Hemodynamic evaluation of extremely low birth weight infants during the first 7 days of life.

BACKGROUND AND AIM: We aimed to investigate the hemodynamic status of extremely low birth weight (ELBW) infants during the transitional period under intensive management. METHODS: This retrospective cohort study analyzed left ventricular ejection fraction (LVEF), left ventricular end-systolic wall stress (ESWS), left ventricular internal dimension in diastole (LVIDd), and mean arterial pressure (MAP) of ELBW infants during their first week of life. Small for gestational age (SGA), histological chorioamnionitis (hCAM), severe intraventricular hemorrhage (IVH), and non-survival to discharge infants were compared to their counterparts. RESULTS: Sixty-two infants (25.7 ± 2.1 weeks, 700.7 ± 165.4 g) were analyzed. MAP gradually increased. Median LVEF was 69.8 % on day 1, decreased to 62.7 % on day 2, then increased throughout the week. ESWS was lowest at birth, rose to 28.2 g/cm2 on day 2, and decreased on day 6. There were no significant changes in LVIDd. SGA infants had higher MAP throughout, higher LVEF on day 2 and 3, but lower LVEF on day 5 to 7. LVIDd was lower in hCAM group. Severe IVH group had a more significant drop in LVEF on day 2, higher ESWS, and a higher incidence of hemodynamic significant patent ductus arteriosus (hsPDA). Non-survival had lower LVIDd. CONCLUSIONS: MAP increased gradually. Hemodynamic instability was observed in the first two days, with decreased LVEF and increased ESWS before stabilization. We observed an alteration in hemodynamic adaptation in SGA and hCAM infants. Severe IVH group experienced early hemodynamic instability and a higher incidence of hsPDA.

Evaluation of Postnatal Complications in Clinical and Histological Chorioamnionitis in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: Terminating pregnancy appropriately before the intrauterine infection has progressed may have an improved prognosis for preterm infants. We evaluate how the combination of histological chorioamnionitis (hCAM) and clinical chorioamnionitis (cCAM) affects the short-term prognosis of infants. STUDY DESIGN: This retrospective multicenter cohort study based on the Neonatal Research Network of Japan included extremely preterm infants born weighing <1,500 g between 2008 and 2018. Demographic characteristics, morbidity, and mortality were compared between the cCAM(-)hCAM(+) and cCAM(+)hCAM(+) groups. RESULTS: We included 16,304 infants. The progression to cCAM in infants with hCAM was correlated with the increase in home oxygen therapy (HOT) (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.11-1.44) and persistent pulmonary hypertension of the newborn (PPHN) (1.20, 1.04-1.38). Furthermore, increased progression of the hCAM stage in infants with cCAM correlated with an increase in bronchopulmonary dysplasia (BPD; 1.05, 1.01-1.11), HOT (1.10, 1.02-1.18), and PPHN (1.09, 1.01-1.18). However, it had a negative impact on hemodynamically significant patent ductus arteriosus (hsPDA; 0.87, 0.83-0.92) and death before discharge from the neonatal intensive care unit (NICU; 0.88, 0.81-0.96). CONCLUSION: Progression to cCAM in infants with hCAM positively correlated with HOT and PPHN. Progression of hCAM staging in infants with cCAM further increases the prevalence of BPD and the need for HOT and PPHN while reducing the prevalence of hsPDA and death before discharge from the NICU. The effects of the progressive hCAM stage in infants with cCAM vary from positive to negative by disease. KEY POINTS: · Retrospective multicenter cohort study based on the Neonatal Research Network of Japan.. · Clinical and histological chorioamnionitis increases the prevalence of BPD, HOT, and PPHN.. · Progression of histological chorioamnionitis in infants reduces the prevalence of hsPDA and death..

Evaluation of newborns with Down syndrome with weight less than 1500 g in the neonatal intensive care unit: A Japanese multicentre study.

