European Society for Sexual Medicine

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) has a highly variable phenotye, with its most severe manifestations being an early (EO) or very early (VEO) onset of the disease. EO and VEO definition implies the occurrence in infancy of ADPKD-related chronic kidney disease (CKD), defined as the contemporary presence of bilateral nephromegaly and one sign of initial kidney function impairment. We argue that, even if not in the presence of such a severe phenotype, it is still worth recognising in utero ADPKD to address the affected patients to early nephrological care. The aim of our study was to describe prenatal characteristics of patients with an in utero diagnosis of ADPKD and define their long-term prognosis in terms of incidence of hypertension and CKD. Method This was a multicentre retrospective observational study. All patients with in utero characteristics of VEO-ADPKD from 1981 to 2024 were enrolled at two centres in France and Italy, namely Hôpital Necker Enfants Malades, Paris, and Meyer Children's Hospital IRCCS, Florence. The definition of VEO-ADPKD was the in utero ADPKD diagnosis due to (i) multiple bilateral cysts and/or (ii) enlarged kidneys at prenatal ultrasound. A cohort of patients with in utero diagnosis of other cystic kidney diseases (i.e. ARPKD, RCAD) was included as control group, together with a cohort of paediatric patients with ADPKD not fulfilling either VEO or EO criteria. Results We enrolled 33 VEO-ADPKD patients. Of 38 patients initially labelled as VEO-ADPKD, 5 were reclassified after genetic testing. The median follow-up was 18 (range 1–38) years. Univariate logistic regression demonstrated that a known familial history of cystic disease before diagnosis (OR 28.846, 95% CI 2.933–210.464) and birth weight (OR 1.001, 95% CI 1.000–1.002) were positively correlated with ADPKD diagnosis, while the presence of microcysts had a strong negative correlation with ADPKD diagnosis (OR 0.042, 95% CI 0.005–0.373). Multivariate analysis confirmed only the predictive role of familiarity. Figure 1 shows Kaplan-Meier curves comparing incidence of hypertension and CKD among patients with VEO-ADPKD, ARPKD, RCAD, and non-VEO-ADPKD patients. For all investigated outcomes, VEO-ADPKD had an event-free survival falling between that of patients with non-VEO-ADPKD and patients with ARPKD, the latter showing the worst renal prognosis (log-rank P < 0.001). Of note, of the four examined patients with RCAD, none developed hypertension, whereas all of them developed CKD (eGFR <90 mL/min/1.73 m2) and one had a sever kidney function impairment (eGFR <60 mL/min/1.73 m2). Conclusion Our study demonstrates that: in patients with prenatal ultrasound features of VEO-ADPKD, a known family history of cystic kidney disease represents a strong predictor of ADPKD diagnosis, whereas the presence of microcysts suggests a diagnosis of ARPKDgenetic testing is a cornerstone of VEO-ADPKD diagnostic workup, since a consistent number of patients might have a complex genetic backgroundeven considering our extended definition criteria for VEO-ADPKD, these patients show a worse long-term renal prognosis than non-VEO-ADPKD patients. Our findings strongly support the need for careful evaluation of prenatal manifestations of polycystic kidney diseases through a detailed family history, genetic testing and early nephrological assessment to guarantee the timely recognition and management of early disease complications.

The role of sex steroid hormones in the etiology of several diseases, including breast and endometrial cancer, has been widely documented. In postmenopausal females, higher concentrations of estrogens and androgens are associated with a higher risk of developing breast cancer. It is therefore important to investigate whether and how diet and physical activity (PA) can modulate sex hormone blood concentrations. We evaluated the effect of a 24-mo dietary and/or PA intervention on plasma concentrations of a series of sex hormones. The 234 study participants were healthy postmenopausal females aged 50-69 y, with high breast density, nonsmokers, and no hormone replacement therapy users. They were randomly assigned to the following 4 intervention arms: 1) isocaloric dietary intervention, mainly plant-based; 2) moderate-intensity exercise intervention with ≥1 h/wk of supervised strenuous activity; 3) both dietary and exercise interventions; 4) control group with general recommendations on healthy lifestyle. In plasma samples collected at baseline and at the end of the intervention, concentrations of estradiol, estrone, progesterone, 17-OH progesterone, testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate were determined by liquid chromatography tandem mass spectrometry methods. Sex hormone-binding globulin was determined by immunoassay, and free estradiol and testosterone were calculated using the Vermeulen method. Statistical analyses were performed using Tobit regression models. After 24 mo, females randomly assigned to dietary treatment (arms 1 + 3) showed significant lower concentrations of estradiol [exp(β) 0.77; 95% confidence interval (CI): 0.61, 0.97; P value 0.03] and free estradiol (exp(β) 0.81; 95% CI: 0.65, 0.998; P value 0.048) compared with the control group (arms 2 + 4). No significant differences emerged for the other sex hormones. No effect of PA intervention was evident. Further adjustment for weight change that occurred during the intervention did not modify the results. Our results suggest that, in healthy postmenopausal females with high breast density, a healthy diet mainly based on plant food may play a role as a modulator of plasma estradiol concentration. This trial was registered at the ISRCTN Registry (www.isrctn.com) as ISRCTN28492718.

