Height benefit of GnRH agonists after age 8 in a Portuguese cohort of central precocious puberty.

OBJECTIVE: Idiopathic central precocious puberty (iCPP) is common in paediatric endocrinology. Gonadotropin-releasing hormone agonists (GnRHa) are safe, but the effect on final height and the ideal timing for treatment remains controversial. This study aims to assess the effectiveness of GnRHa on growth outcomes in girls with iCPP treated before and after the age of 8 years old. DESIGN AND PATIENTS: This retrospective longitudinal study evaluated data from Portuguese girls with iCPP who completed treatment between 2010 and 2021. MEASUREMENTS: Auxological and clinical characteristics were compared according to age at treatment onset. RESULTS: A cohort of 134 girls with iCPP, was divided into early treatment (ET) (<8 years, n = 48) and later treatment (LT) groups (≥8 years, n = 86). In both groups, most children presented with Tanner II and III. Tanner IV was more frequent in LT group (p = .003). At the end of treatment, predicted adult height increased in both groups (ET p = .032; LT p = .04) and bone age significantly slowed down in all participants (p = .008, p = .034). The height gain was greater in the ET group, but without significant differences (p = .065). CONCLUSIONS: Treatment with GnRHa improved final height in all girls with iCPP, even when initiated after 8 years. To achieve better outcomes, treatment should be provided promptly after diagnosis.

Nephron sparing surgery and surgical management of intravascular extension of Wilms tumor.

Although general treatment approaches for Wilms tumor differ between Children's Oncology Group and Société Internationale d'Oncologie Pédiatrique-Renal Tumors Study Group protocols, complex tumors that may be candidates for nephron sparing surgery (NSS) and those with intravascular tumor extension represent a management challenge. In both of these scenarios, anatomic considerations are important in guiding management, making these areas of significant similarities in management between the international groups. This paper aims to explore the current approaches to NSS and intravascular tumor extension by both international groups, with attention to the evidence supporting these approaches and current knowledge gaps.

Influence of conditioned medium from squamous cell carcinoma of the tongue on lymphoblasts and peripheral blood mononuclear cells.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the oral cavity and is associated with high morbidity and mortality. Attention has been given to the role of inflammatory cells in carcinogenesis because of the ability of cancer cells to subvert the immune response. However, little is known about how molecules from neoplastic cells interact with lymphoblasts and circulating immune cells. This study aimed to understand the mechanisms by which SCC cells modulate the immune response by analyzing the influence of conditioned medium derived from SCC cell lines on immune cells. METHODS: Lymphoblastic cells (CEM) and peripheral blood mononuclear cells (PBMC) were cultured in a conditioned medium derived from squamous cell carcinoma cells (SCC9 or SCC4) and analyzed for cell viability, CD4/CD8/FOXP3 profile by flow cytometry, and chemokine levels. RESULTS: Conditioned medium derived from SCC4 and SCC9 presented higher concentrations of IL-6 and IL-8 than IL-1ß, IL-10, and IFN-γ. CEM and PBMCs when cultured with conditioned medium derived from SCC4 and SCC9 reduced IL-1ß, IL-8, and IFN-γ concentrations. Conditioned medium from SCC4 increased CD4+ population in both CEM and PBMCs, while in conditioned medium from SCC9 it occurred only in PBMCs. PBMCs when cultured with both conditioned mediums increased CD8+ /FOXP3+ cells. CEM cells when cultured with conditioned medium derived from SCC4 and SCC9 reduced. CONCLUSION: Collectively, our results suggest that the products derived from squamous cell carcinoma on inflammatory cells can promote an immunosuppressed environment by reducing cell viability, changing cytokine expression, and altering the cell immunoprofile.

Arbitrarily large heteroclinic networks in fixed low-dimensional state space.

We consider heteroclinic networks between n∈N nodes where the only connections are those linking each node to its two subsequent neighboring ones. Using a construction method where all nodes are placed in a single one-dimensional space and the connections lie in coordinate planes, we show that it is possible to robustly realize these networks in R6 for any number of nodes n using a polynomial vector field. This bound on the space dimension (while the number of nodes in the network goes to ∞) is a novel phenomenon and a step toward more efficient realization methods for given connection structures in terms of the required number of space dimensions. We briefly discuss some stability properties of the generated heteroclinic objects.

