Federico Alghisi

The etiology of acute recurrent pancreatitis in children: A challenge for pediatricians

Objectives: To assess specific etiologies of acute recurrent pancreatitis at a single Italian pediatric cystic fibrosis (CF) center. Methods: We studied, retrospectively, 78 young patients (39 female subjects; mean age at diagnosis, 8.8 ± 5.1 years) affected by acute recurrent episodes of pancreatitis, remained etiologically undiagnosed at first-level assessment. All patients were submitted to endoscopic retrograde cholangiopancreatography to exclude biliopancreatic malformations and tested for CF by a sweat chloride test. Most patients also were studied for the research of CFTR, PRSS1, and SPINK1 gene mutations. Results: A high percentage of family history for chronic pancreatitis was observed (20.5%). The sweat test identified 8 subjects (10.3%) with classic CF (2 patients) or at risk for CF (6 patients). Genetic analysis showed mutations in CFTR, SPINK1, and PRSS1 genes in 39.6%, 7.1%, and 4.5% of patients, respectively. A biliopancreatic malformation was diagnosed in 15 patients (19.2%). We also observed biliary lithiasis (5 patients [6.5%]), congenital pancreatic polycystosis (2 patients), a case of dyslipidemia, and 1 patient with a posttransplantation, drug-induced pancreatitis. Conclusions: Recurrent pancreatitis in children has several etiologies. Genetic testing confirms the high frequency of CFTR mutations. This suggests that it is of some value to identify patients with late-onset CF and CFTR-related disorders.

Growth assessment of paediatric patients with CF comparing different auxologic indicators: a multicentre Italian study.

Objectives:To evaluate growth in Italian patients with cystic fibrosis (CF). Patients and Methods:A multicentre cross-sectional study was carried out on patients with CF attending Italian reference centres. Anthropometric data were evaluated using the Centers for Disease Control and Prevention 2000 reference data. Nutritional failure was defined as height-for-age percentile (HAP) <5th (all patients); weight-for-length percentile (WLP) <10th (patients <2 years); body mass index percentile (BMIp) <15th (patients between 2 and 18 years). The risk of malnutrition (defined as HAP, WLP, and BMIp <25th) and the proportion of patients below the “BMIp goal” (BMIp ≥50th) were also evaluated. Nutritional status was evaluated in the whole population and in relation to age, sex, pancreatic insufficiency, meconium ileus, and lung function. Results:A total of 892 patients with CF (50.7% males, mean age 9.2 years, range 0.1–18 years) were enrolled. The proportion of children with HAP <5th, WLP<10th and BMIp<15th was 12.2%. 12.9%, 20.9%, respectively, and 54.4% did not fulfill the BMIp ≥50th goal. HAP <25th identified the highest proportion of children at risk of malnutrition, whereas BMIp <15th identified the highest proportion of children with nutritional failure. Whatever the criterion used to define malnutrition, the highest proportion of children with nutritional failure was found in adolescence (11–18 years). z scores for height, weight, and BMI were significantly associated with pancreatic status and lung function. Differences among centres for the auxologic parameters were not significant, except for BMIp. Conclusions:Nutritional failure is present in a minority of Italian patients with CF, particularly during adolescence. Different auxologic indicators should be used for identifying children at risk for or with actual malnutrition.

Bone and body composition analyzed by Dual-energy X-ray Absorptiometry (DXA) in clinical and nutritional evaluation of young patients with Cystic Fibrosis: a cross-sectional study

Backgroundthe improved general therapy has led to reduced morbidity and mortality from Cystic Fibrosis (CF), and bone status may have a potentially greater clinical impact.We investigated the correlation between the severity of the clinical condition, bone status and body composition parameters, in a group of children and young adults with CF.Methodswe measured lumbar spine bone density and total body composition by dual energy x-ray absorptiometry (DXA) in 82 consecutive CF patients (42 males; median age: 13 years - range: 5-30). Eighty-two healthy subjects, matched for age, gender, height and pubertal stage were recruited as a control group.Results37 patients (45.1%) had a normal bone mineral density (BMD). A BMD reduction were observed in 45 (54.8%) patients. Lumbar spine Z score was positively related to Body Mass Index (BMI) and a higher Shwachman-Kulczycki score, and negatively related to Crispin-Norman score. A positive and significant correlation was also observed between lumbar spine Z score and total body composition.Conclusiona significant BMD reduction can be present early in CF children and adolescents. A careful follow up of bone status is required starting in childhood.

Acoustic radiation force impulse (ARFI) imaging with Virtual Touch Tissue Quantification in liver disease associated with cystic fibrosis in children.

