The Alpine ibex (Capra ibex) gut microbiome, seasonal dynamics, and potential application in lignocellulose bioconversion.

Aiming to shed light on the biology of wild ruminants, we investigated the gut microbiome seasonal dynamics of the Alpine ibex (Capra ibex) from the Central Italian Alps. Feces were collected in spring, summer, and autumn during non-invasive sampling campaigns. Samples were analyzed by 16S rRNA amplicon sequencing, shotgun metagenomics, as well as targeted and untargeted metabolomics. Our findings revealed season-specific compositional and functional profiles of the ibex gut microbiome that may allow the host to adapt to seasonal changes in available forage, by fine-tuning the holobiont catabolic layout to fully exploit the available food. Besides confirming the importance of the host-associated microbiome in providing the phenotypic plasticity needed to buffer dietary changes, we obtained species-level genome bins and identified minimal gut microbiome community modules of 11-14 interacting strains as a possible microbiome-based solution for the bioconversion of lignocellulose to high-value compounds, such as volatile fatty acids.

Hybridization between Alpine Ibex and Domestic Goat in the Alps: A Sporadic and Localized Phenomenon?

The Alpine ibex (Capra ibex) is a mountain ungulate living in the European Alps. Although being currently classified as a species of Least Concern (LC) by the IUCN, a potential threat for its long-term conservation is introgression following hybridization with domestic goats (Capra hircus). Hybridization has been documented in Switzerland in captive and free ranging animals, although accurate data to assess the extent of this phenomenon in natural conditions in the Alps are lacking. Using an online survey and a network of experts, we collected and mapped unpublished evidence of hybridization events that occurred between Alpine ibex and feral domestic goats from 2000 to 2021. The results of this study showed that hybrids are distributed in most of the Alpine countries, and their presence is not a sporadic event, with some clusters including 4-20 probable hybrids. Our results illustrated the need for establishing a standardized and effective protocol to identify hybrids in the field (such as a formal description of the morphological traits characterizing hybrids), as well as clear guidelines for hybrid management. Even more importantly, this study also highlighted the need for actions aimed at avoiding hybridization, such as the effective management of domestic herds grazing in Alpine ibex core areas.

A robust sequencing assay of a thousand amplicons for the high-throughput population monitoring of Alpine ibex immunogenetics.

Polymorphism for immune functions can explain significant variation in health and reproductive success within species. Drastic loss in genetic diversity at such loci constitutes an extinction risk and should be monitored in species of conservation concern. However, effective implementations of genome-wide immune polymorphism sets into high-throughput genotyping assays are scarce. Here, we report the design and validation of a microfluidics-based amplicon sequencing assay to comprehensively capture genetic variation in Alpine ibex (Capra ibex). This species represents one of the most successful large mammal restorations recovering from a severely depressed census size and a massive loss in diversity at the major histocompatibility complex (MHC). We analysed 65 whole-genome sequencing sets of the Alpine ibex and related species to select the most representative markers and to prevent primer binding failures. In total, we designed ~1,000 amplicons densely covering the MHC, further immunity-related genes as well as randomly selected genome-wide markers for the assessment of neutral population structure. Our analysis of 158 individuals shows that the genome-wide markers perform equally well at resolving population structure as RAD-sequencing or low-coverage genome sequencing data sets. Immunity-related loci show unexpectedly high degrees of genetic differentiation within the species. Such information can now be used to define highly targeted individual translocations. Our design strategy can be realistically implemented into genetic surveys of a large range of species. In conclusion, leveraging whole-genome sequencing data sets to design targeted amplicon assays allows the simultaneous monitoring of multiple genetic risk factors and can be translated into species conservation recommendations.

Beware of dogs! Domestic animals as a threat for wildlife conservation in Alpine protected areas.

