Survey on the usage of therapeutic erythrocytapheresis in transfusion services in Italy for the treatment of polycythemia vera, secondary erythrocytosis and hemochromatosis.

INTRODUCTION: Erythrocytapheresis, an apheresis treatment which selectively removes red blood cells, is an alternative to therapeutic phlebotomy, over which it has several advantages. Actually there is a high degree of variability in the use of this treatment. This prompted SIdEM (Italian Society of Hemapheresis and Cell Manipulation) to conduct a survey on the use of erythrocytapheresis in the Italian Transfusion Services. The purpose is to monitor this activity in the treatment of Polycythemia Vera (pv), secondary erythrocytosis and hemochromatosis. MATERIALS AND METHODS: A data collection file was sent to the SIdEM regional delegates who, in turn, involved the Transfusion Centers in the areas they cover. The data collected were processed on a Microsoft Excel spreadsheet. RESULTS: 75 centers from 14 Italian regions responded to the Survey: 36 centers (48 %) use erythrocytapheresis (35 centers perform therapeutic apheresis and 1 center only donor apheresis), 39 centers (52 %) do not (15 centers perform therapeutic apheresis, 18 centers only donor apheresis and 6 centers do not perform either therapeutic apheresis or donor apheresis). Although most centers have a substantially uniform attitude concerning the indications for which erythrocytapheresis is used, the survey shows that there are still differences more evident in the treatment of secondary erythrocytosis than in the treatment of pv or hemochromatosis. CONCLUSIONS: This survey has been useful to document the current Italian reality and to raise awareness about the need for improvement in optimizing and standardizing the use of a therapy with a great potential to exploit properly.

Predictability of a New Orthodontic Extrusion Technique for Implant Site Development: A Retrospective Consecutive Case-Series Study.

In clinical daily practice, there are situations in which implant sites have vertical and/or horizontal bone defects and often we must improve their morphology and dimensions before fixture insertion. It is crucial to carefully evaluate the surgical site as regards the characteristics of both hard and soft tissues. The orthodontic extrusion technique can be used for nonsurgical augmentation of the implant site as an alternative to traditional regenerative/reparative surgical therapies. The orthodontic extrusion is based on a biological mechanism that uses the portion of periodontal ligament, still present on the root before the tooth extraction, for the increase of hard and soft tissues. In the literature, there is no evidence of common guidelines for this technique but only tips based on personal experience and/or previous studies. The aim of this study was to investigate and to validate the reliability of a new orthodontic extrusion technique (MF Extrusion Technique, by Dr. Mauro Fadda) by means of a retrospective consecutive case-series study. After we have done a review of the literature, we evaluated the X-rays of twelve consecutively treated patients before the orthodontic extrusion (T0) and after the stabilization period (T1), in order to quantify, by two different measurements, area and linear, the bone gain obtained by the application of the new technique. All the patients examined showed a significant increase in bone areas with an average value of 31.575 mm2. The linear bone gain had an average value of 4.63 mm. Data collected were statistically analysed by the Wilcoxon signed-rank test. The results obtained both from area and linear measurements at T0 and at T1 times showed that there was a statistically significant bone gain with p < 0.01.

Secondary desmoplastic fibroma-like tissue changes in mandibular fibrous dysplasia: clinicopathological and molecular study of a case.

Fibrous dysplasia may show locally aggressive behaviour reflecting secondary intralesional changes, extension to soft tissue, or malignant transformation. We report the case of a patient with polyostotic fibrous dysplasia who had a giant mandibular lesion consisting of histologically typical, genotypically-confirmed, fibrous dysplasia merged with a fibrotic and hypocellular desmoplastic fibroma-like tissue in which the same Gsα-R201H mutation was detected. The occurrence of the same mutation in both the fibrous dysplasia and areas of desmoplastic fibroma suggests that the fibroma-like tissue reflects an unusual secondary tissue change within an otherwise typical fibrous dysplasia. To the best of our knowledge, only four cases of fibrous dysplasia with desmoplastic fibroma-like tissue changes have been reported.

Our experience in the surgical management of craniofacial fibrous dysplasia: what has changed in the last 10 years?

