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Up to 70% of patients with Wiskott-Aldrich Syndrome (WAS) develop autoimmune and inflammatory manifestations. Dysregulation of interleukin (IL)-1 may be involved in their pathogenesis, yet there is little evidence on treatment with anti-IL-1 agents in these patients. We conducted a multicenter retrospective analysis of nine patients with WAS treated with anti-IL-1 agents (anakinra or canakinumab). All patients had prominent inflammatory manifestations, including systemic, cutaneous, articular, and intestinal symptoms; three patients presented with a severe systemic inflammatory syndrome since the first months of life. Corticosteroid therapy was associated with partial or no response, while treatment with anakinra or canakinumab resulted in prompt, often dramatic, responses in all patients, allowing bridging to gene therapy (four patients) or hematopoietic stem cell transplantation (HSCT, five patients). Treatment was overall well tolerated. Low donor myeloid chimerism developed in four patients after HSCT and was associated with the appearance or the recurrence of inflammatory manifestations. A second HSCT was performed in two patients, achieving full-donor chimerism and resolution of inflammatory manifestation, while the other two patients were treated with prolonged therapy with anti-IL-1 agents. Our experience demonstrates that some inflammatory manifestations of WAS are dependent on IL-1 and respond very well to its pharmacologic blockade.
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Rumination syndrome (RS) is a complex functional disorder characterized by recurrent, repetitive regurgitation of recently swallowed food. RS may have medical and psychosocial implications, compromising the quality of life and causing high rates of school absenteeism. Pediatric RS has been poorly studied and little evidence regarding its treatment is available. This systematic review aims to evaluate the literature on the nonpharmacological treatment of RS in childhood. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, from 2000 to 2023. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different designs of study, and the risk of bias was evaluated with the Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I). Five hundred ninety-six studies were screened, and 7 studies were included in the review. Diaphragmatic breathing was the most used nonpharmacological treatment, and it was always combined with other therapeutic strategies. The vast heterogeneity of the physical or mental comorbidities and the methodology adopted in the publications did not allow a comparative analysis of the different treatments. Regardless of the type of treatment, high-intensity therapeutic programs and specific operators' training emerged as the most influencing factors for patients' outcomes. According to the available evidence, there is not enough high-quality evidence to suggest a defined therapeutic strategy. Large observational studies on selected patients accounting for possible confounders, with adequate follow-up times, and with clearly defined treatment regimens are needed to identify the best therapeutic approach.
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Síndrome de Rumiación , Humanos , Niño , Síndrome de Rumiación/terapia , Calidad de Vida , Ejercicios Respiratorios/métodosRESUMEN
Anomalous aortic origin of a coronary artery (AAOCA), especially the interarterial course of the right or left coronary artery, predisposes paediatric patients to myocardial ischaemia. This rare condition is a leading cause of sudden cardiac death. General paediatricians face challenges when diagnosing this anomaly, and they should pay particular attention to the recurrence of exercise-related syncope without prodromal symptoms, chest pain and dyspnoea. An accurate transthoracic echocardiogram with Doppler colour flow mapping is the best method to use to identify AAOCA. CONCLUSION: Identifying an AAOCA is challenging, and we provide advice on clinical red flags and diagnostic approaches for general paediatricians.
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Anomalías de los Vasos Coronarios , Aorta , Dolor en el Pecho , Niño , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Ecocardiografía , HumanosRESUMEN
AIM: According to the Italian national statistical institute, severe bacterial infections (SBI) in Italy are responsible for 1.7% of mortality under 5 years of age and their recognition is often challenging, especially in the first stages of the disease. We tried to estimate the prevalence of SBI in our target population and to identify signs and symptoms that could guide in the initial evaluation of a child with a possible SBI. METHODS: We designed a prospective, multicentre study and enrolled patients aged 0-14 years at the first evaluation to the emergency department with an acute illness lasting a maximum of 5 days. The presence of variables suggestive of SBI was collected for every enrolled patient. One week after the enrolment, every patient was followed up by telephone. RESULTS: SBI is more likely to be detected with the 'gut feeling' in both univariate and multivariate models (univariate OR: 7.16, 95% CI: 4.08-12.56; multivariate OR: 5.34, 95% CI: 2.78-10.25), while abnormal breathing pattern resulted significative only in univariate model (OR 3.83, 95% CI: 1.98-7.40). Nevertheless, their associated sensitivity is low. CONCLUSION: SBI is uncommon in the absence of paediatricians' gut feeling and abnormal respiratory pattern.