Diseases are natural regulating factors of wildlife populations, but some pathogens may become an important threat in wildlife conservation, especially for endangered species. The presence of domestic animals may foster the spread of diseases in natural population, although their role in the dynamic of infections in wildlife is not clear. In this study, we investigated the presence and prevalence of a range of multi-host pathogens in wild species (red fox, Eurasian badger, beech marten, pine marten, stoat for a total of 89 carcasses analysed) and domestic animals (n = 52 shepherd and n = 25 companion dogs) living in a protected area of the Alps (the Gran Paradiso National Park) and discussed the role of domestic dogs as possible source of infection for wild species. Our results showed that domestic dogs are potential shedder of three important pathogens: Canine distemper virus, Toxoplasma sp. and Neospora caninum. In particular, shepherd dogs seem to represent a threat for wildlife as they are exposed to multiple pathogens because of free-roaming, scavenging lifestyles and close proximity to livestock. However, also companion dogs more subject to veterinary care may foster the spread of pathogens. Our results highlight the importance of regulating the access of domestic dogs to protected areas that aim at preserving biodiversity and enhancing the conservation of endangered species.

Neo-aortic posterior sinus of Valsalva reduction and closed coronary artery transfer as a method to approach aortopulmonary mismatch in transposition of great arteries.

OBJECTIVE: In transposition of great arteries (TGA), aortopulmonary mismatch (APM) can determine postoperative neo-aortic insufficiency after arterial switch operation (ASO). The distortion of sinu-tubular junction may be the geometric mechanism responsible. We developed a strategy able to reduce the mismatch at the timing of ASO, and in this study, we aimed to describe our indications and results. METHODS: Preoperative root circumferences at the level of the mid-portion of sinus of Valsalva and ascending aorta circumference were used to define APM. Indication to surgery was a neo-aortic root (NAR) to ascending aorta ratio ≥ 1.4. Along with standard ASO, posterior neo-aortic sinus inverted conal resection and punch technique for coronary reimplantation was used in all patients to re-establish the more geometric ratio possible between the two components. Hypoplastic aortic arch (HAA) and aortic coarctation (CA) were managed by aortic arch enlargement with an autologous pericardial patch. RESULTS: Twenty patients (20 male), 19 with diagnoses TGA (17 with ventricular septal defect, 85%) and 1 with Taussig-Bing anomaly underwent ASO. HAA was present in three (15%) and CA in two (10%). The mean preoperative neo-aortic to ascending aorta ratio was 1.8 versus 1.1 postoperatively (p < .01). No moderate or severe neo-aortic insufficiency was observed before discharge and at a mean follow-up of 4.3 years (interquartile range = 0.5-12 years). CONCLUSION: Neo-aortic reduction plasty with coronary reimplantation by punch technique is an effective strategy to approach preoperative APM in TGA. This technique confers a more harmonious geometry to NAR that can improve neo-aortic valve function.

Bronchopulmonary Nematodes in Alpine Ibex: Shedding of First Stage Larvae Analyzed at the Individual Host Level.

Pneumonia is the most frequent cause of death for Alpine ibex (Capra ibex) in Gran Paradiso National Park, (Italy). The etiology of this form of pneumonia is currently unknown and the identification of the primary etiological agent remains difficult due to biological and logistic constraints. Uncovering individual differences in Protostrongylid prevalence and intensity is important to further investigate the epidemiology of respiratory diseases and their relationship to heterozygosity and inbreeding in a once almost extinct population like C. ibex. In a group of 21 individually recognizable adult male we monitored monthly prevalence and intensity of Protostrongylid first-stage larvae using Baerman's technique from June to September 2019. First-stage larvae of 5 genera were detected. Muellerius (P = 100%, CI95% = 84-100) and Protostrongylus (P = 86%, CI95%:71-100) were two dominant genera according to Bush's importance index. Neostrongylus (P = 38%,CI95%: 17-59), Cystocaulus (P = 33%,CI95% = 13-53) were classified as co-dominant genera while Dictyocaulus filaria (P = 0.05%, CI95% = 0.04-0.13) was detected, for the first time in Alpine ibex, in one subject. Protostrongylidae larval excretion varied significantly over time, with minimum L1 excretion in July. Individual median larval intensity ranged from 4.4 lpg to 82.2 lpg with Poulin's discrepancy index showing highly aggregated distribution patterns for Muellerius spp. (D = 0.283, CI95% = 0.760-0.895) and Protostrongylus spp. (D = 0.635, CI95% = 0.580-0.705). Presented data provide the necessary base point to further investigate how lungworm infection account for the different rates of progression of pneumonia in C. ibex. Individual aggregation of larval intensity must be further evaluated to determine whether these differences mirror different levels of parasitic infection related to individual differences in immune response, hormonal-states or genetic fitness.

