Survival After Lung Transplant for Cystic Fibrosis in Italy: A Single Center Experience With 20 Years of Follow-up.

OBJECTIVES: Lung transplantation is currently the only treatment for end-stage respiratory failure in patients with cystic fibrosis (CF). In this study we retrospectively analyzed our experience since the start of the transplantation program in 1996 with focus on survival analysis. METHODS: All patients with CF who underwent lung transplant at our center were included (1996-2016). Survival analysis after lung transplant was performed using the Kaplan-Meier estimate, comparing by sex and by 4 eras (1996-2000, 2001-2005, 2006-2010, and 2011-2016). RESULTS: In a 20-year period, 243 patients with CF were listed for lung transplant; 123 patients (61 male, 62 female) underwent transplant, and 85 died while waiting for donor organs. The mean (SD) and median age at transplant was 27.7 (8.7) years and 26.9 years (range, 9.1 - 52.1 years), respectively. Mean (SD) forced expiratory volume in the first second was 27.6 (9.7)% predicted; 115 patients (92.0%) were pancreatic insufficient, and 43 patients (34.0%) had CF-related diabetes. Removing patients with CF who died within the first 3 postoperative months, the mean (SD) and median survival after transplant were 8.2 (5.7) years and 7.5 years (range, 3 months-20 years), respectively. Overall post-lung transplant 1-year survival was 93.6%, 5-year survival was 71.4%, 10-year survival was 53.6%, 15-year survival was 36.7%, and 20-year survival was 31.6%. We found no difference in survival between sex (P = .22) and among the 4 eras (P = .56). CONCLUSIONS: Survival after lung transplant in our single center is similar to international data.

Efficacy of Extracorporeal Photopheresis in Patients With Bronchiolitis Obliterans Syndrome After Lung Transplantation.

BACKGROUND: Lung transplantation (LT) is only therapeutic option for patients affected by chronic respiratory failure. Chronic rejection, also known as bronchiolitis obliterans syndrome (BOS), is still the main cause of death and the most important factor that influences post-transplantation quality of life. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Extracorporeal photopheresis (ECP) seems to reduce the rate of lung function decline in transplant recipients with progressive BOS. METHODS: From 1991 until now, 239 LTs were performed at our center. Fifty-four patients (22.5%) developed BOS; 15 of these (27.7%) were treated with ECP. At the beginning of the treatment, all patients showed a mean decline of forced expiratory volume in 1 second (FEV1) from baseline values of 45.8% ± 17.2%; 2 patients were in long-term oxygen therapy. RESULTS: Mean follow-up from November 2013 to June 2016 was 11.6 ± 7 months. Twelve patients (80%) showed lung function stabilization with an FEV1 range after treatment between -6% to +8% from the pre-treatment values. We did not report any adverse effects or increase of infections incidence. DISCUSSION: ECP seems to be an effective and well-tolerated therapeutic option for LT patients with BOS in terms of stabilization of lung function and increased survival.

Fatty acid profile of oesophageal mucosa in children with gastro-oesophageal reflux disease.

BACKGROUND: Polyunsaturated fatty acids, as precursors of eicosanoids, are involved in the pathogenesis of oesophageal mucosal damage and healing. AIMS: To evaluate a possible role of polyunsaturated fatty acids in the pathogenesis of gastro-oesophageal reflux, we assayed fatty acids profile of oesophageal mucosal specimens obtained by endoscopy in children without oesophageal disease and children affected by gastro-oesophageal reflux disease. PATIENTS: Eighteen children with normal 24-h oesophageal pH monitoring (GOR- group) and 18 children with gastro-oesophageal reflux disease (GOR+ group, eight with oesophagitis and 10 without), were included in the study. METHODS: Fatty acids were extracted from oesophageal mucosal specimens obtained by endoscopy and assayed by gas chromatography. RESULTS: In the GOR+ group we observed an increased percentage of mucosal polyunsaturated fatty acids, mainly arachidonic and docosohexaenoic acids (p<0.01), without differences between groups with and without oesophagitis. Significant positive correlation was found between reflux index and docosahexaenoic acid (r=0.805; p<0.001). CONCLUSIONS: The results obtained show that the current methods are able to reveal changes between normal and pathological mucosa that could be relevant in the pathogenesis of gastro-oesophageal reflux disease.

