Evaluation of continuous flash glucose monitoring in a pediatric ICU setting.

Glucose monitoring is of great importance among patients in intensive care units (ICU). The purpose of this study is to assess the performance of a new flash glucose monitoring (FGM) system in a pediatric ICU setting. Sixteen consecutive patients admitted in pediatric ICU aged > 4 years, expected length stay > 2 days and with no medication or existing diagnosis affecting glucose metabolism were enrolled. FreeStyle Libre sensor was applied to the upper arm of the patients (8 boys). FGM measurements were compared to 3 "references": arterial blood gas analysis, capillary blood analysis and biochemical serum analysis. Mean age of patients was 8.03 ± 2.91 years. Sensors remained in situ for a median of 9.71 ± 5.35 days. Removal of the sensor was mainly attributed to the completion of the predefine life-span of the sensor or discharge of the patient from the ICU. We compared 711 pairs of measurements between the sensor and other glucose measurement methods. Glucose values from the sensor were consistently lower with mean absolute relative difference (MARD) being 28.34%, 25.11% and 18.99% compared to the blood gas analyzer, capillary blood glucose meter, and biochemical serum analysis, respectively, but a wide interindividual variability. Significant linear correlations between age and MARD values were observed. Surveillance error grid (SEG) analysis showed 92.04%, 94.67% and 95.52% of the readings in the none or slight risk zone respectively. FreeStyle Libre is well tolerated although not adequately accurate with a tendency to underestimate glucose levels in critically ill pediatric patients.

miRNAs as predictive biomarkers of response to treatment in pediatric patients with acute lymphoblastic leukemia.

MicroRNAs (miRNAs/miRs) are promising prognostic biomarkers in pediatric acute lymphoblastic leukemia (ALL). The present study aimed to identify miRNAs that could serve as prognostic biomarkers or as novel therapeutic targets in ALL. The expression levels of 84 miRNAs were assessed in the bone marrow aspirates of 10 pediatric patients with newly diagnosed ALL at diagnosis and on day 33 of induction of the ALL Intercontinental Berlin-Frankfurt-Münster 2009 protocol, and associations with established prognostic factors were evaluated. The levels at diagnosis of 25 miRNAs were associated with ≥2 prognostic factors. Higher expression levels of let-7c-5p, miR-106b-5p, miR-26a-5p, miR-155-5p, miR-191-5p, miR-30b-5p and miR-31-5p were significantly associated with a good prednisone response. The expression levels of miR-125b-5p, miR-150-5p and miR-99a-5p were significantly higher in standard- or intermediate-risk patients compared with those in high-risk patients (P=0.017, P=0.033 and P=0.017, respectively), as well as in those with a complete response at the end of induction (P=0.044 for all three miRNAs). The change in expression levels between diagnosis and the end of induction differed significantly between risk groups for three miRNAs: miR-206, miR-210 and miR-99a (P=0.033, P=0.047 and P=0.008, respectively), with the post induction levels of miR-206 increased in high-risk patients, whilst miR-210 and miR-99a levels were increased in intermediate/standard risk patients. Therefore, miRNAs that could be integrated into the risk stratification of pediatric ALL after further evaluation in larger patient cohorts were identified.

Safety and Efficacy of Immune Checkpoint Inhibitors in Children and Young Adults with Haematological Malignancies: Review and Future Perspectives.

Despite the marked improvement in overall survival rates of paediatric patients with haematological malignancies that has been achieved during the last decades, there is still a pressing need for novel therapeutic approaches for the subset of patients with relapsed or refractory disease. Immune checkpoint inhibitors aim to induce potent anti-tumour immune responses by targeted blocking of inhibitory receptors and have shown promising results in preclinical models and studies on the adult population. However, paediatric malignancies present unique features, and so far, experience with these agents is limited. In the current review, we present an overview of efficacy and safety data from case reports, case series, and clinical trials employing the use of immune checkpoint inhibitors in children, adolescents, and young adults with haematological malignancies. We also discuss new possibilities involving novel targets and combination treatments and provide a summary of the currently registered clinical trials.

The Effect of Various, Everyday Practices on Glucose Levels in Critically Ill Children.

BACKGROUND: To evaluate the effect of various, everyday intensive care unit (ICU) practices on glucose levels in critically ill pediatric patients with the use of a continuous glucose monitoring system. METHODS: Seventeen sensors were placed in 16 pediatric patients (8 male). All therapeutic and diagnostic interventions were recorded and 15 minutes later, a flash glucose measurement was obtained by swiping the sensor with a reader. Glucose difference was calculated as the glucose value 15 minutes after the intervention minus the mean daily glucose value for each individual patient. Additionally, the consciousness status of the patient (awake or sedated) was recorded. RESULTS: Two hundred and five painful skin interventions were recorded. The mean difference of glucose values was higher by 1.84 ± 14.76 mg/dL (95% CI: -0.19 to 3.87 mg/dL, P = .076). However, when patients were categorized regarding their consciousness level, mean glucose difference was significantly higher in awake state than in sedated patients (4.76 ± 28.07 vs -2.21 ± 15.77 mg/dL, P < .001). Six hundred forty-nine interventions involving the respiratory system were recorded. Glucose difference during washings proved to be significantly higher than the ones during simple suctions (4.74 ± 14.18 mg/dL vs 0.32 ± 18.22 mg/dL, P = .016). Finally, glucose difference in awake patients was higher by 3.66 ± 13.91 mg/dL compared to glucose difference of -2.25 ± 21.07 mg/dL obtained during respiratory intervention in sedated patients. CONCLUSIONS: Diagnostic and therapeutic procedures in the ICU, especially when performed in an awake state, exacerbate the stress and lead to a significant rise in glucose levels.

