Prenatal echocardiographic assessment of right aortic arch.

OBJECTIVES: To report our experience with fetal diagnosis of right aortic arch (RAA) variants based on the ductus arteriosus (DA) anatomy and brachiocephalic vessel branching pattern in relation to the trachea, and to establish whether the echocardiographic 'V-shaped' or 'U-shaped' appearance of the junction between the DA and aortic arch (AA) in the fetal upper mediastinal view is sufficiently accurate for assessment of fetal AA anatomy. METHODS: This was a retrospective study of pregnancies with a prenatal diagnosis of fetal RAA that had postnatal confirmation of AA anatomy, referred to our tertiary center during 2011-2017. Prenatal and postnatal medical records, including echocardiographic and computed tomography (CT)/magnetic resonance imaging (MRI) scan reports, were reviewed, and cardiac and extracardiac abnormalities and the results of genetic testing were recorded. RESULTS: Of 55 consecutive pregnancies with a prenatal diagnosis of fetal RAA, six were lost to follow-up, one was terminated and three were excluded due to lack of postnatal confirmation of AA anatomy. Of the remaining 45 pregnancies, AA anatomy was assessed postnatally by CT in 39, by MRI in one and by direct examination at cardiac surgery in five. A U-shaped appearance was found in 37/45 (82.2%) patients, all of which had a complete vascular ring (CVR). Of these 37 patients, on postnatal confirmation, 21 (56.8%) had RAA with Kommerell's diverticulum, left posterior ductus arteriosus (LPDA) and aberrant left subclavian artery (ALSA) (RAA/LPDA/ALSA), 11 (29.7%) had a double AA (DAA), four (10.8%) had RAA with Kommerell's diverticulum, LPDA and mirror-image (MI) branching (RAA/LPDA/MI), and one (2.7%) had RAA with Kommerell's diverticulum, LPDA and aberrant left innominate artery (ALIA) (RAA/LPDA/ALIA). A V-shaped appearance was found in 3/45 (6.7%) patients, all of which had RAA with right DA not forming a CVR and MI branching. In the 5/45 (11.1%) fetuses with neither U- nor V-shaped appearance, RAA with left anterior DA arising from the left innominate artery and MI branching, not forming a CVR, was found. Twelve (26.7%) fetuses had a congenital heart defect (CHD). RAA forming a CVR (U-shaped appearance) was associated with a septal defect in 6/37 (16.2%) fetuses, while RAA not forming a CVR (V-shaped appearance or no U- or V-shaped appearance) was associated with major CHD in 6/8 (75.0%) fetuses. CONCLUSIONS: In fetuses with RAA, V-shaped appearance of the junction between the DA and AA indicates only that the transverse AA and DA run together on the same side of the thorax (trachea) while a U-shaped appearance is always a sign of a CVR. Among fetuses with a CVR, RAA/LPDA/MI is more frequent than described previously. Finally, RAA forming a CVR is not usually associated with complex CHD, as opposed to RAA not forming a CVR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

One-hour post-load plasma glucose levels are associated with elevated liver enzymes.

