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CONTEXT: The 2019 AACE guidelines suggested peak GH-cutoffs to glucagon test (GST) of ≤3 µg/L and ≤1 µg/L in the diagnosis of permanent GH deficiency (GHD) during the transition phase. OBJECTIVE: Aim of the study was to evaluate the accuracy of GST compared to insulin tolerance test (ITT) in the definition of GHD at adult height achievement. PATIENTS AND METHODS: Ninety-seven subjects with childhood-onset GHD (median age, 17.39 years) underwent ITT, GST and IGF-1 testing; 44 subjects were idiopathic (isolated GHD), 35 moderate organic GHD (0-2 hormone deficiencies-HDs) and 18 severe organic GHD (≥3 HDs). RESULTS: Bland and Altman analysis showed a high consistency of GH peak measures after ITT and GST. Receiver operating characteristic analysis-ROC- identified 7.3 µg/L as the optimal GH peak cutoff to GST (95% CI 4.15-8.91; sensitivity 95.7%, specificity 88.2%, positive predictive value-PPV-88.0%, negative predictive value-NPV-95.7%), able to correctly classify 91.8% of the entire cohort while 5.8 µg/L was the best GH peak cutoff able to correctly classify 91.4% of moderate organic GHD patients (95% CI 3.16-7.39; sensitivity 96.0%, specificity 80.0%, PPV 92.3%, NPV 88.9%). Patients with ≥3HDs showed a GH peak <5µg/L at ITT and <5.8µg/L at GST but one. The optimal cutoff for IGF1 was -1.4 SDS (95% CI -1.94-0.77; sensitivity 75%, specificity 94%, PPV 91.7%, NPV 81.0%) that correctly classified 85.1% of the study population. CONCLUSIONS: A GH peak to GST <5.8 µg/L represents an accurate diagnostic cutoff for young adults with childhood-onset GHD and high pre-test probability of permanent GHD.
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Achondroplasia is a lifelong condition requiring lifelong management. There is consensus that infants and children with achondroplasia should be managed by a multidisciplinary team experienced in the condition. However, many people are lost to follow-up after the transition from paediatric to adult care, and there is no standardised approach for management in adults, despite the recent availability of international consensus guidelines. To address this, the European Achondroplasia Forum has developed a patient-held checklist to support adults with achondroplasia in managing their health. The checklist highlights key symptoms of spinal stenosis and obstructive sleep apnoea, both among the most frequent and potentially severe medical complications in adults with achondroplasia. The checklist acts as a framework to support individuals and their primary care provider in completing a routine review. General advice on issues such as blood pressure, pain, hearing, weight, adaptive aids, and psychosocial aspects are also included. The checklist provides key symptoms to be aware of, in addition to action points so that people can approach their primary care provider and be directed to the appropriate specialist, if needed. Additionally, the European Achondroplasia Forum offers some ideas on implementing the checklist during the transition from paediatric to adult care, thus ensuring the existing multidisciplinary team model in place during childhood can support in engaging individuals and empowering them to take responsibility for their own care as they move into adulthood.
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Acondroplasia , Adulto , Humanos , Acondroplasia/complicações , Acondroplasia/terapia , Lista de Checagem , Europa (Continente) , Apneia Obstrutiva do Sono/terapia , Estenose Espinal/terapia , Estenose Espinal/complicações , Transição para Assistência do AdultoRESUMO
BACKGROUND: In response to the imperative need for standardized support for adolescent Gender Dysphoria (GD), the Italian Academy of Pediatrics, in collaboration with the Italian Society of Pediatrics, the Italian Society for Pediatric Endocrinology and Diabetes, Italian Society of Adolescent Medicine and Italian Society of Child and Adolescent Neuropsychiatry is drafting a position paper. The purpose of this paper is to convey the author's opinion on the topic, offering foundational information on potential aspects of gender-affirming care and emphasizing the care and protection of children and adolescents with GD. MAIN BODY: Recognizing that adolescents may choose interventions based on their unique needs and goals and understanding that every individual within this group has a distinct trajectory, it is crucial to ensure that each one is welcomed and supported. The approach to managing individuals with GD is a multi-stage process involving a multidisciplinary team throughout all phases. Decisions regarding treatment should be reached collaboratively by healthcare professionals and the family, while considering the unique needs and circumstances of the individual and be guided by scientific evidence rather than biases or ideologies. Politicians and high court judges should address discrimination based on gender identity in legislation and support service development that aligns with the needs of young people. It is essential to establish accredited multidisciplinary centers equipped with the requisite skills and experience to effectively manage adolescents with GD, thereby ensuring the delivery of high-quality care. CONCLUSION: Maintaining an evidence-based approach is essential to safeguard the well-being of transgender and gender diverse adolescents.
