scholarly journals Altered Intracellular ATP Production by Activated CD4+ T-Cells in Very Preterm Infants

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Giulia Aquilano ◽  
Maria Grazia Capretti ◽  
Francesca Nanni ◽  
Luigi Corvaglia ◽  
Arianna Aceti ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Preterm Infants ◽  
Mode Of Delivery ◽  
Cell Activity ◽  
Cd4 T Cell ◽  
Control Group ◽  
Perinatal Factors ◽  
Very Preterm Infants ◽  
Very Preterm

Background. The neonatal immune system is not fully developed at birth; newborns have adequate lymphocytes counts but these cells lack function.Objective. To assess the activity of T-cells and the influence of the main perinatal factors in very preterm infants (birth weight < 1500 g).Design. Blood samples from 59 preterm infants (21/59 were dizygotic twins) were collected at birth and at 30 days of life to measure CD4+ T-cell activity using the ImmuKnow™ assay. Fifteen healthy adults were included as a control group.Results. CD4+ T-cell activity was lower in VLBW infants compared with adults (p<0.001). Twins showed lower immune activity compared to singletons (p=0.005). Infants born vaginally showed higher CD4+ T-cell activity compared to those born by C-section (p=0.031); infants born after prolonged Premature Rupture of Membranes (pPROM) showed higher CD4+ T-cell activity at birth (p=0.002) compared to infants born without pPROM. Low CD4+ T-cell activity at birth is associated with necrotizing enterocolitis (NEC) in the first week of life (p=0.049).Conclusions. Preterm infants show a lack in CD4+ T-cell activity at birth. Perinatal factors such as intrauterine inflammation, mode of delivery, and zygosity can influence the adaptive immune activation capacity at birth and can contribute to exposing these infants to serious complications such as NEC.

67 Are NICUs too busy?

2021 ◽  
Vol 26 (Supplement_1) ◽  
pp. e47-e48
Author(s):  
Marc Beltempo ◽  
Robert Platt ◽  
Anne-Sophie Julien ◽  
Regis Blais ◽  
Bertelle Valerie ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Patient Outcomes ◽  
Gestational Age ◽  
Late Onset ◽  
Mode Of Delivery ◽  
Random Effect ◽  
Organizational Factors ◽  
Neurological Injury ◽  
Very Preterm Infants ◽  
Very Preterm

Abstract Primary Subject area Neonatal-Perinatal Medicine Background In a health care system with limited resources, hospital organizational factors such as unit occupancy and nurse-to-patient ratios may contribute to patient outcomes. Objectives We aimed to assess the association of NICU occupancy and nurse staffing with outcomes of very preterm infants born &lt; 33 weeks gestational age (GA). Design/Methods This was a multicenter retrospective cohort study of infants born 23-32 weeks GA without major congenital anomaly, admitted within 2 days after birth to one of four Level 3 NICUs in Quebec, Canada (2015-2018). For each 8 h shift, data on unit occupancy were obtained from a central provincial database (SiteNeo) and linked to the hospital nursing hours database (Logibec). Unit occupancy rates and nursing provision ratios (nursing hours/recommended nursing hours based on patient dependency categories) were pooled for the first shift, 24 h, and 7 days of admission for each infant. Patient data were obtained from the Canadian Neonatal Network database. Primary outcome was mortality and/or morbidity (severe neurological injury, bronchopulmonary dysplasia, necrotizing enterocolitis, and late-onset sepsis, severe retinopathy of prematurity). Adjusted odds ratios (AOR) for association of exposure with outcomes were estimated using generalized linear mixed models with a random effect for center, while adjusting for confounders (gestational age, small for gestational age, sex, outborn, Score for Neonatal Acute Physiology version 2, mode of delivery, and the other organizational variables). Results Among 1870 infants included in analyses, 796 (43%) had mortality/morbidity. Median occupancy was 89% (IQR 82-94) and median nursing provision was 1.13 (IQR 0.97-1.37). Overall higher NICU occupancy on shift of admission, first 24 h, and 7 days were associated with higher odds of mortality/morbidity (Figure 1) but nursing provision was not (Figure 2). Subgroup analysis by GA (&lt; 29 and 29-32 weeks) yielded similar results (not shown). Generalized linear mixed model analyses showed that a 5% reduction in occupancy in the first 24 h of admission was associated with a 6% reduction in mortality/morbidity. Conclusion NICU occupancy is associated with mortality/morbidity among very preterm infants and may reflect lack of adequate resources in periods of high activity. Interventions aimed at reducing occupancy and maintaining adequate resources need to be considered as strategies to improve patient outcomes.