BACKGROUND AND AIMS: Glucose-tolerant subjects who have 1-h post-load glucose levels ≥155 mg dl(-1) (normal glucose tolerance (NGT)-1h-high) are at an increased risk of developing type 2 diabetes. Prospectively conducted studies indicated that high levels of liver enzymes are predictors of a tendency to develop type 2 diabetes; however, it is unknown whether the NGT-1h-high subjects are at increased risk for secreting higher levels of liver biomarkers. METHODS AND RESULTS: In this study, oral glucose tolerance tests (OGTTs) were performed in a cohort of 1000 non-diabetic Caucasians and levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) were measured in these subjects. The NGT-1h-high subjects had increased levels of ALT and GGT, but not AST, as compared with the NGT-1h-low. Following adjustment for age and gender, the ALT, AST and GGT levels were all found to be significantly correlated with body mass index (BMI), waist circumference, blood pressure, triglycerides as well as fasting and post-challenge glucose and insulin levels. In a logistic regression analysis adjusted for age and gender, NGT-1h-high subjects were found to be at increased risk of having ALT levels in the highest quartile as compared with NGT-1h-low subjects (odds ratio (OR) = 1.71; 95% confidence interval (CI): 1.16-2.52). In addition, NGT-1 h-high subjects exhibited an increased risk for having GGT levels in the highest quartile (OR = 1.50; 95%CI: 1.02-2.17). These associations remained significant after adjustment for BMI, blood pressure and lipids, but were not significant following further adjustment for an insulin sensitivity index. NGT-1h-high subjects were at increased risk of having AST levels in the highest quartile as compared with NGT-1h-low subjects (OR = 1.51; 95%CI: 1.04-2.22). This association ceased to be significant following adjustment for BMI, blood pressure and lipids. CONCLUSIONS: These data suggest that a 1hPG ≥ 155 mg dl(-1) cut-off may facilitate the identification of NGT individuals at risk of developing liver abnormalities.

Renal Volume in ADPKD Patient Evaluation.

The clinical manifestations of ADPKD are related to the growth of renal cysts. Renal volume has been recognised as the biomarker that is able to identify those patients at risk of complications (hypertension and haematuria) and at risk of progression to End Stage Renal Disease (ESRD). Recently, several scores have been introduced to predict the evolution of ADPKD. The Mayo Clinic Group developed a classification based on renal volume as measured by CT or MRI and corrected for age and height (Ht-TKV); this allowed predicting the evolution of the disease, but it has not been fully validated so far. In addition, it is used to identify patients labelled as "fast progressors" and eligible for Tolvaptan therapy according to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) recommendations. We studied 80 patients who underwent MRI and had been classified as ADPKD typical form (class 1A-1E). A significant correlation between renal volume, hypertension, and low GFR was found (p < 0.005). A progressive increase in disease severity has been found across the different Mayo classes; 41.2% were eligible for Tolvaptan therapy. The results demonstrate that the Mayo method is easy to perform and provides valid information in order to identify with rapidly progressing disease.

Interactive data analysis and clustering of genomic data.

In this work a new clustering approach is used to explore a well- known dataset [Whitfield, M. L., Sherlock, G., Saldanha, A. J., Murray, J. I., Ball, C. A., Alexander, K. E., et al. (2002). Molecular biology of the cell: Vol. 13. Identification of genes periodically expressed in the human cell cycle and their expression in tumors (pp. 1977-2000)] of time dependent gene expression profiles in human cell cycle. The approach followed by us is realized with a multi-step procedure: after preprocessing, parameters are chosen by using data sub sampling and stability measures; for any used model, several different clustering solutions are obtained by random initialization and are selected basing on a similarity measure and a figure of merit; finally the selected solutions are tuned by evaluating a reliability measure. Three different models for clustering, K-means, Self-organizing Maps and Probabilistic Principal Surfaces are compared. Comparative analysis is carried out by considering: similarity between best solutions obtained through the three methods, absolute distortion value and validation through the use of Gene Ontology (GO) annotations. The GO annotations are used to give significance to the obtained clusters and to compare the results with those obtained in the work cited above.

Acid reflux into the oesophagus does not influence exercise-induced airway narrowing in bronchial asthma.

