Facial thermal response to non-painful stressor in premature and term neonates.

BACKGROUND: This study is a preliminary clinical investigation with the objective to evaluate the facial thermal response of premature and term neonates to a non-painful stressor (hunger) using infrared thermography (IRT). The development of objective and reliable parameters to monitor pain and stress is of relevance for optimal neonatal outcome and achieving a better management of patient comfort. METHODS: We enrolled 12 neonates ranging from 27 to 39 weeks gestation (median: 34) and aged 3-79 days (median: 13). Recordings were performed before and after feeding, with and without hunger. Six regions of interest were chosen for evaluation (nose tip, periorbital and corrugator region, forehead, perioral and chin region). RESULTS: There was an increase in the facial temperature in infants immediately prior to their next feed relative to infants who were not hungry, with the nasal tip being the facial evaluation site with the greatest temperature change. CONCLUSIONS: The IRT appears to be a feasible and suitable method to detect changes in the neonatal patient. The thermal variations observed seem to reflect an arousal mediated by the parasympathetic nervous system, which has been described in existing infant stress research. IMPACT: This is the first study to examine the use of infrared thermography (IRT) in monitoring the facial thermal response to a mild stressor (hunger) in premature and term neonates. Hunger as a mild, non-pain-associated stressor showed a significant effect on the facial temperature. The thermal signature of the regions of interest chosen showed hunger-related thermal variations. Results suggest the feasibility and suitability of IRT as an objective diagnostic tool to approach stress and changes in the condition of the neonatal patient.

Detection of acute ventilatory problems via magnetic induction in a newborn animal model.

BACKGROUND: Magnetic induction measurement (MIM) is a noninvasive method for the contactless registration of respiration in newborn piglets by using measurement coils positioned at the bottom of an incubator. Acute pulmonary problems may be determinants of poor neurological and psychomotor outcomes in preterm infants. The current study tested the detection of pulmonary ventilation disorders via MIM in 11 newborn piglets. METHODS: Six measurement coils determined changes in magnetic induction, depending on the ventilation of the lung, in comparison with flow resistance. Contactless registration of induced acute pulmonary ventilation disorders (apnea, atelectasis, pneumothorax, and aspiration) was detected by MIM. RESULTS: All pathologies except aspiration were detected by MIM. Significant changes occurred after induction of apnea (three coils), malposition of the tube (one coil), and pneumothorax (three coils) (p ≤ 0.05). No significant changes occurred after induction of aspiration (p = 0.12). CONCLUSIONS: MIM seems to have some potential to detect acute ventilation disorders in newborn piglets. The location of the measurement coil related to the animal's position plays a critical role in this process. In addition to an early detection of acute pulmonary problems, potential information pointing to a therapeutic intervention, for example, inhalations or medical respiratory analepsis, may be conceivable with MIM in the future. IMPACT: MIM seems to be a method in which noncontact ventilation disorders of premature and mature infants can be detected. This study is an extension of the experimental setup to obtain preliminary evidence for detection of respiratory activity in neonatal piglets. For the first time, MIM is used to register acute ventilation problems of neonates. The possibility of an early detection of acute ventilation problems via MIM may provide an opportunity to receive patient-side information for therapeutical interventions like inhalations or medical respiratory analepsis.

Enhancing the Follow-up Assessment of Very Preterm Children with Regard to 5-Year IQ Considering Socioeconomic Status.

BACKGROUND: Specifying peri- and postnatal factors in children born very preterm (VPT) that affect later outcome helps to improve long-term treatment. AIM: To enhance the predictability of 5-year cognitive outcome by perinatal, 2-year developmental and socio-economic data. SUBJECTS AND OUTCOME MEASURES: 92 VPT infants, born 2007-2009, gestational age<32 weeks and/or birthweight of 1500 g, were assessed longitudinally including basic neonatal, socio-economic (SES), 2-year Mental Developmental Index (MDI, Bayley Scales II), 5-year Mental Processing Composite (MPC, Kaufman-Assessment Battery for Children), and Language Screening for Preschoolers data. 5-year infants born VPT were compared to 34 term controls. RESULTS: The IQ of 5-year infants born VPT was 10 points lower than that of term controls and influenced independently by preterm birth and SES. MDI, SES, birth weight and birth complications explained 48% of the variance of the MPC. The MDI proved highly predictive (r=0.6, R2=36%) for MPC but tended to underestimate the cognitive outcome. A total of 61% of the 2-year infants born VPT were already correctly classified (specificity of .93, sensitivity of .54). CHAID decision tree technique identified SES as decisive for the outcome for infants born VPT with medium MDI results (76-91): They benefit from effects associated to a higher SES, while those with a poor MDI outcome and a birth weight≤890 g do not. CONCLUSION: Developmental follow-up of preterm children enhances the quality of prognosis and later outcome when differentially considering perinatal risks and SES.

