Acute respiratory failure due to pulmonary exacerbation in children with cystic fibrosis admitted in a pediatric intensive care unit: outcomes and factors associated with mortality.

BACKGROUND: Children with advanced pulmonary disease due to cystic fibrosis (CF) are at risk of acute respiratory failure due to pulmonary exacerbations leading to their admission to pediatric intensive care units (PICU). The objectives of this study were to determine short and medium-term outcomes of children with CF admitted to PICU for acute respiratory failure due to pulmonary exacerbation and to identify prognosis factors. METHODS: This retrospective monocentric study included patients less than 18 years old admitted to the PICU of a French university hospital between 2000 and 2020. Cox proportional hazard regression methods were used to determine prognosis factors of mortality or lung transplant. RESULTS: Prior to PICU admission, the 29 patients included (median age 13.5 years) had a severe lung disease (median Forced Expiratory Volume in 1 s percentage predicted at 29%). Mortality rates were respectively 17%, 31%, 34%, 41% at discharge and at 3, 12 and 36 months post-discharge. Survival rates free of lung transplant were 34%, 32%, 24% and 17% respectively. Risk factors associated with mortality or lung transplant using the univariate analysis were female sex and higher pCO2 and chloride levels at PICU admission, and following pre admission characteristics: home respiratory and nutritional support, registration on lung transplant list and Stenotrophomonas Maltophilia bronchial colonization. CONCLUSION: Children with CF admitted to PICU for acute respiratory failure secondary to pulmonary exacerbations are at high risk of death, both in the short and medium terms. Lung transplant is their main chance of survival and should be considered early.

Tribal Healing, Suicide, Ethical Issues, Cancer and Measuring Religiosity and Spirituality.

This issue of JORH considers the 'good, the bad and the ugly' of tribal or traditional healers, as well as articles relating to ethical challenges due to contemporary medicine and environmental issues. The concluding series on suicide (Part 2) is also finalized in this issue, as well as a number of research articles from multiple countries relating to cancer. Similar to previous issues, JORH once again adds to its increasing collection of articles relating to the empirical measurement of religion, spirituality and health. Readers are also reminded of the European Congress on Religion, Spirituality and Health (ECRSH) (Salzburg, Austria, May 2024), as well as the inaugural International Moral Injury and Wellbeing Conference (IMIWC) (Brisbane, Australia, September 2024).

Care of the Aged, Women's Health, and Measuring Religion, Spirituality and Health.

This issue of JORH explores various concerns related to the care of the elderly within a number of countries (namely China, India, Iran, Israel, Turkey, USA). Issues relating to Women's Health are also considered across the life span but particularly with regard to gynaecology, paediatrics, cancer, mental health and wellbeing. Research is presented on the empirical measurement of religion, spirituality and health with scales developed and/or tested in Iran, India, Haiti, Taiwan, Jordan and the Netherlands. Finally, readers are reminded of the 9th European Congress on Religion, Spirituality and Health (ECRSH) during May 2024, 16-18th at the Paracelsus Medical University in Salzburg, Austria.

Chaplaincy, Clergy, Prayer, Cancer and Measuring Religion and Health.

This third issue of JORH for 2023 revisits a number of themes previously highlighted in JORH, along with the addition of two new themes. Since JORH's first special issue on 'Chaplaincy' (JORH, 2022, 61:2), this area of research within JORH has now flourished, with a total of three JORH issues now incorporating the allied health discipline of chaplaincy. Two new article collections in this JORH issue relate to clergy 'faith leaders' and research related to 'prayer.' This issue also revisits the topic of cancer-a recurrent focus within JORH which has, over the past six decades, examined nearly every type of known cancer in the context of religion/spirituality. Finally, JORH collates once again, a number of articles relating to the empirical measurement of religion and health-an increasingly important area of research.

Association between nebuliser therapies adherence and visit-to-visit variability of FEV1 in patients with cystic fibrosis.