AIM: This study aimed to clarify the characteristics and their mortality-related factors in very low birthweight infants with Down syndrome (DS) in Japan. METHODS: This retrospective case-control study enrolled newborns with DS weighing <1500 g admitted to neonatal intensive care unit (NICU) of the perinatal centre registered with the Neonatal Research Network of Japan (NRNJ) database from 2008 to 2019. The clinical characteristics and their mortality-related factors were compared among the Dead group (newborns with DS who died in the NICU), the Survival group (newborns with DS who were alive from the NICU) and the Control group (newborns without congenital or chromosomal condition). RESULTS: A total of 53 656 newborns weighing <1500 g were registered in the NRNJ database for 12 years. Of these, 310 (0.6%) were diagnosed with DS: 62 newborns in the Dead group, 248 in the Survival group and 49 786 in the Control group without chromosomal condition. Logistic analysis revealed that there was a significant difference in the mortality-related factors in congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn; the adjusted odds ratios were 8.6, 121 and 9.5, respectively. Newborns with DS weighing <1000 g showed the earliest death in the NICU on the Kaplan-Meier survival curve (P < 0.01). CONCLUSION: The mortality rate for newborns with DS weighing <1500 g was 20% (5% in the Control group). The mortality-related factors were complications of congenital anomalies, pulmonary haemorrhage and persistent pulmonary hypertension of the newborn.

Evaluation of postoperative complications for patent ductus arteriosus in extremely-low-birthweight infants.

BACKGROUND: Patent ductus arteriosus (PDA), which disrupts the hemodynamics early after birth, causes intraventricular hemorrhage and neonatal necrotizing. Unlike medical treatment for hemodynamically significant PDA, there are institutional disparities in the criteria for surgical treatment METHODS: We aimed to clarify the postoperative indications of surgery for hemodynamically significant PDA and the postoperative complications associated with surgery. RESULTS: Thirty-six extremely-low-birthweight infants (median gestational age 25.2 weeks, median birthweight 699 g) required video-assisted thoracoscopic surgery for PDA (VATS-PDA). The treatment indication of VATS-PDA was resistance to medical treatment in 17 cases, relapsed PDA in 15 cases, and no additional administration of indomethacin because of severe side effects in four cases. Complications with VATS-PDA occurred in eight of 36 cases. There were three cases of pneumothorax, two of thoracotomy transition, two of pulmonary hemorrhage, and four of post-ligation cardiac syndrome (PLCS). VATS-PDA-related death occurred in two cases due to PLCS. The frequency of four or more administrations of indomethacin, with or without postoperative complications, was 88% vs. 39%, respectively (P = 0.04). CONCLUSIONS: All postoperative deaths were caused by PLCS, which had the highest risk of poor prognosis. VATS-PDA should be considered for unclosed PDA after one course of indomethacin administration.

Brain-type natriuretic peptide level in pregnant women with congenital heart disease predicts SGA offspring.

BACKGROUND: Women with congenital heart disease (CHD) commonly experience complications related to CHD during pregnancy. The clinical features of neonates born to mothers with CHD, however, have not been fully investigated. The frequency of small for gestational age (SGA) is high in infants born to mothers with CHD, but the risk factors have not been examined sufficiently. Therefore, we analyzed the maternal features associated with SGA infants. METHODS AND RESULTS: We enrolled pregnant women with repaired CHD and infants born to them at Tokyo Women's Medical University Hospital between April 2007 and March 2015. Eleven SGA (11%) and 91 non-SGA infants (89%) were included. On multivariate logistic regression, SGA infants were significantly more likely to be associated with a high maternal brain-type natriuretic peptide (BNP) level (OR, 6.7; 95%CI: 1.3-34.5; P = 0.02) and maternal single ventricle disease (OR, 8.4; 95%CI:1.4-51.8; P = 0.02) than were non-SGA infants. CONCLUSIONS: The incidence of SGA infants born to mothers with CHD was not high in this study. High BNP and maternal single ventricle disease, however, are independent predictors of SGA in infants.

Biological soliton in multicellular movement.

Solitons have been observed in various physical phenomena. Here, we show that the distinct characteristics of solitons are present in the mass cell movement of non-chemotactic mutants of the cellular slime mould Dictyostelium discoideum. During starvation, D. discoideum forms multicellular structures that differentiate into spore or stalk cells and, eventually, a fruiting body. Non-chemotactic mutant cells do not form multicellular structures; however, they do undergo mass cell movement in the form of a pulsatile soliton-like structure (SLS). We also found that SLS induction is mediated by adhesive cell-cell interactions. These observations provide novel insights into the mechanisms of biological solitons in multicellular movement.

