Fog2 is required for normal diaphragm and lung development in mice and humans

Congenital diaphragmatic hernia and other congenital diaphragmatic defects are associated with significant mortality and morbidity in neonates; however, the molecular basis of these developmental anomalies is unknown. In an analysis of E18.5 embryos derived from mice treated with N-ethyl-N-nitrosourea, we identified a mutation that causes pulmonary hypoplasia and abnormal diaphragmatic development. Fog2 (Zfpm2) maps within the recombinant interval carrying the N-ethyl-N-nitrosourea-induced mutation, and DNA sequencing of Fog2 identified a mutation in a splice donor site that generates an abnormal transcript encoding a truncated protein. Human autopsy cases with diaphragmatic defect and pulmonary hypoplasia were evaluated for mutations in FOG2. Sequence analysis revealed a de novo mutation resulting in a premature stop codon in a child who died on the first day of life secondary to severe bilateral pulmonary hypoplasia and an abnormally muscularized diaphragm. Using a phenotype-driven approach, we have established that Fog2 is required for normal diaphragm and lung development, a role that has not been previously appreciated. FOG2 is the first gene implicated in the pathogenesis of nonsyndromic human congenital diaphragmatic defects, and its necessity for pulmonary development validates the hypothesis that neonates with congenital diaphragmatic hernia may also have primary pulmonary developmental abnormalities

Databases for Congenital Heart Defect Public Health Studies Across the Lifespan

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139106/1/jah31841_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139106/2/jah31841.pd

Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease

BackgroundChildren with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages.ObjectivesThe authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease.MethodsPhase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis.Primary endpointa composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy.ResultsFrom 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels.ConclusionsIn this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472)

