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ERJ Open Research May 2023To examine the trajectory of forced expiratory volume in 1 s (FEV) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to...
AIM
To examine the trajectory of forced expiratory volume in 1 s (FEV) using data from the European Cystic Fibrosis Society patient registry (ECFPR) collected from 2008 to 2016, the era before highly effective modulator therapy (HEMT). We evaluated risk factors for FEV decline.
METHODS
The study population included patients with a confirmed diagnosis of cystic fibrosis recorded in the ECFPR (2008-2016). The evolution of FEV % predicted (%FEV) with age, and the yearly change in %FEV were evaluated. Risk factors considered were cystic fibrosis transmembrane conductance regulator () mutation class, gender, age at diagnosis, neonatal screening, meconium ileus, sweat chloride concentration at diagnosis and country's income level.
RESULTS
We used 199 604 FEV recordings from 38 734 patients. The fastest decline was seen during puberty and in patients diagnosed before the age of 10 years. Males had a higher %FEV, but a higher yearly %FEV loss between the ages of 15 and 25 years. We showed stabilisation and even improvement in %FEV over age in adults with a class III mutation, but a steady decline in patients homozygous for F508del or with both mutations of classes I/II. A faster decline in %FEV was found in patients from low-income countries compared to a similar %FEV evolution in patients from middle- and high-income countries.
CONCLUSIONS
These longitudinal FEV data reflect the reality of cystic fibrosis across Europe in the era pre-HEMT, and can serve as baseline for comparison with the post-HEMT era. The similar evolution in middle- and high-income countries underlines opportunities for low-income countries.
PubMed: 37483280
DOI: 10.1183/23120541.00449-2022 -
European Journal of Pediatrics Sep 2023Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to...
UNLABELLED
Necrotizing enterocolitis (NEC) is associated with significant morbidity and mortality in preterm infants. Early recognition and treatment of NEC are critical to improving outcomes. Enteric nervous system (ENS) immaturity has been proposed as a key factor in NEC pathophysiology. Gastrointestinal dysmotility is associated with ENS immaturity and may serve as a predictive factor for the development of NEC. In this case-control study, preterm infants (gestational age (GA) < 30 weeks) were included in two level-IV neonatal intensive care units. Infants with NEC in the first month of life were 1:3 matched to controls based on GA (± 3 days). Odds ratios for NEC development were analyzed by logistic regression for time to first passage of meconium (TFPM), duration of meconial stool, and mean daily defecation frequency over the 72 h preceding clinical NEC onset (DF < T0). A total of 39 NEC cases and 117 matched controls (median GA 27 + 4 weeks) were included. Median TFPM was comparable in cases and controls (36 h [IQR 13-65] vs. 30 h [IQR 9-66], p = 0.83). In 21% of both cases and controls, TFPM was ≥ 72 h (p = 0.87). Duration of meconial stool and DF < T0 were comparable in the NEC and control group (median 4 and 3, resp. in both groups). Odds of NEC were not significantly associated with TFPM, duration of meconial stools, and DF < T0 (adjusted odds ratio [95% confidence interval]: 1.00 [0.99-1.03], 1.16 [0.86-1.55] and 0.97 [0.72-1.31], resp.).
CONCLUSION
In this cohort, no association was found between TFPM, duration of meconium stool, and DF < T0 and the development of NEC.
WHAT IS KNOWN
• Necrotizing enterocolitis (NEC) is a life-threatening acute intestinal inflammatory disease of the young preterm infant. Early clinical risk factors for NEC have been investigated in order to facilitate early diagnosis and treatment. • Signs of disrupted gastrointestinal mobility, such as gastric retention and paralytic ileus, have been established to support the diagnosis of NEC. Nevertheless, defecation patterns have insufficiently been studied in relation to the disease.
WHAT IS NEW
• Defecation patterns in the three days preceding NEC did not differ from gestational age-matched controls of corresponding postnatal age. Additionally, the first passage of meconium and the duration of meconium passage were comparable between cases and controls. Currently, defecation patterns are not useful as early warning signs for NEC. It remains to be elucidated whether these parameters are different based on the location of intestinal necrosis.
PubMed: 37349579
DOI: 10.1007/s00431-023-05035-8 -
Nutrients Mar 2023Necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP) and meconium-related ileus (MI) requiring surgical intervention are associated with a high risk...
Necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP) and meconium-related ileus (MI) requiring surgical intervention are associated with a high risk of severe short- and long-term complications in very-low-birth-weight (VLBW) infants including poor growth, cholestasis and neurodevelopmental impairment. This retrospective study aimed to identify risk factors for such complications in a cohort of 55 VLBW preterm infants requiring surgery with enterostomy creation due to NEC, SIP or MI. Long-term follow-up was available for 43 (78%) infants. Multiple regression analyses revealed that the duration of inflammation and longitudinal growth determined the risk of cholestasis and neurodevelopmental outcome at 2 years corrected age independent of the aetiology of the intestinal complication. Direct bilirubin increased by 4.9 μmol/L (95%CI 0.26-9.5), 1.4 μmol/L (95%CI 0.6-2.2) and 0.8 μmol/L (95%CI 0.22-1.13) with every day of elevated (Interleukin-6) IL-6, (C-reactive protein) CrP and parenteral nutrition. The mental development index at 2 years corrected age decreased by 3.8 (95%CI -7.3--0.36), 0.4 (95%CI 0.07-0.80) and 0.3 (95%CI 0.08-0.57) with every day of elevated IL-6 and every 1 point decrease in weight percentile at discharge and 2 years. These data stress the importance of optimal timing for the initial surgery in order to prevent prolonged inflammation and an early reversal of the enterostomy in case of poor growth or insufficient enteral nutrition.
Topics: Infant; Infant, Newborn; Humans; Infant, Premature; Retrospective Studies; Interleukin-6; Infant, Very Low Birth Weight; Intestinal Perforation; Inflammation; Enterocolitis, Necrotizing; Cholestasis
PubMed: 37049507
DOI: 10.3390/nu15071668 -
Arquivos Brasileiros de Cirurgia... 2023Bishop-Koop ileostomy has been widely used in pediatric patients with the intention of including as much bowel as possible in the intestinal transit early in the... (Review)
Review
BACKGROUND
Bishop-Koop ileostomy has been widely used in pediatric patients with the intention of including as much bowel as possible in the intestinal transit early in the management of children with meconium ileus and intestinal atresia. In recent years, we have been using it as an alternative to test the distal bowel function before closure of a previously constructed ostomy in selected children with questionable distal bowel motility.
AIMS
The aim of this study was to present our experience with this alternative use of the Bishop-Koop ostomy.
METHODS
This is a cross-sectional retrospective review of hospital records, combined with a comprehensive literature review.
RESULTS
Seven children were included: five had suspected aganglionosis, one had gastroschisis complicated with ileal atresia, and one had a colonic stricture secondary to necrotizing enterocolitis. In this short series of patients, motility of the distal bowel was correctly assessed in six patients and partially correctly assessed in one patient. One patient did not pass stools per anus after the Bishop-Koop, and he was later confirmed to have Hirschsprung disease. Four patients resumed normal evacuation pattern after closure of the Bishop-Koop. One patient had a Bishop-Koop colostomy because of recurrent enterocolitis after a transanal pull-through. Although he evacuated normally while having the colostomy, the diarrhea recurred after the ostomy was closed. An additional patient, with a severe behavioral problem, did not evacuate per anus after her colostomy was transformed in a Bishop-Koop-type ostomy, despite the apparent presence of normal ganglia in the bowel wall.
CONCLUSIONS
Data from the present series allow us to affirm that Bishop-Koop-type ostomy is a safe and efficient procedure that can be used to assess distal bowel function before a definitive transit reconstruction, in children with uncertain motility issues.
Topics: Humans; Male; Child; Female; Cross-Sectional Studies; Neoplasm Recurrence, Local; Ostomy; Intestinal Atresia; Intestinal Obstruction; Retrospective Studies
PubMed: 36946847
DOI: 10.1590/0102-672020230002e1722 -
Channels (Austin, Tex.) Dec 2023SLC26A9 is one out of 11 proteins that belong to the SLC26A family of anion transporters. Apart from expression in the gastrointestinal tract, SLC26A9 is also found in... (Review)
Review
SLC26A9 is one out of 11 proteins that belong to the SLC26A family of anion transporters. Apart from expression in the gastrointestinal tract, SLC26A9 is also found in the respiratory system, in male tissues and in the skin. SLC26A9 has gained attention because of its modifier role in the gastrointestinal manifestation of cystic fibrosis (CF). SLC26A9 appears to have an impact on the extent of intestinal obstruction caused by meconium ileus. SLC26A9 supports duodenal bicarbonate secretion, but was assumed to provide a basal Cl- secretory pathway in airways. However, recent results show that basal airway Cl- secretion is due to cystic fibrosis conductance regulator (CFTR), while SLC26A9 may rather secrete HCO-, thereby maintaining proper airway surface liquid (ASL) pH. Moreover, SLC26A9 does not secrete but probably supports reabsorption of fluid particularly in the alveolar space, which explains early death by neonatal distress in Slc26a9-knockout animals. While the novel SLC26A9 inhibitor S9-A13 helped to unmask the role of SLC26A9 in the airways, it also provided evidence for an additional role in acid secretion by gastric parietal cells. Here we discuss recent data on the function of SLC26A9 in airways and gut, and how S9-A13 may be useful in unraveling the physiological role of SLC26A9.