Radiation treatment methods in uveal melanoma.

Background: The most frequent primary ocular malignancy in the western world is the uveal melanoma. While it mainly affects Caucasians, it is extremely uncommon among non-Caucasians. Continuous improvement in therapies for local treatment has allowed sparing of the eye, although this approach apparently does not improve survival. The present review aimed to explain different radiotherapy (RT) methods and compare the pros and cons of each method, along with the main complications that may be encountered in the treatment of uveal melanoma. Methods: Relevant papers published between September 2009 and January 2021 were retrieved, reviewed, and screened. Four databases, including PubMed, MEDLINE, Google Scholar, and GeneCards, were searched for this purpose. Results: Forty-one relevant articles were identified. Based on the selected papers, we highlighted the advantages and disadvantages of the different RT methods that have allowed sparing of the eye, even though they have not, as yet, improved survival. We listed a detailed comparison between therapies that allow an educated choice among the different available RT methods. Conclusions: The choice of uveal melanoma management is determined by the location of the tumor and volume of the extraocular extent. At present, there is no gold standard for the management of all ocular melanomas, and each case should be approached individually. Therefore, classification is a valuable prognostic tool. Many cases in cT3-4 classification categories are treated by primary enucleation and conservative treatment follow-up, while in cT2 and most cT1 classifications (i.e., 3.1-6.0-mm tumor thickness), several forms of RT are used.

Level of knowledge and evaluation of perceptions regarding pediatric diabetes among Greek teachers.

AIM: To assess the knowledge and attitudes of nursery school, preschool and primary school Greek teachers regarding pediatric diabetes. METHODS: Our anonymous questionnaire was comprised of three parts: the first part was regarding sociodemographic characteristics; the second part was assessing basic knowledge about diabetes and the third part was about personal perceptions regarding diabetes management in the school setting. A total of 375 fully completed questionnaires were collected (22.67% from males). RESULTS: Males had a higher percentage of correct answers than females (80.71 ± 10.58% versus 80.17 ± 11.77%), but without reaching statistical significance (p = 0.763). Teachers aged over 45 years, tertiary education graduates and teachers in the public sector proved to be more knowledgeable about the disease. Question scoring the lowest percentage of correct answers were those dealing with the management of diabetic emergencies, such as the course of action in case a diabetic pupil is found unconscious. One out of four participants incorrectly declared that a delay in the diagnosis of diabetes mellitus cannot possibly be life-threatening whereas, an embarrassing 7.47% of the participants stated that diabetes is a contagious disease and another 6.67% declared that diabetic children should stop school. CONCLUSIONS: It is evident that there is an urgent need for providing further information, as well as practical training to schoolteachers with emphasis being placed on the initial symptoms of diabetes and also in the detection and management of diabetic emergencies.

A Review of Last Decade Developments on Epiretinal Membrane Pathogenesis.

Epiretinal membrane (ERM) is a pathologic tissue that develops at the vitreoretinal interface. ERM is responsible for pathological changes of vision with varying degrees of clinical significance. It is either idiopathic or secondary to a wide variety of diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). A great variation in the prevalence of idiopathic ERM among different ethnic groups proposed that genetic and lifestyle factors may play a role in ERM occurrence. Histopathological studies demonstrate that various cell types including retinal pigment epithelium (RPE) cells, fibrocytes, fibrous astrocytes, myofibroblast-like cells, glial cells, endothelial cells (ECs) and macrophages, as well as trophic and transcription factors, including transforming growth factor (TGF), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) etc., are directly or indirectly involved in the pathogenesis of idiopathic or secondary ERMs. These processes are driven (on the last count) by more than 50 genes, such as Tumor Necrosis Factor (TNF), CCL2 (chemokine (C-C motif) ligand )), Metastasis Associated Lung Adenocarcinoma Transcript 1 )MALAT1(, transforming growth factor (TGF)-ß1, TGF-ß2, Interleukin-6 (IL-6), IL-10, VEGF and glial fibrillary acidic protein (GFAP), some of which have been studied more intensely than others. The present paper tried to summarize, highlight and cross-correlate the major findings made in the last decade on the function of these genes and their association with different types of cells, genes and gene expression products in the ERM formation.

Invasive fungal infections in a pediatric hematology-oncology department: A 16-year retrospective study.

