Retrograde tubing as a rescue treatment for megaoesophagus: a case report.

Familial dysautonomia (FD) is a genetic disease of the autonomous and sensory nervous systems. Severe gastro-oesophageal reflux is common and one of the major complications. Some patients with FD develop megaoesophagus. Oesophageal malfunction, accompanied by oesophageal food and secretion retention, results in recurrent aspiration and other severe respiratory complications. Through a traditional case report, we wish to show how reverse tubing of the oesophagus can lead to significant symptomatic improvement in these patients. Moreover, this technique can serve as an alternative treatment for other oesophageal motility disorders.

Cumulative Dose of Prostaglandin E1 Determines Gastrointestinal Adverse Effects in Term and Near-Term Neonates Awaiting Cardiac Surgery: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to assess the association between treatment characteristics of prostaglandin E1 including initiation time and duration, maximal and cumulative doses, and adverse effects. DESIGN: A retrospective cohort study in which medical records of neonates with duct-dependent lesions were studied for treatment parameters and adverse effects. Multivariable logistic regression model was applied for testing the effect PGE1 variables on outcomes. MAIN OUTCOME MEASURES: The primary outcomes of this study were association of adverse effects of PGE1 treatment with maximal dose, cumulative dose, and treatment duration. The secondary outcomes included safety of feeding in infants treated with PGE1. RESULTS: Eighty-two infants with duct-dependent lesions receiving PGE1 were included. Several infants who received early PGE1 treatment required ventilation support. Feeds were ceased more often as the cumulative dose and duration of PGE1 treatment increased. Gastrointestinal adverse effects were significantly associated with the cumulative dose of PGE1 and treatment duration. Apneas, hyperthermia, and tachycardia were associated with maximal dose. Our data did not demonstrate a difference in the incidence of NEC associated with characteristics of PGE1 treatment. CONCLUSION: Cumulative PGE1 dose is associated with gastrointestinal adverse effects in neonates. Lower doses should be considered in neonates expecting prolonged PGE1 treatment.

Post-operative anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery.

Morgagni hernias account for less than 5% of congenital diaphragmatic hernias. They are characteristically retrosternal and bilateral, with right-sided predominance. An association between Trisomy 21 and diaphragmatic hernias resembling Morgagni hernia has been reported, but the effect of cardiac surgery on its formation has not been investigated. The purpose of this study was to determine whether there is a higher incidence of anterior diaphragmatic hernias in children with Trisomy 21 after cardiac surgery. We compared the prevalence of anterior diaphragmatic hernias in 92 patients with Trisomy 21 who underwent cardiac surgery with its prevalence in 100 children without Trisomy 21 who underwent cardiac surgery. All available CXRs of all children underwent revision for the presence of an anterior diaphragmatic hernia by a pediatric radiologist. Within the study group, four cases of an anterior diaphragmatic hernia were detected, all upon presentation to the emergency room due to breathing difficulties. No cases of an anterior diaphragmatic hernia were found in the control group (P = 0.0094). CONCLUSIONS: A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed. In light of our findings, the surgical technique has been modified in patients with DS in our medical center. WHAT IS KNOWN: • Several studies reported an association between Trisomy 21 and diaphragmatic hernia resembling Morgagni hernia, but the effect of cardiac surgery on its formation has not been investigated. WHAT IS NEW: • There is a higher incidence of anterior diaphragmatic hernia resembling a Morgagni hernia in children with Trisomy 21 after cardiac surgery. • A high index of suspicion for an anterior diaphragmatic hernia should be maintained in children with Trisomy 21 who have undergone cardiac surgery and present with breathing difficulty. If CXR findings are uncertain, UGI series and\or CT should be performed.

Acute pancreatitis in pancreatic-insufficient cystic fibrosis patients treated with CFTR modulators.