Supraventricular tachycardias in the first year of life: what is the best pharmacological treatment? 24 years of experience in a single centre.

BACKGROUND: Supraventricular tachycardias (SVTs) are common in the first year of life and may be life-threatening. Acute cardioversion is usually effective, with both pharmacological and non-pharmacological procedures. However, as yet no international consensus exists concerning the best drug required for a stable conversion to sinus rhythm (maintenance treatment). Our study intends to describe the experience of a single centre with maintenance drug treatment of both re-entry and automatic SVTs in the first year of life. METHODS: From March 1995 to April 2019, 55 patients under one year of age with SVT were observed in our Centre. The SVTs were divided into two groups: 45 re-entry and 10 automatic tachycardias. As regards maintenance therapy, in re-entry tachycardias, we chose to start with oral flecainide and in case of relapses switched to combined treatment with beta-blockers or digoxin. In automatic tachycardias we first administered a beta-blocker, later combined with flecainide or amiodarone when ineffective. RESULTS: The patients' median follow-up time was 35 months. In re-entry tachycardias, flecainide was effective as monotherapy in 23/45 patients (51.1%) and in 20/45 patients (44.4%) in combination with nadolol, sotalol or digoxin (overall 95.5%). In automatic tachycardias, a beta-blocker alone was effective in 3/10 patients (30.0%), however, the best results were obtained when combined with flecainide: overall 9/10 (90%). CONCLUSIONS: In this retrospective study on pharmacological treatment of SVTs under 1 year of age the combination of flecainide and beta-blockers was highly effective in long-term maintenance of sinus rhythm in both re-entry and automatic tachycardias.

Neonatal heart failure and noncompaction/dilated cardiomyopathy from mucopolysaccharidosis. First description in literature.

Mucopolysaccharidosis are genetic disorders due to deficiency of lysosomal enzymes, resulting in abnormal glycosaminoglycans accumulation in several tissues. Heart involvement tends to be progressive and worsens with age. We describe the first case of mucopolysaccharidosis type I presenting with noncompaction/dilated-mixed cardiomyopathy and heart failure within neonatal period, which responded successfully to specific metabolic treatment. Cardiac function recovered after enzyme replacement therapy and hematopoietic stem cell transplantation, adding to the existing knowledge of the disease.

Long-term follow-up of coronary artery lesions in children in Kawasaki syndrome.

To describe clinical and epidemiological characteristics of a Kawasaki syndrome cohort. In a monocentric, retrospective, observational study, between February 1982 and August 2018, we enrolled 361 children, aged 1 month to 24.4 years. Coronary artery lesions were detected in 20.2% of patients: 16% had coronary ectasia, and 4.15% had coronary aneurisms. A significant difference regarding age at disease onset (p = 0.025), fever duration (p < 0.0001), CRP (p = 0.001) and day of first IVIG administration (p < 0.0001) was detected among group. A significant correlation between coronary artery lesions and disease onset < 6 months (p = 0.009), second IVIG dose (p < 0.001) and male gender (p = 0.038) has been detected. Median long-term follow-up was 10.2 years (1-36 years). At the last available follow-up, patients without coronary involvement and coronary ectasia had normal cardiological tests, conversely, in patients with aneurisms, 8/13 showed persistent aneurisms at echocardiography, one ECG repolarization alterations, and one ST depression at the peak of effort during ergometric test.Conclusion: Children with lower age, longer fever, higher level of CRP and retard in IVIG administration are at higher risk to develop coronary artery lesions. Our long-term follow-up analysis confirms, over 36 years of observation, the benign course of Kawasaki syndrome even in coronary artery lesion patients, if timely treated. What is already known about this topic? • Stopping cardiologic assessment in no risk patients results economically advantageous, timesaving and able to reduce emotional discomfort in children and their families. • Age at disease onset, fever duration, CRP level, and day of first IVIG administration are possible risk factors for coronary artery lesions What is New? • During 36 years of observation in real life, our study shows the benign course of Kawasaki syndrome without coronary artery lesions after 6-8 weeks from the disease onset. • Age < 6 months at disease onset is strongly related with coronary artery lesion development.

