Explore the vast range of titles available.

Objective Juvenile idiopathic arthritis (JIA) is the most common chronic pediatric rheumatic disease. Early referral to a specialized center is crucial for prompt diagnosis and treatment. This study aims to develop and validate a scoring system to assist clinicians in efficiently identifying and referring patients suspected of having non-systemic JIA. Methods We conducted a cohort study with a mixed design (retrospective and prospective), involving consecutive patients presenting with joint complaints who were referred for the first time to the Pediatric Rheumatology Unit at ASST G. Pini-CTO Hospital. The model was developed using multivariate logistic regression with bootstrap resampling and the Lasso (Least Absolute Shrinkage and Selection Operator) method for variable selection. Results A total of 342 patients were included, of whom 61 (18%) were diagnosed with JIA. The selected variables for the model were: type of joint (large), daily symptoms, joint swelling, activity as a precipitating factor, a positive squeeze test of the metatarsophalangeal/metacarpophalangeal (MTP/MCP) joints, normal bending of the interphalangeal (IF) joints of the hands, morning limping and/or stiffness, and sacroiliac tenderness. The ROC curve, based on the model’s regression score, showed an AUC of 0.92 with an overall accuracy of 0.88 (95% CI: 0.84–0.91) using a cutoff of 3 points, yielding a sensitivity of 95% and a specificity of 71%. Initial internal validation of the model revealed an AUC of 0.92 (95% CI: 0.89–0.95). Conclusion This study presents and initially validates a simple and efficient scoring system to aid clinicians in the early referral of patients suspected of having non-systemic JIA. Clinical trial number Not applicable.

The activity of acid sphingomyelinase (ASMase), a key enzyme in sphingolipid metabolism, has been found to be increased in a variety of human diseases. Studies conducted on animal and cellular models showed that sphingolipids and ASMase play a central role in the pathogenesis of type 1 diabetes (T1D) and T1D-related vascular damage. Currently, no studies have investigated the role of ASMase activity in pediatric patients with T1D. Therefore, we conducted a cross-sectional study to evaluate the activity of the secretory form of ASMase (S-ASMase) in the serum of patients with T1D aged 2-16 years in comparison with a control group (healthy subjects matched for age, gender, and pubertal stage). We recruited children and adolescents affected by T1D (including patients with new-onset and established T1D) aged 2-16 years and healthy normal-weight subjects with normal timing of puberty (matched for age, gender, and pubertal stage), who were consecutively admitted-as outpatients-to our institution for screening purposes. Serum lipid profile, glycated hemoglobin (HbA1c), and urine albumin-creatinine ratio (uACR) were assessed in all T1D patients. S-ASMase activity was measured in all study participants through a colorimetric assay. In total, 68 T1D patients and 51 healthy controls were recruited in this study. None of the T1D patients had T1D-related complications. No difference in S-ASMase activity was observed between subjects with T1D and healthy controls. However, when T1D patients were stratified according to the duration of diabetes, we found a significantly higher activity of S-ASMase in patients with new-onset T1D (recruited within 1 week after the disease diagnosis) as compared to that observed in patients with established T1D. In all patients with T1D, S-ASMase activity correlated positively with HbA1c and triglyceride levels, while it correlated negatively with total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) levels. However, there were no significant differences in S-ASMase activity between T1D patients with new-onset disease who presented with diabetic ketoacidosis (DKA; n = 12) and T1D patients with new-onset disease who did not present with DKA (n = 13). Our study evaluated, for the first time, the in vivo activity of S-ASMase in a pediatric cohort of patients with T1D. In pediatric patients with new-onset T1D, we found a significantly higher S-ASMase activity as compared to that observed in patients with established T1D. In all T1D patients, the positive correlation between S-ASMase activity, HbA1c, and triglyceride levels, as well as the negative correlation between S-ASMase activity and HDL-C levels, suggests a potential role played by sphingolipids in T1D pathophysiology. Further mechanistic studies are needed to better elucidate the role of S-ASMase in patients with T1D at different stages of the disease.

