Neonatal Meningitis Due to Cronobacter sakazakii.

Cronobacter sakazakii is a new emerging foodborne bacterial pathogen associated with fatal infections such as meningitis, necrotizing enterocolitis, and septicemia in neonates. Powdered infant formula milk has been recognized as one of the main transmission vehicles and contaminated sources of this pathogen. Educating parents about the importance of hygienic reconstitution of powdered infant formula, storage practices, and hand hygiene is crucial to reducing the risk of this life-threatening infection. The clinician should be aware of the special considerations for antimicrobial treatment selection as well as further necessary evaluation. Here, we report a case of a twin neonate who presented with C. sakazakii meningitis and septicemia. [Pediatr Ann. 2023;52(11):e430-e433.].

Human parechovirus encephalitis in infants: a retrospective single-center study (2017-2022).

Parechoviruses cause a spectrum of clinical presentations ranging from self-limited to severe encephalitis. In July 2022, state health departments across the USA received an increase in reports of PeV infections among infants. A retrospective cohort study describing the clinical characteristics and outcomes of PeV encephalitis in infants aged < 90 days. Rates of PeV encephalitis were determined based on the number of PeV encephalitis cases out of all meningoencephalitis multiplex polymerase chain reaction panel (MEP) obtained among infants aged < 90 days per year. Out of 2115 infants evaluated for meningoencephalitis, 32 (1.5%) cases of PeV encephalitis were identified. All cases had an absence of pleocytosis and normal protein and glucose levels on CSF analysis. Half of the cases presented with a symptomatic triad (fever, rash, and fussiness). More than one-third of cases (39%) presented with a sepsis-like syndrome, 13% presented with seizures, and 25% were admitted to the pediatric intensive care unit (PICU). MRI of the brain was obtained in four of the cases presented with seizure, all of which demonstrated characteristic radiological findings of the periventricular white matter with frontoparietal predominance and involving the corpus callosum, thalami, and internal and external capsules. Rates of PeV encephalitis varied from year to year, with the highest rates in 2018 and 2022. PeV was the second most detected pathogen in MEP in both 2018 and 2022, and the fifth most detected pathogen in all positive MEP during the study period 2017-2022. CONCLUSION: PeV can cause encephalitis and sepsis-like syndrome in infants, and it should be considered even with normal CSF parameters. Prospective studies are needed to better understand PeV epidemiology and to monitor outbreaks. WHAT IS KNOWN: • PeV is a frequent cause of encephalitis and clinical sepsis in infants in the first 90 days. • Normal CSF parameters in PeV encephalitis and diagnostic importance of MEP to avoid unnecessary prolonged antibiotics and hospitalization.. • Centers for Disease Control and Prevention (CDC) issued a Health Advisory alert in Summer 2022 of uptick PeV encephalitis cases in the USA likely secondary of COVID-19 mitigation measures relaxation, but no comparison with previous years.. WHAT IS NEW: • Knowledge of radiological MRI brain characteristics in PeV encephalitis can be a clue diagnosis. • Knowledge of the biennial seasonality pattern in PeV infection. • PeV was the second most detected pathogen in BIOFIRE ME panel in both 2018 and 2022 in our cohort sample.

Whole-Spine MRI in Children With Suspected Abusive Head Trauma.

