Functional Outcomes and Morbidity in Pediatric Sepsis Survivors: A Tanzanian Experience

Pediatric sepsis remains a significant cause of childhood morbidity and mortality, disproportionately affecting resource-limited settings. As more patients survive, it is paramount that we improve our understanding of post-sepsis morbidity and its impact on functional outcomes. The functional status scale (FSS) is a pediatric validated outcome measure quantifying functional impairment, previously demonstrating decreased function following critical illnesses, including sepsis, in resource-rich settings. However, functional outcomes utilizing the FSS in pediatric sepsis survivors have never been studied in resource-limited settings or in non-critically ill septic children. In a Tanzanian cohort of pediatric sepsis patients, we aimed to evaluate morbidity associated with an acute septic episode using the FSS modified for resource-limited settings. This was a prospective cohort study at an urban referral hospital in Tanzania, including children with sepsis aged 28 days to 14 years old over a 12-month period. The FSS was adapted to the site's available resources. Functional status scale scores were obtained by interviewing guardians both at the time of presentation to determine the child's baseline and at 28-day follow-up. The primary outcome was “decline in functional status,” as defined by a change in FSS score of at least 3. In this cohort, 4.3% of the 1,359 surviving children completing 28-day follow-up had a “decline in functional status.” Conversely, 13.8% of guardians reported that their child was not yet back to their pre-illness state. Three-quarters of children reported as not fully recovered were not identified via the FSS as having a decline in functional status. In our cohort of pediatric sepsis patients, we identified a low rate of decline in functional status when using the FSS adapted for resource-limited settings. A higher proportion of children were subjectively identified as not being recovered to baseline. This suggests that the FSS has limitations in this population, despite being adapted for resource-limited settings. Next steps include developing and validating a further revised FSS to better capture patients identified as not recovered but missed by the current FSS.

Diagnostic Approach to Macrocephaly in Children

Macrocephaly affects up to 5% of the pediatric population and is defined as an abnormally large head with an occipitofrontal circumference (OFC) >2 standard deviations (SD) above the mean for a given age and sex. Taking into account that about 2–3% of the healthy population has an OFC between 2 and 3 SD, macrocephaly is considered as “clinically relevant” when OFC is above 3 SD. This implies the urgent need for a diagnostic workflow to use in the clinical setting to dissect the several causes of increased OFC, from the benign form of familial macrocephaly and the Benign enlargement of subarachnoid spaces (BESS) to many pathological conditions, including genetic disorders. Moreover, macrocephaly should be differentiated by megalencephaly (MEG), which refers exclusively to brain overgrowth, exceeding twice the SD (3SD—“clinically relevant” megalencephaly). While macrocephaly can be isolated and benign or may be the first indication of an underlying congenital, genetic, or acquired disorder, megalencephaly is most likely due to a genetic cause. Apart from the head size evaluation, a detailed family and personal history, neuroimaging, and a careful clinical evaluation are crucial to reach the correct diagnosis. In this review, we seek to underline the clinical aspects of macrocephaly and megalencephaly, emphasizing the main differential diagnosis with a major focus on common genetic disorders. We thus provide a clinico-radiological algorithm to guide pediatricians in the assessment of children with macrocephaly.

