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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 -
Expert Review of Respiratory Medicine 2023Gastrointestinal (GI)-related symptoms, complications, and comorbidities in cystic fibrosis (CF) are common and research to reduce their burden is a priority for the CF... (Review)
Review
INTRODUCTION
Gastrointestinal (GI)-related symptoms, complications, and comorbidities in cystic fibrosis (CF) are common and research to reduce their burden is a priority for the CF community. To enable future research, this review aimed to summarize the range of GI symptoms, complications and comorbidities seen in CF, the underlying pathophysiology, and treatments.
AREAS COVERED
This was a rapid systematic review undertaken using the recommendations from the Cochrane Rapid Reviews Methods Group. We searched databases including PubMed, Embase, Medline and the Cochrane database and identified those studies reporting GI-related symptoms, complications, or comorbidities in CF or their treatment. Our searches identified 2,930 studies and a total 119 studies met our inclusion criteria. Where a prevalence could be determined, GI symptoms were reported in 33.7% of study participants. The range of symptoms reported was broad and the highest median prevalence included flatulence (43.5%), bloating and abdominal distension (36%), and fatty stool (36%). Meconium ileus was reported in 12% and distal intestinal obstruction syndrome in 8.5.
EXPERT OPINION
GI-related symptoms, complications, and comorbidities in CF are common. More consistent characterization and recording of these symptoms in clinical studies may help achieve the priority of reducing the burden of GI disease in CF.
Topics: Humans; Cystic Fibrosis; Intestinal Obstruction; Comorbidity; Prevalence
PubMed: 37345513
DOI: 10.1080/17476348.2023.2228194 -
Pediatric Pulmonology Sep 2023Tracheobronchomalacia (TBM) is estimated to be present in 1 in 2100 children. Previous reports suggest the prevalence is higher in children with cystic fibrosis (CF)....
BACKGROUND
Tracheobronchomalacia (TBM) is estimated to be present in 1 in 2100 children. Previous reports suggest the prevalence is higher in children with cystic fibrosis (CF). This has clinical implications with potential to influence airway clearance and lung health.
AIM
To determine the prevalence and clinical associations of TBM in Western Australian children with CF.
METHODS
Children with CF born between 2001 and 2016 were included. Operation reports from bronchoscopies performed until the age of 4 were retrospectively reviewed. Data were collected on the presence, persistence defined as a repeat diagnosis, and severity of TBM. Data on genotype, pancreatic status, and symptoms at CF diagnosis were extracted from the medical record. Associations between categorical variables were compared using χ and Fisher's exact test.
RESULTS
Of 167 children (79 male), 68 (41%) were diagnosed with TBM at least once, with TBM persistent in 37 (22%) and severe in 31 (19%). TBM was significantly associated with pancreatic insufficiency (χ = 7.874, p < 0.05, odds ratio [OR] 3.4), delta F508 gene mutation (χ = 6.489, p < 0.05, OR 2.3), and a presentation of meconium ileus (χ = 8.615, p < 0.05, OR 5.0). Severe malacia was less likley in females (χ = 4.523, p < 0.05, OR 0.42) . No significant relationship was found with respiratory symptoms at the time of CF diagnosis (χ = 0.742, p = 0.39).
CONCLUSIONS
TBM was common in this group of children under the age of 4 with CF. A high index of suspicion for airway malacia should be considered in children with CF, particularly those who present with meconium ileus and have gastrointestinal symptoms at diagnosis.
Topics: Female; Humans; Male; Child; Cystic Fibrosis; Meconium Ileus; Prevalence; Retrospective Studies; Australia; Cystic Fibrosis Transmembrane Conductance Regulator
PubMed: 37294078
DOI: 10.1002/ppul.26550 -
Journal of Human Genetics Oct 2023Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common...
