Mucosal and Histologic Healing in Children With Inflammatory Bowel Disease Treated With Antitumor Necrosis Factor-Alpha.

OBJECTIVES: Mucosal healing (MH) and histological healing (HH) have been recently proposed as a novel treatment target for inflammatory bowel disease (IBD). The aim of the present study was to evaluate real-life achievement of such outcomes in a cohort of pediatric patients with IBD treated with anti-TNF-alpha (ATA) agents. METHODS: A retrospective analysis was performed on patients affected by IBD who received ATA and were followed up at two referral centers. Incidence and cumulative rates for MH and HH for each group were calculated. RESULTS: Of 170 (105 Crohn's disease [CD] and 65 ulcerative colitis [UC]) patients, 78 with CD and 56 with UC underwent endoscopic re-assessment during the study period. MH was achieved by 32 CD (41%) and 30 UC (53.6%) patients; 26 CD (33.3%) and 22 UC (39.3%) patients achieved HH. MH incidence rate was 19.1/1000 and 47/1000 person-months, whereas HH incidence rate was 15.5/1000 and 34.7/1000 person-months for CD and UC, respectively. Remission at the end of induction was associated with higher MH and HH rates (HR: 2.43, P = 0.049 and HR: 2.94, P = 0.046, respectively) in CD. In UC, adalimumab was associated with lower MH and HH rates (HR: 0.16, P = 0.004 and HR: 0.07, P = 0.003). CONCLUSIONS: We reported a real-life experience arising from a large cohort of pediatric IBD who received ATA scheduled treatment. Less than half of patients with CD and only a little >50% of UC patients achieved MH. Microscopical inflammation was observed in 18.8% CD and 26.7% UC patients who achieved MH. Overall, MH and HH rates appear lower compared to previously published data.

Quantitative MRI-Based Analysis Identifies Developmental Limbic Abnormalities in PCDH19 Encephalopathy.

Protocadherin-19 (PCDH19) is a calcium dependent cell-adhesion molecule involved in neuronal circuit formation with prevalent expression in the limbic structures. PCDH19-gene mutations cause a developmental encephalopathy with prominent infantile onset focal seizures, variably associated with intellectual disability and autistic features. Diagnostic neuroimaging is usually unrevealing. We used quantitative MRI to investigate the cortex and white matter in a group of 20 PCDH19-mutated patients. By a statistical comparison between quantitative features in PCDH19 brains and in a group of age and sex matched controls, we found that patients exhibited bilateral reductions of local gyrification index (lGI) in limbic cortical areas, including the parahippocampal and entorhinal cortex and the fusiform and lingual gyri, and altered diffusivity features in the underlying white matter. In patients with an earlier onset of seizures, worse psychiatric manifestations and cognitive impairment, reductions of lGI and diffusivity abnormalities in the limbic areas were more pronounced. Developmental abnormalities involving the limbic structures likely represent a measurable anatomic counterpart of the reduced contribution of the PCDH19 protein to local cortical folding and white matter organization and are functionally reflected in the phenotypic features involving cognitive and communicative skills as well as local epileptogenesis.

Trends in pediatric epilepsy surgery in Europe between 2008 and 2015: Country-, center-, and age-specific variation.

OBJECTIVE: To profile European trends in pediatric epilepsy surgery (<16 years of age) between 2008 and 2015. METHODS: We collected information on volumes and types of surgery, pathology, and seizure outcome from 20 recognized epilepsy surgery reference centers in 10 European countries. RESULTS: We analyzed retrospective aggregate data on 1859 operations. The proportion of surgeries significantly increased over time (P < .0001). Engel class I outcome was achieved in 69.3% of children, with no significant improvement between 2008 and 2015. The proportion of histopathological findings consistent with glial scars significantly increased between the ages of 7 and 16 years (P for trend = .0033), whereas that of the remaining pathologies did not vary across ages. A significant increase in unilobar extratemporal surgeries (P for trend = .0047) and a significant decrease in unilobar temporal surgeries (P for trend = .0030) were observed between 2008 and 2015. Conversely, the proportion of multilobar surgeries and unrevealing magnetic resonance imaging cases remained unchanged. Invasive investigations significantly increased, especially stereo-electroencephalography. We found different trends comparing centers starting their activity in the 1990s to those whose programs were developed in the past decade. Multivariate analysis revealed a significant variability of the proportion of the different pathologies and surgical approaches across countries, centers, and age groups between 2008 and 2015. SIGNIFICANCE: Between 2008 and 2015, we observed a significant increase in the volume of pediatric epilepsy surgeries, stability in the proportion of Engel class I outcomes, and a modest increment in complexity of the procedures.

