Male disadvantage?:Fetal sex and cardiovascular responses to asphyxia in preterm fetal sheep

Clinically and experimentally male fetuses are at significantly greater risk of dying or suffering injury at birth, particularly after premature delivery. We undertook a retrospective cohort analysis of 60 female and 65 male singleton preterm fetal sheep (103-104 days, 0.7 gestation) with mean arterial blood pressure (MAP), heart rate, and carotid and femoral blood flow recordings during 25 min of umbilical cord occlusion in utero. Occlusions were stopped early if fetal MAP fell below 8 mmHg or if there was asystole for >20 s. Fetuses that were able to complete the full 25-min period of occlusion showed no differences between sexes for any cardiovascular responses. Similar numbers of occlusions were stopped early in males (mean: 21 min, n = 16) and females (mean: 23 min, n = 16); however, they showed different responses. Short-occlusion males (n = 16) showed a slower initial fall in femoral vascular conductance, followed by greater bradycardia, hypotension, and associated organ hypoperfusion compared with full-occlusion fetuses. In contrast, short-occlusion females (n = 16) showed a significantly more rapid early increase in femoral vascular conductance than the full-occlusion fetuses, followed by worsening of bradycardia and hypotension that was intermediate to the full-occlusion fetuses and short-occlusion males. Among all fetuses, MAP at 15 min of occlusion, corresponding with the time of the maximal rate of fall, was correlated with postmortem weight in males (R(2) = 0.07) but not females. In conclusion, male and female fetuses showed remarkably similar chemoreflex and hemodynamic responses to severe asphyxia, but some males did show impaired hemodynamic adaptation within the normal weight range

The prognostic value of testicular microlithiasis as an incidental finding for the risk of testicular malignancy in children and the adult population:A systematic review. On behalf of the EAU pediatric urology guidelines panel

Introduction: The exact correlation of testicular microlithiasis (TM) with benign and malignant conditions remains unknown, especially in the paediatric population. The potential association of TM with testicular malignancy in adulthood has led to controversy regarding management and follow-up. Objective: To determine the prognostic importance of TM in children in correlation to the risk of testicular malignancy or infertility and compare the differences between the paediatric and adult population. Study design: We performed a literature review of the Medline, Embase and Cochrane controlled trials databases until November 2020 according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) Statement. Twenty-six publications were included in the analysis. Results: During the follow-up of 595 children with TM only one patient with TM developed a testicular malignancy during puberty. In the other 594 no testicular malignancy was found, even in the presence of risk factors. In the adult population, an increased risk for testicular malignancy in the presence of TM was found in patients with history of cryptorchidism (6% vs 0%), testicular malignancy (22% vs 2%) or sub/infertility (11–23% vs 1.7%) compared to TM-free. The difference between paediatric and adult population might be explained by the short duration of follow-up, varying between six months and three years. With an average age at inclusion of 10 years and testicular malignancies are expected to develop from puberty on, testicular malignancies might not yet have developed. Conclusion: TM is a common incidental finding that does not seem to be associated with testicular malignancy during childhood, but in the presence of risk factors is associated with testicular malignancy in the adult population. Routine monthly self-examination of the testes is recommended in children with contributing risk factors from puberty onwards. When TM is still present during transition to adulthood a more intensive follow-up could be considered

EAU-ESPU pediatric urology guidelines on testicular tumors in prepubertal boys

Background: Testicular tumors in prepubertal boys account for 1–2% of all solid pediatric tumors. They have a lower incidence, a different histologic distribution and are more often benign compared to testicular tumors in the adolescent and adult group. This fundamental difference should also lead to a different approach and treatment. Objective: To provide a guideline for diagnosis and treatment options in prepubertal boys with a testicular mass. Method: A structured literature search and review for testicular tumors in prepubertal boys was performed. All English abstracts up to the end of 2019 were screened, and relevant papers were obtained to create the guideline. Results: A painless scrotal mass is the most common clinical presentation. For evaluation, high resolution ultrasound has a detection rate of almost 100%, alpha-fetoprotein is a tumor marker, however, is age dependent. Human chorionic gonadotropin (HCG) was not a tumor marker for testis tumors in prepubertal boys. Conclusion: Based on a summary of the literature on prepubertal testis tumors, the 2021 EAU guidelines on Pediatric Urology recommend a partial orchiectomy as the primary approach in tumors with a favorable preoperative ultrasound diagnosis

