Placental clearance not synthesis tempers exaggerated pro-inflammatory cytokine response in neonates exposed to chorioamnionitis.

BACKGROUND: The source and clearance of cytokines in the fetal circulation in term pregnancies complicated by chorioamnionitis remains unclear as are the contributions of placental transport, synthesis, and clearance. The objectives of the study were to determine (1) fetal and/or placental contributions to synthesis and/or clearance of inflammatory and anti-inflammatory cytokines in term pregnancies complicated by chorioamnionitis and (2) whether this differs in pregnancies further complicated by fetal hypoxia. METHODS: Prospective cohort study of pregnancies >37 weeks gestational age that included: Group 1, uncomplicated cesarean delivery without labor (n = 20); Group 2, uncomplicated vaginal delivery (n = 30); Group 3, pregnancies complicated by chorioamnionitis (n = 10); Group 4, complicated by chorioamnionitis + fetal hypoxia (n = 10). Umbilical arterial (UmA) and venous (UmV) blood were assayed for IL-1ß, IL-2, IL-6, IL-8, TNFα, and IL-10. RESULTS: IL-6 and IL-8 were below assay detection in UmA and UmV blood in Group 1 and increased in Group 2 (P < 0.01), UmA¼UmV (P < 0.01). Their concentrations increased further in Groups 3 and 4 (P = 0.003), UmA¼UmV. Placental clearance was concentration dependent that approaches saturation in the presence of chorioamnionitis. CONCLUSIONS: Marked increases in fetal synthesis of IL-6 and IL-8 occur in chorioamnionitis. Synthesis increase further when complicated by fetal hypoxia. Cytokine removal occurs via placental concentration-dependent mechanisms, potentially contributing to adverse fetal effects. IMPACT: The source and role of the placenta in synthesis and/or clearance of inflammatory mediators in term pregnancies complicated by clinical chorioamnionitis are unclear; however, conventional wisdom suggests the placenta is their source. This is the first study demonstrating that circulating concentrations of fetal IL-6 and IL-8 in clinical chorioamnionitis ± birth asphyxia in term pregnancies are of fetal origin. Circulating fetal inflammatory cytokines are cleared by concentration-dependent placental mechanisms that are nearly saturated in chorioamnionitis ± fetal hypoxia. These observations provide additional insight into understanding the fetal immune response in term pregnancies complicated by clinical chorioamnionitis.

Impact of fetal inflammatory response on the severity of necrotizing enterocolitis in preterm infants.

OBJECTIVE: Neonates born with fetal inflammatory response (FIR) are at increased risk for adverse neonatal outcomes. Our objective was to determine whether FIR and its severity is associated with severity of necrotizing enterocolitis (NEC) in preterm infants. METHODS: A case-control retrospective study of infants <33 weeks gestational age or <1500 g birthweight, including 260 with stage I-III NEC and 520 controls matched for gestational age. Placental pathology was evaluated, and FIR progression and its severity were defined according to Amsterdam classification. RESULTS: In this study, mild FIR (i.e., stage 1 FIR) was present in 52 controls (10.0%) and 22 infants with stage I-III NEC (8.5%), while moderate to severe FIR (i.e., ≥stage 2 FIR) was present in 16 controls (3.1%) and 47 infants with stage I-III NEC (18.1%). Both stage and grade of FIR were associated with stage of NEC (P < 0.001). On multinomial logistic regression, stage III NEC was associated with stage of FIR (P < 0.001). CONCLUSION: This is the first report demonstrating the association between progression and increasing severity of FIR and stage of NEC. IMPACT: Fetal Inflammatory Response (FIR) and its progression and severity are associated with the stages of necrotizing enterocolitis (NEC). This is the first study demonstrating the impact of progression and severity of FIR on stage III NEC. These observations provide additional insight into understanding the impact of intrauterine exposure to inflammation on the severity of NEC in preterm infants.

Second instance of co-occurring 22q11.2 deletion syndrome and Williams syndrome.

We present an 18-month-old male with Tetralogy of Fallot, retrognathia, short stature, global developmental delay, and dysmorphic features who was found to have dual diagnoses of both Williams syndrome and 22q11.2 deletion syndrome (22q11.2DS). To our knowledge, this is the second case of such a co-occurrence documented in the medical literature. Our patient presents with a blended physical phenotype of these two conditions and a behavioral phenotype that is distinct from what is typically observed in either disorder alone. We compare our patient's phenotype to the previously reported case and to the typical phenotypes for each individual condition. Additionally, we discuss why the occurrence of these two disorders together seems to be so rare, and the benefit of a genetics evaluation to an inpatient service team and the patient.

Congenital infantile fibrosarcoma mimicking a cutaneous vascular lesion: a case report and review of the literature.

