Use of elexacaftor/tezacaftor/ivacaftor combination in pregnancy.

INTRODUCTION: Management of cystic fibrosis has recently stepped forward with the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, although data on potential adverse effects are lacking for many categories of patients, such as pregnant women. METHODS: We report one of the first reports on the outcome of pregnancy in a woman treated with Elexacaftor/Tezacaftor/Ivacaftor during the second and third trimester of pregnancy, showing a significant improvement of respiratory status, compared with the first trimester when the medication was discontinued due to unknown and, therefore, potential teratogenic effects. Also, we performed the review of the existing literature on the topic. RESULTS: The course of pregnancy was uneventful, with reference to major obstetric complications, and the patient delivered a healthy neonate. These results were similar to those coming from other short series of pregnant women affected by cystic fibrosis and treated with CFTR modulators during pregnancy. CONCLUSIONS: Thus, despite the lack of evidence on the topic, the use of Elexacaftor/Tezacaftor/Ivacaftor in pregnancy seems to be apparently not associated with major adverse events, thus opening optimistic scenarios in terms of management of these patients.

Use of POCUS for the assessment of dehydration in pediatric patients-a narrative review.

In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions and pleural and pericardial effusions, but less to evaluate fluid depletion. The main aim of this review is to analyze the current literature on the assessment of dehydration in pediatric patients by using POCUS. The size of the inferior vena cava (IVC) and its change in diameter in response to respiration have been investigated as a tool to screen for hypovolemia. A dilated IVC with decreased collapsibility (< 50%) is a sign of increased right atrial pressure. On the contrary, a collapsed IVC may be indicative of hypovolemia. The IVC collapsibility index (cIVC) reflects the decrease in the diameter upon inspiration. Altogether the IVC diameter and collapsibility index can be easily determined, but their role in children has not been fully demonstrated, and an estimation of volume status solely by assessing the IVC should thus be interpreted with caution. The inferior vena cava/abdominal aorta (IVC/AO) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS could be a valuable supplementary tool in the assessment of dehydration in several clinical scenarios, enabling rapid identification of life-threatening primary etiologies and helping physicians avoid inappropriate therapeutic interventions.   Conclusion: POCUS can provide important information in the assessment of intravascular fluid status in emergency scenarios, but measurements may be confounded by a number of other clinical variables. The inclusion of lung and cardiac views may assist in better understanding the patient's physiology and etiology regarding volume status. What is Known: • In pediatric practice, POCUS (point-of-care ultrasound) has been mostly implemented to recognize lung conditions (like pneumonia and bronchiolitis) and pleural and pericardial effusions, but less to evaluate fluid depletion. • The size of the IVC (inferior vena cava) and its change in diameter in response to respiration have been studied as a possible screening tool to assess the volume status, predict fluid responsiveness, and assess potential intolerance to fluid loading. What is New: • The IVC diameter and collapsibility index can be easily assessed, but their role in predicting dehydration in pediatric age has not been fully demonstrated, and an estimation of volume status only by assessing the IVC should be interpreted carefully. • The IVC /AO(inferior vena cava/abdominal aorta) ratio may be a suitable parameter to assess the volume status in pediatric patients even though there is a need to define age-based thresholds. A combination of vascular, lung, and cardiac POCUS can be a valuable supplementary tool in the assessment of intravascular volume in several clinical scenarios.

Has Anything Changed in the Frequency of Emergency Department Visits and the Profile of the Adolescent Seeking Emergency Mental Care during the COVID-19 Pandemic?

