Development and Initial Validation of the ONCOREUM Score to Differentiate Childhood Cancer with Arthropathy from Juvenile Idiopathic Arthritis.

OBJECTIVE: To develop and validate a weighted score, the ONCOREUM score, that aids physicians in differentiation of cancer with arthropathy from juvenile idiopathic arthritis (JIA). STUDY DESIGN: Data were extracted from the ONCOREUM Study, a multicenter, cross-sectional investigation aimed at comparing children with cancer and arthropathy to children with JIA. Three statistical approaches were applied to develop the ONCOREUM score and assess the role of each variable in the diagnosis of cancer with arthropathy, including 2 approaches based on multivariable stepwise selection (models 1 and 2) and 1 approach on a Bayesian model averaging method (model 3). The ß coefficients estimated in the models were used to assign score points. Considering that not missing a child with cancer is a mandatory clinical objective, discriminating performance was assessed by fixing sensitivity at 100%. Score performance was evaluated in both developmental and validation samples (representing 80% and 20% of the study population, respectively). RESULTS: Patients with cancer and arthropathy (49 with solid tumors and 46 with hematologic malignancies without peripheral blasts) and 677 patients with JIA were included. The highest area under the receiver operating characteristic (ROC) curve (AUC) in the validation data set was yielded by model 1, which was selected to constitute the ONCOREUM score. The score ranged from -18 to 21.8, and the optimal cutoff obtained through ROC analysis was -6. The sensitivity, specificity, and AUC of the cutoff in the validation sample were 100%, 70%, and 0.85, respectively. CONCLUSIONS: The ONCOREUM score is a powerful and easily applicable tool that may facilitate early differentiation of malignancies with articular complaints from JIA.

Parents' Perspective of Antibiotic Usage in Children: A Nationwide Survey in Italy.

BACKGROUND: Antibiotics represent the most widely prescribed drugs in children worldwide, both in hospital and community settings. A comprehensive approach to understanding the reasons and determinants of antibiotic prescription in the pediatric age is needed. This study aimed to assess parents' attitudes and perspectives about antibiotic use. METHODS: Prospective observational study was conducted in all Italian Regions between February 1 and April 30, 2020, using a standardized questionnaire. RESULTS: Six thousand six hundred twenty-five parents from all Italian regions completed the survey. Seventy-six percent of parents were aware that only bacteria are the target of antibiotics, but 92.9% knew that the antibiotic has no direct effect on fever. Antibiotic self-prescription (10.4%) or by remote consultation by phone call (19.9%) or message (9.6%) were relatively common. Ninety-three percent of parents were aware that excessive use of antibiotics could select resistant bacteria and 84.7% of them knew that they could actively fight antibiotic resistance. About two thirds of participants (66.1%) received information on antibiotic resistance from their family pediatrician. Parents born of Italy or those with lower income had a higher probability of having less information from pediatricians or knowledge of proper antibiotic use. DISCUSSION: Our study suggests that parents' knowledge and attitudes toward antibiotic use and prescription are improving compared with previous studies, while there is still a gap regarding antibiotic resistance, particularly on practices that can reduce its burden. Our study's negative finding is that families from low-income settings or those born abroad have significantly more misconceptions about important antibiotic practices.

Musculoskeletal manifestations of childhood cancer and differential diagnosis with juvenile idiopathic arthritis (ONCOREUM): a multicentre, cross-sectional study.

