Current management of surgical neonates: is it optimal or do we need to improve? A national survey of the Italian Society of Neonatology.

PURPOSE: Few guidelines exist for the perioperative management (PM) of neonates with surgical conditions (SC). This study examined the current neonatal PM in Italy. METHODS: We invited 51 neonatal intensive care units with pediatric surgery in their institution to participate in a web-based survey. The themes included (1) the involvement of the neonatologist during the PM; (2) the spread of bedside surgery (BS); (3) the critical issues concerning the neonatal PM in operating rooms (OR) and the actions aimed at improving the PM. RESULTS: Response rate was 82.4%. The neonatologist is involved during the intraoperative management in 42.9% of the responding centers (RC) and only when the surgery is performed at the patient's bedside in 50.0% of RCs. BS is reserved for extremely preterm (62.5%) or clinically unstable (57.5%) infants, and the main barrier to its implementation is the surgical-anesthesiology team's preference to perform surgery in a standard OR (77.5%). Care protocols for specific SC are available only in 42.9% of RCs. CONCLUSION: Some critical issues emerged from this survey: the neonatologist involvement in PM, the spread of BS, and the availability of specific care protocols need to be implemented to optimize the care of this fragile category of patients.

Hyperactivation and altered selection of B cells in patients with paediatric Sjogren's syndrome.

OBJECTIVES: Paediatric Sjögren's syndrome (pSS) is a rare chronic autoimmune disorder, characterised by inflammation of exocrine glands. B cell hyperactivation plays a central role in adult-onset Sjogren. This study was designed to analyse B cell and T cell phenotype, levels of BAFF, and selection of autoreactive B cells in patients with pSS. METHODS: A total of 17 patients diagnosed with pSS and 13 healthy donors (controls) comparable for age were enrolled in the study. B cell and T cell subsets and frequency of autoreactive B cells in peripheral blood were analysed by flow cytometry. Levels of BAFF were analysed by ELISA. RESULTS: The relative frequency of total B cells, transitional, naïve and switched memory B cells was similar between pSS patients and controls. In patients with pSS, we observed a reduction in the frequency of unswitched memory B cells, an increased frequency of atypical memory B cells and an expansion of PD1hi CXCR5- T peripheral helper cells. Levels of BAFF were higher in patients with pSS compared with controls and correlated with serum levels of total IgG and titres of anti-Ro antibodies. The frequency of autoreactive B cells in the transitional, unswitched memory and plasmablast compartment was significantly higher in pSS patients than in controls. CONCLUSIONS: Our results point to a hyperactivation of B cells in pSS. Current therapies do not seem to affect B cell abnormalities, suggesting that novel therapies targeting specifically B cell hyperactivation need to be implemented for paediatric patients.

Public attitudes, knowledge and educational needs toward genetic testing and omics sciences: a pilot survey conducted in Italy.

Advancements in genomics have significant implications for public health, making citizens' education vital for informed decision-making. Based on two literature reviews' findings and a survey conducted with experts from the Italian Network of Genomics in Public Health, we conducted a pilot survey on Italian citizens' attitudes, knowledge and educational needs toward genetic testing and omics sciences. Our results demonstrate a widespread interest in genetic testing and uncertainties regarding associated risks, with 99% of participants acknowledging insufficient knowledge of genetic testing. There is an urgent need for educational tools to improve citizens' literacy and engagement in this rapidly evolving field.

Characteristics and outcomes of patients with atrial versus ventricular secondary tricuspid regurgitation undergoing tricuspid transcatheter edge-to-edge repair - Results from the TriValve registry.

