Lost in translation: Unveiling medical students' untold errors of medical history documentation.

OBJECTIVE: The accurate documentation of a medical history interview is an important goal in medical education. As students' documentation of medical history interviews is mostly decentralised on the wards, a systematic assessment of documentation quality is missing. We therefore evaluated the extent of details missed in students' medical history reports in a standardised setting. METHODS: In this prospective, observational study, 123 of 380 students (32.4%) participated in an Objective Structured Clinical Examination (OSCE) regarding history taking and documentation. Based on the interviews and nine deductively selected main categories, a categorical system was established using a summarising qualitative content analysis. The items in the transcripts (defined as ground truth) and in students' reports were labelled and assigned to the correct subcategory. The ground truth and students' reports were compared to quantify students' documentation completeness. RESULTS: Next to the nine deductively selected main categories, 61 subcategories were defined. A total of 8943 items were labelled in the 123 interview transcripts (ground truth), compared with 5870 items labelled in students' reports (65.6% completeness of students' reports compared with ground truth). The main category personal details overlapped with 94.2% between students' report and ground truth in contrast to the main category with the highest discrepancy, allergy, with 41.1% overlap. Pertinent negative items and non-numerical quantifications were often missed. CONCLUSIONS: Medical students show incomplete documentation of medical history interviews. Therefore, accurate documentation should be taught as an important goal in medical education.

Monitoring of the microcirculation in children undergoing major abdominal and thoracic surgery: A pilot study.

BACKGROUND: Monitoring of the macrocirculation during surgery provides limited information on the quality of organ perfusion. OBJECTIVE: We investigated the feasibility of perioperative microcirculatory measurements in children. METHODS: Sublingual microvessels were visualized by handheld videomicroscopy in 11 children (19 mo - 10 yrs) undergoing surgery > 120 min at four time points: T0) after induction of anesthesia; T1) before end of anesthesia, T2) 6 h post surgery and T3) 24 h post surgery. RESULTS: Measurements were feasible in all children at T0 and T1. At T2 and T3, imaging was restricted to 6 and 4 infants, respectively, due to respiratory compromise and missing cooperation. The capillary density was reduced at T1 compared to T0 (8.1 mm/mm2 [4.0-17.0] vs. 10.6 mm/mm2 [5.1-19.3]; p = 0.01), and inversely related to norepinephrine dose (Pearson r = -0.65; p = 0.04). Microvascular flow and serum glycocalyx makers Syndecan-1 and Hyaluronan increased significantly from T0 to T1. CONCLUSION: Perioperative microcirculatory monitoring in children requires a high amount of personal and logistic resources still limiting its routine use. Major surgery is associated with microvascular alterations and glycocalyx perturbation. The possible consequences on patient outcome need further evaluation. Efforts should concentrate on the development of next generation devices designed to facilitate microcirculatory monitoring in children.

Online medical history taking course: Opportunities and limitations in comparison to traditional bedside teaching.

Objective: Obtaining a systematic medical history (MH) from a patient is a core competency in medical education and plays a vital role in the diagnosis of diseases. At the Faculty of Medicine at LMU Munich, students have their first course in MH taking during their second year. Due to the COVID-19 pandemic, the traditional bedside MH taking course had to be transformed into an online course (OC). Our objectives were to implement an online MH taking course, to evaluate its feasibility and to compare the evaluation results to a historic cohort that had undertaken the traditional bedside teaching course (BTC). Methods: 874 second-year students participated in the OC (BTC=827). After teaching the theoretical background via asynchronous online lectures, students participated in a practical exercise with fellow students using the video communication platform Zoom where they were able to practice taking a MH on the basis of fictitious, text-based patient cases. Students were then asked to evaluate the course through a standardized online survey with 31 questions on teaching quality and self-perceived learning success, which had also been used in previous years. The survey results were compared to the results of the historic cohort using the Mann-Whitney U test. Results: A total of n=162 students (18.5%) evaluated the OC. In the historic cohort, n=252 (30.5%) completed the survey. 85.3% of the OC respondents thought that the atmosphere during the practical exercise was productive and 83.0% greatly appreciated the flexibility in terms of time management. Moreover, they appreciated the online resources as well as having the opportunity to undertake a MH taking course during the COVID-19 pandemic. 27.7% of the respondents thought that traditional BTCs should be supplemented through more online activities in the future. With respect to the ability of independently taking a MH upon completion of the course, the OC was rated significantly lower relative to the BTC (mean OC=2.4, SD=±1.1 vs. mean BTC=1.9, SD=±1.1 (1=strongly agree; 5=strongly disagree); p<0.0001). Conclusion: OCs are a feasible format and seem to convey the theory and practical implementation in a peer-exercise format of MH taking to medical students. The theoretical background can be acquired with great flexibility. Nevertheless, the students' self-appraisal suggested that the traditional teaching format was more effective at teaching MH taking skills. Thus, we propose a blended learning concept, combining elements of both formats. In this context, we suggest prospective, randomized trials to evaluate blended learning approaches.