Long-term efficacy of add-on stiripentol treatment in children, adolescents, and young adults with refractory epilepsies: A single center prospective observational study.

OBJECTIVE: To assess the long-term efficacy and tolerability of stiripentol (STP) as an adjunctive treatment in different forms of refractory epilepsies. METHODS: The medical records of all individuals consecutively treated with STP as add-on therapy for refractory epilepsies, irrespective of their being focal, generalized, or both, and followed at Meyer Children's Hospital between January 2007 and May 2018, were reviewed. The drug scheme administration consisted of a starting dose of STP of 10-15 mg/kg/d with increments every week, up to a maximum of 50 mg/kg/d, based on both age and weight. Etiology of epilepsy was codified as structural, genetic, infectious, immune, metabolic, and unknown. Responders were defined as patients who achieved a seizure frequency reduction of ≥50%. Retention rate was defined as the probability of continuing STP without additional therapy. Tolerability was assessed by reporting adverse events. RESULTS: A total of 132 individuals aged from 5 months to 43 years received add-on STP, including 30 patients with Dravet syndrome (DS). The median follow-up was 14.8 months (range = 4 months-18 years, interquartile range = 25.72). Twenty-nine individuals (22%) received more than two antiepileptic drugs. Benzodiazepines, mainly clobazam, were the most commonly used add-on drugs. Sixty-six patients (50%) were responders, and 13 of them (9.8%) were seizure-free. Responder rate was higher in the genetic etiology group (57%), especially in DS (18/30; 60%), and in patients with refractory focal onset epilepsy without bilateral tonic-clonic seizures (5/15; 33%). The median relapse-free survival was 27 months in the 66 responders. The median time to STP failure was 24.6 months in all 132 individuals. SIGNIFICANCE: This study confirms the long-term efficacy of add-on STP treatment in patients with different types of refractory epilepsies, including focal onset epilepsy without bilateral tonic-clonic seizures. Further confirmations based on prospectively designed studies are required to confirm STP efficacy in focal epilepsy.

Relaxation-guided imagery reduces perioperative anxiety and pain in children: a randomized study.

Several studies have shown the efficacy of psychological interventions in reducing preoperative anxiety in children undergoing surgery. This study aims to investigate the effectiveness of a specific non-pharmacological technique, the relaxation-guided imagery, in reducing both preoperative anxiety and postoperative pain in a sample of 60 children (6-12 years old) undergoing minor surgery who were randomly assigned to the experimental group (N = 30) or the control group (N = 30). The first group received the relaxation-guided imagery, before the induction of general anesthesia; the second group received standard care. The levels of preoperative anxiety and postoperative pain were assessed using, respectively, the modified Yale Preoperative Anxiety Scale and the Face, Legs, Activity, Cry, and Consolability Scale. The results showed a statistically significant difference between groups, with less anxiety and less pain for children included in the experimental group (p < .001; p < .001).Conclusion: Results suggest that relaxation-guided imagery reduces preoperative anxiety and postoperative pain in children. Future studies should focus on developing protocols and studying the eventual reduction of administered drugs for anesthesia and pain. What is Known: • Literature suggests the usefulness of relaxation-guided imagery in reducing anxiety and pain in the perioperative period. • Stronger evidences are needed to support the application of relaxation-guided imagery as routine care in pediatric surgery. What is New: • To our knowledge, this is the first randomized study to investigate the efficacy of relaxation-guided imagery in reducing preoperative anxiety and postoperative pain within a single pediatric sample. • The present study provides stronger evidence in an area that is lacking in research.

