Pediatric splenic infarction: Assessment of associated clinical conditions and outcome.

Pediatric splenic infarction (SI) is rare yet clinically significant. Publications regarding this complication are mostly limited to case reports. This is a retrospective study examining SI etiology, clinical presentation, management, and outcomes among children. Twenty-two patients (median age: 7.9 years) were included, mostly with pre-existing hematological diseases. Splenomegaly (72%), thrombocytopenia, and anemia were common. Most of the patients did not receive antithrombotic therapy yet only two patients experienced recurrences. During follow up 36% of patients died, however no fatalities were attributed to thrombotic or bleeding complications.

Sonographic diagnosis of spondylodiscitis in a young child.

Sonographic diagnosis of spondylodiscitis is described in a 21-month-old girl who presented with altered gait. Spondylodiscitis, also referred to as discitis-osteomyelitis, is an infection of the intervertebral disc and adjacent vertebrae. The imaging modality of choice is spinal magnetic resonance imaging. Our case is the first description in the English language of the sonographic diagnosis of spondylodiscitis. Pediatric radiologists and sonographers should be acquainted with its features, for both incidental and intentional diagnosis.

Treatment of severe Kaposiform lymphangiomatosis positive for NRAS mutation by MEK inhibition.

BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy. METHODS: The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay. RESULTS: Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib. CONCLUSIONS: Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies. IMPACT: This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation.

Defects of the glycosylphosphatidylinositol (GPI) biosynthesis pathway constitute an emerging subgroup of congenital disorders of glycosylation with heterogeneous phenotypes. A mutation in the promoter of PIGM, resulting in a syndrome with portal vein thrombosis and persistent absence seizures, was previously described in three patients. We now report four additional patients in two unrelated families, with further clinical, biochemical and molecular delineation of this unique entity. We also describe the first prenatal diagnosis of PIGM deficiency, allowing characterization of the natural history of the disease from birth. The patients described herein expand the phenotypic spectrum of PIGM deficiency to include macrocephaly and infantile-onset cerebrovascular thrombotic events. Finally, we offer insights regarding targeted treatment of this rare disorder with sodium phenylbutyrate.

Cross-sectional area of lumbar spinal muscles and vertebral endplates: a secondary analysis of 91 computed tomography images of children aged 2-20.

Spinal muscle cross-sectional area has been highly associated with spinal pathology. Despite the medium-high prevalence of spinal pathology in children, there is very limited knowledge regarding muscle size and growth pattern in individuals younger than 20 years of age. The aim of this study is to analyze the change in size and symmetry of spinal muscles (erector spinae, multifidus, psoas and quadratus lumborum) in children 2-20 years of age. We studied reformatted images from 91 abdominal computed tomographic scans of children aged 2-20 years, from an existing imaging dataset. The cross-sectional area of the muscles was bilaterally measured parallel to the upper endplate of the lumbar vertebrae L3-L5 and at true horizontal for S1. The cross-sectional area of the upper vertebral endplate was measured at spinal levels L3-L5. Results were analyzed according to six groups based on children's age: 2-4 years (group 1), 5-7 years (group 2), 8-10 years (group 3), 11-13 years (group 4), 14-16 years (group 5) and 17-20 years (group 6). Vertebral endplate and spinal muscles cross-sectional area increased with age. Two patterns were observed: Endplate, psoas and quadratus lumborum increased up to our 6th oldest age group (17-20), and multifidus and erector spinae reached their largest size in the 5th age group (14-16). The epaxial muscles (erector spinae and multifidus) reached their maximal cross-sectional area before skeletal maturity (18-21 years of age). The hypaxial muscles (psoas and quadratus lumborum) continued to increase in size at least until spinal maturity. Contributing factors for the differences in developmental pattern between the epaxial and hypaxial muscles might include functional, embryological and innervation factors. In conclusion, this research is the first to describe the cross-sectional area of spinal muscles in children. Future longitudinal studies are needed for further understanding of muscle development during childhood and adolescence. LEVEL OF EVIDENCE: level 2b, Retrospective cohort study.