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Medicina do Adolescente , Diabetes Mellitus , Disforia de Gênero , Neuropsiquiatria , Humanos , Criança , Adolescente , Masculino , Feminino , Identidade de Gênero , Disforia de Gênero/terapia , ItáliaRESUMO
Introduction: The standard of care for pediatric growth hormone deficiency (pGHD) is once-daily recombinant human growth hormone (rhGH). Somatrogon, a long-acting rhGH, requires less frequent, once-weekly, dosing. We describe physicians' preference for, experiences, and satisfaction with once-weekly somatrogon vs once-daily rhGH. Methods: English-speaking investigators from somatrogon's global phase III study (NCT02968004) with prior experience using once-daily rhGH were included. Participants answered an online survey containing 14 closed- and open-ended items. Results: Twenty-four pediatric endocrinologists (41.7% men; 79.2% practiced at public/private hospitals) from 12 countries with 25.8 ± 12.0 years' experience treating pGHD completed the survey. In terms of the time and effort required to explain device instructions, injection regimen, procedure for missed injection, and address patients'/caregivers' concerns, a similar proportion of physicians chose once-weekly somatrogon and once-daily rhGH; 62.5% physicians indicated that once-daily rhGH required greater effort to monitor adherence. Overall, 75% preferred once-weekly somatrogon over once-daily rhGH, 79.2% considered once-weekly somatrogon to be more convenient and less burdensome, and 83.3% were likely to prescribe somatrogon in the future. Overall, 50% felt that once-weekly somatrogon was more beneficial to patients, while 50% chose "No difference". Most physicians (62.5%) felt both regimens were equally likely to support positive long-term growth outcomes and reduce healthcare utilization. More physicians were "very satisfied" with once-weekly somatrogon (62.5%) than with once-daily rhGH (16.7%). Reduced injection frequency, patient and caregiver burden, increased convenience, and improved adherence were reasons for these choices. Conclusion: Physicians had a positive experience with, and perception of, treating pGHD with once-weekly somatrogon.
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Nanismo Hipofisário , Hormônio do Crescimento Humano , Médicos , Masculino , Humanos , Criança , Feminino , Estudos Transversais , Nanismo Hipofisário/tratamento farmacológico , Proteínas RecombinantesRESUMO
Context: Since the COVID-19 outbreak, the number of girls with suspected precocious puberty has increased. Objective: To compare the incidence of idiopathic central precocious puberty (ICPP) during COVID-19 with that of the previous 4 years. Methods: Anthropometric, biochemical, and radiological parameters were collected between January 2016 and June 2021 from 133 girls who met the Rapidly Progressive ICPP criteria (RP-ICPP). Results: We found a higher incidence of RP-ICPP between March 2020 and June 2021 (group 2) compared with January 2016 through March 2020 (group 1) (53.5% vs 41.1%); 2021 showed the highest annual incidence (P < .05). Group 1 and group 2 differed in age at diagnosis (7.96 ± 0.71 vs 7.61 ± 0.94; P < .05), mean Tanner stage (2.86 ± 0.51 vs 2.64 ± 0; P < .05), and in the time between the appearance of thelarche and diagnosis (0.93 ± 0.75 vs 0.71 ± 0.62 years, P < .05). There was an increase in the number of girls aged <8 years in group 2 and a significantly higher number of girls aged >8 years was found in group 1 (42 in group 1 vs 20 in group 2, P < 0.05). Overall body mass index SD score showed higher values ââin group 2 (1.01 ± 1.23 vs 0.69 ± 1.15; P = .18), which spent an average of 1.94 ± 1.81â hours per day using electronic devices; 88.5% of this group stopped any physical activity. Conclusions: A spike in new diagnoses of idiopathic (1.79-fold higher) and RP-CPP coincided with the COVID-19 pandemic. The incidence of RP-ICPP was 1.3-fold higher during COVID-19 with a trend toward an increase in body mass index SD score. The expanding use of digital devices and the reduction of daily physical activity represent possible risk factors.