We described changes caused by the COVID-19 pandemic in the frequency of Emergency Department (ED) visits for mental health disorders (MHDs) in adolescents on a wider temporal range-that is, not just "the waves" of the pandemic-and characterized the profile of the adolescent seeking emergency psychiatric care. We conducted a retrospective longitudinal study by analyzing ED visits for MHDs from 10 March 2019 to 10 March 2021. A total of 1407 ED visits for MHDs were registered: 702 in the pre-COVID-19 and 707 in the COVID-19 period. The cumulative incidence of ED visits for MHDs was 1.22% in the pre-COVID-19 period and 1.77% in the COVID-19 period, with a statistically significant difference (p < 0.001). The principal characteristics of the adolescent with MHDs during the pandemic period: the odds of comorbidities decreased by 26% (p = 0.02), and the odds of transfer from other hospitals decreased by 71% (p < 0.001), while the odds of the ED presentation as first psychiatric episode were twice greater (p < 0.001). The risk of hospitalization increased by 54% (p = 0.001). Regarding psychopathology, the likelihood of attempted suicide increased by 74% during the pandemic (p = 0.02). The rate of mood and eating disorders grew significantly during the COVID-19 pandemic period (p = 0.005 and p = 0.031, respectively). Monitoring ED visits for MHDs and understanding changes in the profile of adolescents presenting to ED helps to reinforce the role of ED in identifying special clinical needs for these vulnerable patients in case of a future public health crisis.

The psychophysical impact of COVID-19 lockdown on pediatric patients with rheumatological disease.

BACKGROUND: COVID-19 was declared a pandemic on 11 March 2020 and unprecedented containment measures were taken to limit its spreading. These exceptional measures may have an impact on the mental health of the population. OBJECTIVES: We hypothesize that children with the rheumatological chronic disease might be a population at higher risk of psychological distress. DESIGN: This study evaluated the psychological effect of social distancing in pediatric rheumatological patients and its possible correlation with disease relapse. SETTING: Pediatric patients diagnosed with juvenile idiopathic arthritis (JIA) were included in the study. SUBJECTS AND METHODS: They completed the Multidimensional Anxiety Scale for Children (MASC-2) to assess anxious symptoms, the Children Depression Inventory Self Report (CDI-2 SR) for depression symptoms and a semi-structured questionnaire to collect their activities. Their parents completed the Children Depression Inventory 2 Parent (CDI-2 P). RESULTS: The MASC-2 test showed high values in anxiety factors. The CDI-2 SR test showed high values for Ineffectiveness and Functional Problems. The CDI-2 P showed high values for Emotional Problems factor. All the patients with high level of depression were females. The result is that those who take therapy were younger, have reduced values in Functional Problems and in Social Anxiety. 47% of the sample had disease relapse. CONCLUSIONS: During the COVID-19 period of isolation, in patients with JIA, there was an increase in anxious and depressive symptoms in female adolescents, a tendency to disease relapse, despite generally good compliance to therapy. Those under treatment were younger and showed reduced values in Functional Problems, Social Anxiety, and Humiliation/Rejection. LIMITATIONS: Limited number of patients to whom questionnaires could be distributed.

Neurological and psychological effects of long COVID in a young population: A cross-sectional study.

Aim: We evaluated the long-term clinical status of pediatric patients after testing positive for COVID-19. We hypothesized that there are similar symptoms to those that have been described in adults and children and that pediatric patients with neurophysiologic symptoms still present 3-5 months after infection have psychological consequences that interfere with their adaptive functioning. Method: We recruited 322 COVID-19-positive pediatric patients, between 1.5 and 17 years old, from the outpatient clinic for COVID-19 follow-up. Neurological symptoms were analyzed at onset, after 1 month, and after 3-5 months. A psychological assessment with standardized questionnaires was also conducted to determine the impact of the disease. Results: At the onset of COVID-19, 60% of the total sample exhibited symptoms; this decreased after 1 month (20%) but stabilized 3-5 months after disease onset (22%). Prevailing long-COVID neurological symptoms were headache, fatigue, and anosmia. In the 1.5-5-year-old subgroup, internalizing problems emerged in 12% of patients. In the 6-18-year-old subgroup, anxiety and post-traumatic stress showed significant associations with neurological symptoms of long COVID. Conclusions: These data demonstrate that long COVID presents various broad-spectrum symptoms, including psychological and long-lasting cognitive issues. If not treated, these symptoms could significantly compromise the quality of life of children and adolescents.