Noninvasive Ventilation in Preterm Infants: Factors Influencing Weaning Decisions and the Role of the Silverman-Andersen Score.

The factors influencing weaning of preterm infants from noninvasive ventilation (NIV) are poorly defined and the weaning decisions are often driven by subjective judgement rather than objective measures. To standardize quantification of respiratory effort, the Silverman-Andersen Score (SAS) was included in our nursing routine. We investigated the factors that steer the weaning process and whether the inclusion of the SAS would lead to more stringent weaning. Following SAS implementation, we prospectively evaluated 33 neonates born ≤ 32 + 0 weeks gestational age. Age-, weight- and sex-matched infants born before routine SAS evaluation served as historic control. In 173 of 575 patient days, NIV was not weaned despite little respiratory distress (SAS ≤ 2), mainly due to bradycardias (60% of days without weaning), occurring alone (40%) or in combination with other factors such as apnea/desaturations. In addition, "soft factors" that are harder to grasp impact on weaning decisions, whereas the SAS overall played a minor role. Consequently, ventilation times did not differ between the groups. In conclusion, NIV weaning is influenced by various factors that override the absence of respiratory distress limiting the predictive value of the SAS. An awareness of the factors that influence weaning decisions is important as prolonged use of NIV has been associated with adverse outcome. Guidelines are necessary to standardize NIV weaning practice.

The Endothelial Glycocalyx: Physiology and Pathology in Neonates, Infants and Children.

The endothelial glycocalyx (EG) as part of the endothelial surface layer (ESL) is an important regulator of vascular function and homeostasis, including permeability, vascular tone, leukocyte recruitment and coagulation. Located at the interface between the endothelium and the blood stream, this highly fragile structure is prone to many disruptive factors such as inflammation and oxidative stress. Shedding of the EG has been described in various acute and chronic diseases characterized by endothelial dysfunction and angiopathy, such as sepsis, trauma, diabetes and cardiovascular disease. Circulating EG components including syndecan-1, hyaluronan and heparan sulfate are being evaluated in animal and clinical studies as diagnostic and prognostic markers in several pathologies, and advances in microscopic techniques have enabled in vivo assessment of the EG. While research regarding the EG in adult physiology and pathology has greatly advanced throughout the last decades, our knowledge of the development of the glycocalyx and its involvement in pathological conditions in the pediatric population is limited. Current evidence suggests that the EG is present early during fetal development and plays a critical role in vessel formation and maturation. Like in adults, EG shedding has been demonstrated in acute inflammatory conditions in infants and children and chronic diseases with childhood-onset. However, the underlying mechanisms and their contribution to disease manifestation and progression still need to be established. In the future, the glycocalyx might serve as a marker to identify pediatric patients at risk for vascular sequelae and as a potential target for early interventions.

Microdialysis sampling to monitor target-site vancomycin concentrations in septic infants: a feasible way to close the knowledge gap.