AIM: Functional or secondary tricuspid regurgitation (STR) is the most common phenotype of tricuspid regurgitation (TR) with atrial STR (ASTR) and ventricular STR (VSTR) being recently identified as two distinct entities. Data on tricuspid transcatheter edge-to-edge repair (T-TEER) in patients with STR according to phenotype (i.e. ASTR vs. VSTR) are lacking. The aim of this study was to assess characteristics and outcomes of patients with ASTR versus VSTR undergoing T-TEER. METHODS AND RESULTS: Patients with STR undergoing T-TEER were selected from the Transcatheter Tricuspid Valve Therapies (TriValve) registry. ASTR was defined by (i) left ventricular ejection fraction ≥50%, (ii) atrial fibrillation, and (iii) systolic pulmonary artery pressure <50 mmHg. Patients not matching these criteria were classified as VSTR. Patients with primary TR and cardiac implantable electronic device were excluded. Key endpoints included procedural success and survival at follow-up. A total of 298 patients were enrolled in the study: 65 (22%) with ASTR and 233 (78%) with VSTR. Procedural success was similar in the two groups (80% vs. 83% for ASTR vs. VSTR, p = 0.56) and TEER was effective in reducing TR in both groups (from 97% of patients with baseline TR ≥3+ to 23% in ASTR and to 15% in VSTR, all p = 0.001). At 12-month follow-up, survival was significantly higher in the ASTR versus VSTR cohort (91% vs. 72%, log-rank p = 0.02), with VSTR being an independent predictor of mortality at multivariable analysis (hazard ratio 4.75). CONCLUSIONS: In a real-world, multicentre registry, T-TEER was effective in reducing TR grade in both ASTR and VSTR. At 12-month follow-up, ASTR showed better survival than VSTR.

Leisure-time physical activity and gastric cancer risk: A pooled study within the Stomach cancer Pooling (StoP) Project.

BACKGROUND: Although physical activity (PA) has been recognized as a favourable factor in the prevention of various diseases, including certain forms of cancer, the relationship between PA and gastric cancer (GC) is not yet fully understood. This study aims to provide data from a pooled analysis of case-control studies within the Stomach cancer Pooling (StoP) Project to estimate the association between leisure-time PA and the occurrence of GC. METHODS: Six case-control studies from StoP project collected data on leisure-time PA, for a total of 2,343 cases and 8,614 controls. Subjects were classified into three leisure-time PA categories, either none/low, intermediate or high, based on study-specific tertiles. We used a two-stage approach. Firstly, we applied multivariable logistic regression models to obtain study-specific odds ratios (ORs) and corresponding 95% confidence intervals (CIs) then, we used a random-effect models to obtain pooled effect estimates. We performed stratified analyses according to demographic, lifestyle and clinical covariates. RESULTS: The meta-analysis showed ORs of GC with no significant differences between intermediate vs low and high vs low PA level (OR 1.05 [95%CI 0.76-1.45]; OR 1.23 [95%CI 0.78-1.94], respectively). GC risk estimates did not strongly differ across strata of selected covariates except for age ≤ 55 years old (high vs low level: OR 0.72 [95%CI 0.55-0.94]) and for control population-based studies (high vs low level: OR 0.79 [95%CI 0.68-0.93]). CONCLUSIONS: No association was found between leisure time PA and GC, apart from a slight suggestion of decreased risk below age 55 and in control population-based studies. These results may reflect specific characteristics of GC at a younger age, or the presence of a cohort effect mediating and interacting with socioeconomic determinants of GC The different distribution of PA levels among hospitalized controls could have led to an underestimated effect of PA on GC risk.