Cystic fibrosis transmembrane conductance regulator modulator therapy is associated with substantial clinical benefit and improved quality of life in patients with cystic fibrosis (CF). While their effect on lung function has been clearly reported, we are still in the process of unraveling the full impact they have on the pancreas. We present two cases of pancreatic-insufficient CF patients who presented with acute pancreatitis shortly after commencing elexacaftor/tezacaftor/ivacaftor modulator therapy. Both patients were treated with ivacaftor for 5 years prior to elexacaftor/tezacaftor/ivacaftor initiation, but had no previous episodes of acute pancreatitis. We suggest that highly effective modulator combination therapy may restore additional pancreatic acinar activity, resulting in the development of acute pancreatitis in the interim until ductal flow is improved. This report adds to the growing evidence for possible restoration of pancreatic function in patients receiving modulator therapy, and highlights that treatment with elexacaftor/tezacaftor/ivacaftor may be associated with acute pancreatitis until ductal flow is restored, even in pancreatic-insufficient CF patients.

Bilateral Intratonsillar Abscesses: A Deceiving Symmetrical Oral Bulging.

BACKGROUND: Unilateral intratonsillar abscess (ITA) is an underreported, well-known complication of acute tonsillitis. The prevalence of unilateral ITA compared to peritonsillar abscess (PTA) is 1:14. However, bilateral ITA is an extremely rare entity, with only four cases reported thus far. OBJECTIVES: To describe past cases and our experience, elaborating the diagnostic challenge and the surgical treatment for bilateral ITA. METHODS: We conducted a literature search in the PubMed database using the key words intra-tonsillar abscess, tonsillar abscess, bilateral tonsillar abscess, bilateral intra-tonsillar abscess and bilateral peritonsillar abscess. Our search was limited to the years 1980 to 2020. RESULTS: We found that only four cases of bilateral ITA were previously published. All were characterized by a delay in diagnosis with a median of 10 days (4-14 days), symmetrical oral cavity appearance, enlarged bilateral kissing tonsils, and subsequent treatment by surgical drainage/paracentesis. Respiratory compromise was a concern in most cases. Our patient was treated with bilateral quinsy tonsillectomy and had a prompt recovery. CONCLUSIONS: Bilateral ITA is a rare, deceiving entity, with a diagnosis delay attributed to the symmetrical oral bulging. We present the fifth case reported and the first ever reported in a pediatric patient. We describe the assumed pathogenesis and the main characteristics among all five patients, emphasizing the important role of a high index of suspicion and appropriate imaging, guiding to proper diagnosis and treatment.

Orbital nodular fasciitis in child with biallelic germline RBL2 variant.

RBL2/p130 is one of three highly conserved members of the retinoblastoma (RB) protein family. It is strongly upregulated during neuronal differentiation and brain development, and is critical for survival of post-mitotic neurons. Similar to RB1, it has been implicated as a tumor suppressor gene and has been shown to be dysregulated in various types of cancer. Recent publications describe biallelic, germline loss of function variants in RBL2 in individuals with profound developmental delay. We report a child with profound developmental delay, microcephaly, and hypotonia, who developed fulminant exophthalmos at age 6 years. Brain MRI followed by a biopsy of an intra-orbital mass revealed a mesenchymal tumor. Post-surgical histopathologic examination of the resected tumor was compatible with diagnosis of nodular fasciitis. Exome sequencing from peripheral blood identified a biallelic frameshift variant (c.901dupT) in RBL2. Notably, no malignancies were reported in previous cases with RBL2 variants. This case provides a possible association between RBL2 and orbital tumors.

Radiation dose reduction for chest radiography of infants in intensive care units using a high peak kilovoltage-technique.

BACKGROUND: Chest radiography is an important tool in the care of infants in intensive care units. Image optimization must be monitored to minimize radiation exposure in this susceptible population. OBJECTIVE: To examine the use of a high tube peak kilovoltage technique to achieve radiation dose reduction while maintaining adequate image quality. MATERIALS AND METHODS: A retrospective study was conducted. Radiation doses of chest radiographs performed in the pediatric intensive care units in our institution were calculated. The radiographs were divided into two groups based on the value of the peak kilovoltage used: above and below 60 kilovolts (kV). Image quality was blindly assessed by two fellowship-trained pediatric radiologists. Air kerma, effective dose and quality score for the high versus the low peak kilovoltage group were compared and analyzed. RESULTS: The study included 376 radiographs. One hundred and seven radiographs were performed using peak kilovoltage values equal to or above 60 kV and 269 radiographs were performed using values under 60 kV. The average air kerma for the lower peak kilovoltage group was 56.6 microgray (µGy) (30.7-81.9) vs. 22.9 µGy (11.8-34.4) for the higher peak kilovoltage group (P<0.0001). The mean difference in effective dose between the groups was 11.68 (P<0.0001). The mean difference for the quality score was 0.06 (±0.03, P=0.10), not statistically significant. CONCLUSION: A high peak kilovoltage technique may enable a statistically significant radiation dose reduction without compromising the diagnostic value of the image.