This work is dedicated to the memory of Hartmut Derendorf (1953-2020), a pioneer of modern pharmacokinetics and valued mentor of this project. OBJECTIVES: Septic infants/neonates need effective antibiotic exposure, but dosing recommendations are challenging as the pharmacokinetics in this age are highly variable. For vancomycin, which is used as a standard treatment, comprehensive pharmacokinetic knowledge especially at the infection site is lacking. Hence, an exploratory clinical study was conducted to assess the feasibility and safety of microdialysis sampling for vancomycin monitoring at the target site. METHODS: Nine infants/neonates with therapeutic indications for vancomycin treatment were administered 15 mg/kg as 1-hour infusions every 8-24 hours. Microdialysis catheters were implanted in the subcutaneous interstitial space fluid of the lateral thigh. Samples were collected every 30 minutes over 24 hours, followed by retrodialysis for catheter calibration. Prior in vitro investigations have evaluated impact factors on relative recovery and retrodialysis. RESULTS: In vitro investigations showed the applicability of microdialysis for vancomycin monitoring. Microdialysis sampling was well tolerated in all infants/neonates (23-255 days) without major bleeding or other adverse events. Pharmacokinetic profiles were obtained and showed plausible vancomycin concentration-time courses. CONCLUSIONS: Microdialysis as a minimally invasive technique for continuous longer-term sampling is feasible and safe in infants/neonates. Interstitial space fluid profiles were plausible and showed substantial interpatient variation. Hence, a larger microdialysis trial is warranted to further characterise the pharmacokinetics and variability of vancomycin at the target site and ultimately improve vancomycin dosing in these vulnerable patients.

Cohort profile: the MUNICH Preterm and Term Clinical study (MUNICH-PreTCl), a neonatal birth cohort with focus on prenatal and postnatal determinants of infant and childhood morbidity.

PURPOSE: The MUNICH Preterm and Term Clinical (MUNICH-PreTCl) birth cohort was established to uncover pathological processes contributing to infant/childhood morbidity and mortality. We collected comprehensive medical information of healthy and sick newborns and their families, together with infant blood samples for proteomic analysis. MUNICH-PreTCl aims to identify mechanism-based biomarkers in infant health and disease to deliver more precise diagnostic and predictive information for disease prevention. We particularly focused on risk factors for pregnancy complications, family history of genetically influenced health conditions such as diabetes and paediatric long-term health-all to be further monitored and correlated with proteomics data in the future. PARTICIPANTS: Newborns and their parents were recruited from the Perinatal Center at the LMU University Hospital, Munich, between February 2017 and June 2019. Infants without congenital anomalies, delivered at 23-41 weeks of gestation, were eligible. FINDINGS: Findings to date concern the clinical data and extensive personal patient information. A total of 662 infants were recruited, 44% were female (36% in preterm, 46% in term). 90% of approached families agreed to participate. Neonates were grouped according to gestational age: extremely preterm (<28 weeks, N=28), very preterm (28 to <32 weeks, N=36), late preterm (32 to <37 weeks, N=97) and term infants (>37+0 weeks, N=501). We collected over 450 data points per child-parent set, (family history, demographics, pregnancy, birth and daily follow-ups throughout hospitalisation) and 841 blood samples longitudinally. The completion rates for medical examinations and blood samples were 100% and 95% for the questionnaire. FUTURE PLANS: The correlation of large clinical datasets with proteomic phenotypes, together with the use of medical registries, will enable future investigations aiming to decipher mechanisms of disorders in a systems biology perspective. TRIAL REGISTRATION NUMBER: DRKS (00024189); Pre-results.

Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates.

Prematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfused Boundary Region (PBR), an inverse measure of glycocalyx thickness, was measured postnatally in 85 term and 39 preterm neonates. Preterm neonates were further analyzed in two subgroups i.e., neonates born < 30 weeks gestational age (group A) and neonates born ≥ 30 weeks (group B). In preterm neonates, weekly follow-up measurements were performed if possible. PBR differed significantly between preterm and term neonates with lowest values representing largest EG dimension in extremely premature infants possibly reflecting its importance in fetal vascular development. Linear regression revealed a dependence of PBR on both, gestational age and postnatal age. Furthermore, hematocrit predicted longitudinal PBR changes. PBR measured in group A at a corrected age of > 30 weeks was significantly higher than in group B at birth, pointing towards an alteration of intrinsic maturational effects by extrinsic factors. These changes might contribute to the increased cardiovascular risk associated with extreme prematurity.

Disparity in Birth Size of Ethiopian Preterm Infants in Comparison to International INTERGROWTH-21st Data.