OBJECTIVES: A few studies on small patient series have investigated the relationship between gastroesophageal reflux and bronchial responsiveness as expressed by exercise-induced bronchoconstriction (EIB), with non-conclusive results. The aim of this study was to evaluate whether the presence of acid in the oesophagus may influence EIB. METHODS: 45 patients with bronchial asthma underwent spirometry, exercise challenge on bicycle ergometer and 24 h oesophageal pH monitoring. Subjects with EIB (Forced expiratory volume in the first second (FEV1)) percentage decrease after exercise (DeltaFEV1) > or =15%, n = 28) were retested after a 2 week treatment course with omeprazole 40 mg/daily. Exercise at baseline was performed at the same time as oesophageal pH monitoring. RESULTS: In basal condition, there was no difference in FEV1, acid exposure time or number of refluxes measured during 24 h pH monitoring between patients with and without EIB. There was no relationship between spirometry results and DeltaFEV1 on one hand, and parameters of gastroesophageal reflux on the other. Nine patients with EIB (31.0%) and six patients without EIB (37.5%) had one or more episodes of GER during exercise challenge, without significant differences between the two groups. After gastric acid inhibition by omeprazole, DeltaFEV1 did not change significantly. CONCLUSIONS: The results indicate that acid in the oesophagus, or its short-term inhibition by proton pump inhibitors, has no influence on exercise-induced bronchoconstriction.

Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts.

Heterozygous somatic mutations affecting the spliceosome gene SF3B1 drive age-related clonal hematopoiesis, myelodysplastic syndromes (MDS) and other neoplasms. To study their role in such disorders, we generated knock-in mice with hematopoietic-specific expression of Sf3b1-K700E, the commonest type of SF3B1 mutation in MDS. Sf3b1K700E/+ animals had impaired erythropoiesis and progressive anemia without ringed sideroblasts, as well as reduced hematopoietic stem cell numbers and host-repopulating fitness. To understand the molecular basis of these observations, we analyzed global RNA splicing in Sf3b1K700E/+ hematopoietic cells. Aberrant splicing was associated with the usage of cryptic 3' splice and branchpoint sites, as described for human SF3B1 mutants. However, we found a little overlap between aberrantly spliced mRNAs in mouse versus human, suggesting that anemia may be a consequence of globally disrupted splicing. Furthermore, the murine orthologues of genes associated with ring sideroblasts in human MDS, including Abcb7 and Tmem14c, were not aberrantly spliced in Sf3b1K700E/+ mice. Our findings demonstrate that, despite significant differences in affected transcripts, there is overlap in the phenotypes associated with SF3B1-K700E between human and mouse. Future studies should focus on understanding the basis of these similarities and differences as a means of deciphering the consequences of spliceosome gene mutations in MDS.

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Prokinetic effect of gut-oriented hypnosis on gastric emptying.

BACKGROUND: No data are available on the effect of hypnosis on gastric emptying. AIM: To determine the effect of a hypnosis session on gastric emptying and dyspeptic symptoms. METHODS: We studied emptying by ultrasonography and epigastric sensations in 11 healthy subjects and in 15 patients affected by functional dyspepsia under three conditions according to a fixed schedule: (a) basal, (b) after cisapride and (c) during a 90 min hypnotic trance. Eight healthy subjects repeated an emptying study listening to relaxing music. Statistical analysis was performed using the Friedman test or RM-ANOVA. RESULTS: In dyspeptics, the postprandial increase in the antral area was significantly smaller during the hypnosis trance than under the basal and the cisapride conditions. For the patients gastric emptying was significantly shortened by cisapride, and even more by hypnosis (basal 274 +/- 16.8 min; cisapride 227 +/- 13.2; hypnosis 150 +/- 9.7) whereas for healthy subjects it was shortened only by hypnosis. The repeated study in healthy subjects listening to relaxing music showed no significant difference compared with the basal. Epigastric sensations were improved in dyspeptics by hypnosis, but not by cisapride. CONCLUSIONS: Gut-oriented hypnosis is effective in shortening gastric emptying both in dyspeptic and in healthy subjects.

Locally vascularized pelvic accessory spleen.

Polysplenism and accessory spleen are congenital, usually asymptomatic anomalies. A rare case of polysplenism with ectopic spleen in pelvis of a 67-year-old, Caucasian female is reported here. A transvaginal ultrasound found a soft well-defined homogeneous and vascularized mass in the left pelvis. Patient underwent MRI evaluation and contrast-CT abdominal scan: images with parenchymal aspect, similar to spleen were obtained. Abdominal scintigraphy with 99mTc-albumin nanocolloid was performed and pelvic region was studied with planar scans and SPECT. The results showed the presence of an uptake area of the radiopharmaceutical in the pelvis, while the spleen was normally visualized. These findings confirmed the presence of an accessory spleen with an artery originated from the aorta and a vein that joined with the superior mesenteric vein. To our knowledge, in the literature, there is just only one case of a true ectopic, locally vascularized spleen in the pelvis.