Surgical Treatment of Gastro-Pulmonary Fistula Following Bariatric Surgery: Possible and Safe.

BACKGROUND: Laparoscopic sleeve gastrectomy is a common surgical management of morbid obesity. Major complication rate is 3-8%. Staple line leak is one of the most serious complications. In a small group of patients, a gastro-pulmonary fistula is formed. Endoscopic and minimally invasive measures are the first line of treatment with considerable success rate. There are very poor data in the literature what should be done in cases of failure. In this paper, we report our positive experience with definitive surgical repair. METHODS: Retrospective evaluation of 13 consecutive patients referred to the general thoracic surgery department for gastro-pulmonary fistula following sleeve gastrectomy. RESULTS: Prior to their referral, all patients underwent surgical or percutaneous drainage and multiple treatment attempts including stent insertion, pyloric dilatation, endo-clip/ring closure, endoscopic argon ablation and glue injection. Two patients underwent emergency thoracotomy for sepsis and bile empyema. One died in the early postoperative period. Eleven patients underwent semi-elective definitive surgery. Surgery included left lower lobectomy, partial diaphragmectomy and digestive system reconstruction. There was no mortality or major complications in this group. Complication rate was 45% mostly local wound infection and pneumonia. CONCLUSIONS: Gastro-pulmonary fistula is a rare devastating complication of sleeve gastrectomy. When minimally invasive measures fail, there is no place for nihilism. Surgical repair is possible and safe. The data presented herein support this treatment policy.

Elevated IgM levels as a marker for a unique phenotype in patients with Ataxia telangiectasia.

BACKGROUND: Ataxia telangiectasia (AT) is a rare, multi-systemic, genetic disorder. Mutations in the ATM gene cause dysfunction in cell-cycle, apoptosis and V (D) J recombination leading to neurodegeneration, cellular, humoral immunodeficiencies and predisposition to malignancies. Previous studies have suggested that a sub-group of AT patients with elevated IgM levels have a distinct and more severe phenotype. In the current study we aimed to better characterize this group of patients. METHODS: We performed a retrospective review of 46 patient records, followed from January 1986 to January 2015 at the Israeli National AT Center. Demographic, clinical, radiological, laboratory data was reviewed and compared between AT patients with elevated IgM levels (EIgM) and patients with normal IgM levels (NIgM). RESULTS: 15/46(32.6%) patients had significantly elevated IgM levels. This group had a unique phenotype characterized mainly by increased risk of infection and early mortality. Colonization of lower respiratory tract with Mycobacterium gordonae and Pseudomonas aeruginosa as well as viral skin infections were more frequent in EIgM patients. Patients with NIgM had a significantly longer survival as compared to patients with EIgM but had an increased incidence of fatty liver or cirrhosis. T-cell recombination excision circles and kappa-deleting element recombination circle levels were significantly lower in the EIgM group, suggesting an abnormal class switching in this group. CONCLUSIONS: EIgM in AT patients are indicative of a more severe phenotype that probably results from a specific immune dysfunction. EIgM in AT should be considered a unique AT phenotype that may require different management.

Increased Renal Echogenicity in Children With Appendicitis.