Background and Purpose: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in immunocompromised children. The purpose of our study was to evaluate the incidence of IFIs in pediatric patients with underlying hematologic malignancies and determine the patient characteristics, predisposing factors, diagnosis, treatment efficacy, and outcome of IFIs. Materials and Methods: For the purpose of the study, a retrospective analysis was performed on cases with proven and probable fungal infections from January 2001 to December 2016 (16 years). Results: During this period, 297 children with hematologic malignancies were admitted to the 2nd Pediatric Department of Aristotle University of Thessaloniki, Greece, and 24 cases of IFIs were registered. The most common underlying diseases were acute lymphoblastic leukemia (ALL; n=19,79%), followed by acute myeloid leukemia (AML; n=4, 17%) and non-Hodgkin lymphoma (NHL; n=1,4%). The crude incidence rates of IFIs in ALL, AML, and NHL were 10.5%, 18.2%, and 2.8% respectively. Based on the results, 25% (n=6) and 75% (n=18) of the patients were diagnosed as proven and probable IFI cases, respectively. The lung was the most common site of involvement in 16 (66.7%) cases. Furthermore, Aspergillus and Candida species represented 58.3% and 29.1% of the identified species, respectively. Regarding antifungal treatment, liposomal amphotericin B was the most commonly prescribed therapeutic agent (n=21), followed by voriconazole (n=9), caspofungin (n=3), posaconazole (n=3), micafungin (n=1), and fluconazole (n=1). In addition, 12 children received combined antifungal treatment. The crude mortality rate was obtained as 33.3%. Conclusion: As the findings of the present study indicated, despite the progress in the diagnosis and treatment of IFIs with the use of new antifungal agents, the mortality rate of these infections still remains high.

The Proteins of Keratoconus: a Literature Review Exploring Their Contribution to the Pathophysiology of the Disease.

INTRODUCTION: Keratoconus (KC) is a complex, genetically heterogeneous multifactorial degenerative disorder characterized by corneal ectasia and thinning. Its incidence is approximately 1/2000-1/50,000 in the general population. KC is associated with moderate to high myopia and irregular astigmatism, resulting in severe visual impairment. KC structural abnormalities primarily relate to the weakening of the corneal collagen. Their understanding is crucial and could contribute to effective management of the disease, such as with the aid of corneal cross-linking (CXL). The present article critically reviews the proteins involved in the pathophysiology of KC, with particular emphasis on the characteristics of collagen that pertain to CXL. METHODS: PubMed, MEDLINE, Google Scholar and GeneCards databases were screened for relevant articles published in English between January 2006 and June 2018. Keyword combinations of the words "keratoconus," "risk factor(s)," "genetics," "genes," "genetic association(s)," "proteins", "collagen" and "cornea'' were used. In total, 272 articles were retrieved, reviewed and selected, with greater weight placed on more recently published evidence. Based on the reviewed literature, an attempt was made to tabulate the up- and down-regulation of genes involved in KC and their protein products and to delineate the mechanisms involved in CXL. RESULTS: A total of 117 proteins and protein classes have been implicated in the pathogenesis and pathophysiology of KC. These have been tabulated in seven distinct tables according to their gene coding, their biochemistry and their metabolic control. CONCLUSION: The pathogenesis and pathophysiology of KC remain enigmatic. Emerging evidence has improved our understanding of the molecular characteristics of KC and could further improve the success rate of CXL therapies.

Genetic Aspects of Keratoconus: A Literature Review Exploring Potential Genetic Contributions and Possible Genetic Relationships with Comorbidities.

INTRODUCTION: Keratoconus (KC) is a complex, genetically heterogeneous, multifactorial degenerative disorder that is accompanied by corneal ectasia which usually progresses asymmetrically. With an incidence of approximately 1 per 2000 and 2 cases per 100,000 population presenting annually, KC follows an autosomal recessive or dominant pattern of inheritance and is, apparently, associated with genes that interact with environmental, genetic, and/or other factors. This is an important consideration in refractive surgery in the case of familial KC, given the association of KC with other genetic disorders and the imbalance between dizygotic twins. The present review attempts to identify the genetic loci contributing to the different KC clinical presentations and relate them to the common genetically determined comorbidities associated with KC. METHODS: The PubMed, MEDLINE, Google Scholar, and GeneCards databases were screened for KC-related articles published in English between January 2006 and November 2017. Keyword combinations of "keratoconus," "risk factor(s)," "genetics," "genes," "genetic association(s)," and "cornea" were used. In total, 217 articles were retrieved and analyzed, with greater weight placed on the more recent literature. Further bibliographic research based on the 217 articles revealed another 124 relevant articles that were included in this review. Using the reviewed literature, an attempt was made to correlate genes and genetic risk factors with KC characteristics and genetically related comorbidities associated with KC based on genome-wide association studies, family-based linkage analysis, and candidate-gene approaches. RESULTS: An association matrix between known KC-related genes and KC symptoms and/or clinical signs together with an association matrix between identified KC genes and genetically related KC comorbidities/syndromes were constructed. CONCLUSION: Twenty-four genes were identified as potential contributors to KC and 49 KC-related comorbidities/syndromes were found. More than 85% of the known KC-related genes are involved in glaucoma, Down syndrome, connective tissue disorders, endothelial dystrophy, posterior polymorphous corneal dystrophy, and cataract.