BACKGROUND: Presenting symptoms of childhood cancers might mimic those of rheumatic diseases. However, the evidence available to guide differential diagnosis remains scarce. Preventing wrong or delayed diagnosis is therefore important to avoid incorrect administration of glucocorticoid or immunosuppressive therapy and worsening of prognosis. As such, we aimed to assess the prevalence and characteristics of presenting musculoskeletal manifestations in patients at cancer onset and to identify the factors that differentiate childhood malignancies with arthropathy from juvenile idiopathic arthritis. METHODS: We did a multicentre, cross-sectional study at 25 paediatric haemato-oncology centres and 22 paediatric rheumatology centres in Italy. We prospectively recruited patients who were younger than 16 years that were newly diagnosed with cancer or juvenile idiopathic arthritis. We excluded patients with glucocorticoid pre-treatment (>1 mg/kg per day of oral prednisone or equivalent for ≥2 consecutive weeks). We collected data for patients with a new diagnosis of cancer or juvenile idiopathic arthritis using an electronic case report form on a web-based platform powered by the Cineca Interuniversity Consortium. The primary outcome was to describe the frequency and characteristics of musculoskeletal manifestations at cancer onset; and the secondary outcome was to identify factors that could discriminate malignancies presenting with arthropathy, with or without other musculoskeletal symptoms, from juvenile idiopathic arthritis using multivariable logistic regression analysis. FINDINGS: Between May 1, 2015, and May 31, 2018, 1957 patients were eligible, of which 1277 (65%) had cancer and 680 (35%) had juvenile idiopathic arthritis. Musculoskeletal symptoms occurred in 324 (25% [95% CI 23·0-27·8]) of 1277 patients with cancer, of whom 207 had arthropathy. Patients with malignant bone tumours had the highest frequency of musculoskeletal symptoms (53 [80%] of 66), followed by patients with Langerhans histiocytosis (16 [47%] of 34), leukaemia (189 [32%] of 582), soft-tissue sarcomas (16 [24%] of 68), and neuroblastoma (21 [19%] of 109). In the 324 patients with cancer and musculoskeletal symptoms, the most common complaints were joint pain (199 [61%]), followed by limb bone pain (112 [35%]). Joint involvement had a prevalent monoarticular pattern (100 [48%] of 207) and oligoarticular pattern (86 [42%] had 2-4 joints involved and 20 [10%] had >4 joints involved), with the most frequently involved joints being the hip (88 [43%] of 207) and knee (81 [39%]). On multivariable analysis, limb bone pain was the independent variable most strongly associated with cancer (odds ratio [OR] 87·80 [95% CI 18·89-408·12]), followed by weight loss (59·88 [6·34-565·53]), thrombocytopenia (12·67 [2·40-66·92]), monoarticular involvement (11·30 [4·09-31·19]), hip involvement (3·30 [1·13-9·61]), and male sex (2·40 [1·03-5·58]). Factors independently associated with juvenile idiopathic arthritis were morning stiffness (OR 0·04 [95% CI 0·01-0·20]), joint swelling (0·03 [0·01-0·09]), and involvement of the small hand joints (0·02 [0-1·05]). INTERPRETATION: Our study provides detailed information about presenting musculoskeletal manifestations of childhood cancers and highlights the clinical and laboratory features that are most helpful in the differential diagnosis with juvenile idiopathic arthritis. FUNDING: Associazione Lorenzo Risolo.

Tolerance of preterm formula versus pasteurized donor human milk in very preterm infants: a randomized non-inferiority trial.

BACKGROUND: Human milk (HM) is the best feeding for premature infants. When own mother's milk (OMM) is insufficient or unavailable, pasteurized donor human milk (PDHM) and preterm formula (PF) are the alternative nutritional sources, but the benefits of donor milk over formula are not defined. This study aimed to assess whether, in the absence of OMM, the PF could guarantee a feeding tolerance not inferior to that seen with the use of PDHM during the first two weeks of life of very preterm infants. METHODS: Infants with gestational age (GA) of ≤32 weeks who started enteral feeding within the first 7 days of life were randomized to receive PDHM or PF as a supplement to the OMM insufficient or unavailable. The primary outcome was the day of life when full enteral feeding (FEF) of 150 mL/Kg/d was achieved. RESULTS: Seventy infants were randomized, 35 in the PF group (GA 30.2 ± 1.7 weeks; BW 1342 ± 275 g), 35 in the PDHM group (GA 30 ± 1.9 weeks; BW 1365 ± 332 g). The time to achieve FEF was the same for infants fed with PF and for infants fed with PDHM (12.3 ± 7.0 days vs 12.8 ± 6.5). CONCLUSIONS: This trial shows that PF could be a valid alternative for the early feeding of very preterm infants when OMM is insufficient or unavailable. TRIAL REGISTRATION: UMIN000013922 . Date of formal registration: December 31, 2014.

Neonatal lupus: Follow-up in infants with anti-SSA/Ro antibodies and review of the literature.

