Cardioprotection and lifespan extension by the natural polyamine spermidine

Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends the lifespan of mice and exerts cardioprotective effects, reducing cardiac hypertrophy and preserving diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy and mitochondrial respiration, and it also improved the mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine feeding failed to provide cardioprotection in mice that lack the autophagy-related protein Atg5 in cardiomyocytes. In Dahl salt-sensitive rats that were fed a high-salt diet, a model for hypertension-induced congestive heart failure, spermidine feeding reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. In humans, high levels of dietary spermidine, as assessed from food questionnaires, correlated with reduced blood pressure and a lower incidence of cardiovascular disease. Our results suggest a new and feasible strategy for protection against cardiovascular disease

Fetal ciliopathies: a retrospective observational single-center study

Purpose!#!Report on the diagnosis of prenatally suspected multisystem ciliopathies in a single center between 2002 and 2020.!##!Methods!#!Retrospective observational single-center study including pregnancies with prenatal ultrasound features of multisystem ciliopathies, such as hyperechogenic kidneys together with polydactyly and/or other skeletal and extraskeletal findings. Cases were compared according to their prenatal findings and outcomes.!##!Results!#!36 cases of multisystem ciliopathies were diagnosed. Meckel-Gruber syndrome (MKS) was the most common ciliopathy (n = 19/36, 52.8%), followed by disorders that belong to the group of short-rib thoracic dysplasia (SRTD, n = 10/36, 27.8%) McKusick-Kaufmann syndrome (MKKS, n = 4/36, 11.1%), Bardet-Biedl syndrome (BBS, n = 2/36, 5.5%) and Joubert syndrome (n = 1/36, 2.8%). All cases showed abnormalities of the kidneys, most often hyperechogenic parenchyma (n = 26/36, 72.2%), cystic dysplasia (n = 24/36, 66.7%), and/or bilateral kidney enlargement (n = 22/36, 61.1%). Oligohydramnios was mainly present in fetuses with MKS. Polydactyly (n = 18/36), abnormalities of the CNS (n = 25/36), and heart defects (n = 10/36) were associated in 50%, 69.4%, and 27.8%, respectively.!##!Conclusion!#!Prenatal detection of renal abnormalities associated with skeletal or brain abnormalities should raise the suspicion for multisystem ciliopathies. Prenatal ultrasound can help to differentiate between different diseases and pave the way for subsequent targeted genetic testing

Vesicoamniotic Shunting before 17 + 0 Weeks in Fetuses with Lower Urinary Tract Obstruction (LUTO): Comparison of Somatex vs. Harrison Shunt Systems

(1) Background: The aim of this study was to compare perinatal outcomes and complication rates of vesicoamniotic shunting (VAS) before 17 + 0 weeks in isolated LUTO (lower urinary tract obstruction) with the Somatex® intrauterine shunt vs. the Harrison fetal bladder shunt. (2) Methods: This is a retrospective cohort study in two tertiary fetal medicine centers. From 2004–2014, the Harrison fetal bladder shunt was used, and from late 2014–2017, the Somatex shunt. Obstetrics and pediatric charts were reviewed for complications, course of pregnancy, perinatal outcome, and postnatal renal function. (3) Results: Twenty-four fetuses underwent VAS with a Harrison (H) shunt and 33 fetuses with a Somatex (S) shunt. Live birth rates and survival to last follow-up were significantly higher in the Somatex group, at 84.8% and 81.8%, respectively, vs. 50% and 33.3% in the Harrison group (p = 0.007 and p < 0.001). The dislocation rate in the Somatex group (36.4%) was significantly lower than in the Harrison group (87.5%) (p < 0.001). The median time to dislocation was significantly different, at 20.6 days (H) vs. 73.9 days (S) (p = 0.002), as was gestational age at dislocation (17 (H) vs. 25 (S) weeks, p < 0.001). Renal function was normal in early childhood in 51% (S) vs. 29% (H) (p = 0.11). (4) Conclusions: VAS before 17 + 0 weeks gestational age with a Somatex shunt improves perinatal survival significantly and might even have a positive effect on renal function, probably due to the lower dislocation rates. A normal amount of amniotic fluid in the third trimester was the best predictor of normal renal function in early childhood

Prenatal ultrasound in fetuses with polycystic kidney appearance - expanding the diagnostic algorithm

Purpose Report on the diagnosis of prenatally detected fetal kidneys with bilateral polycystic appearance in a single center between 1999 and 2020 with special focus on renal morphology and biometry, amniotic fluid and extrarenal findings and proposal for an diagnostic algorithm. Methods Retrospective observational study including pregnancies with prenatally detected kidneys with bilateral polycystic appearance (n = 98). Cases and outcomes were compared according to prenatal findings with special focus on renal morphology, amount of amniotic fluid, and presence of extrarenal abnormalities. Results Most frequent diagnoses were autosomal recessive polycystic kidney disease (ARPKD, 53.1%), Meckel-Gruber syndrome (MKS, 17.3%) and autosomal dominant polycystic kidney disease (ADPKD, 8.2%). Other diagnoses included: Joubert-, Jeune-, McKusick-Kaufman- and Bardet-Biedl syndrome, overgrowth syndromes, Mainzer-Saldino syndrome and renal tubular dysgenesis. Renal abnormalities most frequently observed were hyperechogenic parenchyma, kidney enlargement, changes of corticomedullary differentiation and cystic changes of various degree. Oligo- and anhydramnios were mainly seen in ARPKD, RTD and second-trimester MKS. Extrarenal findings included skeletal (35.7%) and cardiac (34.7%) abnormalities as well as abnormalities of the central nervous system (27.6%). Conclusion Gestational age at manifestation, kidney size, visibility of cysts, echogenicity, amniotic fluid volume, and the presence of associated extrarenal malformations allow to differentiate between the most frequent underlying diseases presenting with bilateral polycystic kidneys on prenatal ultrasound by following a diagnostic algorithm

Intrauterine Thoracoamniotic Shunting of Fetal Hydrothorax with the Somatex Intrauterine Shunt: Intrauterine Course and Postnatal Outcome

(1) Background: Severe fetal hydrothorax can be treated by intrauterine thoracoamniotic shunting (TAS). The aim of this study was to assess perinatal outcome and complication rates of TAS with a novel Somatex intrauterine shunt. (2) Methods: This is a single-center retrospective study of all fetuses with hydrothorax treated with TAS using a Somatex shunt between 2014 and 2020. (3) Results: A total of 39 fetuses were included in the study. Mean gestational age at first intervention was 27.4 weeks (range 19-33). Of these, 51% (n = 20) of fetuses had fetal hydrops, which resolved in 65% (13/20) before delivery. The live birth rate was 97% (n = 38), and 74% (n = 29) survived the neonatal period. The rate of postnatal pulmonary complications was high, with 88% of neonates requiring any kind of ventilatory support. There were 23% (n = 9) genetic abnormalities (trisomy 21 and Noonan syndrome). (4) Conclusions: TAS with a Somatex shunt has a high technical success rate, leading to high neonatal survival rates. Pregnancy and neonatal outcome is comparable to TAS for fetal hydrothorax using different shunt types