OBJECTIVES: Ultrasound (US) is an important modality for the detection of acute appendicitis in children but has limited sensitivity and specificity. Therefore, additional US findings may contribute to the diagnosis. In our experience, children with acute appendicitis often have increased renal cortical echogenicity on US imaging. The purpose of this study was to examine the association of increased renal cortical echogenicity with appendicitis. METHODS: This study included 240 consecutive pediatric patients with no renal or liver disease who underwent US examinations for suspected appendicitis between February 2014 and January 2016. Ultrasound images of the liver and right kidney were retrospectively reviewed, and the echogenicity of the renal cortex was classified as less than the liver, equal to the liver, or greater than the liver. RESULTS: The renal cortex was abnormally hyperechoic in 38 (50%) of all of the patients who had appendicitis according to US (P < .001) and in 47% of patients who underwent appendectomy (P = .002). Overall, 36% of patients with increased renal cortical echogenicity had a diagnosis of appendicitis. After correction for variables, patients with renal hyperechogenicity had a 2.5 times chance of appendicitis (odds ratio, 2.5). CONCLUSIONS: There is a statistically significant association between increased renal cortical echogenicity and appendicitis. In the absence of hepatic or renal disease, this finding may increase the accuracy of the US diagnosis of appendicitis. Increased renal cortical echogenicity may be added to the list of US findings accompanying acute appendicitis in children.

The Added Value of the Lateral Chest Radiograph for Diagnosing Community Acquired Pneumonia in the Pediatric Emergency Department.

BACKGROUND: Opinions differ as to the need of a lateral radiograph for diagnosing community acquired pneumonia in children referred to the emergency department. A lateral radiograph increases the ionizing radiation burden but at the same time may improve specificity and sensitivity in this population. OBJECTIVES: To determine the value of the frontal and lateral chest radiographs compared to frontal view stand-alone images for the management of children with suspected community acquired pneumonia seen in a pediatric emergency department. METHODS: Chest radiographs from 451 children with clinically suspected pneumonia were retrospectively reviewed. Interpretation of frontal views was compared to interpretation of combined frontal and lateral view, the latter being the gold standard. RESULTS: Findings consistent with bacterial pneumonia were diagnosed in 94 (20.8%) of the frontal stand-alone radiographs and in 109 (24.2%) of the combined frontal and lateral radiographs. The sensitivity, specificity, positive predictive value, and negative predictive value of the frontal radiograph alone were 86.2%, 93.9%, 81.7%, and 95.5%, respectively. False positive and false negative rates were 15% and 21%, respectively, for the frontal view alone. The number of lateral radiographs needed to diagnose one community acquired pneumonia was 29. CONCLUSIONS: The lateral chest radiograph improves the diagnosis of pediatric community acquired pneumonia to a certain degree and may prevent overtreatment with antibiotics.

Torsed and Nontorsed Inguinal Undescended Testis: Comparison of Computed Tomography Findings.

OBJECTIVE: The aim of this study was to compare the computed tomography imaging features of a torsed inguinal testis with nontorsed inguinal testes. METHODS: Computed tomography scans of patients with undescended testes were retrospectively collected (2011-2016). Imaging features of nontorsed undescended testis were compared with a case of an inguinal torsed testis. Observations included location of the undescended testis, size (length × width) and texture of each testis, peritesticular findings, position of testicular vessels, and enhancement patterns. RESULTS: Twelve nontorsed inguinal undescended testes were compared with 1 torsed undescended testicle. Torsed testis was larger than nontorsed (44 × 27 mm vs 32.9 ± 6.1 × 22.9 ± 4.9 mm), surrounded by fat stranding and fluid, with heterogeneous texture, enhancement of its outer layers, and an upward kink of its vessels. CONCLUSIONS: Because torsed undescended testis can mimic a groin abscess and because torsion is a medical emergency, radiologists should be aware of this entity and its distinguishing imaging features. Color Doppler examination can ascertain absence/reduction of blood flow.

Pediatric chest ultrasound: a practical approach.

Chest ultrasonography is an important imaging adjunct for diagnosing and managing disease in children. Compared with CT and MRI, ultrasound is cheaper, portable and provides vascular or flow-related information that cannot otherwise be obtained noninvasively. The spatial and temporal resolution of ultrasound is excellent, particularly for superficial structures. In cases where a suspicious abnormality is found, tissue sampling can be performed percutaneously with US guidance. Ultrasound also excels at demonstrating and characterizing pleural fluid collections. As concerns about radiation exposure increase among laypersons and doctors alike, there is a compelling argument for making ultrasonography the initial imaging study of choice for many thoracic abnormalities in a child. In this review the authors discuss and illustrate the US findings of some of the more common chest complaints in children.

