Long-term renal function and hypertension in adult survivors of childhood sarcoma

Aim: Little data is available on long-term renal impairment in survivors from childhood sarcoma. We investigated the prevalence of renal impairment and hypertension after very long-term follow-up in survivors who reached adulthood after treatment for childhood sarcoma. Methods. A cross-sectional single center study was performed. Outcomes included estimating glomerular filtration rate (eGFR), albuminuria, glycosuria, serum phosphate and magnesium, tubular reabsorption phosphate (TRP), chronic kidney disease (CKD) according to the “Kidney Disease: Improving Global Outcomes” (KDIGO) guidelines and blood pressure (BP). Results: Out of 87>5-year sarcoma survivors, 30 adults (10F/20M, median age at diagnosis 9 years, median age at investigation 26 years, median follow-up 16 years, mean 19 years) were identified. Renal impairment was detected in 4 cases (13.3%); 3 of these fulfilled the criteria for CKD. Among the adult survivors, a subgroup of 15 cases (50%) had received ifosfamide without confounding factors such as a diagnosis of genito-urinary rhabdomyosarcoma or administration of other potentially nephrotoxic chemotherapy (platinum-based drugs or methotrexate); no renal dysfunction was detected in this subgroup. In the whole cohort of sarcoma survivors, hypertension was diagnosed in 4 cases (13.3%); BP was significantly correlated with body mass index [p 0.014] Conclusion: In our series of adult survivors treated for a diagnosis of sarcoma in their childhood, the prevalence of CKD was 10%. We found survivors treated with ifosfamide as the only nephrotoxic agent did not present glomerular or tubular toxicity at long term follow-up, but further studies including a larger number of cases are required to confirm it.

Paediatric recurrent pericarditis: Appropriateness of the standard of care and response to IL1-blockade

Objective: To analyse, in a cohort of paediatric patients with recurrent pericarditis (RP) undergoing anti-IL-1 treatment: the agent and dosing used as first line treatment, the long-term efficacy of IL1-blockers, the percentage of patients achieving a drug-free remission, the presence of variables associated with drug-free remission. Study design: Data were collected from patients' charts. Annualized relapse rate (ARR) was used for evaluation of treatment efficacy, bivariate logistic regression analysis for variables associated with drug-free remisison. Results: 58 patients, treated between 2008 and 2018, were included in the study (mean follow-up 2.6 years). 14/56 patients non-responsive to first line drugs were under-dosed. 57 patients were treated with anakinra: the ARR before and during daily treatment was 3.05 and 0.28, respectively (p<0.0001); an increase to 0.83 was observed after the reduction/withdrawal of treatment (p<.0001). The switch from anakinra to canakinumab (5 patients) was associated to an increase of the ARR (0.49 vs 1.46), but without statistical significance (p=0.215). At last follow-up only 9/58 patients had withdrawn all treatments. With the limits of a retrospective study and the heterogeneity between the patients enrolled in the study, a shorter duration of treatment with anakinra was the only variable associated with drug-free remission. Conclusion: This study shows that most of the pediatric patients with RP needing IL-1 blockade received an inadequate treatment with first line agents. The effectiveness of anakinra is supported by this study, but few patients achieved drug free-remission. The different rate of response to anakinra and canakinumab may suggest a possible role of IL1α in the pathogenesis of RP

Preliminary data revealing efficacy of Streptococcus salivarius K12 (SSK12) in Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome: A multicenter study from the AIDA Network PFAPA syndrome registry

