Sex- and gender-based medicine in pediatric nutrition.

Consistent evidence increasingly highlights the significance of integrating sex and gender medicine to ensure a precision approach according to individual patient needs. Gender discrepancies emerge across various areas, even from pediatric age. The importance of recognizing these differences in pediatric nutrition is critical for the development of targeted nutritional strategies and interventions, particularly in cases of associated pathologies, including obesity, metabolic-associated fatty liver disease, eating disorders, and inflammatory bowel disease. The review highlights the biological and sociocultural factors that contribute to different nutritional needs and health outcomes in male and female children. By examining current evidence, we underscore the necessity for precision medicine approaches in pediatric care that consider these sex- and gender-based differences. Moreover, differences in dietary requirements and dietary patterns between males and females are evident, underscoring the need for precise nutrition strategies for a more accurate management of children and adolescents. This approach is essential for improving clinical outcomes and promoting equitable healthcare practices. This review aims to provide an overview of nutrition-related medical conditions exhibiting sex- and gender-specific discrepancies, which might lead to distinct outcomes requiring unique management and prevention strategies. Future research and public health initiatives should address these differences in designing effective lifestyle education programs and nutrition interventions targeting both children and adolescents.

Telemedicine in nutritional management of children with severe neurological impairment: implication for quality of life.

Children with severe neurological impairment (SNI) frequently present feeding problems requiring a close monitoring of their nutritional status. In addition to constant clinical monitoring of body composition and nutritional indexes in these patients, frequent reports of dietary intake and weight gain variations are useful to ensure proper nutritional management. Furthermore, non-oral feeding is often needed to avoid malnutrition or aspiration pneumonia, constantly necessitating medical assistance. Despite their necessity for frequent hospital accesses, these patients' disabilities represent an important obstacle to accessing care, generating anxiety and concern in children and their families. Telemedicine has proven to be a promising instrument for improving pediatric patients' healthcare in several fields. By breaking down geographical and temporal barriers, telehealth may represent a valuable tool to implement in clinical practice, in order to improve patients' outcomes and quality of life. The aim of this narrative review is to provide an overview of the main nutritional issues in children with SNI, the potential implications of telemedicine in their management and the available evidence regarding the effects and benefits of telehealth.

Long-term health outcome and quality of life in children with multisystem inflammatory syndrome: findings from multidisciplinary follow-up at an Italian tertiary-care paediatric hospital.

Multisystem inflammatory syndrome is a severe complication of SARS-CoV-2 infection in children (MIS-C). To date, data on long-term sequelae mainly concern cardiac outcomes. All ≤ 18 year olds consecutively admitted to the Buzzi Children's Hospital with a diagnosis of MIS-C between October 1, 2020, and May 31, 2022, were followed up for up to 12 months by a dedicated multidisciplinary team. They underwent laboratory tests, multi-organ clinical and instrumental assessments, and psychosocial evaluation. 56/62 patients, 40 M, mean age 8.7 years (95% CI 7.7, 9.7), completed the follow-up. Cardiological, gastroenterological, pneumological, and neurological evaluations, including IQ and EEG, were normal. Alterations of HOMA-IR index and/or TyG index, observed in almost all patients during hospitalisation, persisted in about a third of the population at 12 months. At 6 and 12 months respectively, impairment of adaptive functions was observed in 38/56 patients (67.9%) and 25/56 (44.6%), emotional and behavioural problems in 10/56 (17.9%) and 9/56 (16.1%), and decline in QoL in 14/56 (25.0%) and 9/56 (16.1%). Psychosocial well-being impairment was significantly more frequent in the subgroup with persistent glycometabolic dysfunction at 12 months (75% vs. 40.9% p < 0.001). CONLUSION: The mechanisms that might explain the long-term persistence of both metabolic alterations and neuro-behavioural outcomes and their possible relationship are far from being clarified. Our study points out to the potential long-term effects of pandemics and to the importance of a multidisciplinary follow-up to detect potential negative sequelae in different areas of health, both physical and psychosocial. WHAT IS KNOWN: • Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. • Few data exist on the medium- and long-term outcomes of MIS-C, mostly focused on cardiac involvement. Emerging evidence shows neurological and psychological sequelae at mid- and long-term follow-up. WHAT IS NEW: • This study reveals that MIS-C may lead to long-term glycometabolic dysfunctions joined to impairment in the realm of general well-being and decline in quality of life, in a subgroup of children. • This study highlights the importance of a long-term multidisciplinary follow-up of children hospitalised with MIS-C, in order to detect the potential long-term sequelae in different areas of health, both physical and psychosocial well-being.