Abstract Background and Aims Sirenomelia is a rare congenital malformation driven by fused lower extremities and associated with other anomalies of genital, urinary and gastrointestinal systems, single umbilical artery and sever oligohydramnios. It is a lethal condition in the perinatal period and only 1% of cases can survive the 1st week after birth. The survival and prognosis are closely connected to an appropriate kidney function. Method We describe 5 years of experience after renal transplantation (RT) in a rare case of sirenomelia. Results A 22-years-old gravida delivered at 40 weeks’ gestation a 2450-g female infant. No malformations were documented prenatally. At the birth, the newborn presented sireniform malformation. Radiological imaging showed a single dysplastic and ectopic kidney located in pelvic region with bladder and urethral agenesis. Alteration of the excretory tracts was characterized by absence of ureteral with a cutaneous orifice that allowed the urinary outflow. A single median ovary was recognizable; but uterus, vagina and external genitals were absent. On second day of life a terminal ileostomy was performed for anorectal and descending colon atresia. Furthermore, a surgical team succeeded in total separation of the lower limbs. The girl had progressive chronic renal failure with initial serum creatinine of 1.7 mg/dL. Subsequently, during a pyelonephritis, she developed an acute kidney injury (serum creatinine 9.2 mg/dL). We started continuous renal replacement therapy. No improvement in clinical condition was observed; pelvic nephrectomy surgery had to be performed. The gradual resolution of illness allowed us to start intermittent hemodialysis. At 16 years old, the patient received cadaveric RT and contextual ureterocutaneostomy was performed. The induction regimen consisted in basiliximab; whereas the maintenance immunosuppressive treatment consisted of tacrolimus, mycophenolate mofetil and corticosteroid. No surgical or immunological complications were reported. Her post-transplant course was characterized by some infectious events, particularly pyelonephritis. Therefore, we decided to insert a ureteral stent to allow the urinary outflow. Five years after RT, patient presents good general condition with normal blood pressure. The ureteral stent is replaced every three weeks. The most recent laboratory test reveals normal blood count, creatinine 1.14 mg/dl (eGFR 69 mL/min/1.73 m2), no electrolytic alteration, no significant proteinuria, no inflammatory markers and negative screening for viruses. Conclusion We report a rare case of sirenomelia with overall survival of approximately 21 years old and 5 years after RT. Our experience demonstrates a greater survival rate in patients with maintained renal function. The kidney transplantation may represent a management strategy in patient with similar urinary tracts anomalies.

SAD has been associated with severe asthma (SA) in several studies. Recently a positive effect of anti-IL5 drugs on SAD has been shown in small samples. The novel biologic Tezepelumab has shown an effect on reduction in airway hyperresponsiveness to mannitol and on airway remodelling in randomized controlled trials, but data on small airways measured by forced oscillometry (FOT) are still lacking. The aims of the study are: to investigate clinical, functional and biohumoral changes from the baseline (T0) to 3 months follow-up (T3) in SA patients on Tezepelumab; to investigate different response in patients with and without SAD. This is a real-world prospective single-centre study. We measured spirometry, plethysmography, FeNO, FOT and blood tests at T0 and T3. SAD was defined as the presence of both X5exp<LLN and R5-R19≥0.03. Differences between the two groups and changes between T0 and T3 were assessed with Student T-test. Significance was set at p<0.05. We included 16 patients, mean age 56±17 yrs, 94% females. 8/16 (50%) patients had SAD at baseline. At T0, patients with SAD had significantly more severe lung function impairment, higher blood neutrophil count, higher need for chronic treatment with azitromicin and higher number of hospital admissions. At T3, we observed a significantly lower number of exacerbation and corticosteroid use in both groups. There were no diffrences in quality of life, spirometry, FOT and biohumoral parameters between T0 and T3. We concluded that SAD identifies a more severe population among severe asthmatics. Although we expect the efficacy of this drug on small airways, we believe that the lack of differences in the two groups may be due to the short observation period.