COVID-19 Lockdown Impacts Among Patients with Cystic Fibrosis: An Italian Regional Reference Centre Experience.

BACKGROUND: Coronavirus pandemic has influenced our society with social distancing and management of chronic disease such as cystic fibrosis (CF). During the Italian lockdown from March to May 2020, CF patients reduced the number of outpatient visits, limited social interactions and spent more time at home. The aim of this study is to evaluate the impact of the lockdown on body mass index (BMI) and lung function tests on CF patients. METHODS: We retrospectively reviewed clinical data about 111 CF patients followed in our Regional Cystic Fibrosis Reference Centre (Policlinico Umberto I, Rome) according to two periods: pre-lockdown (from October 2019-March 2020) and post-lockdown (from May 2020-October 2020). We collected data on nutritional (BMI and body weight) and lung function status; we chose the best values of the 'pre-lockdown' and 'post-lockdown' period for each patient. Patients were divided into 3 groups according to FEV1 value (Forced Expiratory Volume in the 1st second): group 1 (FEV1 <40%), group 2 (FEV1 40-70%), group 3 (FEV1 >70%). All patients received a telephone interview asking for the number of hours per week devoted to physical activity, number of pulmonary acute exacerbations and subjective evaluation of adherence to medical therapy, respiratory physiotherapy and diet, during the two periods. RESULTS: Comparing weight, BMI and respiratory function between pre and post lockdown periods, we noticed an increase in weight during among overall patients. Male patients improved weight, BMI, FEF 25-75% (Forced Expiratory flow between 25% and 75% of vital capacity) and Tiffenau index more than female patients. The most severely compromised patients (group 1), showed a significant loss of both weight and BMI. Instead, patients with moderate respiratory function (group 2) showed a significant increase of both weight and BMI and a slightly reduced CVF (Forced Vital capacity). We found no differences among patients with good respiratory function (group 3). Comparing each clinical sub-groups, we noticed a significative improvement of weight (p = 0.018) and BMI (p = 0.030) among patients with moderate respiratory function compared to patients with compromised respiratory function. During lockdown, patients reported less physical activity, no variation in food amount and composition, more adherence to therapy (43%) and more consistent daily respiratory physiotherapy (47.6%). CONCLUSIONS: Lockdown period had benefit among CF patients in terms of weight in particular in male patient. The greatest benefit on nutritional state was observed in patients with moderate reduction of respiratory function. In addition, we noted a stabilization and sometimes a slight improvement of lung function, instead of a continuous and steady decline that is normally observed in CF patients. These beneficial effects are slight but significative, bearing in mind the general worsening that CF patients experience annually.

Infant Cardiopulmonary Resuscitation Quality While Walking Fast: A Simulation Study.

OBJECTIVE: This study focuses on the characteristics (feasibility, resuscitation quality, and physical demands) of infant cardiopulmonary resuscitation (CPR) on the forearm during fast walking, performed by a trained lay rescuer. METHODS: Twenty-one university students from the infant education degree participated in a randomized crossover simulation study to compare a standard pediatric CPR versus a walking pediatric CPR with a manikin on the rescue forearm. Each rescuer performed 2 resuscitation tests of 2 minutes on the infant manikin. Cardiopulmonary resuscitation, physiological, and perceived effort variables were measured. RESULTS: The quality of chest compressions was higher in standard pediatric CPR than in walking pediatric CPR (72% vs 51%; P < 0.001) and overall CPR quality (59% vs 49%; P = 0.02). There were no differences between ventilation quality (47% vs 46%). Walking pediatric CPR presented a higher percentage of maximum heart rate (52% vs 69%; P < 0.001) and perceived exertion rate (2 vs 5; P < 0.001). Participants walked an average of 197 m during the test. CONCLUSIONS: In conclusion, pediatric walking CPR is feasible although it represents a slight quality decrease in a simulation infant CPR setting. The option "CPR while walking fast to a safe place" seems to be suitable in terms of safety both for the victim and the rescuer, as well as CPR quality in special circumstances.