Long-term efficacy of add-on lacosamide treatment in children and adolescents with refractory epilepsies: A single-center observational study.

OBJECTIVE: To assess long-term efficacy and tolerability of lacosamide (LCM) as adjunctive treatment through a retrospective study in children and adolescents with refractory epilepsies. METHODS: All patients consecutively treated with LCM as add-on for refractory focal and generalized epilepsy and followed at the Neuroscience Center of Excellence of the Meyer Children's Hospital of Florence between January 2011 and September 2015 were included in the study. Responder rate, relapse-free survival, and retention rate were calculated. Tolerability was assessed by reporting adverse events. RESULTS: A total of 88 individuals (41 female) aged 4 months to 18 years (median 10.5 years; mean ± SD 10.6 ± 4.8 years) received add-on LCM treatment for refractory epilepsy. Thirty-four patients (38.6%) were responders with a median time to relapse of 48 months. Nine (26.4%) of the 34 responders were seizure-free. For all 88 patients, the probability of remaining on LCM without additional therapy was 74.4% at 6 months, 47.7% at 12 months, 27.9% at 24 months, 18.0% at 48 months, and 8.2% at 72 months of follow-up. No statistically significant differences in relapse and retention time were observed with regard to epilepsy and seizure types, duration and course of epilepsy, number and type of antiepileptic drugs (AEDs; sodium channel blockers vs others) used in add-on. The most frequent adverse events were dermatological (4/11) and behavioral (3/11). SIGNIFICANCE: This study documents a real-world progressive and significant loss of LCM efficacy over time in a pediatric population. Further prospective studies on larger populations are required to confirm the remarkable loss of LCM efficacy over time.

Comparative efficacy of antiepileptic drugs in children and adolescents: A network meta-analysis.

OBJECTIVE: To estimate the comparative efficacy among antiepileptic drugs in the pediatric population (0-18 years). METHODS: Using the Embase and MEDLINE databases, we updated to February 2017 the search strategy of the National Institute for Health and Care Excellence guidelines for epilepsy. We only included randomized clinical trials conducted in children and mixed-age populations. According to the PRISMA network meta-analysis guideline, the study-level quality assessment was made with the Cochrane risk-of-bias tool. Three investigators independently selected articles. The efficacy outcome was considered to be seizure freedom or ≥50% seizure reduction. RESULTS: We selected 46 randomized clinical trials. A total of 5652 individuals were randomized to 22 antiepileptic drugs and placebo. The point estimates of carbamazepine and lamotrigine efficacy showed their superiority with respect to all comparator antiepileptic drugs for the treatment of newly diagnosed focal epilepsy. In refractory focal epilepsy, levetiracetam (odds ratio [OR] = 3.3, 95% credible interval [CrI] = 1.3-7.6) and perampanel (OR = 2.5, 95% CrI = 1.1-5.8) were more effective compared to placebo. Ethosuximide and valproic acid were both superior to lamotrigine against absence seizures. The OR point estimate showed the superiority of adrenocorticotropic hormone over all comparators in infantile spasms. A wide heterogeneity in the length of follow-up was observed among the studies. SIGNIFICANCE: This network meta-analysis suggests that the quality of studies should be improved through the use of comparative designs, relevant outcomes, appropriate follow-up length, and more reliable inclusion criteria.