Congenital infantile fibrosarcoma (CIFS) is a rare neoplasm of infancy that occurs most frequently in the extremities, and when presenting in the skin, may sometimes resemble infantile hemangiomas or other vascular lesions. Clinically, these tumors differ from hemangiomas in the time of onset, morphology, and growth pattern and must be evaluated histologically for definitive diagnosis. We describe an infant with a neoplasm involving the distal left forearm initially presumed to be a vascular lesion after evaluation by two separate ultrasound studies. He presented at seven weeks of life with a multinodular lesion that had enlarged significantly since birth, and the skin biopsy revealed a fibrosarcoma. This case highlights an unusual cutaneous presentation of CIFS, which varies in appearance from the previous 12 cases reported in the literature. We review the clinical manifestations of these congenital masses and emphasize early diagnosis for conservative therapy and improved prognosis.

Magnetic resonance imaging improves diagnosis of placenta accreta spectrum requiring hysterectomy compared to ultrasound.

BACKGROUND: Magnetic resonance imaging has been used increasingly as an adjunct for ultrasound imaging for placenta accreta spectrum assessment and preoperative surgical planning, but its value has not been established yet. The ultrasound-based placenta accreta index is a well-validated standardized approach for placenta accreta spectrum evaluation. Placenta accreta spectrum-magnetic resonance imaging markers have been outlined in a joint guideline from the Society of Abdominal Radiology and the European Society of Urogenital Radiology. OBJECTIVE: This study aimed to compare placenta accreta spectrum-magnetic resonance imaging parameters with the ultrasound-based placenta accreta index in pregnancies at high risk for placenta accreta spectrum and to assess the additional diagnostic value of magnetic resonance imaging for placenta accreta spectrum that requires a cesarean hysterectomy. STUDY DESIGN: This was a single-center, retrospective study of pregnant patients who underwent magnetic resonance imaging, in addition to ultrasonography, because of suspected placenta accreta spectrum. The ultrasound-based placenta accreta index and placenta accreta spectrum-magnetic resonance imaging parameters were obtained. Student's t test and Fisher's exact test were used to compare the groups in terms of the primary outcome (hysterectomy vs no hysterectomy). The diagnostic performance of magnetic resonance imaging and the ultrasound-based placenta accreta index was assessed using multivariable logistic regressions, receiver operating characteristics curves, the DeLong test, McNemar test, and the relative predictive value test. RESULTS: A total of 82 patients were included in the study, 41 of whom required a hysterectomy. All patients who underwent a hysterectomy met the International Federation of Gynecology and Obstetrics clinical evidence of placenta accreta spectrum at the time of delivery. Multiple parameters of the ultrasound-based placenta accreta index and placenta accreta spectrum-magnetic resonance imaging were able to predict hysterectomy, and the parameter of greatest dimension of invasion by magnetic resonance imaging was the best quantitative predictor. At 96% sensitivity for hysterectomy, the cutoff values were 3.5 for the ultrasound-based placenta accreta index and 2.5 cm for the greatest dimension of invasion by magnetic resonance imaging. Using this sensitivity, the parameter of greatest dimension of invasion measured by magnetic resonance imaging had higher specificity (P=.0016) and a higher positive predictive value (P=.0018) than the ultrasound-based placenta accreta index, indicating an improved diagnostic threshold. CONCLUSION: In a suspected high-risk group for placenta accreta spectrum, magnetic resonance imaging identified more patients who will not need a hysterectomy than when using the ultrasound-based placenta accrete index only. Magnetic resonance imaging has the potential to aid patient counseling, surgical planning, and delivery timing, including preterm delivery decisions for patients with placenta accreta spectrum requiring hysterectomy.

Heat and mass transport in an electrically conducting nanofluid flow over two-dimensional geometries.

Engineering equipment in medicine, chemical and power engineering, electronics, and other human endeavours use nanofluids. The ability to improve mass and heat transport because of the low concentration of nanoparticles is the primary driver behind the vast array of nanofluid applications. Thus, the famous problems of viscous, incompressible, Newtonian, and 2-D laminar flow are revisited to investigate the mass and heat transmission rates for water-based carbon nanotubes (CNTs) with variable magnetic fields and external pressure gradients. Flow cases considered with varying pressure gradients are the flows upon a flat plate, flow in a planar diverging and converging channel, flow over a wedge, and plane stagnation flows, which are investigated. The impressions of thermophoresis and Brownian motion parameters are examined through the Buongiorno model. Using the Görtler transformation, the leading boundary layer (BL) equations are converted into dimensionless forms of ordinary differential equations (ODEs). Runge-Kutta Fehlberg Method (RKF45) is operated to tackle the ensuing ODEs to find the mass, heat, and skin friction rates. It has been found that the rates of shear stress, mass, and heat transport slow down with an escalating magnetic field. Although mass transport rates are decreased, shear stress and heat transport (HT) rates escalate due to the solid volume portion of carbon nanotubes. Furthermore, the pressure gradient parameter facilitates faster heat and shear stress transmission rates.

