Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature.Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1-β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature.In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment.Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV.
Asymptomatic scrotal enlargement can occur in pediatric and adult patients [1,2]. A key immediate evaluation should provide early differentiation of a malignant from a benign mass, the most frequent condition in this group being hydrocele [3], a painless swelling of the scrotum due to an abnormal collection of fluid in the tunica vaginalis that surrounds the testicle [4]. A scrotal enlargement can initially be associated with significant anxiety for the patient, unable to differentiate a benign from a malignant mass. The diagnosis is clinical, after a medical consultation and examination from a physician and an ultrasound. Transillumination of the scrotum, usually performed by physicians in the office, is also a good and straight-forward method to differentiate a hydrocele from a solid testicular mass, a scrotal hernia or post-traumatic hematocele [5,6]. At present though, with the wide-spread availability of smart phones equipped with powerful lights, patients could use these tools as a smart and easy way to transilluminate the scrotum while they are home (Figure 1).
We have investigated the mitochondrial and cellular effects of the lipoxygenase inhibitor MK886. Low concentrations (1 μm) of MK886 selectively sensitized the permeability transition pore (PTP) to opening, whereas higher concentrations of MK886 (10 μm) caused depolarization through combination of an ionophoretic effect with inhibition of respiration. MK886 killed prostate cancer PC3 cells only at the higher, toxic concentration (10 μm), whereas the lower concentration (1 μm) had no major effect on cell survival. However, 1 μm MK886 alone demonstrably induced PTP-dependent mitochondrial dysfunction; and it caused cell death through the mitochondrial pathway when it was used in combination with the cyclooxygenase inhibitor, indomethacin, which had no effectsper se. Treatment with 1 μm MK886 plus indomethacin sensitized cells to killing by exogenous arachidonic acid, which induces PTP opening and cytochrome c release (Scorrano, L., Penzo, D., Petronilli, V., Pagano, F., and Bernardi, P. (2001) J. Biol. Chem. 276, 12035–12040). Combination of MK886 and cyclooxygenase inhibitors may represent a viable therapeutic strategy to force cell death through the mitochondrial pathway. This approach should be specifically useful to kill cells possessing a high flux of arachidonic acid and its metabolites like prostate and colon cancer cells.
Abstract The spontaneous adrenal hematoma is a rare event. An 83-year-old male patient presented a 26-cm asymptomatic retroperitoneal mass of doubtful renal–adrenal origin. He had been evaluated 10 years before for an adrenal incidentaloma of 2.3 cm and had refused surgery when it had reached 7 cm. Later, the mass enlarged to 26 cm and was surgically removed through an open anterior approach. The histopathology showed a solid 4 kg mass of fibrinoid–hemorrhagic material, partially necrotic, mixed with adrenal tissue, with a well-vascularized capsule. No relapse is present at 6-month follow-up. This is the largest case described of spontaneous intra-adrenal hematoma in a case with previous non-secreting adrenal adenoma. The hematoma (a 4 kg mass) developed 10 years after the first diagnosis and exposed the patient to potential damage of the surrounding organs and to high-risk abdominal surgery. Long-term follow-up of non-secreting adrenal adenomas should be recommended.
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