A congenital neutrophil defect syndrome associated with mutations in VPS45.

BACKGROUND: Neutrophils are the predominant phagocytes that provide protection against bacterial and fungal infections. Genetically determined neutrophil disorders confer a predisposition to severe infections and reveal novel mechanisms that control vesicular trafficking, hematopoiesis, and innate immunity. METHODS: We clinically evaluated seven children from five families who had neutropenia, neutrophil dysfunction, bone marrow fibrosis, and nephromegaly. To identify the causative gene, we performed homozygosity mapping using single-nucleotide polymorphism arrays, whole-exome sequencing, immunoblotting, immunofluorescence, electron microscopy, a real-time quantitative polymerase-chain-reaction assay, immunohistochemistry, flow cytometry, fibroblast motility assays, measurements of apoptosis, and zebrafish models. Correction experiments were performed by transfecting mutant fibroblasts with the nonmutated gene. RESULTS: All seven affected children had homozygous mutations (Thr224Asn or Glu238Lys, depending on the child's ethnic origin) in VPS45, which encodes a protein that regulates membrane trafficking through the endosomal system. The level of VPS45 protein was reduced, as were the VPS45 binding partners rabenosyn-5 and syntaxin-16. The level of ß1 integrin was reduced on the surface of VPS45-deficient neutrophils and fibroblasts. VPS45-deficient fibroblasts were characterized by impaired motility and increased apoptosis. A zebrafish model of vps45 deficiency showed a marked paucity of myeloperoxidase-positive cells (i.e., neutrophils). Transfection of patient cells with nonmutated VPS45 corrected the migration defect and decreased apoptosis. CONCLUSIONS: Defective endosomal intracellular protein trafficking due to biallelic mutations in VPS45 underlies a new immunodeficiency syndrome involving impaired neutrophil function. (Funded by the National Human Genome Research Institute and others.).

Liver Disease in Pediatric Patients With Ataxia Telangiectasia: A Novel Report.

OBJECTIVE: Ataxia telangiectasia (A-T) is a rare genetic multiorgan disease. Although gastrointestinal involvement is known, hepatic involvement in A-T has not been investigated. We aimed to study the hepatic involvement in a large cohort of patients with A-T. METHODS: A retrospective review of patients, studied from January 1986 to January 2015 at a National A-T Center. Clinical data including demographic, genetic, laboratory, nutritional, radiographic, and histological data were retrieved. RESULTS: Fifty-three patients, 27 (49%) boys, age 14.6 ±â€Š5.2 years (range 5.9-26.1 years), were included. Twenty-three patients (43.4%), age 9.9 ±â€Š5.1 years, had consistently abnormal liver enzymes. The mean enzyme levels were alanine aminotransferase 76.8 ±â€Š73.8 IU/L, aspartate aminotransferase 70 ±â€Š50 IU/L, alkaline phosphatase 331 ±â€Š134 IU/L, and gamma glutamyl transferase 114.7 ±â€Š8 IU/L. Evaluation of other etiology of liver disease was negative. Ultrasonography revealed fatty liver in 9 of them (39%). Liver biopsy was performed in 2 patients, revealing mild-to-moderate steatosis in both, and fibrosis in 1 patient. Progression to advanced liver disease occurred in 2 of 23 (9%) patients within 2 to 5 years. Dyslipidemia was significantly associated with abnormal liver enzymes: 3 of 30 (10%) patients without abnormal liver enzymes versus 10 of 23 (45.5%) patients with abnormal liver enzymes, respectively (P < 0.05, Fisher exact test). No correlation was found between hepatic involvement and HbA1C, sex, presence of malignancy, or type of mutation. CONCLUSIONS: Abnormal liver enzymes and fatty liver are common in patients with A-T and may progress to advanced liver disease at a young age. These findings are novel and implicate that patients with A-T with abnormal liver enzymes should be evaluated for the presence of liver disease.