At the same level of lung function, some patients with cystic fibrosis have large variations in their FEV1 percent predicted (FEV1pp) values while others have stable values. We hypothesised that lower adherence to nebuliser therapies was associated with higher FEV1pp variability. We conducted a post hoc analysis of the ACtiF trial data. Adherence was calculated using data from data-logging nebulisers, and FEV1pp variability using the coefficient of variation equation. Amongst the 543 patients included in the analysis, those poorly adherent (adherence < 50%) had a higher FEV1pp variability than patients moderately (50 to < 80%) and highly adherent (≥ 80%), with median values (IQR1-3) of 8.1% (4.9-13.7), 6.3% (3.9-9.8), and 6.3% (3.9-9.3) respectively (p < 0.01). This result was confirmed by a multiple linear regression including adherence as a continuous variable (p < 0.01). Further studies are needed to determine the implications of these differences in FEV1pp variability on the prognosis of patients.

Cancer, Religious Philosophy, Death and Dying.

This final issue of JORH for 2022 revisits the topics of (1) cancer, (2) religious philosophy, and (3) uniquely collates a number of papers discussing the theme of death and dying-which seems an appropriate topic given the conclusion and celebration of life for one of the most internationally admired monarchs, Queen Elizabeth II (1926-2022). Lastly a call for papers is issued regarding religion, spirituality, suicide, and its prevention: https://www.springer.com/journal/10943/updates/23471166 .

Lumacaftor-ivacaftor effects on cystic fibrosis-related liver involvement in adolescents with homozygous F508 del-CFTR.

BACKGROUND: The effects of lumacaftor-ivacaftor on cystic fibrosis transmembrane conductance regulator (CFTR)-associated liver disease remain unclear. The objective of the study was to describe the effect of this treatment on features of liver involvement in a cystic fibrosis (CF) adolescent population homozygous for F508del. METHODS: Clinical characteristics, liver blood tests, abdominal ultrasonography (US), and pancreas and liver proton density fat fraction (PDFF) by magnetic resonance imaging, were obtained at treatment initiation and at 12 months for all patients. Biomarkers of CFTR activity (sweat chloride test, nasal potential difference, and intestinal current measurement) were assessed at initiation and at 6 months therapy. RESULTS: Of the 37 patients who started ivacaftor/lumacaftor treatment, 28 were eligible for analysis. In this group, before treatment initiation, 4 patients were diagnosed with multinodular liver and portal hypertension, 19 with other forms of CF liver involvement, and 5 with no signs of liver involvement. During treatment, no hepatic adverse reactions were documented, and no patient developed liver failure. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gammaglutamyl transferase (GGT) decreased significantly following initiation of lumacaftor-ivacaftor, and remained so after 12 months treatment. This was not correlated with changes in clinical status, liver and pancreas US and PDFF, fecal elastase, or lumacaftor-ivacaftor serum levels. The most "responsive" patients demonstrated a significant increase in biomarkers of CFTR activity. CONCLUSIONS: These results may suggest a potential beneficial effect of CFTR modulators on CF liver disease and warrant further investigation in larger, prospective studies.

French translation and validation of the Sinus and Nasal Quality of Life Survey (SN-5) in children.