Spatio-temporal and -spectral feature maps in photoplethysmography imaging and infrared thermograph.

BACKGROUND: Only a small fraction of the information available is generally used in the majority of camera-based sensing approaches for vital sign monitoring. Dedicated skin pixels, for example, fall into this category while other regions are often disregarded early in the processing chain. METHODS: We look at a simple processing chain for imaging where a video stream is converted to several other streams to investigate whether other image regions should also be considered. These streams are generated by mapping spatio-temporal and -spectral features of video segments and, thus, compressing the information contained in several seconds of video and encoding these in a new image. Two typical scenarios are provided as examples to study the applicability of these maps: face videos in a laboratory setting and measurements of a baby in the neonatal intensive care unit. Each measurement consists of the synchronous recording of photoplethysmography imaging (PPGI) and infrared thermography (IRT). We report the results of a visual inspection of those maps, evaluate the root mean square (RMS) contrast of foreground and background regions, and use histogram intersections as a tool for similarity measurements. RESULTS: The maps allow us to distinguish visually between pulsatile foreground objects and an image background, which is found to be a noisy pattern. Distortions in the maps could be localized and the origin could be discovered. The IRT highlights subject contours for the heart frequency band, while silhouettes show strong signals in PPGI. Reflections and shadows were found to be sources of signals and distortions. We can testify advantages for the use of near-infrared light for PPGI. Furthermore, a difference in RMS contrast for pulsatile and non-pulsatile regions could be demonstrated. Histogram intersections allowed us to differentiate between the background and foreground. CONCLUSIONS: We introduced new maps for the two sensing modalities and presented an overview for three different wavelength ranges. The maps can be used as a tool for visualizing aspects of the dynamic information hidden in video streams without automation. We propose focusing on an indirect method to detect pulsatile regions by using the noisy background pattern characteristic, for example, based on the histogram approach introduced.

Leucine Reconstitutes Phagocytosis-Induced Cell Death in E. coli-Infected Neonatal Monocytes-Effects on Energy Metabolism and mTOR Signaling.

MΦ differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after E. coli infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic signaling. To this end, we supplemented Mo from neonates and from adults with the branched amino acid leucine. In neonatal Mo, we observed increased energy production via oxidative phosphorylation (Oxphos) after E. coli infection via Seahorse assay. Leucine did not change phagocytic properties. In neonatal Mo, we detected temporal activation of the AKT and mTOR pathways, accompanied with subsequent activation of downstream targets S6 Kinase (S6K) and S6. FACS analyses showed that once mTOR activation was terminated, the level of anti-apoptotic BCL-2 family proteins (BCL-2; BCL-XL) decreased. Release of cytochrome C and cleavage of caspase-3 indicated involvement of the intrinsic apoptotic pathway. Concomitantly, the PICD of neonatal Mo was initiated, as detected by hypodiploid DNA. This process was sensitive to rapamycin and metformin, suggesting a functional link between AKT, mTOR and the control of intrinsic apoptotic signaling. These features were unique to neonatal Mo and could not be observed in adult Mo. Supplementation with leucine therefore could be beneficial to reduce sustained inflammation in septic neonates.

The iRhom2/ADAM17 Axis Attenuates Bacterial Uptake by Phagocytes in a Cell Autonomous Manner.