Cystic fibrosis (CF) is an autosomal recessive disease caused by pathogenic variants in CF transmembrane conductance regulator (CFTR). While CF is the most common hereditary disease in Caucasians, it is rare in East Asia. In the present study, we have examined clinical features and the spectrum of CFTR variants of CF patients in Japan. Clinical data of 132 CF patients were obtained from the national epidemiological survey since 1994 and CF registry. From 2007 to 2022, 46 patients with definite CF were analyzed for CFTR variants. All exons, their boundaries, and part of promoter region of CFTR were sequenced and the presence of large deletion and duplications were examined by multiplex ligation-dependent probe amplification. CF patients in Japan were found to have chronic sinopulmonary disease (85.6%), exocrine pancreatic insufficiency (66.7%), meconium ileus (35.6%), electrolyte imbalance (21.2%), CF-associated liver disease (14.4%), and CF-related diabetes (6.1%). The median survival age was 25.0 years. The mean BMI percentile was 30.3%ile in definite CF patients aged < 18 years whose CFTR genotypes were known. In 70 CF alleles of East Asia/Japan origin, CFTR-dele16-17a-17b was detected in 24 alleles, the other variants were novel or very rare, and no pathogenic variants were detected in 8 alleles. In 22 CF alleles of Europe origin, F508del was detected in 11 alleles. In summary, clinical phenotype of Japanese CF patients is similar to European patients, but the prognosis is worse. The spectrum of CFTR variants in Japanese CF alleles is entirely different from that in European CF alleles.
Topics: Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Mutation; Japan; Genotype
PubMed: 37217688
DOI: 10.1038/s10038-023-01160-2 -
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 -
Fetal Diagnosis and Therapy 2023Cystic fibrosis (CF) is a potentially severe disease. The development of new therapies with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has...
INTRODUCTION
Cystic fibrosis (CF) is a potentially severe disease. The development of new therapies with cystic fibrosis transmembrane conductance regulator (CFTR) modulators has been a great advance in the management of this condition because they improve the function of the faulty CFTR protein rather than palliate its consequences. CFTR modulator therapy improves pancreatic and lung function and, therefore, quality of life, with greater benefits the sooner treatment is started. For this reason, the use of these therapies is being approved for increasingly younger patients. Only two cases of pregnant women taking CFTR modulator therapy with CF fetuses have been reported, suggesting that it could resolve meconium ileus (MI) prenatally and delay/prevent other consequences of CF.
CASE PRESENTATION
We report a case of a healthy pregnant patient who underwent CFTR modulator therapy with elexacaftor-tezacaftor-ivacaftor (ETI) in order to treat her fetus with CF (F508del homozygous CFTR mutation) and MI. Ultrasound findings suggestive of MI were observed at 24 weeks. Both parents were tested for CFTR mutations, and both were carriers of the F508del CFTR mutation. The fetus was diagnosed with CF by amniocentesis at 26+2 weeks. Maternal ETI therapy was initiated at 31+1 weeks, and no dilated bowel was observed at 39 weeks. There were no signs of bowel obstruction after birth. Maternal ETI treatment was continued during breastfeeding, with normal liver function. Immunoreactive trypsinogen in the newborn was 58.1 ng/mL, sweat chloride test was 80 mmol/L, and fecal elastase on the second day of life was 58 μg/g.
CONCLUSION
Prenatal ETI treatment, as well as during breastfeeding, could solve, prevent, and/or delay CF complications.
Topics: Humans; Pregnancy; Infant, Newborn; Female; Cystic Fibrosis Transmembrane Conductance Regulator; Cystic Fibrosis; Quality of Life; Mutation; Fetus
PubMed: 36996799
DOI: 10.1159/000530261 -
Zhonghua Jie He He Hu Xi Za Zhi =... Apr 2023Cystic fibrosis (CF) is one of the most common autosomal recessive genetic diseases in Caucasians, but CF patients in China are rare, and it was listed as the first...