Homozygous variants in MAPRE2 and CDON in individual with skin folds, growth delay, retinal coloboma, and pyloric stenosis.

Cases with multiple molecular diagnoses are challenging to diagnose clinically, yet may be resolved by unbiased exome sequencing analysis. We report an infant with developmental delay, severe growth delay, dysmorphic features, and multiple congenital anomalies including retinal coloboma, congenital pyloric stenosis, and circumferential skin creases. Exome sequencing identified a homozygous missense variant in MAPRE2 and a homozygous stopgain (nonsense) variant in CDON. Variants in MAPRE2, encoding a regulator of microtubule dynamics, lead to congenital symmetric circumferential skin creases type 2, with associated dysmorphism, small growth parameters, and congenital cardiac and genital anomalies. Monoallelic variants in CDON, encoding a coreceptor for sonic hedgehog, have been associated with autosomal dominant pituitary stalk interruption syndrome and holoprosencephaly. Cdon-/- mice have multiple eye defects including coloboma, consistent with the observed human phenotype. Thus, the complex phenotypic presentation of the infant may potentially be attributed to a dual molecular diagnosis. Furthermore, we present CDON as a candidate gene for coloboma formation in addition to the known holoprosencephaly phenotype, and propose to expand the allelic spectrum of CDON to variants associated with autosomal recessive inheritance in addition to dominant inheritance.

Questionnaire-based study showed that neonatal chest radiographs could be reliably interpreted using the WhatsApp messaging application.

AIM: We surveyed whether clinicians used the WhatsApp messaging application to view neonatal chest radiographs and asked a sub-sample to compare them with computer screen viewings. METHODS: The study was conducted at three university-affiliated medical centres in Israel from June-December 2016. Questionnaires on using smartphones for professional purposes were completed by 68/71 paediatric residents and 20/28 neonatologists. In addition, 11 neonatologists viewed 20 chest radiographs on a computer screen followed by a smartphone and 10 viewed the same radiographs in the opposite order, separated by a washout period of 2 months. After another 2 months, five from each group viewed the same radiographs on a computer screen. Different interpretations between viewing modes were assessed. RESULTS: Most respondents used WhatsApp to send chest radiographs for consultation: 82% of the paediatric residents and 80% of the neonatologists. The mean number of inconsistencies in diagnosis was 3.7/20 between two computer views and 2.9/20 between computer and smartphone views (p = 0.88) and the disease severity means were 3.7/20 and 2.85/20, respectively (p = 0.94). Neonatologists using WhatsApp only determined umbilical line placement in 80% of cases. CONCLUSION: WhatsApp was reliable for preliminary interpretation of neonatal chest radiographs, but caution was needed when assessing umbilical lines.

Early recurrence of ileocolic intussusception after successful air enema reduction: incidence and predisposing factors.

PURPOSES: Early recurrent ileocolic intussusception (RICI) is a rare event. We aimed to estimate the rate of RICI and identify predisposing factors for early recurrence for children treated in a tertiary-care academic medical center. METHODS: Consecutive children who were diagnosed with ileocolic intussusception (ICI) during the years 2005-2015 and had successful enema reduction were included. Demographic, clinical, imaging, and laboratory data were recorded for analysis. Ultrasound and fluoroscopy images were reviewed. Early RICI was defined as recurrence within 48 h. RESULTS: Two hundred forty-five episodes of intussusception in 210 patients, ages 2 to 77 months (mean 12.7), were included. Six patients (2.45%) had a RICI between 7 and 28 h (mean 17 h) after initial successful reduction. A total of 5/6 recurrences (83.3%) were in winter months. In the group without early recurrence, only 19.6% of the cases presented during the winter (p = 0.001). Mean age in the early recurrence group was 23 months compared to 12.4 months children with no early recurrence (p = 0.016). All other analyzed parameters were comparable for the groups. CONCLUSION: Early RICI is a relatively rare event that may not justify routine admission and long observation. The approach should be individual, based on the clinical picture.