PurposeCystic-fibrosis-associated liver disease (CFLD) may lead to portal hypertension (PHT) and cirrhosis. Clinical signs and biochemistry of liver involvement are not discriminating. The aim of the study was to evaluate the performance of acoustic radiation force impulse (ARFI) with virtual tissue quantification in comparison with clinical signs, biochemistry and standard hepatic ultrasound (US) patterns.Materials and methodsVirtual Touch Tissue Quantification, an implementation of US ARFI with shear-wave velocity (SWV) measurements was used in 75 children with cystic fibrosis (CF) and suspected CFLD to quantify hepatic stiffness. In each patient, ten measurements of SWV were performed on the right hepatic lobe. Patients were also evaluated by standard diagnostic tools (standard US, liver- and lung function tests, oesophagogastroscopy).ResultsAmong CF patients, median SWV was significantly higher in patients with clinical, biochemical and US signs of hepatic involvement than in patients without US evidence of liver disease 1.08 m/s [(95% confidence interval (CI), 1.02–1.14]. Median SWV values in patients with portal hypertension, splenomegaly and oesophageal varices were 1.30 (95% CI, 1.17–1.43), 1.54 (95% CI, 1.32–1.75) and 1.63 (95% CI, 1.26–1.99), respectively. Differences were significant (p<0.001).ConclusionsARFI is an innovative screening technique able to help identify CFLD in children.RiassuntoObiettivoIl coinvolgimento epatico nella fibrosi cistica (CFLD) può condurre ad ipertensione portale (IP) e cirrosi. I segni clinici e biochimici della malattia epatica non sono discriminanti. Scopo dello studio è la valutazione della performance della tecnica ecografica acoustic radiation force impulse (ARFI) con Virtual Touch Tissue Quantification, a confronto con i rilievi ecografici standard, i segni clinici e i dati di laboratorio.Materiali e metodiIl Virtual Touch Tissue Quantification, una applicazione quantitativa della tecnica ecografica ARFI che fornisce valori numerici (shear wave velocity, SWV: velocità di propagazione dell’onda) della elasticità del parenchima epatico è stato utilizzato in 75 pazienti pediatrici affetti da fibrosi cistica (FC) nel sospetto di CFLD. Per ogni paziente sono state effettuate a livello del lobo destro del fegato, 10 misurazioni della velocità di propagazione dell’onda (SWV). Gli stessi pazienti sono stati sottoposti a valutazione standard (esame ecografico del fegato, test di funzionalità epatica e polmonare e esofagogastroscopia).RisultatiNei bambini affetti da FC si è riscontrato che la mediana della SWV è significativamente più alta nei pazienti con i segni clinici, biochimici e ecografici di coinvolgimento epatico rispetto ai valori riscontrati nei pazienti senza evidenza ecografica di malattia 1,08 m/s [95% intervallo di confidenza (CI) 1,02–1,14]. La mediana dei valori SWV nei pazienti con ipertensione portale, splenomegalia e varici esofagee è stata documentata rispettivamente di: 1,30 m/s (95%CI 1,17–1,43), 1,54 m/s (95%CI 1,32–1,75), 1,63 m/s (95%CI 1,26–1,99). Le differenze sono state significative (p<0,001).ConclusioniL’ARFI è una tecnica innovativa di imaging in grado di aiutare nella identificazione del coinvolgimento epatico nei pazienti pediatrici affetti da FC.

Safety and immunogenicity of a monovalent MF59®-adjuvanted A/H1N1 vaccine in HIV-infected children and young adults.

BACKGROUND This Phase IV study evaluated the safety and immunogenicity of a two-dose, MF59®-adjuvanted (Novartis Vaccines, Marburg, Germany), monovalent, A/H1N1 pandemic influenza vaccination schedule in Human Immunodeficiency Virus (HIV) positive children and young adults. METHODS A total of 83 children infected with HIV-1, and 37 non-immunocompromised, age-matched controls were enrolled. All participants received two vaccine doses administered three weeks apart. Antibody responses were assessed by haemagglutination assay at baseline, three weeks after each vaccine dose, and six months after immunization. Vaccines were evaluated according to European influenza vaccine licensure criteria. RESULTS The investigational vaccine was well tolerated. After the first vaccine dose, seroconversion rates were significantly lower in HIV-positive patients (60%) than controls (82%), with GMTs of 419 and 600, respectively. No significant differences in seroconversion rates were observed between the two study groups in response to the second vaccine dose. Persisting antibody titers were similar for both HIV-positive and non-infected controls, six months after immunization. CONCLUSION One dose of MF59-adjuvanted vaccine was sufficient to provide adequate levels of seroprotection against A/H1N1 influenza disease in HIV-positive children. However, a two-dose vaccination schedule may be optimal for this population.

Totally implantable central venous access ports in patients with cystic fibrosis: a multicenter prospective cohort study.

Purpose The aim of this study was to assess the incidence of late onset complications of totally implantable venous access devices (TIVAD) in patients with cystic fibrosis (CF) and to investigate possible associations between the rate of complications and different policies of TIVAD management. Methods A multicenter prospective cohort study was performed in 11 Italian CF Centers. Patients with CF and a TIVAD were recruited and followed-up. Results The study commenced on May 2008 and ended on September 2010. Eighty subjects were studied (77.5% women - mean age 27.2 years). Eighteen late complications of ports were observed (22.5%; incidence 0.96 per 1000 days of observation): three lumen occlusions, seven catheter-related infections, three port-related venous thrombosis, in addition to five other complications. A statistically significant association was found between the onset of catheter-related infection and the presence of CF-related diabetes (CFRD) (P=.0064) Conclusions Our data suggest that TIVADs represent a safe and effective device for the intermittent IV administration of drugs in people with CF. However, people with CFRD have a higher risk of developing TIVAD-related infection.

