A Case of an Extremely Preterm Infant with Intussusception Triggered by Acquired Cytomegalovirus Infection.

Intussusception is a common cause of intestinal obstruction in infants aged 6-18 months. However, intussusception in preterm neonates (IPN) is an exceedingly rare disorder. The etiology of IPN remains unclear, but common prenatal injuries, such as those causing intestinal hypoxia/hypoperfusion, dysmotility, and strictures, have been proposed as possible contributing factors. Diagnosis is often delayed because the symptoms closely resemble those of necrotizing enterocolitis (NEC). Given the divergent treatments for IPN and NEC, establishing an early and accurate diagnosis is crucial. IPN is predominantly located in the small intestine (91.6%), and ultrasonography proves useful in its diagnosis. We present a case of a very preterm infant who developed intussusception triggered by acquired cytomegalovirus (aCMV) infection, necessitating surgical treatment. The cause of intussusception in this case was diagnosed as aCMV enteritis because no organic lesions were observed in the advanced part of the intussusception. The presence of CMV was confirmed by CMV-DNA-PCR examination of the resected intestinal tract. Intestinal edema and decreased intestinal peristalsis due to aCMV enteritis are likely the primary causes of the intussusception.

Challenging management of a baby with congenital multiple intestinal atresia, trisomy 18 and extremely low birth weight: a case report.

BACKGROUND: Extremely low birth weight (< 1000 g) still influences postsurgical prognosis in the neonatal and infantile periods. Additionally, the life expectancy of neonates with trisomy 18 is extremely poor owing to various comorbidities. Therefore, it takes courage to perform laparotomy for the purpose of treatment of congenital multiple intestinal atresia in a baby with an unpredictable life prognosis. CASE PRESENTATION: Fetal ultrasonography revealed cardiac malformation, intestinal dilation, and physical characteristics suggestive of a chromosomal abnormality in this case. The patient was diagnosed with trisomy 18 after birth, with an extremely low birth weight. An atrial septal defect, ventricular septal defect, dilated jejunum, and a very thin collapsed small intestine were found on ultrasonography. With a diagnosis of congenital small intestinal atresia, a challenging laparotomy was done at 3 days of age, with jejunal atresia and multiple distal small intestinal atresia were observed. The jejunal end and distal small intestinal stump were separated into stomas at the wound edge. Hypertrophic pyloric stenosis developed at the age of 3 months and resolved with medication. The patient gained weight (2 kg) by daily stool injection into anal side of the intestine and decompression against poor peritonitis of dilated jejunum using enteral feeding tube for the long period. Finally, we could perform intestinal reconstruction safely and successfully at the age of 9 months. Tracheotomy was performed due to difficulty in extubation associated with chronic lung disease. The patient was discharged at the age of 1 year and 3 months, and no major problems were noted at the age of 2 years. CONCLUSIONS: We treat congenital intestinal atresia in extremely low birth weight infants with severe chromosomal abnormalities and severe cardiac malformations as follows: Stoma creation is performed quickly to avoid deterioration of the patient's hemodynamics. After that, while continuing enteric management, palliative cardiovascular surgery is performed as necessary, and the patient's body weight and intestinal tract status are determined to allow safe intestinal reconstruction.

Clinical influence of multiplex polymerase chain reaction routine uses in urgent pediatric admissions.

BACKGROUND: The coronavirus disease 2019 outbreak has prompted some hospitals to implement screening tests upon admission since 2020. FilmArray® Respiratory 2.1 Panel (FilmArray) is a multiplex polymerase chain reaction (PCR) test with high sensitivity and specificity for detecting respiratory pathogens. We aimed to assess the clinical influence of the routine use of FilmArray for pediatric patients, including those without symptoms suggestive of an infection. METHODS: We conducted a single-center retrospective observational study, which investigated patients aged ≤15 years who underwent FilmArray on admission in 2021. We collected the patients' epidemiological information, symptoms, and FilmArray results from their electronic health records. RESULTS: A positive result was observed in 58.6% of patients admitted to the general ward or intensive care unit (ICU) but only in 1.5% of patients in the neonatal ward. Among the patients admitted to the general ward or ICU who tested positive, 93.3% had symptoms suggestive of infections, 44.6% had a sick contact before admission, and 70.5% had siblings. However, 62 (28.2%) out of 220 patients without the four (fever, respiratory, gastrointestinal, and dermal) symptoms also had positive results. Among them, 18 patients with adenovirus and three with respiratory syncytial virus were isolated to private rooms. However, 12 (57.1%) patients were discharged without symptoms suggestive of viral infection. CONCLUSION: Multiplex PCR routine use for all inpatients may lead to excessive management of positive cases because FilmArray cannot quantify microorganisms. Thus, targets for testing should be considered carefully based on patients' symptoms and histories of sick contacts.

