Modelling metabolic performance in paediatric obstructive sleep disordered breathing: A case-control study.

Paediatric obstructive sleep disordered breathing (OSDB) has a considerable impact on cardiovascular physiology, but the consequences on children's basal metabolism and response to exercise are far from being known. The objective was to propose model estimations for paediatric OSDB metabolism at rest and during exercise. A retrospective case-control analysis of data from children submitted to otorhinolaryngology surgery was performed. The heart rate (HR) was measured, while oxygen consumption (VO2 ) and energy expenditure (EE) at rest and during exercise were obtained using predictive equations. The results for the patients with OSDB were compared with controls. A total of 1256 children were included. A total of 449 (35.7%) had OSDB. The patients with OSDB showed a significantly higher resting heart rate (94.55 ± 15.061 bpm in OSDB vs. 92.41 ± 15.332 bpm in no-OSDB, p = 0.041). The children with OSDB showed a higher VO2 at rest (13.49 ± 6.02 mL min-1 kg-1 in OSDB vs. 11.55 ± 6.83 mL min-1 kg-1 in no-OSDB, p = 0.004) and a higher EE at rest (67.5 ± 30.10 cal min-1 kg-1 in OSDB vs. 57.8 + 34.15 cal min-1 kg-1 in no-OSDB, p = 0.004). At maximal exercise, patients with OSDB showed a lower VO2 max (33.25 ± 5.82 mL min-1 kg-1 in OSDB vs. 34.28 ± 6.71 in no-OSDB, p = 0.008) and a lower EE (166.3 ± 29.11 cal min-1 kg-1 in OSDB vs. 171.4 ± 33.53 cal min-1 kg-1 in no-OSDB, p = 0.008). The VO2 /EE increment with exercise (Δ VO2 and Δ EE) was lower in OSDB for all exercise intensities (p = 0.009). This model unveils the effect of paediatric OSDB on resting and exercise metabolism. Our findings support the higher basal metabolic rates, poorer fitness performance, and cardiovascular impairment found in children with OSDB.

Can Denosumab cure giant cell tumors of the spine? A case report and literature review.

BACKGROUND: Bone giant cell tumors, although benign, may be locally aggressive and cause severe morbidity; in some cases, they can also disseminate at distance and cause death. Denosumab has been approved to treat unresectable bone giant cell tumors or when surgery is likely to result in severe morbidity. Furthermore, its curative potential has been recently suggested. CASE: An 18-year-old girl presented with a spinal giant cell tumor at T9. Neo-adjuvant denosumab was administered for 9 months with great clinical and analytical tolerance. A posterior left T9 costo-transversectomy and vertebral body curettage was performed and the spine stabilized. Interestingly, histopathology examination of the surgical specimens found no evidence of tumoral cells. Denosumab was reinstated until completion of 12 months of treatment. CONCLUSION: Denosumab has an important but still limited role in the treatment of spinal giant cell tumors. Here, it resulted in complete histological resolution of the tumor, potentially widening its applicability from a strictly neo-adjuvant to a curative role.

Cost of asthma in children: A nationwide, population-based, cost-of-illness study.

BACKGROUND: Childhood asthma is very prevalent and costs can be high, especially in severe disease. This study aimed to estimate the cost of asthma in Portuguese children and the variations by level of asthma control. METHODS: A nationwide, population- and prevalence-based cost-of-illness study with a societal perspective was conducted. We measured direct and indirect costs using a bottom-up approach and a human capital method, respectively, for 208 children (<18 years), from two national repositories. Generalized linear modelling for analysis of asthma costs' determinants and sensitivity analysis to assess uncertainty were performed. RESULTS: The mean annualized asthma cost per child was €929.35 (95% CI, 809.65-1061.11): €698.65 (95% CI, 600.88-798.27) for direct costs and €230.70 (95% CI, 197.36-263.81) for indirect costs. Extrapolations for the Portuguese children amounted to €161 410 007.61 (95% CI, 140 620 769.55-184 293 968.55) for total costs. Direct costs represent 75.2% with the costliest domain (51.1% of total costs) being the healthcare service use: 20.7% for scheduled medical visits and 30.4% for acute asthma care-non-scheduled medical visits (7.9%, €12 766 203.20), emergency department visits (11.7%, €18 932 464.80) and hospitalizations (10.8%, €17 406 946.00). Children with partly controlled and uncontrolled asthma had higher mean costs per year (adjusted coefficients: 1.46 [95% CI, 1.12-1.90] and 2.25 [95% CI, 1.56-3.24], respectively). CONCLUSIONS: Costs of childhood asthma are high (0.9% of the healthcare expenditures in Portugal). Direct costs represented three-fourth of total costs, mainly related to the use of healthcare services for acute asthma care. Policies and interventions to improve asthma control and reduce acute use of healthcare services have the potential to reduce asthma costs.