scholarly journals Serial Assessment of Body Fat and Fat-Free Mass Accretion in Very Preterm Infants: A Randomized Trial

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1067-1067
Author(s):  
Ariel Salas ◽  
Maggie Jerome ◽  
Paula Chandler-Laney ◽  
Namasivayam Ambalavanan
Keyword(s):  
Body Composition ◽  
Preterm Infants ◽  
Body Fat ◽  
Intervention Group ◽  
Feeding Practices ◽  
Control Group ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Study Participants ◽  
Serial Assessments

Abstract Objectives To incorporate assessment of body composition in the routine care of preterm infants to guide feeding practices before and after hospital discharge. Methods Very preterm infants with gestational ages between 29 and 32 weeks of gestation were included. Infants with gastrointestinal or neurologic malformations and terminal illness needing to limit or withhold support were excluded. All study participants were eligible for serial assessments of body composition between birth and 32 weeks PMA, at 36 weeks PMA or hospital discharge, and at 3 months of corrected age. Infants randomly assigned to the intervention group had the information about infant body composition available to the clinicians caring for them (including reference data). Infants randomly assigned to the control group also underwent serial assessments, but this information on infant body composition was not shown to the clinicians caring for them. The primary outcome was % body fat (%BF) estimated by air displacement plethysmography. Results Fifty very preterm infants were randomized. Mean birthweight of study participants was 1387 g +/– SD 283 and median gestational age at birth was 30 weeks (IQR: 30 – 31). Sociodemographic characteristics did not differ between groups. Mean %BF between birth and 32 weeks PMA (n = 45) was 6 +/– 4, mean %BF at 36 weeks PMA (n = 35) was 14 +/– 4, and mean %BF at 3 months of corrected age (n = 25) was 20 +/– 4. Mean differences in %BF between the intervention group and the control group were not statistically significant at 36 weeks PMA (−0.8) or 3 months corrected age (−1.2). Similarly, feeding practices during hospitalization did not differ between groups. Growth outcomes did not differ between groups. Conclusions Serial assessments of body composition at birth, 36 weeks PMA, and 3 months corrected age in very preterm infants show increased %BF in both intervention and control groups without an apparent influence of the intervention on feeding practices. While 36 weeks PMA has been a common assessment point for research purposes, body composition assessments may need to be done at earlier intervals in order to make meaningful clinical changes to the infant diet in order to affect body composition later in infancy. Funding Sources UAB OHDRC.

scholarly journals Immune Tolerance Developed in Platelet-Targeted FVIII Gene Therapy in Hemophilia Mice Is CD4+ T Cell-Mediated

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1071-1071
Author(s):  
Yingyu Chen ◽  
Xiaofeng Luo ◽  
Juan Chen ◽  
Jocelyn Schroeder ◽  
Christina K Baumgartner ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Immune Tolerance ◽  
Cd4 T Cells ◽  
Memory B Cells ◽  
Cd4 T Cell ◽  
Control Group