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Lactic acidosis is characterized by an excessive production of lactic acid or by its impaired clearance. Thiamine deficiency is an uncommon cause of lactic acidosis, especially in countries where malnutrition is rare. We describe the case of a 5-year-old boy who presented with a central nervous system relapse of acute lymphoblastic leukemia. During the chemotherapy regimen, the patient developed drug-induced pancreatitis with paralytic ileus requiring prolonged glucosaline solution infusion. In the following days, severe lactic acidosis (pH 7.0, lactates 253 mg/dL, HCO3- 8 mmol/L) was detected, associated with hypoglycemia (42 mg/dL) and laboratory signs of acute liver injury. Due to the persistent hypoglycemia, the dextrose infusion was gradually increased. Lactates, however, continued to raise, so continuous venovenous hemodiafiltration was started. While lactates initially decreased, 12 h after CVVHDF suspension, they started to raise again. Assuming that it could have been caused by mitochondrial dysfunction due to vitamin deficiency after prolonged fasting and feeding difficulties, parenteral nutrition and thiamine were administered, resulting in a progressive reduction in lactates, with the normalization of pH during the next few hours. In the presence of acute and progressive lactic acidosis in a long-term hospitalized patient, thiamine deficiency should be carefully considered and managed as early as possible.
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The clinical features of achondroplasia can cause acute self-limited pain that can evolve into chronic pain. Pain causes a low quality of life, in terms of physical, emotional, social, and school functioning in both adult and children with achondroplasia. We conducted a systematic review according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement to describe prevalence, assessment tools, causes and management strategies of pain in this rare disease. We found that shoulder and knee pain is typically referred during infancy, while knee pain is generally referred around 5-6 years of age. The prevalence of general pain in adolescence can be as high as 90%. Chronic pain in the achondroplasia population increases with age, with up to 70% of adults reporting general pain and back pain. Recognizing the multiple determinants of acute and chronic pain in patients with achondroplasia may enable physicians to better understand and manage this burden, particularly with the advent of new drugs that may modify some of the striking features of achondroplasia.
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Acondroplasia , Dor Crônica , Adolescente , Humanos , Criança , Adulto , Qualidade de Vida , Acondroplasia/complicações , Acondroplasia/epidemiologiaRESUMO
Background: Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males. Methods: In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS. Conclusions: According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
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Criptorquidismo , Síndrome de Noonan , Masculino , Criança , Adulto , Feminino , Humanos , Síndrome de Noonan/genética , Gônadas , Puberdade/genética , Proteínas Quinases Ativadas por MitógenoRESUMO
CONTEXT: The European Increlex® Growth Forum Database (Eu-IGFD) is an ongoing surveillance registry (NCT00903110) established to collect long-term safety and effectiveness data on the use of recombinant human insulin-like growth factor-1 (rhIGF-1, mecasermin, Increlex) for the treatment of children/adolescents with severe primary insulin-like growth factor-1 deficiency (SPIGFD). OBJECTIVE: This analysis of Eu-IGFD data aimed to identify the frequency and predictive factors for hypoglycemia adverse events (AEs) in children treated with rhIGF-1. METHODS: Data were collected from December 2008 to May 2021. Logistic regression was performed to identify predictive risk factors for treatment-induced hypoglycemia AEs. Odds ratios (ORs) are presented with 95% CIs for each factor. RESULTS: In total, 306 patients were enrolled in the registry; 84.6% were diagnosed with SPIGFD. Patients who experienced ≥ 1 hypoglycemia AE (n = 80) compared with those with no hypoglycemia AEs (n = 224) had a lower mean age at treatment start (8.7 years vs 9.8 years), a more frequent diagnosis of Laron syndrome (27.5% vs 10.3%), and a history of hypoglycemia (18.8% vs 4.5%). Prior history of hypoglycemia (OR 0.25; 95% CI: [0.11; 0.61]; P = .002) and Laron syndrome diagnosis (OR 0.36; 95% CI: [0.18; 0.72]; P = .004) predicted future hypoglycemia AEs. Total hypoglycemia AEs per patient per treatment year was 0.11 and total serious hypoglycemia AEs per patient per treatment year was 0.01. CONCLUSION: Hypoglycemia occurs more frequently in patients with prior history of hypoglycemia and/or Laron syndrome compared with patients without these risk factors, and these patients should be carefully monitored for this AE throughout treatment.