BACKGROUND. Abusive head trauma (AHT) in children has recently been associated with findings on cervical spine MRI. OBJECTIVE. The purpose of this study was to evaluate whether whole-spine MRI in children with suspected AHT shows additional abnormalities not identified on cervical spine MRI. METHODS. This retrospective study included 256 children younger than 3 years old (170 boys, 86 girls; mean age, 5.9 months) who underwent skeletal survey and head MRI for suspected child abuse from January 2019 to December 2020. Per institutional protocol, children with suspected AHT also underwent whole-spine MRI. AHT diagnoses were established by a combination of clinical information from medical record review and injuries described in reports from skeletal survey, head MRI, and head CT (if performed). Two pediatric neuroradiologists independently reviewed whole-spine MRI examinations for presence and level of intraspinal hemorrhage (classified as subarachnoid, subdural, or epidural), ligamentous injury, spinal cord edema, and vertebral fractures; subdural hematoma, epidural hematoma, ligamentous injury, and fracture unidentified by skeletal survey were considered major findings. Interobserver agreement was assessed; a third radiologist resolved discrepancies. Findings were summarized with attention to injuries isolated to the thoracolumbar spine. RESULTS. A total of 148 of 256 (57.8%) children underwent whole-spine MRI. AHT was diagnosed in 79 of 148 (53.4%) children who underwent whole-spine MRI versus in 2 of 108 (1.9%) who did not undergo whole-spine MRI (p < .001). Interobserver agreement, expressed as kappa coefficient, was 0.90 for intraspinal hemorrhage, 0.69 for ligamentous injury, 0.66 for spinal cord edema, and 0.95 for fracture. A total of 57 of 148 (38.5%) whole-spine MRI examinations showed injuries, and 34 of 148 (23.0%) showed injuries localized to the thoracolumbar spine. A total of 47 of 148 (31.8%) whole-spine MRI examinations showed major findings, of which 24 (51.1%) were localized to the thoracolumbar spine. Isolated thoracolumbar injuries included 23 of 34 spinal subdural hematomas, 2 of 3 spinal epidural hematomas, and 9 of 11 vertebral fractures, including five fractures not identified by skeletal survey. Diagnosis of AHT was more common in children with positive, versus negative, whole-spine MRI examinations (76.8% vs 39.1%; p < .001). CONCLUSION. In children with suspected AHT, whole-spine MRI commonly shows isolated thoracolumbar injuries. CLINICAL IMPACT. The results support performing whole-spine MRI rather than cervical spine MRI in children with suspected AHT.

Enteric Distribution of Oral Contrast in Emergency Department Patients Undergoing Abdominal-Pelvic Computed Tomography.

PURPOSE: The study sought to assess the gastrointestinal (GI) distribution of oral contrast (OC) among emergency department (ED) patients and determine if contrast reaches the terminal ileum or site of pathology to assist in diagnosis. METHODS: Retrospectively, adults undergoing abdominal-pelvic computed tomography (APCT) in the ED at 2 hospitals were identified over a 3-month period. APCTs were reviewed for location of OC. Presence, site, type of bowel pathology, and prior gastrointestinal surgery were documented. When applicable, the site of bowel pathology was evaluated for the presence or absence of OC. RESULTS: There were 1349 exams with mean age 50.5 years (range 18-97 years), 41% male, with 530 (39%) receiving OC. In 271 of 530 (51%), OC reached the terminal ileum (TI). Bowel pathology was present in 31% of cases (165 of 530). When bowel pathology was present, 47% (77 of 165) had OC present at the pathology site. The GI tract was divided into 4 anatomic segments: OC most frequently reached pathology in stomach and duodenum (84%), but was present less frequently at sites of pathology from jejunum to TI (35%), proximal colon (57%), and distal colon (28%). In only 84 of 530 OC cases (16%) did contrast extend from the stomach to distal colon. OC administration contributed to longer mean APCT order to final report of 0.5 hours and longer mean ED length of stay of 0.8 hours compared with all patients who received APCT. CONCLUSIONS: Optimal OC distribution is not achieved in more than half of ED patients, raising questions about the continued use of OC in the ED.

Signaling pathways involved in megakaryocyte-mediated proliferation of osteoblast lineage cells.