Abstract Immune response to factor VIII (FVIII) is not only a severe complication in protein replacement therapy, but also a major concern in gene therapy of hemophilia A. Our previous studies have demonstrated that platelet-targeted FVIII (2bF8) gene therapy together with in vivo drug-selection of transduced cells can not only rescue the bleeding diathesis but also induce anti-FVIII specific immune tolerance in FVIIInull mice. In the current study, we investigated 1) whether our non-selectable lentiviral vector (LV) for the induction of platelet-FVIII expression is sufficient to induce immune tolerance and 2) which cell compartment is tolerized after platelet gene therapy. Platelet-specific FVIII expression was introduced by 2bF8LV-transduction of hematopoietic stem cells followed by syngeneic transplantation into FVIIInull mice preconditioned with 660 cGy total body irradiation (TBI) or Busulfan (Bu) plus ATG (anti-thymocyte globulin). After bone marrow transplantation and reconstitution, animals were analyzed by PCR, qPCR, FVIII:C assay, and tail clipping test to confirm the success of 2bF8 gene therapy. Sixteen weeks after transplantation, animals were challenged with recombinant human FVIII (rhF8) via retro-orbital venous administration at a dose of 50 U/kg weekly for 4 weeks. The titers of anti-FVIII inhibitory antibodies (inhibitors) were determined by Bethesda assay. The CFSE-labeled CD4 T cell proliferation assay and ELISPOT-based memory B cell maturation assay were used to determine which cell compartment is tolerized to FVIII after 2bF8 gene therapy. The level of platelet-FVIII expression was 1.44 ± 0.39 mU/108 platelets (n = 6) in the 660 cGy group, which is not significantly different from the level obtained from the Bu+ATG group [3.04 ± 1.19 mU/108 platelets (n = 6)]. Even after rhF8 challenge, no antibodies were detected in 2bF8LV-transduced recipients in either group. In contrast, all animals in the control group that did not undergo gene therapy developed various levels of inhibitors (204±97 BU/ml, n=7). The frequency of regulatory T cells in both 660 cGy TBI (11.01±0.52%) and Bu+ATG (11.02±0.68%) groups were significantly higher than the control group (8.05±0.57%). T cell proliferation assay demonstrated that CD4+ T cells from 2bF8 LV-transduced recipients that had been challenged with rhF8 did not proliferate when restimulated with rhF8 in vitro. The daughter CD4+ T cells in the group with 10 U/ml of rhF8 were 5.84 ± 2.49% (n = 6), which was not significantly different from the control group without no rhF8 stimulation (0 U/ml) (5.33 ± 1.72%). CD4+ T cells from primed FVIIInull mice did proliferate after rhF8 restimulation. The proliferated daughter cell was 13.12 ± 6.76% (n = 7) in the group with rhF8 (10 U/ml) re-stimulation, which is significantly higher than the group without rhF8 co-culture (4.99 ± 1.16%). Since FVIII-specific memory B cell maturation is CD4+ T cell dependent, we isolated CD4+ T and memory B cells from 2bF8LV-transduced or FVIIInull mice after rhF8 immunization and co-cultured with rhF8 followed by ELISPOT assay to examine the antibody secreting cells. No spots were detected when memory B cells from rhF8-primed FVIIInull mice were co-cultured with CD4+ T cells from 2bF8LV-transduced recipients. In contrast, when memory B cells from either rhF8 immunized 2bF8LV-transduced or untreated FVIIInull mice were cultured with CD4+ T cells from rhF8-primed FVIIInull mice, there were 142 and 205 anti-FVIII antibody secreting cells, respectively, detected per 106 cells seeded. These results indicate that CD4+ T cells from 2bF8LV-transduced mice are tolerized to rhF8 stimulation. In conclusion, 2bF8 lentiviral gene transfer without in vivo selection of genetically manipulated cells can introduce FVIII-specific immune tolerance in hemophilia A mice and this immune tolerance is CD4+ T cell-mediated. Disclosures Baumgartner: Novo Nordisk: Research Funding. Shi:BloodCenter of Wisconsin: Patents & Royalties: METHOD OF INDUCING IMMUNE TOLERANCE THROUGH TARGETTED GENE EXPRESSION..