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Hipoglicemia , Síndrome de Laron , Criança , Adolescente , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Estudos Longitudinais , Fator de Crescimento Insulin-Like I , Proteínas Recombinantes/efeitos adversos , Bases de Dados Factuais , Modelos LogísticosRESUMO
Context: Rapid-onset obesity with central hypoventilation, hypothalamic dysfunction, and autonomic dysregulation with neural crest tumors (ROHHAD-NET) syndrome pathophysiology remains elusive. Acquired neuroimmunological dysfunction has been proposed as a possible pathogenetic pathway. Objective: The aim of our study was to characterize lymphocyte subpopulations subsets in peripheral blood (PB) and to evaluate a panel of proinflammatory cytokines/chemokines in ROHHAD(NET) patients vs controls. Methods: We included 11 ROHHAD(NET) patients, 7 ROHHAD and 4 ROHHAD-NET, selected by clinical criteria. Controls were 11 simple obese children, matched for age and sex. Flow cytometric analysis and enzyme-linked immunosorbent assay were performed on PB and serum samples of the 2 groups. Results: Analysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients (P = .04) with a prevalence of CD4-T cells (P = .03) and a lower number of activated CD8-T cells (P = .02). With regard to regulatory subset, patients displayed increased regulatory B cells (P = .05) and type-1 regulatory T cells (P = .03). With regard to CD8-T cells, a lower number of T effector memory was observed (P = .02). In contrast, among CD4-T cells, we found a higher number of T naive (P = .04) and T effector (P = .0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls (P = .008 and P = .01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor (P = .0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls (P = .03). Conclusion: Our findings contribute to support the hypothesis of immune dysregulation, which may underlie this complex, often fatal disease. Because ROHHAD(NET) syndrome is an ultra-rare disease, multicentric studies are needed to improve the effect of our data in the management of this condition.
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The fecal microbiome of 55 obese children and adolescents (BMI-SDS 3.2 ± 0.7) and of 25 normal-weight subjects, matched both for age and sex (BMI-SDS - 0.3 ± 1.1) was analysed. Streptococcus, Acidaminococcus, Sutterella, Prevotella, Sutterella wadsworthensis, Streptococcus thermophilus, and Prevotella copri positively correlated with obesity. The inferred pathways strongly associated with obesity concern the biosynthesis pathways of tyrosine, phenylalanine, tryptophan and methionine pathways. Furthermore, polyamine biosynthesis virulence factors and pro-inflammatory lipopolysaccharide biosynthesis pathway showed higher abundances in obese samples, while the butanediol biosynthesis showed low abundance in obese subjects. Different taxa strongly linked with obesity have been related to an increased risk of multiple diseases involving metabolic pathways related to inflammation (polyamine and lipopolysaccharide biosynthesis). Cholesterol, LDL, and CRP positively correlated with specific clusters of microbial in obese patients. The Firmicutes/Bacteroidetes-ratio was lower in obese samples than in controls and differently from the literature we state that this ratio could not be a biomarker for obesity.
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Microbioma Gastrointestinal , Microbiota , Obesidade Infantil , Criança , Adolescente , Humanos , Lipopolissacarídeos , AlgoritmosRESUMO
Foramen magnum stenosis is a serious, and potentially life-threatening complication of achondroplasia. The foramen magnum is smaller in infants with achondroplasia, compared with the general population, and both restricted growth in the first 2 years and premature closure of skull plate synchondroses can contribute to narrowing. Narrowing of the foramen magnum can lead to compression of the brainstem and spinal cord, and result in sleep apnoea and sudden death. There is a lack of clarity in the literature on the timing of regular monitoring for foramen magnum stenosis, which assessments should be carried out and when regular screening should be ceased. The European Achondroplasia Forum (EAF) is a group of clinicians and patient advocates, representative of the achondroplasia community. Members of the EAF Steering Committee were invited to submit suggestions for guiding principles for the detection and management of foramen magnum stenosis, which were collated and discussed at an open workshop. Each principle was scrutinised for content and wording, and anonymous voting held to pass the principle and vote on the level of agreement. A total of six guiding principles were developed which incorporate routine clinical monitoring of infants and young children, timing of routine MRI screening, referral of suspected foramen magnum stenosis to a neurosurgeon, the combination of assessments to inform the decision to decompress the foramen magnum, joint decision making to proceed with decompression, and management of older children in whom previously undetected foramen magnum stenosis is identified. All principles achieved the ≥ 75% majority needed to pass (range 89-100%), with high levels of agreement (range 7.6-8.9). By developing guiding principles for the detection and management of foramen magnum stenosis, the EAF aim to enable infants and young children to receive optimal monitoring for this potentially life-threatening complication.