Persistently active interferon-γ pathway and expansion of T-bet+ B cells in a subset of patients with childhood-onset systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease causing significant morbidity and mortality, despite important improvements in its management in the last decades. The objective of this work is to investigate the role of IFN-γ in the pathogenesis of childhood-onset systemic lupus erythematosus (cSLE), evaluating the crosstalk between IFN-α and IFN-γ and the expression of T-bet, a transcription factor induced by IFN-γ, in B cells of patients with cSLE. Expression levels of both IFN-α and IFN-γ-induced genes were upregulated in patients with cSLE. We found increased serum levels of CXCL9 and CXCL10 in patients with cSLE. Type I IFN score decreased with initiation of immunosuppressive treatment; conversely, type II IFN score and levels of CXCL9 were not significantly affected by immunosuppressive treatment. Type II IFN score and CXCL9 were significantly higher in patients with lupus nephritis. We observed the expansion of a population of naïve B cells expressing T-bet in a cluster of patients with cSLE. IFN-γ, but not IFN-α, induced the expression of T-bet in B cells. Our data suggest that IFN-γ is hyperactive in cSLE, especially in patients with lupus nephritis, and it is not modulated by therapy. Our data reinforce the potential of IFN-γ as a therapeutic target in SLE.

10 Years of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): A Systematic Review and Meta-Analysis.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel intraperitoneal drug delivery method of low-dose chemotherapy as a pressurized aerosol in patients affected by peritoneal cancer of primary or secondary origin. We performed a systematic review and meta-analysis with the aim of assessing the feasibility, safety, and efficacy of PIPAC. METHODS: A systematic literature search was performed using Medline and Web of Science databases from 1 January 2011, to inception, to 31 December 2021. Data were independently extracted by two authors. The Newcastle-Ottawa Scale was used to assess the quality and risk of bias of studies. Meta-analysis was performed for pathological response, radiological response, PCI variation along treatment, and for patients undergoing three or more PIPAC. Pooled analyses were performed using the Freeman-Tukey double arcsine transformation, and 95% CIs were calculated using Clopper-Pearson exact CIs in all instances. RESULTS: A total of 414 papers on PIPAC were identified, and 53 studies considering 4719 PIPAC procedure in 1990 patients were included for analysis. The non-access rate or inability to perform PIPAC pooled rate was 4% of the procedures performed. The overall proportion of patients who completed 3 or more cycles of PIPAC was 39%. Severe toxicities considering CTCAE 3-4 were 4% (0% to 38.5%). In total, 50 studies evaluated deaths within the first 30 postoperative days. In the included 1936 patients were registered 26 deaths (1.3%). The pooled analysis of all the studies reporting a pathological response was 68% (95% CI 0.61-0.73), with an acceptable heterogeneity (I2 28.41%, p = 0.09). In total, 10 papers reported data regarding the radiological response, with high heterogeneity and a weighted means of 15% (0% to 77.8%). PCI variation along PIPAC cycles were reported in 14 studies. PCI diminished, increased, or remained stable in eight, one and five studies, respectively, with high heterogeneity at pooled analysis. Regarding survival, there was high heterogeneity. The 12-month estimated survival from first PIPAC for colorectal cancer, gastric cancer, gynecological cancer and hepatobiliary/pancreatic cancer were, respectively, 53%, 25%, 59% and 37%. CONCLUSIONS: PIPAC may be a useful treatment option for selected patients with PM, with acceptable grade 3 and 4 toxicity and promising survival benefit. Meta-analysis showed high heterogeneity of data among up-to-date available studies. In a subset analysis per primary tumor origin, pathological tumor regression was documented in 68% of the studies with acceptable heterogeneity. Pathological regression seems, therefore, a reliable outcome for PIPAC activity and a potential surrogate endpoint of treatment response. We recommend uniform selection criteria for patients entering a PIPAC program and highlight the urgent need to standardize items for PIPAC reports and datasets.

Effect of Lockdowns on Hospital Staff in a COVID Center: A Retrospective Observational Study.