Sonographic Detection of Accessory Adrenal Tissue in Neonates.

OBJECTIVES: The purpose of this study was to describe the incidence and appearance of accessory adrenal tissue in neonates, as diagnosed by high-resolution sonography, and increase the awareness of this entity. METHODS: We examined the adrenal glands in 153 neonates referred for renal and urinary tract sonography at our institution between January 2014 and January 2015. All kidneys and adrenal glands, except for ectopic kidneys, were scanned with the neonate prone and a linear array transducer with frequency of 11 or 14 MHz. RESULTS: In 9 neonates (5.9%), sonography showed a round, well-defined structure adjacent to the adrenal gland with a hyperechoic center and hypoechoic periphery, similar to the echogenicity of the normal adrenal medulla and cortex, respectively. The largest diameter of the structure measured 2.9 to 4.5 mm. On follow-up studies, which were available for 7 neonates, the structure was not evident, and the suprarenal area was normal. CONCLUSIONS: Accessory adrenal tissue can be identified in the suprarenal area in neonates with high-resolution sonography. Radiologists and sonographers caring for neonates should be aware of this finding and not confuse it with disease.

BCGitis and BCGosis in children with primary immunodeficiency - imaging characteristics.

BACKGROUND: When administered to an immune-compromised patient, BCG (Bacille Calmette-Guérin) can cause disseminated and life-threatening infections. OBJECTIVE: To describe the imaging findings in children with primary immunodeficiency and BCG-related infections. MATERIALS AND METHODS: We reviewed the imaging findings of children with primary immunodeficiency treated at a children's hospital during 2012-2014 with localized or disseminated BCG infection. Imaging modalities included US, CT and radiography. RESULTS: Nine children with primary immunodeficiency had clinical signs of post-vaccination BCGitis; seven of these children showed disseminated disease and two showed only regional lesions with characteristic ipsilateral lymphadenopathy. Overall, lymphadenopathy was the most prevalent feature (n = 8) and characteristically appeared as a ring-enhancing hypodense (CT) or hypoechoic (US) lesion. Visceral involvement with multiple abscesses appeared in the spleen (n = 2), liver (n = 1) and bones (n = 1). All lesions regressed following appropriate anti-tuberculosis treatment. CONCLUSION: BCG infection needs to be considered in children with typical findings and with suspected primary immunodeficiency.

Hybrid video-assisted and limited open (VALO) resection of superior sulcus tumors.

PURPOSE: To compare the postoperative recovery of patients with superior sulcus tumors (Pancoast tumors) following conventional open surgery vs. a hybrid video-assisted and limited open approach (VALO). METHODS: The subjects of this retrospective study were 20 patients we operated on to resect a Pancoast tumor. All patients received induction chemo-radiation followed by surgery, performed via either a conventional thoracotomy approach (n = 10) or the hybrid VALO approach (n = 10). In the hybrid VALO group, lobectomy and internal chest wall preparation were performed using a video technique, with rib resection and specimen removal through a limited incision. RESULTS: There was no mortality in either group. Two patients from the thoracotomy group required mechanical ventilation, but there was no major morbidity in the hybrid VALO group. The operative times were similar for the two procedures. The average length of hospital stay was shorter and the average pain scores were significantly lower in the hybrid VALO group. The incidence of chronic pain was 10 % in the hybrid VALO group vs. 50 % in the thoracotomy group. CONCLUSIONS: Hybrid VALO resection of Pancoast tumors is feasible and safe, resulting in faster patient recovery and a significantly lower incidence of severe chronic pain than open thoracotomy. We conclude that centers experienced with video-assisted lobectomy should consider hybrid VALO surgery as the procedure of choice for Pancoast tumors.

Sonographic appearances of torsion of the appendix testis and appendix epididymis in children.