The mainstay of treatment of craniofacial dysplasia (CFD) remains surgery once clinical observation has been excluded. Nevertheless, disagreement remains about the type of surgical intervention (remodelling versus radical resection). The aim of this paper is to present our experience until 2013 comparing CFD management between 1980 and 2002 and between 2003 and 2013 and to propose our surgical algorithm. From January 2003 to December 2013, 41 new patients (18 males and 23 females) with histologically demonstrated CFD presented to our Department. Data were compared with those of 95 patients observed and/or treated between 1980 and 2002. Considering the last period, we noted that observation (26/41 patients) was the most used method; radical resection was performed in most cases (8/15 patients), but in proportion the numbers of patients undergoing bone shaving has increased (6% between 1980 and 2002 vs 15% between 2003 and 2013), while a decrease in the number of patients undergoing excision was seen (63% between 1980 and 2002 vs. 19% between 2003 and 2013). On this basis, we believe that radical resection is the only technique to obtain resolution of fibrous dysplasia. Wait-and-see is indicated in case of stable lesions. Reconstructive techniques allow obtaining adequate aesthetical and functional results; nevertheless, in most cases adjunctive surgical refinements are required and recovery time is higher than with surgical shaving, so that most patients prefer to perform remodelling. Nevertheless, in case of aggressive lesions radical resection is mandatory, except in paediatric patients with residual large defects in which it can be acceptable to try to resolve symptoms via bone shaving, reserving more aggressive treatments in case of relapse or after skeletal maturity.

Self-reported adherence to diet and preferences towards type of meal plan in patient with type 2 diabetes mellitus. A cross-sectional study.

BACKGROUND AND AIMS: Few studies have evaluated the attitudes of patients with type 2 diabetes mellitus (T2DM) towards the given dietary plans. In this study, we aimed to evaluate: i) the self-reported adherence of T2DM patients to the prescribed diets; ii) the use of other types of diet schemes; iii) the patients' preferences towards the type of meal plans. METHODS AND RESULTS: A 16 multiple-choice items questionnaire was administered to 500 T2DM patients; 71.2% (356/500) of them had the perception of having received a dietary plan; only 163/356 declared to be fully adherent. The latter had lower BMI (25.8 ± 4.5 vs 29.1 ± 4.5 kg/m2, p < 0.001) than patients who were partly adherent. Among patients not following the given diet, 61.8% was eating in accordance to a self-made diet and 20.9% did not follow any diet. Only a few patients (2.4%) had tried a popular diet/commercial program. Most patients preferred either a "sufficiently free" (201/500) or a "free" (218/500) scheme. The use of supplements attracted younger, obese individuals, with higher education, and most managers. In a multinomial regression model, age and diabetes duration were inversely associated with the choice of a "rigid" scheme, diabetes duration and glycated hemoglobin levels were inversely correlated with a "free" diet choice, obesity was associated with a "strategic" scheme choice, while lower education (inversely) and obesity (directly) correlated with the preference for "supplement use". CONCLUSIONS: Socio-cultural/individual factors could affect attitudes and preferences of T2DM patients towards diet. These factors should be considered in order to draw an individually tailored dietary plan.

Is the timing of caloric intake associated with variation in diet-induced thermogenesis and in the metabolic pattern? A randomized cross-over study.

BACKGROUND/OBJECTIVES: Food-induced thermogenesis is generally reported to be higher in the morning, although contrasting results exist because of differences in experimental settings related to the preceding fasting, exercise, sleeping and dieting. To definitively answer to this issue, we compared the calorimetric and metabolic responses to identical meals consumed at 0800 hours and at 2000 hours by healthy volunteers, after standardized diet, physical activity, duration of fast and resting. SUBJECTS/METHODS: Twenty subjects (age range 20-35 years, body mass index=19-26 kg m(-)(2)) were enrolled to a randomized cross-over trial. They randomly received the same standard meal in the morning and, 7 days after, in the evening, or vice versa. A 30-min basal calorimetry was performed; a further 60-min calorimetry was done 120-min after the beginning of the meal. Blood samples were drawn every 30-min for 180-min. General linear models, adjusted for period and carry-over, were used to evaluate the 'morning effect', that is, the difference of morning delta (after-meal minus fasting values) minus evening delta (after-meal minus fasting values) of the variables. RESULTS: Fasting resting metabolic rate (RMR) did not change from morning to evening; after-meal RMR values were significantly higher after the morning meal (1916; 95% confidence interval (CI)=1792, 2041 vs 1756; 1648, 1863 kcal; P<0.001). RMR was significantly increased after the morning meal (90.5; 95% CI=40.4, 140.6 kcal; P<0.001), whereas differences in areas-under-the-curve for glucose (-1800; -2564,-1036 mg dl(-1) × h, P<0.001), log-insulin (-0.19; -0.30,-0.07 µU ml(-1) × h; P=0.001) and fatty free acid concentrations (-16.1;-30.0,-2.09 mmol l(-1) × h; P=0.024) were significantly lower. Delayed and larger increases in glucose and insulin concentrations were found after the evening meals. CONCLUSIONS: The same meal consumed in the evening determined a lower RMR, and increased glycemic/insulinemic responses, suggesting circadian variations in the energy expenditure and metabolic pattern of healthy individuals. The timing of meals should probably be considered when nutritional recommendations are given.