A multinational and multidisciplinary approach to treat CHD in paediatric age in Angola: initial experience of a medical-surgical centre for children with heart disease in Angola.

BACKGROUND: Epidemiological patterns of cardiac disease differ between developed countries and African nations. Despite the collaborative efforts of developed countries, several obstacles hinder the implementation of successful programmes for the management of children with heart disease in Africa. Materials and methods This study is a retrospective analysis of a bi-national two-institution partnership programme for the treatment of children with congenital and acquired heart disease. In April, 2011, a continuous medical-surgical programme was inaugurated at Clínica Girassol in Luanda. The main goals were to initiate permanent and local delivery of services while training local teams, allowing autonomous medical and surgical management of children with heart disease. RESULTS: Between April, 2011 and August, 2015, a total of 1766 procedures were performed on 1682 children. Of them, 1539 had CHD and 143 had acquired heart disease; 94 children underwent interventional treatment. A total of 1672 paediatric surgeries were performed on 1588 children: 1087 (65%) were performed with extracorporeal circulation and 585 (35%) were off-pump. The age distribution of the children was 4.5% (n=76) neonatal, 40.4% (n=675) between 30 days and 1 year, and 55.1% (n=921) over 1 year. There were 76 re-operations (4.5%) due to complications. The 30-day mortality rate was 4.2% (71 patients). Education-wise, several Angolan medical and surgical specialists were trained, allowing near-autonomous cardiac care delivery in children with heart disease. CONCLUSION: An innovative cooperation model between a European and an African centre based on permanent delivery of care and education allowed for effective training of local teams and treatment of children with heart disease in their own environment.

Asthma-like symptoms, diagnostic tests, and asthma medication use in children and adolescents: a population-based nationwide survey.

OBJECTIVE: This study aimed to estimate the prevalence of asthma-like symptoms, current asthma (CA), asthma diagnostic tests, and inhaled medication use in a nationwide pediatric population (<18 years). METHODS: Pediatric-specific data from a cross-sectional, population-based telephone survey (INAsma study) in Portugal were analyzed. CA was defined as lifetime asthma and (1) wheezing, (2) waking with breathlessness, or (3) asthma attack in the previous 12 months, and/or (4) taking asthma medication at the time of the interview. RESULTS: In total, 716 children were included. The prevalence of asthma-like symptoms was 39.4% [95% confidence interval (95% CI): 35.7-43.3]. The most common symptoms were waking with cough (30.9%) and wheezing (19.1%). The prevalence of CA was 8.4% (95% CI: 6.6-10.7). Among children with CA, 79.9% and 52.9% reported prior allergy testing and pulmonary function testing (PFT), respectively. Inhaled medication use in the previous 12 months was reported by 67.6% (reliever inhalers, 40.1%; controller inhalers, 41.5%). Those who only used inhaled reliever medications experienced more asthma attacks [odds ratio (OR): 2.69]. Significantly fewer children with CA living in rural areas than those living in urban areas had undergone PFT or used inhaled medication (OR: 0.06 for PFT, 0.20 for medication]. CONCLUSIONS: The prevalence of CA in the Portuguese pediatric population was 8.4%. Only half of children with CA had ever undergone PFT; more than half did not use controller inhalers, and those who only used reliever inhalers reported more asthma attacks. These findings suggest that asthma management has been substandard, mainly in rural areas.

Submitral aneurysm in children.

BACKGROUND: We report a surgical series of submitral aneurysm in children. METHODS: Between March 2011 and December 2015, eight consecutive patients less than 18 years old with submitral aneurysm underwent surgical correction. RESULTS: Six patients were female, the mean age was 7 ± 3.8 years old, and mean weight was 21.4 kg. Six patients were in NYHA functional class III or IV. Six patients underwent repair via a transatrial approach, another with a transatrial combined with transaneurysmal approach, and another with a transventricular approach. There were no in-hospital deaths but one 30-day mortality. One patient required reoperation. Two patients required mitral valve replacement. At discharge, one patient had severe and another had moderate mitral regurgitation. The mean follow-up time was 26.4 months and five patients were alive. No reintervention was required. CONCLUSIONS: Submitral aneurysm is not restricted to adults. Heart failure is the commonest clinical presentation in the pediatric age. The transatrial approach is feasible, safe, and associated with good short-term results. The mitral valve can be preserved in the majority of cases.