PURPOSE: The most common cause of acute scrotum in prepubertal boys is torsion of the testicular or epididymal appendages. The purpose of this retrospective study was to characterize the features of these lesions as viewed on sonographic (US) and color Doppler US examination. METHODS: During a 220-week period, 527 male patients 0-17 years old had been referred from the pediatric emergency department for scrotal US evaluation. Torsion of the appendix testis or appendix epididymis had been diagnosed in 19 (3.6%) patients, 3-14 years old (mean, 9.4 years); those patients became our study cohort. The clinical diagnoses in 15 of those patients had been suspected testicular torsion (n = 7), trauma (n = 4), suspected epididymitis and/or orchitis (n = 3), and suspected hydrocele (n = 1). The remaining four patients had been referred owing to nonspecific pain. None of the 19 patients had had the "blue-dot sign" on physical examination. RESULTS: In the 19 patients diagnosed with torsion of the intrascrotal appendages, color Doppler US demonstrated a round or oval avascular lesion with heterogeneous echotexture (n = 18), posterior enhancement (n = 13), and hyperemia of the surrounding structures (n = 15). All lesions (appendages) were adjacent (n = 16) or in close proximity (n = 3) to the upper pole of the testis. Fifteen of the appendages were adjacent to both the testis and the epididymis, four were adjacent to the epididymis alone, and none were adjacent to the testis alone. Owing to the close proximity of the upper pole of the testis, the epididymis, and the appendage, differentiation between testicular and epididymal appendages was not possible. CONCLUSIONS: Torsion of the intrascrotal appendages has a typical appearance on color Doppler US; thus, we believe that it is the method of choice for diagnosing torsion of the scrotal appendages and safely ruling out other disorders as well as avoiding unwarranted surgical intervention or antibiotic treatment.

Renal hypodysplasia associates with a WNT4 variant that causes aberrant canonical WNT signaling.

Abnormal differentiation of the renal stem/progenitor pool into kidney tissue can lead to renal hypodysplasia (RHD), but the underlying causes of RHD are not well understood. In this multicenter study, we identified 20 Israeli pedigrees with isolated familial, nonsyndromic RHD and screened for mutations in candidate genes involved in kidney development, including PAX2, HNF1B, EYA1, SIX1, SIX2, SALL1, GDNF, WNT4, and WT1. In addition to previously reported RHD-causing genes, we found that two affected brothers were heterozygous for a missense variant in the WNT4 gene. Functional analysis of this variant revealed both antagonistic and agonistic canonical WNT stimuli, dependent on cell type. In HEK293 cells, WNT4 inhibited WNT3A induced canonical activation, and the WNT4 variant significantly enhanced this inhibition of the canonical WNT pathway. In contrast, in primary cultures of human fetal kidney cells, which maintain WNT activation and more closely represent WNT signaling in renal progenitors during nephrogenesis, this mutation caused significant loss of function, resulting in diminished canonical WNT/ß-catenin signaling. In conclusion, heterozygous WNT4 variants are likely to play a causative role in renal hypodysplasia.

Cerebellar hemorrhage in very low birth weight premature infants: the advantage of the posterolateral fontanelle view.

OBJECTIVE: The purpose of this study was to determine the prevalence of cerebellar hemorrhage in very low birth weight infants using the posterolateral fontanelle for ultrasound (US) examination. METHODS: The study included 125 very low birth weight premature infants (defined as equal or less than 1500 grams at birth) hospitalized in the premature or neonatal intensive care departments that had at least one head US examination including both anterior and posterolateral fontanelle scans. RESULTS: On US performed through the posterolateral fontanelle, four (3.2%) infants had echogenic posterior fossa lesions interpreted as hemorrhages. None of these lesions were initially or retrospectively observed through the standard anterior fontanelle scan. Two infants died at age 4 and 39 days, respectively. All survivors are being followed up in the hospital's neurodevelopment outpatient clinic. CONCLUSIONS: Cerebellar hemorrhage may be overlooked on standard anterior fontanelle views. The posterolateral approach may assist in diagnosing these lesions.