Background. Patterns of fetal growth are largely influenced by environmental, nutritional, and socioeconomic factors more than differences in populations. The aim of this study was to assess anthropometric measurements of Ethiopian preterm infants at birth and compare the results with the international INTERGROWTH-21st data. Patients and methods. We analyzed anthropometric data on live-born singleton preterm infants enrolled in a hospital-based multicenter study of illness in preterm infants (SIP). Eligible newborns with gestational age of 28-36 weeks were included. Gestational age (GA) and sex-specific mean and standard deviations (SD), 10th, 50th, 90th, centile values for birth weight, length and head circumference (HC) were calculated and compared with INTERGROWTH-21st data. Result. A total of 2763 preterm infants were included in the study, 54% were male. The prevalence of small for GA (SGA) (<10th percentile) and large for GA (LGA) (>90th percentile) were 10.8% and 9.9%, respectively. In all 3 parameters, the mean values of boys were higher than of girls. Birth weight centiles were comparable to international averages at lower GA, then after GA of 32 weeks the 10th, 50th, and 90th centile values were 100-500 g less than the international averages. The head circumference centiles were mostly comparable, and the 90th centile values were greater than the international averages across the GA and in both sexes. Conclusion. The infants' birth weights were smaller at higher GA, which may indicate maternal undernutrition in the third trimester of pregnancy. Strengthening antenatal nutrition counseling and providing nutrition supplementation might improve the birth weight.

Incidence and associated factors of extrauterine growth restriction (EUGR) in preterm infants, a cross-sectional study in selected NICUs in Ethiopia.

BACKGROUND: Preterm infants have high risk of developing growth restriction and long-term complications. Enteral feeding is often delayed in neonatal intensive care units (NICUs) for the fear of feeding intolerance and the associated necrotising enterocolitis, and recent advances in nutritional support are unavailable in low-income countries. OBJECTIVE: The aim of this study was to assess the incidence and associated factors of extrauterine growth restriction (EUGR) among preterm infants in selected NICUs in Ethiopia. METHOD: This was a cross-sectional study involving a subgroup analysis of preterm infants admitted to hospitals, from a multicentre descriptive study of cause of illness and death in preterm infants in Ethiopia, conducted from 2016 to 2018. EUGR was defined as weight at discharge Z-scores <-1.29 for corrected age. Clinical profiles of the infants were analysed for associated factors. SPSS V.23 software was used for analysis with a significance level of 5% and 95% CI. RESULT: From 436 preterm infants included in the analysis, 223 (51%) were male, 224 (51.4%) very low birth weight (VLBW) and 185 (42.4%) small for gestational age (SGA). The mean (SD) of weight for corrected age Z-score at the time of discharge was -2.5 (1.1). The incidence of EUGR was 86.2%. Infants who were SGA, VLBW and longer hospital stay over 21 days had increased risk of growth restriction (p-value<0.01). SGA infants had a 15-fold higher risk of developing EUGR at the time of discharge from hospital than those who were appropriate or large for gestational age (OR (95% CI)=15.2 (4.6 to 50.1). CONCLUSION: The majority of the infants had EUGR at the time of discharge from the hospital, which indicates suboptimal nutrition. Revision of national guidelines for preterm infants feeding and improvement in clinical practice is highly required.

Comparison of neonatal outcomes of small for gestational age and appropriate for gestational age preterm infants born at 28-36 weeks of gestation: a multicentre study in Ethiopia.

PURPOSE: The aim of this study was to assess morbidity and mortality pattern of small for gestational age (SGA) preterm infants in comparison to appropriate for gestational age (AGA) preterm infants of similar gestational age. METHOD: We compared neonatal outcomes of 1336, 1:1 matched, singleton SGA and AGA preterm infants based on their gestational age using data from the study 'Causes of Illness and Death of Preterm Infants in Ethiopia (SIP)'. Data were analysed using SPSS V.23. ORs and 95% CIs and χ2 tests were done, p value of <0.05 was considered statistically significant. RESULT: The majority of the infants (1194, 89%) were moderate to late preterm (32-36 weeks of gestation), 763 (57%) were females. Male preterm infants had higher risk of being SGA than female infants (p<0.001). SGA infants had increased risk of hypoglycaemic (OR and 95% CI 1.6 (1.2 to 2.0), necrotising enterocolitis (NEC) 2.3 (1.2 to 4.1), polycythaemia 3.0 (1.6 to 5.4), late-onset neonatal sepsis (LOS) 3.6 (1.1 to 10.9)) and prolonged hospitalisation 2.9 (2.0 to 4.2). The rates of respiratory distress syndrome (RDS), apnoea and mortality were similar in the SGA and AGA groups. CONCLUSION: Neonatal complications such as hypoglycaemic, NEC, LOS, polycythaemia and prolonged hospitalisation are more common in SGA infants, while rates of RDS and mortality are similar in SGA and AGA groups. Early recognition of SGA status, high index of suspicion and screening for complications associated and timely intervention to prevent complications need due consideration.