Immediate sequential bilateral cataract surgery in adults with Down's syndrome.

PURPOSE: To describe the cataract surgery outcomes in 34 adult patients with Down's syndrome in our center between 1996 and 2019. SETTING: Clinical practice, tertiary hospital in Madrid, Spain. DESIGN: Retrospective, descriptive study in which 34 patients with Down's syndrome who underwent cataract surgery in our center between 1996 and 2019 were included. METHODS: Socio-demographic and clinical data such as the type of cataract, the keratometry and biometry, the type of surgery, the IOL material, and the complications before and after surgery were recovered. RESULTS: Fifty-four eyes of 34 patients (23 female, 11 male, mean age 49 ± 8 years) underwent cataract surgery with general anesthesia. Immediately sequential, bilateral cataract surgery was performed in 18 patients (90% of bilateral cases). White cataract was found in 11 eyes (20.4%). Phacoemulsification technique was used in 51 eyes, extracapsular technique in 2 eyes (3.7%), and intracapsular technique in 1 eye (1.85%) (the only aphakic eye after surgery). The mean Km was 48.73 ± 4D, and the mean axial length was 25.2 ± 2.5 mm. The most frequent ocular comorbidity was myopia (27 eyes, 50%) followed by strabismus (11 eyes, 20.4%) and keratoconus (10 eyes, 18.5%). Posterior capsular rupture as a complication during surgery was found in 3 eyes (5.5%). The mean preoperative visual acuity was 0.8 ± 0.2 logMAR, and the mean postoperative visual acuity was 0.5 ± 0.18 logMAR. CONCLUSIONS: Phacoemulsification technique can be performed in adults with Down's syndrome with an acceptable rate of complications. The lack of patient cooperation, the ocular comorbidities and the challenging biometric estimation must be considered in surgical planning. It seems reasonable to perform immediately sequential, bilateral cataract surgery when possible, in order to reduce the exposure to general anesthesia.

Improved survival in patients with thyroid function test abnormalities secondary to immune-checkpoint inhibitors.

Immune-checkpoint inhibitors (ICI) are monoclonal antibodies which target molecules to enhance antitumor response. Several adverse events have been described and the major ICI-related endocrinopathies are thyroid dysfunction and hypophysitis. Its occurrence has been associated with improved outcomes, but it is still to be proven. We performed a retrospective study of patients treated with ICI between 2014 and 2019 at an oncologic center to characterize thyroid function test abnormalities (TFTA) and to evaluate clinical outcomes. We excluded patients without regular monitoring of thyroid function, with previous thyroid or pituitary disease, previous head/neck radiotherapy and who performed only one ICI cycle. We included 161 of 205 patients treated with pembrolizumab, nivolumab or ipilimumab for several neoplasms, with a median duration of 18.9 weeks (9.1-42.6) of ICI treatment and 49.4 weeks (26.5-75.8) of follow-up. New-onset TFTA was diagnosed in 18% of patients (n = 29), in median at 10.6 weeks (6.1-31.1) of ICI therapy. On the whole, 8.7% had primary hypothyroidism, 4.3% central hypothyroidism, 2.5% biphasic thyroiditis and 2.5% thyrotoxicosis. Patients who experienced primary or central thyroid dysfunction had a significantly improved overall response rate (58.6% vs 34.2%, p = 0.015) and overall survival (3.27 vs 1.76 years, p = 0.030), compared to the control group. The risk of mortality was two times higher for control group (adjusted HR = 2.43, 95% CI 1.13-5.23, p = 0.023). This study recognizes that primary and central thyroid dysfunction can be a predictive clinical biomarker of a better response to ICI across several neoplasms.

Simultaneous Testicular and Appendix Testis Torsion: A Novel Clinically Relevant Association.

ABSTRACT: Torsion of the appendix testis (TAT) and testicular torsion (TT) are the most common causes of acute scrotum in the pediatric population. They usually present as separate conditions and have distinct managements. We report a unique case of a 16-year-old boy with concomitant TAT and TT. The role of TAT as a trigger factor to TT is addressed, and its clinical repercussion on the management of acute scrotum is discussed.

The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study.

