Experience of a tertiary referral center in managing bladder cancer in conjunction with neurogenic bladder

Study design: Case series. Objectives: The aim of this study was to present our experience with the management of bladder cancer (BCa) in individuals followed for neurogenic bladder (NB). Setting: An Italian tertiary referral center for NB. Methods: We retrospectively collected all pre-operative, intra-operative, and post-operative data of our NB cases with BCa, diagnosed from 2004 to 2019. Results: We included ten cases: eight with acquired spinal cord injury (SCI) and two with myelomeningocele (MMC). Considering individuals with acquired SCI, the median age at BCa diagnosis and time since SCI were 53 and 34 years, respectively. One out of seven cases had positive urine cytology. All cases underwent a radical cystectomy, diagnosing squamous cell carcinoma (SCC) and transitional cell carcinoma in 60 and 40% cases, respectively. Surgical-related complications occurred after 90% procedures. Three out of eight individuals with acquired SCI died 2, 12, and 80 months after the diagnosis. Both individuals with MMC presented no evidence of disease after 24 and 27 months. Conclusions: BCa in individuals with NB proved to be associated with a diagnosis at an advanced stage and a high rate of surgical complications. In this population we advocate annual genitourinary ultrasound exam and urine cytology, and cystoscopy in all cases of macrohematuria. Considering the low accuracy of urine cytology and the difficult-to-interpret inflamed bladder walls at cystoscopy in NB, a patient-tailored follow-up schedule based on specific risk factors (e.g., smoking status, indwelling urinary catheter) is mandatory to diagnose and treat BCa at an early stage

Robotic-assisted, laparoscopic, and open radical cystectomy: surgical data of 1400 patients from The Italian Radical Cystectomy Registry on intraoperative outcomes

Introduction: The Italian Radical Cystectomy Registry (Registro Italiano Cistectomie - RIC) aimed to analyse outcomes of a multicenter series of patients treated with radical cystectomy (RC) for bladder cancer. Material and methods: An observational, prospective, multicenter, cohort study was performed to collect data from RC and urinary diversion via open (ORC), laparoscopic (LRC), or robotic-assisted (RARC) techniques performed in 28 Italian Urological Departments. The enrolment was planned from January 2017 to June 2020 (goal: 1000 patients), with a total of 1425 patients included. Chi-square and t-tests were used for categorical and continuous variables. All tests were 2-sided, with a significance level set at p <0.05. Results: Overall median operative-time was longer in RARCs (390 minutes, IQR 335-465) than ORCs (250, 217-309) and LRCs (292, 228-350) (p <0.001). Lymph node dissection (LND) was performed more frequently in RARCs (97.1%) and LRCs (93.5%) than ORCs (85.6%) (p <0.001), with extended-LND performed 2-fold more frequently in RARCs (61.6%) (p <0.001). The neobladder rate was significantly higher (more than one-half) in RARCs. The median estimated blood loss (EBL) rate was lower in RARCs (250 ml, 165-400) than LRCs (330, 200-600) and ORCs (400, 250-600) (p <0.001), with intraoperative blood transfusion rates of 11.4%, 21.7% and 35.6%, respectively (p <0.001). The conversion to open rate was slightly higher in RARCs (6.8%) than LRCs (4.3%). Intraoperative complications occurred in 1.3% of cases without statistically significant differences among the approaches. Conclusions: Data from the RIC confirmed the need to collect as much data as possible in a multicenter manner. RARCs proves to be feasible with perioperative complication rates that do not differ from the other approaches

Open versus laparoscopic partial nephrectomy for clinical T1a renal masses: a matched-pair comparison of 280 patients with TRIFECTA outcomes (RECORd Project).

To report a matched-pair comparative analysis between open (OPN) and laparoscopic partial nephrectomy (LPN) for clinical (c) T1a renal masses from a large prospective multicenter dataset.The RECORd Project includes all patients who underwent OPN and LPN for kidney cancer between January 2009 and January 2011 at 19 Italian centers. Open and laparoscopic groups were compared regarding clinical, surgical, pathologic, functional results and TRIFECTA outcome. Multivariable logistic regression models were used to analyze predictors of WIT >25 min, surgical complications (SC) and the achievement of the TRIFECTA outcome.Overall, 301 patients had OPN and 149 LPN. Groups were matched 1:1 (140 matched pairs) for clinical diameter, tumor location and type of indication. Laparoscopic partial nephrectomy was associated with a significantly mean longer WIT (19.9 vs. 15.1 min; p 25 min (RR 6.29, p < 0.0001). The TRIFECTA was achieved in 78.6 and 74.3\% after OPN and LPN (p = ns), respectively, and the surgical approach was not a predictor of a negative TRIFECTA and SC at multivariable analysis. At 6-month follow-up, no significant differences were observed between the OPN and LPN group both in estimated glomerular filtration rate (eGFR) (∆GFR 1.1 vs. 4.1 mL/min) and in new-onset stage III-V chronic kidney disease (CKD) rate (0 vs. 0.7\%).No significant difference in achieving the TRIFECTA outcome was reported after OPN and LPN. LPN was associated with a significantly longer WIT. However, eGFR at 6-month follow-up did not differ significantly between the two surgical approaches

Surgical activity in the COVID-19 era. Trend of slowdown from a multicentre observational study

COVID-19 outbreak represented an unprecedented event that led to a redefinition of health care systems worldwide. The impact of the emergency required a deviation of the care toward the assistance to COVID-19 patients, with reduction of resources for elective activities, including surgery. We aim to report the decrease of urological surgical activity during the first weeks from the beginning of the pandemic, aiming to highlight the prioritization we applied to select patients for surgery