Cardiopulmonary Function Assessment in Children With Pulmonary Valve Stenosis

ObjectivePulmonary valve (PV) stenosis affects cardiac pulmonary function and exercise performance. A cardiopulmonary exercise test (CPET) combined with a transthoracic echocardiogram (TTE) can measure exercise performance, disease progression, and treatment effects. We assessed the exercise capacity in children with PV stenosis by conducting CPET and TTE.MethodsFrom 2005 to 2021, 84 patients with PV stenosis aged 6–18 years were enrolled; 43 were treated with balloon pulmonary valvuloplasty (BPV) (Group A), and 41 received follow-up care (Group B), and their CPET and pulmonary function test results were compared with 84 healthy, matched individuals (Control). We also conducted TTE to compare the peak pulmonary artery pulse wave velocity and pulmonary valve (PV) area before and after catheterization and follow-up care.ResultsThere were no significant differences among the CPET parameters of the patient groups and controls in anaerobic metabolic equivalent (MET) (group A: 6.44 ± 0.58; group B: 6.28 ± 0.47, control: 6.92 ± 0.39, p = 0.110), peak MET (group A: 9.32 ± 0.74; group B: 9.13 ± 0.63; control: 9.80 ± 0.52, p = 0.263), and heart rate recovery (group A: 28.04 ± 4.70; group B: 26.44 ± 3.43, control:26.10 ± 2.42, p = 0.718). No significant differences were found in the pulmonary functions between the three groups. The pulmonary artery pulse wave velocity significantly decreased after catheterization (3.97 ± 1.50 vs. 1.95 ± 0.94, p < 0.0001), but not after follow-up care (1.67 ± 0.77 vs. 1.75 ± 0.66, p = 0.129). The pulmonary vale area significantly improved in group A (0.89 ± 0.71 vs. 1.16 ± 0.58, p < 0.0001), whereas only insignificant progression of PV stenosis was observed in group B (1.60 ± 0.64 vs. 1.57 ± 0.65, p = 0.110).ConclusionsPatients treated with BPV had a similar exercise capacity with that of patients under follow-up care and the healthy controls. Larger or multi-center studies should be conducted to confirm the physical fitness of pediatric patients with PV stenosis after management.

SARS-CoV-2 Infection and Active, Multiorgan, Severe cGVHD After HSCT for Adolescent ALL: More Luck Than Understanding? A Case Report

Graft-vs. -host disease (GvHD) is a serious and complex immunological complication of haematopoietic stem cell transplantation (HSCT) and is associated with prolonged immunodeficiency and non-relapse mortality. Standard treatment of chronic GvHD comprises steroids in combination with other immunosuppressive agents. Extracorporeal photopheresis (ECP), with its immunomodulatory mechanism, is applied as part of steroid-sparing regimens for chronic GvHD. Immunocompromised, chronically ill patients are at particular risk of severe disease courses of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. T-cell immunity in SARS-CoV-2 infection is well-described but the role of the humoral immune responses is not fully understood. This case report describes a moderate course of SARS-CoV-2 infection in a patient <9 months after HSCT who was suffering from active, severe, chronic GvHD treated with prednisone and ECP. Following HSCT from a matched unrelated donor to cure acute lymphoblastic leukaemia, the 25-year-old male patient experienced multiple infectious complications associated with cytopenia, B-cell dyshomeostasis and autoantibody production followed by development of severe chronic GvHD thereafter at day +212. The steroid-sparing treatment plan consisted of supportive care, topical treatment, prednisone and ECP. He was diagnosed with SARS-CoV-2 infection at day +252, experiencing loss of smell and taste as well as a cough. The patient's oxygen saturation was between 94 and 97% on room air, and computed tomography images showed evolution of typical of SARS-CoV-2 infiltrates. In addition to cytopenia and immune dyshomeostasis, laboratory tests confirmed macrophage activating syndrome, transaminitis and Epstein-Barr virus viraemia. At that time, anti-SARS-CoV-2 monoclonal antibodies were not available in Austria and remdesivir seemed contraindicated. Surprisingly, despite severe lymphopenia the patient developed SARS-CoV-2-specific antibodies within 15 days, which was followed by clearance of SARS-CoV-2 and EBV with resolution of symptoms. Thereafter, parameters of immune dysregulation such as lymphopenia and B-cell dyshomeostasis, the latter characterised by elevated CD21low B cells and autoantibody expression, normalised. Moreover, we observed complete response of active chronic GvHD to treatment.

What Is Most Suitable for Children With Cystic Fibrosis—The Relationship Between Spirometry, Oscillometry, and Multiple Breath Nitrogen Washout