Effect of Bifidobacterium administration on very-low-birthweight infants.

BACKGROUND: The aim of this study was to evaluate the efficacy and safety of early administration of Bifidobacterium bifidum OLB6378 (B. bifidum) on accelerating enteral feeding and bacterial colonization in very-low-birthweight (VLBW) infants. METHODS: We conducted a single-center prospective pilot study. Thirty-six VLBW infants were randomly divided into two groups: group E, wherein B. bifidum was supplemented within 48 h of birth, and group L, wherein it was supplemented more than 48 h after birth. RESULTS: Group E and group L reached a total feeding volume of 100 mL/(kg/day) after 10 [7-13] days and 11 [10-15] days, respectively (median [quartile]). The daily bodyweight gain in group E was significantly higher (21.4 ± 3.2 g/day vs 18.3 ± 4.0 g/day, P < 0.02; 11.1 ± 1.5 g/kg/day vs 10.4 ± 1.2 g/kg/day, P < 0.04). No significant differences were found in the fecal Bifidobacterium level between the groups quantitated with a real-time polymerase chain reaction assay at 1 and 4 weeks of age. However, the highest colonization rate of Bifidobacterium was observed when the supplementation started between 24 and 48 h after birth. The incidence of morbidities between the groups was similar. CONCLUSION: The early administration of B. bifidum to VLBW infants seems effective in promoting growth during the stay in the neonatal intensive care unit without increasing the incidence of morbidity. Furthermore, the preferable timing of starting the probiotic supplementation for VLBW infants is at latest less than 48 h after birth.

Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants.

Moderate consumption of red wine has been shown to exert cardioprotection against ischemia/reperfusion. Because oxidant-dependent leukocyte infiltration plays a critical role in ischemia/reperfusion-induced tissue injury, we hypothesized that resveratrol, a red wine constituent polyphenol would attenuate postischemic leukocyte recruitment and subsequent endothelial dysfunction. Intravital microscopic approaches were used to quantify leukocyte/endothelial cell interactions and venular protein leakage in rat mesenteries exposed to either 20 min ischemia and 60 min reperfusion (I/R), oxidants generated by the reaction of hypoxanthine and xanthine oxidase (HX/XO), platelet-activating factor (PAF), or leukotriene B4 (LTB4). I/R or HX/HX produced marked increases in the number of adherent (LA) and emigrated (LE) leukocytes, which were associated with significant increases in venular albumin leakage (VAL). Intravenous administration of resveratrol or superoxide dismutase (SOD) attenuated these increases in LA, LE, and VAL. Superfusion of the mesentery with PAF or LTB4 also markedly increased LA, LE, and VAL. While resveratrol attenuated the proinflammatory effects of PAF, LTB4-induced changes were not affected by resveratrol. Resveratrol prevents leukocyte recruitment and endothelial barrier disruption induced by a number of superoxide-dependent proinflammatory stimuli, including I/R, HX/XO, or PAF. These salutary effects appear to be related to the antioxidant properties of resveratrol and contribute to the cardioprotective actions associated with consumption of red wine.

Bradykinin-induced proinflammatory signaling mechanisms.

Intravital microscopic techniques were used to examine the mechanisms underlying bradykinin-induced leukocyte/endothelial cell adhesive interactions (LECA) and venular protein leakage (VPL) in single postcapillary venules of the rat mesentery. The effects of bradykinin superfusion to increase LECA and VPL were prevented by coincident topical application of either a bradykinin-B(2) receptor antagonist, a cell-permeant superoxide dismutase (SOD) mimetic or antioxidant, or inhibitors of cytochrome P-450 epoxygenase (CYPE) or protein kinase C (PKC) but not by concomitant treatment with either SOD, a mast cell stabilizer, or inhibitors of nitric oxide synthase, cyclooxygenase, xanthine oxidase, NADPH oxidase, or platelet-activating factor. Immunoneutralizing P-selectin or intercellular adhesion molecule-1 (ICAM-1) completely prevented bradykinin-induced leukocyte adhesion and emigration but did not affect VPL. On the other hand, stabilization of F-actin with phalloidin prevented bradykinin-induced leukocyte emigration and VPL but did not alter leukocyte adhesion. These data indicate that bradykinin induces LECA in rat mesenteric venules via a B(2)-receptor-initiated, CYPE-, oxidant- and PKC-mediated, P-selectin- and ICAM-1-dependent mechanism. Bradykinin also produced VPL, an effect that was initiated by stimulation of B(2) receptors and involved CYPE and PKC activation, oxidant generation, and cytoskeletal reorganization but was independent of leukocyte adherence and emigration.