Use of PCR-restriction fragment length polymorphism analysis for identification of yeast species isolated from bovine intramammary infection.

This study reports a rapid PCR-based technique using a one-enzyme RFLP for discrimination of yeasts isolated from bovine clinical and subclinical mastitis milk samples. We analyzed a total of 1,486 milk samples collected over 1 yr in south Sardinia and northern Italy, and 142 yeast strains were preliminarily grouped based on their cultural morphology and physiological characteristics. Assimilation tests were conducted using the identification kit API ID 32C and APILAB Plus software (bioMérieux, Marcy l'Etoile, France). For PCR-RFLP analysis, the 18S-ITS1-5.8S ribosomal(r)DNA region was amplified and then digested with HaeIII, and dendrogram analysis of RFLP fragments was carried out. Furthermore, within each of the groups identified by the API or PCR-RFLP methods, the identification of isolates was confirmed by sequencing of the D1/D2 region using an ABI Prism 310 automatic sequencer (Applied Biosystems, Foster City, CA). The combined phenotypic and molecular approach enabled the identification of 17 yeast species belonging to the genera Candida (47.9%), Cryptococcus (21.1%), Trichosporon (19.7%), Geotrichum (7.1%), and Rhodotorula (4.2%). All Candida species were correctly identified by the API test and their identification confirmed by sequencing. All strains identified with the API system as Geotrichum candidum, Cryptococcus uniguttulatus, and Rhodotorula glutinis also produced characteristic restriction patterns and were confirmed as Galactomyces geotrichum (a teleomorph of G. candidum), Filobasidium uniguttulatum (teleomorph of Crypt. uniguttulatus), and R. glutinis, respectively, by D1/D2 rDNA sequencing. With regard to the genus Trichosporon, preliminary identification by API was problematic, whereas the RFLP technique used in this study gave characteristic restriction profiles for each species. Moreover, sequencing of the D1/D2 region allowed not only successful identification of Trichosporon gracile where API could not, but also correct identification of misidentified isolates. In conclusion, the 18S-ITS1-5.8S region appears to be useful in detecting genetic variability among yeast species, which is valuable for taxonomic purposes and for species identification. We have established an RFLP database for yeast species identified in milk samples using the software GelCompar II and the RFLP database constitutes an initial method for veterinary yeast identification.

Safety of hematopoietic stem cell donation in glucose 6 phosphate dehydrogenase-deficient donors.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common RBC enzymatic disorder in humans capable of producing hemolytic events. Recently, concern has been raised about using G6PD-deficienct subjects as hemopoietic stem cell (HSC) donors. In a 10-year period, 101 consecutive HSC donors were submitted to donation procedures for transplantation inside their families in our Center. All donors were tested for G6PD and 19 (19%) turned out to be G6PD-deficient. The donors' safety and the effectiveness of these transplant outcomes were compared with those of the remaining 82 donors. No difference could be observed in any safety parameter between the two groups. No difference was recorded in donors' complications rates, in HSC production, in quantity of growth factor required, in Hb early drop or in Hb recovery. No difference was found in transplant outcome. From this retrospective analysis, we conclude that a G6PD-deficient but otherwise healthy volunteer can be selected as a HSC donor.

Looking for Candida nivariensis and C. bracarensis among a large Italian collection of C. glabrata isolates: results of the FIMUA working group.