Procedural analgesia with nitrous oxide at home for epidermolysis bullosa: A case report.

RATIONALE: Epidermolysis bullosa (EB) is an inherited disease characterized by fragile skin with painful blistering, which requires lifelong skin and wound care. This case report describes the use of inhaled nitrous oxide (N2O) for procedural pain control at home during wound care in a young man with severe dystrophic EB. To our knowledge, only 1 case was reported by Ingelmo et al in 2017 regarding the use of N2O at home in a 4-year-old-child. To date, no such attempt has been made in adult patients. PATIENT CONCERNS: Our patient was a 28-year-old man. Frequent blisters appear spontaneously, and are often preceded by erythema and itching. Patient required daily treatment daily consisting of lancing blisters with a needle and emptying them by compression. DIAGNOSES: Severe recessive dystrophic EB diagnosed at the time of delivery. INTERVENTIONS: Procedural pain control was managed by the auto-administration of an inhaled N2O and air gas mixture. OUTCOMES: Conscious sedation with N2O leads to beneficial effects, such as reduction in dressing duration, acute procedural pain, local antibiotic needing, medication memory, anxiety, anticipatory pain, and fatigue after the dressing session. LESSONS: N2O analgesia is safe and effective, resulting in a significant reduction in procedural pain and an improvement in the quality of life of patients and their caregivers.

Hemoperfusion with CytoSorb to Manage Multiorgan Dysfunction in the Spectrum of Hemophagocytic Lymphohistiocytosis Syndrome in Critically Ill Children.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by a state of hyperinflammation. Blood purification techniques can blunt the inflammatory process with a rapidly relevant nonselective effect on the cytokine storm, thus potentially translating into survival benefit for these patients. In this cohort, we evaluated the impact of hemoadsorption with CytoSorb combined with continuous kidney replacement therapy used as adjunctive therapy in 6 critically ill children with multiple organ dysfunction due to HLH. In our series, we found a reduction in inflammatory biomarkers in patients with HLH secondary to infection. Ferritin, one of the most important bedside biomarkers of HLH, showed a reduction in most of the treated patients. The same results were found measuring interleukin-6 and interleukin-10. The same patients showed hemodynamic stabilization measured by the Vasopressor-Inotropic-Score, and reduction in the organ disease score measured with the Pediatric Logistic Organ Dysfunction score. In our cohort, mortality was less than expected based on the Pediatric Index of Mortality 3 score at pediatric intensive care unit admission. Our study shows that hemoperfusion could be a valuable therapeutic option in HLH: stronger scientific evidence is needed to confirm our preliminary experience.

Breastfeeding in Pediatric Acute-Onset Neuropsychiatric Syndrome: An Italian Observational Study.