Recurrent Pneumonia due to Fibrosing Mediastinitis in a Teenage Girl: A Case Report with Long-Term Follow-Up.

A teenage girl was evaluated for recurrent right pneumonia. The evaluation revealed a calcified mediastinal mass that compressed the right intermediate and middle lobar bronchi, as well as the right pulmonary artery and veins. The clinical picture together with imaging studies and borderline positive serology testing suggested a diagnosis of fibrosing mediastinitis associated with histoplasmosis. This rare condition is characterized by the local proliferation of invasive fibrous tissue within the mediastinum due to a hyperimmune reaction to Histoplasma capsulatum. Antifungal and anti-inflammatory therapies are usually ineffective, and surgical intervention contains a high morbidity risk. Palliative surgery and stenting of the compressed airway have been suggested. In the past, the prognosis was thought to be poor, but recent studies demonstrate a more positive outcome. Our patient had been radiologically and functionally stable under follow-up for over thirteen years and has married and delivered two healthy children, both following an uneventful pregnancy.

Complicated community acquired pneumonia in childhood: Different types, clinical course, and outcome.

The incidence of pediatric community acquired complicated pneumonia (PCACP) is increasing. Questions addressed: Are different types of PCACP one disease? How do different treatment protocols affect the outcome? METHODS: Retrospective analysis of medical records of PCACP hospitalizations in the three major hospitals in Jerusalem in the years 2001-2010 for demographics, clinical presentation, management, and outcome. RESULTS: Of the 144 children (51% aged 1-4 years), 91% of Jewish origin; 40% had para-pneumonic effusion (PPE), 40% empyema (EMP), and 20% necrotizing pneumonia (NP). Bacterial origin was identified in 42% (empyema 79%, P = 0.009), most common S. pneumoniae (32%), group A streptococcus (9%). Patients with EMP, compared to PPE and NP, were less likely to receive prior antibiotic treatment (35% vs. 57% and 59%, respectively, P = 0.04). Mean hospitalization was longer in patients with NP followed by EMP and PPE (16.4 ± 10.6, 15.2 ± 7.9, and 12.7 ± 4.7 days, respectively), use of fibrinolysis was not associated with the outcome. All children had recovered to discharge regardless of antibiotic therapy or fibrinolysis. ANSWER: NP is a more severe disease with prolonged morbidity and hospitalization in spite of prior antibiotic treatment. All types had favorable outcome regardless of treatment-protocol. Complicated pneumonia has an ethnic predominance. Pediatr Pulmonol. 2017;52:247-254. © 2016 Wiley Periodicals, Inc.

Neonatal sigmoid volvulus.

BACKGROUND: Neonatal sigmoid volvulus is a rare entity. It is associated with Hirschsprung's disease. Presentation is acute abdominal distention, vomiting and obstipation. Abdominal radiograph will show the "coffee bean" sign, but this is frequently missed and the diagnosis requires a high index of suspicion. Treatment options include contrast enema, colonoscopy or laparotomy, depending on the condition of the baby and local availability. POPULATION AND RESULTS: During the last 6years, 6 infants with sigmoid volvulus were treated in our department. Four presented during the first 48h since birth, and 2 presented at the age of 2 and 7weeks of age. One child was operated and 5 had primary contrast enema with radiologic de-volvulus. Rectal biopsy was performed in all cases; three children had Hirschsprung's disease. Those with normal biopsies responded well to rectal washouts. Two patients had early one stage transanal pullthrough and one had 2 further occasions of sigmoid volvulus prior to definitive surgery. All three recovered with an uneventful course. CONCLUSIONS: Neonatal sigmoid volvulus requires a high level of suspicion. Contrast enema is efficient for primary de-volvulus. Rectal biopsy should be performed and if positive for Hirschsprung's disease, surgery should be performed sooner rather than later.