Comprehensive stratum corneum ceramide profiling reveals reduced acylceramides in ichthyosis patient with CERS3 mutations.

The stratum corneum (SC) of the epidermis acts as a skin permeability barrier, and abnormalities in SC formation lead to several skin disorders. Lipids, especially the epidermis-specific ceramide classes ω-O-acylceramides (acylceramides) and protein-bound ceramides, are essential for skin barrier formation. Ceramide synthase 3 (CERS3) is involved in the synthesis of acylceramides and protein-bound ceramides, and CERS3 mutations cause autosomal recessive congenital ichthyosis. In the present study, we measured ceramide synthase activity and performed comprehensive SC ceramide profiling in an ichthyosis patient with compound heterozygous CERS3 mutations: nonsense mutation p.Arg75* and missense mutation p.Arg229His. The activity of p.Arg75* and p.Arg229His mutant CERS3 proteins was reduced to 4% and 56%, respectively, of the wild-type protein. In the patient's SC, acylceramide levels were greatly reduced, but the levels of protein-bound ceramides remained almost unchanged. Non-acylated ceramide levels were also affected in the patient; in particular, the levels of ceramides composed of sphingosine and non-hydroxy or α-hydroxy fatty acid were substantially higher than in healthy controls. These results suggest that a reduction in acylceramide levels alone leads to ichthyosis. Although protein-bound ceramides are synthesized from acylceramides, levels of acylceramides and protein-bound ceramides are not necessarily correlated.

An infant with refractory cytomegalovirus-induced thrombocytopenia.

The present case underscores the importance of considering the association of severe thrombocytopenia or immune thrombocytopenia with cytomegalovirus (CMV) infection because CMV-induced thrombocytopenia occasionally requires antiviral therapy.

Combination of furosemide and fludrocortisone as a loading test for diagnosis of distal renal tubular acidosis in a pediatric case.

Renal tubular acidosis (RTA) is a rare disease caused by a defect of urinary acidification. The ammonium chloride loading test is the gold standard method for determining the type of RTA. However, because this test has some side effects (e.g., nausea, vomiting, and stomach discomfort), applying this test for pediatric cases is difficult. Recently, a loading test with the combination of furosemide and fludrocortisone was reported to be an alternative to the ammonium chloride loading test, with 100% sensitivity and specificity in adult's cases. We report the first pediatric case of distal RTA in a patient who was successfully diagnosed by a drug loading test with the combination of furosemide and fludrocortisone without any side effects. We also performed genetic analysis and detected a known pathogenic variant in the SLC4A1 gene. The combination loading test of furosemide and fludrocortisone is a useful and safe diagnostic tool for pediatric cases of RTA.

Pyogenic spondylitis and paravertebral abscess caused by Salmonella Saintpaul in an immunocompetent 13-year-old child: a case report.