CDH12 as a Candidate Gene for Kidney Injury in Posterior Urethral Valve Cases:A Genome-wide Association Study Among Patients with Obstructive Uropathies

Background: Posterior urethral valves (PUVs) and ureteropelvic junction obstruction (UPJO) are congenital obstructive uropathies that may impair kidney development. Objective: To identify genetic variants associated with kidney injury in patients with obstructive uropathy. Design, setting, and participants: We included 487 patients born in 1981 or later who underwent pyeloplasty or valve resection before 18 yr of age in the discovery phase, 102 PUV patients in a first replication phase, and 102 in a second replication phase

The role of the sympathetic nervous system in postasphyxial intestinal hypoperfusion in the pre-term sheep fetus

Asphyxia in utero in pre-term fetuses is associated with evolving hypoperfusion of the gut after the insult. We examined the role of the sympathetic nervous system (SNS) in mediating this secondary hypoperfusion. Gut blood flow changes were also assessed during postasphyxial seizures. Preterm fetal sheep at 70% of gestation (103–104 days, term is 147 days) underwent sham asphyxia or asphyxia induced by 25 min of complete cord occlusion and fetuses were studied for 3 days afterwards. Phentolamine (10 mg bolus plus 10 mg h(−1) i.v.) or saline was infused for 8 h starting 15 min after the end of asphyxia or sham asphyxia. Phentolamine blocked the fall in superior mesenteric artery blood flow (SMABF) after asphyxia and there was a significant decrease in MAP for the first 3 h of infusion (33 ± 1.6 mmHg versus vehicle 36.7 ± 0.8 mmHg, P < 0.005). During seizures SMABF fell significantly (8.3 ± 2.3 versus 11.4 ± 2.7 ml min(−1), P < 0.005), and SMABF was more than 10% below baseline for 13.0 ± 1.7 min per seizure (versus seizure duration of 78.1 ± 7.2 s). Phentolamine was associated with earlier onset of seizures (5.0 ± 0.4 versus 7.1 ± 0.7 h, P < 0.05), but no change in amplitude or duration, and prevented the fall in SMABF. In conclusion, the present study confirms the hypothesis that postasphyxial hypoperfusion of the gut is strongly mediated by the SNS. The data highlight the importance of sympathetic activity in the initial elevation of blood pressure after asphyxia and are consistent with a role for the mesenteric system as a key resistance bed that helps to maintain perfusion in other, more vulnerable systems

Are EAU/ESPU pediatric urology guideline recommendations on neurogenic bladder well received by the patients? Results of a survey on awareness in spina bifida patients and caregivers

AIMS: The Paediatric Urology Guidelines Panel reports initial experience with patient involvement in spina bifida patient groups to gather information on their awareness of the guidelines and reflection of guideline recommendations. METHODS: The survey was delivered to spina bifida patients/parents via the national society groups in Turkey, Germany, and The Netherlands. Questions included demographic features, medical status, awareness, and agreement on the recommendations given in the guidelines and future expectations. RESULTS: A total of 291 patients from 3 countries responded to the survey. Mean age was 13.9 ± 12.2 years, male/female ratio 138/151, 75% of all surveys were completed by the caregivers. The medication was taken by 78% of patients (64% anticholinergics). Complete dryness rates for urine and stool were 24% and 47%, respectively. The agreement rates on the recommendations regarding urodynamics, intermittent catheterization, anticholinergics drug use, bowel management, and life-long follow-up were 97%, 82%, 91%, 77%, and 98%, respectively. Only 8% of responders were aware of the European Association of Urology/European Society for Pediatric Urology guidelines. The priorities of patients for future expectations were as the following: quality of life (QoL), surgical techniques, development of new medications and sexuality/fertility issues. Male spina bifida patients preferred new medications and sex/fertility issues more, whereas females favored QoL issues improvement more. CONCLUSIONS: Although the native language of the involved patients was different from English, awareness of guidelines was 8%. The general approval of the recommendations given in the guidelines is quite high. The national society groups showed a great interest to get involved in the creation of the guidelines to improve health care for spina bifida patients.status: publishe