Two recently described pathogenic Candida species, C. nivariensis and C. bracarensis, share many phenotypic characteristics with C. glabrata and are easily misidentified as such. The aim of this study was to determine the occurrence of these cryptic species in Italy. One thousand yeast isolates collected in 14 Italian regions and identified as C. glabrata by phenotypic and biochemical methods were included in this study: 928 were screened on CHROMagar and 72 were analysed by a multiplex PCR. None of these cryptic species was identified despite the nationwide distribution and the variety of biological origin of the isolates.

Two clinical cases of prosthetical rehabilitation after a tumor of the upper maxilla.

The most frequent type of treatment for patients diagnosed with a malignant neoplasia of the oral cavity is surgical removal of the tumor. As a result of the resection performed, it is difficult to obtain satisfactory results in the oral rehabilitation of these patients. When possible, fixed prostheses are the best option, because they guarantee stability, but they should be made so that the operator can remove them periodically to check the health of the oral tissues underneath and to intercept any relapse of the tumor. This study analyses two cases of patients surgically treated for a tumor of the upper maxilla at the Oral and Maxillo-Facial Surgery of Sapienza University, in Rome. In the first case the surgical site was covered with local flaps, and the patient was rehabilitated with an implant-supported removable prosthesis. In the second case the maxilla was reconstructed with a fibula vascularized free flap, and the patient was rehabilitated with an implant-supported prosthesis screwed to a titanium bar solidarizing the implants. Therefore, this prosthesis was fixed, but could be removed by the dentist. The different approach to these two cases was influenced by the different anatomic situations after the reconstruction. It is important for the dentist to approach these patients knowing the kind of surgery they received because this aspect will influence rehabilitative choices. Rehabilitation should be planned, when possible, before surgical treatment, in order to cooperate with the maxillo-facial surgeon in choosing the most appropriate restorative treatment.

The obesity gene and colorectal cancer risk: a population study in Northern Italy.

BACKGROUND: Representing the second cause of cancer-related death after lung cancer in men and breast cancer in women, colorectal cancer (CRC) is a major health problem in Italy. Obesity is reckoned to favor CRC; however, the underlying mechanisms are unclear. Recently, a single nucleotide polymorphism (SNP) in the fat mass and obesity associated (FTO) gene was found to be significantly associated with obesity. AIMS: To establish whether the FTO SNP rs9939609 may represent a risk factor for CRC and adenoma in the Italian population. PATIENTS AND METHODS: 1,037 subjects were enrolled in the study and divided in 3 groups: CRC (341 pts., M/F=197/144, mean age=65.17±11.16 years), colorectal adenoma (385 pts., M/F=247/138, mean age=62.49±13.01 years), healthy controls (311 pts., M/F=150/161, mean age=57.31±13.84 years). DNA was extracted from whole blood, and stored frozen for rs9939609 genotyping by real-time PCR. RESULTS: The frequency of the obesity-associated mutated A allele (AA+AT) on the FTO gene was 69.77% among controls, and 71.85% and 65.71% respectively among CRC and polyp patients. Compared to control subjects the AA+AT genotype had no significant effect on the risk for either CRC (OR=1.106; CI 95%=0.788-1.550; p=0.561) or colorectal adenomas (OR=0.830; CI 95%=0.602-1.144; p=0.255). We did not observe any association between the AA genotype and CRC/polyp localization and age at diagnosis. As measured in a patient subset, carriership of the risk alleles did not reflect in a significantly altered BMI. CONCLUSION: The obesity-linked FTO variants do not play a significant role in modulating the colorectal cancer risk in the Italian population.

Molecular detection of virulence factors and antibiotic resistance pattern in clinical Enterococcus faecalis strains in Sardinia.

In this study, the antibiotic resistance pattern and the presence of genes encoding several virulence factors in 91 Enterococcus faecalis strains isolated from different human clinical sources in Sardinia were investigated. Genotypic determination of virulence genes (gelE, esp, agg, ace, cylA,B,M,L(L),L(S), efaA, fsrB) was carried out by PCR. The production of gelatinase and haemolytic activity were also determined. Antimicrobial susceptibility tests were performed by an automated microdilution test (Vitek). The strains examined in this study contained at least one and up to as many as all virulence genes investigated. Examining the distribution of these factors in the different groups of clinical strains, we found that all but one virulence determinant were detected more frequently among urinary isolates. The detection of some factors by PCR did not always correlate with its phenotypic expression. Antibiotic susceptibilities among the Enterococcus faecalis strains investigated in our study were typical for the species, with expected levels of acquired resistance. Faecal isolates had the highest percentage of resistance, especially to high level-gentamicin, ciprofloxacin and norfloxacin. In summary, a wide variety of genes encoding virulence factors have been detected among our clinical Enterococcus faecalis strains, and those isolated from UTI were characterized by a higher virulence potency compared with strains from other clinical sources. Silent virulence genes (cyl or gelE) were frequently detected, therefore both the genotypic and phenotypic assays seem necessary for a better characterization of the strains. Our results may serve as a basis for additional surveillance studies of infections caused by this microorganism.