IntroductionIn cystic fibrosis (CF), pathological lung changes begin early in life. The technological progress currently gives many diagnostic possibilities. However, pulmonary function testing in children remains problematic.ObjectivesOur study aimed to correlate the results of impulse oscillometry (IOS) with those of multiple breath nitrogen washout (MBNW) in our pediatric CF population. We also compared those parameters between the groups with and without spirometric features of obturation.MethodsWe collected 150 pulmonary function test sets, including spirometry, IOS, and MBNW in patients with CF aged 12.08 ± 3.85 years [6–18]. The study group was divided into two subgroups: IA (without obturation) and IB (with obturation). We also compared Sacin, Scond, and oscillometry parameters of 20 patients aged 14–18 years who reached the appropriate tidal volume (VT) during MBNW.ResultsStatistical analysis showed a negative correlation between lung clearance index (LCI) and spimoetric parameters. Comparison of subgroups IA (n = 102) and IB (n = 48) indicated a statistically significant difference in LCI (p < 0.001) and FEV1z-score (p < 0.001), FEV1% pred (p < 0.001), MEF25z-score (p < 0.001), MEF50 z-score (p < 0.001), MEF75 z-score (p < 0.001), R5% pred (p < 0.05), and R20% pred (p < 0.01). LCI higher than 7.91 was found in 75.33% of the study group, in subgroup IB—91.67%, and IA−67.6%.ConclusionsLCI derived from MBNW may be a better tool than IOS for assessing pulmonary function in patients with CF, particularly those who cannot perform spirometry.

Establishing Surgical Care Sustainability in Sub-Saharan Africa for Global Child Health: Insights From Pediatric Cardiac Surgical Capacity-Building Programs in Ethiopia and Côte d'Ivoire

The global surgery research team of the JW LEE Center for Global Medicine, Seoul National University College of Medicine, introduced team-based health workforce training programs for pediatric cardiac surgery in Ethiopia and Côte d'Ivoire. A team-based collaborative capacity-building model was implemented in both countries, and details of the program design and delivery were documented. The research team shared their experiences and identified achievements, lessons, and challenges for cardiac surgical interventions in Sub-Saharan Africa. Future directions were put forward to advance and strengthen the low-and middle-income countries “Safe Surgery.”

Role of GDNF, GFRα1 and GFAP in a Bifidobacterium-Intervention Induced Mouse Model of Intestinal Neuronal Dysplasia

ObjectiveTo investigate the effects of glial cell-derived neurotrophic factor (GDNF), GDNF family receptor alpha 1 (GFRα1), and glial fibrillary acidic protein (GFAP) on colonic motility in a mouse model of intestinal neuronal dysplasia by intervention with Bifidobacterium and to explore the influence of Bifidobacterium on enteric glial cells (EGCs).MethodsWestern blotting and qRT-PCR were employed to detect the expression of GFRα1 and GFAP in colonic tissues of mice with or without Tlx2 mutations, and ELISA was used to detect the expression of GDNF in serum. IHC was used to detect the appearance of the ganglion cells. Subsequently, Tlx2 homozygous mutant (Tlx2−/−) mice were treated with Bifidobacterium. Colonic motility was measured before and after intervention by measuring the glass bead expelling time. The variations in abdominal circumference and GDNF, GFRα1, and GFAP expression were measured. In addition, 16SrRNA gene sequencing was performed to detect the abundance of the intestinal microbiota.ResultsThe mRNA and protein expression of GFRα1 and GFAP was decreased in the colonic tissues of Tlx2−/− mice and GDNF expression was decreased in serum compared with Tlx2+/− and WT mice. After confirming the colonization of Bifidobacterium by 16S rRNA gene sequencing, the expelling time and abdominal distension were ameliorated, and the expression of GFAP, GDNF, and GFRα1 was increased.ConclusionsThe expression of GDNF, GFRα1, and GFAP is associated with colonic motility. The altered expression of EGC-related factors suggested that Bifidobacterium may be involved in the EGC activation process. The amelioration of IND symptoms after intervention with Bifidobacterium prompted the elicitation of adjuvant therapy.

Assessing the Utility of an Outpatient Exercise Program for Children With Cystic Fibrosis: A Quality Improvement Project

Children with cystic fibrosis (CF) (cwCF) suffer from inadequate weight gain, failure to thrive, and muscle weakness. The latter may be secondary to disuse atrophy (muscle wasting or reduction in muscle size associated with reduced physical activity and inflammation). Handgrip strength (HGS) is a reliable surrogate for muscle strength and lean body mass. Data from our CF center have shown an association between low HGS and forced expiratory volume in 1 s (FEV1) in cwCF. High-intensity interval training (HIIT) improves physical strength. Therefore, we devised a project to assess implementing a HIIT exercise program in the home setting, in order to improve physical strength in cwCF with HGS ≤ 50th percentile. Patients were instructed to complete 3–5 sessions of HIIT exercises per week. Wilcoxon matched-pairs signed-rank tests were used to compare HGS, FEV1, and body mass index (BMI) percentile at baseline and at a follow-up clinic visit. Follow-up was limited due to the COVID pandemic. Adherence to the HIIT regimen was poor. A total of twenty-nine cwCF participated in the program. However, a total of 13 individuals reported some form of moderate activity at follow-up and therefore constituted our final study population. There was a statistically significant increase in absolute grip strength (AGS) and FEV1 for these individuals. Even though the home HIIT protocol was not followed, the project demonstrated that moderate physical activity in cwCF can lead to significant improvement in HGS and overall physical strength.