Uptake of bacteria by phagocytes is a crucial step in innate immune defence. Members of the disintegrin and metalloproteinase (ADAM) family critically control the immune response by limited proteolysis of surface expressed mediator molecules. Here, we investigated the significance of ADAM17 and its regulatory adapter molecule iRhom2 for bacterial uptake by phagocytes. Inhibition of metalloproteinase activity led to increased phagocytosis of pHrodo labelled Gram-negative and -positive bacteria (E. coli and S. aureus, respectively) by human and murine monocytic cell lines or primary phagocytes. Bone marrow-derived macrophages showed enhanced uptake of heat-inactivated and living E. coli when they lacked either ADAM17 or iRhom2 but not upon ADAM10-deficiency. In monocytic THP-1 cells, corresponding short hairpin RNA (shRNA)-mediated knockdown confirmed that ADAM17, but not ADAM10, promoted phagocytosis of E. coli. The augmented bacterial uptake occurred in a cell autonomous manner and was accompanied by increased release of the chemokine CXCL8, less TNFα release and only minimal changes in the surface expression of the receptors TNFR1, TLR6 and CD36. Inhibition experiments indicated that the enhanced bacterial phagocytosis after ADAM17 knockdown was partially dependent on TNFα-activity but not on CXCL8. This novel role of ADAM17 in bacterial uptake needs to be considered in the development of ADAM17 inhibitors as therapeutics.

Plasma-derived Factor X therapy for treatment of intracranial bleeding in a patient with Factor X deficiency: a case report.

BACKGROUND: Factor X (FX) deficiency (FXD) is an extremely rare autosomal recessive hereditary hematologic disorder, affecting approximately one in 1,000,000 of the general population. CASE REPORT: This case report describes an infant with hereditary severe FXD who presented with a spontaneous, life-threatening intracranial hemorrhage and was treated with the first licensed plasma-derived FX (pdFX) concentrate. On admission, laboratory assays showed severe coagulopathy of unknown cause; the patient was empirically treated using a multimodal hemostatic approach with prothrombin complex concentrate, fresh-frozen plasma, and tranexamic acid. Subsequent single-factor coagulation and genetic analyses confirmed the hereditary FXD diagnosis, and the therapeutic regimen was changed to a targeted regimen of 250 IU pdFX daily. Based on careful monitoring of the coagulation profile, pdFX administration frequency was increased to twice daily, followed by a reduction to once every 18 hours. The patient was discharged after 7 weeks of hospitalization in good clinical condition and now receives prophylactic pdFX three times weekly.

Cord blood granulocytic myeloid-derived suppressor cells impair monocyte T cell stimulatory capacity and response to bacterial stimulation.

BACKGROUND: Neonatal sepsis is a leading cause of perinatal morbidity and mortality. In comparison to adults, neonates exhibit a higher susceptibility to infections. Myeloid-derived suppressor cells (MDSCs) are myeloid cells with suppressive activity on other immune cells accumulating during foetal life and controlling inflammation in neonates. Most studies investigating the mechanisms for MDSC-mediated immune suppression have been focused on T-cells. Thus far, little is known about the role of MDSC for monocyte function. METHODS: The impact of human cord blood MDSCs (CB-MDSCs) on monocytes was investigated in an in vitro model. CB-MDSCs were co-cultured with peripheral blood mononuclear cells and monocytes were analysed for expression of surface markers, T cell stimulatory and phagocytic capacity, as well as the production of intracellular cytokines by flow cytometry. RESULTS: CB-MDSCs increased the expression of co-inhibitory molecules and decreased the expression of major histocompatibility complex class II molecules on monocytes, leading to an impaired T-cell stimulatory capacity. Upon bacterial stimulation, expression of phagocytosis receptors, phagocytosis rates and production of tumor necrosis factor-α by monocytes was diminished by CB-MDSCs. CONCLUSION: We show that CB-MDSCs profoundly modulate monocyte functions, thereby indirectly impairing T-cell activation. Further research is needed to figure out if MDSCs could be a therapeutic target for inflammatory diseases in neonates like neonatal sepsis.

Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and the Bcl-2 Protein Family.

Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphiregulin (AREG) is increasingly expressed on the cell surface of neonatal monocytes, resulting in remarkably higher soluble AREG levels after proteolytic shedding. In this study, we found that E. coli-infected neonatal monocytes show an increased phosphorylation of ERK, increased expression of Bcl-2 and Bcl-XL, and reduced levels of cleaved caspase-3 and caspase-9 compared to adult monocytes. In both cell types, additional stimulation with soluble AREG further increased ERK activation and expression of Bcl-2 and Bcl-XL and reduced levels of cleaved caspase-3 and caspase-9 in an EGFR-dependent manner. These data suggest that reduced PICD of neonatal monocytes could be due to reduced intrinsic apoptosis and that AREG can promote protection against PICD. This reduction of the intrinsic apoptosis pathway in neonatal monocytes could be relevant for severely prolonged inflammatory responses of neonates.

Metalloproteinases TACE and MMP-9 Differentially Regulate Death Factors on Adult and Neonatal Monocytes After Infection with Escherichia coli.