Impact of cardiovascular involvement on the clinical course of paediatric mitochondrial disorders.

BACKGROUND: Primary mitochondrial disorders (PMD) are rare conditions resulting in progressive multi-organ failure. Cardiovascular involvement (CVI) has been reported in paediatric patients. However, its age-related prevalence, clinical presentation and prognostic impact are unresolved. We detailed CVI in a cohort of children diagnosed with PMD over two decades at a tertiary referral centre. RESULTS: We enrolled 86 PMD patients (M/F = 30/56; mean age 6.4 ± 8.58 years). CVI was detected in 31 patients (36%), with mean age at onset of 5.7 ± 7.8 years including the pre- and neonatal phase in 14, often representing the first sign of PMD (42% of those with CVI). Heart disease resulted more common in males and in children with specific aetiologies (Barth, TMEM70 and MELAS syndromes). Hypertrophic, non-compaction and dilated cardiomyopathies were the prevalent disorders, although pulmonary arterial hypertension was also found. Adverse cardiac events (heart failure, resuscitated cardiac arrest, ICD/PM implantation, sudden death) occurred in 19% of children with CVI over a follow-up period of 5.4 ± 4.3 years. All-cause mortality was higher in patients with CVI compared to those without CVI (45.1% vs 21.8%; p < 0.01); female sex, age at onset < 5 years, acute heart failure at presentation and diabetes also proved independent predictors of outcome. CONCLUSION: Cardiovascular involvement occurred in over one-third of children diagnosed with PMD, often at a very early age, and was associated with adverse prognosis. Final outcome of PMD-related CVI was influenced by the specific underlying aetiology, suggesting the need for tailored management of heart failure and sudden death prevention.

Combined Surgical and Endoscopic Approach for Ring-Sling Complex.

BACKGROUND: Left pulmonary artery (LPA) sling (PAS) is a vascular ring, which is frequently associated with long-segment tracheal stenosis (TS). Mortality rate in operated children is still high, especially in cases of severe tracheal hypoplasia and/or associated congenital heart defects (CHDs). We report our experience of treatment and follow-up in a pediatric cohort of patients affected by PAS with severe tracheobronchial involvement. METHODS: From 2005 to 2017, we enrolled 11 children diagnosed with PAS and congenital TS requiring surgical intervention. Echocardiography, computed tomography, and bronchoscopy were performed in all patients. Associated CHD were present in 5 (45%) patients. Tracheal reconstruction techniques included slide tracheoplasty (7/11; 63%), slide tracheoplasty and costal cartilage graft (2/11; 18%), and Hazekamp technique (2/11; 18%).Nine patients underwent LPA direct reimplantation and concomitant tracheoplasty; concomitant surgical repair for CHD was performed in three children. RESULTS: Over a mean follow-up of 30 months (range: 3-75 months), a late mortality of 18% was registered; no early death occurred. Good flow through LPA could be documented in all patients. Ten children required operative bronchoscopies (mean: 16/patients) aimed at stent positioning/removal, treatment of granulomas, and tracheobronchial dilatation. CONCLUSIONS: Severe tracheobronchial stenosis and associated CHD were the main determinants for hospitalization time, intensive assistance, and repeated endoscopic procedures.Patients affected by PAS/TS complex require a careful management at high-specialized centers providing multidisciplinary team.Respiratory endoscopy may play a central role both in preoperatory assessment and in postoperative management of patients showing severe tracheobronchial involvement.