Preterm Nutrition and Clinical Outcomes.

Background. In low-income countries, preterm nutrition is often inadequately addressed. The aim of the study was to assess the patterns of feeding and associated clinical outcomes of preterm neonates admitted to neonatal intensive care units in Ethiopia. Method. This was a multicenter, prospective study. Infants' clinical characteristics at birth, daily monitoring of feeding history, and weight measurements were collected. An outcome assessment was completed at 28 days. Result. For this analysis, 2560 infants (53% male) were eligible. The mean (SD) gestational age was 33.1 (2.2) weeks. During the hospital stay the proportion of infants on breast milk only, preterm formula, term formula, and mixed feeding was 58%, 27.4%, 1.6%, and 34.1%, respectively. Delay in enteral feeding was associated with increased risk of death (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.33-2.78; P < .001) and (OR = 5.06, 95% CI = 3.23-7.87; P < .001) for 1 to 3 and 4 to 6 days of delay in enteral feeding, respectively, after adjusting for possible confounders. The length of delay in enteral feeding was associated with increased risk of hypoglycemia (OR = 1.2, 95% CI = 1.1-1.2; P = .005). The mortality rate was lower in hospitals providing preterm formula more often (P = .04). Half of the infants continued losing weight at the time of discharge. Conclusion. Delayed enteral feeding significantly increases the risk of mortality before discharge and hypoglycemia in preterm infants in resource-limited settings. Ensuring adequate nutritional support of preterm infants is highly needed.

Impact of refugee influx on the epidemiology of late-presenting HIV-infected pregnant women and mother-to-child transmission: comparing a southern and northern medical centre in Germany.

PURPOSE: Due to early antenatal screening and treatment, HIV mother-to-child transmission (MTCT) rarely occurs in Germany. The study aimed to investigate the impact on prevalence of HIV infection in the antenatal population and the incidence of late-presenting HIV-infected mothers attributable to increased numbers of refugees. METHODS: Retrospective analysis and comparison were performed for all deliveries in HIV-infected pregnant women presenting to medical care in Munich (southern Germany) and Hamburg (northern Germany) covering two time periods, A (2010-2012) and B (2013-2015). RESULTS: In Munich, deliveries in HIV-infected pregnant women increased 1.6-fold from period A (n = 50) to B (n = 79) with late-presenting cases rising significantly from 2% (1/50) in period A to 13% (10/79) in B. In contrast, late-presenting cases in Hamburg decreased from 14% (14/100) in period A to 7% (7/107) in B, while the total number of HIV-infected women giving birth remained stable. From 2010 to 2015, one late-presenting pregnant woman transmitted HIV in Munich by presumed in utero mode of infection (case reviewed here), while no MTCT occurred in Hamburg. CONCLUSIONS: HIV infections diagnosed late in pregnancy and leading to delayed ART initiation are rising in Munich compared to Hamburg. Antenatal care of HIV-infected pregnant women in Munich appears to have been more affected by the recent refugee influx than Hamburg. Our study highlights the importance of screening all pregnant women for HIV early in pregnancy and providing timely health care access for pregnant refugees and asylum seekers to effectively prevent MTCT in Germany.

Effects of Prematurity on the Cutaneous Microcirculatory Network in the First Weeks of Life.