Growth and body mass index in a cohort of patients with juvenile idiopathic arthritis: effects of second line treatments.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) may affect natural growth. The aim of the study has been to assess auxological parameters of JIA patients, receiving different anti-rheumatic treatments. METHODS: This is a retrospective study; JIA patients were recruited from the Rheumatology Unit of Anna Meyer Children's University Hospital of Florence, Italy from March 1996 to June 2016. RESULTS: Two hundred and thirty-two patients were included in the current study. The best result in terms of catch-up growth occurred in systemic JIA patients. All JIA categories showed standard deviation score (SDS) gain for height except those belonging to enthesitis related arthritis category. Patients treated with disease-modifying anti-rheumatic drugs (DMARDs) only maintained constant growth during study follow-up. Patients who needed biologic therapy showed an impaired growth during pre-DMARDs treatment and an increased growth velocity mostly during biologic therapy. Body mass index (BMI) decreased in almost all JIA categories. The best BMI reduction was observed among patient receiving biologic drugs. CONCLUSIONS: Patients with JIA followed in our centre had a gain of height SDS and lost BMI SDS in 5 years of follow-up. We observed a stable and good pattern of growth in patients treated with DMARDs and an increased growth velocity during biologic treatment.

Increasing volume and complexity of pediatric epilepsy surgery with stable seizure outcome between 2008 and 2014: A nationwide multicenter study.

OBJECTIVE: The objective of the study was to assess common practice in pediatric epilepsy surgery in Italy between 2008 and 2014. METHODS: A survey was conducted among nine Italian epilepsy surgery centers to collect information on presurgical and postsurgical evaluation protocols, volumes and types of surgical interventions, and etiologies and seizure outcomes in pediatric epilepsy surgery between 2008 and 2014. RESULTS: Retrospective data on 527 surgical procedures were collected. The most frequent surgical approaches were temporal lobe resections and disconnections (133, 25.2%) and extratemporal lesionectomies (128, 24.3%); the most frequent etiologies were FCD II (107, 20.3%) and glioneuronal tumors (105, 19.9%). Volumes of surgeries increased over time independently from the age at surgery and the epilepsy surgery center. Engel class I was achieved in 73.6% of patients (range: 54.8 to 91.7%), with no significant changes between 2008 and 2014. Univariate analyses showed a decrease in the proportion of temporal resections and tumors and an increase in the proportion of FCDII, while multivariate analyses revealed an increase in the proportion of extratemporal surgeries over time. A higher proportion of temporal surgeries and tumors and a lower proportion of extratemporal and multilobar surgeries and of FCD were observed in low (<50surgeries/year) versus high-volume centers. There was a high variability across centers concerning pre- and postsurgical evaluation protocols, depending on local expertise and facilities. SIGNIFICANCE: This survey reveals an increase in volume and complexity of pediatric epilepsy surgery in Italy between 2008 and 2014, associated with a stable seizure outcome.

Central-line associated bloodstream infections in a tertiary care children's University hospital: a prospective study.

BACKGROUND: The central-line associated bloodstream infections (CLABSI) are the most common healthcare-associated infections in childhood. Despite the international data available on healthcare-associated infections in selected groups of patients, there is a lack of large and good quality studies. The present survey is the first prospective study monitoring for 6 months the occurrence of central-line associated bloodstream infections in all departments of an Italian tertiary care children's university hospital. METHODS: The study involved all children aged less than 18 years admitted to Meyer Children's University Hospital, Florence, Italy who had a central line access between the October 15th, 2014 and the April 14th, 2015. CLABSI were defined according to the Center for Disease Control and Prevention criteria. CLABSI incidence rates with 95% confidence limits were calculated and stratified for the study variables. For each factor the relative risk and 95% confidence intervals were evaluated. Statistical analysis was performed using the statistical software SPSS for Windows, version 22.0 (SPSS Inc., Chicago, IL), p < 0.05 was considered statistically significant. RESULTS: CLABSI rate was 3.73/1000 (95% CI: 2.54-5.28) central line-days. A higher CLABSI incidence was seen with female gender (p = 0.045) and underlying medical conditions (excepting prematurity, surgical diseases and malignancy) (p = 0.06). In our study 5 infections, were caused by extended-spectrum ß-lactamase producing organisms and in one case by carbapenem-resistant Klebsiella pneumoniae. CONCLUSIONS: Our study confirms the spreading of multi-resistant pathogens as causes of healthcare associated infections in children. An increased incidence rate of CLABSI in our study was related to underlying medical conditions. Pediatric studies focusing on healthcare infections in this type of patients should be done in order to deepen our understanding on associated risk factors and possible intervention areas.