At the onset of the SARS-CoV-2 pandemic, individual and social measures were strengthened through restrictive non-pharmaceutical interventions, labelled with the term "lockdown". In Italy, there were two lockdowns (9 March 2020−3 May 2020 and 3 November 2020−27 March 2021). As part of preventive measures, healthcare workers and the administrative staff population of Policlinico A. Gemelli underwent nasopharyngeal swab tests from 1 March 2020 to 9 February 2022, a long time interval that includes the two aforementioned lockdowns. The population included 8958 people from 1 March 2020 to 31 December 2020; 8981 people from 1 January 2021 to 31 December 2021; and 8981 people from 1 January 2022 to 9 February 2022. We then analysed pseudo-anonymized data, using a retrospective observational approach to evaluate the impact of the lockdown on the incidence of SARS-CoV-2 infections within the population. Given the 14 day contagious period, the swab positivity rate (SPR) among the staff decreased significantly at the end of the first lockdown, every day prior to 18 May 2020, by 0.093 (p < 0.0001, CI = (−0.138−−0.047)). After the fourteenth day post the end of the first lockdown (18 May 2020), the SPR increased daily at a rate of 0.024 (p < 0.0001, 95% CI = (0.013−0.034)). In addition, the SPR appeared to increase significantly every day prior to 17 November 2020 by 0.024 (p < 0.0001, CI = (0.013−0.034)). After the fourteenth day post the start of the second lockdown (17 November 2020), the SPR decreased daily at a rate of 0.039 (p < 0.0001, 95% CI = (−0.050−−0.027)). These data demonstrate that, in our Institution, the lockdowns helped to both protect healthcare workers and maintain adequate standards of care for COVID and non-COVID patients for the duration of the state of emergency in Italy.

Severe Acquired Brain Injury: Prognostic Factors of Discharge Outcome in Older Adults.

Severe Acquired Brain Injury (sABI) is a leading cause of disability and requires intensive rehabilitation treatment. Discharge from the rehabilitation ward is a key moment in patient management. Delays in patient discharge can adversely affect hospital productivity and increase healthcare costs. The discharge should be structured from the hospital admission toward the most appropriate environment. The purpose of our study is to investigate early predictors of outcome for discharge in older adults with sABI. A retrospective study was performed on 22 patients who were admitted to an intensive neurorehabilitation unit between June 2019 and December 2021. Patients were divided into two outcome categories, good outcome (GO) or poor outcome (PO), based on discharge destination, and the possible prognostic factors were analyzed at one and two months after admission. Among the factors analyzed, changes in the Disability Rating Scale (DRS) and Level of Cognitive Functioning (LCF) at the first and second month of hospitalization were predictive of GO at discharge (DRS, p = 0.025; LCF, p = 0.011). The presence of percutaneous endoscopic gastrostomy at two months after admission was also significantly associated with PO (p = 0.038). High Body Mass Index (BMI) and the presence of sepsis at one month after admission were possible predictors of PO (BMI p = 0.048; sepsis p = 0.014). An analysis of dynamic predictors could be useful to guarantee an early evaluation of hospital discharge in frail patients with sABI.

Incidence and predictors of pericardial effusion following surgical closure of atrial septal defect in children: A single center experience.

Objectives: To evaluate the incidence of pericardial effusion (PE) after surgical atrial septal defect (ASD) closure and to investigate the presence of predictive risk factors for its development. Methods: We collected data from 203 patients followed at Bambino Gesù Children's Hospital of Rome who underwent cardiac surgery for ASD repair between January 2015 and September 2019. Results: A total of 200/203 patients with different types of ASD were included. Patients were divided into two groups: Group 1) 38 (19%) who developed PE and Group 2) 162 (81%) without PE. No differences were noted between the two groups with regard to gender or age at the surgery. Fever in the 48 h after surgery was significantly more frequent in group 1 than in group 2 (23.7 vs. 2.5%; p < 0.0001). ECG at discharge showed significant ST-segment elevation in children who developed PE, 24.3 vs. 2.0% in those who did not (p < 0.0001). Group 1 patients were divided into two subgroups on the basis of the severity of PE, namely, 31 (81.6%) with mild and 7 (18.4%) with moderate/severe PE. Patients with moderate/severe PE had a significantly higher BMI value (median 19.1 Kg/m2) (range 15.9-23.4, p = 0.004). Conclusion: The presence of fever and ST-segment elevation after surgery predicts subsequent development of PE suggesting a closer follow-up for these categories of patients. A higher BMI appears to be associated with a higher risk of moderate/severe PE.