How Can Promoting Skeletal Muscle Health and Exercise in Children and Adolescents Prevent Insulin Resistance and Type 2 Diabetes?

Skeletal muscle secretome, through its paracrine and endocrine functions, contributes to the maintenance and regulation of overall physiological health. We conducted a narrative review on the role of skeletal muscle and exercise in maintaining glucose homeostasis, driving insulin resistance (IR), and preventing type 2 diabetes in pediatric populations, especially in the context of overweight and obesity. Myokines such as interleukin (IL)-6, IL-8, and IL-15, as well as irisin, myonectin, and myostatin, appear to play a crucial role in IR. Skeletal muscle can also become a target of obesity-induced and IR-induced inflammation. In the correlation between muscle, IR, and inflammation, the role of infiltration of the immune cells and the microvasculature may also be considered. It remains unclear which exercise approach is the best; however, combining aerobic exercise with resistance training seems to be the most effective strategy for managing IR, with high-intensity activities offering superior metabolic benefits and long-term adherence. Encouraging daily participation in enjoyable and engaging exercise is key for long-term commitment and effective glucose metabolism management. Promoting physical activity in children and adolescents must be a top priority for public health, not only in terms of individual quality of life and well-being but also for community health.

Menstrual Dysfunction in Adolescent Female Athletes.

Despite the benefits of exercise on mental and physical health, excessive training loads can lead to health problems in the long term, including a wide spectrum of menstrual dysfunction (MD). This narrative review aims to analyze the relationship between physical exercise and MD in adolescent female athletes to support regular menstrual health monitoring and promote educational programs on reproductive risks. When dealing with MD in young athletes, several factors entangled with maturation of the hypothalamus-pituitary-ovarian axis should be considered. Firstly, some disciplines seem to have a higher prevalence of MD due to the high loads of training regimes and the early introduction of athletes to a competitive career. Moreover, low energy intake and a low body mass index appear to exacerbate existing MD. Lastly, disordered eating behaviors and psychological stress can contribute to MD in female athletes. The type of sport, influencing the intensity and duration of exercise, as well as individual psycho-physiological and environmental factors, may influence the role of physical activity in the manifestation of MD. Early recognition and management of MD, along with collaboration between sports organizations and health professionals, are crucial to minimize risks, ensure proper nutrition, and balance training with recovery. Keeping an open discussion on the topic may prospectively improve awareness, early diagnosis, and treatment strategies, as well as reduce injury risk and enhance sports performance.

Evaluating Phthalates and Bisphenol in Foods: Risks for Precocious Puberty and Early-Onset Obesity.

Recent scientific results indicate that diet is the primary source of exposure to endocrine-disrupting chemicals (EDCs) due to their use in food processing, pesticides, fertilizers, and migration from packaging to food, particularly in plastic or canned foods. Although EDCs are not listed on nutrition labels, their migration from packaging to food could inadvertently lead to food contamination, affecting individuals by inhalation, ingestion, and direct contact. The aim of our narrative review is to investigate the role of phthalates and bisphenol A (BPA) in foods, assessing their risks for precocious puberty (PP) and early-onset obesity, which are two clinical entities that are often associated and that share common pathogenetic mechanisms. The diverse outcomes observed across different studies highlight the complexity of phthalates and BPA effects on the human body, both in terms of early puberty, particularly in girls, and obesity with its metabolic disruptions. Moreover, obesity, which is independently linked to early puberty, might confound the relationship between exposure to these EDCs and pubertal timing. Given the potential public health implications, it is crucial to adopt a precautionary approach, minimizing exposure to these EDCs, especially in vulnerable populations such as children.

Eating disorder risks and psychopathological distress in Italian high school adolescents.

