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.

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.

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.

The earliest Pleistocene record of a large-bodied hominin from the Levant supports two out-of-Africa dispersal events.

The paucity of early Pleistocene hominin fossils in Eurasia hinders an in-depth discussion on their paleobiology and paleoecology. Here we report on the earliest large-bodied hominin remains from the Levantine corridor: a juvenile vertebra (UB 10749) from the early Pleistocene site of 'Ubeidiya, Israel, discovered during a reanalysis of the faunal remains. UB 10749 is a complete lower lumbar vertebral body, with morphological characteristics consistent with Homo sp. Our analysis indicates that UB-10749 was a 6- to 12-year-old child at death, displaying delayed ossification pattern compared with modern humans. Its predicted adult size is comparable to other early Pleistocene large-bodied hominins from Africa. Paleobiological differences between UB 10749 and other early Eurasian hominins supports at least two distinct out-of-Africa dispersal events. This observation corresponds with variants of lithic traditions (Oldowan; Acheulian) as well as various ecological niches across early Pleistocene sites in Eurasia.

The Modified Bosniak Classification for Intermediate-Risk Renal Cysts in Children.

OBJECTIVES: To examine correlations of the modified Bosniak categories assigned by radiologists to histological results and inter-rater reliability, focusing on intermediate-risk lesions. MATERIALS AND METHODS: The data of pediatric patients who underwent surgery for intermediate-risk complex renal cyst at a tertiary medical center in 2006-2019 were collected retrospectively. Four pediatric radiologists from 2 different medical centers reviewed the available imaging scans, and assigned each to one of the four modified Bosniak classification categories. Binary cohorts of the Bosniak categories (I-II vs III-IV) were compared to the histological results. Diagnostic accuracy (benign- vs intermediate-risk lesion) was calculated for each radiologist and for each imaging modality. Krippendorff's α test was used to measure inter-rater reliability. RESULTS: The cohort included seven children, each with 1 complex cyst that was rated as intermediate-risk on pathological study. The median age was 1.5 years (IQR 1, 11.9). A correct classification was made in 41/56 imaging readings (sensitivity 73.2%). Applying Krippendorff's test to the binary Bosniak cohorts yielded poor inter-rater agreement (α = 0.08). CONCLUSION: Implementation of the modified Bosniak classification in children caused a disconcerting underestimation of intermediate risk. There was a low inter-rater consistency for the categories intended to guide decisions regarding surgery or conservative management. The findings suggest that clinicians should be cautious using the modified Bosniak system for children.

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.

Development of Pelvic Incidence and Lumbar Lordosis in Children and Adolescents.

Pelvic incidence (PI) is a measure of the sagittal orientation of the sacrum relative to the acetabula and is not dependent on posture. In asymptomatic adults, PI correlates with lumbar lordosis. Lumbar lordosis is shown to increase with age following the onset of unassisted bipedal locomotion in children, but to what extent PI changes in relation to lumbar lordosis during skeletal maturation is unclear. The purpose of this study is to understand how PI, lumbar lordosis, and age are related in children and adolescents. PI, supine lumbar lordosis (SLL), and individual wedging angles of the lumbar vertebral bodies were measured on mid-sagittal reformatted images from 144 abdominal computed tomographic scans of individuals aged 2-20 years old, divided into three separate age categories representing pre-growth spurt (ages 2-9), growth spurt (10-15), and post-growth spurt (16-20). Our results showed that, while SLL significantly increased with age during development, PI did not. Despite the fact that PI hardly changed with age, the difference between PI and SLL decreased nonlinearly with age. SLL did not correlate with PI in the youngest age category, but positively correlated with PI in the middle and oldest age categories. The relationship between lumbar lordosis and PI, which is correlated in adults, was significant in our older age categories and not in our youngest age category. Our results indicate that PI in children and adolescents may have some predictive value for adult lumbar lordosis. Anat Rec, 302:2132-2139, 2019. © 2019 American Association for Anatomy.

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.

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.

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.

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.

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.

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.

The first Neanderthal remains from an open-air Middle Palaeolithic site in the Levant.

The late Middle Palaeolithic (MP) settlement patterns in the Levant included the repeated use of caves and open landscape sites. The fossil record shows that two types of hominins occupied the region during this period-Neandertals and Homo sapiens. Until recently, diagnostic fossil remains were found only at cave sites. Because the two populations in this region left similar material cultural remains, it was impossible to attribute any open-air site to either species. In this study, we present newly discovered fossil remains from intact archaeological layers of the open-air site 'Ein Qashish, in northern Israel. The hominin remains represent three individuals: EQH1, a nondiagnostic skull fragment; EQH2, an upper right third molar (RM3); and EQH3, lower limb bones of a young Neandertal male. EQH2 and EQH3 constitute the first diagnostic anatomical remains of Neandertals at an open-air site in the Levant. The optically stimulated luminescence ages suggest that Neandertals repeatedly visited 'Ein Qashish between 70 and 60 ka. The discovery of Neandertals at open-air sites during the late MP reinforces the view that Neandertals were a resilient population in the Levant shortly before Upper Palaeolithic Homo sapiens populated the region.

Evolution of Spinopelvic Alignment in Hominins.