Cross-Cultural Adaptation and Validation of the Chinese Version of the Brace Questionnaire

Objective: To adapt the questionnaire cross-culturally and to analyze the adaptation and validation of the Chinese version of the Brace Questionnaire (C-BrQ).Methods: The adaptation was based on the International Quality of Life Assessment Project guidelines. A total of 79 patients with AIS were included to examine the psychometric properties of the C-BrQ. The reliability was assessed using internal consistency (the Cronbach's alpha coefficient) and test–retest reliability (intraclass correlation coefficient ICC2.1, 95% CI). Floor and ceiling effects were calculated. Lin's concordance correlation coefficient (CCC, 95% CI) was used to compare the agreement between the Scoliosis Research Society-22 patient questionnaire (SRS-22) and C-BrQ.Results: There were strong correlations between each item and its corresponding domain significantly. The correlations between the C-BrQ domains and their related questions vary from moderate to strong (r = 0.311–0.933, P < 0.05). The Cronbach's was 0.891, showing good internal consistency of each domain of the BrQ, and the ICC in test–retest was 0.860 (0.8776, 0.912), which means an excellent test–retest reliability. The Lin's CCC between SRS-22 and C-BrQ was 0.773 (0.669, 0.848), showing great agreement. However, no significant floor and ceiling effects in C-BrQ was observed except the ceiling effect in school activity and bodily pain.Conclusion: BrQ was translated and cross-culturally adapted for use in China with good internal consistency and excellent test–retest reliability.

Expressed Breast Milk Analysis: Role of Individualized Protein Fortification to Avoid Protein Deficit After Preterm Birth and Improve Infant Outcomes

Background: Expressed breast milk (EBM) protein content is highly variable between mothers and often below published values that are still used for EBM protein fortification strategies. This approach may result in significant protein deficit and suboptimal protein energy (P/E) ratio. The study aim was to determine whether individualized EBM protein analysis and fortification will reduce preterm infant protein deficits and improve growth and neurodevelopmental outcome.Study Methods: In a single-center randomized, blinded study of infants born at 24 0/7–29 6/7 weeks, mother-specific protein values measured by a milk analyzer were used to individualize infant-specific protein intake (interventional group, IG), and compared this to a standardized protein fortification scheme based on published values of EBM protein content of 1.4 g/dL (control group, CG). For IG, milk analyzer protein values of mother's EBM were used to adjust protein content of the EBM. The CG EBM protein content was adjusted using the standard published value of 1.4 g/dL and not based on milk analyzer values. EBM protein content, protein intake, protein/energy (P/E) ratio, weight (WT), head circumference (HC), length (L), growth velocity (GV) from 2 to 6 weeks of age, WT, HC and L Z-Scores at 32- and 35-weeks PMA, and lean body mass (35 weeks PMA skin fold thickness) were measured. Neurodevelopment was assessed by Bayley III at average 24 months corrected gestational age (CGA).Results: EBM protein content before fortification was significantly below published values of 1.4 g/dL at all time points in both CG and IG. CG protein deficit was significantly decreased and progressively worsened throughout the study. Individualized protein fortification in IG avoided protein deficit and optimized P/E ratio. Although no significant change in short-term GV (at 6 weeks of age) was seen between groups, IG infants born at <27 weeks had significant improvements in WT and L z-scores, and leaner body mass at 32 and 35 weeks PMA. IG exhibited significantly improved cognitive scores at 24 months CGA.Conclusions: Infant-specific protein supplementation of mother's EBM optimized P/E ratio by eliminating protein deficit and improved growth z scores at 32- and 35-weeks PMA and neurocognitive testing at 24 months.