Objective: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a condition defined by sudden onset of obsessive-compulsive symptoms and/or severe eating restrictions, along with at least two other cognitive, behavioral, or neurological symptoms. Its pathogenesis is unknown but it seems triggered by infections, metabolic disturbances, and other inflammatory reactions. PANS represents a neurodevelopmental problem and infant feeding can play a role. Breast milk is the ideal food for infants and influences children's brain, cognitive, and socio-emotional development. Methods: We enrolled 52 children diagnosed with PANS. We interviewed their parents in order to investigate perinatal history, infant feeding, neurologic development, and confounding factors like socio-economic status and region of origin. We subgrouped PANS patients into three subsets: those who only received human milk (HMO), those who only received infant formula, and those who received mixed feeding. Results: The cohort is composed of 78.9% males, with a median age of 11 years (range 7-17). We found some neurodevelopmental problems (13.5%): walking disorders, ASD, ADHD, oppositional attitude, and delayed psychomotor development. We found scholar performance deficits (25%), including language problems like dysgraphia, dyslexia, and dyscalculia. The achievement of some milestones in the development of the infant is affected in 73.1% of cases. Breastfeeding is not homogeneously practiced in Italy because of social, economic, and cultural phenomena. The richest and the poorest families (100%) in the sample choose breastfeeding, probably with a different approach and for different reasons (awareness or need). In the group of PANS patients fed with HMO, compared to the rest of the patients, we registered fewer cases of growth problems (0 vs. 12.9%; p = 0.14), school performance problems or the need for school support (19.1% vs. 29%; p = 0.42), and a delay in the age of babbling/speaking (range 4-20 vs. 7-36 months; p = 0.066). Conclusion: This is the first study that investigates the role of breastfeeding in the development of PANS. Promoting breastfeeding is important in the general population and also in PANS patients because it has an important social and global health impact, also during adult life. Further studies with a bigger population are needed to investigate the mechanisms underlying PANS and the role that breastfeeding may play in their short- and long-term neurodevelopment.

Myoclonic Epilepsy: Case Report of a Mild Phenotype in a Pediatric Patient Expanding Clinical Spectrum of KCNA2 Pathogenic Variants.

We report on the rare case of a male toddler presenting with myoclonic epilepsy characterized by daily episodes of upward movements of the eyebrows, and myoclonic jerks of both head and upper limbs. In addition, the child showed speech delay, tremors, and lack of motor coordination. Next Generation Sequencing analysis (NGS) performed in trio revealed in the proband the c.889C>T de novo missense variant in the KCNA2 gene in heterozygous state. This is the first case of myoclonic epilepsy in a toddler due to a c.889C>T KCNA2 missense variant. The patient was treated with valproic acid and ethosuximide with a good clinical response. At 6 years old, follow-up revealed that the proband was seizure-free with tremors and clumsiness in movements. According to the literature, this case supports the correlation between myoclonic epilepsy and KCNA2 alterations. This evidence suggests that performing genomic testing including the KCNA2 gene in preschool patients affected by myoclonic epilepsy, especially when associated with delayed neurodevelopment. Our goal is to expand the phenotypical spectrum of this rare condition and adding clinical features following a genotype-first approach.

Inhaled sedation with sevoflurane in critically ill children during extracorporeal membrane oxygenation.

Sedation can be challenging in critically ill children. Inhaled anesthetics such as sevoflurane have proved to be useful in difficult or long-term sedation. However, its use in children out of the operating room is still limited and little is yet known about its use in patients undergoing ECMO with no previous reports in children. The objective is to assess the effectiveness and safety of sevoflurane during ECMO in two pediatric patients. Sedation was successfully achieved in both patients, and patients' contribution to breathing was possible even with deep sedation. There were not any side effects during sevoflurane treatment or after withdrawal.

Physiological demands of quality cardiopulmonary resuscitation performed at simulated 3250 meters high.

AIM: To analyse the effect of oxygen fraction reduction (O2 14%, equivalent to 3250 m) on Q-CPR and rescuers' physiological demands. METHODOLOGY: A quasi-experimental study was carried out in a sample of 9 Q-CPR proficient health care professionals. Participants, in teams of 2 people, performed 10 min CPR on a Laerdal ResusciAnne mannequin (30:2 compression/ventilation ratio and alternating roles between rescuers every 2 min) in two simulated settings: T21-CPR at sea level (FiO2 of 21%) and T14 - CPR at 3250 m altitude (FiO2 of 14%). Effort self-perception was rated from 0 (no effort) to 10 (maximum demand) points. RESULTS: Quality of chest compressions was good and similar in both conditions (T21 vs T14). However, the percentage of ventilations with adequate tidal volume was lower in altitude than at sea level conditions (35.9 ± 25.2% vs. 54.7 ± 23.2%, p = 0.035). The subjective perception of effort was significantly higher at simulated altitude (5 ± 2) than at sea level (3 ± 2) (p = 0.038). Maximum heart rate during the tests was similar in both conditions; however, mean oxygen saturation was significantly lower in altitude conditions (90.5 ± 2.5% vs. 99.3 ± 0.5%, p < 0.001). CONCLUSION: Although performing CPR under simulated hypoxic altitude conditions significantly increases the physiological demands and subjective feeling of tiredness compared to sea level CPR, trained rescuers are able to deliver good Q-CPR in such conditions, at least in the first 10 min of resuscitation.