Spinopelvic alignment refers to the interaction between pelvic orientation, spinal curvatures, and the line of gravity. In a healthy modern human, this alignment is characterized by reciprocal curves/orientation of the sacrum, lumbar lordosis, thoracic kyphosis, and cervical lordosis. In an economic sagittal posture, these curvatures keep the line of gravity close to the center of the acetabulum. The purpose of this study is to explore the spinopelvic alignment in extinct hominins. We examined spinopelvic alignment of a single representative from each of the following hominin groups: Australopithecus, Homo erectus (H. erectus), H. neanderthalensis, and early H. sapiens. Pelvic incidence, lumbar lordosis, thoracic kyphosis, and cervical lordosis for each representative was estimated and compared with that of modern humans. Three basic spinopelvic alignments were found: (1) the sinusoidal alignment with moderate to high spinal curvatures and pelvic incidence found in H. erectus and H. sapiens; (2) the straight alignment with small spinal curvatures and small pelvic incidence found in Neandertal lineage hominins; (3) the compound alignment found in Australopithecus, with moderate pelvic incidence and lumbar lordosis, and nearly straight cervical spine. Our results indicate that balanced upright posture can be achieved in different alignments. Each hominin group solved the requirements of erect posture in a slightly different way. Moreover, we propose the term "cranio-spino-pelvic balance" to substitute "spino-pelvic balance." From an evolutionary perspective, not only changes in the pelvis have conditioned the evolution of the spinal curvatures but also changes in the equilibrium of the head likely also affected this balance. Anat Rec, 300:900-911, 2017. © 2017 Wiley Periodicals, Inc.

Cervical lordosis: the effect of age and gender.

BACKGROUND CONTEXT: Cervical lordosis is of great importance to posture and function. Neck pain and disability is often associated with cervical lordosis malalignment. Surgical procedures involving cervical lordosis stabilization or restoration must take into account age and gender differences in cervical lordosis architecture to avoid further complications. PURPOSE: Therefore, the purpose of the present study was to evaluate differences in cervical lordosis between males and females from childhood to adulthood. STUDY DESIGN: This is a retrospective descriptive study. PATIENT SAMPLE: A total of 197 lateral cervical radiographs of patients aged 6-50 years were examined. These were divided into two age groups: the younger group (76 children aged 6-19; 48 boys and 28 girls) and the adult group (121 adults aged 20-50; 61 males and 60 females). The retrospective review of the radiographs was approved by the institutional review board. METHODS: On each radiograph, six lordosis angles were measured including total cervical lordosis (FM-C7), upper (FM-C3; C1-C3) and lower (C3-C7) cervical lordosis, C1-C7 lordosis, and the angle between foramen magnum and the atlas (FM-C1). Wedging angles of each vertebral body (C3-C7) and intervertebral discs (C2-C3 to C6-C7) were also measured. Vertebral body wedging and intervertebral disc wedging were defined as the sum of the individual body or disc wedging of C3 to C7, respectively. Each cervical radiograph was classified according to four postural categories: A-lordotic, B-straight, C-double curve, and D-kyphotic. RESULTS: The total cervical lordosis of males and females was similar. Males had smaller upper cervical lordosis (FM-C3) and higher lower cervical lordosis (C3-C7) than females. The sum of vertebral body wedging of males and females is kyphotic (anterior height smaller than posterior height). Males had more lordotic intervertebral discs than females. Half of the adults (51%) had lordotic cervical spine, 41% had straight spine, and less than 10% had double curve or kyphotic spine. Children had similar total cervical lordosis (FM-C7) to adults. The sum of vertebral body wedging for children was more kyphotic-by 7°-than that of adults, whereas the sum of intervertebral disc wedging in children was more lordotic-by11°-than that of adults. Seventy-one percent of the children had lordotic cervical spine, 23% had straight spine, and less than 6% had double curve spine. Gender differences are already apparent in children as girls had higher upper cervical lordosis (FM-C3; C1-C3) than boys do. CONCLUSIONS: Although the total cervical lordosis (FM-C7) did not change between age groups, and between males and females, the internal architecture of the cervical lordosis changed significantly. Practitioners before neck stabilization procedures or correction and restoration should therefore take into account the gender and age differences in cervical lordosis.

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.

Superb Microvascular Imaging: Added Value and Novel Applications.

Determining the presence and characteristics of vascular flow is an essential part of sonography interrogation. However, small vessels and low velocities are not always possible to depict with conventional color and power Doppler ultrasound. This can be frustrating, especially when the diagnosis depends mainly on the existence of vascular flow, the sonographic examination will be inconclusive, further imaging examinations will be required and diagnosis delayed. Superb microvascular imaging (SMI) is a novel vascular imaging mode, which provides visualization of low velocity and microvascular flow. SMI uses a clutter suppression algorithm to extract flow signals and depicts this information as a color overlay image or as a monochrome or color map of flow. By using SMI, high frame rates and high-resolution images remain maintained. With SMI, it is possible to visualize small vessels including their branches that, until now, it is possible to demonstrate only using contrast-enhanced ultrasound. Availability of this additional technology on all ultrasound machines may make some of the computed tomography scans unnecessary. In our paper, we describe six patients, aged 16-73 years, in which final diagnosis was achieved only with SMI and where conventional color and power Doppler failed. All these examinations were performed using Aplio 500 Platinum ultrasound unit (Toshiba Medical Systems, Tokyo, Japan).

Mutations in STN1 cause Coats plus syndrome and are associated with genomic and telomere defects.

The analysis of individuals with telomere defects may shed light on the delicate interplay of factors controlling genome stability, premature aging, and cancer. We herein describe two Coats plus patients with telomere and genomic defects; both harbor distinct, novel mutations in STN1, a member of the human CTC1-STN1-TEN1 (CST) complex, thus linking this gene for the first time to a human telomeropathy. We characterized the patients' phenotype, recapitulated it in a zebrafish model and rescued cellular and clinical aspects by the ectopic expression of wild-type STN1 or by thalidomide treatment. Interestingly, a significant lengthy control of the gastrointestinal bleeding in one of our patients was achieved by thalidomide treatment, exemplifying a successful bed-to-bench-and-back approach.