Infections caused by Fusobacterium in children: a 14-year single-center experience.

PURPOSE: This study aimed at reviewing our experience with infections caused by Fusobacterium in children. METHODS: A retrospective analysis of medical records of children admitted to Hadassah-Hebrew University Medical Center from 2000 to 2013, in whom Fusobacterium spp. was identified in any specimen. RESULTS: A total of 22 patients (males = 12) at a mean ± SE age of 5 ± 1 (range 1-17) years, were identified. The most common complication was abscess formation (n = 11, 50 %). Eight children (36.4 %) had intracranial complications, including brain abscess (n = 4), meningitis (n = 4) and cerebral sinus vein thrombosis (CSVT, n = 5). Seventeen children (77 %) had bacteremia. Primary site of infection was otogenic (n = 9), oropharyngeal (n = 7), respiratory (n = 2), sinuses (n = 2), intra-abdominal (n = 1) and mucositis (n = 1). Fourteen cases were caused by Fusobacterium necrophorum, including four cases with CSVT, 7/8 cases of mastoiditis, four of them with subperiosteal abscess formation; all four cases with meningitis and two brain abscesses. Fifteen (68 %) patients required surgical intervention and 3 (14 %) received anti-coagulation therapy. Excluding one patient with overwhelming sepsis with fatal outcome, all patients recovered. CONCLUSIONS: Fusobacterium infections in children can cause a diverse spectrum of disease and is associated with high rates of abscess formation and intracranial complications. Although Fusobacterium nucleatum is abundant in the oral cavity, F. necrophorum is the main pathogen that causes severe infections in healthy children.

Truncating mutation in the nitric oxide synthase 1 gene is associated with infantile achalasia.

Nitric oxide is thought to have a role in the pathogenesis of achalasia. We performed a genetic analysis of 2 siblings with infant-onset achalasia. Exome analysis revealed that they were homozygous for a premature stop codon in the gene encoding nitric oxide synthase 1. Kinetic analyses and molecular modeling showed that the truncated protein product has defects in folding, nitric oxide production, and binding of cofactors. Heller myotomy had no effect in these patients, but sildenafil therapy increased their ability to drink. The finding recapitulates the previously reported phenotype of nitric oxide synthase 1-deficient mice, which have achalasia. Nitric oxide signaling appears to be involved in the pathogenesis of achalasia in humans.

Factors associated with bacteremia in young infants with urinary tract infection.

BACKGROUND: Urinary tract infection (UTI) is the most frequent severe bacterial infection in infants. Up to 31% of infants with UTI have bacteremia. METHODS: We retrospectively identified all infants aged 0-2 months who were managed in our hospital with UTI during a 1-year period. Those with bacteremia were compared with those without bacteremia, according to the following variables: ethnicity, age, gender, white blood cell and polymorphonuclear counts, C-reactive protein, urinalysis and blood creatinine values as related to age-appropriate norms, imaging and outcome. RESULTS: We identified 81 infants with 82 episodes of UTI. Most occurred in males (72.8%) and 35 (42.7%) were in infants of non-Jewish origin. In 14/81 (17.3%) of episodes, Escherichia coli was cultured from blood. In multivariate analysis, increased blood creatinine levels (P = 0.004) and non-Jewish origin (P = 0.006) were associated with bacteremia. Time to defervescence was significantly longer in bacteremic versus nonbacteremic children (P = 0.018). Duration of hospitalization was longer in bacteremic infants-10 (7-17) days in bacteremic versus 7 (1-14) days in nonbacteremic children (P < 0.001). CONCLUSIONS: In infants aged 0-2 months with UTI, increased blood creatinine value at admission was associated with bacteremia. This value provides an additional clue on admission, independent of personal judgment, to help identify infants at higher risk for bacteremia, prolonged hospitalization and possible complications.