The development of new medical diagnostic technologies and procedures and the drop in the birth rate observed in the last decades represent the main causes of increased incidence of uterine disorders. Endometriosis, adenomyosis and uterine fibroids are benign uterine disorders whose understanding have greatly increased and clinical management have improved in recent times. Molecular pathogenetic aspects, new imaging technologies (transvaginal ultrasound and magnetic resonance), biochemical markers, hormonal drugs, minimally invasive surgical technologies were studied for diagnosis and treatment of endometriosis, adenomyosis and uterine fibroids. Sex steroid hormones, inflammation and fibrosis are key pathogenetic mechanisms of uterine disorders. Endometriosis is characterized by endometrial cells migrating outside the uterus and implanting in the pelvis, associated with inflammation, neuroangiogenesis and fibrosis causing dysmenorrhea, pelvic pain, dysuria and dyschezia. The painful symptoms may activate central sensitization and stress responses. Adenomyosis is caused by the presence of endometrial cells within the myometrium, characterized by pelvic pain, abundant menstrual bleeding and infertility. Heavy menstrual bleeding can cause the reduction of iron reserves and consequently iron deficiency anemia. Uterine fibroids are the most common benign tumors of the uterus in women of reproductive age. They can be asymptomatic, but they frequently manifest with abnormal uterine bleeding, pelvic discomfort, and challenges with fertility. Submucosal or intramural fibroids can hinder embryo implantation and potentially lead to pregnancy-related complications such as miscarriage, placenta previa, preterm labor, or postpartum hemorrhage. The increased incidence of uterine disorders has a major clinical impact on women’s health and a very poor quality of life is often reported. Therefore, prompt diagnosis and effective management are mandatory.

Aging is the result of several complex and multifactorial processes, where several agents contribute to an increased intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms that are finely regulated and strictly interconnected, initiating or contributing to biological changes and anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic effects. Vitamin D (VitD) is known to have a positive impact not only on muscle and bone health but also on several extra-skeletal districts, due to the widespread presence of Vitamin D Receptors (VDRs). VitD and VDR could be molecules potentially targeting the hallmarks of the aging network. To date, evidence about the potential effects of VitD on the hallmarks of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seem to confirm the modulatory effect of VitD on some hallmarks of aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

To recognize patients at high risk of refractory disease, the identification of novel prognostic parameters improving stratification of newly diagnosed Hodgkin Lymphoma (HL) is still needed. This study investigates the potential value of metabolic and texture features, extracted from baseline 18F-FDG Positron Emission Tomography/Computed Tomography (PET) and Contrast-Enhanced Computed Tomography scan (CECT), together with clinical data, in predicting first-line therapy refractoriness (R) of classical HL (cHL) with mediastinal bulk involvement. We reviewed 69 cHL patients who underwent staging PET and CECT. Lesion segmentation and texture parameter extraction were performed using the freeware software LIFEx 6.3. The prognostic significance of clinical and imaging features was evaluated in relation to the development of refractory disease. Receiver operating characteristic curve, Cox proportional hazard regression and Kaplan-Meier analyses were performed to examine the potential independent predictors and to evaluate their prognostic value. Among clinical characteristics, only stage according to the German Hodgkin Group (GHSG) classification system significantly differed between R and not-R. Among CECT variables, only parameters derived from second order matrices (gray-level co-occurrence matrix (GLCM) and gray-level run length matrix (GLRLM) demonstrated significant prognostic power. Among PET variables, SUVmean, several variables derived from first (histograms, shape), and second order analyses (GLCM, GLRLM, NGLDM) exhibited significant predictive power. Such variables obtained accuracies greater than 70% at receiver operating characteristic analysis and their PFS curves resulted statistically significant in predicting refractoriness. At multivariate analysis, only HISTO_EntropyPET extracted from PET (HISTO_EntropyPET ) and GHSG stage resulted as significant independent predictors. Their combination identified 4 patient groups with significantly different PFS curves, with worst prognosis in patients with higher HISTO_EntropyPET values, regardless of the stage. Imaging radiomics may provide a reference for prognostic evaluation of patients with mediastinal bulky cHL. The best prognostic value in the prediction of R versus not-R disease was reached by combining HISTO_EntropyPET with GHSG stage.