Background: Cleaving ligands and receptors of the tumor necrosis factor (TNF) superfamily can critically regulate the induction of apoptosis. Matrix metalloproteinases (MMPs) such as MMP-9 and tumor necrosis factor-α-converting enzyme (TACE) have been shown to cleave CD95-Ligand (CD95L) and TNF/(TNF receptor-1) TNFR1 which induce phagocytosis induced cell death (PICD) in adult monocytes. This process is reduced in neonatal monocytes. Methods: Here we tested in vitro, whether Escherichia coli infection mounts for activation of MMP-9 and TACE in monocytes and whether this process regulates PICD. Results: The surface expression of TACE was most prominent on infected adult monocytes. In contrast, surface presentation of MMP-9 was highest on infected neonatal monocytes. Selective blocking of MMP-9 decreased CD95L secretion, while inhibition of TACE left CD95L secretion unaltered. Blocking of MMP-9 increased surface CD95L (memCD95L) expression on infected neonatal monocytes to levels comparable to infected adult monocytes. Moreover, MMP-9 inhibition raised PICD of infected neonatal monocytes to levels observed for infected adult monocytes. In contrast, TACE inhibition decreased PICD in infected monocytes. Addition of extracellular TNF effectively induced memCD95L presentation and PICD of adult monocytes and less of neonatal monocytes. Conclusion: MMP-9 activity is crucial for downregulating cell-contact dependent PICD in E. coli infected neonatal monocytes. By this mechanism, MMP-9 could contribute to reducing sustained inflammation in neonates.

Amphiregulin Regulates Phagocytosis-Induced Cell Death in Monocytes via EGFR and Matrix Metalloproteinases.

Neonates are highly susceptible to microbial infections which is partially attributable to fundamental phenotypic and functional differences between effector cells of the adult and neonatal immune system. The resolution of the inflammation is essential to return to tissue homeostasis, but given that various neonatal diseases, such as periventricular leukomalacia, necrotizing enterocolitis, or bronchopulmonary dysplasia, are characterized by sustained inflammation, newborns seem predisposed to a dysregulation of the inflammatory response. Targeted apoptosis of effector cells is generally known to control the length and extent of the inflammation, and previous studies have demonstrated that phagocytosis-induced cell death (PICD), a special type of apoptosis in phagocytic immune cells, is less frequently triggered in neonatal monocytes than in adult monocytes. We concluded that a rescue of monocyte PICD could be a potential therapeutic approach to target sustained inflammation in neonates. The EGFR ligand amphiregulin (AREG) is shed in response to bacterial infection and was shown to mediate cellular apoptosis resistance. We hypothesized that AREG might contribute to the reduced PICD of neonatal monocytes by affecting apoptosis signaling. In this study, we have examined a cascade of signaling events involved in extrinsic apoptosis by using a well-established in vitro E. coli infection model in monocytes from human peripheral blood (PBMO) and cord blood (CBMO). We found that CBMO shows remarkably higher pro-AREG surface expression as well as soluble AREG levels in response to infection as compared to PBMO. AREG increases intracellular MMP-2 and MMP-9 levels and induces cleavage of membrane-bound FasL through engagement with the EGF receptor. Our results demonstrate that loss of AREG rescues PICD in CBMO to the level comparable to adult monocytes. These findings identify AREG as a potential target for the prevention of prolonged inflammation in neonates.

Preterm Pulmonary Hemorrhage Is Associated with Multiple Births but Not with Intracytoplasmic Sperm Injection: A Cohort Study on Medical Records.

OBJECTIVE: Pulmonary hemorrhage (PH) is a severe complication in preterm neonates. This study aims to identify risk factors and comorbidities of PH. STUDY DESIGN: A single-center cohort study on medical records including all preterm neonates of <30 weeks' gestational age was conducted in the neonatal intensive care unit of Universitätsklinikum Aachen, Germany. The occurrence of PH served as a primary end point. Gestational age, birthweight, sex, multiple births, intracytoplasmic sperm injection (ICSI), intubation, surfactant, antenatal steroids, intraventricular hemorrhage (IVH), amniotic infection syndrome, and persistent ductus arteriosus were studied as risk factors. RESULTS: In this study, 344 preterm neonates were included, of whom 36 suffered from PH (10.5%). The mean time of the first occurrence was the third day of life (standard deviation [SD]: 1.2). On average, the patients suffered from 1.5 incidents (SD: 0.8) of PH, of whom 50% were severe. Preterm neonates born as multiples (95% confidence interval [CI]: 3.1, 26.9) and those who suffered from IVH (95% CI: 2.7, 18.9) had a significantly increased risk of PH. ICSI was not an independent risk factor. CONCLUSION: PH is significantly associated with IVH and multiple births but not with ICSI. The identification of patients at risk allows to apply prophylactic strategies of ventilation and pharmacological treatment.

