Encephalitis and cytokine storm secondary to respiratory viruses in children: Two case reports.

Introduction: Encephalitis is a syndrome characterized by brain damage secondary to an inflammatory process that is manifested by cognitive impairment and altered cerebral spinal fluid analysis; it may evolve with seizures and coma. Despite viral infections representing the main cause of encephalitis in children, respiratory syncytial virus (RSV) and parainfluenza virus are mostly associated with respiratory presentations. Uncommonly, the inflammatory phenomena from encephalitis secondary to viral agents may present with an exacerbated host response, the so-called cytokine storm. The link between these infectious agents and neurologic syndromes resulting in a cytokine storm is rare, and the underlying pathophysiology is still poorly understood. Case presentation: A 5-year-old girl and a 2-year-old boy infected with parainfluenza and RSV, respectively, were identified through nasopharyngeal polymerase chain reaction. They were admitted into the pediatric intensive care unit due to encephalitis and multiple organ dysfunction manifested with seizures and hemodynamic instability. Magnetic resonance imaging findings from the first patient revealed a bilateral hypersignal on fluid-attenuated inversion recovery in the cerebral hemispheres, especially in the posterior parietal and occipital regions. The girl also had elevated IL-6 levels during the acute phase and evolved with a fast recovery of the clinical presentations. The second patient progressed with general systemic complications followed by cerebral edema and death. Conclusion: Encephalitis secondary to respiratory viral infection might evolve with cytokine storm and multiorgan inflammatory response in children.

ABM Clinical Protocol #35: Supporting Breastfeeding During Maternal or Child Hospitalization.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. The Academy of Breastfeeding Medicine recognizes that not all lactating individuals identify as female. Using gender-inclusive language, however, is not possible in all languages and all countries and for all readers. The position of the Academy of Breastfeeding Medicine (https://doi.org/10.1089/bfm.2021.29188.abm) is to interpret clinical protocols within the framework of inclusivity of all breastfeeding, chestfeeding, and human milk-feeding individuals.

ABM Clinical Protocol #32: Management of Hyperlactation.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breast-feeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient.

Procalcitonin and C-reactive protein as markers of bacterial infection in critically ill children at onset of systemic inflammatory response syndrome.

OBJECTIVE: To compare the accuracy of procalcitonin and C-reactive protein as diagnostic markers of bacterial infection in critically ill children at the onset of systemic inflammatory response syndrome (SIRS). DESIGN: Prospective cohort study. SETTING: Tertiary care, university-affiliated pediatric intensive care unit (PICU). PATIENTS: Consecutive patients with SIRS. INTERVENTIONS: From June to December 2002, all PICU patients were screened daily to include cases of SIRS. At inclusion (onset of SIRS), procalcitonin and C-reactive protein levels as well as an array of cultures were obtained. Diagnosis of bacterial infection was made a posteriori by an adjudicating process (consensus of experts unaware of the results of procalcitonin and C-reactive protein). Baseline and daily data on severity of illness, organ dysfunction, and outcome were collected. MEASUREMENTS AND MAIN RESULTS: Sixty-four patients were included in the study and were a posteriori divided into the following groups: bacterial SIRS (n = 25) and nonbacterial SIRS (n = 39). Procalcitonin levels were significantly higher in patients with bacterial infection compared with patients without bacterial infection (p = .01). The area under the receiver operating characteristic curve for procalcitonin was greater than that for C-reactive protein (0.71 vs. 0.65, respectively). A positive procalcitonin level (>or=2.5 ng/mL), when added to bedside clinical judgment, increased the likelihood of bacterial infection from 39% to 92%, while a negative C-reactive protein level (<40 mg/L) decreased the probability of bacterial infection from 39% to 2%. CONCLUSIONS: Procalcitonin is better than C-reactive protein for differentiating bacterial from nonbacterial SIRS in critically ill children, although the accuracy of both tests is moderate. Diagnostic accuracy could be enhanced by combining these tests with bedside clinical judgment.

Pediatric Anti-N-Methyl-d-Aspartate Receptor Encephalitis: A Review with Pooled Analysis and Critical Care Emphasis.

