Lung transplantation for cystic fibrosis in Italy.

Lung transplantation (LT) is the only effective form of therapy for cystic fibrosis (CF) associated with end-stage pulmonary failure. In Italy, the management of CF is regulated by national law, which has instituted regional centers for care and follow-up of all CF patients. LT has been performed since 1992 in only nine LT certified centers. The structured national organization has led to a unified database for LT for CF. As of December 2006, 197 bilateral LT (96 male and 94 female patients; 7 retransplants) have been performed. Of these, four had also liver or heart and liver transplantation, and three are long-term survivors. Overall median survival is 7 years. Mean age at transplantation is 26.5 years, and the mortality on the waiting list is 33.6%. Patients listed for transplant either received a suitable donor within a mean of 10 months or died within a mean of 5.5 months. The most frequent cause of death is bronchiolitis obliterans syndrome (BOS). Our nationwide database indicates the excellent results obtained by LT in FC. Still, mortality on the waiting list remains a challenge and long-term outcome is limited by BOS.

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.

Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis.

BACKGROUND: Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. AIMS: To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. PATIENTS: Patients with pancreatic exocrine insufficiency due to cystic fibrosis. METHODS: Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. RESULTS AND CONCLUSIONS: Of the 33/60 patients who expressed a preference for one of the two treatments, 30 preferred Creon while only 3 patients preferred Pancrease (p<0.001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon. The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease.

Partial monosomy for a 21 chromosome. Report of a new case of r(21) and review of the literature.

A 21-month-old male infant with 46,XY,r(21) constitution identified by G and R banding is reported. The main clinical features were mental and physical retardation, microcephaly, antimongoloid slant of eyelids, malformed and low set ears. The clinical and cytogenetic findings of previously reported cases of r(21) are reviewed. Clinical resemblance to the eleven cases described in the literature is striking. The assays for superoxide dismutase (SOD-1) activity in the red blood cells from patient and his parents gave normal results. This findings is compatible with the hypothesis that only the segment distal to the SOD-1 locus, i.e. 21q22.2 leads to qter, has been lost during ring formation.

Beneficial effect of prolonged total parenteral nutrition in a very malnourished cystic fibrosis patients.

A very malnourished Cystic Fibrosis (CF) patient was treated with integrative Parenteral Nutrition (PN). With a mean caloric supplementation of 2,550 Kcal/day a weight gain of 6.5 Kg was achieved. In spite of severe pulmonary complications (pneumotorax and pneumomediastinum), pO2 increased from 53 to 72 mmHg and pCO2 from 38 to 56 mm Hg. General conditions improved, appetite was restored and the patient cleared off continuous oxygen therapy; he left the hospital and did not present any more pulmonary exacerbations. In the following 8-month period he maintained a daily caloric intake of 80 Kcal/kg with a further weight gain of 4.5 Kg.

Leukocyte locomotory function in children with the immotile cilia syndrome.

The random motility of polymorphonuclear leucocytes (PMN), cellular chemotaxis and chemokinesis in kinetic fashion in 4 patients with immotile cilia syndrome (ICS) have been evaluated. No impairment of granulocyte ability of orientation and migration was found. Ultrastructural alterations of cilia which are the primary factor in the pathogenesis of respiratory tract disease in patients with ICS do not impair the PMN function.

Gallstones in cystic fibrosis: a critical reappraisal.

Radiolucent gallstones are common in young adults with cystic fibrosis. In the mid-1970s, it was suggested that gallstones are made of cholesterol, but this hypothesis has never been tested. Several recent studies have shown that the detection of cholesterol monohydrate crystals in bile has high sensitivity and specificity for the diagnosis of cholesterol gallstones. We therefore used this approach to study 17 young adults with cystic fibrosis, 10 of whom had radiolucent gallstones. The two groups of patients were comparable in age and gender (all patients but one were male). Duodenal bile was obtained after gallbladder contraction with intravenous cerulein; it was used for lipid and protein chemistry studies and for polarizing microscopy. The latter was performed both in whole bile and in the postultracentrifugation (100,000 g) sediment. Bile cholesterol saturation did not significantly differ between patients with (1.21 +/- 0.28) or without gallstones (0.99 +/- 0.54). Slight cholesterol supersaturation was found in 7 of 10 gallstone and three of seven nongallstone patients. At no time were cholesterol crystals detected in either the group, even after bile ultracentrifugation. Two more cystic fibrosis patients with gallstones died of severe bronchopneumopathy, and small pigment gallstones were obtained at autopsy. At stone analysis, cholesterol content was 44% and 28% of dry weight, respectively. Infrared spectroscopy of stone powder was compatible with the presence of calcium bilirubinate and proteins as major components. We conclude that radiolucent gallstones of cystic fibrosis are not of the conventional cholesterol type.

Hepatobiliary involvement in adolescents and adults with cystic fibrosis.

Fifty nine C.F. pts (38 males) aged 14-41 years have been considered, for all of them the following parameters were taken into account: Shwachman clinical score modified (radiological evaluation emended), steatorrhea, liver function tests (SGOT, SGPT, GT, Bilirubin, AP, Quick T.), A and B hepatitis markers and ultrasonographic scan of pancreas and hepatobiliary system. 23 pts (38%) presented well recognized hepatobiliary involvement: 2 pts (3%) evident cirrhosis, 3 pts (5%) cirrhosis with portal hypertension and esophageal varices, 5 pts (8%) were affected with signs of chronic hepatopathy, 13 pts (22%) presented gallbladder stones.

Spondylodiscitis after bilateral sequential lung transplantation in a patient with cystic fibrosis.

We report the case of a 24-year-old woman with cystic fibrosis in whom spondylodiscitis developed after bilateral sequential transplantation. The diagnostic work-up included magnetic resonance imaging, computed tomography-guided disk biopsy, histological examination, and cultures of disk specimens. The infective organism was D group Streptococcus and the patient was successfully treated with intravenous piperacillin followed by oral ampicillin. To our knowledge, this is the first reported case of spondylodiscitis after lung transplantation.

Effect of a medium dose of ursodeoxycholic acid with or without taurine supplementation on the nutritional status of patients with cystic fibrosis: a randomized, placebo-controlled, crossover trial.

Ursodeoxycholic acid administration has been reported to improve cholestasis and inflammatory activity in primary biliary cirrhosis and, in an uncontrolled study, also in young adults with cystic fibrosis (CF) and chronic cholestasis. As an improvement in nutritional status was also observed in these young adult patients, we investigated whether the administration of a medium dose of ursodeoxycholic acid ameliorates the nutritional status of malnourished young adult CF patients with chronic liver disease. The study included 51 patients (27 male patients and 24 female patients; age range, 8-32 years; median, 14) with body mass percentiles < 90%. Patients were randomly assigned to receive either ursodeoxycholic acid (10-12 mg/kg/day) alone or with taurine (18-22 mg/kg/day). Patients were followed in a crossover fashion within each group; 6 months of treatment was randomly alternated with 6 months of placebo. Nine patients dropped out before concluding the study. Liver function tests, nutritional status, and coefficients of fat absorption were determined at entry and after each 6 months of placebo or treatment. Nutritional status and fat absorption were not significantly modified by either treatment. Liver function tests improved after ursodeoxycholic acid administration only in patients with concomitant chronic liver disease. Our findings indicate that 6 months of therapy with a medium dose of ursodeoxycholic acid, either alone or with taurine, does not improve the nutritional status of young malnourished CF patients. Higher doses given for longer periods might be worth investigating.