Objective: To evaluate the potential role of Streptococcus salivarius K12 (SSK12) in controlling febrile flares in patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Further aims were to assess the impact of SSK12 on (i) flare duration, (ii) variation in the degree of the highest body temperature during flares, (iii) steroid-sparing effect, and (iv) change of PFAPA accompanying symptoms before and after SSK12 introduction. Patients and methods: The medical charts from 85 pediatric patients with PFAPA syndrome (49 males and 36 females) enrolled in the AIDA registry and treated with SSK12 for a median period of 6.00 ± 7.00 months in the period between September 2017 and May 2022 were examined. Children recruited had a median time of disease duration of 19.00 ± 28.00 months. Results: The number of febrile flares significantly decreased comparing the 12 months before [median (IQR), 13.00 (6.00)] and after SSK12 initiation [median (IQR), 5.50 (8.00), p &lt; 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [p &lt; 0.001]. Similarly, the highest temperature in°C was found significantly lower in the last follow-up assessment [median (IQR), 39.00 (1.00)] compared to the period prior to SSK12 start [median (IQR), 40.00 (1.00), p &lt; 0.001]. Steroid load (mg/year) of betamethasone (or any equivalent steroid) significantly decreased between 12 months before treatment with SSK12 [median (IQR), 5.00 (8.00) mg/year] and the last follow-up visit [median (IQR), 2.00 (4.00) mg/year, p &lt; 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis (p &lt; 0.001), oral aphthae (p &lt; 0.001) and cervical lymphadenopathy (p &lt; 0.001) significantly decreased following SSK12. Conclusion: SSK12 prophylaxis given for at least 6.00 months was found to reduce febrile flares of PFAPA syndrome: in particular, it halved the total number per year of fever flares, shortened the duration of the single febrile episode, lowered body temperature by 1°C in the febrile flare, provided a steroid-sparing effect, and significantly reduced the accompanying symptoms related to the syndrome

Treating allergic rhinitis by sublingual immunotherapy: a review

OBJECTIVE: Allergic rhinitis (AR) is a disease with high and increasing prevalence. The management of AR includes allergen avoidance, anti-allergic drugs, and allergen specific immunotherapy (AIT), but only the latter works on the causes of allergy and, due to its mechanisms of action, modifies the natural history of the disease. Sublingual immunotherapy (SLIT) was proposed in the 1990s as an option to traditional, subcutaneous immunotherapy. MATERIAL AND METHODS: We reviewed all the available controlled trials on the efficacy and safety of SLIT. RESULTS AND CONCLUSION: Thus far, more than 60 trials, globally evaluated in 6 meta-analyses, showed that SLIT is an effective and safe treatment for AR. However, it must be noted that to expect clinical efficacy in the current practice SLIT has to be performed following the indications from controlled trials, that is, sufficiently high doses to be regularly administered for at least 3 consecutive years

Pathogenesis of vernal keratoconjunctivitis and associated factors

Aim: To investigate the role of some variables, including allergy and autoimmunity, in the pathogenesis of vernal keratoconjunctivitis (VKC). The VKC is a chronic and often severe form of bilateral keratoconjunctivitis. Usually, it begins during the first decade and disappears during the end of the second decade of life. Materials and methods: 26 patients with VKC were selected. The diagnosis was performed by the ophthalmologist through a score based on ocular signs and subjective symptoms before and after administration of 1% cyclosporine A (Cy) eyedrops. Each variable was graded: 0 = absent; 1 = mild; 2 = moderate; 3 = severe. Patients with a total score ≥7 were included in the study. Blood samples were collected at the initial time for the determination of autoimmunity by total IgE and antinuclear antibodies (ANA). A Skin Prick Test (SPT) was performed on each patient to common inhalants and food allergens. Results: 53.8% of the children resulted atopic. The most important allergens were house dust mites and grasses. 46.1% of the patients showed total IgE &gt;100 UI/ml and 30.8% had ANA positivity at the first determination. The photophobia occurred in 42.3% of children, most frequently with respect to other symptoms like secretion or tearing (30.8%), foreign body sensation (15.4%), itching and conjunctival hyperemia (11.5%). Conclusions: Fortunately all children improved their symptoms after Cy eyedrop therapy. Moreover, there was an elevated percentage (30.8%) of children with ANA positivity compared with the values in the general pediatric population. Despite the fact that it is a non-specific autoantibody, its high presence in a population of children with VKC may have an important role in clarifying etiopathogenesis and chronic inflammation

Anti IgE antibody as treatment of allergic bronchopulmonary aspergillosis in a patient with cystic fibrosis.