Pilot study on the use of acoustic radiation force impulse imaging in the staging of cystic fibrosis associated liver disease.

BACKGROUND Acoustic radiation force impulse (ARFI) is a novel technique for the measurement of hepatic stiffness, which could be valuable in clinical follow-up of patients affected by cystic fibrosis liver disease (CFLD). METHODS Seventy-five patients with suspected CFLD (35 males) underwent clinical and ultrasonographic evaluations, liver and pulmonary function tests, ARFI investigation, and upper gastrointestinal endoscopy. Ten ARFI measurements were taken at the deep right hepatic lobe to compute median values of Shear Wave Velocity (SWV) for each individual. RESULTS SWV increased progressively from 1.02m/s (95%, Confidence Interval, CI, 0.92-1.126) in patients with no evidence of CFLD at ultrasonography (N=16), to 1.12 (95%CI 1.049-1.19) in patients with CFLD and no signs of portal hypertension (PHT, N=23), and to 1.25 (95%CI 1.14-1.358) in those with CFLD and signs of PHT (N=28). SWV was 1.63 (95%CI 1.26-1.99) in patients with oesophageal varices (N=8) (p<0.0001). CONCLUSIONS ARFI may represent an easy, fast and non-invasive tool for the clinical follow-up of patients with cystic fibrosis associated liver disease.

Immunogenicity and safety profile of the monovalent A/H1N1 MF59-adjuvanted vaccine in patients affected by cystic fibrosis

Viral respiratory tract infections may determine lung function deterioration in patients affected by cystic fibrosis (CF). Viruses may have a synergistic action with bacteria to damage the respiratory tract; they may also promote airway bacterial colonisation.1 Influenza virus infection has been described to increase the number of CF pulmonary exacerbations and the incidence of hospitalisation.2 For this reason, vaccination is strongly recommended annually. The immunogenic effect and safety of influenza vaccines in CF children are comparable with that of healthy individuals.3 The reported adverse events after vaccination are mild and not persisting. In 2009, a novel swine pandemic influenza A virus (A/H1N1) was identified. To date, the …

Extensive molecular analysis suggested the strong genetic heterogeneity of idiopathic chronic pancreatitis

Genetic features of chronic pancreatitis (CP) have been investigated extensively, mainly by testing genes associated to the trypsinogen activation pathway. However, different molecular pathways involving other genes may be implicated in CP pathogenesis. A total of 80 patients with idiopathic chronic pancreatitis (ICP) were investigated using a Next-Generation Sequencing (NGS) approach with a panel of 70 genes related to six different pancreatic pathways: premature activation of trypsinogen, modifier genes of cystic fibrosis phenotype, pancreatic secretion and ion homeostasis, calcium signaling and zymogen granules (ZG) exocytosis, autophagy and autoimmune pancreatitis-related genes. We detected mutations in 34 out of 70 genes examined; of the 80 patients, 64 (80.0%) were positive for mutations in one or more genes and 16 (20.0%) had no mutations. Mutations in CFTR were detected in 32 of the 80 patients (40.0%) and 22 of them exhibited at least one mutation in genes of other pancreatic pathways. Of the remaining 48 patients, 13/80 (16.3%) had mutations in genes involved in premature activation of trypsinogen and 19/80 (23.8%) had mutations only in genes of the other pathways: 38 (59.3%) of the 64 patients positive for mutations showed variants in two or more genes. Our data, although to be extended with functional analysis of novel mutations, suggest a high rate of genetic heterogeneity in CP and that trans-heterozygosity may predispose to the ICP phenotype.

Cystic fibrosis: a surgical matter?

BACKGROUND Gastroesophageal reflux disease (GERD) is very common in patients with chronic lung diseases. We evaluated the incidence of GERD in young patients with cystic fibrosis (CF) and defined the characteristics of gastroesophageal reflux episodes analyzed by pH-multichannel intraluminal impedance (pH-MII) and esophagogastric scintigraphy. PATIENTS AND METHODS Since 2010, 31 patients with CF underwent pH-MII. Scintigraphy and upper endoscopy were performed in positive GERD patients. Forced expiratory volume in 1 second (FEV1%) predicted was detected. RESULTS pH-MII was positive in 17/31 (54.8%) patients (mean age: 12.4 years; range: 4-17 years). pH monitoring detected an average of 64.6 acid reflux events 4.4 episodes >5 minutes in duration. The DeMeester score was 38.5. Impedance identified a mean number of reflux episodes of 66 (65.2% acid; 32% weakly acidic; 2.8% nonacidic), 28% of which reached the proximal esophagus. Esophageal transit and gastric emptying were delayed in 6/13 (46.1%) and in 5/15 (33.3%) cases, respectively. No differences were found in lung function between positive and negative GERD patients (P=0.88). CONCLUSIONS Pediatric patients with CF have a high incidence of GERD with acidic events. These patients should be investigated with pH-MII and scintigraphy in order to make an early diagnosis and determine the most appropriate follow-up.