Frequent Ventricular Premature Beats in Children and Adolescents: Natural History and Relationship with Sport Activity in a Long-Term Follow-Up.

Premature ventricular complexes (PVCs) are frequently documented in children. To date, few studies report long-term follow-up in pediatric cohorts presenting with frequent PVCs. The aim of this study is to assess the clinical relevance and long-term outcomes of frequent PVCs (≥ 500/24 h) in a large pediatric cohort. From 1996 to 2016, we enrolled all consecutive patients evaluated at Anna Meyer Children Hospital for frequent PVCs. Symptomatic children were excluded together with those patients with known underlying heart diseases; thus, our final cohort of study included 103 patients (male 66%; mean age 11 ± 3.4 years), with a mean follow-up of 9.5 ± 5.5 years. All patients were submitted to complete non-invasive cardiologic evaluation. The mean number of PVCs at Holter Monitoring (HM) was 11,479 ± 13,147/24 h; couplets and/or triplets were observed in 5/103 (4.8%) cases; 3 patients (2.9%) presented runs of non-sustained ventricular tachycardia (NSVT). High-burden PVCs (> 30,000/24 h) was confirmed in 11/103 (10.6%) patients. During the follow-up, only five patients (4.8%) developed clinical symptoms (3 for palpitations, 1 myocardial dysfunction due to frequent PVCs and NTSV; 1 arrhythmogenic cardiomyopathy); no deaths occurred. Basal PVCs were still present in 45/103 (43.7%) patients. Our data suggest that frequent PVCs may be addressed as a benign condition and should not preclude sport participation if not associated with cardiac malformations, heart dysfunction, or cardiomyopathy. This seems to be true also in presence of very frequent/high-burden PVCs. Otherwise, a careful follow-up is mandatory since sport eligibility should be reconsidered in case of onset of symptoms and/or ECG/echocardiographic changes.

Sudden Diplopia at a Pediatric Emergency Department: A Case of Gradenigo Syndrome in a Child.

OBJECTIVE: Otitis media, facial pain in trigeminal region, and ipsilateral abducens nerve palsy clinically define Gradenigo syndrome, a rare but serious complication of suppurative middle ear infection. Radiological investigation is required to confirm petrous apex involvement and to exclude further consequences as sinus thrombosis, meningitis, and intracranial abscess. METHODS/RESULTS: We report the case of an 8-year-old child referred to our emergency department for recurrent headache and sudden strabismus. Clinical evidence of suppurative otitis media raised the suspicion for Gradenigo syndrome, definitively confirmed at computed tomography and magnetic resonance imaging scans. Conservative treatment alone enabled complete clinical and radiological remission, without long-term sequelae. CONCLUSIONS: Despite being a rare condition, Gradenigo syndrome should be taken into account as potential differential diagnosis in children referred to emergency department for recurrent headache and strabismus. An accurate anamnesis to document recent ear infection is mandatory to orientate the diagnosis and focus radiological investigations. Early recognition and timely intervention may allow conservative management to succeed, avoiding the need for surgery and serious sequelae.

Clinical profile and outcome of cardiac involvement in MELAS syndrome.

