Digestive enzyme replacement relieves growth failure in preterm infants with poor exocrine pancreatic function: a retrospective case series

In orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (<200 mu g/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease kg(-1) d(-1). Among 46 of 132 preterm infants < 1250g birth weight surviving to at least 14 days in whom FPE-1 was determined, 38 infants had low FPE-1 (< 200 mu g/g), and 33 infants received exogenous digestive enzyme replacement. Average daily weight gain significantly increased from 14.4 [range 2.6-22.4] g kg(-1) d(-1) to 17.4 [8.4-29.0] g kg(-1) d(-1) (P = 0.001), as did weight gain per kcal, from 0.08 [0.02-0.13] g kcal(-1) d(-1) to 0.11 [0.05-0.18] g kcal(-1) d(-1). Conclusion: In preterm infants with signs and symptoms of exocrine pancreatic insufficiency, exogenous digestive enzyme replacement is associated with improved growth. What is Known: center dot Very preterm infants on full enteral nutrition may display growth failure linked to transient poor exocrine pancreatic function. center dot Porcine pancreatic enzymes covered with an acid-resistant coating are too large to pass the internal diameter of most gavage tubes used in very preterm infants. What is New: center dot Administration of a liquid formulation of acid-resistant microbial digestive enzymes in preterm infants with growth failure and low fecal pancreatic elastase-1 values was associated with improved weight gain. center dot Response to exogenous digestive enzyme replacement was associated with the prior extent of growth failure

Aberrant phase separation and nucleolar dysfunction in rare genetic diseases

Thousands of genetic variants in protein-coding genes have been linked to disease. However, the functional impact of most variants is unknown as they occur within intrinsically disordered protein regions that have poorly defined functions1-3. Intrinsically disordered regions can mediate phase separation and the formation of biomolecular condensates, such as the nucleolus4,5. This suggests that mutations in disordered proteins may alter condensate properties and function6-8. Here we show that a subset of disease-associated variants in disordered regions alter phase separation, cause mispartitioning into the nucleolus and disrupt nucleolar function. We discover de novo frameshift variants in HMGB1 that cause brachyphalangy, polydactyly and tibial aplasia syndrome, a rare complex malformation syndrome. The frameshifts replace the intrinsically disordered acidic tail of HMGB1 with an arginine-rich basic tail. The mutant tail alters HMGB1 phase separation, enhances its partitioning into the nucleolus and causes nucleolar dysfunction. We built a catalogue of more than 200,000 variants in disordered carboxy-terminal tails and identified more than 600 frameshifts that create arginine-rich basic tails in transcription factors and other proteins. For 12 out of the 13 disease-associated variants tested, the mutation enhanced partitioning into the nucleolus, and several variants altered rRNA biogenesis. These data identify the cause of a rare complex syndrome and suggest that a large number of genetic variants may dysregulate nucleoli and other biomolecular condensates in humans.© 2023. The Author(s)

Digestive enzyme replacement relieves growth failure in preterm infants with poor exocrine pancreatic function: a retrospective case series

In orally fed preterm infants, poor weight gain may be linked to low fecal pancreatic elastase-1 (FPE-1) activity, indicative of exocrine pancreatic insufficiency. The objective of this study was the retrospective assessment of the effect of exogenous digestive enzyme replacement by gavage in preterm infants with growth failure and low FPE-1 (&amp;lt;200 μg/g). We analyzed weight gain relative to baseline and caloric intake during 14-day periods before and after institution of digestive enzyme replacement containing 6000 U lipase and 240 U protease k

Milk Curd Obstruction in Human Milk-Fed Preterm Infants

Background: Milk curd obstruction as a cause of intestinal obstruction has been known since 1959, but has nearly disappeared. However, in recent years it has experienced a revival in small premature infants. Objective: The aim of this study was to evaluate the clinical characteristics of milk curd obstruction (lactobezoar) in preterm infants. Methods: Data of preterm infants with milk curd obstruction cared for at a large tertiary neonatal intensive care unit between 2012 and 2016 were retrieved from the electronic registry and paper records. Results: A total of 10 infants (2 girls, 8 boys) were identified: the median birth weight was 595 g (range 270-922), gestational age was 24.4 weeks (23.4-27.0), weight-for-gestational age percentile was 16 (0-62), and age at diagnosis was 28 days (16-64). Five infants (50%) were small for gestational age. All neonates had received fortified human milk (added protein 2.0 g/100 mL, range 0-2.8; added calcium 2,400 μmol/100 mL, range 0-6 844; added phosphate 2,400 μmol/100 mL, range 0-5,178). Seven neonates underwent surgery, and 2 infants died. Hyperechoic masses in extended bowel loops, visualised by abdominal ultrasound, and pale/acholic faeces were hallmarks of milk curd obstruction. Conclusions: In this study, milk curd obstruction occurred exclusively in infants with a birth weight < 1,000 g (2.2%) and <28 weeks' gestational age (2.4%). Male and small for gestational age infants appeared to be at increased risk. Paying attention to the colour of the faeces of infants at risk might help to diagnose milk curd obstruction at an early stage

Anatomic accuracy, physiologic characteristics, and fidelity of very low birth weight infant airway simulators

Background!#!Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators.!##!Methods!#!We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators' physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity.!##!Results!#!The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 ± 1.0, Premature Anne 4.9 ± 1.1, Preterm Baby 5.0 ± 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 ± 1.0) an unfavorable rating.!##!Conclusion!#!The simulator physiology deviated significantly from preterm infants' reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique.!##!Impact!#!Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators

Anatomic accuracy, physiologic characteristics, and fidelity of very low birth weight infant airway simulators

Background Medical simulation training requires realistic simulators with high fidelity. This prospective multi-center study investigated anatomic precision, physiologic characteristics, and fidelity of four commercially available very low birth weight infant simulators. Methods We measured airway angles and distances in the simulators Premature AirwayPaul (SIMCharacters), Premature Anne (Laerdal Medical), Premie HAL S2209 (Gaumard), and Preterm Baby (Lifecast Body Simulation) using computer tomography and compared these to human cadavers of premature stillbirths. The simulators' physiologic characteristics were tested, and highly experienced experts rated their physical and functional fidelity. Results The airway angles corresponded to those of the reference cadavers in three simulators. The nasal inlet to glottis distance and the mouth aperture to glottis distance were only accurate in one simulator. All simulators had airway resistances up to 20 times higher and compliances up to 19 times lower than published reference values. Fifty-six highly experienced experts gave three simulators (Premature AirwayPaul: 5.1 +/- 1.0, Premature Anne 4.9 +/- 1.1, Preterm Baby 5.0 +/- 1.0) good overall ratings and one simulator (Premie HAL S2209: 2.8 +/- 1.0) an unfavorable rating. Conclusion The simulator physiology deviated significantly from preterm infants' reference values concerning resistance and compliance, potentially promoting a wrong ventilation technique. Impact Very low birth weight infant simulators showed physiological properties far deviating from corresponding patient reference values. Only ventilation with very high peak pressure achieved tidal volumes in the simulators, as aimed at in very low birth weight infants, potentially promoting a wrong ventilation technique. Compared to very low birth weight infant cadavers, most tested simulators accurately reproduced the anatomic angular relationships, but their airway dimensions were relatively too large for the represented body. The more professional experience the experts had, the lower they rated the very low birth weight infant simulators