A toddler with an unusually severe polyarticular arthritis and a lung involvement: a case report.

BACKGROUND: COPA syndrome is a rare hereditary inflammatory disease caused by mutations in the gene encoding the coatomer protein subunit alpha, causing excessive production of type I interferon. This case is a reminder for the general paediatrician, highlighting the relevance of the association between arthritis and lung involvement in toddlers. CASE PRESENTATION: We report the case of a 2-year-old girl with intermittent limping and joint pain. Her family history was relevant for a Still disease with lung involvement in the mother. Physical examination showed moderate wrist swelling. Laboratory findings on admission showed an increase in inflammatory markers, positive rheumatoid factor, antibodies antinuclear antibody (ANA) and cyclic citrullinated peptide (anti-CCP). Wrists' ultrasound documented synovial thickening, and chest X-rays showed an unexpected severe interstitial pneumopathy. Genetic testing confirmed the diagnosis of a heterozygous mutation of the COPA gene in c.841C > T (p.R281W). Janus kinase treatment was started (baricitinib, 4 mg daily per os) with a remarkable improvement in limping and joint pain after two weeks. CONCLUSIONS: In cases of recurrent arthritis with family history and multiple involvement organs, a genetic disorder should be suspected and genetic testing should be performed. Furthermore, this case suggests that therapy with jak inhibitors may be effective and safe in interferonopathies.

Prevalence and clinical features of severe diabetic ketoacidosis treated in pediatric intensive care unit: a 5-year monocentric experience.

BACKGROUND: Diabetic ketoacidosis (DKA) is one of the most alarming concerns in the management of type 1 diabetes (T1D) in pediatric age. Prevalence of DKA at the onset of diabetes ranges from 30 to 40%. In selected cases of severe DKA, admission to pediatric intensive care unit (PICU) should be considered. METHODS: This study aims to assess the prevalence of severe DKA treated in PICU in our 5-year monocentric experience. Secondary outcome of the study was to describe the main demographical and clinical features of individuals who required admission to PICU. All clinical data were collected by retrospectively reviewing the electronic medical records of children and adolescents with diabetes hospitalized in our University Hospital from January 2017 to December 2022. RESULTS: During the study period, 103 children and adolescents were newly diagnosed with T1D. Among these, 51.5% presented clinical criteria for DKA and almost 10% needed to be treated in PICU. A higher rate of new T1D diagnoses was observed in 2021, as well as episodes of severe DKA being more frequent than in previous years. Due to severe clinical manifestations of DKA, 10 subjects (9.7%) with T1D onset needed to be treated in PICU. Of these, four children were younger than 5. The great majority came from a low household income and some of them had also immigrant background. The most common complication of DKA was acute kidney injury presented by four children. Other complications were cerebral edema, papilledema and acute esophageal necrosis. A 15-year-old girl had deep vein thrombosis (DVT) that evolved into multiple organ failure leading to death. CONCLUSIONS: Our findings demonstrated that severe DKA is still quite common in children and adolescents at T1D onset, especially in some areas such as Southern Italy. Public awareness campaigns should be increasingly promoted to facilitate the recognition of early symptoms of diabetes and to reduce morbidity and mortality related to DKA.

Molecular and Metabolic Imaging of Castration-Resistant Prostate Cancer: State of Art and Future Prospects.

Prostate cancer (PCa) represents to be the most common tumor in male and one of the most relevant causes of death in the Western countries. Androgen deprivation therapy (ADT) constitutes a widely used approach in advanced PCa. When PCa progresses in spite of ADT and castrate levels of testosterone, the severe clinical condition termed as metastatic castration-resistant prostate cancer (mCRPC) takes place. The only approach to mCRPC has been represented by chemotherapy with taxanes for many years. Nevertheless, recently introduced treatments such as 2nd generation antiandrogens (i.e., enzalutamide and abiraterone), cell immunotherapy with sipuleucel-T or targeted alpha therapy with 223Ra-dichloride, have dramatically changed mCRPC prognosis. These novel therapies call for an unmet need for imaging biomarkers suitable for patients' pre-treatment stratification and response assessment. In this scenario, nuclear medicine can provide several metabolic and molecular probes for investigating pathological processes at a cellular and sub-cellular level. The aim of this paper is to review the most relevant findings of the literature published to date on this topic, giving particular emphasis on the pros and cons of each tracer and also covering future prospects for defining personalized therapeutic approaches.

Has COVID-19 lockdown improved glycaemic control in pediatric patients with type 1 diabetes? An analysis of continuous glucose monitoring metrics.

