In adolescent survivors of cardiopulmonary bypass surgery for CHD, specific brain regions such as the hippocampus may show long-term persistent alteration and correlate with intellectual deficits, particularly with verbal and memory functions.

Probiotics, particularly lactic acid bacteria, are biologic agents which limit the growth, virulence, and survival/colonization of various enteric bacterial pathogens and serve as potential alternatives to antibiotics. Mechanisms that contribute to this antimicrobial effect include producing bioactive metabolites/acids, increasing nutrient and receptor-mediated competition, and modulating gut microbiome ecology. However, these functions of common probiotic strains are limited due to the finite quantity of metabolites they produce and their total number in the gut ecosystem. Conjugated linoleic acids (CLAs), critical metabolites of Lactobacillus, have multiple beneficial effects on human health including anti-carcinogenesis, anti-inflammation, anti-oxidation, and anti-pathogenicity. In this study, we aim to overexpress the myosin cross-reactive antigen gene (mcra) in Lactobacillus casei (LC) to enhance the production of CLA and investigate its effectiveness against enteric bacterial pathogens, specifically Salmonella enterica serovar Typhimurium (ST) and enterohaemorrhagic Escherichia coli (EHEC). By inserting mcra in L. casei, we generated LC-CLA and found the total linoleic acid production by an individual bacterial cell was raised by 21-fold. The adherence ability of LC-CLA on human epithelial cells increased significantly and LC-CLA competitively excluded both ST and EHEC in a mixed-culture condition. Furthermore, LC-CLA significantly altered the physicochemical properties, biofilm formation abilities, interactions with host cells of both ST and EHEC, and triggered anti-inflammatory activities of host cells. These findings offer insights on applying a genetically engineered probiotic to control gut intestinal infections caused by ST and EHEC and prevent foodborne enteric illness in human.

PURPOSE The Pediatric Oncology COVID-19 Case Report registry supplies pediatric oncologists with data surrounding the clinical course and outcomes in children with cancer and SARS-CoV-2. METHODS This observational study captured clinical and sociodemographic characteristics for children (≤ 21 years) receiving cancer therapy and infected with SARS-CoV-2 from the pandemic onset through February 19, 2021. The demographic and clinical characteristics of the cohort were compared with population-level pediatric oncology data (SEER). Multivariable binomial regression models evaluated patient characteristics associated with hospitalization, intensive care unit (ICU) admission, and changes in cancer therapy. RESULTS Ninety-four institutions contributed details on 917 children with cancer and SARS-CoV-2. Median age at SARS-CoV-2 infection was 11 years (range, 0-21 years). Compared with SEER, there was an over-representation of Hispanics (43.6% v 29.7%, P < .01), publicly insured (59.3% v 33.5%, P < .01), and patients with hematologic malignancies (65.8% v 38.3%, P < .01) in our cohort. The majority (64.1%) were symptomatic; 31.2% were hospitalized, 10.9% required respiratory support, 9.2% were admitted to the ICU, and 1.6% died because of SARS-CoV-2. Cancer therapy was modified in 44.9%. Hispanic ethnicity was associated with changes in cancer-directed therapy (adjusted risk ratio [aRR] = 1.3; 95% CI, 1.1 to 1.6]). Presence of comorbidities was associated with hospitalization (aRR = 1.3; 95% CI, 1.1 to 1.6) and ICU admission (aRR = 2.3; 95% CI, 1.5 to 3.6). Hematologic malignancies were associated with hospitalization (aRR = 1.6; 95% CI, 1.3 to 2.1). CONCLUSION These findings provide critical information for decision making among pediatric oncologists, including inpatient versus outpatient management, cancer therapy modifications, consideration of monoclonal antibody therapy, and counseling families on infection risks in the setting of the SARS-CoV-2 pandemic. The over-representation of Hispanic and publicly insured patients in this national cohort suggests disparities that require attention.

The novel severe acute respiratory syndrome coronavirus 2 is a worldwide pandemic. The severe morbidity and mortality associated with coronavirus disease 2019 has mostly affected the elderly or those with underlying medical conditions. We present a case of a 12-year-old girl with no past medical history who presented with fever, cough, and vomiting. Laboratory evaluation revealed severe thrombocytopenia and elevated markers of inflammation. The patient progressed to respiratory failure, and testing results for the severe acute respiratory syndrome coronavirus 2 returned positive. Because of the severity of her thrombocytopenia, she was treated with intravenous immunoglobulin and steroids with prompt improvement in platelets. The patient’s severe acute respiratory distress syndrome was managed with mechanical ventilation, inhaled nitric oxide, and then airway pressure release ventilation. After azithromycin and hydroxychloroquine were given without improvement, our patient received tocilizumab, an anti–interleukin-6 receptor antibody, and remdesivir, a broad antiviral agent, with significant clinical benefit soon afterward. Given that severe pediatric coronavirus disease 2019 is rare, we hope to inform pediatric providers on the clinical course and management considerations as this pandemic continues to spread.