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Infecciones Bacterianas , Niño , Humanos , Lactante , Preescolar , Estudios Prospectivos , Infecciones Bacterianas/diagnóstico , Pediatras , Servicio de Urgencia en Hospital , Italia/epidemiologíaRESUMEN
BACKGROUND AND OBJECTIVES: Febrile urinary tract infection (fUTI) in well-appearing children is conventionally treated with a standard 10-day course of oral antibiotic. The objective of this study is to determine the noninferiority (5% threshold) of a 5-day amoxicillin-clavulanate course compared with a 10-day regimen to treat fUTIs. METHODS: This is a multicenter, investigator-initiated, parallel-group, randomized, controlled trial. We randomly assigned children aged 3 months to 5 years with a noncomplicated fUTI to receive amoxicillin-clavulanate 50 + 7.12 mg/kg/day orally in 3 divided doses for 5 or 10 days. The primary end point was the recurrence of a urinary tract infection within 30 days after the completion of therapy. Secondary end points were the difference in prevalence of clinical recovery, adverse drug-related events, and resistance to amoxicillin-clavulanic acid and/or to other antibiotics when a recurrent infection occurred. RESULTS: From May 2020 through September 2022, 175 children were assessed for eligibility and 142 underwent randomization. The recurrence rate within 30 days of the end of therapy was 2.8% (2/72) in the short group and 14.3% (10/70) in the standard group. The difference between the 2 groups was -11.51% (95% confidence interval, -20.54 to -2.47). The recurrence rate of fUTI within 30 days from the end of therapy was 1.4% (1/72) in the short group and 5.7% (4/70) in the standard group (95% confidence interval, -10.4 to 1.75). CONCLUSIONS: This study demonstrates that a 5-day course is noninferior to a 10-day course of oral amoxicillin-clavulanate.
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Recurrencia Local de Neoplasia , Infecciones Urinarias , Humanos , Combinación Amoxicilina-Clavulanato de Potasio , Antibacterianos/uso terapéutico , Recurrencia Local de Neoplasia/inducido químicamente , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/complicaciones , Lactante , PreescolarRESUMEN
BACKGROUND: Plexiform neurofibromas are benign neoplasms that develop in 20-50% children with neurofibromatosis type 1 (NF1). Selumetinib was approved as treatment for symptomatic and inoperable plexiform neurofibromas. Subclinical left ventricular ejection fraction reduction is a less common effect of selumetinib. OBJECTIVE: We aimed to investigate the contractile function of the heart in a cohort of children with NF1 treated with selumetinib. METHODS: We designed a cross-sectional study including 17 patients with NF1 who received selumetinib. Echocardiographic parameters were compared with a cohort of 17 healthy children matched by sex and age and another group of 17 children with untreated NF1. RESULTS: Compared with healthy controls, patients with NF1 treated with selumetinib had lower mean values of global longitudinal strain (- 22.9 ± 2% vs -25.5 ± 2%; p = 0.001), fractional shortening (36 ± 4% vs 43 ± 8%; p = 0.02) and tricuspid annular plane systolic excursion (19 ± 3 mm vs 23 ± 2 mm; p = 0.001); no difference was found in left ventricular ejection fraction (63 ± 4% vs 65 ± 3%; p = 0.2 respectively). Median treatment time with selumetinib at the time of the echocardiographic evaluation was 22 ± 16 months. CONCLUSIONS: Patients with NF1 treated with selumetinib may experience subtle changes in systolic function identified by global longitudinal strain and not revealed by left ventricular ejection fraction. Global longitudinal strain might be useful to monitor cardiac function in this cohort of patients for the duration of therapy.