"Acquired" subvalvular aortic stenosis after repair of a ventricular septal defect.

Of 353 children who underwent surgical repair of a congenital heart defect, including closure of a ventricular septal defect (VSD), 12 patients (four with tetralogy of Fallot, five with a VSD, and three with a double-outlet right ventricle) developed subaortic stenosis, which was diagnosed one to six years after the surgical procedure. Five patients required surgical treatment of the subaortic stenosis, and one required percutaneous balloon angioplasty. Postsurgical subaortic stenosis appears to be an uncommon progressive acquired disease.

Combined mustard and Rastelli operations. An alternative approach for repair of associated anomalies in congenitally corrected transposition in situs inversus [I,D,D].

We report on two patients with congenitally corrected transposition of the great arteries in situs inversus who underwent successful anatomic repair of associated cardiac anomalies--ventricular septal defect and pulmonary outflow tract obstruction. Surgical intervention was influenced by the recently introduced technique of Ilbawi and colleagues in cases of congenitally corrected transposition in situs solitus. Principles of the correction are as follows: (1) patch redirection of venous flows at the atrial level through an incision in the left-sided right atrium; (2) patch closure of the ventricular septal defect through a right ventriculotomy, baffling the left ventricle to the aorta; and (3) valved conduit interposition between the right ventricle and the pulmonary artery. If the ventricular septal defect is restrictive, it can be safely enlarged by extensive resection of the anterosuperior border, because of the posteroinferior location of the bundle of His in this anomaly. With this technique, the left ventricle and the native mitral and aortic valves are recruited for systemic work, with intrinsic long-term advantages. It is, however, a complex procedure involving substantial use of prosthetic material. More experience is necessary to establish whether this approach is superior to currently available physiologic repairs.

Revision of previous Fontan connections to total extracardiac cavopulmonary anastomosis: A multicenter experience.

BACKGROUND: Conversion to total extracardiac cavopulmonary anastomosis is an option for managing patients with dysfunction of a prior Fontan connection. METHODS: Thirty-one patients (19.9 +/- 8.8 years) underwent revision of a previous Fontan connection to total extracardiac cavopulmonary anastomosis at four institutions. Complications of the previous Fontan connection included atrial tachyarrhythmias (n = 20), progressive heart failure (n = 17), Fontan pathway obstruction (n = 10), effusions (n = 10), pulmonary venous obstruction by an enlarged right atrium (n = 6), protein-losing enteropathy (n = 3), right atrial thrombus (n = 2), subaortic stenosis (n = 1), atrioventricular valve regurgitation (n = 3), and Fontan baffle leak (n = 5). Conversion to an extracardiac cavopulmonary connection was performed with a nonvalved conduit from the inferior vena cava to the right pulmonary artery, with additional procedures as necessary. RESULTS: There have been 3 deaths. Two patients died in the perioperative period of heart failure and massive effusions. The third patient died suddenly 8 months after the operation. All surviving patients were in New York Heart Association class I (n = 20) or II (n = 7), except for 1 patient who underwent heart transplantation. Early postoperative arrhythmias occurred in 10 patients: 4 required pacemakers, and medical therapy was sufficient in 6. In 15 patients, pre-revision arrhythmias were improved. Effusions resolved in all but 1 of the patients in whom they were present before revision. The condition of 2 patients with protein-losing enteropathy improved within 30 days. CONCLUSIONS: Conversion of a failing Fontan connection to extracardiac cavopulmonary connection can be achieved with low morbidity and mortality. Optimally, revision should be undertaken early in symptomatic patients before irreversible ventricular failure ensues.

