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International Journal of Neonatal... Jun 2020Screening metrics are essential to both quality assessment and improvement, but are highly dependent on the way positive tests and cases are counted. In cystic fibrosis... (Review)
Review
Screening metrics are essential to both quality assessment and improvement, but are highly dependent on the way positive tests and cases are counted. In cystic fibrosis (CF) screening, key factors include how mild cases of late-presenting CF and CF screen positive, inconclusive diagnosis (CFSPID) are counted, whether those at prior increased risk of CF are excluded from the screened population, and which aspects of the screening pathway are considered. This paper draws on the New Zealand experience of almost forty years of newborn screening for CF. We demonstrate how different definitions impact the calculation of screening sensitivity. We suggest that, to enable meaningful comparison, CF screening reports should clarify what steps in the screening pathway are included in the assessment, as well as the algorithm used and screening target.
PubMed: 33073037
DOI: 10.3390/ijns6020047 -
Medicine Oct 2020Congenital syphilis (CS) can manifest as a variety of clinical presentations according to the severity in symptomatic infants during neonatal period. Preterm neonates...
RATIONALE
Congenital syphilis (CS) can manifest as a variety of clinical presentations according to the severity in symptomatic infants during neonatal period. Preterm neonates with CS may have more clinical evidences of infection and be more severely affected by CS compared with term ones. With increasing survival of markedly premature infants for recent decades, CS may be a challenging problem in those with severe manifestations associated with combined pathophysiologies of CS and prematurity.
PATIENT CONCERNS
A very low birth weight infant at 32 weeks gestation presented with an unusual CS presentation consisting of prematurity-associated severe neonatal morbidities including meconium obstruction, prolonged cholestatic jaundice with elevated liver enzymes, and disseminated intravascular coagulation with a bleeding diathesis, in addition to common or typical manifestations of CS.
DIAGNOSES
Congenital syphilis.
INTERVENTIONS
Therapy consisting of a complete course of parenteral penicillin, blood component therapy, proximal ileotomy with inspissated meconium evacuation and distal loop ileostomy, and other conservative treatments.
OUTCOMES
Resolution with normal gastrointestinal function and improved liver function was observed.
LESSONS
This case suggests that in premature infants CS may manifest as unusual severe neonatal morbidities that may result from combination of syphilitic pathologies and contributors or conditions associated with prematurity including multisystem immaturity.
Topics: Blood Component Transfusion; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Very Low Birth Weight; Meconium Ileus; Penicillins; Severity of Illness Index; Syphilis, Congenital
PubMed: 33019408
DOI: 10.1097/MD.0000000000022321 -
Genes Sep 2020The goal was to study the phenotypic manifestations of c.3844T>C (p.Trp1282Arg, W1282R) variant, a CF-causing mutation, in patients from the Russian Federation. Clinical...
The goal was to study the phenotypic manifestations of c.3844T>C (p.Trp1282Arg, W1282R) variant, a CF-causing mutation, in patients from the Russian Federation. Clinical manifestations and complications (the age at CF diagnosis, sweat test, pancreatic status, lung function, microbial infection, body mass index (BMI), the presence of meconium ileus (MI), diabetes, and severe liver disease) were compared in four groups: group 1-patients carrying c.3844T>C and severe class I or II variant in trans; group 2-3849+10kbC>T/F508del patients; group 3-F508del/F508del patients; and group 4-patients with W1282R and "mild" variant in trans. Based on the analyses, W1282R with class I or II variant in trans appears to cause at least as severe CF symptoms as F508del homozygotes as reflected in the early age of diagnosis, high sweat chloride concentration, insufficient pancreatic function, and low lung function, in contrast to 3849+10kbC-T/F508del compound heterozygotes having milder clinical phenotypes. The W1282R pathogenic variant is seemed to lead to severe disease phenotype with pancreatic insufficiency similarly to the F508del homozygous genotype.
Topics: Adolescent; Adult; Child; Child, Preschool; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Genotype; Homozygote; Humans; Infant; Mutation; Phenotype; Russia; Young Adult
PubMed: 32992607
DOI: 10.3390/genes11101137 -
Microorganisms May 2020Hyperechogenic bowel (HB) is a nonspecific ultrasound finding that can be associated with human cytomegalovirus (CMV) congenital infection. In this study, we...