Are EAU/ESPU pediatric urology guideline recommendations on neurogenic bladder well received by the patients? Results of a survey on awareness in spina bifida patients and caregivers

Aims The Paediatric Urology Guidelines Panel reports initial experience with patient involvement in spina bifida patient groups to gather information on their awareness of the guidelines and reflection of guideline recommendations. Methods The survey was delivered to spina bifida patients/parents via the national society groups in Turkey, Germany, and The Netherlands. Questions included demographic features, medical status, awareness, and agreement on the recommendations given in the guidelines and future expectations. Results A total of 291 patients from 3 countries responded to the survey. Mean age was 13.9 +/- 12.2 years, male/female ratio 138/151, 75% of all surveys were completed by the caregivers. The medication was taken by 78% of patients (64% anticholinergics). Complete dryness rates for urine and stool were 24% and 47%, respectively. The agreement rates on the recommendations regarding urodynamics, intermittent catheterization, anticholinergics drug use, bowel management, and life-long follow-up were 97%, 82%, 91%, 77%, and 98%, respectively. Only 8% of responders were aware of the European Association of Urology/European Society for Pediatric Urology guidelines. The priorities of patients for future expectations were as the following: quality of life (QoL), surgical techniques, development of new medications and sexuality/fertility issues. Male spina bifida patients preferred new medications and sex/fertility issues more, whereas females favored QoL issues improvement more. Conclusions Although the native language of the involved patients was different from English, awareness of guidelines was 8%. The general approval of the recommendations given in the guidelines is quite high. The national society groups showed a great interest to get involved in the creation of the guidelines to improve health care for spina bifida patients

Total Warm Ischemia and Reperfusion Impairs Flow in All Rat Gut Layers but Increases Leukocyte–Vessel Wall Interactions in the Submucosa Only

OBJECTIVE: To study the effect of warm ischemia and reperfusion (I/R) on local perfusion and leukocyte–vessel wall interactions in vivo in all small bowel layers, and to quantify small bowel tissue injury histologically and by measuring intestinal fatty acid binding protein (I-FABP) release from the enterocytes. SUMMARY BACKGROUND DATA: Gut injury as a result of I/R plays a pivotal role in a variety of clinical conditions, such as small bowel transplantation, heart or aortic surgery, and (septic) shock. The precise mechanism behind I/R injury and the role of microvascular changes remain unclear. The influence of warm I/R of the gut on microvascular parameters in the different gut layers has not been studied before. METHODS: Anesthetized Lewis rats were either subjected to 30 minutes of ischemia and 1 hour of reperfusion or sham-treated as controls. After ligating the inferior mesenteric artery, total warm ischemia was induced by clamping the superior mesenteric artery. Intravital video microscopic measurements were obtained at intervals. Tissue injury of the small bowel and other organs was histologically evaluated afterward. In addition, plasma levels of I-FABP were determined to measure enterocyte damage. RESULTS: After ischemia, mean red blood cell velocity decreased significantly in all layers of the small bowel, but no diameter changes were observed. Leukocyte–vessel wall interactions increased in the submucosa but not in the muscle layers. Plasma levels of I-FABP significantly increased from 30 minutes of reperfusion onward. The intestinal mucosa was severely injured; no histologic damage was detected in other tissues. CONCLUSIONS: This is the first in vivo study showing that total warm ischemia of the rat gut impairs perfusion in the whole small bowel, whereas leukocyte–vessel wall interactions increase in the submucosal layer only. Therefore, the early inflammatory response to I/R seems to be limited to the submucosa. Both microvascular effects may have contributed to the severe morphologic and functional mucosal injury observed after I/R