[Situs inversus and dextrocardia. Analysis of the associated congenital heart diseases (author's transl)]. / Situs inversus con destrocardia. Analisi delle cardiopatie congenite associate.

13 cases of congenital heart diseases in patients having atrial situs inversus and dextrocardia, all studied by means of angiography, are described following an up to date segmental approach. The type of atrioventricular connection was concordant in the 11 biventricular hearts; double inlet in the 2 univentricular hearts. The mode was always via two atrioventricular valves. In two cases the atrioventricular flows realized a criss-cross condition, being horizontal the interventricular septum, superior the morphologically right ventricle and inferior the morphologically left ventricle. In none of the univentricular hearts was an accessory chamber identified; they were both considered to be of indeterminate type. Ventriculo-arterial connections were: concordant in 3 cases (23%), including one case of Tetralogy with pulmonary atresia; discordant in 3 cases (23%); double outlet in 7 cases *54%). The aortic valve was in the assumed position (left and posterior to the pulmonary valve) only in the 3 cases with concordant as a rule. A ventricular septal defect was actually found in all cases; in one it was associated with pulmonary vascular disease. Obstruction to the pulmonary flow (subvalvular, valvular or vascular) was ascertained in 85% of cases, whereas aortic obstruction was never found. Overall, important congenital heart malformations appear to be frequently associated with situs inversus and dextrocardia. The ventriculo-arterial junction is identified as the most affected point.

Erythrocyte and plasma levels of glutamate and aspartate in children affected by migraine.

In this study we determined plasma and erythrocyte amino acids in children affected by migraine, in order to evaluate glutamate and aspartate metabolism in the pathogenesis of this disorder. Fifteen children with migraine with aura (mean age +/- SD = 10.3 +/- 1.56), 19 children with migraine without aura (mean age +/- SD = 10.4 +/- 1.48) and 16 healthy normal controls (mean age +/- SD 10.6 +/- 1.53) were investigated. In both migraine groups there were significantly lower plasma glutamate and aspartate levels and significantly higher erythrocyte/plasma concentration (E/P) ratios of these amino acids with respect to the controls. Erythrocyte aspartate concentrations were significantly elevated in migraine children compared to the controls, while erythrocyte glutamate concentrations showed no significant differences between groups. Similar results were observed in both migraine groups. These results seem to suggest the presence of a higher activity of the erythrocytes' glutamate/aspartate transport system that could reflect a similar alteration at the neuronal/glial cell level in the CNS. Our study suggests an imbalance of the excitatory amino acid turnover in the pathogenesis of migraine in children.

Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure.

We present the results of a cyanide-nitroprusside test (CNT) after a standardized dilution procedure of urine samples and report the efficiency of this method in detecting heterozygotes for cystinuria when applied on an open pediatric population. In the preliminary study we assayed by quantitative determination of amino acids 162 urine samples from a hospital population identifying 24 type III heterozygotes and 2 type II heterozygotes for cystinuria. The classic CNT gave 38 false positive results and 5 false negative results showing a sensitivity and specificity of 0.808 and 0.721, respectively. When progressively diluted, all samples of heterozygotes remained CNT positive up to a creatinine concentration of 90 mg/dl. At this level of dilution 31 out of 38 false positive turned to negative, thus obtaining a specificity of 0.922 without a lowering of the sensitivity in detecting heterozygotes. The standardized dilution at 90 mg/dl of creatinine concentration was applied to 74.7% of a population of 1024 schoolchildren. In this way 163 out of 210 positive results were eliminated and thus the specificity of CNT rose from 0.789 to 0.953. On the basis of these results, the method proposed can be regarded as reliable and useful for a screening program in detecting heterozygotes for cystinuria.

[Situs ambiguus and atrial isomerism. Angiographic analysis of associated congenital heart diseases]. / Situs ambiguus e isomerismo atriale. Analisi angiografica delle cardiopatie congenite associate.