Recent studies suggest that megakaryocytes (MKs) may play a significant role in skeletal homeostasis, as evident by the occurrence of osteosclerosis in multiple MK related diseases (Lennert et al., 1975; Thiele et al., 1999; Chagraoui et al., 2006). We previously reported a novel interaction whereby MKs enhanced proliferation of osteoblast lineage/osteoprogenitor cells (OBs) by a mechanism requiring direct cell-cell contact. However, the signal transduction pathways and the downstream effector molecules involved in this process have not been characterized. Here we show that MKs contact with OBs, via beta1 integrin, activate the p38/MAPKAPK2/p90RSK kinase cascade in the bone cells, which causes Mdm2 to neutralizes p53/Rb-mediated check point and allows progression through the G1/S. Interestingly, activation of MAPK (ERK1/2) and AKT, collateral pathways that regulate the cell cycle, remained unchanged with MK stimulation of OBs. The MK-to-OB signaling ultimately results in significant increases in the expression of c-fos and cyclin A, necessary for sustaining the OB proliferation. Overall, our findings show that OBs respond to the presence of MKs, in part, via an integrin-mediated signaling mechanism, activating a novel response axis that de-represses cell cycle activity. Understanding the mechanisms by which MKs enhance OB proliferation will facilitate the development of novel anabolic therapies to treat bone loss associated with osteoporosis and other bone-related diseases.

Impact of maturational status on the ability of osteoblasts to enhance the hematopoietic function of stem and progenitor cells.

Osteoblasts (OBs) exert a prominent regulatory effect on hematopoietic stem cells (HSCs). We evaluated the difference in hematopoietic expansion and function in response to co-culture with OBs at various stages of development. Murine calvarial OBs were seeded directly (fresh) or cultured for 1, 2, or 3 weeks prior to seeding with 1000 Lin-Sca1 + cKit+ (LSK) cells for 1 week. Significant increases in the following hematopoietic parameters were detected when comparing co-cultures of fresh OBs to co-cultures containing OBs cultured for 1, 2, or 3 weeks: total hematopoietic cell number (up to a 3.4-fold increase), total colony forming unit (CFU) number in LSK progeny (up to an 18.1-fold increase), and percentage of Lin-Sca1+ cells (up to a 31.8-fold increase). Importantly, these studies were corroborated by in vivo reconstitution studies in which LSK cells maintained in fresh OB co-cultures supported a significantly higher level of chimerism than cells maintained in co-cultures containing 3-week OBs. Characterization of OBs cultured for 1, 2, or 3 weeks with real-time PCR and functional mineralization assays showed that OB maturation increased with culture duration but was not affected by the presence of LSK cells in culture. Linear regression analyses of multiple parameters measured in these studies show that fresh, most likely more immature OBs better promote hematopoietic expansion and function than cultured, presumably more mature OBs and suggest that the hematopoiesis-enhancing activity is mediated by cells present in fresh OB cultures de novo.

Osteoblast lineage cells expressing high levels of Runx2 enhance hematopoietic progenitor cell proliferation and function.

Although osteoblasts (OB) play a key role in the hematopoietic stem cell (HSC) niche, little is known as to which specific OB lineage cells are critical for the enhancement of stem and progenitor cell function. Unlike hematopoietic cells, OB cell surface phenotypic definitions are not well developed. Therefore, to determine which OB lineage cells are most important for hematopoietic progenitor cell (HPC) function, we characterized OB differentiation by gene expression and OB function, and determined whether associations existed between OB and HPC properties. OB were harvested from murine calvariae, used immediately (fresh OB) or cultured for 1, 2, or 3 weeks prior to their co-culture with Lin(-)Sca1(+)c-kit(+) (LSK) cells for 1 week. OB gene expression, alkaline phosphatase activity, calcium deposition, hematopoietic cell number fold increase, CFU fold increase, and fold increase of Lin(-)Sca1(+) cells were determined. As expected, HPC properties were enhanced when LSK cells were cultured with OB compared to being cultured alone. Initial alkaline phosphatase and calcium deposition levels were significantly and inversely associated with an increase in the number of LSK progeny. Final calcium deposition levels and OB culture duration were inversely associated with all HPC parameters, while Runx2 levels were positively associated with all HPC properties. Since calcium deposition is associated with OB maturation and high levels of Runx2 are associated with less mature OB lineage cells, these results suggest that less mature OB better promote HPC proliferation and function than do more mature OB.