LEFT INTRAVENTRICULAR BALLOON PUMP ORTIMIZATION DURING INTRACTABLE CARDIAC ARREST

Η ΑΡΙΣΤΕΡΗ ΕΝΔΟΚΟΙΛΙΑΚΗ ΑΝΤΛΙΑ ΔΙ'ΑΕΡΟΘΑΛΑΜΟΥ ΕΙΝΑΙ ΜΙΑ ΜΕΘΟΔΟΣ ΤΑΧΕΙΑΣ ΕΦΑΡΜΟΓΗΣ ΠΟΥ ΜΠΟΡΕΙ ΝΑ ΔΙΑΤΗΡΗΣΕΙ ΙΚΑΝΟΠΟΙΗΤΙΚΗ ΚΑΡΔΙΑΚΗ ΠΑΡΟΧΗ ΕΠΙ ΠΕΙΡΑΜΑΤΟΖΩΩΝΜΕ ΠΑΥΣΗ ΤΗΣ ΚΑΡΔΙΑΚΗΣ ΛΕΙΤΟΥΡΓΙΑΣ ΤΟΥΣ.ΣΤΗΝ ΠΑΡΟΥΣΑ ΠΕΙΡΑΜΑΤΙΚΗ ΜΕΛΕΤΗ ΕΞΕΤΑΖΕΤΑΙ Η ΔΥΝΑΤΟΤΗΤΑ ΒΕΛΤΙΣΤΟΠΟΙΗΣΗ ΤΗΣ ΑΠΟΔΟΣΗΣ ΤΗΣ ΜΕ ΕΠΙΛΟΓΗ ΤΩΝ ΚΑΤΑΛΛΗΛΟΤΕΡΩΝ ΦΥΣΙΚΩΝ ΧΑΡΑΚΤΗΡΙΣΤΙΚΩΝ ΤΟΥ ΧΡΗΣΙΜΟΠΟΙΟΥΜΕΝΟΥ ΑΕΡΟΘΑΛΑΜΟΥ.ΕΙΔΙΚΟΤΕΡΑ,ΕΞΕΤΑΖΕΤΑΙ Η ΑΙΜΟΔΥΝΑΜΙΚΗ ΕΠΙΔΡΑΣΗ ΔΙΑΦΟΡΟΥ ΟΓΚΟΥ ΚΑΙ ΣΧΗΜΑΤΟΣ ΑΕΡΟΘΑΛΑΜΩΝ ΕΠΙ ΠΕΙΡΑΜΑΤΟΖΩΩΝ ΕΥΡΙΣΚΟΜΕΝΩΝ ΣΕ ΚΟΙΛΙΑΚΗ ΜΑΡΜΑΡΥΓΗ.ΣΕ 12 ΑΝΑΙΣΘΗΤΟΠΟΙΗΜΕΝΑ ΠΕΙΡΑΜΑΤΟΖΩΑ ΚΑΘΟΡΙΖΕΤΑΙ ΥΠΕΡΗΧΟΓΡΑΦΙΚΑ Ο ΤΕΛΟΔΙΑΣΤΟΛΙΚΟΣ ΟΓΚΟΣ ΤΗΣ ΑΡΙΣΤΕΡΑΣ ΚΟΙΛΙΑΣ(ΤΔΟΑΚ).ΕΝ ΣΥΝΕΧΕΙΑ,ΠΡΟΚΑΛΕΙΤΑΙ ΚΟΙΛΙΑΚΗ ΜΑΡΜΑΡΥΓΗ ΚΑΙ ΕΙΣΑΓΕΤΑΙ ΔΙΑ ΤΗΣΚΟΡΥΦΗΣ ΤΗΣ ΑΡΙΣΤΕΡΑΣ ΚΟΙΛΙΑΣ,ΜΕ ΤΗ ΒΟΗΘΕΙΑ ΕΙΣΑΓΩΓΕΩΣ, ΑΕΡΟΘΑΛΑΜΟΣ ΑΠΙΟΕΙΔΟΥΣ ΣΧΗΜΑΤΟΣ,ΤΟΥ ΟΠΟΙΟΥ Ο ΟΓΚΟΣ ΜΠΟΡΕΙ ΝΑ ΜΕΤΑΒΑΛΛΕΤΑΙ ΕΝΤΟΣ ΟΡΙΣΜΕΝΩΝ ΟΡΙΩΝ.ΔΟΚΙΜΑΖΟΝΤΑΙ ΤΡΕΙΣ ΔΙΑΦΟΡΕΤΙΚΟΙ ΟΓΚΟΙ ΠΡΙΜΟΔΟΤΗΣΕΩΣ ΤΟΥ ΑΕΡΟΘΑΛΑΜΟ:10ΚΑΤΑ 25% ΜΙΚΡΟΤΕΡΟΣ 2)ΚΑΤΑ 25% ΜΕΓΑΛΥΤΕΡΟΣ ΚΑΙ 3) ΙΣΟΣ ΜΕ ΤΟΝ ΤΔΟΑΚ ΚΑΙ ΣΥΓΚΡΙΝΕΤΑΙ Η ΑΠΟΔΟΣΗ ΤΟΥΣ.(ΑΠΟΚΟΠΗ ΠΕΡΙΛΗΨΗΣ)THE LEFT INTRAVENTRICULAR BALLON PUMP HAS BEEN PROVED AN EFFECTIVE METHOD OF MECHANICAL CIRCULATORY SUPPORT,WHEN IT WAS USED IN EXPERIMENTAL SETTING ON DOGS WITH CARDIAC ARREST.ITS PERFORMANCE,THOUGH,CAN BE OPTIMIZED BY IMPROVING THE FEATURES OF THE CATHETER-MOUNTED BALLON.THIS EXPERIMENTAL WORK EXPLORES THE HEMODYNAMIC EFFECT OF INTRAVENTRICULAR BALLON PUMPING DURING VENTRICULAR FIBRILATION,WITH BALLONS DIFFERING IN SHAPE AND VOLUME.THE LEFT VENTRICULAR AND DIASTOLIC VOLUME(LVEDV)WAS DETERMINED (BY MEANS OF 2D ECHO)IN 12 ANESTHETIZED DOGS AND VENTRICULAR FILBRILATION WAS INDUCED BY DIRECT CURRENT APPLICATION.A CATHETER-MOUNTED BALLON WAS INSERTED INTO THE LEFT VENTRICLE THROUGH AN INTRODUCER PLACED AT THE CARDIAC APEX.BALLON PUMPING WITH A FIXED RATE OF 75 CYCLES/MIN WAS INITIATED.THE PRIMING VOLUME COULD RANGE WITHIN CERTAIN LIMITS(LVEDV+-25%).BALLON PRIMED WITH VOLUME EQUAL TO THE LVEDV MAINTAINED THE HIGHEST MEAN SYSTOLIC AORTIC PRESSURE AND AORTIC FLOW(106,4+-2,7 MMHG AND 84,7+-2.35 ML/KG/MIN RESPECTIVELY)COMPARED TO THE SMALLER BY 25% OR THE LARGER BY 25% BALLON(P =0,002).FIVE DIFFERENT BALLON SHAPES(AT LEAST TWO IN EVERY DOG)WERE SUBSEQUENTLY IN 12 ANESTHETIZED DOGS WITH VENTRICULAR FIBRILATION :1)SPHERICAL 2)PEAR-SHAPED BALLON WITH THE GATHETER RUNNING THROUGH THE BALLON3)WITH A SHAPE BEING THE CAST OF THE LEFT VENTRICLE 4)BICONVEX-SHAPED BALLON 5)PEAR-SHAPED BALLON MOUNTED AT THE DISTAL TIP OF TTHE GATHETER.(ΑΠΟΚΟΠΗ ΠΕΡΙΛΗΨΗΣ