Risk for cancer development in familial Mediterranean fever and associated predisposing factors: an ambidirectional cohort study from the international AIDA Network registries.

Objective: Inflammation has been associated with an increased risk for cancer development, while innate immune system activation could counteract the risk for malignancies. Familial Mediterranean fever (FMF) is a severe systemic inflammatory condition and also represents the archetype of innate immunity deregulation. Therefore, the aim of this study is to investigate the risk for cancer development in FMF. Methods: The risk ratio (RR) for malignancies was separately compared between FMF patients and fibromyalgia subjects, Still's disease patients and Behçet's disease patients. Clinical variables associated with cancer development in FMF patients were searched through binary logistic regression. Results: 580 FMF patients and 102 fibromyalgia subjects, 1012 Behçet's disease patients and 497 Still's disease patients were enrolled. The RR for the occurrence of malignant neoplasms was 0.26 (95% Confidence Interval [CI.] 0.10-0.73, p=0.006) in patients with FMF compared to fibromyalgia subjects; the RR for the occurrence of malignant cancer was 0.51 (95% CI. 0.23-1.16, p=0.10) in FMF compared to Still's disease and 0.60 (95% CI. 0.29-1.28, p=0.18) in FMF compared to Behçet's disease. At logistic regression, the risk of occurrence of malignant neoplasms in FMF patients was associated with the age at disease onset (ß1 = 0.039, 95% CI. 0.001-0.071, p=0.02), the age at the diagnosis (ß1 = 0.048, 95% CI. 0.039-0.085, p=0.006), the age at the enrolment (ß1 = 0.05, 95% CI. 0.007-0.068, p=0.01), the number of attacks per year (ß1 = 0.011, 95% CI. 0.001- 0.019, p=0.008), the use of biotechnological agents (ß1 = 1.77, 95% CI. 0.43-3.19, p=0.009), the use of anti-IL-1 agents (ß1 = 2.089, 95% CI. 0.7-3.5, p=0.002). Conclusions: The risk for cancer is reduced in Caucasic FMF patients; however, when malignant neoplasms occur, this is more frequent in FMF cases suffering from a severe disease phenotype and presenting a colchicine-resistant disease.

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 < 0.001]. The duration of fever was significantly reduced from 4.00 (2.00) days to 2.00 (2.00) days [p < 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 < 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 < 0.001]. The number of patients experiencing symptoms including pharyngitis/tonsillitis (p < 0.001), oral aphthae (p < 0.001) and cervical lymphadenopathy (p < 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.

Development and implementation of the AIDA International Registry for patients with Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis syndrome.

Objective: Aim of this paper is to illustrate the methodology, design, and development of the AutoInflammatory Disease Alliance (AIDA) International Registry dedicated to patients with the Periodic Fever, Aphthous stomatitis, Pharyngitis, and cervical Adenitis (PFAPA) syndrome. Methods: This is a physician-driven, non-population- and electronic-based registry proposed to gather real-world demographics, clinical, laboratory, instrumental and socioeconomic data from PFAPA patients. Data recruitment is realized through the on-line Research Electronic Data Capture (REDCap) tool. This registry is thought to collect standardized information for clinical research leading to solid real-life evidence. The international scope and the flexibility of the registry will facilitate the realization of cutting-edge study projects through the constant updating of variables and the possible merging and transfer of data between current and future PFAPA registries. Results: A total of 112 centers have already been involved from 23 countries and 4 continents starting from August 24th, 2021, to April 6th, 2022. In total 56/112 have already obtained the formal approval from their local Ethics Committees. The platform counts 321 users (113 principal investigators, 203 site investigators, two lead investigators, and three data managers). The registry collects retrospective and prospective data using 3,856 fields organized into 25 instruments, including PFAPA patient's demographics, medical histories, symptoms, triggers/risk factors, therapies, and impact on the healthcare systems. Conclusions: The development of the AIDA International Registry for PFAPA patients will enable the on-line collection of standardized data prompting real-life studies through the connection of worldwide groups of physicians and researchers. This project can be found on https://clinicaltrials.gov NCT05200715.

One-Year Real-World Study on Comparison among Different Continuous Subcutaneous Insulin Infusion Devices for the Management of Pediatric Patients with Type 1 Diabetes: The Supremacy of Hybrid Closed-Loop Systems.