BACKGROUND: Psychopathological disorders are often comorbid diagnosis in eating disorders (EDs). We aimed to assess the presence of psychopathological traits and symptoms associated with EDs in an Italian high school adolescent population. METHODS: A sample of high school adolescents was enrolled, and demographic and clinical data were collected. Two self-report questionnaires, the Eating Disorder Inventory-3 (EDI-3) and the Questionnaire for the Assessment of Psychopathology in Adolescence (Q-PAD), were administered. RESULTS: 548 adolescents (333 F/215 M; 16.89 ± 0.85 years) were included. Symptoms associated with EDs of clinical or high clinical concern were prevalent in a range of individuals, with percentages varying from 26.82% for body dissatisfaction to 51.83% for Interoceptive Deficits. The findings from the Q-PAD assessment indicated the presence of psychological distress, leading to discomfort or challenging situations requiring potential intervention in a percentage of adolescents ranging from 2.93% for psychosocial risks to 23.77% for anxiety. These percentages showed differences between genders (F > M, p < 0.001). Our study also highlighted an association between symptoms of EDs and lifestyle factors within families. We observed correlations between Q-PAD measures and EDI-3 scores, including a positive correlation between Q-PAD and EDI-3 body dissatisfaction (r = 0.7), Q-PAD interpersonal conflicts and EDI-3 interpersonal problems (r = 0.6) and a negative correlation between Q-PAD self-esteem and well-being and EDI-3 ineffectiveness Composite (r=-0.7). CONCLUSIONS: a substantial prevalence of ED symptoms and psychological distress among high school adolescents were recorded. These conditions are interrelated, suggesting the importance of addressing them comprehensively. Early detection is essential to improve treatment outcomes and to implement preventive strategies.

The impact of vitamin D status on lipid profiles and atherogenic dyslipidemia markers in children and adolescents with obesity.

BACKGROUND AND AIM: Adequate serum vitamin D levels correlate with a more favorable lipid profile compared to deficient levels. Despite the well-established prevalence of vitamin D deficiency in children with obesity, studies investigating its influence on lipid profiles in this population are scarce. We explored the impact of vitamin D status on lipid profiles and markers of atherogenic dyslipidemia in a cohort of children and adolescents with obesity. METHODS AND RESULTS: A total of 271 Caucasian children and adolescents with overweight/obesity and a control group of 54 pediatric patients with normal weight. All participants underwent outpatient visits for the assessment of clinical parameters and venous blood collection for biochemical analysis such as triglycerides (TG)/HDL-C ratio, LDL-C/HDL-C ratio, atherogenic index of plasma AIP), vitamin D level. Individuals with obesity displayed severe vitamin D deficiency (25-OH-D ≤10 ng/ml) at a higher frequency compared to those with normal weight (p = 0.03). In patients with overweight/obesity and low 25-OH-D levels show higher values of glycemia (p = 0.001), insulin resistance (HOMA-IR and TRYG p < 0.001), TG (p < 0.001), TG/HDL-C (p = 0.001), AIP (p < 0.001), SBP (p = 0.01), and DBP (p = 0.04). In normal-weight individuals with low 25-OH- D levels an increased values of glycemia (p = 0.01), insulin resistance (HOMA-IR p = 0.01 and TRYG p = 0.002), TG (p = 0.01), TG/HDL-C (p = 0.02), AIP (p = 0.01). A direct correlation between 25-OH-D levels and metabolic parameters is observed. CONCLUSIONS: A correlation between vitamin D levels and the lipid/atherosclerotic profile was recorded. Vitamin D deficiency may represent a preventable and easily treatable cardiometabolic risk factor, emphasizing the importance of early intervention and preventive measures.

Long-term cytokine profile in multisystem inflammatory disease among children.