Topics: Animals; Biological Transport; Cystic Fibrosis; Intestines; Respiratory System; Sulfate Transporters; Antiporters
PubMed: 36866602
DOI: 10.1080/19336950.2023.2186434 -
Cureus Dec 2022Apart from meconium ileus, amniotic fluid plug syndrome, malrotation of the gut, Hirschprung's disorder, trauma, and other rare causes, bowel atresia is one of the most...
Apart from meconium ileus, amniotic fluid plug syndrome, malrotation of the gut, Hirschprung's disorder, trauma, and other rare causes, bowel atresia is one of the most common causes of bowel obstruction in newborns. Jejunal atresia can affect multiple lengths of the bowel. The higher the level of atresia, the greater the severity. The outcome of bowel atresia related to surgical repair is favorable. In general, both mortality and morbidity are affected by affiliated medical conditions such as preterm birth, cystic fibrosis, and other congenital anomalies; the sophistication of the lesion; and surgical complications. We present the case of a one-day-old baby who had two episodes of bilious vomiting with abdominal distension within 10 minutes of birth. The baby was advised to undergo ultrasonography of the abdomen and pelvis for further evaluation, and the findings were reported.
PubMed: 36694481
DOI: 10.7759/cureus.32766 -
Journal of Clinical Medicine Nov 2022Perforation of the ileum in the antepartum period resulting in meconial peritonitis is a condition that, although rare, is burdened by several complications. In 80-90%...
Perforation of the ileum in the antepartum period resulting in meconial peritonitis is a condition that, although rare, is burdened by several complications. In 80-90% of cases, meconial ileus is the first manifestation of a disease, cystic fibrosis. In the remaining 10-20% of cases, it is caused by other situations, such as prematurity. In most cases, the diagnosis of meconial ileus occurs after birth, although in some cases it can be suspected prenatally, with the finding of a hyperechoic intestine on second trimester ultrasound. The prognosis depends on the gestational age, the location of the obstruction and the presence of fetal abnormalities. Mortality is very high and the recovery of intestinal function in the postoperative course is very high risk. In this case series, we describe two meconial peritonitis and our experience at the center.
PubMed: 36498701
DOI: 10.3390/jcm11237127 -
International Journal of Neonatal... Oct 2022Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This...
Testing immunoreactive trypsinogen (IRT) is the first step in cystic fibrosis (CF) newborn screening. While high IRT is associated with CF, some cases are missed. This survey aimed to find factors associated with missed CF cases due to IRT levels below program cutoffs. Twenty-nine states responded to a U.S-wide survey and 13 supplied program-related data for low IRT false screen negative cases (CFFN) and CF true screen positive cases (CFTP) for analysis. Rates of missed CF cases and odds ratios were derived for each factor in CFFNs, and two CFFN subgroups, IRT above ("high") and below ("low") the CFFN median (39 ng/mL) compared to CFTPs for this entire sample set. Factors associated with "high" CFFN subgroup were Black race, higher IRT cutoff, fixed IRT cutoff, genotypes without two known CF-causing variants, and meconium ileus. Factors associated with "low" CFFN subgroup were older age at specimen collection, Saturday birth, hotter season of newborn dried blood spot collection, maximum ≥ 3 days laboratories could be closed, preterm birth, and formula feeding newborns. Lowering IRT cutoffs may reduce "high" IRT CFFNs. Addressing hospital and laboratory factors (like training staff in collection of blood spots, using insulated containers during transport and reducing consecutive days screening laboratories are closed) may reduce "low" IRT CFFNs.
PubMed: 36412584
DOI: 10.3390/ijns8040058 -
HGG Advances Jan 2023Phasing of heterozygous alleles is critical for interpretation of -effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using...
Phasing of heterozygous alleles is critical for interpretation of -effects of disease-relevant variation. We sequenced 477 individuals with cystic fibrosis (CF) using linked-read sequencing, which display an average phase block N50 of 4.39 Mb. We use these samples to construct a graph representation of haplotypes, demonstrating its utility for understanding complex CF alleles. These are visualized in a Web app, CFTbaRcodes, that enables interactive exploration of haplotypes present in this cohort. We perform fine-mapping and phasing of the chr7q35 trypsinogen locus associated with CF meconium ileus, an intestinal obstruction at birth associated with more severe CF outcomes and pancreatic disease. A 20-kb deletion polymorphism and a missense variant p.Thr8Ile (rs62473563) are shown to independently contribute to meconium ileus risk (p = 0.0028, p = 0.011, respectively) and are pancreas eQTLs (p = 9.5 × 10 and p = 1.4 × 10, respectively), suggesting the mechanism by which these polymorphisms contribute to CF. The phase information from linked reads provides a putative causal explanation for variation at a CF-relevant locus, which also has implications for the genetic basis of non-CF pancreatitis, to which this locus has been reported to contribute.
Topics: Infant, Newborn; Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Meconium Ileus; Meconium; Intestinal Obstruction; Trypsin; Trypsinogen
PubMed: 36386424
DOI: 10.1016/j.xhgg.2022.100156