The diagnosis of juvenile idiopathic arthritis (JIA) is often entrusted to the pediatric rheumatologist specialist. Timely referral to a specialized center is crucial. This study aims to assess the consultation and investigation patterns of patients with joint complaints before rheumatology referral. This longitudinal cohort study included patients with joint complaints who were referred to the Pediatric Rheumatology Unit. The cohort included 301 patients (58% female), 50 of them (17%) diagnosed with JIA. Compared to patients with orthopedic conditions or functional diseases, JIA patients had seen more specialists (p < 0.01) and received a quicker diagnosis (p < 0.01). Patients with early JIA diagnosis (within 3 months from symptoms onset) were younger (8.46 vs. 11.5 years old; p = 0.04), more frequently female (78% vs. 47%, p = 0.03), and with higher erythrocyte sedimentation rate (ESR) values (37 vs. 9 mm/h; p = 0.02) than those diagnosed later. Patients with a late diagnosis of JIA had a significantly longer median time between the first healthcare visit and the PR referral (25 vs. 101 days; p < 0.01). The main contributor to diagnostic delay in JIA was the time required for PR referral after the first healthcare consult. Younger age, female sex, and higher ESR values were associated with earlier diagnosis of JIA.

Food-protein-induced allergic proctocolitis (FPIAP) is an increasingly reported transient and benign form of colitis that occurs commonly in the first weeks of life in healthy breastfed or formula-fed infants. Distal colon mucosal inflammation is caused by a non-IgE immune reaction to food allergens, more commonly to cow’s milk protein. Rectal bleeding possibly associated with mucus and loose stools is the clinical hallmark of FPIAP. To date, no specific biomarker is available, and investigations are reserved for severe cases. Disappearance of blood in the stool may occur within days or weeks from starting the maternal or infant elimination diet, and tolerance to the food allergen is typically acquired before one year of life in most patients. In some infants, no relapse of bleeding occurs when the presumed offending food is reassumed after a few weeks of the elimination diet. Many guidelines and expert consensus on cow’s milk allergy have recently been published. However, the role of diet is still debated, and recommendations on the appropriateness and duration of allergen elimination in FPIAP are heterogeneous. This review summarizes and compares the different proposed nutritional management of infants suffering from FPIAP, highlighting the pros and cons according to the most recent literature data.

Background/Objectives: Food protein-induced allergic proctocolitis (FPIAP) is a non-IgE-mediated gastrointestinal food allergy. Although tolerance to the culprit food is usually achieved within the first year of life, late acquisition occurs and remains poorly predictable. This study aimed to analyze clinical characteristics and explore factors that may potentially function as predictors of late tolerance acquisition to cow’s milk (CM). Methods: We conducted a cross-sectional study at two Italian pediatric clinics (2020–2024), including infants diagnosed with FPIAP. Clinical, dietary, and immunological variables; onset and duration of rectal bleeding (visible blood in the stools); and time to CM tolerance were analyzed. Late tolerance was defined as acquisition after 19 months according to the distribution of tolerance achievement in our population. Statistical analyses included χ2, Mann–Whitney U, Spearman’s correlation, and logistic regression. Results: Ninety-four infants were included (median age at onset 2.9 months [IQR 1.9–4.7]); 58 (62%) were exclusively breastfed and 18 (19%) were born preterm (<37 completed weeks of gestation). CM was the culprit food in all cases; tolerance was achieved in all infants at a median age of 12 months. Family history of atopy and atopic dermatitis were reported in 44% and 19% of infants, respectively. Late CM tolerance was associated with preterm birth, fortification of human milk, early antibiotic exposure, growth faltering, and recurrent infections. Logistic regression identified family history of atopy (OR 5.4 [95% CI 1.2–25.4]; p = 0.031), atopic dermatitis (OR 8.2 [1.7–40.7]; p = 0.010), rectal bleeding >18 days before elimination diet (OR 5.9 [1.3–27.7]; p = 0.023), and IgE sensitization (OR 6.4 [1.2–35.0]; p = 0.034) as factors that may potentially function as predictors of late tolerance acquisition to CM. Conclusions: Identification of factors that may potentially function as predictors of late tolerance acquisition to CM in infants with FPIAP may help providing a personalized clinical management for these patients.

