The Optimal State Scoring Tool: guidance for interdisciplinary care of infants with severe bronchopulmonary dysplasia and its relation to linear growth.

OBJECTIVE: Infants with severe bronchopulmonary dysplasia (sBPD) have complex medical courses. We developed the clinician-rated Optimal State Scoring Tool (OSST) that measures factors relevant to clinical improvement of sBPD and investigated preliminary validity using linear growth outcome and OSST scores in sBPD patients. METHODS: Tool development process and pilot findings are provided for 13 patients evaluated longitudinally. OSST scores, length measurements, and steroid dependency values were obtained. Changes in OSST scores and lengths were examined using linear mixed-effect models. RESULTS: OSST scores were significantly correlated with linear growth (95% CI 0.36, 0.57). The steroid-dependent group showed significantly slower rate of linear growth (95% CI 0.74, 1.05) and slower rate of increase in OSST scores (95% CI 0.99, 2.13) compared to the non-steroid-dependent group, with the OSST showing the largest effect size. CONCLUSION: Pilot data reflect promising evidence for OSST construct validity in monitoring clinical outcomes in sBPD patients.

Discrete role for maternal stress and gut microbes in shaping maternal and offspring immunity.

Psychosocial stress is prevalent during pregnancy, and is associated with immune dysfunction, both for the mother and the child. The gut microbiome has been implicated as a potential mechanism by which stress during pregnancy can impact both maternal and offspring immune function; however, the complex interplay between the gut microbiome and the immune system is not well-understood. Here, we leverage a model of antimicrobial-mediated gut microbiome reduction, in combination with a well-established model of maternal restraint stress, to investigate the independent effects of and interaction between maternal stress and the gut microbiome in shaping maternal and offspring immunity. First, we confirmed that the antimicrobial treatment reduced maternal gut bacterial load and altered fecal alpha and beta diversity, with a reduction in commensal microbes and an increase in the relative abundance of rare taxa. Prenatal stress also disrupted the gut microbiome, according to measures of both alpha and beta diversity. Furthermore, prenatal stress and antimicrobials independently induced systemic and gastrointestinal immune suppression in the dam with a concomitant increase in circulating corticosterone. While stress increased neutrophils in the maternal circulation, lymphoid cells and monocytes were not impacted by either stress or antimicrobial treatment. Although the fetal immune compartment was largely spared, stress increased circulating neutrophils and CD8 T cells, and antibiotics increased neutrophils and reduced T cells in the adult offspring. Altogether, these data indicate similar, but discrete, roles for maternal stress and gut microbes in influencing maternal and offspring immune function.

Biochemical Parameters in Extremely Preterm Infants Receiving Mixed Lipid Emulsions.

OBJECTIVE: A mixture of soybean, medium-chain triglycerides, olive, and fish oils (SMOF) contains higher α-tocopherol and n-3 polyunsaturated fatty acids and lower phytosterol content compared with conventional soybean oil lipid emulsions (SOLE). We sought to characterize plasma total fatty acid profiles (FAPs) and assess the tolerability of long-term SMOF therapy in extremely preterm infants. METHODS: We retrospectively evaluated infants born <28 weeks gestational age who received at least 30 consecutive days of SMOF between July 2016 and June 2019. We evaluated monthly FAPs and biochemical tolerance to SMOF using direct bilirubin (DB) and triglyceride (TG) levels. Growth parameters were evaluated longitudinally until discharge. RESULTS: Sixteen patients with median gestational age 24 weeks (IQR, 23-25 weeks) received SMOF for median 76 days (IQR, 52-130 days). Fourteen patients had necrotizing enterocolitis (NEC) requiring surgical intervention and 15 patients received SOLE for median 19 days (IQR, 14-26 days) prior to switching to SMOF. Median docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) levels were elevated, whereas the remaining fatty acid levels fell within reported reference ranges. There were no incidents of essential fatty acid deficiency (triene to tetraene ratio >0.2) or hypertriglyceridemia (TG >200 mg/dL) with a general downtrend in DB after the first month on SMOF. All growth Z-scores declined throughout hospital stay. CONCLUSIONS: Infants who received SMOF had a more pronounced elevation in DHA than EPA, of which the clinical significance remains unknown. Growth Z-scores declined with SMOF but were confounded by a high prevalence of surgically treated NEC.

Programmed death 1 receptor changes ex vivo in HIV-infected adults following initiation of highly active antiretroviral therapy.

This study investigates the short-term effects of highly active antiretroviral therapy (HAART) on programmed death 1 receptor (PD-1) expression and lymphocyte function. We compared lymphocytes from human immunodeficiency virus (HIV)-infected adults prior to the initiation of HAART with lymphocytes from the same subjects following 2 months of treatment. Short-term HAART resulted in a moderate increase in the expression of PD-1 on both CD4(+) and CD8(+) T cells; yet, there was still a significant reduction in viral load and recovery of CD4(+) T cells. After 2 months of HAART, lymphocytes from the subjects had a reduction in lymphoproliferative responses to phytohemagglutinin (PHA) and an increased response to the Candida recall antigen and the HIV antigen p24 compared to pretreatment lymphocytes. PHA-stimulated peripheral blood mononuclear cells (PBMCs) from samples obtained 2 months after HAART produced higher levels of Th-1 cytokines (gamma interferon [IFN-γ] and tumor necrosis factor alpha[TNF-α]) than the levels observed for samples taken before treatment was initiated. There were no significant changes in the proinflammatory cytokine interleukin-2 (IL-2) or Th-2 cytokines (IL-4, IL-5, and IL-10) in the corresponding samples. Ex vivo PD-1 blockade significantly augmented PHA-induced lymphoproliferation as well as the levels of Th-1 cytokines and to a lesser extent the levels of Th-2 cytokines in PBMC cultures. The ability to downregulate PD-1 expression may be important in enhancing immune recovery in HIV infection.