A prospective study to evaluate the contribution of the pediatric appendicitis score in the decision process.

BACKGROUND: The objective of this study was to assess the likelihood of acute appendicitis (AA) in children presenting with abdominal symptoms at the emergency department (ED), based on their prior primary care (PC) consultation history. METHODS: Between February and June 2021, we prospectively enrolled all children presenting at the ED with acute abdominal pain indicative of possible acute appendicitis (AA). Subsequently, they were categorized into three groups: those assessed by a PC physician (PG), those brought in by their family without a prior consultation (FG), and those admitted after a PC consultation without being assessed as such. The primary objective was to assess the probability of AA diagnosis using the Pediatric Appendicitis Score (PAS). Secondary objectives included analyzing PAS and C-reactive protein (CRP) levels based on the duration of pain and final diagnoses. RESULTS: 124 children were enrolled in the study (PG, n = 56; FG, n = 55; NG, n = 13). Among them, 29 patients (23.4%) were diagnosed with AA, with 13 cases (23.2%) from the PG and 14 cases (25.4%) from the FG. The mean PAS scores for AA cases from the PG and FG were 6.69 ± 1.75 and 7.57 ± 1.6, respectively, (p = 0.3340). Both PAS scores and CRP levels showed a significant correlation with AA severity. No cases of AA were observed with PAS scores < 4. CONCLUSIONS: There was no significant difference in PAS scores between patients addressed by PG and FG, even though PAS scores tended to be higher for patients with AA. We propose a new decision-making algorithm for PC practice, which incorporates inflammatory markers and pain duration. TRIAL REGISTRATION: Institutional Ethics Committee registration number: 447-2021-103 (10/01/2021). CLINICAL TRIALS REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT04885335 (Registered on 13/05/2021).

Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid-Dependent Idiopathic Nephrotic Syndrome.

BACKGROUND AND OBJECTIVES: Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid-dependent nephrotic syndrome. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective multicenter study including 95 children with steroid-dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model. RESULTS: In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30-60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89; P=0.01). CONCLUSIONS: Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid-dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population.

C3 nephritic factor can be associated with membranous glomerulonephritis.

BACKGROUND: C3 nephritic factor (C3NeF) has been described in association with membranoproliferative glomerulonephritis and is involved in 80 % of cases of dense deposit disease. C3NeF is an immunoglobulin G (IgG) autoantibody which binds to the complement component 3 (C3) convertase C3bBb, thereby inhibiting its decay and leading to massive C3 cleavage. Commonly associated with C3NeF are low C3 levels, decreased total haemolytic complement (CH50) and normal C4 levels. C3NeF patients often present with proteinuria, haematuria and high blood pressure. Evolution to end-stage renal disease is common. Treatment consists of steroids and/or immunosuppressants, with variable efficiency. Renal transplantation is marked by histological recurrence, leading to higher rates of allograft loss. CASES: We report C3NeF in association with membranous glomerulonephritis type 3-4 in two unrelated children. We also demonstrate that, under adequate immunosuppressive therapy, proteinuria is significantly lowered, blood pressure is kept within normal range and long-term renal function remains normal. CONCLUSIONS: C3NeF can be associated with membranous glomerulonephritis in children. Clinical presentation is mild, and mid-term outcome is favourable under adequate therapy. However, complement anomalies persist for several years.

Occurrence of inflammatory bowel disease during treatment of juvenile idiopathic arthritis with etanercept: a French retrospective study.

OBJECTIVES: To identify juvenile idiopathic arthritis (JIA) patients who developed IBD during treatment with anti-TNF-alpha agents and better characterize the IBD clinical and pathological presentation. METHODS: A retrospective French multicentre study included patients with a diagnosis of JIA according to the ILAR criteria who developed IBD while under anti-TNF-alpha therapy before 18 years of age. Intestinal biopsies were collected and reviewed by the same pathologist. RESULTS: Eight patients were included. They had been treated with etanercept from 11 to 78 months before IBD onset. Gastro-intestinal symptoms included abdominal pain (six patients), diarrhoea (four patients), anorexia (four patients), anal abscess (three patients) and oral ulcers (one patient). Five patients presented with Crohn's disease (CD) and three with indeterminate IBD, of whom four had severe pancolitis. Clinical remission of IBD was obtained in all patients after discontinuation of etanercept and initiation of IBD-specific therapy, including infliximab in six patients. CONCLUSION: IBD must be suspected in JIA patients treated with etanercept who develop intestinal symptoms, including anal abscess. This series raises the possibility of a relationship between etanercept therapy and the occurrence of IBD in a subset of patients with JIA.

Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 cases.

Several case reports suggest that rituximab (RTX) could be effective in steroid-dependent nephrotic syndrome, but RTX efficacy has not yet been studied in a series of patients. Safety and efficacy of RTX were assessed in a multicenter series of 22 patients aged 6.3-22 years with severe steroid-dependent nephrotic syndrome or steroid-resistant but cyclosporin-sensitive idiopathic nephrotic syndrome. Patients were treated with two to four infusions of RTX. Seven patients were nephrotic at the time of RTX treatment. Peripheral B cells were depleted in all subjects. Remission was induced in three of the seven proteinuric patients. One or more immunosuppressive (IS) treatments could be withdrawn in 19 patients (85%), with no relapse of proteinuria and without increasing other IS drugs. RTX was effective in all patients when administered during a proteinuria-free period in association with other IS agents. When relapses occurred, they were always associated with an increase in CD19 cell count. Adverse effects were observed in 45% of cases, but most of them were mild and transient. This study suggests that RTX could be an effective treatment for severe steroid-dependent nephrotic syndrome.