Cystic fibrosis (CF) is one of the most common autosomal recessive genetic diseases in Caucasians, but CF patients in China are rare, and it was listed as the first batch of rare diseases in China in 2018. In recent years, CF has been gradually recognized in China, and the number of CF patients reported in China in the past 10 years is more than 2.5 times the total number in the previous 30 years, and the total number of CF patients is estimated to be more than 20 000. The research progress of CF gene modification has led to the innovation of CF treatment. However, the sweat test as an important test for the diagnosis of CF has not been widely implemented in China. At present, the diagnosis and treatment of CF in China still lacks standardized recommendations. In view of these updates, the Chinese Experts Cystic Fibrosis Consensus Committee has formed "the Chinese experts consensus statement: diagnosis and treatment of cystic fibrosis" based on extensive opinion gathering, literatures review, multiple meetings and discussions. This consensus collects 38 core issues related to CF, including pathogenesis, epidemiology, clinical characteristics, diagnosis, treatment, rehabilitation, and patient management. Finally, 32 recommendations were formulated. The consensus used the modified GRADE methodology to grade the evidence evaluation and recommendations. This is the current state of CF consensus in China, and we hope to improve the diagnosis and treatment of CF in China in the future.CF should be suspected if there is: (1) a family history of CF; (2) delayed meconium expulsion or meconium ileus; (3) pancreatic exocrine insufficiency, mainly characterized by long-standing steatorrhea and malnutrition; (4) recurrent lower respiratory tract infections of infantile onset, especially infections of respiratory aetiology; (5) chronic sinusitis, especially when combined with juvenile presentation of nasal polyps; (6) chest CT abnormalities such as the presence of air trapping, bronchiectasis (upper lobe predominant); (7) pseudo-Bartter syndrome; (8) absence of vas deferens in males; (9) clubbing in young bronchiectasis patients(1C).1.1 Presence of one or more of the characteristic clinical manifestations or family history consistent with CF, and meeting at least one of the following definite diagnostic criteria in 1.2 or 1.3.1.2 Sweat chloride testing:(1) Concentrations of more than 60 mmol/L are diagnostic; (2) concentrations between 30-59 mmol/L are intermediate, and genetic variation must be considered to confirm the diagnosis; (3) concentrations less than 30 mmol/L are considered normal.1.3 Genetic testing:(1) Detection of two disease-causing (cystic fibrosis transmembrane conductance regulator) mutations on biallelic alleles; (2) The variants are of undetermined significance, but tests such as sweat chloride concentration, intestinal current measurement, or nasal mucosal potential difference suggest abnormal CFTR function, then CF is diagnostic(1C).Sweat chloride testing and gene analysis are recommended in all patients suspected of CF(1D).Sweat chloride testing is the gold standard for the clinical diagnosis of CF(1C).Biallelic pathogenic variants of are a definitive diagnosis of CF(1D).Chest CT is a sensitive test for early stages of lung disease in patients with CF and is appropriate in younger patients and to assess disease progression. The imaging findings of abdominal visceral involvement in CF lack specificity(2C).Fecal elastase may be used as the first indicator to assess pancreatic exocrine function in patients with CF (2C).CF related liver disease was diagnosed when CF was confirmed and 2 of the following 4 criteria were met: (1) hepatomegaly and/or splenomegaly confirmed by ultrasound; (2) ALT, AST, and GGT on three consecutive occasions above the upper limit of normal on three consecutive occasions for more than 12 months and excluding other causes; (3) had evidence of liver involvement, portal hypertension, or bile duct dilatation by ultrasound; (4) liver biopsy confirmation (focal biliary cirrhosis or multilobular cirrhosis) may be indicated if the diagnosis is suspected(2D).Pulmonary exacerbations are indicated when any 4 of the following 12 signs or symptoms are met: increased sputum; new onset haemoptysis or increased haemoptysis; exacerbation of cough; increased dyspnea; malaise, fatigue, or somnolence; body temperature above 38 ℃; anorexia or weight loss; sinus pain or tenderness; increased sinus secretions; new chest signs; FEV≥10% decline from previous; imaging changes suggestive of pulmonary infection(2D).Diagnostic criteria for CF related diabetes are the same as those for diabetes in the population(1D).Anthropometric parameters reflecting nutritional status should be assessed regularly. And the goal of nutritional assessment is to evaluate and monitor whether pediatric patients are achieving normal standards of growth and development or whether adult patients are maintaining adequate nutritional