Spleen surgery in pediatric age: seven-year unicentric experience.

BACKGROUND: Either "open" and laparoscopic spleen surgery in pediatric age are well known and performed with ease in children. Yet, few data regarding follow-up and outcome are discussed in the international literature. MATERIALS AND METHODS: Clinical notes of all patient who underwent spleen surgery in a single center between 2000 and 2007 were reviewed and a specific follow-up questionnaire was administered, aiming to evaluate pre- and postoperative data, especially considering underlying disease, cosmetic results, and quality of life after surgery. RESULTS: Fifty-one patients underwent spleen surgery in our series, 33 of whom returned a complete follow-up questionnaire and were included in the study. Splenectomy was performed in 26 patients, whereas 7 patients underwent a partial splenectomy; 19 cases (57.6%) were approached laparoscopically. A total of 4 complications (12%) occurred in our series, none of them being intraoperative. Hospital stay resulted as significantly shorter in laparoscopic cases (5.5 +/- 2.9 vs. 8.7 +/- 4.8 days; P < 0.01), with better results in terms of cosmetics. Quality of life is strictly related to underlying disease, as well as long-term survival. CONCLUSIONS: Whatever surgical approach is adopted, spleen surgery is safe, effective, and reproducible. When feasible, the laparoscopic approach should be preferred to the traditional open approach, as far as efficacy and safety are similar, in order to reduce hospital stay, abdominal wall traumatism, and consequently, improve postoperative pain control and cosmetic results.

Clinical use of Haemate P in inherited von Willebrand's disease: a cohort study on 100 Italian patients.

BACKGROUND AND OBJECTIVES: Plasma-derived concentrates containing von Willebrand factor and factor VIII (VWF/FVIII concentrates) are the mainstay of treatment of patients with inherited von Willebrand's disease (VWD) who are unresponsive or have a contraindication to desmopressin (DDAVP) therapy. Only a few clinical studies are available on the use of these VWF/FVIII concentrates in large numbers of cases and within the same country. The aim of our study was to collect retrospective data on the efficacy and safety of Haemate P (CSL Behring, Marburg, Germany) in a large cohort of well-characterized VWD patients after the introduction of the guidelines for VWD management in Italy. DESIGN AND METHODS: A retrospective survey of data records was organized among ten Italian Hemophilia Centers in order to retrieve information on the clinical use of Haemate P. Data on 100 VWD patients (44 males and 56 females, median age 41.5, range 2-87 years) were available relating to the period from January 2002 to December 2004. All patients were diagnosed according to the criteria proposed by the Italian guidelines for VWD management. RESULTS: Of the 100 VWD patients enrolled, 23 had type 1 VWD, 40 had type 2 (2A=7, 2B=11, 2M=9, 2M Vicenza=13) and 37 had type 3. Seventy-one percent were severely affected, as shown by VWF:RCo levels <10 IU/dL. Fifty-nine patients were treated with Haemate P because of 280 spontaneous bleeding episodes. These patients required 1,003 infusions of Haemate P with a median daily dose of 72 (27-135) VWF:RCo IU/kg. In ninety-five per cent of patients, clinical responses were rated as excellent/good. Fifty-six patients underwent major surgery (n=17), minor surgery (n=28), invasive procedures (n=9) or dental procedures (n=19), with a total consumption of 1.97x10(6) IU of VWF:RCo through 366 infusions of Haemate P. The median daily dose was 80 (range, 27-146) VWF:RCo IU/kg, with clinical responses rated as excellent/good in 97% of patients. Twelve patients (type 1=1, type 2B=1, type 2M Vicenza=1, type 3=9, with a median age of 34.5, range 11-71 years) also underwent 17 long-term secondary prophylaxis regimens to prevent recurrent bleeding at the same site (47% in the gastrointestinal tract, 35% in joints). During the 4,358 days of prophylaxis, the patients received 1,424 infusions of Haemate P, given three times (53%) or twice (47%) a week, with clinical responses rated as excellent/good in 100%. No serious adverse events, including thrombosis, were reported in the 370 evaluated treatments. INTERPRETATION AND CONCLUSIONS: Based on this retrospective study conducted in a large cohort of Italian patients (n=100) and covering a long period of observation (36 months), Haemate P was shown to be effective and safe for the clinical management of patients with VWD, whether given on demand or as prophylaxis.