BACKGROUND: Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like (MELAS) syndrome is a rare condition with heterogeneous clinical presentation. Cardiac involvement commonly develops during adulthood, comprising both structural and conduction/arrhythmic abnormalities; early paediatric onset has rarely been reported. We describe the clinical profile, outcome and clinical implication of MELAS-associated cardiomyopathy at a tertiary referral centre. METHODS: From 2000 to 2016 we enrolled 21 patients affected by genetically-proven MELAS. Patients were followed-up at least annually over a mean of 8.5 years. RESULTS: All patients carried the MT-TL1 3243A>G mutation. Cardiac involvement was documented in 8 (38%) patients (three <18 years; five ≥18 years), including 6 (75%) with hypertrophic cardiomyopathy, 1 (12.5%) with dilated cardiomyopathy, and 1 (12.5%) with persistent pulmonary hypertension. During follow-up, 3 patients died, all with cardiac onset <18 years. The cause of death, however, was non-cardiac (infections, respiratory failure, stroke). Neither events nor cardiac progression were recorded among patients with onset ≥18 years. Adult cardiologists were responsible for 5/8 of referrals, even in patients with long-standing extra-cardiac involvement. CONCLUSIONS: Cardiac involvement was found in over 1/3 of patients with MELAS syndrome, and exhibited a bimodal age-related distribution with distinct final outcomes. Paediatric-onset cardiomyopathy represented a hallmark of systemic disease severity, without being the main determinant of outcome. Conversely, adult-onset cardiomyopathy appeared to represent a mild and non-progressive mid-term manifestation. Adult cardiologists played an important role in the diagnostic process, triggering suspicion of MELAS in most of patients diagnosis >18 years.

Heterozygosity-fitness correlation at the major histocompatibility complex despite low variation in Alpine ibex (Capra ibex).

Crucial for the long-term survival of wild populations is their ability to fight diseases. Disease outbreaks can lead to severe population size reductions, which makes endangered and reintroduced species especially vulnerable. In vertebrates, the major histocompatibility complex (MHC) plays an important role in determining the immune response. Species that went through severe bottlenecks often show very low levels of genetic diversity at the MHC. Due to the known link between the MHC and immune response, such species are expected to be at particular risk in case of disease outbreaks. However, so far, only few studies have shown that low MHC diversity is correlated with increased disease susceptibility in species after severe bottlenecks. We investigated genetic variation at the MHC and its correlations with disease resistance and other fitness-related traits in Alpine ibex (Capra ibex), a wild goat species that underwent a strong bottleneck in the last century and that is known to have extremely low genetic variability, both genome-wide and at the MHC. We studied MHC variation in male ibex of Gran Paradiso National Park, the population used as a source for all postbottleneck reintroductions. We found that individual MHC heterozygosity (based on six microsatellites) was not correlated with genome-wide neutral heterozygosity. MHC heterozygosity, but not genome-wide heterozygosity, was positively correlated with resistance to infectious keratoconjunctivitis and with body mass. Our results show that genetic variation at the MHC plays an important role in disease resistance and, hence, should be taken into account for successfully managing species conservation.

Pediatric Scurvy: When Contemporary Eating Habits Bring Back the Past.

Vitamin C deficiency is anecdotal in developed countries, mainly associated with underling clinical morbidities as autism or neurological impairment. Chronic insufficient dietary supply is responsible for vascular fragility and impaired bone formation, resulting in gingival bleeding, petechial lesions, articular and bone pain or limb swelling. Children may present anorexia, irritability, failure to thrive, limping or refusal to walk. Accordingly, pediatric scurvy is frequently misdiagnosed with osteomyelitis, septic arthritis, bone and soft tissue tumor, leukemia, bleeding disorders, and rheumatologic conditions. We report the case of a 3-years old child developing scurvy as consequence of strict selective diet; extensive and invasive investigations were undertaken before the correct diagnosis was considered. Despite being considered a rare condition, scurvy still exists nowadays, even in children with no apparent risk factors living in wealthy families. The increasing popularity of dietary restriction for children, especially those with allergies, may potentially enhance the occurrence of scurvy in apparently healthy children. Appropriate dietary anamnesis is fundamental in order to highlight potential nutritional deficit and to avoid unnecessary invasive diagnostic procedures. Patients without considerable risk factors may benefit from psychological support in order to investigate possible eating disorders.

Side effects and their impact on the success of milk oral immunotherapy (OIT) in children.