Acute and chronic Food Protein-Induced Enterocolitis Syndrome (FPIES) has been well characterized in children; otherwise, neonatal FPIES (N-FPIES) remains poorly understood. In terms of pathophysiology, neonatal FPIES appears to have a more prevalent TH2 response and is characterized by specific clinical features that make the diagnosis challenging. Genetic and environmental risk factors may predispose to the development of FPIES. Recent evidence indicates that a characteristic microbiota signature may lead to barrier dysfunction, reduced regulatory T cells, and abnormal intestinal production of serotonin, responsible for the symptoms of FPIES. Regarding clinical presentation, newborns with FPIES may not fully meet the current guideline’s diagnostic criteria at disease onset, being more similar to clinical entity specific of neonatal age than to acute FPIES in infants and children. Hence, differentiation from other neonatal medical and surgical conditions—particularly necrotizing enterocolitis (NEC)—remains a critical challenge for clinicians. This present review highlights our current understanding of N-FPIES, in term of pathophysiology, clinical presentation diagnosis, and treatment strategies. Refining diagnostic criteria for N-FPIES represents a clinical priority to help physicians in diagnosing and managing this challenging condition. Last, but not least, larger clinical trials are needed to optimize treatment practices in term and preterm newborns with FPIES.

The study aimed to evaluate bone repair using three osteoinductive polymers in bone defects created in rabbit tibias. Forty-eight adult rabbits were assessed at various time points: three, seven, fourteen, and thirty days. The groups included a control group (without biomaterial), M1 (Poly L Lactide co Polycaprolactone/Polyethylene Glycol), M2 (Poly L Lactide co Polycaprolactone/Polyethylene Glycol/β-Tricalcium Phosphate), and M3 (Poly L Lactide co Polycaprolactone/Polyethylene Glycol/nano hydroxyapatite). Histomorphometric analysis was conducted to evaluate new bone formation within and around the bone defect. At 14 (p<0.05) and 30 days (p<0.05), the callus area in the membrane groups, particularly in M3, was also significantly larger than in the control group, indicating the osteoinductive potential of these biomaterials. The callus consisted of both bone and cartilaginous matrix, suggesting a robust activation of endochondral ossification. The number of osteoclast was higher in the membrane groups, especially at 14 days in the M3 group, indicating increased bone remodeling activity. The membranes were not fully absorbed by 30 days, creating a space between the defect and the periosteum. In conclusion, all three membranes showed significant chondro and osteoinductive potential, with the membrane containing nano-hydroxyapatite demonstrating the most pronounced potential.

Cushing’s disease (CD) is rare in paediatric practice but requires prompt investigation, diagnosis and therapy to prevent long-term complications. Key presenting features are a change in facial appearance, weight gain, growth failure, virilization, disturbed puberty and psychological disturbance. Close consultation with an adult endocrinology department is recommended regarding diagnosis and therapy. The incidence of CD, a form of ACTH-dependent Cushing’s syndrome (CS), is equal to approximately 5% of that seen in adults. The majority of ACTH-secreting adenomas are monoclonal and sporadic, although recent studies of pituitary tumours have shown links to several deubiquitination gene defects. Diagnosis requires confirmation of hypercortisolism followed by demonstration of ACTH-dependence. Identification of the corticotroph adenoma by pituitary MRI and/or bilateral inferior petrosal sampling for ACTH may contribute to localisation before pituitary surgery. Transsphenoidal surgery (TSS) with selective microadenomectomy is first-line therapy, followed by external pituitary irradiation if surgery is not curative. Medical therapy to suppress adrenal steroid synthesis is effective in the short-term and bilateral adrenalectomy should be considered in cases unfit for TSS or radiotherapy or when urgent remission is needed after unsuccessful surgery. TSS induces remission of hypercortisolism and improvement of symptoms in 70–100% of cases, particularly when performed by a surgeon with experience in children. Post-TSS complications include pituitary hormone deficiencies, sub-optimal catch-up growth, and persisting excess of BMI. Recurrence of hypercortisolism following remission is recognised but infrequent, being less common than in adult CD patients. With experienced specialist medical and surgical care, the overall prognosis is good. Early referral to an experienced endocrine centre is advised.