Rhabdomyosarcoma With Epithelioid Features And NSD3::FOXO1 Fusion: Evidence For Reconsideration Of Previously Reported FOXO1::FGFR1 Fusion.

Epithelioid rhabdomyosarcoma is a rare rhabdomyosarcoma variant for which no diagnostic recurrent driver genetic events have been identified. Here we report a rapidly progressive and widely metastatic rhabdomyosarcoma with epithelioid features that arose in the thigh of a male infant. Conventional cytogenetics revealed a t(8;13)(p11.2;q14) translocation. Fluorescence in situ hybridization studies showed rearrangement of FOXO1 and amplification of its 3" end, and rearrangement of NSD3 and amplification of its 5` end. Next generation sequencing identified a NSD3::FOXO1 fusion, which is a previously unreported gene fusion. We also review the historic report of a FOXO1::FGFR1 fusion in a solid variant of alveolar rhabdomyosarcoma and propose that NSD3::FOXO1 fusion may have been the more appropriate interpretation of the data presented in that report.

Spindle Cell/Sclerosing Rhabdomyosarcoma With PAX8::PPARG Fusion.

The spindle cell/sclerosing subtype of rhabdomyosarcoma is classified based on genetic features into the three categories of MYOD1-mutated, gene fusion-driven, and a subset without a currently identified genetic driver event. The gene fusion-driven spindle cell/sclerosing rhabdomyosarcomas are heterogenous and characterized by increasing numbers of gene fusions, the most common gene partners being VGLL2, NCOA2, and TFCP2. Here we report a spindle cell/sclerosing rhabdomyosarcoma that arose in the orbit of a 4-year-old male. This tumor harbored a unique PAX8::PPARG fusion. PAX8::PPARG fusions have previously only been described in follicular thyroid carcinoma and follicular variant of papillary thyroid carcinoma. Our report adds to the growing number of gene fusions in spindle cell/sclerosing rhabdomyosarcomas.

Congenital Myenteric Hypoganglionosis.

Congenital myenteric hypoganglionosis is a rare developmental disorder characterized clinically by severe and persistent neonatal intestinal pseudoobstruction. The diagnosis is established by the prevalence of small myenteric ganglia composed of closely spaced ganglion cells with sparse surrounding neuropil. In practice, the diagnosis entails familiarity with the normal appearance of myenteric ganglia in young infants and the ability to confidently recognize significant deviations in ganglion size and morphology. We review clinical, histologic, and immunohistochemical findings from 12 patients with congenital myenteric hypoganglionosis in comparison with similar data from age-matched controls and clearly delineate the diagnostic features of the condition. Practical guidelines are provided to assist surgical pathologists, who are likely to encounter this condition only infrequently. The diagnosis typically requires full-thickness intestinal biopsy as the abnormality is confined to the myenteric plexus in many patients. Immunohistochemistry for Hu C/D may be used to confirm hypoganglionosis. Reduced staining for calretinin and NeuN implicates a selective deficiency of intrinsic primary afferent neurons in this disease.

Development and Clinical Validation of a Multiplex Gene Fusion Assay.

OBJECTIVE: The detection of gene fusion events is important for the diagnosis and management of malignancies. In this study, we describe the validation of a next-generation sequencing assay for multiplex detection of gene fusions. METHODS: Based on previously described gene fusion events that occur in pediatric oncology, a custom anchored multiplex next-generation sequencing assay was designed to target 93 genes. RESULTS: A total of 24 previously characterized specimens were examined. Twenty specimens had 1 or more previously described fusion events, and 4 specimens were negative for fusion events. The accuracy across specimens was 100% (20 of 20 specimens). The analytical sensitivity and specificity were both 100%. Interday reproducibility for fusion events was 94%; in comparison, intraday reproducibility was 90%. CONCLUSION: This multiple-gene fusion assay demonstrated appropriate sensitivity, specificity, and accuracy for clinical use. We anticipate that this assay will improve the diagnosis and management of patients with pediatric solid tumors.

Cytogenetic and molecular characterization of a partial trisomy 2p arising from inverted duplication of 2p with terminal deletion of 2pter.