PURPOSE: Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis is being recognized with increasing frequency among children. Given the paucity of evidence to guide the critical care management of these complex patients, we provide a comprehensive review of the literature with pooled analysis of published case reports and case series. METHODS: We performed a comprehensive literature search using PubMed, Scopus, EMBASE, and Web of Science for relevant published studies. The literature search was conducted using the terms NMDA, anti-NMDA, Anti-N-methyl-d-aspartate, pediatric encephalitis, and anti-NMDAR and included articles published between 2005 and May 1, 2016. RESULTS: Forty-eight references met inclusion criteria accounting for 373 cases. For first-line treatments, 335 (89.8%) received high-dose corticosteroids, 296 received intravenous immunoglobulin (79.3%), and 116 (31%) received therapeutic plasma exchange. In these, 187 children (50.1%) had a full recovery with only minor deficits, 174 patients (46.7%) had partial recovery with major deficits, and 12 children died. In addition, 14 patients were reported to require mechanical ventilation. CONCLUSION: Anti-NMDA encephalitis is a formidable disease with great variation in clinical presentation and response to treatment. With early recognition of this second most common cause of pediatric encephalitis, a multidisciplinary approach by physicians may provide earlier access to first- and second-line therapies. Future studies are needed to examine the efficacy of these current therapeutic strategies on long-term morbidity.

Dissecting the basis of nongenomic activation of endothelial nitric oxide synthase by estradiol: role of ERalpha domains with known nuclear functions.

Estradiol stimulates endothelial nitric oxide synthase (eNOS) via the activation of plasma membrane (PM)-associated estrogen receptor (ER) alpha. The process requires Src and erk signaling and eNOS phosphorylation by phosphoinositide 3-kinase (PI3 kinase)-Akt kinase, with Src and PI3 kinase associating with ERalpha upon ligand activation. To delineate the basis of nongenomic eNOS stimulation, the potential roles of ERalpha domains necessary for classical nuclear function were investigated in COS-7 cells. In cross-linking studies, estradiol-17beta (E2) caused PM-associated ERalpha to form dimers. However, eNOS activation by E2 was unaltered for a dimerization-deficient mutant ERalpha (ERalphaL511R). In contrast, ERalpha mutants lacking the nuclear localization signals (NLS), NLS2,3 (ERalphaDelta250-274) or the DNA binding domain (ERalphaDelta185-251), which targeted normally to PM and caveolae/rafts, were incapable of activating eNOS. The loss of NLS2/NLS3 prevented Src and erk activation, and it altered ligand-induced PI3 kinase-ERalpha interaction and prevented eNOS phosphorylation. Loss of the DNA binding domain did not change E2 activation of Src or erk, but ligand-induced PI3 kinase-ERalpha binding and eNOS phosphorylation did not occur. Thus, dimerization is not required for ERalpha coupling to eNOS; however, NLS2/NLS3 plays a role in Src activation, and the DNA binding region is involved in the dynamic interaction between ERalpha and PI3 kinase.

Serum procalcitonin and C-reactive protein levels as markers of bacterial infection: a systematic review and meta-analysis.

A meta-analysis was performed to evaluate the accuracy of determination of procalcitonin (PCT) and C-reactive protein (CRP) levels for the diagnosis of bacterial infection. The analysis included published studies that evaluated these markers for the diagnosis of bacterial infections in hospitalized patients. PCT level was more sensitive (88% [95% confidence interval [CI], 80%-93%] vs. 75% [95% CI, 62%-84%]) and more specific (81% [95% CI, 67%-90%] vs. 67% [95% CI, 56%-77%]) than CRP level for differentiating bacterial from noninfective causes of inflammation. The Q value for PCT markers was higher (0.82 vs. 0.73). The sensitivity for differentiating bacterial from viral infections was also higher for PCT markers (92% [95% CI, 86%-95%] vs. 86% [95% CI, 65%-95%]); the specificities were comparable (73% [95% CI, 42%-91%] vs. 70% [95% CI, 19%-96%]). The Q value was higher for PCT markers (0.89 vs. 0.83). PCT markers also had a higher positive likelihood ratio and lower negative likelihood ratio than did CRP markers in both groups. On the basis of this analysis, the diagnostic accuracy of PCT markers was higher than that of CRP markers among patients hospitalized for suspected bacterial infections.