Oral immunotherapy (OIT) has been introduced as a new immune-modulating treatment under investigation for food allergies. The aim of our study was to evaluate the success of OIT in a cohort of children with milk allergy. These children underwent OIT in a clinical practice and were followed for up to ten years. The secondary endpoint was to describe the main adverse events during OIT and compare them to those reported in the literature. Eighty-two milk-allergic children started OIT. According to the OIT endpoint reached after one year, all of the children enrolled in the study were divided into four groups: complete desensitization; partial desensitization; step down; and stop groups. Any adverse events that occurred during OIT were also recorded. Of the 82 patients, eight were recruited in the last months of 2010 so they were still ongoing at the end of the study. For that reason, they were excluded from the analysis. The majority (73%) of the 74 children evaluated (51 boys, 23 girls; median age, 7 years; age range, 2-18 years; specific serum IgE for cow's milk, 36 KUA/L [range, 3-100 KUA/L]; milk SPT wheal diameter, 7 mm [range, 2-15 mm]) reached complete (58.1%) or partial (14.9%) desensitization, 9.4% were subjected to step down. The remaining 17.6% of the children discontinued OIT because of the occurrence of chronic gastroenteric (GE) symptoms (46.1%) or acute asthma (15.3%) following milk intake. In agreement with the literature, we found that chronic GE symptoms was the main reason for OIT discontinuation. OIT represents a valid tool for the treatment of food allergies in children; however, the risk of potential adverse reactions, both IgE- and non-IgE-mediated, should be discussed with parents prior to the initiation of OIT.

Predictors of Relapse after Discontinuing Systemic Treatment in Childhood Autoimmune Chronic Uveitis.

OBJECTIVE: To identify clinical predictors of relapse in childhood autoimmune chronic uveitis after stopping systemic treatment. METHODS: A retrospective, multicenter, cohort study. RESULTS: Ninety-four children in remission, receiving no treatments and with at least a 6-month followup, were enrolled. A higher probability of maintaining remission after discontinuing treatment was shown in idiopathic compared with juvenile idiopathic arthritis uveitis (Mantel-Cox chi-square = 23.21) if inactivity had been obtained within 6 months from starting systemic treatment (Mantel-Cox chi-square = 24.17) and by antitumor necrosis factor-α treatment (Mantel-Cox chi-square = 6.43). CONCLUSION: Type of disease, time, and type of systemic therapy to achieve inactivity predict different duration of uveitis remission after treatment withdrawal.

Mycophenolate mofetil as induction and long-term maintaining treatment in childhood: Primary angiitis of the central nervous system.

OBJECTIVE: To report our single centre experience in treating 4 children affected by childhood primary central nervous system vasculitis (cPACNS) using mycophenolate mofetil (MMF). METHODS: From December 2011 to August 2015, 4 patients (3 males; age range: 9 months-13 years) affected by cPACNS were collected. Enrolled children received the following treatment protocol: acetylsalicylic acid and/or anticoagulant therapy with low molecular weight heparin (LMWH) 100 U/k BID replaced by acenocoumarol; methyl-prednisolone (30mg/kg/day for 3-5 days) followed by prednisone (2mg/kg/day), tapered and discontinued over 7-8 months; MMF used for induction therapy and subsequent maintenance phase (750-1000mg/m2 BID, half-dose for the first 10-15 days followed by full-dose). RESULTS: In all children, no relapse of cerebral vasculitis occurred during the whole follow-up period and all of them improved while in MMF treatment. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), performed at 6, 9 or 12 months intervals, showed no progression or even improvement of the typical radiological findings. Medium period of MMF treatment was 29 months (range: 10-42 months). No major drug-related adverse events were documented. CONCLUSION: We report for the first time on the efficacy and safety of MMF in the induction and maintenance of clinical remission in cPACNS. Our single centre experience of MMF use in treating cPACNS seems represent an appealing, alternative and safe option in this clinical setting over a long-term follow-up.