G-CSF Activated Granulocytes Inhibit Experimental Graft-versus-Host Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4989-4989
Author(s):  
Zilton F.M. Vasconcelos ◽  
Julia Farache ◽  
Bruna M. Santos Grad ◽  
Tereza S. Palmeira Grad ◽  
Luis Fernando Bouzas ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Cell Activity ◽  
Control Group ◽  
Low Density ◽  
Graft Versus Host ◽  
The One

Abstract Acute Graft versus host diseas (aGVHD) is a major complication of stem cell transplantation. The disease is mediated by T cells and a higher incidence/severity would be expected when higher numbers of T cells are inoculated. However, the incidence of aGVHD in PBST, which carries about 10 times more T cells then BMT, is not higher than the one found in later. This finding indicates a modulatory role for G-CSF over T cell activity. We had previously shown that T cells from G-CSF treated PBSC donors do not produce g-IFN nor IL-4 and that this inhibition was mediated by low density, G-CSF activated, granulocytes. In order to test if in fact G-CSF activated granulocytes could inhibit disease, we first checked if G-CSF could generate low density granulocytes, in vivo and in vitro. Indeed, either in vivo(21mg /day - 5 days) or in vitro (150 ng -12hs) with G-CSF generates low density granulocytes which co-purify with the mononuclear cells in the ficoll® gradient. Moreover, as we had shown in humans, these low density cells, inhibit the production of g-IFN by anti-CD3 activated T cells on flow cytometry studies (17%-T cells alone versus 3% T cells with granulocytes 1:1). Radiation quimaeras were set with (B6 X BALB/c)F1 as hosts reconstituted with T cell depleted C57Bl6 bone marrow, in the presence or absence of nylon wool selected spleen cells (NWSC), as T cell source, from normal or G-CSF treated mice. As previously shown by others, NWSC from G-CSF treated mice diminishes the incidence of acute disease on day 20 post-transplant, from 75 to 25%. In order to investigate if this inhibition was dependent on the activated granulocytes present in the NWSC from G-CSF treated mice, granulocytes were depleted with anti-GR1 and complement. In this case, the incidence of disease is the same or even higher (75% experiment#1 and 100% in experiment #2) than the one observed on the control group (NWSC from control mice). These results strongly suggest that activated granulocytes could indeed inhibit aGVHD. We then generated activated granulocytes in vitro, by treating spleen derived high density granulocytes with 150ng of G-CSF for 12 hs. After the incubation period, a new ficoll® gradient was performed and the low density cells were obtained. T cell contamination on the second gradient was eliminated by anti-CD4 and CD8 complement lysis. These activated granulocytes were inoculated together with NWSC from control mice in the radiation quimaeras at a 1:1 ratio. In this case 100% disease inhibition was observed when compared to the positive control group, where 75% of the animals got sick. Our data indicate that activated granulocytes are the major mediators of the G-CSF immunossupressive effects and that these cells can be used as a novel immune modulator in clinical transplantation to prevent acute GVHD.

Perinatal factors associated with death or handicap in very preterm infants

1985 ◽  
Vol 151 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Andrew T. Shennan ◽  
John E. Milligan ◽  
Elizabeth M. Hoskins
Keyword(s):  
Preterm Infants ◽  
Perinatal Factors ◽  
Very Preterm Infants ◽  
Factors Associated ◽  
Very Preterm

scholarly journals Cardio-Respiratory Events and Food Autonomy Responses to Early Uni-Modal Orofacial Stimulation in Very Premature Babies: A Randomized, Controlled Study

Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1188
Author(s):  
Sahra Méziane ◽  
Véronique Brévaut-Malaty ◽  
Aurélie Garbi ◽  
Muriel Busuttil ◽  
Gaelle Sorin ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Controlled Study ◽  
Control Group ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Randomized Controlled ◽  
Respiratory Events ◽  
Experimental Group