Fetal programming and systemic sclerosis.

OBJECTIVE: This study investigated whether birthweight is linked to an increased risk of the development of systemic sclerosis. STUDY DESIGN: This was a multicenter case-control study with perinatal data that were obtained from 332 cases with systemic sclerosis and 243 control subjects. Birthweight was treated as a dichotomous variable (<2500 g vs ≥2500 g); low birthweight was defined as a weight <2500 g; small for gestational age was defined as birthweight <10th percentile for gestational age adjusted for sex. The relationship between systemic sclerosis and both low birthweight and small for gestational age was expressed with the crude (univariate analysis) and adjusted (multivariate analysis) odds ratio (OR). RESULTS: Significantly increased ORs were observed in the univariate analysis for low birthweight (OR, 2.59; 95% confidence interval [CI], 1.39-5.05) and small for gestational age (OR, 2.60; 95% CI, 1.34-5.32) subjects. Similarly increased risks were confirmed for both conditions in the multivariate analysis (OR, 3.93; 95% CI, 1.92-8.07; and OR, 2.58; 95% CI, 1.28-5.19), respectively. CONCLUSION: Low birthweight and small for gestational age at birth are risk factors for the adult onset of systemic sclerosis.

Sleeping problems in mothers and fathers of patients suffering from congenital central hypoventilation syndrome.

PURPOSE: Advanced medical technology has resulted in an increased survival rate of children suffering from congenital central hypoventilation syndrome. After hospitalization, these technology-dependent patients require special home care for assuring ventilator support and the monitoring of vital parameters mainly during sleep. The daily challenges associated with caring for these children can place primary caregivers under significant stress, especially at night. Our study aimed at investigating how this condition affects mothers and fathers by producing poor sleep quality, high-level diurnal sleepiness, anxiety, and depression. METHODS: The study included parents of 23 subjects with congenital central hypoventilation syndrome and 23 healthy subjects. All parents filled out the Pittsburgh Sleep Quality Index (PSQI) questionnaire, Epworth Sleepiness Scale (ESS), Beck Depression Inventory (BDI-II), and Beck Anxiety Inventory (BAI). RESULTS: A comparison between the two groups showed that parents of patients had poorer sleep quality, greater sleepiness, and higher BDI-II scores compared to that of parents of healthy subjects (respectively, PSQI score 6.5 vs 3.8, ESS score 6.2 vs 4.3, BDI-II score 8.4 vs 5.7). Specifically, mothers of patients showed poorer sleep quality and higher BDI-II scores compared to that of mothers of controls (respectively, PSQI score 7.5 vs 3.8, BDI-II score 9.3 vs 5.9), whereas fathers of patients showed greater levels of sleepiness with respect to fathers of healthy children (respectively, ESS score 6.8 vs 4.0). These differences emerged in parents of younger children. CONCLUSIONS: Congenital central hypoventilation syndrome impacts the family with different consequences for mothers and fathers. Indeed, while the patients' sleep is safeguarded, sleeping problems may occur in primary caregivers often associated with other psychological disorders. Specifically, this disease affects sleep quality and mood in the mothers and sleepiness levels in the fathers.

Single-day trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis pneumonia in children with cancer.