BACKGROUND: Salmonella spondylitis is an uncommon complication of Salmonella infection in immunocompetent children. To prevent treatment failure and neurological deficits, it needs prompt diagnosis and sufficient effort to identify the causative organism. There are some options to identify the causative organism such as Computed Tomography (CT) guided biopsy or surgical debridement, however when to perform these invasive interventions remains controversial. CASE PRESENTATION: A 13-year-old boy presented with occasional high fever and lower back pain. He was diagnosed with spondylitis of the L4-5 vertebral bodies and paravertebral abscess. Initial blood cultures were negative, therefore empirical antibiotic treatment was started. He responded well to conservative management, and was discharged after clinical improvement. However, he was re-hospitalized 2 weeks after discharge, and surgical debridement was performed which led to the detection of Salmonella Saintpaul as the causative pathogen. It was revealed that the possible source of infection was consumption of raw poultry eggs, or contact with poultry. Definitive antibiotic therapy was started. He was discharged with good recovery after a 6-week hospitalization. CONCLUSIONS: This is the very first case report of pyogenic spondylitis caused by Salmonella Saintpaul. Salmonella should be considered as a causative pathogen of pyogenic spondylitis in immunocompetent children. Identifying the causative organism is essential to prevent treatment failure, and a high index of suspicion is needed for prompt diagnosis especially when blood cultures are negative. Invasive interventions such as CT-guided biopsy should be considered even if the clinical course seems to be uncomplicated.

A Fatal Case of Congenital Langerhans Cell Histiocytosis with Disseminated Cutaneous Lesions in a Premature Neonate.

Background. The outcome of neonates with congenital cutaneous Langerhans cell histiocytosis (LCH) is variable. Observations. We report a case of LCH in a female premature neonate born at 33-week gestation. She had disseminated cutaneous lesions, which consisted of hemorrhagic papules and vesicles, with sparse healthy skin areas, and the hands and feet were contracted with scarring and blackened. She was in respiratory failure although no apparent pulmonary or bone lesions on X-rays were noted. Skin biopsy confirmed a diagnosis of LCH due to observation of CD1a+ Langerhans cells, which lacked expression of E-cadherin and CD56. The patient died 57 hours after birth. Conclusions. Based on this case and the literature survey, the outcome of premature babies with congenital cutaneous LCH lesions is noted to be unfavorable, with the majority of such cases suffering from multisystem disease.

Yersinia pseudotuberculosis infection in Kawasaki disease and its clinical characteristics.

BACKGROUND: The etiology of Kawasaki disease (KD) is unknown. Reportedly, there is an association between KD and Yersinia pseudotuberculosis (YPT). Steroid therapy for KD patients with high risk of cardiac sequelae (CS) has been reported; however, the number of reports is limited. METHODS: We conducted a prospective study of 108 patients with newly diagnosed KD in one year to determine how many KD patients have positive anti-YPT antibody titers and/or positive anti-YPT-derived mitogen (YPM) antibody titers. In addition, we tried to identify clinical differences between KD patients in whom YPT infection was or not a contributing factor. We also compared clinical characteristics of patients treated with the protocol of the Randomized controlled trial to Assess Immunoglobulin plus Steroid Efficacy for Kawasaki disease (RAISE) study (RAISE group) and with the conventional Intravenous immunoglobulin (IVIG) protocol (conventional group). RESULTS: Eleven patients (10%) were positive for anti-YPT and/or anti-YPM antibodies (positive group) and 97 (90%) were negative (negative group). Cardiac sequelae (CS) occurred significantly more frequently in the positive than the negative group (two patients, 18% vs one patient, 1%, p = 0.027). Forty patients were in the RAISE group. Two of 40 (5%) in the RAISE group and one of 68 (1.47%) in the conventional group had CS (p = 0.55). CONCLUSIONS: KD patients with YPT infection had CS significantly more frequently and treatment with RAISE protocol did not decrease the frequency of CS in our cohort, nor did YPT infection affect risk scores of no response to IVIG. However, our sample size was overly small to draw such conclusions. Further investigation in a larger cohort is necessary to confirm our findings. Additionally, further research is needed to determine whether early diagnosis of YPT can prevent KD from developing and reduce the incidence of CS.

Culture-proven neonatal sepsis in Japanese neonatal care units in 2006-2008.