Granulocytic myeloid-derived suppressor cells from human cord blood modulate T-helper cell response towards an anti-inflammatory phenotype.

Infections are a leading cause of perinatal morbidity and mortality. The outstandingly high susceptibility to infections early in life is mainly attributable to the compromised state of the neonatal immune system. One important difference to the adult immune system is a bias towards T helper type 2 (Th2) responses in newborns. However, mechanisms regulating neonatal T-cell responses are incompletely understood. Granulocytic myeloid-derived suppressor cells (GR-MDSC) are myeloid cells with a granulocytic phenotype that suppress various functions of other immune cells and accumulate under physiological conditions during pregnancy in maternal and fetal blood. Although it has been hypothesized that GR-MDSC accumulation during fetal life could be important for the maintenance of maternal-fetal tolerance, the influence of GR-MDSC on the immunological phenotype of neonates is still unclear. Here, we investigated the impact of GR-MDSC isolated from cord blood (CB-MDSC) on the polarization of Th cells. We demonstrate that CB-MDSC inhibit Th1 responses and induced Th2 responses and regulatory T (Treg) cells. Th1 inhibition was cell-contact dependent and occurred independent of other cell types, while Th2 induction was mediated independently of cell contact through expression of ArgI and reactive oxygen species by CB-MDSC and partially needed the presence of monocytes. Treg cell induction by CB-MDSC also occurred cell-contact independently but was partially mediated through inducible nitric oxide synthase. These results point towards a role of MDSC in regulating neonatal immune responses. Targeting MDSC function in neonates could be a therapeutic opportunity to improve neonatal host defence.

Serum cholesterol acceptor capacity in intrauterine growth restricted fetuses.

AIM: Intrauterine growth restriction (IUGR) is an independent risk factor for the development of cardiovascular diseases later in life. The mechanisms whereby slowed intrauterine growth confers vascular risk are not clearly established. In general, a disturbed cholesterol efflux has been linked to atherosclerosis. The capacity of serum to accept cholesterol has been repeatedly evaluated in clinical studies by the use of macrophage-based cholesterol efflux assays and, if disturbed, precedes atherosclerotic diseases years before the clinical diagnosis. We now hypothesized that circulating cholesterol acceptors in IUGR sera specifically interfere with cholesterol transport mechanisms leading to diminished cholesterol efflux. METHODS: RAW264.7 cells were used to determine efflux of [3H]-cholesterol in response to [umbilical cord serum (IUGR), n=20; controls (CTRL), n=20]. RESULTS: Cholesterol efflux was lower in IUGR as compared to controls [controls: mean 7.7% fractional [3H]-cholesterol efflux, standard deviation (SD)=0.98; IUGR: mean 6.3%, SD=0.79; P<0.0001]. Values strongly correlated to HDL (ρ=0.655, P<0.0001) and apoE (ρ=0.510, P=0.0008), and mildly to apoA1 (ρ=0.3926, P=0.0122) concentrations. CONCLUSIONS: Reduced cholesterol efflux in IUGR could account for the enhanced risk of developing cardiovascular diseases later in life.

Neonatal monocytes express antiapoptotic pattern of Bcl-2 proteins and show diminished apoptosis upon infection with Escherichia coli.