THE EFFECTS OF CYCLIC AMP ON DIFFERENTIATION OF A MUTANT DICTYOSTELIUM DISCOIDEUM CAPABLE OF DEVELOPING WITHOUT MORPHOGENESIS.

The dev 1510 mutant of Dictyostelium discoideum differs from the wild type in that unaggregated cells are capable of differentiating into either spores or stalk cells depending on the culture conditions (12). Taking advantage of this fact, the effects of cyclic AMP (cAMP) on differentiation of the mutant cells were examined under conditions that prevent normal morphogenesis. In the presence of low concentrations of exogenous cAMP, the cells differentiated into only stalk cells, whereas in the presence of high concentrations they differentiated into only spores. Untreated cells formed stalk cells, but this was inhibited by addition of phosphodiesterase, indicating that it was induced by a low concentration of cAMP which they produced themselves. Cyclic GMP and dibutyryl cAMP also induced spore formation though less effectively, while 5'AMP, ADP and ATP had no effect. During development, the cells increased in sensitivity to cAMP in that spore formation was induced at lower concentration of cAMP after 4 hr of starvation. Treatment of cells that had been starved for 6hr with 10-4 M cAMP for as short a time as 30 min was enough to induce 8% of the cells to form spores. The effects on cAMP-induced differentiation of chemicals that are known to influence development of the wild type were also examined. Both NH4 Cl and KCl inhibited cAMP-induced stalk formation, but had no effect on spore formation. In the presence of arginine, spore formation was induced at a lower concentration of cAMP with higher efficiency. CaCl2 , LiCl and KF had no effect on cAMP-induced differentiation.

A MUTANT OF DICTYOSTELIUM DISCOIDEUM CAPABLE OF DIFFERENTIATING WITHOUT MORPHOGENESIS.

A mutant which is capable of differentiating into spores and stalk cells without forming a cell aggregate was isolated from the cellular slime mould, Dictyostelium discoideum. The mutant stopped developing at various stages, before formation of mature fruits, and the cells differentiated into spores and stalk cells at whichever stage the development stopped. Unaggregated cells also differentiated into spores or stalk cells, depending on the culture conditions; differentiation into spores predominated in nutrient rich medium, while differentiation into stalk cells predominated in nutrient poor medium. The ratio of spores to stalk cells or of prespores to total cells in cell masses depended on the terminal structures formed; the ratio was unusually high or unusually low in a structure which stopped developing before papilla formation, while the ratio was normal in a structure formed after that stage. When isolated from a cell mass, prespore cells of the mutant did not dedifferentiate or resumed vegetative growth, indicating that they had lost plasticity of differentiation. The conditioned medium in which the mutant cells had grown was effective in inducing differentiation of wild type slug cells into spore-like or stalk-like cells.

A "CELL-CONTACT TEMPERATURE-SENSITIVE" MUTANT OF THE CELLULAR SLIME MOLD DICTYOSTELIUM MUCOROIDES.

A mutant (TS-2) that is temperature-sensitive with respect to cell contact was isolated from the cellular slime mold, Dictyostelium mucoroides. The TS-2 were able to grow and develop normally at 21°C, but unable to grow at 31.5°C. When TS-2 were allowed to develop until the aggregation stage at 21°C and then shifted to 31.5°C, they instantly lost cell-to-cell contact, resulting in disintegration of the aggregation stream and flattening of the aggregation center. Although a slug transferred to 31.5°C retained its original shape, loss of cell-to-cell contact within the cell mass was evidenced by several facts. The TS-2 interphase amebas, at 31.5°C, also lost cell-to-substratum contact, and the loss of contact was followed by the production of cell-wall substance on their surface. The production of the same substance at 31.5°C was also observed in cells at aggregation and migration stages, but not in those at the vegetative stage. When TS-2 cells at various developmental stages were kept at 31.5°C for various periods of time and returned to 21°C they lost morphogenetic capacity in proportion to the production of the cell-wall substance.