BACKGROUND: Multisystem inflammatory disease in children (MIS-C) is a post-infectious condition following coronavirus disease-19 infection. Long-term follow-up data suggests that initial clinical severity does not necessarily correlate with long-term outcomes. The long-term immunological response in children with MIS-C remains poorly understood. We analyzed cytokine profiles at diagnosis and during follow-up, in pediatric patients with MIS-C, exploring correlations among cytokine expressions and standard biochemical and hormonal test results. METHODS: Twenty-five MIS-C patients (mean 9.4 ± 3.9) with complete test results at diagnosis and at 6- and 12-months follow-up were included in the study. Selected cytokines, such as IL-9, eotaxin, IP-10, MIP-1ß, RANTES, MCP-1(MCAF), TNF-α, PDGF-B, IL-4, and MIP-1α, were included in the analysis. RESULTS: IP-10, MCP-1 (MCAF), and MIP-1α levels normalized or nearly normalized at 6-12 months, the remaining cytokines, including IL-9, eotaxin, MIP-1ß, RANTES, TNF-α, PDGF-B, IL-4, remained higher in MIS-C than in controls at our last follow-up time. At 6 months post-diagnosis, a mild negative correlation between triglycerides and HOMA-IR with MCP-1 (MCAF), IL-4, and Eotaxin was noted. At the 12-month follow-up we found a mild positive correlation of cortisol and ACTH levels with PDGF-B, MIP-1α, and TNF-α. Conversely, a negative correlation between these cytokines with fasting glucose and HOMA-IR was observed. CONCLUSIONS: Our study findings highlight a notable cytokine-mediated inflammatory response in pediatric patients with MIS-C, characterized by sustained elevated levels over a 12-month monitoring period compared to the control group. We have identified various interrelationships among different cytokines, as well as correlations between heightened cytokine levels and metabolic and hormonal patterns. The pronounced inflammatory response underscores its involvement in acute organ damage, while its persistence suggests potential implications for long-term metabolic disorders.

Mastication and oral myofunctional status in excess weight children and adolescents: A cross-sectional observational study.

BACKGROUND: Masticatory function seems to play a role in the aetiology of obesity. However, literature on the association between oral myofunctional status and overweight and obesity in children and adolescents is scarce and contrasting. OBJECTIVE: To compare masticatory performance, orofacial myofunctional status and tongue strength and endurance between children and adolescents with overweight and obesity and those with normal weight. METHODS: Thirty children and adolescents with overweight and obesity and 30 subjects with normal weight matched for age and sex were recruited. All subjects were evaluated with the Test of Masticating and Swallowing Solids in Children (TOMASS-C) for masticatory performance and with the Italian Orofacial Myofunctional Evaluation with Scores (I-OMES) for the orofacial myofunctional status. Anterior and posterior maximum tongue pressures and tongue endurance were measured. Parents-reported (PRO) duration of meals was recorded. Data were compared between the groups through the paired samples t-test or the Wilcoxon signed-rank test. RESULTS: Children and adolescents with overweight showed significantly lower number of bites (p = .033), lower I-OMES scores (p < .05), and shorter meal duration (p = .005) compared to their peers with normal weight. No significant differences were found between the two groups for the number of swallows, the number of masticatory cycles and the total time of the TOMASS-C, and none of the tongue pressure measurements. CONCLUSIONS: Eating in children and adolescents with overweight and obesity is characterised by a larger bolus sizes and shorter PRO meal duration. Additionally, overweight and obesity seem to be associated with poorer orofacial skills and structures in the paediatric population.

The digital readiness of future physicians: nurturing the post-pandemic medical education.

BACKGROUND: The COVID-19 pandemic has accelerated the integration of digital technologies in the healthcare sector. Telemedicine has notably emerged as a significant tool, offering a range of benefits. However, various barriers, such as healthcare professionals' insufficient technological skills and competencies, can hinder its effective implementation. Scholars have examined the readiness of future physicians, with some studies exploring their readiness before or during the COVID-19 crisis. There is, however, a noteable gap in the literature concerning the post-pandemic period. This study aims to identify gaps in current medical education programs by examining two primary aspects: (1) technical readiness (encompassing general and health-related digital competencies) and (2) behavioural readiness, which includes prior experiences and future intentions related to telemedicine education and implementation among medical students and residents. METHODS: A cross-sectional study was conducted using a web-based questionnaire administered to medical students and residents at a major Northern Italian university. The survey responses were analyzed to ascertain whether their distributions varied across demographic variables such as gender and level of education. RESULTS: The most commonly owned technologies were laptops and smartphones, with smartphones perceived as the easiest to use, while desktop computers presented more challenges. Approximately 38% of respondents expressed apprehension about applying digital health information in decision-making processes. There was a significant lack of both personal and academic experience, with only 16% of students and residents having used telemedicine in a university setting. Despite this, 83% of participants expressed a desire for training in telemedicine, and 81% were open to experimenting with it during their academic journey. Moreover, 76% of respondents expressed interest in incorporating telemedicine into their future clinical practice. CONCLUSIONS: This study highlights the need for medical students and residents to receive specific education in digital health and telemedicine. Introducing curricula and courses in this domain is critical to addressing the challenges of digital healthcare.