BACKGROUND: Neonates show sustained inflammation after a bacterial infection, which is associated with inflammatory diseases like bronchopulmonary dysplasia or periventricular leucomalacia. Physiologically, inflammation is terminated early after the removal of the invading pathogens by phagocytosis-induced cell death (PICD) of immune effector cells. Earlier results showed reduced PICD in neonatal monocytes. The underlying molecular mechanisms are unknown. We hypothesize that the reduced PICD in neonatal monocytes is regulated through the proteins of the B-cell lymphoma 2 (Bcl-2) protein family. METHODS: mRNA and protein expression of Bcl-2 family proteins in cord blood and adult peripheral blood monocytes infected with Escherichia coli were analyzed by quantitative real-time PCR and flow cytometry and cytochrome c release by fluorescence microscopy. RESULTS: mRNA expression of antiapopototic Bcl-xL was upregulated in cord blood monocytes (CBMO), whereas proapoptotic Bim tended to be higher in peripheral blood monocytes (PBMO). Upon infection, Bax was more strongly expressed in PBMO compared with CBMO. The pro/antiapoptotic balance was skewed toward survival in CBMO and apoptosis in PBMO. Cytochome c release into the cytosol was enhanced in PBMO compared with CBMO. CONCLUSION: Bcl-2 proteins are involved in reduced PICD in neonatal monocytes. These findings are another step toward the understanding of sustained inflammation in neonates.

Miniaturization: the clue to clinical application of the artificial placenta.

The artificial placenta as a fascinating treatment alternative for neonatal lung failure has been the subject of clinical research for over 50 years. Pumpless systems have been in use since 1986. However, inappropriate dimensioning of commercially available oxygenators has wasted some of the theoretical advantages of this concept. Disproportional shunt fractions can cause congestive heart failure. Blood priming of large oxygenators and circuits dilutes fetal hemoglobin (as the superior oxygen carrier), is potentially infectious, and causes inflammatory reactions. Flow demands of large extracorporeal circuits require cannula sizes that are not appropriate for use in preterm infants. NeonatOx, a tailored low-volume oxygenator for this purpose, has proven the feasibility of this principle before. We now report the advances in biological performance of a refined version of this specialized oxygenator.

The CD95/CD95L pathway is involved in phagocytosis-induced cell death of monocytes and may account for sustained inflammation in neonates.

BACKGROUND: The propensity for sustained inflammation after bacterial infection in neonates, resulting in inflammatory sequelae such as bronchopulmonary dysplasia and periventricular leucomalacia, is well known, but its molecular mechanisms remain elusive. Termination of inflammatory reactions physiologically occurs early after removal of bacteria by phagocytosis-induced cell death (PICD) of immune effector cells such as monocytes. PICD from cord blood monocytes (CBMOs) was shown to be reduced as compared with that of peripheral blood monocytes (PBMOs) from adult donors in vitro. METHODS: PBMOs, CBMOs, and Fas (CD95)-deficient (lpr) mouse monocytes were analyzed in an in vitro infection model using green fluorescence protein-labeled Escherichia coli (E. coli-GFP). Phagocytosis and apoptosis were quantified by flow cytometry and CD95L secretion was quantified by enzyme-linked immunosorbent assay. RESULTS: We demonstrate the involvement of the CD95/CD95 ligand pathway (CD95/CD95L) in PICD and provide evidence that diminished CD95L secretion by CBMOs may result in prolonged activation of neonatal immune effector cells. CONCLUSION: These in vitro results offer for the first time a molecular mechanism accounting for sustained inflammation seen in neonates.

Infrared thermography for detailed registration of thermoregulation in premature infants.

OBJECTIVE: To evaluate skin temperature by using different positions with non-contact infrared thermography (IRT) in multiple body areas of preterm infants for detailed information about temperature regulation and distribution. METHODS: The temperature of ten premature infants (median: 27 weeks; age 36 days; weight 1322 g) was determined via IRT (leg, back, arm, head, upper abdomen; diameter 1 cm, scale 0.00°C), and comparison was made with two conventional sensors. There were measurements of 10 min each: first incubator phase (I1), standardized skin-to-skin care (SSC) at the beginning (SSC1), after 90 min (SSC2), and then there was a second incubator phase (I2). RESULTS: From I1 to SSC1, patients cooled down (max. 0.62°C; both methods). From SSC1 to SSC2 temperature on central areas (abdomen, back) was maintained but rose distinctively on the head and leg (P<0.05). In the incubator (I2), temperature niveau in all IRT-areas was significantly lower than before SSC. CONCLUSION: Via IRT, it is possible to detect fluctuations in temperature of premature infants. The cooling in I2 after SSC should be taken into account before routine daily care.

[Strategies for airway management in neonates : Results of a survey of German perinatal centers levels II and III]. / Strategien zur Atemwegssicherung bei Neugeborenen : Ergebnisse einer Befragung deutscher Perinatalzentren der Level I und II.

