T cells in human skin play an important role in the immune defense against pathogens and tumors. T cells are present already in fetal skin, where little is known about their cellular phenotype and biological function. Using single-cell analyses, we identified a naive T cell population expressing αβ and γδ T cell receptors (TCRs) that was enriched in fetal skin and intestine but not detected in other fetal organs and peripheral blood. TCR sequencing data revealed that double-positive (DP) αβγδ T cells displayed little overlap of CDR3 sequences with single-positive αβ T cells. Gene signatures, cytokine profiles and in silico receptor–ligand interaction studies indicate their contribution to early skin development. DP αβγδ T cells were phosphoantigen responsive, suggesting their participation in the protection of the fetus against pathogens in intrauterine infections. Together, our analyses unveil a unique cutaneous T cell type within the native skin microenvironment and point to fundamental differences in the immune surveillance between fetal and adult human skin.

Background The psychosexual outcome in adolescents and young adults (AYA) men born with hypospadias is precarious. However, the factors responsible for impaired outcome in some AYA men have been understudied. Aim To explore the outcome after hypospadias repair in childhood of AYA men aged 16–21 years and examine their opinion and their parents’ opinion about this type of surgery. Methods Cross-sectional assessment of 193 AYA men born with hypospadias and 50 male controls was performed. Questionnaires such as the Decision Regret Scale, Pediatric Penile Perception Score, Sexual Quality of Life–Male, International Index of Erectile Function, and a custom-made questionnaire were used. The Decision Regret Scale and a custom-made questionnaire were also completed by the participants' parents. Physical examination including Hypospadias Objective Penile Evaluation and measuring stretched penile length was performed. Outcomes This study reports the psychosexual functioning (ie, social, relational, and sexual), erectile and sexual function after childhood hypospadias repair, using ad hoc measures. In addition, the opinion about hypospadias repair of patients and their parents is represented. Results The number of surgeries and satisfaction regarding penile appearance were the most important factors associated with the opinion on hypospadias repair and the psychosexual outcome. Most AYA men were more satisfied with their penile appearance than the physician. 80% of men were satisfied with having had a childhood hypospadias repair, even though they had not been able to consent to surgery themselves. Erectile and ejaculation problems were mild and seen in approximately 10% of the population. Clinical Implications Based on our data, deferring hypospadias repair until the patient can decide himself is not warranted. However, physicians who accept a suboptimal esthetic outcome and withdraw from repeated surgery may contribute importantly to the patient's well-being, especially in proximal forms of hypospadias. Strengths & Limitations This is one of the rare studies addressing the AYA's psychosexual outcome after childhood hypospadias repair. Strengths include the combination of clinical and psychosexual data from a very large cohort of men and their parents to provide a more holistic view. By entering this study, participants might have a different comfort level regarding their sexuality or have a different body image than the overall population of young men. Conclusion Uncomplicated hypospadias surgery results in equal psychosexual outcome as controls and in high satisfaction rates; multiple surgeries are a risk factor for poorer outcomes. 80% of men are satisfied with childhood hypospadias repair.

PurposeTo investigate the association between Apparent Diffusion Coefficient (ADC) values and cell cycle and proliferative biomarkers (p53, p21, Ki67,) in order to establish its potential role as a noninvasive biomarker for prediction of cell cycle, proliferative activity and biological aggressiveness in bladder cancer.Materials and MethodsPatients with bladder cancer who underwent 3,0 Tesla DW-MRI of the bladder before TUR-B or radical cystectomy were eligible for this prospective IRB-approved study. Histological specimen were immunohistochemically stained for the following markers: p53, p21 and ki67. Two board-certified uropathologists reviewed the specimens blinded to DW-MRI results. Histological grade and T-stage were classified according to the WHO 2004 and the 2009 TNM classification, respectively. Nonparametric univariate and multivariate statistics including correlation, logistic regression and ROC analysis were applied.ResultsMuscle invasive bladder cancer was histologically confirmed in 10 out of 41 patients. All examined tissue biomarkers were significantly correlated with ADC values (p<0.05, respectively). Based on multivariate analysis, p53 and ADC are both independent prognostic factors for muscle invasiveness of bladder cancer (>/ = T2). (p = 0.013 and p = 0.018).ConclusionADC values are associated with cell cycle and proliferative biomarkers and do thereby reflect invasive and proliferative potential in bladder cancer. ADC and p53 are both independent prognostic factors for muscle invasiveness in bladder cancer.

Very few among us faced the last global pandemic: the 9 "Spanish flu" pandemic of 1918-1919 transformed the 10 world a century ago [1]. The modern world in 2020 is facing 11 a new pandemic with . We initially followed 12 from afar, as the pandemic started in China and then spread 13 further to South Korea, Iran, Italy, and Spain, and now 14 further on worldwide. The COVID-19 pandemic is now in 15 our hospitals and houses. While people feel united in the fight against this 16 common threat, it is becoming obvious that the lack of 17 coordination between countries makes a united fight 18 more difficult [3]. Worldwide, health care systems 19 strongly depend on the politics and culture of individual 20 countries, with wide variations seen. The spectrum of 21 possibilities ranges from health systems in which (almost) 22 55 preventing morbidity (urinary tract infections [UTIs]) as on 56 a long-term perspective of preventing renal function loss 57 and assuring normal genital cosmesis and function. One 58 might wonder how urgent surgery is for a congenital 59 malformation. Life-threatening malformations, such as in 60 the heart or lung, are considered urgent without any doubt, 61 but how urgent is repair of hypospadias or bladder 62 exstrophy? As we have to expect major limitations in 63 access to surgical capacity over the coming months, the 64 variety of surgical indications that need to be considered for 65 prioritisation includes obstructive uropathy and recurrent 66 febrile UTIs putting children at intermediate-term risk of 67 loss of renal function. However, it is nearly impossible to 68 translate these issues to a definitive recommendation of 69 how long such interventions could be postponed, as the 70 dynamics of renal function loss depend on many variables 71 that are mostly impossible to predict [6]. It is likely that a 72 timeframe of 6-12 wk might be relevant for severe 73 obstruction, but for UTI-associated renal function loss such 74 a timeframe is harder to quantify.75 Paediatric urology guidelines are based on expert 76 opinions and these have shifted over time. Exstrophy E U R O P E A N U R O L O G Y X X X ( 2 0 1 9 ) X X X -X X X a v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e u r o p e a n u r o l o g y . c o mEURURO 8816 1-2 77 vesicae used to be considered an emergency requiring 78 immediate closure, whereas the current trend now is for 79 delayed closure. Wilms tumour has two different scientifi-80 cally validated treatments: chemotherapy first or surgery 81 first. 82 The result of this lack of evidence regarding "high 83 priority" surgery has led to variations in the delay of 84 paediatric urology procedures in many European countries. 85 In Belgium, France, Turkey, and Germany, all outpatient 86 cases have been cancelled and only surgeries related to 87 organ viability have been performed since the first week of 88 March 2020 (testicular torsion, incarcerated inguinal 89 hernia, obstructing ureteral stones, Wilms tumour in the 90 timeframe...

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