Asthma control in children is associated with nasal symptoms, obesity, and health insurance: a nationwide survey.

BACKGROUND: This study aimed to estimate the prevalence of asthma control and determinants of poor control in the Portuguese pediatric population (<18 years); secondarily, we described asthma-related healthcare services and medication use. METHODS: Data of 98 children with current asthma, from the second phase of a nationwide population-based telephone survey (INAsma study), were analyzed. Asthma control definition was based on GINA criteria, grouping partially controlled and uncontrolled asthma as 'not-controlled asthma' (NCA). We used multivariate logistic regression to study factors associated with NCA and with unscheduled medical visits for asthma. RESULTS: About half of the children had NCA (49%, 95% CI 39-59%). In the multivariate model, risk factors for NCA were as follows: substantial nasal symptoms (a OR 6.80), overweight/obesity (a OR 3.44), and not having health insurance (a OR 3.78). All the children with NCA had nasal symptoms, and the lack of asthma control was also associated with the increasing number of nasal symptoms (p < 0.001). In the previous year, 90% (95% CI 84-96%) of children with current asthma had healthcare visits and 67% (95% CI 58-77%) used medication for asthma. The risk of unscheduled medical visits was higher in children with nasal symptoms (a OR 3.63) and in those without health insurance (a OR 2.79), and lower in adolescents (a OR 0.19). CONCLUSIONS: Half of the children with asthma were poorly controlled. Nasal symptoms and obesity are important determinants of asthma control. Children without health insurance are at greater risk of poor asthma outcomes; this association is reported for the first time in a European country.

Mitro-aortic aneurysms in children: single-centre experience and review of the literature.

OBJECTIVES: This publication aims to report the cases of four children with pseudoaneurysm of the mitral-aortic intervalvular fibrosa and carry out a review of the literature. BACKGROUND: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a very rare anomaly in children. It can be either congenital or acquired, namely, after bacterial endocarditis or cardiac trauma. This pathology does not usually cause specific symptoms but its outcome may be potentially fatal. METHODS: We report the cases of four patients presenting with pseudoaneurysm of the mitral-aortic intervalvular fibrosa, referred for treatment in a paediatric cardiology clinic. Patient clinical notes were retrospectively reviewed for aetiology, clinical presentation, diagnostic work-up, surgical treatment, and follow-up. Literature on the subject was extensively reviewed. RESULTS: In three patients, pseudoaneurysm of the mitral-aortic intervalvular fibrosa was acquired, being secondary to bacterial endocarditis in two cases and establishing after mitral surgery in another case. The remaining patient had a "congenital" aetiology - no other cause could be traced. The diagnosis was achieved by transthoracic echocardiography for all patients, and confirmed in all by trans-oesophageal echocardiography, to better define morphological details and to access flow into the aneurysmal formation. All patients were submitted to corrective cardiac surgery. Of the patients, three survived and were cured by surgery, staying asymptomatic, and one died after repeated interventions, for persistent endocarditis. CONCLUSIONS: Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare but potentially fatal anomaly. In our experience, surgical cure was achieved for the majority of the cases, except for a case for which infection could not be locally eradicated, leading to multiple reinterventions.

Telemonitoring of pediatric asthma in outpatient settings: A systematic review.