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Neurofibroma Plexiforme , Neurofibromatosis 1 , Humanos , Niño , Neurofibromatosis 1/complicaciones , Neurofibromatosis 1/diagnóstico por imagen , Neurofibromatosis 1/tratamiento farmacológico , Neurofibroma Plexiforme/tratamiento farmacológico , Volumen Sistólico , Estudios Transversales , Tensión Longitudinal Global , Función Ventricular Izquierda , EcocardiografíaRESUMEN
In the maintenance phase of Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP)- Berlin-Frankfurt-Muenster (BFM) acute lymphoblastic leukemia (ALL) 2009 protocol, mercaptopurine (MP) is given at the planned dose of 50 mg/m2 /day; however, dose adjustments are routinely performed to target patients' white blood cells to the optimal range of 2,000-3,000 cells/µL. Pediatric patients with ALL (n = 290, age: median (1st-3rd quartile): 4.8 (3.0-8.1) years; boys: 56.9%) were enrolled mainly in 4 medium-large Italian pediatric hospitals; 14.1% of patients relapsed after a median (1st-3rd quartile) follow-up time of 4.43 (3.82-5.46) years from maintenance beginning. MP metabolites (thionucleotide (TGN) and methyl-derivatives (MMPN)) were measured in the erythrocytes of 387 blood samples of 200 patients by high performance liquid chromatography with ultraviolet detection. Single-nucleotide polymorphisms (SNPs; (rs1800462, rs1800460, and rs1142345 in TPMT gene, rs116855232 in NUDT15, rs1127354, rs7270101, rs6051702 in ITPA, and rs2413739 in PACSIN2) were characterized by Taqman SNP genotyping assays. Cox proportional hazard models did not show an impact of TGN levels and variability on relapse. In contrast, after multivariate analysis, relapse hazard ratio (HR) increased in children with ALL of the intermediate risk arm compared with those in standard risk arm (3.44, 95% confidence interval (CI), 1.31-9.05, P = 0.012), and in carriers of the PACSIN2 rs2413739 T allele compared with those with the CC genotype (heterozygotes CT: HR, 2.32, 95% CI, 0.90-5.97, P = 0.081; and homozygous TT: HR, 4.14, 95% CI, 1.54-11.11, P = 0.005). Future studies are needed to confirm the lack of impact of TGN levels and variability on relapse in the AIEOP-BFM ALL trials, and to clarify the mechanism of PACSIN2 rs2413739 on outcome.
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According to the latest version of the Diagnostic and Statistical Manual of Mental Disorders, somatic symptom and related disorders (SSRDs) are defined as psychopathological manifestations characterized by physical signs not attributable to organic pathology. Their incidence has grown dramatically over the past few decades, and treatment is challenging. Besides other interventions on the child and the family, physiotherapy is considered an integral part of the treatment, although there is no evidence for its efficacy.The study aimed to review the available proof on the effectiveness of physiotherapy in children and adolescents with SSRDs. A systematic literature search was conducted on MEDLINE/PubMed, CINAHL, Cochrane Library, PsycINFO, and PEDro, including 1999 to 2021. The methodological quality of the publications was assessed by applying the guidelines proposed by the Equator network, according to the different study designs. The scientific bibliography on the subject was minimal and had poor methodological quality. The choice of outcome indicators and the scales to measure them varied from study to study and were not standardized, making comparison and meta-analysis challenging.Conclusion: According to the available evidence, it is impossible to answer the review question regarding the effectiveness of physiotherapy in children and adolescents with SSRDs. It is necessary to improve the methodological quality of the studies. Definition of standard rehabilitation treatments, identification of appropriate result indicators, and adoption of standardized evaluation scales are needed.
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Síntomas sin Explicación Médica , Modalidades de Fisioterapia , Adolescente , Niño , Humanos , Resultado del TratamientoRESUMEN
Background: Left ventricular non-compaction (LVNC) is an abnormality of the myocardium, characterized by prominent left ventricular trabeculae and deep inter-trabecular recesses. Long QT syndrome (LQTS) is a cardiac ion channelopathy presenting with a prolonged QT interval on resting electrocardiogram and is associated with increased susceptibility to sudden death. The association between LVNC and LQTS is uncommon. Case presentation: We report an Italian family with a novel pathogenic KCNH2 variant who presented with clinical features of LVNC and LQTS. The proband came to our attention after two syncopal episodes without prodromal symptoms. His ECG showed QTc prolongation and deep T wave inversion in anterior leads, and the echocardiogram fulfilled LVNC criteria. After that, also his sister was found to have LQTS and LVNC, while his father only presented LQTS. Conclusions: Physicians should be aware of the possible association between LVNC and LQTS. Even if this association is rare, patients with LVNC should be investigated for LQTS to prevent possible severe or even life-threatening arrhythmic episodes.