AIMS: Our observational study aimed to evaluate the impact of the lockdown period due to 2019 Coronavirus disease pandemic on glycaemic control in a cohort of paediatric patients with type 1 diabetes (T1D). METHODS: Eighty-five patients with T1D aged 5-18 years using continuous glucose monitoring (CGM) systems were enrolled. Demographic and clinical data, including glucose metrics generated by CGM-specific web-based cloud platforms, were collected in three different periods (pre-lockdown phase, lockdown phase, and post-lockdown phase) of 90 days each and were statistically analysed. RESULTS: During the lockdown period, a clear improvement in almost all CGM metrics (time in range, time above range, coefficient of variation, and glucose management indicator) was observed in our study population, regardless of age and insulin type treatment. In the months following lockdown, maintaining satisfactory diabetes outcomes was confirmed only in younger patients (aged 5-9 years) and in those individuals on hybrid closed loop therapy. CONCLUSIONS: The increasing use of innovative technological devices together with data sharing systems and interaction with multidisciplinary diabetes team through telemedicine allowed paediatric patients with T1D to improve glucose metrics during the lockdown period. However, our findings showed that the achievement of better glycaemic control was transient for most patients.

The Relationship Between Total Lesion Activity on 18F Choline Positron Emission Tomography-Computed Tomography and Clinical Outcome in Patients with Castration-Resistant Prostate Cancer Bone Metastases Treated with 223Radium.

The aim of the study was to assess the correlation between metabolic response measured through positron emission tomography-computed tomography (PET-CT) with 18F choline (18F FCH) and overall survival (OS) in patients affected by bone lesions from metastatic castration-resistant prostate cancer treated with 223Ra dichloride. Eleven subjects were subjected to PET-CT with 18F FCH before and 1 month after 223Ra treatment. Reduction in total lesion activity (ΔTLA) between pretreatment and post-treatment scan was determined and patients were divided into responders (ΔTLA >50%) and nonresponders (ΔTLA <50%). The OS of the entire cohort was 12.7 ± 3.8 months. Kaplan-Meier analysis showed that responders presented a significantly longer survival than nonresponders (16.5 ± 1.9 months vs. 10.5 ± 0.9 months, p < 0.05). Reduction in TLA after 223Ra treatment seems to be correlated with a trend toward a longer survival.

Positron Emission Tomography for the Response Evaluation following Treatment with Chemotherapy in Patients Affected by Colorectal Liver Metastases: A Selected Review.

The aim of the present paper is to review the scientific literature concerning the usefulness of (18)F-FDG PET/CT in the evaluation of response to chemotherapy in patients affected by liver metastases from colorectal cancer. Material and Methods. Studies were identified by searching PubMed electronic databases. Both prospective and retrospective studies were included. Information regarding the figure of merit of PET for the evaluation of therapy response was extracted and analyzed. Results. Existing data suggests that (18)F-FDG PET/CT may have an outstanding role in evaluating the response. The sensitivity of PET in detecting therapy response seems to be greater than conventional imaging (CT and MRI). PET/CT response is strictly related to better overall survival and progression-free survival. Conclusions. PET/CT is more than a promising technique to assess the response to chemotherapy in colorectal and liver metastases. However, to be fully validated, this examination needs further studies by recruiting more patients.

ImmunoPET in Neoplasms of Gastrointestinal Tract, Liver and Pancreas in the XXIst Century: Bridging the Gap Between Diagnosis and Therapy.

Monoclonal antibodies (mAbs) are produced by clones of a unique parent cell which has monovalent affinity and can bind to the same epitope. The chronological breakthrough in mAbs clinical utilization was in 1975, when it becomes possible to produce mAbs to known antigens and immortalize the cell lines. However, the clinical usefulness of mAbs was hampered for many years, basically because of their immunogenicity due to the murine origin. This situation lasted until 1988 when a technique to humanize mAbs was defined. Nuclear Medicine researchers were very quick to gathered the opportunity provided by the development of mAbs. The first papers reporting the preclinical use of radiolabelled mAbs date the early 80's soon followed by the first pivotal use in humans. However, mAbs did not gain a wide clinical use for several reasons connected to the chemistry and biochemistry of radiolabelled mAbs the emergence of clinical 18F-FDG PET. However, the "magic bullet" concept has resisted in the cultural background of Nuclear Medicine physicians for almost twenty years, and has regained importance with the development of engineered mAbs. Herein we present a selected review of preclinical and clinical studies of PET/CT with mAbs in gastrointestinal malignancies.

Comparison between F-Fluorodeoxyglucose Positron Emission Tomography and Sentinel Lymph Node Biopsy for Regional Lymph Nodal Staging in Patients with Melanoma: A Review of the Literature.

Aim. to compare (18)F-Fluorodeoxyglucose positron emission tomography (FDG-PET) to sentinel lymph node biopsy (SLNB) for regional lymph nodal staging in patients with melanoma. Methods. We performed a literature review discussing original articles which compared FDG-PET to SLNB for regional lymph nodal staging in patients with melanoma. Results and Conclusions. There is consensus in the literature that FDG-PET cannot replace SLNB for regional lymph nodal staging in patients with melanoma.