The dramatic COVID-19 outbreak in italy is responsible of a huge drop in urological surgical activity: A multicenter observational study

OBJECTIVE: Italy is facing the COVID-19 outbreak with an abrupt reorganization of its national health-system, in order to augment care provision to symptomatic patients. The sudden shift of personnel and resources towards COVID-19 care has led to the reduction of surgery, with possible severe drawbacks. The aim of the study is to describe the trend in surgical volume in urology, in Italy. MATERIALS AND METHODS: Thirty-three urological units with physicians affiliated to the AGILE consortium were involved in a survey. Urologists were asked to report the amount of surgical elective procedures week-by-week, from the beginning of the emergency to the following month. RESULTS: The 33 hospitals involved in the study account, globally, for 22,945 beds and are distributed in 13/20 Italian regions. Before the outbreak, the involved urology units performed an overall amount of 1,213 procedures per week, half of which were oncological. One month later, the amount of surgery declined by 78%. Lombardy, the first region with positive-cases, experienced a 94% reduction. The decrease in oncological and non-oncological surgical activity was 35,9% and 89%, respectively. The trend of the decline showed a delay of roughly 2 weeks for the other regions. CONCLUSION: Italy, the country with the highest fatality rate from COVID-19, is experiencing a sudden decline in surgical activity. It is inversely related to the increase in COVID-19 care, with potential harm particularly in the oncological field. The Italian experience can be helpful for future surgical pre-planning in other countries not so hardly hit by the disease yet

A genome-wide association study of northwestern Europeans involves the C-type natriuretic peptide signaling pathway in the etiology of human height variation

Northwestern Europeans are among the tallest of human populations. The increase in body height in these people appears to have reached a plateau, suggesting the ubiquitous presence of an optimal environment in which genetic factors may have exerted a particularly strong influence on human growth. Therefore, we performed a genome-wide association study (GWAS) of body height using 2.2 million markers in 10 074 individuals from three Dutch and one German population-based cohorts. Upon genotyping, the 12 most significantly height-associated single nucleotide polymorphisms (SNPs) from this GWAS in 6912 additional individuals of Dutch and Swedish origin, a genetic variant (rs6717918) on chromosome 2q37.1 was found to be associated with height at a genome-wide significance level (Pcombined= 3.4 × 10-9). Notably, a second SNP (rs6718438) located ∼450 bp away and in strong LD (r2= 0.77) with rs6717918 was previously found to be suggestive of a height association in 29 820 individuals of mainly northwestern European ancestry, and the over-expression of a nearby natriuretic peptide precursor type C (NPPC) gene, has been associated with overgrowth and skeletal anomalies. We also found a SNP (rs10472828) located on 5p14 near the natriuretic peptide receptor 3 (NPR3) gene, encoding a receptor of the NPPC ligand, to be associated with body height (Pcombined= 2.1 × 10-7). Taken together, these results suggest that variation in the C-type natriuretic peptide signaling pathway, involving the NPPC and NPR3 genes, plays an important role in determining human body height

A Genome-Wide Association Study of Neuroticism in a Population-Based Sample

Neuroticism is a moderately heritable personality trait considered to be a risk factor for developing major depression, anxiety disorders and dementia. We performed a genome-wide association study in 2,235 participants drawn from a population-based study of neuroticism, making this the largest association study for neuroticism to date. Neuroticism was measured by the Eysenck Personality Questionnaire. After Quality Control, we analysed 430,000 autosomal SNPs together with an additional 1.2 million SNPs imputed with high quality from the Hap Map CEU samples. We found a very small effect of population stratification, corrected using one principal component, and some cryptic kinship that required no correction. NKAIN2 showed suggestive evidence of association with neuroticism as a main effect (p<10−6) and GPC6 showed suggestive evidence for interaction with age (p≈10−7). We found support for one previously-reported association (PDE4D), but failed to replicate other recent reports. These results suggest common SNP variation does not strongly influence neuroticism. Our study was powered to detect almost all SNPs explaining at least 2% of heritability, and so our results effectively exclude the existence of loci having a major effect on neuroticism

Nck adapter proteins: functional versatility in T cells

Nck is a ubiquitously expressed adapter protein that is almost exclusively built of one SH2 domain and three SH3 domains. The two isoproteins of Nck are functionally redundant in many aspects and differ in only few amino acids that are mostly located in the linker regions between the interaction modules. Nck proteins connect receptor and non-receptor tyrosine kinases to the machinery of actin reorganisation. Thereby, Nck regulates activation-dependent processes during cell polarisation and migration and plays a crucial role in the signal transduction of a variety of receptors including for instance PDGF-, HGF-, VEGF- and Ephrin receptors. In most cases, the SH2 domain mediates binding to the phosphorylated receptor or associated phosphoproteins, while SH3 domain interactions lead to the formation of larger protein complexes. In T lymphocytes, Nck plays a pivotal role in the T cell receptor (TCR)-induced reorganisation of the actin cytoskeleton and the formation of the immunological synapse. However, in this context, two different mechanisms and adapter complexes are discussed. In the first scenario, dependent on an activation-induced conformational change in the CD3ε subunits, a direct binding of Nck to components of the TCR/CD3 complex was shown. In the second scenario, Nck is recruited to the TCR complex via phosphorylated Slp76, another central constituent of the membrane proximal activation complex. Over the past years, a large number of putative Nck interactors have been identified in different cellular systems that point to diverse additional functions of the adapter protein, e.g. in the control of gene expression and proliferation