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- Hoffsten, Alice, et al.
(author)
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Paneth cell proteins DEFA6 and GUCA2A as tissue markers in necrotizing enterocolitis
- 2023
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In: European Journal of Pediatrics. - : Springer Nature. - 0340-6199 .- 1432-1076. ; 182:6, s. 2775-2784
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Journal article (peer-reviewed)abstract
- Previous studies suggest that Paneth cells are involved in NEC development. Defensin alpha 6 (DEFA6) and guanylate cyclase activator 2A (GUCA2A) are selective protein markers of Paneth cells. The objective was to explore DEFA6 and GUCA2A expression in intestinal tissue samples from newborn infants with and without NEC. Tissue samples from histologically intact intestine were analyzed from 70 infants: 43 underwent bowel resection due to NEC and 27 controls were operated due to conditions such as intestinal atresia, dysmotility, aganglionosis, pseudo-obstruction or volvulus. Each tissue sample was immunohistochemically stained for DEFA6 and GUCA2A. Semi-automated digital image analysis was performed to determine protein expression. Clinical data and protein expressions were compared between the groups. DEFA6 expression was lower in the NEC group (p = 0.006). Low DEFA6 correlated with risk of developing NEC in a logistic regression analysis, independently of gestational age and birth weight (OR 0.843 [CI 0.732–0.971]; p = 0.018). GUCA2A expression did not differ between the two groups.Conclusion: Lower expression of DEFA6 together with intact GUCA2A expression indicates that NEC patients have well-defined Paneth cells but diminished defensin activity. Our results suggest that DEFA6 could be used as a biomarker for NEC.What is Known:• Previous studies of defensin activity in NEC have been inconsistent, showing that defensin levels may be increased or diminished in NEC. GUCA2A has to our knowledge never been studied in NEC.What is New:• This study benchmarks two specific Paneth cell markers (DEFA6 and GUCA2A) and their activity in individuals with and without NEC.• The key finding is that the NEC group had a lower DEFA6 expression compared to the Controls, while the expression of GUCA2A did not differ between the groups.
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| 2. |
- Kielt, Matthew, et al.
(author)
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Classifying multicenter approaches to invasive mechanical ventilation for infants with bronchopulmonary dysplasia using hierarchical clustering analysis
- 2023
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In: Pediatric Pulmonology. - : John Wiley & Sons. - 8755-6863 .- 1099-0496. ; 58:8, s. 2323-2332
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Journal article (peer-reviewed)abstract
- IntroductionEvidence-based ventilation strategies for infants with severe bronchopulmonary dysplasia (BPD) remain unknown. Determining whether contemporary ventilation approaches cluster as specific BPD strategies may better characterize care and enhance the design of clinical trials. The objective of this study was to test the hypothesis that unsupervised, multifactorial clustering analysis of point prevalence ventilator setting data would classify a discrete number of physiology-based approaches to mechanical ventilation in a multicenter cohort of infants with severe BPD.MethodsWe performed a secondary analysis of a multicenter point prevalence study of infants with severe BPD treated with invasive mechanical ventilation. We clustered the cohort by mean airway pressure (MAP), positive end expiratory pressure (PEEP), set respiratory rate, and inspiratory time (Ti) using Ward's hierarchical clustering analysis (HCA).ResultsSeventy-eight patients with severe BPD were included from 14 centers. HCA classified three discrete clusters as determined by an agglomerative coefficient of 0.97. Cluster stability was relatively strong as determined by Jaccard coefficient means of 0.79, 0.85, and 0.77 for clusters 1, 2, and 3, respectively. The median PEEP, MAP, rate, Ti, and PIP differed significantly between clusters for each comparison by Kruskall–Wallis testing (p < 0.0001).ConclusionsIn this study, unsupervised clustering analysis of ventilator setting data identified three discrete approaches to mechanical ventilation in a multicenter cohort of infants with severe BPD. Prospective trials are needed to determine whether these approaches to mechanical ventilation are associated with specific severe BPD clinical phenotypes and differentially modify respiratory outcomes.
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| 3. |
- Munsters, Josanne, 1986-, et al.
(author)
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Skin conductance measurement as a selective and continuous pain assessment method during eye examinations for retinopathy of prematurity
- 2023
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In: Global Pediatrics. - : Elsevier. - 2667-0097. ; 4
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Journal article (peer-reviewed)abstract
- BackgroundAssessing and managing pain in newborns is important for normal development and reduction of morbidity.AimTo assess whether skin conductance measurements (SCM) can be used as an objective method for measuring procedural pain during screening for retinopathy of prematurity (ROP) in preterm infants and to identify painful components of the examination.Methods65 separate SCM were performed in 33 infants born at <32 weeks gestational age (wGA) eligible for ROP screening (median 26+4 wGA, range 23+3 to 31+3; median weeks postmenstrual age 37+2, range 31+0 to 49+6). SCM was measured before, during and after eye examination (fundoscopy and/or wide-field digital retinal imaging [WFDRI]), and compared to changes in heart rate (HR), pulse oximetry saturation (SpO2) and behavioral state measured with the Neonatal Pain, Agitation and Sedation Scale (N-PASS).ResultsA major increase of SCM could be seen during both fundoscopy and WFDRI (p<0.01, respectively). No correlation was found between SCM and wGA. N-PASS changed significantly during ROP examination (p<0.01). While N-PASS could only distinguish painful response from baseline during fundoscopy and WFDRI, SCM detected responses during each stage of the investigations i.e. the application of mydriatics, fundoscopy, anesthetic drops, speculum and WFDRI. HR increased only during digital retinal imaging (p = 0.049), while SpO2 decreased only during fundoscopy (p = 0.042).ConclusionSCM may be used as a continuous and objective method to evaluate pain and its intensity during screening for ROP, enabling the separation of the different painful components of the investigation. Selecting and grading the different painful stages improves the possibility to assess and continue to improve pain management more specifically in these patients.
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