Morphology of the atrioventricular valve in asplenia syndrome: A peculiar type of atrioventricular canal defect.

The high risk of atrioventricular (AV) valve regurgitation is a major point of concern in the natural history of patients with atrioventricular canal defect (AVCD) and asplenia syndrome (AS). The morphology of the common AV valve in patients with AVCD and AS was therefore studied and compared with the anatomy of patients with AVCD but with atrial situs solitus. We compared the anatomic features of hearts with common AV valve (ventricular loop; AV valve alignment on ventricles; number of leaflets; number and morphology of papillary muscles and relationship of the bridging leaflets with the ventricular septum) in the hearts of 33 patients with AVCD and asplenia syndrome (Group 1) with those of 44 patients with common AV valve, complete AVCD, and atrial situs solitus (Group 2). Hearts featuring asplenia syndrome showed a significantly higher occurrence of anomalies of the ventricular loop (p < .0001), right ventricular dominance (p < .01), and a reduced number of valvular leaflets and papillary muscles (p < .0005). On the contrary, hearts with situs solitus of the atria showed a significantly higher frequency of balanced ventricles (p < .0001) and a common AV valve with five leaflets and five papillary muscles (p < .000001). These data suggest that AVCDs in association with asplenia syndrome present morphologic peculiarities that may be considered as the substrate for the abnormal regurgitation. Recognizing the presence of these features could be of great value for the planning of a specific surgical treatment. These anatomic differences support the hypothesis of a genetic heterogeneity of AVCDs.

Reversal of protein-losing enteropathy after ligation of systemic-pulmonary shunt.

A 21-year-old white woman, born with a univentricular heart, had undergone staged procedures before Fontan correction. She then began to develop edema, protein-losing enteropathy, and ascites refractory to diuretic therapy. Cardiac angiography showed a patent right Blalock-Taussig shunt, with turbulent cavopulmonary circulation. After undergoing an unsuccessful attempt at coil embolization she then underwent shunt ligation, with resolution of symptoms and normalization of protein levels. This report draws attention to the importance of cavopulmonary laminar flow to prevent the development of protein-losing enteropathy.

Partial atrioventricular canal with congestive heart failure in the first year of life: surgical options.

BACKGROUND: An important subgroup of patients with partial atrioventricular canal require an operation in the first year of life because of refractory congestive heart failure. METHODS: From June 1982 to April 1995, of 128 patients with partial atrioventricular canal, 35 patients (27%) underwent surgical treatment at less than 1 year of life. Associated cardiac anomalies were present in 22 patients. Only 7 patients (20%) had Down's syndrome. Five patients with left ventricular hypoplasia underwent aortic coarctectomy (3 patients) or Norwood operation (2 patients). The other 30 patients underwent anatomic repair in 24 cases and aortic coarctectomy in 6. The surgical results of patients submitted for anatomic repair were retrospectively correlated with the echocardiographic mitral valve diameter. RESULTS: There were 7 deaths (29%) after anatomic repair, 2 (22%) after aortic coarctectomy, and 2 (100%) after Norwood operation. Infants with a mitral valve diameter less than 2.5 x 10-2 m/m2 died at repair. In a mean follow-up of 73.5 months there were five secondary mitral valve plasties and three repairs after aortic coarctectomy. CONCLUSIONS: Among patients with partial atrioventricular canal, there is an important subgroup with clinical signs of heart failure in the first year of life. Left-sided obstructive lesions and complex mitral valve anomalies seem to play a fundamental role in the clinical evolution and prognosis of these patients. The echocardiographic mitral valve diameter may be useful for determining the correct surgical indication.

Total cavopulmonary direct anastomosis: a logical approach in selected patients.

A 2.5-year-old boy with a diagnosis of situs solitus, tricuspid atresia, anatomically corrected malposition of the great arteries (S,D,L), left juxtaposition of atrial appendages, and pulmonary stenosis underwent successful total cava-to-pulmonary connection by means of a superior vena cava-to-pulmonary artery end-to-side anastomosis associated with an inferior vena cava-to-pulmonary artery direct anastomosis. Anatomic features and surgical technique are described.

