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.

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.

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.

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.

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.

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.

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.

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.

Use of recombinant human deoxyribonuclease in pediatric intensive care unit - a single-center experience.

OBJECTIVE: Dornase alfa (rhDNase) reduces the viscosity of purulent sputum in the lungs. The use in patients with cystic fibrosis (CF) is proven. However, the evidence of its applicability to other conditions is limited. This study aims to present the authors' experience with the use of rhDNase in non-CF patients admitted to the Pediatric Intensive Care Unit (PICU). At the study center, rhDNase was used during flexible bronchoscopies in 24 cases, of which 20 (83%) had atelectasis and seven (29%) were admitted to PICU. Four patients (57%) were on invasive mechanical ventilation (MV). CASE DESCRIPTION: Two cases of daily rhDNase administration at PICU are presented: patient A was an 8-year-old boy admitted with septic shock and acute respiratory distress syndrome (ARDS). The patient required mechanical ventilation with aggressive settings and experienced several clinical complications. On D50, he started rhDNase treatment with an improvement in FiO2, PaCO2 and PaO2/FiO2 ratio according to radiologic findings. He was extubated on D23 of treatment.Patient B was a 17-month-old girl admitted with a convulsive status epilepticus who experienced respiratory complications (infectious and barotrauma) with ARDS, requiring aggressive ventilation. She initiated rhDNase treatment on D60. During the treatment an improvement in FiO2, PaO2/FiO2 ratio and a tendency of PaCO2 decrease were found. She had radiological improvement. No complications were described. COMMENTS: RhDNase may be a helpful and safe tool to use in PICU prolonged intubated patients with ventilator-induced lung injury. Further studies are needed to assess and propose valid indications.

Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30-35 kg/m2). METHODS: DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass-RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. RESULTS: Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. CONCLUSIONS: This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. TRIAL REGISTRATION: ISRCTN53984585.

Feasibility and Acceptability of an Asthma App to Monitor Medication Adherence: Mixed Methods Study.

BACKGROUND: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). METHODS: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. RESULTS: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). CONCLUSIONS: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

Profiling Persistent Asthma Phenotypes in Adolescents: A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies.

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.

Monitoring Adherence to Asthma Inhalers Using the InspirerMundi App: Analysis of Real-World, Medium-Term Feasibility Studies.

Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support. Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use. Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app ≥30 days was used as the cut-off for higher app use. Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25-P75) 16-36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3-45] days, translated on a median use rate of 15 [3-38]%. Median inhaler adherence assessed through the app was 34 [4-73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6-83]% and 43 [3-73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen. Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.

COMPLICATED PNEUMONIA WITH EMPYEMA CAUSED BY STREPTOCOCCUS ANGINOSUS IN A CHILD.

OBJECTIVE: To highlight the pathogenicity of Streptococcus anginosus, which is rare in pediatric patients, but can cause severe infections that are known to have a better outcome when treated early with interventional procedures and prolonged antibiotic therapy. CASE: description: The patient is a 6-year-old boy with global developmental delay, examined in the emergency room due to fever and respiratory distress. The physical examination and diagnostic workout revealed complicated pneumonia with empyema of the left hemithorax; he started antibiotic therapy and underwent thoracic drainage. Pleural fluid cultures grew Streptococcus anginosus. On day 11, the child had a clinical deterioration with recurrence of fever, hypoxia, and respiratory distress. At this point, considering the causative agent, he was submitted to video-assisted thoracoscopic decortication, with good progress thereafter. COMMENTS: Streptococcus anginosus is a commensal bacterium of the human oral cavity capable of causing severe systemic infections. Although reports of complicated thoracic infections with this agent are rare in the pediatric population, they have been increasing in adults. Streptococcus anginosus has a high capacity to form abscess and empyema, requiring different therapeutic approaches when compared to complicated pneumonia caused by other agents.

Maxillary mesenchymal chondrosarcoma leading to a diagnosis of Li-Fraumeni syndrome.

Mesenchymal chondrosarcoma (MCS) is a rare histological variant of chondrosarcoma, with aggressive behaviour. Due to the unique nature of this disease, management strategies are not well established. Li-Fraumeni syndrome (LFS) is a rare cancer predisposition syndrome with a wide tumour spectrum, associated with TP53 germline mutations. We report a case of MCS of the maxilla, treated with surgical excision and adjuvant chemotherapy, in a patient with a past medical history of choroid plexus papilloma and a family history of early age first-degree cervical uterine cancer, that led to the clinical suspicion of a cancer predisposition syndrome and the subsequent diagnosis of LFS. This is the first MCS described in a LFS case. It demonstrates that adjuvant chemotherapy should be considered, in conjunction with surgical excision, in MCS and that cancer predisposition syndromes should be suspected in patients with multiple neoplasms and a strong family history of cancer.

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.