OBJECTIVE: To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET). METHODS: Data were collected from 55 centers with documented patients' height. All subjects below 20 years of age, diabetes duration >1 year, and without celiac disease were included. World Health Organization growth charts were used to calculate height and body mass index z-scores. Multiple hierarchic regression models adjusting for known confounders were applied. RESULTS: Data on 22 941 subjects (51.8% male) were analyzed with a median and interquartile range for age 14.8 years (11.2, 17.6), diabetes duration 5.6 years (3.1, 8.9), and height z-score 0.34 (-0.37, 1.03). Children were taller in the youngest age groups: adjusted height z-scores of 0.31 (±0.06) and 0.39 (±0.06), respectively; with shorter diabetes duration (<2 years: 0.36 [±0.06]; 2-<5 years: 0.34 [±0.06]; ≥5 years: 0.21 [±0.06]) and if they were pump users: 0.35 ± 0.05 vs 0.25 ± 0.05 (>three injections/day and 0.19 ± 0.06 [0-3 injections daily]), respectively. High hemoglobin A1c (HbA1c) and low to normal weight were associated with a lower height z-score. Trends were identical in all models except for gender. No gender differences were found except in the final height model where females exhibited higher z-score than males. CONCLUSION: For youths treated at centers offering modern diabetes management, major growth disturbances are virtually eliminated. For children with a young age at onset, high HbA1c, injections, and/or non-intensive diabetes, treatment still requires attention in order to attain normal growth.

Insulin pump therapy in children with type 1 diabetes: analysis of data from the SWEET registry.

BACKGROUND: Intensified insulin delivery using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) is recommended in children with type 1 diabetes (T1D) to achieve good metabolic control. OBJECTIVE: To examine the frequency of pump usage in T1D children treated in SWEET (Better control in Paediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers and to compare metabolic control between patients treated with CSII vs MDI. METHODS: This study included 16 570 T1D children participating in the SWEET prospective, multicenter, standardized diabetes patient registry. Datasets were aggregated over the most recent year of treatment for each patient. Data were collected until March 2016. To assess the organization of pump therapy a survey was carried out. RESULTS: Overall, 44.4% of T1D children were treated with CSII. The proportion of patients with pump usage varied between centers and decreased with increasing age compared with children treated with MDI. In a logistic regression analysis adjusting for age, gender and diabetes duration, the use of pump was associated with both: center size [odd ratio 1.51 (1.47-1.55), P < .0001) and the diabetes-related expenditure per capita [odd ratio 1.55 (1.49-1.61), P < .0001]. Linear regression analysis, adjusted for age, gender, and diabetes duration showed that both HbA1c and daily insulin dose (U/kg/d) remained decreased in children treated with CSII compared to MDI (P < .0001). CONCLUSIONS: Insulin pump therapy is offered by most Sweet centers. The differences between centers affect the frequency of use of modern technology. Despite the heterogeneity of centers, T1D children achieve relatively good metabolic control, especially those treated with insulin pumps and those of younger age.

Geographic patterns and hotspots of pediatric tuberculosis: the role of socioeconomic determinants.

OBJECTIVE: Children are an important demographic group for understanding overall tuberculosis epidemiology, and monitoring of childhood tuberculosis is essential for appropriate prevention. The present study sought to characterize the spatial distribution of childhood tuberculosis notification rates in continental Portugal; identify high-risk areas; and evaluate the association between childhood tuberculosis notification rates and socioeconomic deprivation. METHODS: Using hierarchical Bayesian spatial models, we analyzed the geographic distribution of pediatric tuberculosis notification rates across 278 municipalities between 2016 and 2020 and determined high-risk and low-risk areas. We used the Portuguese version of the European Deprivation Index to estimate the association between childhood tuberculosis and area-level socioeconomic deprivation. RESULTS: Notification rates ranged from 1.8 to 13.15 per 100,000 children under 5 years of age. We identified seven high-risk areas, the relative risk of which was significantly above the study area average. All seven high-risk areas were located in the metropolitan area of Porto or Lisbon. There was a significant relationship between socioeconomic deprivation and pediatric tuberculosis notification rates (relative risk = 1.16; Bayesian credible interval, 1.05-1.29). CONCLUSIONS: Identified high-risk and socioeconomically deprived areas should constitute target areas for tuberculosis control, and these data should be integrated with other risk factors to define more precise criteria for BCG vaccination.

Digital Thoracic Drainage System: A New Tool For Pediatric Thoracic Surgery.