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Acondroplasia , Doenças Ósseas , Síndromes da Apneia do Sono , Criança , Lactente , Humanos , Adolescente , Pré-Escolar , Forame Magno/cirurgia , Constrição Patológica/diagnóstico , Constrição Patológica/complicações , Acondroplasia/diagnóstico , Acondroplasia/terapia , Acondroplasia/complicações , Síndromes da Apneia do Sono/diagnóstico , Medula Espinal , Doenças Ósseas/complicaçõesRESUMO
Background: Achondroplasia is a rare genetic disorder caused by a mutation in the FGFR3 gene, leading to skeletal changes and other systemic complications that greatly impact the patient's quality of life. There currently are differences in achondroplasia patients' management among countries and centers within the same country. Method: A group of Italian experts discussed the best practice and the current unmet needs in the management of patients with achondroplasia though a two-round Delphi panel, between September and November 2022. The Delphi survey consisted of 32 questions covering organizational aspects, diagnosis and follow-up, and management of achondroplasia patient, and was shared among 54 experts from 25 different centers in Italy. The consensus was determined on the basis of the percentage of agreement or disagreement to each statement on a 5-point Likert scale. Results: Pediatricians (including specialists in pediatrics, medical genetics, and pediatric endocrinology) orthopedics and medical geneticists were the most represented specialists accounting for 64%, 9% and 9% of participants, respectively. The panel highlighted the need for standardized procedures to identify reference centers, the crucial role of multidisciplinary team, and effective communication among centers (Hub and Spoke model) as the essential organizational features; the importance of genetic counseling, presence of a psychologist, and clear communication during prenatal diagnosis as main points for diagnosis; early intervention by different specialists, personalized care, and promotion of a healthy lifestyle as major points for patient management. Conclusion: To ensure an adequate continuity of care over the whole lifespan of a patient with achondroplasia a shared model for patient management is suggested by Italian specialists.
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BACKGROUND: Collection of real-world evidence (RWE) is important in achondroplasia. Development of a prospective, shared, international resource that follows the principles of findability, accessibility, interoperability, and reuse of digital assets, and that captures long-term, high-quality data, would improve understanding of the natural history of achondroplasia, quality of life, and related outcomes. METHODS: The Europe, Middle East, and Africa (EMEA) Achondroplasia Steering Committee comprises a multidisciplinary team of 17 clinical experts and 3 advocacy organization representatives. The committee undertook an exercise to identify essential data elements for a standardized prospective registry to study the natural history of achondroplasia and related outcomes. RESULTS: A range of RWE on achondroplasia is being collected at EMEA centres. Whereas commonalities exist, the data elements, methods used to collect and store them, and frequency of collection vary. The topics considered most important for collection were auxological measures, sleep studies, quality of life, and neurological manifestations. Data considered essential for a prospective registry were grouped into six categories: demographics; diagnosis and patient measurements; medical issues; investigations and surgical events; medications; and outcomes possibly associated with achondroplasia treatments. CONCLUSIONS: Long-term, high-quality data are needed for this rare, multifaceted condition. Establishing registries that collect predefined data elements across age spans will provide contemporaneous prospective and longitudinal information and will be useful to improve clinical decision-making and management. It should be feasible to collect a minimum dataset with the flexibility to include country-specific criteria and pool data across countries to examine clinical outcomes associated with achondroplasia and different therapeutic approaches.