Bone metabolism has been rarely investigated in children affected by Neurofibromatosis type 1 (NF1). Aim of the present study was to assess bone mineral metabolism in children and adults NF1 patients, to determine the relevant factors potentially involved in the development of reduced bone mineral density (BMD), and provide possible therapeutic intervention in NF1 patients. 114 NF1 patients and sex and age matched controls were enrolled into the study. Clinical and biochemical factors reflecting bone metabolism were evaluated. Factors potentially affecting BMD were also investigated including: physical activity, sun exposure, vitamin D intake. Whenever the presence of vitamin D deficiency was recorded, cholecalciferol supplementation was started and z-score data obtained at Dual-Energy X-ray Absorptiometry (DXA) during supplementation were compared with previous ones. NF1 patients showed lower Z-scores at Dual-Energy X-ray Absorptiometry DXA than controls. Physical activity was significantly reduced in NF1 patients than in controls. Sun exposure was significantly lower in NF1 compared to control subjects. At linear regression analysis vitamin D was the most predictive factor of reduced z-score at DXA (p = 0.0001). Cholecalciferol supplementation significantly increased BMD z-score (p < 0.001). We speculated that a combination of different factors, including reduced sun exposure, possibly associated with reduced serum vitamin D levels, and poor physical activity, concur to the impaired bone status in NF1 patients. We also demonstrated that treatment with vitamin D can be effective in improving z-score value in NF1 patients, including children. In conclusion, the findings of the current study are expected to have important implications for the follow-up and prevention of osteopenia/osteoporosis in this common genetic disease.

Background Peripheral precocious puberty (PPP) is an endocrine disorder characterized by premature, autonomous gonadal or extragonadal sexual steroid secretion. Accounting for about 20% of cases of precocious puberty, PPP is usually caused by rare diseases, including congenital adrenal hyperplasias, hormone-secreting gonadal and adrenal tumours, and McCune-Albright Syndrome (MAS). MAS is a rare, genetic disorder, mainly characterized by bone dysplasia, skin hyperpigmentation, and endocrine, hyperfunctioning disorders, including, as reported, PPP. Being a rare disease, PPP management in MAS patients is currently anecdotically reported, and no systematic approach is granted. Case presentation A four years and two months boy was admitted in our department due to precocious pubarche and recent growth acceleration. At physical examination, he showed cafè-au-lait skin macules on thorax, abdomen, and posterior neck, and at hormonal evaluation he showed evidence of PPP, confirmed at both baseline and stimulated gonadotropin and testosterone levels. Due to the clinical features, he was diagnosed with MAS, that was further confirmed by the evidence of bone skull and testicular lesions; a thyroid lesion was also reported, but its relationship with MAS was questioned. He therefore started combined treatment with androgen receptor blocker bicalutamide and aromatase inhibitor anastrazole, that were able to significantly reduce growth acceleration and to stop pubertal progression. He safely continued combined treatment for three years, showing good efficacy on growth and pubertal outcome. Conclusion Combined treatment with bicalutamide and anastrozole is a safe and effective long-term therapeutic approach to PPP in MAS boys, although evidences on its use are scarce; therefore, wider studies including larger populations deriving from different centres should be performed to obtain general consensus.