INTRODUCTION: Digital thoracic drainage systems usage in pediatrics is underreported, making current recommen- dations based on those for adults. We aim to review our experience on the use of this digital system and to evaluate the adequacy of those recommendations. METHODS: Retrospective analysis of patients in whom digital thoracic drainage system was used. All patients were submitted to thoracoscopic bleb/apical lung resection for primary spontaneous pneumothorax. Initially patients were man- aged using the few existing recommendations for children, but after 2 unsuccessful cases we changed our approach into tube clamping after continuous air leak < 5mL/min for at least 24 hours. RESULTS: Seventeen procedures (median 17.2-years) were performed; there were no intraoperative complications. After changing the air leak target, 11 procedures were consecutively managed without complications; the median number of chest radiographs per procedure was 3.0 and the median number of days with chest tube was 4.0 days. CONCLUSIONS: This is the first report on the usage of this system in children in Portugal. This system constitutes an important technological innovation, but it needs more data gathering and prospective trials in order to maximize its use in children. The authors suggest an algorithm for the management of thoracic digital drainage in children: removal of chest tubes when the air leak is <5mL/min for 24 hours and to perform chest tube clamping for a minimum of 6 hours before removal.

Successful technical note-Identification of the Adamkievicz artery with 1.5 Tesla MR angiography in a 14-month-old child.

Posterior mediastinal tumors surgery may be complicated by their proximity to the artery of Adamkiewicz (AKA) and its segmental supplier, increasing the risk of ischemia of the spinal cord. We describe a case of preoperative identification of the AKA with magnetic resonance angiography (MRA) in a 14-month-old boy diagnosed with a thoracic neuroblastoma, thus allowing an accurate surgical planning in order to avoid injury to those vessels. Given the relatively high incidence of posterior mediastinal tumors in the pediatric age, MRA may establish itself as a viable alternative for this purpose, even in young children.

Nickel Allergy After a Negative Test Result Following Nuss Procedure for Pectus Excavatum: a Case Report.

.

Preoperative Metal Patch Testing and Titanium Bar Use Criteria in Nuss Procedure: A 56-Patients' Cohort Study.

INTRODUCTION: Nuss procedure is the main reason for metal implants use by pediatric and thoracic surgeons. There is an ongoing debate on how to avoid allergic complications. Herein we describe our 8-year experience with systematic preoperative metal patch testing and our selective titanium bar use in Nuss procedure. MATERIALS AND METHODS: This is a single center retrospective observational cohort study of patients who underwent the Nuss procedure from 2013 to 2020. Preoperative metal patch testing was done in all cases. Criteria for titanium bar utilization were: a positive test for a major component of the stainless-steel bar; or a positive metal patch test and a positive history of atopy, food or metal allergy, or previous allergic reaction to an implant or device. RESULTS: In total, 56 patients were included. Most were male (91.1%) with a median age of 15.0 (13.0-22.0) years old. 19.6% had a positive preoperative metal patch test and 54.5% of these had no personal history of atopy. Stainless-steel bars were used in 27.3% of those patients and titanium bars were used in 72.7%. One patient had a documented minor allergy reaction. None of the 56 patients required early bar removal. CONCLUSION: Our study suggests that routine preoperative allergy testing and a judicious use of titanium bar are safe and avoid metal allergic complications.

Am I truly monolingual? Exploring foreign language experiences in monolinguals.

Monolingualism has typically been understood as a homogeneous phenomenon. The linguistic experiences of monolinguals are usually overlooked when analysing the impact of foreign language experiences on language processing and cognitive functioning. In this study, we analyse the linguistic experiences of 962 English-speaking individuals from the United Kingdom (UK) who identified as monolinguals. Through an online survey, we found that more than 80% of these monolinguals had learned at least one foreign language, dialect, or type of jargon. More than half of this 80% of monolinguals also used languages they had learned at some point in their lives. Moreover, nearly 40% of all the studied monolinguals confirmed that they had been passively exposed to foreign languages or dialects in their environment; approximately a fourth of these monolinguals who declared exposure to at least one foreign language (or dialect) confirmed that they also used these languages. Furthermore, activities that involved passive use of languages (i.e., activities that require reading or listening but do not require speaking or writing; e.g., watching TV) were occasionally carried out in foreign languages: around 26% of these monolinguals confirmed the passive use of more than one language. Lastly, around 58% of monolinguals who had visited one or more non-English-speaking countries declared the active use of foreign languages during their stay(s). These results suggest that the linguistic experiences of monolinguals from the UK often include exposure to and use of foreign languages. Moreover, these results show the need to consider the specificity of the monolingual language experience when analysing the impact of foreign languages on cognitive functioning, as differences in the language experiences of bilinguals also have divergent impacts on cognition. Lastly, monolingual experiences are different from bilingual experiences; therefore, existing questionnaires that evaluate language experiences should be adapted to capture the particular linguistic experiences of monolinguals.