OBJECTIVE: To determine whether a simplified, 1-day/week regimen of trimethoprim/sulfamethoxazole is sufficient to prevent Pneumocystis (jirovecii [carinii]) pneumonia (PCP). Current recommended regimens for prophylaxis against PCP range from daily administration to 3 consecutive days per week dosing. STUDY DESIGN: A prospective survey of the regimens adopted for the PCP prophylaxis in all patients treated for childhood cancer at pediatric hematology-oncology centers of the Associazione Italiana Ematologia Oncologia Pediatrica. RESULTS: The 20 centers participating in the study reported a total of 2466 patients, including 1093 with solid tumor and 1373 with leukemia/lymphoma (or primary immunodeficiency; n = 2). Of these patients, 1371 (55.6%) received the 3-day/week prophylaxis regimen, 406 (16.5%) received the 2-day/week regimen, and 689 (27.9%), including 439 with leukemia/lymphoma, received the 1-day/week regimen. Overall, only 2 cases of PCP (0.08%) were reported, both in the 2-day/week group. By intention to treat, the cumulative incidence of PCP at 3 years was 0.09% overall (95% CI, 0.00-0.40%) and 0.51% for the 2-day/week group (95% CI, 0.10%-2.00%). Remarkably, both patients who failed had withdrawn from prophylaxis. CONCLUSION: A single-day course of prophylaxis with trimethoprim/sulfamethoxazole may be sufficient to prevent PCP in children with cancer undergoing intensive chemotherapy regimens. This simplified strategy might have implications for the emerging need for PCP prophylaxis in other patients subjected to the increased use of biological and nonbiological agents that induce higher levels of immune suppression, such as those with rheumatic diseases.

[National Guidelines System: the Italian experience]. / Il Sistema nazionale linee guida italiano.

The Italian's experience of the guidelines development group is discussed through the evaluation of its ten years of activity. Focus is placed on the Italian guidelines working group organization and on the kind of documents developed. The horizontal architecture of the system and the several partnerships settled over time allowed the definition of a small coordinating group connected with a multitude of territorial stakeholders, such as scientific societies and local health units pertaining to the Italian National Health System. Different kinds of documents were produced, as adaptations of already existing guidelines elaborated by international institutions, short reviews addressing specific clinical issues and consensus conferences aimed at providing clinical governance on issues which lack on evidence. The steps needed to produce a high quality guideline are presented, considering and comparing all the different international experiences, to define and discuss a common and well-structured methodology, and to face the ethical and epistemological implications of each method. The multidisciplinary of the working groups, the importance of the active surveillance on conflicts of interests, the definition of a minimum set of rules to be followed during the whole activity and the transparency of all the steps are the milestones of the Italian experience. The lack of a continuous and stable source of funding and the subsequent instability of the central structure are endangering all the knowledge and the experience gained during these years of activity. It is therefore crucial to guarantee and safeguard the role of a national, independent and public institution in the supervision of the guidelines development process and the provision of clinical governance.

Screening for central precocious puberty by single basal Luteinizing Hormone levels.

PURPOSE: To identify cut-off for basal LH levels and for pelvic ultrasound uterine and ovarian parameters indicating an Hypotalamic-Pituitary-Gonadal (HPG) axis activation as diagnostic of Central Precocious Puberty (CPP). METHODS: 248 girls referred for suspected precocious/early puberty who had undergone a GnRH stimulation test were enrolled and divided into three groups: Premature Idiopathic Thelarche (PIT), CPP, and Early Puberty (EA). For every patient basal serum Luteinising Hormone (LH) and Follicle Stimulating Hormone (FSH), basal LH/FSH ratio and pelvic ultrasonographic parameters were also collected. Through the use of Receiver Operating Curves (ROCs) the sensitivity (Se) and specificity (Sp) of basal LH, FSH, LH/FSH ratio and ultrasonographic parameters were evaluated at each level and Area Under the Curve (AUC) was measured. RESULTS: Basal LH model ≥0.14 mIU/mL reached the highest predictability (90.6% and 78.2%, Se and Sp, respectively). Basal LH/FSH ratio ≥0.1 showed a sensitivity of 85.90% and a specificity of 78.14%, while basal FSH cut-off (≥2.36 mIU/mL) had the lowest predictability, with a less favourable sensitivity (71%) and specificity (70.5%). Cut-off point for uterine length as 35 mm, (83.5% and 42.9% of Se and Sp, respectively) was calculated. For ovarian volumes, ROC curves showed very low sensitivity and specificity. CONCLUSION: A single basal LH measurement under the cut-off limit may be adequate to exclude an HPG axis activation as CPP.