Telemonitoring technologies are rapidly evolving, offering a promising solution for remote monitoring and timely management of asthma acute episodes. We aimed to describe current pediatric asthma telemonitoring technologies. A systematic review was conducted until September 2023 on Medline, Scopus, and Web of Science. We included studies of children (0-18 years) with asthma or recurrent wheezing whose respiratory condition was telemonitored outside the healthcare setting. A narrative synthesis was performed. We identified 40 telemonitoring technologies described in 40 studies. The more frequently used technologies for telemonitoring were mobile applications (n = 21) and web-based systems (n = 14). Telemonitoring duration varied between 2 weeks and 32 months. Data collection included asthma symptoms (n = 30), patient-reported outcome measures (PROMs) (n = 11), spirometry/peak flow readings (n = 20), medication adherence (n = 17), inhaler technique (n = 3), air quality (n = 2), and respiratory sounds (n = 2). Both parents and children were the technology target users in most studies (n = 23). Technology training was reported in 23 studies of which 3 provided ongoing support. Automatic feedback was found in 30 studies, mostly related with asthma control. HCP were involved in data management in 27 studies. Technologies were tested in samples from 4 to 327 children, with most studies including school-aged children and/or adolescents (n = 38) and eight including preschool children. This review provides an overview of existing technologies for the outpatient telemonitoring of pediatric asthma. Specific technologies for preschool children represent a gap in the literature that needs to be specifically addressed in future research.

A study of multiple deliveries in Portugal: indications of an Iberian Peninsula pattern.

Information on multiple deliveries with regard to Portugal is scarce. Based on data provided by the Portuguese Institute of Statistics (INE), the rates for double and triple deliveries were calculated since 1930. The results obtained show for twins a uniform temporal pattern up to the 1970s. At this time rates decreased, but later they gradually recovered, reaching their maximum level in 2010. For triplets, the highest rates occurred between 1999 and 2002. For the period 1988-2011, the rates of multiple deliveries were related to a set of variables recorded in the INE database on live births. Significant differences (p < .001) between simple and multiple deliveries were obtained for maternal age, parity and marital status. Considering the year when the delivery occurred, significant differences (p < .001) persisted for maternal age regardless of the year. For the type of mating, significance was consistently found since the year 2002 (either by using the marital or the cohabitation criteria), and for parity since 2003. With regard to territorial variation, throughout seven periods between 1930 and 2011, the rates among the 20 administrative Portuguese territories, including the two insular districts of Açores and Madeira, were mostly stable for twinning rates, with a minimum level in 1970-1989. Regarding triplets, the greatest inter-district variation was found after 1980. The results of the Portuguese study on multiple deliveries are interpreted in the context of the Iberian Peninsula based on findings reported for Spain.

Ewing Sarcoma Developed at the Site of Previous Mast Cell Proliferation.

KIT gene mutations in Ewing sarcomas are rare; however, they are much more frequent in other neoplasms, namely mastocytosis. We describe a case of an adult male with a one-year duration of recurrent episodes of pain, swelling, and redness on the proximal phalanx of the third finger of his right hand. A core biopsy suggested a possible mastocytosis. After four years of recurrent episodes and worsening symptoms, an incisional biopsy revealed an Ewing sarcoma with a KIT gene mutation (M541L, on exon 10). KIT gene mutations with gain-of-function were identified in 2.6% of Ewing sarcomas. In this case, the detection of a KIT mutation in an Ewing sarcoma developed at the site of previous mast cell proliferation raises the hypothesis of a possible sarcomatous evolution of the original lesion. To the best of our knowledge, similar cases are not described in the current literature. This is also the first report describing the KIT M541L mutation (exon 10) in Ewing sarcoma.

Characteristics and Outcomes of COVID-19 Cancer Patients Admitted to a Portuguese Intensive Care Unit: A Case-Control Study.

Cancer patients appear to be a vulnerable group in the COVID-19 pandemic. This study aims to compare clinical characteristics and outcomes of cancer and non-cancer patients with COVID-19 admitted to the ICU. All COVID-19 cancer patients (cases) admitted to a Portuguese ICU between March 2020 and January 2021 were included and matched on age, sex and comorbidities with COVID-19 non-cancer patients (controls); 29 cases and 29 controls were enrolled. Initial symptoms were similar between the two groups. Anemia was significantly superior among cases (76% vs. 45%; p = 0.031). Invasive mechanical ventilation (IMV) need at ICU admission was significantly higher among cases (48% vs. 7%; odds ratio (OR) = 12.600, 95% CI: 2.517-63.063, p = 0.002), but there were no differences for global need for IMV during all-length of ICU stay and mortality rates. In a multivariate model of logistic regression, the risk of IMV need at ICU admission among cases remained statistically significant (adjusted OR = 14.036, 95% CI: 1.337-153.111, p = 0.028). Therefore, compared to critical non-cancer patients, critical cancer patients with COVID-19 had an increased risk for IMV need at the moment of ICU admission, however, not for IMV need during all-length of ICU stay or death.