BACKGROUND: Recent Japanese epidemiology of neonatal sepsis and its predominant pathogens has not been reported. It is also unknown whether there are center differences in the incidence of neonatal sepsis, including early-onset sepsis (EOS) and late-onset sepsis (LOS) in Japan. OBJECTIVES: To investigate the morbidity and characteristics of neonatal sepsis in recent years and the differences in the incidence of sepsis among Japanese neonatal care units. METHODS: We retrospectively collected the data of newborn infants with culture-proven sepsis that occurred in five Japanese centers of perinatal care from 2006 to 2008. The incidence of sepsis was calculated, including EOS and LOS, and compared among centers. RESULTS: Morbidity from sepsis occurred in 51/6,894 (0.74%) infants. The incidence of EOS and LOS was 0.13 and 0.61%, respectively. The incidence of total sepsis and LOS in infants <1,000 g of birth weight was significantly higher than that in infants who weighed >1,000 g at birth, whereas there were no significant differences in the incidence of EOS between the different birth weights. Methicillin-resistant Staphylococcus aureus was the most common pathogen involved in morbidity and mortality of neonatal sepsis. Significant center differences were observed in the incidence of LOS, but not EOS. CONCLUSIONS: The majority of culture-proven neonatal sepsis is LOS, which differs among centers, especially in infants who weigh <1,000 g at birth in Japan. We consider that it is important to control nosocomial infection in newborn care units to further reduce the morbidity of neonatal sepsis in Japan.

The pharmacological characteristics of molecular-based inherited salt-losing tubulopathies.

CONTEXT: Our understanding of inherited salt-losing tubulopathies has improved with recent advances in molecular genetics. However, the terminology of Bartter syndrome and Gitelman syndrome does not always accurately reflect their pathophysiological basis or clinical presentation, and some patients are difficult to diagnose from their clinical presentations. OBJECTIVE: In the present study, we conducted molecular analysis and diuretic tests for patients with inherited salt-losing tubulopathies to clarify the pharmacological characteristics of these disorders. PATIENTS: We detected mutations and subsequently conducted diuretic tests using furosemide and thiazide for 16 patients with salt-losing tubulopathies (two with SLC12A1; two with KCNJ1; nine with CLCNKB; and three with SLC12A3). RESULTS: Patients with SLC12A1 mutations showed no response to furosemide, whereas those with SLC12A3 mutations showed no response to thiazide. However, patients with CLCNKB mutations showed no response to thiazide and a normal response to furosemide, and those with KCNJ1 mutations showed a good response to both diuretics. This study revealed the following characteristics of these disorders: 1) subjects with CLCNKB mutations showed one or more biochemical features of Gitelman syndrome (including hypomagnesemia, hypocalciuria, and fractional chloride excretion insensitivity to thiazide administration); and 2) subjects with KCNJ1 mutations appeared to show normal fractional chloride excretion sensitivity to furosemide and thiazide administration. CONCLUSIONS: These results indicate that these disorders are difficult to distinguish in some patients, even when using diuretic challenge. This clinical report provides important findings that can improve our understanding of inherited salt-losing tubulopathies and renal tubular physiology.

Mutation analysis of the ornithine transcarbamylase (OTC) gene in five Japanese OTC deficiency patients revealed two known and three novel mutations including a deep intronic mutation.

Ornithine transcarbamylase (OTC) deficiency is the most common inborn error of the urea cycle. Although a combination of molecular methods have been used including DNA sequencing of all 10 exons and exon-intron boundaries of OTC gene, only approximately 80% of patients with OTC deficiency are found to have mutations. We report two known and three novel mutations of the OTC gene in five Japanese patients including two neonatal-onset, one late-onset, and two symptomatic female patients. Known nonsense mutations (c.578G>A and c.421C>T) were detected in a neonatal-onset male and a symptomatic female patient, respectively. Mutation analysis revealed two novel mutations including one splice site mutation (c.386+1G>C) in a symptomatic female patient and one missense mutation (c.515T>A) in a late-onset male patient. In the remaining case, which was a neonatal-onset male patient, no mutation was disclosed by direct sequencing of all 10 exons and their flanking intron sequences. Therefore, OTC mRNA in the liver was analyzed by RT-PCR, and remarkably, a 135-nt insertion was detected between exons 5 and 6. Genomic DNA analysis of intron sequences revealed a single nucleotide change at 265 bp downstream from the 3' end of exon 5, which created the novel splice acceptor site. Thereby, a 135-nt exon was created from the central part of an intron sequence. This is the first report of mutation deep in the intronic sequence in the OTC gene. Molecular analysis using genomic DNA and mRNA will increase the mutation detection ratio in the OTC gene.