Partial trisomy 2p is typically associated with partial monosomy of another chromosomal segment and results from a balanced translocation in one of the parents. Inverted duplications with terminal deletions have been reported in an increasing number of chromosomes. Several cases initially interpreted as terminal duplications have instead been documented to represent inverted duplications with terminal deletions. Inv dup del(2p) has been reported in patients who manifest the clinical findings of trisomy 2p syndrome. Here we report on a 2-month-old girl with inv dup del(2p) and clinical manifestations that overlap those found commonly in partial 2p trisomy, as previously reported in the literature. Her clinical picture helps delineate the phenotype of 2p duplication disorders.

Multimodal depiction of a rare immature gastric teratoma from fetus to infant.

Immature gastric teratomas are rare gastrointestinal tumors. Presented here are imaging findings of this neoplasm which was first seen via antenatal ultrasound. Subsequent fetal magnetic resonance imaging demonstrated a partially calcified mass that contained areas of diffusion restriction. Meconium pseudocyst was originally entertained as a differential consideration. Follow-up computed tomography and upper gastrointestinal fluoroscopy after delivery revealed a bilobed mass that was at least partially endogastric. Resection was performed, and the diagnosis was uncovered via histologic analysis.

Epidermoid cyst of the uvula in a child.

OBJECTIVE: Epidermoid cysts are rarely located in the uvula. To date, epidermoid cyst of the uvula has not been reported in a child at preschool age. We present clinical and histopathological characteristics of an epidermoid cyst in a child with uvula mass. METHODS: Retrospective chart review. RESULTS: A 5-year-old boy was seen in the pediatric otolaryngology clinic for assessment of a uvula mass. The mass was detected during a tonsillectomy and adenoidectomy performed for sleep-related breathing disorder. The mass was completely removed and the final diagnosis was epidermoid cyst. CONCLUSION: Pediatricians, otolaryngologists, and pathologists should be cognizant of the occurrence of uvular epidermoid cyst in preschool children.

Colonic perforations in enteric fever.

We report a case of multiple colonic perforations in a 5-year-old boy due to typhoid fever. The main objective is to present the occurrence of this complication and discuss the management. The patient was admitted with nine days history of high-grade fever and abdominal pain. On examination, he was very sick looking child with acute abdomen. After initial workup and resuscitation, laparotomy was performed which revealed multiple colonic perforations with feacal peritonitis. The case revealed that one must not forget to inspect entire intestine including colon, as there may be perforations present in the large bowel.

Fetal akinesia deformation sequence and neuroaxonal dystrophy without PLA2G6 mutation.

We present autopsy findings of a stillborn female infant at 20 to 21 weeks' gestation with neuroaxonal dystrophy. External examination showed features of fetal akinesia deformation sequence. Internal examination showed hypoplasia of the cerebellum, corpus callosum, and optic nerves, as well as nuclear cataracts. Light and electron microscopic examinations showed widespread axonal spheroids in the central and peripheral nervous systems. Gene sequencing failed to reveal PLA2G6 mutations, indicating that fetal neuroaxonal dystrophy presenting as fetal akinesia deformation sequence is genetically distinct from infantile neuroaxonal dystrophy and related disorders. In addition, placental examination showed α-fetoprotein-positive, eosinophilic, globular inclusions in the cytoplasm of a few villous macrophages. The significance of this novel histologic finding is unclear.

Acute myeloid leukemia with inv(16) with CBFB-MYH11, 3'CBFB deletion, variant t(9;22) with BCR-ABL1, and del(7)(q22q32) in a pediatric patient: case report and literature review.

Coexistence of inv(16) and t(9;22) is a rare chromosomal aberration, one that has been described in chronic myelogenous leukemia (CML), mainly in myeloid blast crisis, and de novo acute myeloid leukemia (AML). Approximately 14 cases have been reported, including only 1 pediatric case. Here we present the case of a 13-year-old boy with a new diagnosis of AML with some features of monocytic differentiation. Conventional cytogenetic analyses on unstimulated blood showed three related abnormal clones with inv(16) in the stemline: 46,XY,inv(16)(p13.1q22)[2]/46,idem,del(7)(q22q32)[16]/46,idem,t(9;22;19)(q34;q11.2;p13.1)[2]. Fluorescence in situ hybridization (FISH) studies on interphase nuclei and previously G-banded metaphases showed a 3'CBFB deletion and confirmed the presence of the Philadelphia chromosome in a t(9;22;19) rearrangement. Deletion 7q31 was also confirmed by interphase FISH analysis. The patient was treated with standard AML chemotherapy plus gemtuzumab as part of a clinical trial. At 10-months follow-up, he was in remission. To the best of our knowledge, this is the first description of a pediatric case of de novo AML with a stemline showing inv(16) along with 3'CBFB deletion, an abnormal clone revealing in addition a del(7)(q22q32), and another clone with a t(9;22;19)(q34;q11.2;p13.1) as an additional abnormality.