella Marsala 5 , Guido N. Zanghi 6 , Giovanni Messina 2 , Michele D’Amico 1 and Clara Di Filippo 1 1 Department of Experimental Medicine, Division of Pharmacology, University of Campania L. Vanvitelli, Naples, Italy 2 Department of Clinical and Experimental Medicine University of Foggia, Foggia, Italy 3 Department of Experimental Medicine, Section of Human Physiology and Dietetic and Sport Medicine, University of Campania L. Vanvitelli, Naples, Italy 4 Department of Biomedical and Biotecnological Sciences, University of Catania, Catania, Italy 5 Struttura Complessa di Farmacia, Azienda Ospedaliero-Universitaria, Ospedali Riuniti di Foggia, Foggia, Italy 6 Department of Surgery, Policlinico Vittorio Emanuele University Hospital, University of Catania, Catania, Sicily, Italy * These authors contributed equally to this work Correspondence to: Giovanni Messina, email: giovanni.messina@unifg.it Keywords: long qt interval; hyperglycemia; sudden cardiac death; BF-5m; KCNQ1 and KCNE1 ion channels; Gerotarget Received: November 27, 2017 Accepted: December 08, 2017 Epub: December 14, 2017 Published: April 03, 2018 ABSTRACT Long QT syndrome (LQTS) is characterized by prolonged QT interval, leading to sudden cardiac death. Hyperglycemia is an important risk factor for LQTS, inhibiting the cardiac rapid component delayed rectifier K+ current (Iks), responsible for QT interval. We previously showed that the new ALR2 inhibitor BF-5m supplies cardioprotection from QT prolongation induced by high glucose concentration in the medium, reducing QT interval prolongation and preserving morphology. Here we investigated the effects of BF-5m on cell cytotoxicity and viability in H9c2 cells, and on cellular potassium ion channels expression. H9c2 cells were grown in medium with high glucose and high glucose plus the BF-5m by assessing the cytotoxic effects and the cell survival rate. In addition, KCNE1 and KCNQ1 expression in plasma and mitochondrial membranes were monitored. Also, the expression levels of miR-1 proved to suppress KCNQ1 and KCNE1, were analyzed. BF-5m treatment reduced the cytotoxic effects of high glucose on H9c2 cells by increasing cell survival rate and improving H9c2 morphology. Plasmatic KCNE1 and KCNQ1 expression levels were restored by BF-5m in H9c2 exposed to high glucose, down-regulating miR-1. These results suggest that BF-5m exerts cardioprotection from high glucose in rat heart ventricle H9c2 cells exposed to high glucose.

Recent studies have demonstrated that obesity is a significant risk factor for the development of several malignancies such as cancer. Colorectal cancer is among the most common cancers worldwide and is strong linked to obesity. A healthy lifestyle, characterized by hypocaloric diet and physical activity, is important to reduce a chronic inflammation, oxidative stress and metabolic disorders typical of obesity (Messina et al, 2018; Messina et al, 2017; Messina et al, 2015). It is well known that the chronic inflammation state and oxidative stress are responsible for the aging and development of many diseases, such as cancer. Dysregulation of cytokine's secretion probably participates in the establishment of cancer in obese patients. The aim of this study is to analyse the effects of sera from obese patients subjected to a physical activity program before and after weight loss on cell viability, apoptosis and oxidative stress in HCT116 carcinoma cell line treated for 24, 48 and 72 hours through MTT test. We analysed the expression of cytokines in HCT116 cells. We found that sera from obese after physical activity intervention compared to treatment with sera from obese patients before physical activity intervention reduce the survival rate of HCT116 cells through induction of apoptosis and oxidative stress. Finally, we found a reduction of mRNA levels corresponding to the pro-inflammatory IL-6 and IL-8 cytokines together with an increase of the anti-inflammatory IL-10 cytokine. We can conclude that the physical activity has numerous beneficial effects also in colorectal cancer cell, indeed the physical activity and weight loss in obese subjects have an inhibitory and anti-inflammatory effects in a short period on carcinoma cell line.

Objectives: To compare segmental ureterectomy (SU) and radical nephroureterectomy (RNU) in terms of overall survival (OS) and impact on postoperative renal function in patients treated for upper tract urothelial carcinoma (UTUC) of the ureter with preoperatively reduced estimated glomerular filtration rate (eGFR). Materials and methods: We retrospectively collected the data of consecutive patients treated for UTUC, in 6 Italian tertiary referral centers, from 2003 to 2013, and analyzed those treated with RNU or SU for ureteral cancer and with a preoperative eGFR

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.