Procedures for the content, conduct and format of EULAR/PReS paediatric musculoskeletal ultrasound courses.

BACKGROUND: Despite the worldwide increasing request of education on paediatric musculoskeletal ultrasound (PedMSUS), content, conduct and format of PedMSUS courses have never been internationally agreed. OBJECTIVES: To produce educational procedures for the conduct, content and format of EULAR/PReS PedMSUS courses. METHODS: After a systemic literature review and expert opinion collection, a panel of items for the development of procedures on PedMSUS courses was identified. Agreement on the items was assessed through Delphi surveys among a taskforce of 24 members, which included 18 experts in PedMSUS (8 rheumatologists, 1 radiologist, 9 paediatric rheumatologists), 1 methodologist and rheumatologist expert in MSUS, 2 patient research partners, 1 health professional in rheumatology and 2 EMEUNET/EMERGE members, from 8 different European countries. Each item was assessed through a 5-point Likert scale (0, full disagreement; 5, full agreement); agreement was reached for >75% of answers rating 4-5. All items with agreement were included in the preliminary core set of educational procedures, which underwent external assessment by a broader Consensus group (Faculty and Tutors of previous EULAR PedMSUS courses and PReS Imaging Working Party members), through Delphi survey. RESULTS: Two Delphi surveys produced the preliminary core set of procedures for basic, intermediate, advanced and teach-the-teachers (TTT) PedMSUS courses. A Delphi survey within the Consensus group produced agreement on the proposed procedures. CONCLUSIONS: Shared EULAR/PReS procedures for the conduct, content and format of basic, intermediate, advanced and TTT PedMSUS courses were identified on international basis.

Canakinumab in systemic juvenile idiopathic arthritis: real-world data from a retrospective Italian cohort.

OBJECTIVE: The objective of this study was to use real-world data to evaluate the effectiveness and safety of canakinumab in Italian patients with systemic JIA (sJIA). METHODS: A retrospective multicentre study of children with sJIA was performed. Clinical features, laboratory parameters and adverse events were collected at baseline, and 6 and 12 months after starting canakinumab. The primary outcome measure of effectiveness was clinically inactive disease (CID) off glucocorticoids (GCs) treatment at 6 months. RESULTS: A total of 80 children from 15 Italian centres were analysed. Of the 12 patients who started canakinumab in CID while receiving anakinra, all maintained CID. Of the 68 with active disease at baseline, 57.4% achieved CID off GCs at 6 months and 63.8% at 12 months. In univariate analysis, the variables significantly related to non-response were number of active joints (NAJs) ≥5, history of macrophage activation syndrome (MAS) and disease duration. Multivariate analysis confirmed the association between non-response and NAJs ≥5 [odds ratio (OR) 6.37 (95% CI: 1.69, 24.02), P = 0.006] and between non-response and history of MAS [OR 3.53 (95% CI: 1.06, 11.70), P = 0.039]. No serious adverse events were recorded in this series. There were two cases of MAS during canakinumab, leading to a rate of 2.9 episodes per 100 patient years. CONCLUSION: We have confirmed, using real-world data, the efficacy of canakinumab in sJIA in a multicentric cohort. History of MAS and higher NAJ were associated with lower probability of achieving CID.

Assessment of disease activity using a whole-body MRI derived radiological activity index in chronic nonbacterial osteomyelitis.