Renal involvement and metabolic alterations in adults patients affected by cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is one of the most frequent genetic diseases and the median survival of these patients has improved in the last few decades, therefore it becomes necessary to evaluate the long-term complications as renal and cardiovascular risk factors. AIM OF THE STUDY: To evaluate the incidence, the manifestations of renal disease and the possible association with metabolic and endothelial dysfunction markers in the CF population. MATERIALS AND METHODS: We performed a cross-sectional, observational study on 226 CF patients. Clinical and laboratory instrumental parameters (metabolic, inflammatory and endothelial dysfunction markers) were evaluated. RESULTS: We showed 65 patients with chronic kidney disease (CKD) and 158 patients with a reduced value of forced expiratory volume in 1 s (FEV1), of which 58 patients with a severe reduction of FEV1. Moreover 28 patients had undergone lung transplantation and them had a significant lower estimated Glomerular Filtration Rate (eGFR) with respect to the non-transplanted patients (p < 0.001). We reported also a significant association between lower eGFR value and serum triglycerides, total cholesterol and low-density lipoproteins (LDL) (p = 0.005, p < 0.001, p = 0.040; respectively), with a significant negative correlation between eGFR and serum triglycerides (r = - 0.28; p < 0.01). Moreover we found a significant association between lower eGFR value and serum uric acid (SUA) (p = 0.005), while we did not found an association with 25-hydroxy-vitamin-D value, serum glucose and hemoglobin A1c levels. CONCLUSIONS: Our study showed a high prevalence of CKD in CF patients. Moreover we showed an increase of endothelial dysfunction and metabolic indexes in patients with reduced renal function, as SUA, serum triglycerides and LDL, suggesting the need for an early and complete screening of the main metabolic indexes to reduce cardiovascular risk and progression of renal damage, in particular in patients with lung transplant.

Focus on Cardiologic Findings in 30 Children With PANS/PANDAS: An Italian Single-Center Observational Study.

Objective: Cardiac involvement in PANS has not been clarified relying on the scientific literature available until today. It is known that streptococcal infections play a role in the etiology of a great number of diseases including Sydenham chorea and rheumatic fever, among others. Based on the suspected pathogenesis of PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) reported in the medical literature, we decided to investigate the cardiologic involvement in children with a recent PANS/PANDAS diagnosis. Methods: The study population satisfies PANS (1) and PANDAS (2) criteria of diagnoses. Cardiologic assessment was performed through clinical examination, electrocardiography, and echocardiography. Results: In the selected pediatric population, a significant number of children presented mitral valve involvement, systolic murmurs and electrocardiographic abnormalities. High ASLOT levels did not seem to be associated to a cardiac involvement. Conclusions: Often PANS is difficult to diagnose because it is little known by physicians and most of the cardiologic findings described in this study are common among the healthy pediatric population. Also, ASLOT levels seems not to be predictive of cardiac involvement. Furthermore, the existence of PANDAS as a clinical entity is associated with a group of anti-neuronal autoantibodies found in Sydenham chorea is still controversial. We recommend a complete cardiologic evaluation in those children who meet the PANS/PANDAS diagnostic criteria.