Familial nonrandom inactivation linked to the X inactivation centre in heterozygotes manifesting haemophilia A.

A basic tenet of the Lyon hypothesis is that X inactivation occurs randomly with respect to parental origin of the X chromosome. Yet, nonrandom patterns of X inactivation are common - often ascertained in women who manifest recessive X-linked disorders despite being heterozygous for the mutation. Usually, the cause of skewing is cell selection disfavouring one of the cell lineages created by random X inactivation. We have identified a three generation kindred, with three females who have haemophilia A because of extreme skewing of X inactivation. Although they have both normal and mutant factor VIII (FVIII) alleles, only the mutant one is transcribed; and, they share an XIST allele that is never transcribed. The skewing in this case seems to result from an abnormality in the initial choice process, which prevents the chromosome bearing the mutant FVIII allele from being an inactive X.

Changes in the quality of life of people with thalassemia major between 2001 and 2009.

BACKGROUND: The prolonged survival of patients with thalassemia major as a result of the novel therapeutic strategies introduced in the last decade makes patient quality of life an important issue. This study investigated the changes occurring in overall quality of life in patients with thalassemia in the last decade. METHODS: This was a population-based cross-sectional survey of quality of life in the entire population with thalassemia major resident in the Liguria region of Italy from 2001 to 2009. The self-administered Short Form-36 (SF-36) questionnaire was used to measure quality of life in patients with thalassemia. RESULTS: Forty-nine and 52 eligible patients were assessed in 2001 and 2009, respectively. A total of 43 patients were assessed in both 2001 and 2009. Almost 40% of these 43 patients received deferasirox in 2009, a drug which was not available in 2001. The distribution of ferritin levels was lower in 2009 (median 730) as compared with 2001 (median 1107). Analysis of the raw differences between the two years did not show a significant difference. An improvement was observed in most SF-36 scales in 2009 as compared with 2001, particularly in the Mental Health scale (mean difference in Z score +4.0; 95% confidence interval 0.4-7.5; P = 0.030) and in the Mental Component Summary scale (mean difference in Z score +3.2; 95% confidence interval 0.2-6.2; P = 0.039). CONCLUSION: The challenge associated with new therapies and improvement in mental quality of life dimensions indicates that implementation of effective interventions for screening and evaluation of quality of life is now urgent.

Unrelated HSCT in an adolescent affected by congenital erythropoietic porphyria.

CEP is a rare inborn error of porphyrin-heme synthesis. Clinical manifestations can range from mild to severe and include erythrodontia, reddish-colored urine, and hemolytic anemia that can be mild or severe and may result in splenomegaly. Completely avoiding exposure to the sun is crucial. Attempts to reduce erythropoiesis and to lower circulating porphyrin levels by means of erythrocyte transfusions have been successful in reducing the expression of the disease. However, the complications of a chronic transfusion regimen are potentially severe. Successful bone marrow transplantation has been reported in CEP. We report a case of successful bone marrow transplantation and prolonged follow-up in an adolescent CEP patient.

Analysis of 18 novel mutations in the factor VIII gene.

We describe 18 novel mutations, unreported in the Haemophilia A mutation Databases, that have been identified in a cohort of unrelated, Italian patients affected with haemophilia A (HA). Screening of the factor VIII gene (FVIII) was performed using denaturing high-performance liquid chromatography (DHPLC) and direct sequencing. Eight mutations were characterized as non-missense alterations, and the remaining 10 were missense mutations. Heterozygosity for the identified mutations was observed in the female relatives of patients belonging to eight families with sporadic cases. In an attempt to understand better the causative effect of the mutations and the clinical variability of the patients, missense mutation consequences were investigated for: (1) the nature of the new amino acid; (2) the location of the substituted amino acid within crystallographic and theoretical models; and (3) the degree of conservation of the native residue in factor VIII (FVIII) protein and FVIII-related protein family aligned sequences. These research tools have provided evidence that the mutations we describe involve residues that were conserved, at least in FVIII proteins, in all the species we compared.