BACKGROUND: Based on the recently developed ChRonic nonbacterial Osteomyelitis MRI Scoring tool (CROMRIS), we developed a radiological activity index (RAI-CROMRIS) to obtain a quantification of the overall bone involvement in individual patients. METHODS: Whole Body Magnetic Resonance Imaging (WB-MRI) images were scored according to parameters included in the RAI-CROMRIS: bone marrow hyperintensity, signal extension, soft tissue/periosteal hyperintensity, bony expansion, vertebral collapse. These parameters were evaluated for each bone unit yielding a score from 0 to 7 and summed up as RAI-CROMRIS including all bone units. We assessed clinical disease activity using a physician global assessment (PGA) and radiological findings in 76 treatment-naïve patients; 46 of 76 were evaluated at 6 and 12 months after initial WB-MRI. Quantitative variables were compared using the Mann-Whitney U test for unmatched groups and the Wilcoxon signed-rank test for paired groups. Correlation was evaluated using Spearman's rank coefficient (rs). RESULTS: There was a significant correlation between RAI-CROMRIS and PGA (rs = 0.32; p = 0.0055), between RAI-CROMRIS and presence of elevated erythrocyte sedimentation rate (p = 0.013) and C-reactive protein (p = 0.0001) at baseline. The RAI-CROMRIS decreased from a median of 17 at baseline to 12 at 6 months (p = 0.004) and remained stable (median 11) at 12 months. A correlation between the RAI-CROMRIS and the PGA was observed at baseline (rs = 0.41; p = 0.004) and during follow up at 6 months (rs = 0.33; p = 0.025) and 12 months (rs = 0.38; p = 0.010). The baseline RAI-CROMRIS (median 20) was significantly higher in patients who subsequently received bisphosphonates than in patients who received other treatments (median 12) and decreased significantly after bisphosphonates (p = 0.008). CONCLUSIONS: The RAI-CROMRIS was correlated with clinical and laboratory measures of disease activity showing significant short-term changes following treatment with bisphosphonates. This tool could be used in clinical practice and clinical trials after validation.

Early Treatment and IL1RN Single-Nucleotide Polymorphisms Affect Response to Anakinra in Systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: To evaluate the impact of early treatment and IL1RN genetic variants on the response to anakinra in systemic juvenile idiopathic arthritis (JIA). METHODS: Response to anakinra was defined as achievement of clinically inactive disease (CID) at 6 months without glucocorticoid treatment. Demographic, clinical, and laboratory characteristics of 56 patients were evaluated in univariate and multivariate analyses as predictors of response to treatment. Six single-nucleotide polymorphisms (SNPs) in the IL1RN gene, previously demonstrated to be associated with a poor response to anakinra, were genotyped by quantitative polymerase chain reaction (qPCR) or Sanger sequencing. Haplotype mapping was performed with Haploview software. IL1RN messenger RNA (mRNA) expression in whole blood from patients, prior to anakinra treatment initiation, was assessed by qPCR. RESULTS: After 6 months of anakinra treatment, 73.2% of patients met the criteria for CID without receiving glucocorticoids. In the univariate analysis, the variable most strongly related to the response was disease duration from onset to initiation of anakinra treatment, with an optimal cutoff at 3 months (area under the curve 84.1%). Patients who started anakinra treatment ≥3 months after disease onset had an 8-fold higher risk of nonresponse at 6 months of treatment. We confirmed that the 6 IL1RN SNPs were inherited as a common haplotype. We found that homozygosity for ≥1 high-expression SNP correlated with higher IL1RN mRNA levels and was associated with a 6-fold higher risk of nonresponse, independent of disease duration. CONCLUSION: Our findings on patients with systemic JIA confirm the important role of early interleukin-1 inhibition and suggest that genetic IL1RN variants predict nonresponse to therapy with anakinra.

Chronic nonbacterial osteomyelitis - clinical and magnetic resonance imaging features.

BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder. Little information exists on the use of imaging techniques in CNO. MATERIALS AND METHODS: We retrospectively reviewed clinical and MRI findings in children diagnosed with CNO between 2012 and 2018. Criteria for CNO included unifocal or multifocal inflammatory bone lesions, symptom duration >6 weeks and exclusion of infections and malignancy. All children had an MRI (1.5 tesla) performed at the time of diagnosis; 68 of these examinations were whole-body MRIs including coronal short tau inversion recovery sequences, with additional sequences in equivocal cases. RESULTS: We included 75 children (26 boys, or 34.7%), with mean age 10.5 years (range 0-17 years) at diagnosis. Median time from disease onset to diagnosis was 4 months (range 1.5-72.0 months). Fifty-nine of the 75 (78.7%) children presented with pain, with or without swelling or fever, and 17 (22.7%) presented with back pain alone. Inflammatory markers were raised in 46/75 (61.3%) children. Fifty-four of 75 (72%) had a bone biopsy. Whole-body MRI revealed a median number of 6 involved sites (range 1-27). Five children (6.7%) had unifocal disease. The most commonly affected bones were femur in 46 (61.3%) children, tibia in 48 (64.0%), pelvis in 29 (38.7%) and spine in 20 (26.7%). Except for involvement of the fibula and spine, no statistically significant differences were seen according to gender. CONCLUSION: Nearly one-fourth of the children presented with isolated back pain, particularly girls. The most common sites of disease were the femur, tibia and pelvic bones. Increased inflammatory markers seem to predict the number of MRI sites involved.

Acute rheumatic fever prophylaxis in high-income countries: clinical observations from an Italian multicentre, retrospective study.

OBJECTIVES: The aim of the study is to evaluate the compliance rate to secondary prophylaxis and the presence of rheumatic heart disease (RHD) in a cohort of Italian patients with acute rheumatic fever (ARF). METHODS: This is a multicentre retrospective study. The patients were divided into two groups by the presence or absence at last follow-up of RHD. Clinical features, ARF recurrences and the rate of compliance to secondary prophylaxis were evaluated. RESULTS: Two-hundred and ninety patients were enrolled (137 females; 153 males). Carditis at onset was present in 244 patients (84.7%). At the end of follow-up, 173 patients manifested RHD. Adherence to secondary prophylaxis was low in 26% of patients. The presence of RHD at follow-up was associated with the presence of carditis and its severity at onset (p=0.001), but it was not related to secondary prophylaxis adherence (p=NS). No association between prophylaxis adherence and ARF recurrence was found (p=NS) nor between ARF recurrence and RHD at the end of follow-up (p=NS). CONCLUSIONS: Poor adherence to secondary prophylaxis does not seem to be associated with increased risk of RHD in developed countries. Further studies are needed to confirm our data in a larger population.

Role of ocular cytology in vernal keratoconjunctivitis.

BACKGROUND: Children with vernal keratoconjunctivitis (VKC) present symptoms that are similar to other ocular allergies, but more pronounced, and are controlled using topical steroids. To avoid excessive and prolonged use of topical steroid eye drops, over the past 20 years galenic eye drops of cyclosporine with a concentration of 1% to 2% and tacrolimus with a concentration of 0.1% have been introduced as a treatment for the severe and unresponsive forms. The main symptoms of VKC occur most frequently during the spring and tend to get worse during the summer, meaning that affected children tend to avoid exposure to sunlight. The aim of this study was to assess the most common cell types present in the conjunctiva of children with VKC, how ocular treatment can influence them, and whether affected children express a typical conjunctival pattern, which could be useful as a pathognomonic pattern of VKC, allowing us to study this rare eye disease. METHOD: This was a cohort study of 56 children, of whom 17 were not receiving any treatment at the time of testing, 14 were using steroid eye drops or had taken them in the previous 10 days, and 25 were treated with cyclosporine eye drops or tacrolimus eye drops 0.1%. RESULT: Children in group 1 (no topical therapy) express more epithelial cells, neutrophils, mast cells, eosinophils, and lymphocytes than the other two groups. CONCLUSION: Given the ease of performance, when conducting further longitudinal studies, the conjunctival cytology examination could be used, on the one hand, to diagnose VKC, especially when the clinical diagnosis is uncertain, and, on the other, to follow disease evolution and monitor the response to topical treatment.