[Phenotypic and molecular characterization of Candida species in ICU]. / Caratterizzazione fenotipica e molecolare di Candida isolate in un reparto di Terapia Intensiva.

Two hundred sixty three Candida isolates were obtained from specimens of patients hospitalized in a Intensive Care Unit. Candida albicans was the predominant species, followed by C. tropicalis, C. krusei, C. glabrata e C. parapsilosis. For C. albicans isolates, amphotericin B was the more efficient antifungal (2.3% of resistant strains), while voriconazole was the more efficient for C. krusei and C. glabrata, known for their lower susceptibility to fluconazole. RAPD-PCR technique with CDU primer was used for the molecular characterization of 48 C. albicans strains isolated from 10 patients. Genetic similarity at 90% level was observed for some Candida strains isolated from the same patient, indicating a possible colonization from the original strain. Moreover the high similarity coefficient observed between isolates from different patients may indicate an exogenous colonization originating from hospital-endemic strains or inadequate manipulation by health care workers.

Characterization of yeast population and molecular fingerprinting of Candida zeylanoides isolated from goat's milk collected in Sardinia.

The occurrence of yeast microflora in raw goat's milk collected from 62 dairy farms located in different areas of Sardinia was evaluated. Candida zeylanoides was the most frequently occurring species followed by different Basidiomycetous species. In the strains isolated some biochemical characteristics of technological interest were investigated and a predominance of lipolytic yeast species was found. We employed a simple method of DNA extraction that in a minimal time and with low-cost provided a high quality of DNA for RAPD analysis of 32 isolates of C. zeylanoides. The primers M13 and CDU were used and at 40% of similarity, two distinct clusters were observed. The presence of C. krissii species was supposed but further molecular studies are needed to exclude the presence of an as-yet-undescribed species.

Tyrosinase inhibitor activity of coumarin-resveratrol hybrids.

In the present work we report on the contribution of the coumarin moiety to tyrosinase inhibition. Coumarin-resveratrol hybrids 1-8 have been resynthesized to investigate the structure-activity relationships and the IC(50) values of these compounds were measured. The results showed that these compounds exhibited tyrosinase inhibitory activity. Compound 3-(3',4',5'-trihydroxyphenyl)-6,8-dihydroxycoumarin (8)is the most potentcompound (0.27 mM), more so than umbelliferone (0.42 mM), used as reference compound. The kinetic studies revealed that compound 8 caused non-competitive tyrosinase inhibition.

Clinical and biochemical parameters related to cardiovascular disease after Helicobacter pylori eradication.

AIM: Since the major established risk factors explain the pathogenesis of ischemic heart disease (IHD) in a proportion of cases, it is crucial to search for other causal mechanisms. The possible link between IHD and Helicobacter pylori (H.pylori) infection has been reported. However, the precise mechanism of this potential relationship, by a proinflammatory activity or metabolic disorder, is unclear. In order to investigate this issue, the authors assessed changes in clinical and biochemical parameters related to IHD after bacterial eradication. METHODS: A total of 496 patients (281 males; mean age 59.7+/-2.3) with H.pylori-positive dyspepsia and/or peptic ulcer were studied after cure of the bacterium. H.pylori status was determined by histology or 13C-urea breath testing. Examinations for body mass index, diastolic blood pressure and blood testing (C-reactive protein, fibrinogen, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, fasting glucose) were performed before eradication and annually for up to five years thereafter. For statistical analyses, the Student's t test was performed. RESULTS: HDL-C increased (P=0.02) while C-reactive protein and fibrinogen levels diminished (P<0.0001) significantly. BMI and diastolic blood pressure increased in a significant (P=0.032 and P=0.039 respectively) manner compared to baseline. CONCLUSIONS: H.pylori eradication is associated with modification of some clinical and biochemical parameters related to IHD during a follow-up of five years. There is a need for large interventional randomized studies in order to prove a causal association.