Vaccinome landscape in nearly 620,000 patients with diabetes.

INTRODUCTION: Type 1 (T1D) and type 2 diabetes (T2D) are associated with an elevated incidence of infectious diseases and a higher risk of infections-related hospitalization and death. In this study, we delineated the "vaccinome" landscape obtained with a large immunization schedule offered by the Regional Government of Lombardy in a cohort of 618,396 patients with diabetes (T1D and T2D). METHODS: Between September 2021 and September 2022, immunization coverage for influenza, meningococcus, pneumococcus, and herpes zoster was obtained from the public computerized registry of the healthcare system of Lombardy Region (Italy) in 618,396 patients with diabetes and in 9,534,087 subjects without diabetes. Type of diabetes, age, mortality, and hospitalizations were retrospectively analyzed in vaccinated and unvaccinated patients. RESULTS: Among patients with diabetes (T1D and T2D), 44.6% received the influenza vaccine, 10.9% the pneumococcal vaccine, 2.5% the anti-meningococcus vaccine and 0.7% the anti-zoster vaccine. Patients with diabetes immunized for influenza, zoster and meningococcus showed a 2-fold overall reduction in mortality risk and a decrease in hospitalizations. A 3-fold lower risk of mortality and a decrease in hospitalizations for both cardiac and pulmonary causes were also observed after influenza, zoster, and meningococcus immunization in older patients with diabetes. CONCLUSIONS: Immunization coverage is still far from the recommended targets in patients with diabetes. Despite this, influenza vaccination protected nearly 3,800 per 100,000 patients with diabetes from risk of death. The overall impressive decrease in mortality and hospitalizations observed in vaccinated patients strengthens the need for scaling up the "vaccinome" landscape in patients with diabetes.

Microbiota gut-brain axis: implications for pediatric-onset leukodystrophies.

Neurodegenerative disorders are a group of diseases characterized by progressive degeneration of the nervous system, leading to a gradual loss of previously acquired motor, sensory and/or cognitive functions. Leukodystrophies are amongst the most frequent childhood-onset neurodegenerative diseases and primarily affect the white matter of the brain, often resulting in neuro-motor disability. Notably, gastrointestinal (GI) symptoms and complications, such as gastroesophageal reflux disease (GERD) and dysphagia, significantly impact patients' quality of life, highlighting the need for comprehensive management strategies. Gut dysbiosis, characterized by microbial imbalance, has been implicated in various GI disorders and neurodegenerative diseases. This narrative review explores the intricate relationship between GI symptoms, Gut Microbiota (GM), and neurodegeneration. Emerging evidence underscores the profound influence of GM on neurological functions via the microbiota gut-brain axis. Animal models have demonstrated alterations in GM composition associated with neuroinflammation and neurodegeneration. Our single-centre experience reveals a high prevalence of GI symptoms in leukodystrophy population, emphasizing the importance of gastroenterological assessment and nutritional intervention in affected children. The bidirectional relationship between GI disorders and neurodegeneration suggests a potential role of gut dysbiosis in disease progression. Prospective studies investigating the GM in leukodystrophies are essential to understand the role of gut-brain axis dysfunction in disease progression and identify novel therapeutic targets. In conclusion, elucidating the interplay between GI disorders, GM, and neurodegeneration holds promise for precision treatments aimed at improving patient outcomes and quality of life.

Long-COVID symptom monitoring: Insights from a two-year telemedicine study.