Neonatal pulmonary autograft implantation for cardiac tumor involving aortic valve.

We diagnosed in a 4-day-old neonate a cardiac tumor involving the left atrium, left atrioventricular junction, left ventricular outflow tract, and aortic valve with severe subvalvular and valvular aortic stenosis. The critical involvement of the aortic valve and the scarcity of neonatal cardiac donors led us to perform a successful replacement of the aortic root with a pulmonary autograft, using a very small homograft for the native pulmonary valve (Ross operation).

Fast-track congenital heart operations: a less invasive technique and early extubation.

BACKGROUND: Many novel techniques have been described for "minimally invasive" congenital cardiac operations to achieve an improved cosmetic result. There is little information on incorporation of such techniques into fast-track congenital heart operations. METHODS: We have developed an approach to fast-track congenital heart operations, which includes a cosmetic approach for repair of congenital heart defects without sacrificing adequate exposure or requiring specialized equipment, along with a simple approach to intraoperative anesthetic management that allows extubation in the operating room. The heart is exposed through a short midline skin incision and a full median sternotomy. The conventional technique of cannulation is performed. Between October 1997 and January 1999, 88 patients were operated on with this method. Cardiac anomalies included simple and complex ostium secundum atrial septal defect, sinus venous atrial septal defect, partial atrioventricular septal defect, simple and complex ventricular septal defect, and bicuspid aortic valve stenosis. RESULTS: There were no operative or late deaths. The majority of patients were extubated in the operating room or within 2 hours of operation. No patient underwent reoperation and the mean length of hospital stay was 3.9 days. Sternal instability or wound infection were not observed. CONCLUSIONS: We believe that our approach to fast-track congenital heart operation is safe and effective. The surgical technique provides good exposure and has excellent cosmetic results. Moreover, it is easy to learn and, if necessary, the surgeon can quickly gain direct access to the heart. The anesthetic management facilitates early tracheal extubation and a shorter duration of postoperative stay.

Shelhigh No-React porcine pulmonic valve conduit: a new alternative to the homograft.

BACKGROUND: The Shelhigh No-React pulmonic valve conduit is a new porcine conduit that is glutaraldehyde-treated and detoxified using a proprietary heparin process. In our institution it has been implanted in 25 patients. The aim of this present contribution is to evaluate the short-term follow-up after its implantation. METHODS: From November 1997 to August 1999, 25 patients (mean age, 20.2 years; range, 0.6 to 28.3 years) were operated on using this conduit. Seventeen patients underwent a Ross procedure for aortic valve disease, with the conduits implanted in anatomic position; 6 patients underwent right ventricular outflow tract reconstruction; 2 patients underwent the Rastelli operation. The follow-up was complete. Preoperative and postoperative two-dimensional echocardiography data were collected. RESULTS: There were two non-conduit-related deaths. Two conduits needed to be exchanged because of an increase in the gradient. Overall, all patients were improved in terms of New York Heart Association class. Comparison of preoperative and postoperative two-dimensional echocardiography gradient showed significant improvement. At the 30-month follow-up, no calcification was seen on the explanted conduits or on the two-dimensional echocardiography, although many of the patients are children. CONCLUSIONS: The Shelhigh conduits seem to be an alternative to homograft especially in infants. These experiences are preliminary, and longer follow-up is required.

Papillary muscle rupture and pericardial injuries after blunt chest trauma.

Non-penetrating cardiac trauma resulting in mitral valve rupture is uncommon, requiring a high degree of suspicion for diagnosis. Sudden and severe mitral regurgitation, unless surgically corrected rapidly lead to congestive heart failure and death. We report a patient with traumatic rupture of the antero-lateral papillary muscle of the mitral valve and pericardial injury, after a lateral blunt chest trauma, who successfully underwent emergency mitral valve replacement.