L-DOPA Test in the Diagnosis of Childhood Short Stature: Evaluation of Growth Hormone Peaks Over Time.

INTRODUCTION: In childhood, growth hormone (GH) deficiency (GHD) diagnosis is based on auxological assessment and biochemical provocative tests, whose reliability remains disputed. Recently, several papers have been published on standardising the duration of some tests. The aim of our study was to analyse the possible length reduction of the L-DOPA provocative test. METHODS: We retrospectively investigated the response of GH to L-DOPA in 256 children, analysing 267 tests (some patients were retested over time for the persistence of severe auxopathy). We studied the same data considering GH peak threshold both at 8 ng/mL (Italian GHD cut-off) and at 10 ng/mL (international cut-off). Based on stimulation tests, patients were divided into two groups: GHD and no-GHD short children. We described the results in the whole population and then clustering for gender and pubertal stage. We termed as index the test stopped at 90 min. RESULTS: The GH peak after L-DOPA mostly occurred at 60 min. The sensitivity of the index test was the highest, while the specificity was slightly higher using the 8 ng/mL threshold (specificity = 0.68; 95% CI 0.60-0.76) then using the 10 ng/mL threshold (specificity = 0.56; 95% CI 0.47-0.65) at 90 min. The two ROC curves showed moderate performance of the test at 90 min. While the negative predictive value was 100% in both tests, the positive predictive value was slightly better with 10 ng/mL cut-off. Considering the two groups established by GHD definition and placing a GH threshold at 10 ng/mL, stopping L-DOPA test time at 90 min would have changed the test result and subsequentially patient's classification in 3/267 of the analysed tests (1.1%), while with the Italian GH threshold value at 8 ng/mL in 7/267 of the tests (2.6%). CONCLUSIONS: Our research shows that omitting 120-min time reduces L-DOPA test specificity, especially with GHD cut-off at 10 ng/mL.

To switch or to swap? Evidence from a meta-analysis for the best treatment approach in childhood chronic uveitis resistant to the I anti-TNF.

Objective: Since adalimumab approval in childhood chronic non-infectious uveitis (cNIU), the prognosis has been dramatically changed, but the 25 % failed to achieve inactivity. There is not accordance if it is better to switch to another anti-TNF or to swap to another category of biologic. Thus, we aim to summarize evidence regarding the best treatment of cNIU refractory to the first anti-TNF. Methods: A systematic literature review and meta-analysis, according to PRISMA Guidelines, was performed(Jan2000-Aug2023). Studies investigating the efficacy of treatment in cNIU refractory to the first anti-TNF were considered for inclusion. The primary outcome was the improvement of intraocular inflammation according to SUN. A combined estimation of the proportion of children responding to switch or swap and for each drug was performed. Results: 23 articles were eligible, reporting 150 children of whom 109 switched anti-TNF (45 adalimumab, 49 infliximab, 9 golimumab) and 41 swapped to another biologics (31 abatacept, 8 tocilizumab and 1 rituximab). The proportion of responding children was 46 %(95 % CI 23-70) for switch and 38 %(95 % CI 8-73) for swap (χ20.02, p = 0.86). Instead analysing for each drug, the proportion of responding children was the 24 %(95 % CI 2-55) for adalimumab, 43 %(95 % CI 2-80) for abatacept, 79 %(95 % CI 61-93) for infliximab, 56 %(95 % CI 14-95) for golimumab and 96 %(95 % CI 58-100) for tocilizumab. We evaluated a superiority of tocilizumab and infliximab compared to the other drugs(χ2 27.5 p < 0.0001). Conclusion: Although non-conclusive, this meta-analysis suggests that, after the first anti-TNF failure, tocilizumab and infliximab are the best available treatment for the management of cNIU.