Probiotics are recognized for outcompeting pathogenic bacteria by competitive receptormediated colonization and secretion of functional metabolites which are antimicrobial against certain microbes as well as improving host's gut health and immunity. Recently, we have constructed a bioactive Lactobacillus casei (LC) strain, LC +mcra , by inserting mcra (myosin crossreactive antigen) gene, which stimulates the conversion of conjugated linoleic acids. In this study, we evaluated the modulation of gut microbiome and protective roles of LC +mcra against pathogenic Salmonella enterica serovar Typhimurium (ST) and enterohemorrhagic E. coli (EHEC) infections in BALB/cJ mice. We observed that LC +mcra colonized efficiently in mice gut intestine and competitively reduced the infection with ST and EHEC in various locations of small and large intestine, specifically cecum, jejunum, and ileum (p < 0.05). Positive modulation of the cecal microbiota, for example, higher relative abundances of Firmicutes, lower relative abundances of Proteobacteria, and increased bacterial species diversity/richness, was detected in ST-challenged mice pretreated with LC +mcra based on 16S metagenomic sequencing. Cytokine gene expression analysis indicated that mice pretreated with LC +mcra associated with attenuated bacterial pathogen-induced gut inflammation. Furthermore, mice fed daily with LC +mcra for one week could protect themselves from the impairments caused by enteric infections with ST or EHEC. These impairments include weight loss, negative hematological changes, intestinal histological alterations, and potential death. This in vivo study suggests that daily consumption of novel conjugated linoleic acids over-producing probiotic effectively improves intestinal microbiota composition and prevents/combats foodborne enteric bacterial infections with pathogenic Salmonella and diarrheagenic E. coli.

Thermosensitive liposomal doxorubicin (LTSL-Dox) combined with mild hyperthermia enhances the localized delivery of doxorubicin (Dox) within a heated region. The optimal heating duration and the impact of extended heating on systemic drug distribution is unknown. Here we evaluated local and systemic Dox delivery with two different mild hyperthermia durations (42°C for 10 or 40 minutes) in a Vx2 rabbit tumor model. We hypothesized that longer duration of hyperthermia would increase Dox concentration in heated tumors without increasing systemic exposure. Temporally and spatially accurate controlled hyperthermia was achieved using a clinical MR-HIFU system for the prescribed heating durations. Forty minutes of heating resulted in a nearly 6-fold increase in doxorubicin concentration in heated vs unheated tumors in the same animals. Therapeutic ratio, defined as the ratio of Dox delivered into the heated tumor vs the heart, increased from 1.9-fold with 10 minutes heating to 4.4-fold with 40 minutes heating. MR-HIFU can be used to guide, deliver and monitor mild hyperthermia of a Vx2 tumor model in a rabbit model, and an increased duration of heating leads to higher Dox deposition from LTSL-Dox in a target tumor without a concomitant increase in systemic exposure. Results from this preclinical study can be used to help establish clinical treatment protocols for hyperthermia mediated drug delivery.

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BackgroundChronic kidney disease (CKD) remains an independent predictor of cardiovascular morbidity and mortality. CKD complicates referral for percutaneous coronary intervention (PCI) in non–ST‐segment–elevation myocardial infarction (NSTEMI) patients because of the risk for acute kidney injury and the need for dialysis, with American College of Cardiology/American Heart Association guidelines underscoring the limited data on these patients.Methods and ResultsUsing the National Inpatient Sample to analyze hospitalizations in the United States from 2004 to 2014, we sought to assess PCI utilization and in‐hospital outcomes in NSTEMI admissions with CKD. NSTEMI admissions were identified by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD‐9‐CM) code 410.7. CKD admissions were identified by ICD‐9‐CM code 585. Propensity score–matched cohorts of patients with NSTEMI were matched for age, sex, comorbidities, race, median household income, primary payer status, and hospital characteristics. Of 4 488 795 hospitalizations for NSTEMI, 31% underwent PCI. Overall, 89% of admissions had no CKD. In addition, 32% of NSTEMI admissions with no CKD and 23%, 14%, and 22% with CKD stages 3, 4, and 5 underwent PCI, respectively. Hospitalized NSTEMI patients with CKD stages 4 and 5 had 41% and 20% less likelihood, respectively, of undergoing PCI compared with those with no CKD. Among hospitalized NSTEMI patients with no CKD or CKD stage 3, 4, or 5, PCI‐treated groups had 63%, 57%, 39%, and 59% lower likelihood, respectively, of all‐cause, in‐hospital mortality compared with propensity score–matched medically managed groups.Conclusions PCI use decreased among hospitalized NSTEMI patients as CKD severity increased, and all‐cause, in‐hospital mortality was greater for NSTEMI patients admitted with more severe CKD regardless of treatment strategy.