Allergic bronchopulmonary aspergillosis (ABPA) occurs in 7-9% of patients with cystic fibrosis (CF) and causes a worsening of lung function and respiratory symptoms. Standard treatment of ABPA consists of oral steroids; however, higher corticosteroid therapy associated to antifungal agent (itraconazole) long-term treatments are often required to reduce respiratory exacerbations and to prevent progressive lung damage. Here we describe the case of a girl with CF who experienced clinical and functional improvement over 12-months treatment with omalizumab. At birth, our patient was diagnosed with mild-to-moderate CF and from childhood she underwent annual cycles of antibiotic and corticosteroid therapies. At 12 years, she presented with a worsening respiratory condition, asthma symptoms and reduced lung function (FEV1 of 78%). Blood tests showed an increased concentration of plasma total IgE and positive specific IgE antibodies to Aspergillus fumigatus; allergic skin tests were also positive for A. fumigatus. The patient started steroid therapy but had impaired glucose tolerance due to long-term steroid use. Subcutaneous omalizumab 300 mg every two weeks was initiated and after 14 weeks she had improved respiratory symptoms (FEV1 99%) and a marked reduction in the use of systemic antibiotic and corticosteroid therapies. No side effects were reported. Our case shows that therapy with omalizumab for a prolonged period can resolve symptoms of asthma

Determination of marbofloxacin in plasma and synovial fluid by ultrafiltration followed by HPLC-MS/MS

A rapid LC-MS/MS method for the determination of marbofloxacin in plasma and synovial fluid is presented in this study. The method uses a rapid sample preparation which only requires an ultrafiltration step with centrifugal filter devices. The optimized procedure allows a minimal need of sample (175μL), particularly useful for synovial fluid samples which amount is rather limited; it is simple, rapid and easily applicable providing anyhow a satisfactory clean up, demonstrated by post-infusion experiments. On the other hand to maximize the speed of the analysis an ultrafast chromatographic separation has been obtained by selecting a column of 20mm; the reduced run-time is suitable for processing numerous samples on a daily basis. Linearity was assessed in the range 5-2500ngmL(-1); ofloxacin was used as internal standard. LOD and LOQ were respectively 1 and 5ng/mL. The method was successfully applied to a set of samples generated during an experimental veterinary study

AN INFANT WITH DIAPHRAGMATIC EVENTRATION AND RESPIRATORY DISTRESS

The authors report a rare case of partial diaphragmatic eventration in a 4-month-old infant with recurrent wheezing and low serum IgA values. Because of persistent respiratory symptoms after therapy with inhaled short-acting beta 2 agonists and inhaled nebulized corticosteroids, surgery was undertaken to correct the defect. Despite surgery, the clinical symptoms did not improve. Consequently, gatroesophagel reflux was considered and the diagnosis was confirmed with pH-metry, after which the infant was started on a protonic pump inhibitor therapy (PPI), achieving clinical improvement. Our experience suggests that in infants with congenital diaphragmatic eventration who present with respiratory distress gastro-oesophageal reflux should be suspected, and PPI therapy should be started before planning surgery

Serum levels of IL-17 in patients with vernal keratoconjunctivitis: a preliminary report

BACKGROUND AND AIM: Vernal Keratoconjunctivitis (VKC) is a chronic and often severe form of bilateral tarsal and/or bulbar conjunctivitis. The purpose of the present study is to measure the Interleukin-17 (IL-17) serum levels in children with VKC evaluating the role of the systemic inflammation in patients affected by VKC. PATIENTS AND METHODS: Fifteen patients were enrolled with VKC aged between 6 and 10 years of life. Serum were obtained from the peripheral blood samples collected from all the children included in the study to evaluate serum level of IL-17. RESULTS: Serum levels of IL-17 were significantly higher in patients with VKC than in healthy controls (10.3 +/- 9.36 pg/ml vs. 3.3 +/- 6.20 pg/ml respectively; p < 0.04). CONCLUSIONS: The presence of a significantly higher level of IL-17 in patients with VKC suggests a possible role of this cytokine in the pathogenesis of VKC. Further studies on larger samples of patients are warranted to confirm These findings in order to identify new possible therapeutic targets