Uni-modal orofacial stimulation (OFS) for preventing very preterm infants’ oral disorders is highly controversial. Our study sought to demonstrate that OFS reduced cardio-respiratory events and improved food autonomy in a population of very preterm infants. Our study was randomized, controlled, prospective, and unicentric. The preterm included were born between 26–29 weeks gestational age (GA) with a corrected postnatal age <33 weeks GA. They were randomized into two groups: the experimental group underwent OFS, according to a protocol established, over 10 consecutive days, and the control group underwent no OFS. The primary outcome was the number of cardiorespiratory events: apnea–bradycardia (with or without desaturations) or number of isolated desaturations, which were evaluated at four separate times. Measurements occurred during the first, fourth and eighth independent feedings. Seventeen patients were included in the experimental group and 18 in the control group. The number of cardiorespiratory events for all independent feeding times was significantly reduced in the OFS group (p = 0.003) with univariate analysis, but not with multivariable analysis. The quantity of milk ingested during the first autonomous feeding was higher in the experimental group. The acquisition of food autonomy and the duration of hospitalization were similar in the two groups. While our study does not affirm that an early unimodal OFS improves premature infants’ cardiorespiratory evolution and/or the acquisition of food autonomy, it does indicate an improved food efficiency during their first autonomous feedings.

scholarly journals T-Cell Subpopulations αβ and γδ in Cord Blood of Very Preterm Infants: the Influence of Intrauterine Infection

2013 ◽  
Vol 61 (6) ◽  
pp. 495-501 ◽  
Author(s):  
Agata Serwatowska-Bargieł ◽  
Maria Wąsik ◽  
Maria Katarzyna Kornacka ◽  
Elżbieta Górska ◽  
Robert Kozarski
Keyword(s):  
T Cell ◽  
Cord Blood ◽  
Preterm Infants ◽  
Intrauterine Infection ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Cell Subpopulations ◽  
T Cell Subpopulations

EFFECTS OF THYROXINE ON T-CELL COUNTS AND TUMOUR CELL REJECTION IN MICE

1976 ◽  
Vol 81 (1) ◽  
pp. 104-109 ◽  
Author(s):  
N. Aoki ◽  
G. Wakisaka ◽  
I. Nagata
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tritiated Thymidine ◽  
Cell Activity ◽  
Treated Group ◽  
Carcinoma Cells ◽  
Ehrlich Carcinoma ◽  
Control Group ◽  
Cell Counts ◽  
And Control

ABSTRACT In an attempt to study the effect of thyroxine on peripheral T-cell (thymus derived lymphocyte) counts or immunological functions, inbred C3H/He mice (8–10 weeks old) were injected subcutaneously with thyroxine for more than 3 months. After treatment for 3 months the mice were examined for peripheral T-cell counts, thymic incorporation of tritiated thymidine and rejection of tumour transplants. The number of T-cells was counted by the indirect immunoflourescence method using anti-ΘC3H serum after separation of lymphocytes on "Ficoll-Conray". It was revealed that the peripheral counts of both lymphocytes and T-cells were increased in the thyroxine treated group as compared with the control group, as was reported in the patients with Graves' disease. Thymic incorporation of tritiated thymidine was also found to be significantly increased in the thyroxine treated group. In addition, in order to study T-cell activity of the host, thyroxine treated and control mice were challenged with Ehrlich carcinoma cells at several concentrations (102, 104 and 2 × 106 per mouse). It was found that rejection of tumour transplants was significantly enhanced in the T-cell rich mice. Thus, it is possible that thyroxine affects peripheral T-cell counts and enhances immunological functions of the host.

scholarly journals Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Huiqing Sun ◽  
Juan Song ◽  
Wenqing Kang ◽  
Yong Wang ◽  
Xiantao Sun ◽  
...  
Keyword(s):  
Birth Weight ◽  
Preterm Infants ◽  
Gestational Age ◽  
Recombinant Human Erythropoietin ◽  
Low Dose ◽  
Control Group ◽  
Very Preterm Infants ◽  
Very Preterm ◽  
Human Erythropoietin

Abstract Background Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants. Methods A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks. Results The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96–1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28–296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000–1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment. Conclusions Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT 02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500.

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