PURPOSE: Chronic rhinosinusitis (CRS) is a frequent, quality-of-life (QOL) impairing disease in pediatrics. The SN-5 is a reliable, sensitive and reproductible QOL questionnaire, validated in English for evaluation of CRS disease-specific QOL in children. This study aims to adapt and validate the French version of this test. METHODS: The SN-5 score was adapted into French language through a forward-backwards translation process, and validated through a monocentric prospective controlled study. Inclusion criteria were 2-12 years of age, CRS symptoms for at least 12 weeks, or absence of sino-nasal symptom for controls. Reproducibility was assessed through Spearman's correlation between initial answers and a re-test conducted 15 days later. Internal consistency was measured through Cronbach's alpha, construct validity through Spearman's correlation between items, discriminative ability through Mann-Whitney tests. RESULTS: 40 patients and 37 controls filled the score between November 2019 and March 2020. Retest was returned by 35 patients and 35 controls. Mean cases age was 8.5 ± 2.6 years old. 26 patients had primary CRS, 10 had cystic fibrosis, 4 had ciliary dyskinesia. All had diffuse disease. Mean SN-5 overall score was 3.63/7 ± 6.4 for CRS patients and 1.89/7 ± 0.9 for controls (p < 0.001). Test-retest coefficient was 0.84 (0.70-0.92; p < 0.001), Cronbach's alpha was 0.83 for CRS patient. Item per item construct validity was good to excellent. CONCLUSIONS: The French version of the SN-5 showed good statistical properties, with good test-retest reliability, internal consistency, structural validity and discriminative ability between CRS and control patients.

Intravenous pulses of methylprednisolone for infants with severe bronchopulmonary dysplasia and respiratory support after 3 months of age.

INTRODUCTION: There are few published data on the efficacy of systemic corticosteroids in preterm infants with very severe forms of bronchopulmonary dysplasia (BPD), requiring respiratory support after 3 months of age. The aim of this study was to report the use of pulses of methylprednisolone in this population and its consequences on the level of respiratory support. METHODS: This retrospective monocentre study included infants over 3 months of age with severe BPD who received at least one pulse of methylprednisolone (300 mg/m2 /day intravenous [IV] over 3 days). The primary outcome was the evolution of the pulmonary severity score (PSS) during the 3 months preceding and the 5 months following the first pulse. The evolution of the median PSS over time was analyzed using linear segmented regression for interrupted time series. RESULTS: Ten infants were included. During the 3 months preceding the first pulse, a significant increase in the median PSS was observed (p = .01), followed by a progressive decrease during the 5 months after administration of the first pulse (p < .01). Greater effects were observed in more severe infants requiring mechanical or noninvasive ventilation than in those receiving supplemental oxygen through nasal cannula. CONCLUSION: High-dose IV pulses of methylprednisolone were associated with a decrease in the level of respiratory support required by infants with very severe forms of BPD, with a greater effect in those on mechanical or noninvasive ventilation. Further studies are warranted to confirm these preliminary results and assess the long-term safety of this therapy.

Alveolar proteinosis of genetic origins.

Pulmonary alveolar proteinosis (PAP) is a rare form of chronic interstitial lung disease, characterised by the intra-alveolar accumulation of lipoproteinaceous material. Numerous conditions can lead to its development. Whereas the autoimmune type is the main cause in adults, genetic defects account for a large part of cases in infants and children. Even if associated extra-respiratory signs may guide the clinician during diagnostic work-up, next-generation sequencing panels represent an efficient diagnostic tool. Exome sequencing also allowed the discovery of new variants and genes involved in PAP. The aim of this article is to summarise our current knowledge of genetic causes of PAP.

Educational and health outcomes associated with bronchopulmonary dysplasia in 15-year-olds born preterm.

INTRODUCTION: To evaluate the consequences of bronchopulmonary dysplasia (BPD) on academic outcomes and healthcare use in adolescents born very preterm. METHODS: This cohort study included 15-year-old adolescents born very preterm (< 32 weeks) between 2011 and 2013, with and without BPD, and controls born full term. Data regarding academic performance, current medical follow-up, and family characteristics were collected. Multivariate logistic regression was used to quantify relationships between academic outcomes and BPD. RESULTS: From the 1341 children included in the initial cohort, 985 adolescents were eligible and 351 included (55 preterms with a history of BPD, 249 without, and 47 controls). Among adolescents born very preterm, a history of BPD was associated with a higher risk to attend a school for children with special needs (p < 0.05) and to have repeated a grade (p = 0.01). It was also associated with an increased number of medical and paramedical consultations. A history of BPD was not associated with the parents' employment status, family structure, or the presence of younger siblings. CONCLUSION: This study highlights that a history of BPD is associated with poorer academic outcomes and high healthcare use in adolescence.