Impact of COVID-19 vaccines in patients on hemodialysis: an Italian multicentre cohort study.

BACKGROUND: The aim of this study was to evaluate the impact on the national health system of COVID-19 infection in vaccinated patients undergoing haemodialysis. METHODS: From the cohort of vaccinated dialysis patients enrolled in 118 dialysis centres, we calculated hospitalisation incidence in COVID-19-infected subjects. COVID-19-related hospitalisations and ICU admissions were analysed over two time periods (prior to administration of the third dose and following administration of the third dose of vaccine) and adjusted for several co-variates. Using the general population as the reference, we then calculated the Standardized Incidence Ratio (SIR) of hospitalisation. RESULTS: Eighty-two subjects out of 1096 infected patients were hospitalised (7.5%) and sixty-four hospitalisations occurred among the 824 infected persons after the third dose. Age ≥ 60 years (Adj RR 2.91; 95% CI 1.34-6.30) and lung disease (Adj RR = 2.45; 95% CI 1.32-4.54) were the only risk factors associated with hospitalisation. The risk of ICU admission in the second time period (Time 2) was reduced by 86% (RR = 0.14; 95% CI 0.03-0.71) compared to the first time period (Time 1). The SIR of hospitalisation (SIR 14.51; 95% CI 11.37-17.65) and ICU admission (SIR 14.58; 95% CI 2.91-26.24) showed an increase in the number of events in dialysis patients compared to the general population. CONCLUSIONS: Our analysis revealed that while the second variant of the virus increased infection rates, it was concurrently associated with mitigated severity of infections. Dialysis patients exhibited a higher susceptibility to both COVID-19 hospitalisation and ICU admission than the general population throughout the pandemic.

[The transition from paediatric to adult care: a new paradigm]. / La transizione bambino-adulto: un nuovo paradigma.

In healthcare, the child-adult transition is the point of intersection between two health care systems organized in a network (pediatric and adult care), each with its own specificities and dysfunctions. Information, education and empowerment of young adults are crucial in preparing them for the transition to adult care while centrality of the patient, patient preferences, sharing with patients and their families, and multi-disciplinary approach, are the key words of the transition process. Barriers to overcome include the reluctance of patients and their families to separate from the pediatric care system, the tendency of pediatric healthcare workers not to favour the emancipation process and the inability of healthcare workers providing adult care to perceive the sense of insecurity and dependence experienced by young adults.

Safety and efficacy of COVID-19 vaccines in patients on dialysis: a multicentre cohort study in Italy.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of COVID-19 vaccines in patients undergoing haemodialysis in Italy compared to the general population. METHODS: In this cohort study, 118 dialysis centres from 18 Italian Regions participated. Individuals older than 16 years on dialysis treatment for at least 3 months, who provided informed consent were included. We collected demographic and clinical information, as well as data on vaccination status, hospitalisations, access to intensive care units and adverse events. We calculated the incidence, hospitalisation, mortality, and fatality rates in the vaccinated dialysis cohort, adjusted for several covariates. The incidence rates of infection in the dialysis cohort and the general population were compared through Standardised Incidence Rate Ratio. RESULTS: The study included 6555 patients vaccinated against SARS-CoV-2 infection according to the schedule recommended in Italy. Between March 2021 and May 2022, there were 1096 cases of SARS-CoV-2 infection, with an incidence rate after completion of the three-dose vaccination cycle of 37.7 cases per 100 person-years. Compared to the general population, we observed a 14% reduction in the risk of infection for patients who received three vaccine doses (Standardised Incidence Rate Ratio: 0.86; 95% Confidence Interval: 0.81-0.91), whereas no statistically significant differences were found for COVID-19-related hospitalisations, intensive care unit admissions or death. No safety signals emerged from the reported adverse events. CONCLUSIONS: The vaccination program against SARS-CoV-2 in the haemodialysis population showed an effectiveness and safety profile comparable to that seen in the general population.