Hyperechogenic bowel (HB) is a nonspecific ultrasound finding that can be associated with human cytomegalovirus (CMV) congenital infection. In this study, we investigated HB pathophysiology in CMV-infected fetuses. We examined small and large intestine as well as pancreas in 8 fetuses at 22 weeks of gestation with congenital CMV infection. Ultrasound findings showed 4 fetuses with HB and 4 without. As negative group, 4 fetuses without CMV infection and without HB were studied. Immunohistochemistry for CMV, lymphocytic infiltrate, B-cell leukemia/lymphoma-2 (bcl-2), CD-117, cystic fibrosis transmembrane regulator (CFTR) were performed. HB fetuses showed multiple and sequential CMV-positive ganglion cells of Auerbach's myenteric plexus. In the ganglia, bcl-2 was weakly expressed representing a reduced neuronal functionality. CD-117 revealed a regular distribution of Cajal cells, the pacemakers of intestinal contractility. Pancreas showed normal CFTR staining, indicating a preserved exocrine secretion, thus unlikely a contributory factor in HB. In CMV-infected fetuses without HB, CMV-positive cells were scatteredly found in ganglion cells and bcl-2 was strongly expressed. Intestinal CD-117 and pancreatic CFTR expression were similar to fetuses with HB. In conclusion, fetal CMV infection of the bowel may lead to peristalsis impairment (paralytic ileus) due to intestinal plexus involvement, which at ultrasound appeared as HB.
PubMed: 32455864
DOI: 10.3390/microorganisms8050779 -
Molecular Therapy. Methods & Clinical... Jun 2020Cystic fibrosis (CF) is the main genetic cause of death among the Caucasian population. The disease is characterized by abnormal fluid and electrolyte mobility across...
Cystic fibrosis (CF) is the main genetic cause of death among the Caucasian population. The disease is characterized by abnormal fluid and electrolyte mobility across secretory epithelia. The first manifestations occur within hours of birth (meconium ileus), later extending to other organs, generally affecting the respiratory tract. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator () gene. encodes a cyclic adenosine monophosphate (cAMP)-dependent, phosphorylation-regulated chloride channel required for transport of chloride and other ions through cell membranes. There are more than 2,000 mutations described in the gene, but one of them, phenylalanine residue at amino acid position 508 (p.F508del), a recessive allele, is responsible for the vast majority of CF cases worldwide. Here, we present the results of the application of genome-editing techniques to the restoration of CFTR activity in p.F508del patient-derived induced pluripotent stem cells (iPSCs). Gene-edited iPSCs were subsequently used to produce intestinal organoids on which the physiological activity of the restored gene was tested in forskolin-induced swelling tests. The seamless restoration of the p.F508del mutation resulted in normal expression of the mature CFTR glycoprotein, full recovery of CFTR activity, and a normal response of the repaired organoids to treatment with two approved CF therapies: VX-770 and VX-809.
PubMed: 32373648
DOI: 10.1016/j.omtm.2020.04.005 -
IUBMB Life Jun 2020Guanylyl cyclase C (GC-C) is the receptor for the heat-stable enterotoxin, which causes diarrhea, and the endogenous ligands, guanylin and uroguanylin. GC-C is... (Review)
Review
Guanylyl cyclase C (GC-C) is the receptor for the heat-stable enterotoxin, which causes diarrhea, and the endogenous ligands, guanylin and uroguanylin. GC-C is predominantly expressed in the intestinal epithelium and regulates fluid and ion secretion in the gut. The receptor has a complex domain organization, and in the absence of structural information, mutational analysis provides clues to mechanisms of regulation of this protein. Here, we review the mutational landscape of this receptor that reveals regulatory features critical for its activity. We also summarize the available information on mutations in GC-C that have been reported in humans and contribute to severe gastrointestinal abnormalities. Since GC-C is also expressed in extra-intestinal tissues, it is likely that mutations thus far reported in humans may also affect other organ systems, warranting a close observation of these patients in future.
Topics: Allosteric Regulation; Humans; Meconium Ileus; Mutation; Protein Domains; Receptors, Enterotoxin; Signal Transduction
PubMed: 32293781
DOI: 10.1002/iub.2283 -
Scientific Reports Mar 2020Very low birth weight (VLBW) neonates experience various problems, including meconium-related ileus (MRI). This study investigated the risk factors of MRI and surgical...
Very low birth weight (VLBW) neonates experience various problems, including meconium-related ileus (MRI). This study investigated the risk factors of MRI and surgical MRI in VLBW infants. VLBW neonates admitted to the Neonatal Intensive Care Unit of Seoul National University Children's Hospital from October 2002 to September 2016 were included in the study. The diagnostic criteria for MRI were a decreased frequency of defecation with intolerable feeding, vomiting, and increased gastric residue (>50%); meconium-filled bowel dilatation in an imaging study; and no evidence of necrotizing enteritis or spontaneous intestinal perforation. Medical MRIs and surgical MRIs were managed through conventional treatment and surgical intervention. Of 1543 neonates, 69 and 1474 were in the patient and control groups, respectively. The risk factors for MRI include low birth weight (BW), cesarean section delivery, fetal distress, maternal diabetes, maternal hypertension, and maternal steroid use. Low BW and fetal distress were independent risk factors for MRI. Compared to the medical MRI group (n = 44), the risk factors for surgical MRI (n = 25) included males, younger gestational age, low BW, and meconium located at the small bowel. Male gender and low BW were independent risk factors for surgical MRI. Low BW and fetal distress were independent risk factors for MRI and male gender and low BW were independent risk factors for surgical MRI. In VLBW neonates, careful attention to the risk factors for MRI could minimize or avoid surgical interventions.