Since their advent in daily clinical practice, continuous subcutaneous insulin infusion (CSII) systems have been increasingly improved, leading to a high percentage of both adult and pediatric patients with diabetes now using insulin pumps. Different types of CSII systems are currently available, which are characterized by different settings and technical features. This longitudinal observational study aims to evaluate real-word glycemic outcomes in children and adolescents with type 1 diabetes using three different CSII devices: hybrid closed-loop (HCL) systems, predictive low glucose (PLGS) systems, and non-automated insulin pumps. The secondary objective was to identify clinical variables that may significantly influence the achievement of therapeutic goals in our study cohort. One-hundred-and-one patients on CSII therapy attending our pediatric diabetes center were enrolled. When compared with the non-automated group, patients using HCL systems showed higher levels of time in target glucose range (p = 0.003) and lower glucose variability (p = 0.008). Similarly, we found significantly better glucose metrics in HCL users in comparison to PLGS patients (time in range p = 0.008; coefficient of variation p = 0.009; time above 250 mg/dL p = 0.007). Multiple linear regression models showed that HCL systems (time in range p < 0.001) and high daily percentage of glycemic sensor use (time in range p = 0.031) are predictors for good glycemic control. The introduction and increasing availability of novel technologies for diabetes represent a promising strategy to improve glycemic control and quality of life in pediatric patients with type 1 diabetes. Our real-world data confirm the superiority of HCL systems in terms of improvement of time spent in the target glucose range, prevention of hypoglycemia, and reduction of glycemic variability.

Optimal Monitoring Technology for Pediatric Thyroidectomy.

This retrospective study aimed to describe, firstly, characteristics and outcomes of the intraoperative neural monitoring technology in the pediatric population, and secondarily the recurrent laryngeal nerve complication rate. Thirty-seven patients (age <18 years) operated on from 2015 to 2021 by conventional open thyroid surgery were included. Twenty-four (64.9%) total thyroidectomies and 13 (35.1%) lobectomies were performed. Seven central and six lateral lymph node dissections completed 13 bilateral procedures. Histology showed malignancy in 45.9% of the cases. The differences between the electromyographic profiles of endotracheal tubes or electrodes for continuous monitoring were not statistically significant. In our series of young patients, both adhesive (even in 4- or 5-year-olds) and embedded endotracheal tubes were used, while in patients 3 years old or younger, the use of a more invasive detection method with transcartilage placement recording electrodes was required. Overall, out of 61 total at-risk nerves, 5 (8.2%) recurrent laryngeal nerves were injured with consequent intraoperative loss of the signal; however, all these lesions were transient, restoring their normal functionality within 4 months from surgical procedure. To our knowledge, this is the first study of intraoperative neural monitoring management in a cohort of Italian pediatric patients.

Considerations for Balance Between Fundamental Treatment and Improvement of Quality of Life of Pediatric Thyroid Cancer Patient: Comparative Analysis With Adult Using Propensity Score Matching.

Background: Thyroid cancer is very rarely observed in children and adolescents, some reports have shown that the long-term outcome of treatment is better than that of adult patients, despite many treatment failures or a high risk of recurrence. This study considers whether it is appropriate to treat pediatric thyroid cancer patients aggressively, as per the ATA guidelines, based on the balance between the fundamental treatment of thyroid cancer and the improvement of the long-term quality of life of pediatric patients. Methods: A total of 1,950 patients were recruited, including 83 pediatric and 1,867 adult patients, who were diagnosed with thyroid cancer and underwent surgical treatment at one of our medical center hospitals from March 2000 to January 2020. Results: Sixty-nine pairs of pediatric and adult patients were matched in a ratio of 1:2 through propensity score matching. When compared through propensity score matching, there was no significant difference in prognosis such as recurrence rate in children and adults at the same stage. Conclusion: This study showed that the prognosis of both pediatric and adult patients who underwent a total thyroidectomy and lobectomy was not significantly different. If more pediatric patients can be considered for the less-aggressive lobectomy than a total thyroidectomy through various preoperative examinations and meticulous pre-diagnosis, it may be possible to properly determine the balance between improving long-term quality of life while providing fundamental cancer treatment.