PEG-immobilization of cardol and soluble polymer-supported synthesis of some cardol-coumarin derivatives: preliminary evaluation of their inhibitory activity on mushroom tyrosinase.

In this work, the PEG-immobilization and the liquid phase synthesis of some coumarins derived from cardol are presented. Some preliminary results on their tyrosinase inhibitory activity are also included.

Prevalence of Candida species in different hospital wards and their susceptibility to antifungal agents: results of a three year survey.

Over a three years period, 472 Candida isolates were obtained from specimens of patients hospitalized either in "at risk", Bone Marrow Transplant Unit and Intensive Care Unit, or in conventional wards, Pneumological Divisions of the "Binaghi" Hospital of Cagliari (Italy). Antifungal susceptibility profile to amphotericin B, voriconazole, fluconazole and ketoconazole was determined. Candida albicans was the predominant species while Candida krusei was the most frequent non-albicans species. C. krusei was significantly more common among Bone Marrow Transplant Unit and Intensive Care Unit than Pneumological Divisions patients (17.9% and 14.1% vs. 6.0%; p < 0.05). No significant differences were observed when the same distribution was analysed with regard to the other Candida species or when Bone Marrow Transplant Unit and Intensive Care Unit were compared. The profiles of susceptibility to the antifungal drugs among isolates from the different hospital wards showed no significant differences, even though most of MIC values were higher for Intensive Care Unit isolates compared to those for Bone Marrow Transplant Unit and Pneumological Divisions. For C. albicans isolates, amphotericin B was the more efficient antifungal (97.7% S), while fluconazole (6.1% R [Resistant] and 2.6% SDD [Susceptible Dose Dependent]) and ketoconazole (4.1% R and 3.2% SDD) showed the lowest activity. Voriconazole was the more efficient antimycotic for C. krusei (96.7% S) and Candida glabrata (100% S [Sensible]) isolates. This study has shown a significantly higher presence of non-albicans Candida in at risk wards as well as a decreased susceptibility to the older azoles (ketoconazole and fluconazole) among C. albicans isolates.

Intra-parotid facial nerve multiple plexiform neurofibroma in patient with NF1.

INTRODUCTION: Primary neurogenic tumours of facial nerve are uncommon with the majority found intra-temporally. Intracranial and intra-parotid neoplastic involvement of cranial nerve VII is much less common. There are 11 reported cases, in the English-language literature, of intra-parotid facial nerve plexiform neurofibromas with eight of them associated with NF1. MATERIALS AND METHODS: A child, 10 years old, with NF1, reached us for a cheek swelling, slowly increased in previous 8 years. At the age of 3 years, a plexiform neurofibroma was diagnosed by biopsy of the lesion. Clinical examination and NMR showed in the sub-cutaneous tissue of the right cheek, two contiguous nodular lesions, about 2 cm x 1.5 cm in diameter; a third neoformed lesion, about 1cm in diameter, was located above the ipsilateral labial commissure. No facial nerve impairment was seen. The patient underwent superficial parotidectomy with removal of the lesions and preservation of the facial nerve. RESULTS: The patient had a considerable regional swelling in the immediate post-operative course; no facial nerve impairment was observed. The swelling of the cheek did not show a fully regression in the post-operative course. Ultrasonography at 3 months showed a recurrence of disease. DISCUSSION: Plexiform neurofibromas should be distinguished due to their risk of malignant transformation seen in up to 15% of patients affected by NF1. Surgery is the only effective option currently available for the treatment of PNF. However, success of surgical intervention is limited by the infiltrating nature of the tumours, resulting in a high rate of tumour re-growth. Facial nerve preservation during surgery is unlikely and significant morbidity can result from their excision. The age of the patient at surgical resection seemed to influence outcome: tumours resected before age 10 years recurred in 60% of cases compared with only 30% recurrence in patients older than the age of 10 years. CONCLUSION: Indication and timing of surgery, in paediatrics patients with NF1, are complex. To avoid eventual physical and psychological consequences, it seems prudent to delay surgery as long as it is feasible for otherwise asymptomatic paediatric patients with facial plexiform neurofibroma.