status(1C).Pathohistological biopsy is not recommended as a first-line diagnostic method in patients with a suspected diagnosis of CF(1D).At least 6 months of azithromycin treatment is recommended for CF patients with chronic PA infection(2A).Long term treatment with hypertonic saline is recommended for patients with CF(1A).Long term use of DNase is recommended in patients with CF aged 6 years and older(1A).Inhaled mannitol therapy is recommended for more than 6 months in patients with CF aged 18 years and older when other inhaled treatments are unavailable or intolerable(2A).When sputum cultures from patients with CF are positive for , it needs to determine the characteristics of the infection first. The purpose for acute infection is to eradicate . Chronic colonization does not need to be eradicated, and the main purpose is to reduce the bacterial load and improve symptoms(1A).Inhaled antibiotic therapy is recommended for CF patients with infection(1A).In patients with CF without asthma or ABPA, routine inhaled or systemic glucocorticoids are not recommended (2A).Bronchodilators can be used in the short term to improve symptoms in patients with CF in the presence of airway obstruction, but the long-term benefit is insufficient (2B).Patients with CF can take acetylcysteine orally or aerosolized(2A).Intensive implementation of non-antimicrobial therapy is recommended during pulmonary exacerbations in patients with CF. Antimicrobials with activity against PA were selected for empirical treatment, and the treatment was adjusted according to the results of bacterial culture and drug susceptibility testing. A 21-day long course of anti-infective therapy is not recommended(1B).Medical therapy is recommended for CF patients with ABPA who meet any of the following criteria: patients with elevated immunoglobulin E levels and concomitant worsening of pulmonary function and/or pulmonary symptoms, or imaging suggesting new infiltrative foci in the chest(1D).Glucocorticoids are recommended for ABPA exacerbations in CF patients without contraindications(2D).Itraconazole should be added if the patient presents with poor response to corticosteroids, recurrence of ABPA, corticosteroid dependence, or corticosteroid toxicity(2D).Patients with CF may be evaluated for lung transplantation when they meet the following criteria after optimal medical therapy: (1) FEV<30% predicted; (2) FEV<40% predicted (<50% predicted in children) with the following: 6-minute walk distance<400 meters; PaCO>50 mmHg(1 mmHg=0.133 kPa); hypoxia at rest or after activity; pulmonary artery pressure measured by cardiotocography>50 mmHg or right heart dysfunction; continued deterioration despite aggressive supplementation of nutritional support; two exacerbations requiring intravenous antibiotic therapy per year; massive hemoptysis (>240 ml) requiring pulmonary artery embolization; presented with pneumothorax; (3) FEV<50% predicted and rapid decline in lung function or rapid worsening of symptoms; (4) Presented with an acute exacerbation requiring positive pressure mechanical ventilation(2C).Pancreatic enzyme replacement therapy is recommended in patients with CF pancreatic disease(1A).Ursodeoxycholic acid is not recommended in asymptomatic patients with CF hepatobiliary disease(2B).Acid suppression is recommended for CF patients with gastrointestinal symptoms such as acid regurgitation (2B).Insulin therapy is recommended in CF related diabetes(1B).Energy intake in patients with CF is recommended to be 110%-200% of the energy requirement of a healthy person under equivalent physiological conditions. And maintaining adequate protein, appropriate intake of fats, electrolytes, and fat-soluble vitamins are recommanded(1A).Airway clearance therapy and appropriate exercise are recommended for patients with CF(1A).Patients with CF should have regular follow-up. Adult patients are recommended to be followed every 3-6 months, and children should be followed more frequently(2A).Inpatients and outpatients are recommended to be separated according to microbiota carriage status(1D).Good hand hygiene is recommended for the patients with CF and their contacts(1D).It is recommended that CF patients wear masks in healthcare settings. This may reduce the release of potentially infectious aerosols during coughing (1D).Annual influenza vaccination is recommended for patients with CF>6 months of age and for all family members of patients with CF and all healthcare workers caring for these patients(2D).Palivizumab may be considered for the prevention of respiratory syncytial virus infection in patients with CF under two years of age(2A).
Topics: Adult; Child; Child, Preschool; Humans; Male; Adrenal Cortex Hormones; Anti-Bacterial Agents; Bronchiectasis; Bronchodilator Agents; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Deoxyribonucleases; Hemoptysis; Mannitol
PubMed: 36990700
DOI: 10.3760/cma.j.cn112147-20221214-00971 -
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