Topics: Apgar Score; Birth Weight; Case-Control Studies; Disease Susceptibility; Enterocolitis, Necrotizing; Female; Gestational Age; Humans; Ileus; Infant, Extremely Low Birth Weight; Male; Meconium; Prognosis; Republic of Korea; Risk Assessment; Risk Factors
PubMed: 32170203
DOI: 10.1038/s41598-020-60016-3 -
Cellular and Molecular Life Sciences :... Sep 2020The solute carrier family 6 member 14 (SLC6A14) protein imports and concentrates all neutral amino acids as well as the two cationic acids lysine and arginine into the... (Review)
Review
The solute carrier family 6 member 14 (SLC6A14) protein imports and concentrates all neutral amino acids as well as the two cationic acids lysine and arginine into the cytoplasm of different cell types. Primarily described as involved in several cancer and colonic diseases physiopathological mechanisms, the SLC6A14 gene has been more recently identified as a genetic modifier of cystic fibrosis (CF) disease severity. It was indeed shown to have a pleiotropic effect, modulating meconium ileus occurrence, lung disease severity, and precocity of P. aeruginosa airway infection. The biological mechanisms explaining the impact of SLC6A14 on intestinal and lung phenotypes of CF patients are starting to be elucidated. This review focuses on SLC6A14 in lung and gastrointestinal physiology and physiopathology, especially its involvement in the pathophysiology of CF disease.
Topics: Amino Acid Transport Systems; Colonic Diseases; Cystic Fibrosis; Gastrointestinal Tract; Genetic Variation; Humans; Linkage Disequilibrium; Lung; Neoplasms; Severity of Illness Index
PubMed: 32166393
DOI: 10.1007/s00018-020-03487-x -
BMC Pediatrics Mar 2020Meconium peritonitis is defined as aseptic chemical inflammation caused by intrauterine bowel perforation. The underlying causes of bowel perforation include intestinal...
BACKGROUND
Meconium peritonitis is defined as aseptic chemical inflammation caused by intrauterine bowel perforation. The underlying causes of bowel perforation include intestinal atresia, midgut volvulus, intussusception, congenital bands, and meconium ileus.
CASE PRESENTATION
Siblings with prenatally diagnosed meconium peritonitis of different etiologies were found. The elder sister was born at 36 + 6 weeks gestation with a birth weight of 3110 g. She was diagnosed with meconium peritonitis caused by ileal atresia. Two years later, the younger brother was born at 34 + 3 weeks gestation with a birth weight of 2850 g. He was diagnosed with meconium peritonitis caused by midgut volvulus.
CONCLUSIONS
Among the previously reported cases of meconium peritonitis, familial occurance of meconium peritonitis is extremely rare. We present a case of prenatally diagnosed meconium peritonitis in siblings to promote further understanding of its etiology and clinical course.
Topics: Cesarean Section; Female; Humans; Infant, Newborn; Intestinal Atresia; Intestinal Volvulus; Male; Meconium; Peritonitis; Pregnancy; Siblings
PubMed: 32138710
DOI: 10.1186/s12887-020-2016-3 -
Cureus Dec 2019Hydrogen peroxide is a disinfectant commonly used for cleansing superficial wounds due to its oxidizing capacity. In the past, it has also been used for the management...
Hydrogen peroxide is a disinfectant commonly used for cleansing superficial wounds due to its oxidizing capacity. In the past, it has also been used for the management of meconium ileus in children as the oxidizing action of hydrogen peroxide potentiates peristalsis that relieves ileus or fecal impaction. The potential dangers were unknown till Pumphrey, in 1951, described the harmful effects of its use as an enema. We present a case of a 32-year-old female who was admitted for complaints of perianal pain. She used an enema, consisting of water and hydrogen peroxide, for constipation. It improved her symptoms but subsequently, she developed a burning sensation in her rectum. The patient had a colonoscopy which revealed severe proctitis up to 15 cm from the anal verge manifested by superficial mucosal ulceration, marked erythema, and edema with friable mucosa and hemorrhage. The patient was subsequently given mesalamine, and the symptoms resolved.
PubMed: 32025395
DOI: 10.7759/cureus.6468