Neonatal Lupus Syndrome (NLS) is a distinct clinical entity caused by transplacental passage of maternal anti-SSA/Ro antibodies (Ab). Mothers may have systemic lupus erythematosus, Sjögren syndrome, or other connective tissue disease, or may be completely healthy at the time of giving birth. NLS includes several clinical manifestations: complete congenital heart block (CCHB) and cutaneous lupus are the most common, while hepatobiliary disease, hematological manifestations and central nervous system involvement may occur. Data from literature on the incidence of the different clinical manifestations of NLS are difficult to compare because they come mostly from retrospective studies or prospective studies, but up to date no systematic follow-up was carried out. We performed a large prospective single-center study with a systematic clinical and instrumental follow-up until 9months of life, in order to evaluate the incidence and the clinical impact of NLS features. From 2004 to 2014 all infants born in our center to mothers with anti-SSA/Ro Ab were enrolled in a specific diagnostic and follow-up (FU) program. At birth, 50 infants born to mothers with anti-SSA/Ro Ab were found positive for anti-SSA/Ro Ab. Infants were tested for anti SSA/Ro Ab at 3months of life, if positive they were re-tested at 6 and 9months. At 9months anti-SSA/Ro Ab were positive in 10% of children. In two cases (4%) a CCHB was identified during pregnancy and required pacemaker implantation at birth. In 10% of cases a transient ECG alterations was found during follow-up. Hematological NLS features (anemia, neutropenia, thrombocytopenia) were found at birth and during FU in several patients, in all cases without clinical manifestations and in most cases with complete normalization at 9months. Mild and transient elevation of aminotransferases between 3 and 6months of life were found in 56% and 40% of patient, respectively; non-specific ultrasound cerebral anomalies in absence of clinical neurological signs were found at birth in 9 patients (18%), subsequently normalized. Prenatal maternal screening is of primary importance in order to early detect CCHB, which requires maternal treatment and pacemaker implantation at birth. Infants born to mothers with anti-SSA/Ro Ab should be monitored for all NLS features at birth. However, during the first months of life, these infants seem to develop only mild, transient and self-limited clinical manifestations, which in most cases are completely solved at 9months of life. This consideration, together with the evidence that only 10% of infants had anti-SSA/Ro Ab persistent in blood at 9months, suggests that follow-up of these children can be performed until 6-9months of life with good clinical safety. Moreover, a clinical and laboratory monitoring at 3months of life, when the highest incidence of hematological features and liver tests alterations are observed, is strongly recommended. In the future, it would be clarified if a follow-up until adulthood would be indicated in cases with persistent anti SSA/Ro or in all infants born to mother with anti SSA/Ro.

Epidural analgesia, neonatal care and breastfeeding.

The objective of our study is to evaluate the correlation between epidural analgesia during labor, start of breastfeeding and type of maternal-neonatal care.Two different assistance models were considered: Partial and Full Rooming-in.In this cohort study, 2480 healthy infants were enrolled, 1519 in the Partial Rooming-in group and 1321 in the Full Rooming-in group; 1223 were born to women subjected to epidural analgesia in labor.In case of Partial Rooming-in the rate of exclusive or prevailing breastfeeding is significant more frequent in newborns born to mothers who didn't receive analgesia. Instead, in case of Full Rooming-in the rate of exclusive or prevailing breastfeeding is almost the same and there's no correlation between the use or not of epidural analgesia.The good start of lactation and the success of breastfeeding seems to be guaranteed by the type of care offered to the couple mother-infant, that reverses any possible adverse effects of the use of epidural analgesia in labor.

Anti-Rh(c), "little c," isoimmunization: the role of rHuEpo in preventing late anemia.

The overall prevalence of non-Rh-D isoimmunization seems to lie between 0.15% and 1.1%. Anti-Rh(c) alloimmunization, "little c," occurs in 0.07% of pregnancies and shows a quite broad clinical presentation. Late anemia is a frequent problem occurring in the setting of isoimmunization. It occurs more frequently after intrauterine blood transfusions or exsanguinotransfusion, and it can be thought as a hyporegenerative anemia. The authors describe the use of human recombinant erythropoietin in preventing late anemia in a case of anti-Rh(c) isoimmunization. The use of human recombinant erythropoietin is a valid tool for preventing late-onset anemia due to either anti-Rh-D or non-anti-Rh-D isoimmunization.

Toward a bioethical issue: induced multiple pregnancies and neonatal outcomes.

Assisted reproductive technology has made great progress during the last three decades. After the initial enthusiasm, many ethical, legal and social issues related to the application of these procedures began to evolve. Multifetal pregnancy and fetal reduction, embryo cryopreservation, preimplantation genetic diagnosis, risks of birth defects and other adverse outcome associated with assisted reproductive technology are issues that have to be addressed building future collaborative studies and continuing the debate on related ethical issues.