Forty-seven cases of situs ambiguus have been analyzed angiographically: 24 had right atrial isomerism and 23 left atrial isomerism. The following criteria were considered for identification: auricular morphology; inferior vena cava: azygos continuation or connection in median position to the atrial cavity; bronchial anatomy; anatomy of the pulmonary arteries and their relation to the bronchi. In the group with right atrial isomerism we observed levocardia in 15 cases, dextrocardia in 7 and mesocardia in 2. Bilateral superior vena cava was identified in 13 cases. Inferior vena cava drained in most cases (21) in the middle portion of the atrial cavity; it was on the same side of the abdominal aorta in 20 cases. Pulmonary venous drainage was visualized in 19 patients: in 8 cases it followed the usual pattern of the total anomalous drainage, supracardiac (7) or infracardiac (1); in 2 cases mixed forms were found; in 9 cases the pulmonary veins entered directly the common atrial cavity. Common atrium was seen in 80% of the cases; in the remaining a huge atrial septal defect was present. The atrioventricular connection was double inlet in the 16 cases of univentricular heart; in all of them, and in additional 7 biventricular hearts, the mode was via a common atrio-ventricular valve; only in one case the atria connected to the ventricles through two distinct atrioventricular valves. The univentricular hearts in most cases (22) were, angiographically, of indeterminate type. The interventricular relationship was normal (left ventricle posterior and to the left) in 6 of the 8 biventricular hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

Double outlet right ventricle with atrioventricular discordance. Report on cases having situs solitus, dextrocardia, pulmonary stenosis and levomalposition of the aorta.

We describe six patients with situs solitus of viscera and atria, dextrocardia, atrioventricular discordance, ventricular septal defect, double outlet from the morphological right ventricle, pulmonic stenosis and levomalposition of the aorta. Four patients were male and two female; their age ranged from 3.5 to 31 years (mean 13.8 years). All had various degrees of disability, and presented with cyanosis, clubbing and high hematocrit levels. One patient had an atrio-ventricular block that varied from first to third degree; another patient showed intermittent junctional rhythm. At angiography the ventricular septum appeared to be almost perpendicular to the frontal plane in most cases, so that the anteroposterior projection resulted in a true axial view. One overriding left atrioventricular valve and one straddling right atrio-ventricular valve were demonstrated; no significant incompetence of either valve was observed. The ventricular septal defect was always single and related to the subpulmonary outflow. Pulmonic stenosis was valvular in every patient; an additional infundibular obstruction was present in one case. In two cases an additional stenosis was discovered at the supravalvular level. The left pulmonary branch was stenotic in one case; it was hypoplastic, with controlateral dilatation, in two cases; both pulmonary arteries were dilated in one case. The aorta was always to the left of the pulmonary artery, either anterior or side by side. Three patients were operated on in different Institutions: one had a pulmonic valvotomy at the age of six years; one, aged twenty, had a right Blalock-Taussig shunt; the third, with overriding left atrioventricular valve, underwent a modified Fontan operation at the age of thirty years with success.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased taurine content in esophageal mucosa of children affected by gastroesophageal reflux.

We studied the possible involvement of mucosal amino acid metabolism in the pathogenesis of gastroesophageal reflux disease in children. Eighteen children with gastroesophageal reflux disease (8 with reflux esophagitis and 10 without) and 10 children with normal 24-h esophageal pH monitoring as a comparative group underwent esophagogastroduodenoscopy with biopsies. Plasma and esophageal mucosa amino acids were assayed by liquid chromatography. In children affected by gastroesophageal reflux disease we found an increase of mucosal taurine (P < 0.01) and a decrease of serine (P < 0.01). No differences were noted between patients with and without esophagitis. Significant positive correlations (P < 0.001; r = 0.626) were found between mucosal taurine content and reflux index. Plasma amino acid concentrations did not show any significant differences among groups. Our results indicate that biochemical alterations precede the histological findings of inflammation, likely reflecting the adaptive response of the esophageal mucosa to the gastric contents exposure.