BACKGROUND: Airway management in children, especially in patients with a difficult airway, remains a major challenge for anesthesiologists, pediatricians, and emergency medicine physicians. In recent years new tools have been introduced into the clinical practice. OBJECTIVE: The aim was to present the current strategies for securing the airway in neonates in perinatal centers levels II and III in Germany, and to collect data on the rare event of coniotomy. MATERIAL AND METHODS: From 5 April 2021 to 15 June 2021, physicians practicing intensive care in pediatrics and neonatology at perinatal centers levels II and III in Germany were surveyed by means of an anonymized online questionnaire. The questionnaire was designed by the authors and verified by pretesting with the help of five pediatric specialists. Contact was made digitally via the e­mail addresses provided on the websites of the respective centers. The survey was administered through the fee for service provider LimeSurvey©. The collected data were transferred to the IBM© statistical package for the social scientists (SPSS, version 28, IBM© Corporation, Armonk, NY, USA) and statistically analyzed. Pearson's χ2-test was used to perform significance testing (significance level p = < 0.05). Only completed questionnaires were included in the analysis. RESULTS: A total of 219 participants completed the questionnaire. Available airway devices: 94.5% (n = 207) nasopharyngeal tubes, 79.9% (n = 175) video laryngoscope/fiber optic, 73.1% (n = 160) laryngeal masks, 64.8% (n = 142) oropharyngeal tube (Guedel). Of the participants 6 (2.7%) performed coniotomy (⌀ 1.6 children). Out of six cases five (83.3%) were resuscitation situations caused by complex anatomical malformations. Training of coniotomy was not provided in 98.6% (n = 216). A Standard Operating Procedure (SOP) for difficult airway in neonates was possessed by 20.1% (n = 44). CONCLUSION: The comparison with international studies showed that the equipment of German perinatal centers is above average. The trend towards acquisition of a video laryngoscope and its importance in clinical routine could be confirmed by our data; however, the fact that 20% of the respondents did not have access to video laryngoscopy suggests that further acquisitions will have to be made here in the future. Front of neck access (FONA) methods remain a critically questioned component of neonatal difficult airway algorithms due to their rarity and the resulting lack of data. In summary of the recommendations of the British Association of Perinatal Medicine (BAPM) and the collected data on the theoretical and practical education of the FONA methods in Germany, the implementation of the FONA methods by pediatricians and neonatologists cannot be recommended. As most resuscitation situations were caused by complex anatomical malformations, the early detection of such malformations by means of high-resolution ultrasound seems to be of particular importance. With improvement of early detection, neonates with potentially unmanageable airway problems can be left on uteroplacental circulation for a prolonged period in order to perform necessary interventions, such as tracheostomy, bronchoscopy, or extracorporeal membrane oxygenation (ECMO) device known as the ex utero intrapartum treatment (EXIT) procedure.

EGF-Receptor against Amphiregulin (AREG) Influences Costimulatory Molecules on Monocytes and T Cells and Modulates T-Cell Responses.

Amphiregulin (AREG) is a ligand of the epidermal growth factor receptor (EGFR) and has been shown to regulate the phagocytosis-induced cell death of monocytes in peripheral blood. AREG-dependent apoptotic signaling engages factors of the intrinsic and extrinsic apoptotic pathway, such as BCL-2, BCL-XL, and death ligand/receptor CD95/CD95L. Here, we tested the hypothesis that AREG influences costimulatory monocyte functions, which are crucial for T-cell responses. We found a stronger expression of AREG and EGFR in monocytes compared to lymphocytes. As a novel function of AREG, we observed reduced T-cell proliferation following polyclonal T-cell stimulation with OKT3. This reduction of proliferation occurred in the presence of monocytes as well as in their absence, monocyte signaling being replaced by crosslinking of OKT3. Increasing concentrations of AREG down-modulated the concentration of costimulatory B7 molecules (CD80/CD86) and HLA-DR on monocytes. In proliferation assays, CD28 expression on T cells was down-modulated on the application of OKT3 but unaltered by AREG. LcK activation, following OKT3-stimulation, was reduced in T cells that had been coincubated with AREG. The effects of AREG on T-cell phenotypes were also present when monocytes were depleted and OKT3 was crosslinked. The rearranged expression of immunological synapse proteins was accompanied by an alteration of T-cell polarization. Although the proportion of regulatory T cells was not shifted by AREG, IL-17-expressing T cells were significantly enhanced, with a bias toward TH1-polarization. Taken together, these results suggest that AREG acts as an immunoregulatory molecule at the interface between antigen-presenting cells and T cells.