BACKGROUND: The diverse manifestations of Long-COVID have become increasingly important due to their significant impact on patients' lives. Telemedicine has emerged as an important tool for post COVID-19 follow-up. This study is part of a large cohort study involving COVID-positive patients monitored by the COD19 telemedicine platform operations center. We recontacted patients who were initially monitored from February 2020 to May 2020 to assess the presence of Long-COVID symptoms at a 2-year follow-up. METHODS: We conducted interviews to evaluate Long-COVID symptoms at the 2-year mark and investigated whether patients had contracted a second COVID-19 infection between the 1-year and 2-year follow-ups, and recorded their vaccination status. RESULTS: Out of 165 patients, 139 (84%) reported symptoms at the 1-year follow-up, while only 101 (61%) reported symptoms at the 2-year follow-up. Among patients with Long-COVID symptoms at the 2-year follow-up, the majority (80, 49%) had experienced Long-COVID at the 1-year follow-up, received the SARS-CoV-2 vaccine, and had not experienced a second infection between the two follow-ups. Both having Long-COVID at the 1-year follow-up and contracting a second infection were significant risk factors for presenting with Long-COVID at the 2-year follow-up. CONCLUSIONS: To the best of our knowledge, this study stands out as one of the few that includes a 2-year follow-up on Long-COVID symptoms using telemedicine. Telemedicine has proven to be an effective and innovative tool for long-term patient monitoring, early diagnosis, and treatment. Telemedicine represents a significant future challenge for healthcare.

COVID-19-Associated Multisystem Inflammatory Syndrome in Children and Cardiovascular Autonomic Control: A Prospective Cohort Study Nine Months after SARS-CoV-2 Infection.

Background: Multisystem Inflammatory Syndrome in Children (MIS-C) has emerged as a severe pediatric complication during the SARS-CoV-2 pandemic, with potential long-term cardiovascular repercussions. We hypothesized that heart rate and blood pressure control at rest and during postural maneuvers in MIS-C patients, months after the remission of the inflammatory syndrome, may reveal long-term autonomic dysfunctions. Methods: We assessed 17 MIS-C patients (13 males; 11.9 ± 2.6 years, m ± SD) 9 months after acute infection and 18 age- (12.5 ± 2.1 years) and sex- (13 males) matched controls. Heart rate and blood pressure variability, baroreflex function, and hemodynamic parameters were analyzed in supine and standing postures. Results: MIS-C patients exhibited reduced heart rate variability, particularly in parasympathetic parameters during standing (pNN50+: 6.1 ± 6.4% in controls, 2.5 ± 3.9% in MIS-C; RMSSD: 34 ± 19 ms in controls, 21 ± 14 ms in MIS-C, p < 0.05), with no interaction between case and posture. Blood pressure variability and baroreflex sensitivity did not differ between groups except for the high-frequency power in systolic blood pressure (3.3 ± 1.2 mmHg2 in controls, 1.8 ± 1.2 mmHg2 in MIS-C, p < 0.05). The MIS-C group also showed lower diastolic pressure-time indices (DPTI) and systolic pressure-time indices (SPTI), particularly in standing (DPTI: 36.2 ± 9.4 mmHg·s in controls, 29.4 ± 6.2 mmHg·s in MIS-C; SPTI: 26.5 ± 4.3 mmHg·s in controls, 23.9 ± 2.4 mmHg·s in MIS-C, p < 0.05). Conclusions: Altered cardiovascular autonomic control may persist in MIS-C patients with, however, compensatory mechanisms that may help maintain cardiovascular homeostasis during light autonomic challenges, such as postural maneuvers. These results highlight the importance of assessing long-term cardiovascular autonomic control in children with MIS-C to possibly identify residual cardiovascular risks and inform targeted interventions and rehabilitation protocols.

Unsaturated fatty acids, omega-3 index and hospitalization in MISC.