Recombinant human erythropoietin in the prevention of late anemia in intrauterine transfused neonates with Rh-isoimmunization.

The majority of neonates with Rh-isoimmunization develops late anemia between the second and the sixth week of life. We report the effectiveness of recombinant human erythropoietin (rHuEPO) in preventing late anemia in 25 intrauterine and nonintrauterine-transfused neonates. The neonates were treated from 11+/-4 days after birth to 26+/-14 days (400 U/kg/d of rHuEpo, administered subcutaneously). During rHuEpo therapy, vitamin E, calcium folinate, and iron maltose were administered intramuscularly on a daily basis. Hematocrit, platelet, and neutrophil counts did not differ significantly before and after 21-days therapy. However, average values for reticulocyte showed a significant increase. The hematocrit values in the non-intrauterine transfusion (IUT) group increased progressively from the beginning to the end of the treatment, whereas that in the IUT group remained stable. Reticulocyte count increased during treatment in both groups, but it was significantly elevated in the non-IUT group only. Moreover, we observed that only neonates transfused with IUTs needed transfusions before and after treatment. This study suggests the effectiveness of rHuEpo therapy in the treatment of neonates with Rh-isoimmunization and it highlights how IUTs decrease the neonatal response efficacy. Larger, better if multicentric, randomized controlled trial are needed to definitely state whether rHuEPO safely decreases the incidence of late onset anemia.

Different fetal-neonatal outcomes in siblings born to a mother with Graves-Basedow disease after total thyroidectomy: a case series.

INTRODUCTION: We describe three different fetal or neonatal outcomes in the offspring of a mother who had persistent circulating thyrotropin receptor antibodies despite having undergone a total thyroidectomy several years before. CASE PRESENTATION: The three different outcomes were an intrauterine death, a mild and transient fetal and neonatal hyperthyroidism and a severe fetal and neonatal hyperthyroidism that required specific therapy. CONCLUSIONS: The three cases are interesting because of the different outcomes, the absence of a direct correlation between thyrotropin receptor antibody levels and clinical signs, and the persistence of thyrotropin receptor antibodies several years after a total thyroidectomy.

Weight loss and jaundice in healthy term newborns in partial and full rooming-in.

BACKGROUND: An inadequate start of breastfeeding has been associated with reduced caloric intake, excessive weight loss and high serum bilirubin levels in the first days of life. The rooming-in has been proposed as an optimal model for the promotion of breastfeeding. AIM: The aim of this study was to compare two different feeding models (partial and full rooming-in) to evaluate differences as regard to weight loss, hyperbilirubinemia and prevalence of exclusive breastfeeding at discharge. METHODS: A total of 903 healthy term newborns have been evaluated; all the newborns were adequate for gestational age, with birth weight > or = 2800 g and gestational age > or = 37 weeks. RESULTS: The maximum weight loss (mean +/- SD), expressed as percent of birth weight, was not different in the two models (partial vs. full rooming-in 5.8% +/- 1.7%vs. 6% +/- 1.7%). A weight loss > or = 10% occurred in less than 1% in both groups. There were no statistical differences neither as mean of total serum bilirubin (partial vs. full rooming-in 10.5 +/- 3.3 vs. 10.1 +/- 2.9 mg/dl), nor as prevalence of hyperbilirubinemia (total serum bilirubin > or = 12 mg/dl). The prevalence of severe hyperbilirubinemia (total serum bilirubin > or = 18 mg/dl) and the use of phototherapy were not statistically different. Maximum weight loss was similar in the two models, even dividing by total serum bilirubin levels. At the discharge, exclusively breastfed newborns were 81% in full rooming-in and 42.9% in partial rooming-in. CONCLUSIONS: In conclusion, our results allow considering our assistance models similar as regards to severe hyperbilirubinemia and pathological weight loss in term healthy newborns even if full rooming-in is associated with higher prevalence of exclusive breastfeeding at the discharge.

A severe case of intracranial hemorrhage due to alloimmune thrombocytopenia.

Alloimmune thrombocytopenia (AIT) is an important cause of intrauterine hemorrhagic lesions that result from platelet-antigen incompatibility between mother and foetus. Foetal platelets are destroyed by cross-reactive maternal antibodies that cross the placenta. The most serious complication of AIT is foetal intracranial bleeding that may eventually result in intrauterine death or severe neurological impairments.