Stability of Locking Plate and Compression Screws for Lapidus Arthrodesis: A Biomechanical Comparison of Plate Position.

Lapidus (first tarsometatarsal joint) arthrodesis is an established and widely used procedure for the management of moderate to severe hallux valgus, especially in cases involving hypermobility of the first tarsometatarsal joint. Multiple fixation methods are available, and several previous investigations have studied the relative strengths of these methods, including dorsomedial and plantar plating comparisons. However, these studies compared plates of varying designs and mechanical properties and used varying modes of compression and interfragmentary screw techniques. The present study mechanically investigated the resulting motion, stiffness, and strength of identical locking plate constructs fixed at various anatomic positions around the first tarsometatarsal joint. In a bench-top study, fourth-generation composite bones were divided into 3 fixation groups, each having identical interfragmentary screw applications, and randomized to 1 of 3 plate positions: dorsal, medial, or plantar. The plates applied in each case were identical locking plates, precontoured to fit the anatomy. Each construct was experimentally tested using a cantilever bending approach. The outcomes obtained were stiffness, yield force, displacement at yield, ultimate force, and displacement at ultimate force. The plantar plate position showed superior initial stiffness and force to ultimate failure. The plantar and medial plate positions exhibited superior force to yield. The medial plate position was superior regarding displacement tolerated before the yield point and catastrophic failure. The dorsal plate position was not superior for any outcome measured. Plantar and medial plating each offered biomechanical benefits. Clinical studies using similarly matched constructs are required to show whether these findings translate into improved clinical outcomes.

Combined Effects of in Utero and Adolescent Tobacco Smoke Exposure on Lung Function in C57Bl/6J Mice.

BACKGROUND: Fetal determinants of airway function, such as in utero exposure to maternal cigarette smoke (CS), may create a predisposition to adult airflow obstruction and chronic obstructive pulmonary disease (COPD) in adulthood. It has been suggested that active smoking in adolescence and preexisting airflow obstruction have synergistic deleterious effects. OBJECTIVE: We used a mouse model to investigate whether there is a synergistic effect of exposure to CS in utero and during adolescence on lung function. METHODS: Female C57Bl/6J mice were exposed to CS or to filtered room air during pregnancy. Exposure to CS began 2 weeks before mating and continued until delivery. After birth, the pups were not exposed to CS until day 21 (D21). Between D21 and D49, corresponding to "adolescence," litters were randomized for an additional 4 weeks of exposure to CS. Lung morphometry, lung mechanics, and the expression of genes involved in senescence were evaluated in different subsets of mice on D21 and D49. RESULTS: In utero exposure to CS induced significant lung function impairment by D21. CS exposure between D21 and D49 induced significant functional impairment only in mice exposed to CS prenatally. On D49, no difference was observed between subgroups in terms of lung p53, p16, p21, and Bax mRNA levels. CONCLUSIONS: Our findings suggest that prenatal and adolescent CS exposure have a synergistic effect on lung function in mice. The combined effect did not appear to be a consequence of early pulmonary senescence. Citation: Drummond D, Baravalle-Einaudi M, Lezmi G, Vibhushan S, Franco-Montoya ML, Hadchouel A, Boczkowski J, Delacourt C. 2017. Combined effects of in utero and adolescent tobacco smoke exposure on lung function in C57Bl/6J mice. Environ Health Perspect 125:392-399; http://dx.doi.org/10.1289/EHP54.

Splenic infarction in a child revealing chronic myeloid leukemia.

A 7-year-old girl was admitted with a severe abdominal pain. Abdominal ultrasound and CT revealed a large splenic infarction, leading to the diagnosis of chronic myeloid leukemia.