The growing interest in Omega-3 fatty acids as diagnostic markers or new therapeutic approaches also for COVID-19 disease, led us to investigate the presence of potential correlations between Omega-3 fatty acids' levels in whole blood and days of hospitalization or admission to the paediatric intensive care unit (PICU) in 51 children with MIS-C diagnosis following SARS-CoV-2 infection. A statistically significant negative correlation was observed between days of hospitalization and docosapentaenoic acid (22:5n-3,DPA), docosahexaenoic acid (DHA) and total Omega-3 FA levels. Dividing the study group into quartiles according to Omega-3-Index (O3I), no statistically significant difference was observed with respect to the PICU admission rate. In contrast, the number of days of hospitalization in Q4 (O3I ≥ 2.51 %) was different from the number observed in groups Q1-3 (O3I < 2.51 %), with subjects showing higher O3I needing shorter hospitalizations than the subjects with lower O3I. According to previous study investigating O3I in adults affected by Sars-cov-2 we explored the levels of this nutrients in children with MIS-C. Our exploratory study shows that high DPA, DHA and O3I levels could be effective in reducing the length of hospitalization.

Safety and Psychological Outcomes of Tandem t:Slim X2 Insulin Pump with Control-IQ Technology in Children, Adolescents, and Young Adults with Type 1 Diabetes: A Systematic Review.

The Tandem t:slim X2 insulin pump is a second-generation automated insulin delivery system with Control-IQ technology. It consists of an X2 insulin pump, an integrated Dexcom sensor, and an embedded 'Control-IQ' algorithm, which predicts glucose levels 30 min in the future, adapting the programmed basal insulin rates to get glucose levels between 112.5 and 160 mg/dl (8.9 mmol/l). The system delivers automatic correction boluses of insulin when glucose levels are predicted to rise > 180 mg/dl (10 mmol/l). It has been commercially available since 2016. We reviewed the current evidence about the psychological, safety, and exercise-related outcomes of this device in children, adolescents, and young adults living with type 1 diabetes. We screened 552 papers, but only 21 manuscripts were included in this review. Fear of hypoglycemia is significantly reduced in young people with diabetes and their parents. Interestingly, diabetes-related distress is decreased; thus, the system is well accepted by the users. The sleeping quality of subjects living with diabetes and their caregivers is improved to a lesser extent as well. Despite the small number of data, this system is associated with a low rate of exercise-related hypoglycemia. Finally, evidence from the literature shows that this system is safe and effective in improving psychological personal outcomes. Even if further steps toward the fully closed loop are still mandatory, this second-generation automated insulin delivery system reduces the burden of diabetes. It properly addresses most psychological issues in children, adolescents, and young adults with type 1 diabetes mellitus; thus, it appears to be well accepted.

Desensitization of olipudase alfa-induced anaphylaxis in a child with chronic neurovisceral acid sphingomyelinase deficiency.

Olipudase alfa is indicated for the non-central nervous system manifestations of Acid sphingomyelinase deficiency (ASMD). Anaphylaxis is a very rare and life-threatening adverse reaction described for this drug. Here, we report the case of a 2-year-old boy affected by chronic neurovisceral ASMD who experienced signs of hypersensitivity reactions to olipudase alfa since the administered dose of 1 mg/kg during dose escalation and a proper anaphylactic reaction during the second administration of the target therapeutic dose of 3 mg/kg. The treatment was stopped for 15 weeks and then a 7-step desensitization protocol with the infused dose of 0.03 mg/kg was applied. Subsequent gradual dose escalation was resumed, successfully reaching the dose of 0.3 mg/kg. Moreover, biochemical, and radiological disease indexes, which were increased during treatment discontinuation, have gradually improved since the restart of treatment. However, at the second administration of the dose of 0.6 mg/kg, the patient experienced another adverse drug reaction with facial urticarial rash and bronchospasm, requiring the administration of adrenaline, methylprednisolone, and inhaled salbutamol. This case report highlights the need to customize the olipudase alfa desensitization protocol according to individual tolerance and raises the issue of achieving the established therapeutic target in the most sensitive children. Synopsis: We report a case of anaphylaxis to olipudase alfa in a child affected by chronic neurovisceral Acid sphingomyelinase deficiency (ASMD) and describe a 7-step desensitization procedure. This procedure, with the total administered dose of 0.03 mg/kg, followed by gradual dose escalation, allowed to reach the dose of 0.3 mg/kg without adverse reactions; however, at the second administration of the dose of 0.6 mg/kg our patient presented another adverse reaction suggesting the need of a different desensitization strategy.