Development and validation of a composite disease activity score for measurement of muscle and skin involvement in juvenile dermatomyositis.

OBJECTIVE: To develop a composite DAS for JDM and provide preliminary evidence of its validity. METHODS: The Juvenile DermatoMyositis Activity Index (JDMAI) is composed of four items: physician's global assessment of overall disease activity; parent's/child's global assessment of child's wellbeing; measurement of muscle strength; and assessment of skin disease activity. The score of the JDMAI is the arithmetic sum of the scores of each individual component. Six versions of the JDMAI were tested, which differed in the tools used to assess the third and fourth items. Validation procedures were conducted using three large multinational patient samples including a total of 627 patients. RESULTS: The JDMAI was found to possess face and content validity, good construct validity, satisfactory internal consistency (Cronbach's alpha = 0.58-0.89), fair responsiveness to clinically important change (standardized response mean = 0.82-3.12 among patients improved) and strong capacity to discriminate patients judged as being in the state of inactive disease or low, moderate or high disease activity by the physician (P < 0.001) or whose parents were satisfied or not satisfied with the course of their child's illness (P < 0.001). Overall, the six versions of the JDMAI showed similar metrological performances in validation analyses. CONCLUSION: The JDMAI was found to possess good measurement properties in a large population of patients with a wide range of disease activity, and is, therefore, suitable for use in both clinical and research settings. The final version of the JDMAI will be selected after its prospective validation.

Muscle Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histologic Features.

OBJECTIVE: To evaluate the expression of type I interferon (IFNα/ß)- and type II IFN (IFNγ)-inducible genes in muscle biopsy specimens from patients with juvenile dermatomyositis (DM) and to correlate their expression levels with histologic and clinical features. METHODS: Expression levels of IFN-inducible genes and proinflammatory cytokines were assessed by quantitative polymerase chain reaction in muscle biopsy specimens from patients with juvenile DM (n = 39), patients with Duchenne's muscular dystrophy (DMD), and healthy controls. Muscle biopsy sections were stained and scored for severity of histopathologic features. The charts of patients with juvenile DM were reviewed for clinical features at the time of sampling and long-term outcomes. RESULTS: Muscle expression levels of IFNα/ß-inducible genes (type I IFN score), IFNγ, IFNγ-inducible genes (type II IFN score), and tumor necrosis factor (TNF) were significantly higher in juvenile DM patients not receiving glucocorticoid therapy before muscle biopsy (n = 27) compared to DMD patients (n = 24) (type I IFN score, P < 0.0001; type II IFN score, P < 0.001; TNF, P < 0.05) and healthy controls (n = 4) (type I IFN score, P < 0.01; type II IFN score, P < 0.01; TNF, P < 0.05). Immunofluorescence staining of muscle biopsy sections from untreated juvenile DM patients showed increased immunoreactivity for IFNγ and HLA class II molecules compared to controls. Type I and type II IFN scores were correlated with typical histopathologic features of juvenile DM muscle biopsy samples, such as infiltration of endomysial CD3+ cells (type I IFN score, r = 0.68; type II IFN score, r = 0.63), perimysial CD3+ cells (type I IFN score, r = 0.59; type II IFN score, r = 0.66), CD68+ cells (type II IFN score, r = 0.46), and perifascicular atrophy (type I IFN score, r = 0.61; type II IFN score, r = 0.77). Juvenile DM patients with a high type I IFN score, a high type II IFN score, and high TNF expression levels showed more severe disease activity at biopsy (P < 0.05). In addition, juvenile DM patients with a high type II IFN score at biopsy reached clinically inactive disease significantly later than patients with low type II IFN score (log rank chi-square value 13.53, P < 0.001). CONCLUSION: The increased expression of IFN-inducible genes in the muscle in juvenile DM patients and their association with histologic and clinical features further support a pathogenic role for both type I and type II IFNs in juvenile DM.