Preservation of fertility in female patients with hematologic diseases.

Recent developments of assisted reproduction techniques turned possible to avoid the infertility consequences of oncologic treatments, but fertility preservation (FP) has been somewhat neglected in women with hematologic diseases undergoing gonadotoxic treatments. For these specific cases, the current options for FP include the cryopreservation of embryos, mature oocytes and ovarian tissue, and oocyte in-vitro maturation. We intend to make patients and clinicians aware of this important and relevant issue, and provide hematologists, assisted reproduction physicians and patients, with updated tools to guide decisions for FP. The physicians of the units responsible for female FP should always be available to decide on the best-individualized FP option in strict collaboration with hematologists. With a wide range of options for FP tailored to each case, a greater level of training and information is needed among clinicians, so that patients proposed to gonadotoxic treatments can be previously advised for FP techniques in hematological conditions. ABBREVIATED ABSTRACT: Recent developments of assisted reproduction techniques turned possible to preserve the fertility of women with hematologic diseases undergoing gonadotoxic treatments. Current options for fertility preservation in women with hematologic diseases are presented. It is imperative to offer fertility preservation to all women before starting any gonadotoxic treatment and in some cases after treatment. Fertility preservation methods enable to later achieve the desired pregnancy.

Respiratory and non-respiratory outcomes of bronchopulmonary dysplasia in adolescents: A systematic review.

BACKGROUND: There is lack of evidence synthesis on the global consequences of bronchopulmonary dysplasia (BPD) in adolescence. AIM: Assess the impact of bronchopulmonary dysplasia on respiratory and non-respiratory outcomes in adolescents. METHODS: A systematic review of studies assessing the outcomes of adolescents aged 10 to 19 years-old with BPD was conducted. We independently screened studies published until 6th March 2023 in PubMed® and Scopus® databases. Data on methodologic design, sample descriptive and findings were extracted from each study. Risk of bias was assessed using quality assessment tools. RESULTS: Thirty-one studies were included. Adolescents with a history of BPD present with more respiratory symptoms (wheezing, respiratory exacerbations, need for respiratory medication) and twenty-five studies showed a reduction in pulmonary function, with varying impact according to BPD severity and no differences before and after the surfactant era. Spirometry evaluation throughout the years is not consensual, but methacholine and salbutamol response in BPD groups is increased compared to non-BPD groups. Markers of eosinophilic airway inflammation are not increased as in asthma patients. Exercise potential is identical, but data regarding physical capacity and activity are inconsistent. More frequent radiologic abnormalities translate into higher high-resolution computed tomography scores, with linear (72.2 %) and triangular subpleural opacities (58.3 %) as the most common findings. There is a higher risk for special needs in education, but quality of life seems to be equal to non-BPD adolescents. CONCLUSIONS: BPD negatively impacts both pulmonary and non-pulmonary outcomes in adolescents.

Symptoms of anxiety and depression in patients with persistent asthma: a cross-sectional analysis of the INSPIRERS studies.

OBJECTIVES: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms. METHODS: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built. RESULTS: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression. CONCLUSION: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.

The Role of ROS as a Double-Edged Sword in (In)Fertility: The Impact of Cancer Treatment.

Tumor cells are highly resistant to oxidative stress resulting from the imbalance between high reactive oxygen species (ROS) production and insufficient antioxidant defenses. However, when intracellular levels of ROS rise beyond a certain threshold, largely above cancer cells' capacity to reduce it, they may ultimately lead to apoptosis or necrosis. This is, in fact, one of the molecular mechanisms of anticancer drugs, as most chemotherapeutic treatments alter redox homeostasis by further elevation of intracellular ROS levels or inhibition of antioxidant pathways. In traditional chemotherapy, it is widely accepted that most therapeutic effects are due to ROS-mediated cell damage, but in targeted therapies, ROS-mediated effects are mostly unknown and data are still emerging. The increasing effectiveness of anticancer treatments has raised new challenges, especially in the field of reproduction. With cancer patients' life expectancy increasing, many aiming to become parents will be confronted with the adverse effects of treatments. Consequently, concerns about the impact of anticancer therapies on reproductive capacity are of particular interest. In this review, we begin with a short introduction on anticancer therapies, then address ROS physiological/pathophysiological roles in both male and female reproductive systems, and finish with ROS-mediated adverse effects of anticancer treatments in reproduction.