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Acondroplasia , Qualidade de Vida , Humanos , Europa (Continente) , Sistema de Registros , Acondroplasia/epidemiologiaRESUMO
Next-generation sequencing (NGS) has revolutionized the field of genomics and created new opportunities for basic research. We described the strategy for the NGS validation of the "dysglycaemia panel" composed by 44 genes related to glucose metabolism disorders (MODY, Wolfram syndrome) and familial renal glycosuria using Ion AmpliSeq technology combined with Ion-PGM. Anonymized DNA of 32 previously genotyped cases with 33 different variants were used to optimize the methodology. Standard protocol was used to generate the primer design, library, template preparation, and sequencing. Ion Reporter tool was used for data analysis. In all the runs, the mean coverage was over 200×. Twenty-nine out of thirty three variants (96.5%) were detected; four frameshift variants were missed. All point mutations were detected with high sensitivity. We identified three further variants of unknown significance in addition to pathogenic mutations previously identified by Sanger sequencing. The NGS panel allowed us to identify pathogenic variants in multiple genes in a short time. This could help to identify several defects in children and young adults that have to receive the genetic diagnosis necessary for optimal treatment. In order not to lose any pathogenic variants, Sanger sequencing is included in our analytical protocol to avoid missing frameshift variants.
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[This corrects the article DOI: 10.3389/fendo.2022.975511.].
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BACKGROUND: Achondroplasia, caused by a pathogenic variant in the fibroblast growth factor receptor 3 gene, is the most common skeletal dysplasia. The Lifetime Impact of Achondroplasia Study in Europe (LIAISE; NCT03449368) aimed to quantify the burden of achondroplasia among individuals across a broad range of ages, including adults. METHODS: Demographic, clinical and healthcare resource use data were collected from medical records of achondroplasia patients enrolled in 13 sites across six European countries in this retrospective, observational study. Descriptive statistics or event rates per 100 person-years were calculated and compared across age groups as well as by history of limb lengthening. Patient-reported outcomes (quality of life [QoL], pain, functional independence, work productivity and activity impairments) were evaluated using questionnaires at the time of enrolment. An exploratory analysis investigated correlations between height (z-score or centimetres) and patient-reported outcomes. RESULTS: Overall, 186 study patients were included, with a mean age of 21.7 ± 17.3 years (range 5.0-84.4). At least one complication or surgery was reported for 94.6% and 72.0% of patients, respectively, at a rate of 66.6 and 21.5 events per 100 person-years. Diverse medical and surgical complications were reported for all ages in a bimodal distribution, occurring more frequently in the youngest and oldest age groups. A total of 40 patients had previously undergone limb lengthening (capped at 20% per the study protocol). The most frequent surgery types varied by age, in line with complication profiles. Healthcare resource use was high across all age groups, especially among the youngest and oldest individuals, and did not differ substantially according to history of limb lengthening. Compared to general population values, patients reported impaired QoL particularly for physical functioning domains. In addition, patients reported difficulty carrying out daily activities independently and pain starting in childhood. Patient height correlated with multiple patient-reported outcomes. CONCLUSIONS: The findings of this study suggest that, across an individual's lifetime, achondroplasia is associated with multisystem complications, reduced QoL and functionality, and increased pain. These results highlight the large amount of healthcare resources that individuals with achondroplasia require throughout their lifespans and provide novel insights into current achondroplasia management practices across Europe. Trial registration ClinicalTrials.gov, NCT03449368, Submitted 14 December 2017 - prospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT03449368.
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Acondroplasia , Qualidade de Vida , Adulto , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Acondroplasia/epidemiologia , Acondroplasia/genética , Inquéritos e Questionários , Europa (Continente)RESUMO
Type 1 diabetes (T1D) patients' lifestyle and prognosis has remarkably changed over the years, especially after the introduction of insulin pumps, in particular advanced hybrid closed loop systems (AHCL). Emerging data in literature continuously confirm the improvement of glycemic control thanks to the technological evolution taking place in this disease. As stated in previous literature, T1D patients are seen to be more satisfied thanks to the use of these devices that ameliorate not only their health but their daily life routine as well. Limited findings regarding the use of new devices in different age groups and types of patients is their major limit. This review aims to highlight the main characteristics of each Automated Insulin Delivery (AID) system available for patients affected by Type 1 Diabetes Mellitus. Our main goal was to particularly focus on these systems' efficacy and use in different age groups and populations (i.e., children, pregnant women). Recent studies are emerging that demonstrate their efficacy and safety in younger patients and other forms of diabetes.
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BACKGROUND: Prader-Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients' care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. MATERIALS AND METHODS: The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. RESULTS: A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019-2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. CONCLUSIONS: The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.