Do GnRH Agonists Really Increase Body Weight Gain? Evaluation of a Multicentric Portuguese Cohort of Patients With Central Precocious Puberty.

Introduction: There are several concerns associated with gonadotropin-releasing hormone agonist (GnRHa) treatment for central precocious puberty (CPP), such as obesity and changes in body mass index (BMI). We aimed to investigate whether any anthropometric differences exist and if they persist over time. Methods: We conducted an observational study of Portuguese children (both sexes) diagnosed with CPP between January 2000 and December 2017, using a digital platform, in order to analyze the influence of GnRHa treatment on BMI-SD score (BMI-SDS). Results: Of the 241 patients diagnosed with CPP, we assessed 92 patients (8% boys) in this study. At baseline, 39% of the patients were overweight. BMI-SDS increased with treatment for girls but then diminished 1 year after stopping GnRHa therapy (p = 0.018). BMI-SDS variation at the end of treatment was negatively correlated with BMI-SDS at baseline (p < 0.001). Boys grew taller and faster during treatment than did girls (p < 0.001), and therefore, their BMI-SDS trajectory might be different. Conclusions: This study showed an increase of body weight gain during GnRHa treatment only in girls, which reversed just 1 year after stopping treatment. The overall gain in BMI-SDS with treatment is associated with baseline BMI-SDS.

ULTRASOUND-GUIDED CENTRAL LINE INSERTION IN CHILDREN: HOW MUCH IMAGING IS REALLY NEEDED?

INTRODUCTION: A recent survey revealed that most pediatric surgeons use intraoperative fluoroscopy and routine postoperative chest radiography for catheter tip location in central line placement. The aim of this study is to review all cases of ultrasound-guided central line placements and to evaluate the role of postoperative chest radiography. METHODS: Retrospective data analysis of children submitted to percutaneous central line insertion under ultrasound control over a 2-year period in a pediatric surgery department. Data collected included: age, indication for central venous access, catheter type, usage of intraoperative fluoroscopy and postoperative chest radiography, complications, and whether chest radiography dictated any catheter-related intervention. RESULTS: Fifty-five long-term central lines were successfully established in children aged between 1 month and 17 years. All patients had the catheter tip position confirmed either by intraoperative fluoroscopy (96%), chest radiography (85%) or both (82%). Catheter tip overlying the cardiac silhouette (right atrium) on chest radiography was reported in 4 cases; these findings led to no change in catheter positioning or other catheter-related intervention. There were no catheter-related complications. CONCLUSIONS: Percutaneous central line insertion under US-control is safe and effective even in small children. Post- operative chest radiography did not dictate any modification of catheter tip positioning after central line placement with ultrasound and fluoroscopic control or identified any other complication, thus should not be used routinely.

COMPLEX CHEST WALL DEFORMITY CAUSING CARDIAC ARREST: A PECULIAR PEDIATRIC CASE.

INTRODUCTION: Congenital chest wall deformities are common in children, causing self and parental concern mainly due to cosmesis. These defects rarely cause severe symptoms in patients. CASE REPORT: 11-year-old girl with a complex chest wall deformity and severe scoliosis causing progressive neurological loss of function. When mobilized to prone position for orthopedic surgery, she suffered sudden hypotension immediately followed by a cardiac arrest, that reverted after moving the child back to supine position. The cardiac arrest was interpreted as a result of a decrease in venous blood return secondary to heart and great vessels compression. She was then proposed and submitted to a modified Ravitch procedure with retrosternal metal bar placement in order to allow ventral positioning. This was successfully achieved, and the patient underwent scoliosis correction 3 months later. After more than a year of follow up, she reduced the need for non-invasive ventilation and tolerates prone positioning. CONCLUSION: This case report alerts medical community that beyond cosmesis concerns, severe chest wall deformities can cause life-threatening events if not correctly managed.