A sequential treatment algorithm for infants with stage 4s neuroblastoma and massive hepatomegaly.

Infants with 4s neuroblastoma (NB) and massive hepatomegaly have a guarded prognosis and mortality approaches 30%. We report on eight patients with 4s NB and massive hepatomegaly treated with multiple modalities. One patient had spontaneous tumor regression. Three patients had progressive disease and responded to chemotherapy. Four patients progressed despite intravenous chemotherapy, of whom two died, and two were salvaged with hepatic intra-arterial chemoembolization. Treatment of infants with stage 4s NB with massive hepatomegaly should be individualized based on disease course. A sequential approach with observation, intravenous chemotherapy, and intra-arterial chemoembolization, may improve the outcome of these infants.

Spondyloepimetaphyseal dysplasia, short limb-abnormal calcifications type: progressive radiological findings from fetal age to adolescence.

BACKGROUND: Spondyloepimetaphyseal dysplasia, short limb-abnormal calcifications type (SEMD, SL-AC) is a rare autosomal recessive condition with a grave prognosis. OBJECTIVE: We aimed to describe the progression of symptoms from fetal age to adolescence in SMED, SL-AC patients. MATERIALS AND METHODS: We retrospectively evaluated radiological findings on plain films, CT and MRI for eight children with genetically proven SEMD (male:female ratio 4:4, ages 30-week fetus to 18 years) and summarized findings from case reports and case series in the literature. RESULTS: Early and persistent radiological signs of SEMD were platyspondyly, chest narrowing, short ribs, and broad and short bones in the extremities and pelvis. In five children, we observed an unusually massive C2 vertebral body with narrowing of the spinal canal. Disease progression was characterized by anterior dislocation of C1, kyphoscoliosis, bowing of the limbs, metaphyseal and epiphyseal changes and abnormal calcifications. Earliest appearance of abnormal calcifications was 1.5 years; four children had no abnormal calcifications at diagnosis. There were persistent large open fontanelles in all children with skull radiographs, including a 17-year-old boy. Disease severity and progression were variable. Complications included cord compression and restrictive lung changes. CONCLUSION: Disease severity and progression vary. Absence of abnormal calcifications does not preclude the diagnosis. An unusual, massive C2 vertebral body may contribute to spinal cord compression. Persistent open fontanelles should be added to the clinical characteristics of SEMD, SL-AC.

An outbreak of adenovirus type 7 in a residential facility for severely disabled children.

BACKGROUND: Adenoviruses cause a variety of clinical symptoms, involving the respiratory, gastrointestinal, urogenital, and neurologic systems. Only a few of the 55 known serotypes of adenovirus that affect humans can cause outbreaks of respiratory tract infection. AIM: To describe the characteristics and clinical manifestations of severe respiratory disease contracted by 8 physically and cognitively disabled children during a very short outbreak of adenovirus serotype 7 infection in a residential facility. METHODS: The clinical, imaging, and laboratory findings of the patients who were hospitalized with severe respiratory symptoms were retrospectively reviewed. Molecular typing of the adenovirus was performed. RESULTS: During 10 days in February 2010, 8 severely disabled children, 9 months to 5 years of age (median 22.5 months), from the same residential facility, were hospitalized due to severe acute respiratory disease with hypoxemia. Four of them (50%) needed mechanical ventilation for 2 to 8 days and one developed multisystem failure, including acute renal failure. Adenovirus serotype 7 was detected in the respiratory specimens of all 8 children. Two patients were treated with intravenous cidofovir. All 8 patients survived and were discharged after hospitalization of 6 to 15 (median: 11.5) days. The epidemiologic investigation revealed that all the 8 affected children shared a playroom and a caregiver worked with them while suffering fever, sore throat, and conjunctivitis before the onset of the outbreak. CONCLUSIONS: Adenovirus type 7 may cause short outbreaks of infection in institutions, causing children to develop life-threatening disease. Early detection of pathogens causing respiratory infections in institutions, isolation, and other preventive precautions are advocated. Moreover, vaccination of health care providers in institutions with the currently available live, oral adenovirus vaccine for types 4 and 7 should be considered.