Background: Preterm infants are at increased risk for hypertension in adolescence. Microcirculatory dysfunction has been identified as an underlying cause for cardiovascular disease. Our goal was to document the development of the cutaneous microcirculation in preterm infants during the first weeks of life and to compare it to the situation in term infants at birth. Methods: In 20 preterm infants, microcirculatory parameters were obtained prospectively by Sidestream Dark Field (SDF) Imaging at the upper inner arm once a week until discharge or 37 weeks of gestational age. A single microcirculatory measurement was obtained in 30 term infants during the first 3 days of life. Videos were blinded and analyzed with the AVA software. Results: Microcirculatory parameters in preterm infants differ significantly from term infants with a lower vessel surface (VS), a lower percentage of large and medium but higher percentage of small vessels, a higher Functional Vessel Density (FVD), and a higher Microcirculatory Flow Index (MFI). In multivariable linear regression models we could demonstrate a statistically significant association between the dependent microcirculatory variables (VS, diameter distribution, MFI) and gestational age as independent predictor variable while adjusting for postnatal days of life. Looking at the longitudinal follow-up data of preterm infants by means of a multivariable mixed-effects linear regression model adjusting for clinical variables, there is a significant decrease in FVD with increasing postnatal age, however no other significant changes in microcirculatory parameters over time. Accordingly, comparing the microcirculatory parameters of near term former preterm infants with term born neonates, we could still find significant differences with a higher FVD, lower VS and differences in vessel diameters in the former premature group. Conclusion: Infants born prematurely exhibit distinct microcirculatory alterations compared to term neonates with gestational age at birth being associated with microvascular parameters. Interestingly, this premature vascular phenotype persists even close to corrected term age. In view of the known increased cardiovascular risk of former preterm infants, our observations might have important clinical impact. The factors governing the development of the microvascular network in preterm infants and the contribution of microcirculatory changes observed here to vascular pathology in later life need to be further investigated.

Permissive Hypercapnia Results in Decreased Functional Vessel Density in the Skin of Extremely Low Birth Weight Infants.

BACKGROUND: Ventilator-induced lung injury with subsequent bronchopulmonary dysplasia remains an important issue in the care of extremely low-birth-weight infants. Permissive hypercapnia has been proposed to reduce lung injury. Hypercapnia changes cerebral perfusion, but its influence on the peripheral microcirculation is unknown. METHODS: Data were collected from 12 infants, who were randomized to a permissive high PCO2 target group (HTG) or a control group (CG). Inclusion criteria were birth weight between 400 and 1,000 g, gestational age from 23 to 28 6/7 weeks, intubation during the first 24 h of life, and no malformations. The PCO2 target range was increased stepwise in both groups for weaning and was always 15 mmHg higher in the HTG than in the CG. Skin microvascular parameters were assessed non-invasively with sidestream dark field imaging on the inner side of the right arm every 24 h during the first week of life and on the 14th day of life. RESULTS: Infants in the HTG had significantly higher max. PCO2 exposure, which was associated with a significantly and progressively reduced functional vessel density (FVD, p < 0.01). Moreover, there were significant differences in the diameter distribution over time, with HTG subjects having fewer small vessels but more large vessels. CONCLUSION: High PCO2 levels significantly impaired peripheral microcirculation in preterm infants, as shown by a decreased FVD, presumably secondary to peripheral vasoconstriction. ISRCTN: 56143743.

Influence of PCO2 Control on Clinical and Neurodevelopmental Outcomes of Extremely Low Birth Weight Infants.

BACKGROUND: Levels or fluctuations in the partial pressure of CO2 (PCO2) may affect outcomes for extremely low birth weight infants. OBJECTIVES: In an exploratory analysis of a randomized trial, we hypothesized that the PCO2 values achieved could be related to significant outcomes. METHODS: On each treatment day, infants were divided into 4 groups: relative hypocapnia, normocapnia, hypercapnia, or fluctuating PCO2. Ultimate assignment to a group for the purpose of this analysis was made according to the group in which an infant spent the most days. Statistical analyses were performed with analysis of variance (ANOVA), the Kruskal-Wallis test, the χ2 test, and the Fisher exact test as well as by multiple logistic regression. RESULTS: Of the 359 infants, 57 were classified as hypocapnic, 230 as normocapnic, 70 as hypercapnic, and 2 as fluctuating PCO2. Hypercapnic infants had a higher average product of mean airway pressure and fraction of inspired oxygen (MAP × FiO2). For this group, mortality was higher, as was the likelihood of having moderate/severe bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), and poorer neurodevelopment. Multiple logistic regression analyses showed an increased risk for BPD or death associated with birth weight (p < 0.001) and MAP × FiO2 (p < 0.01). The incidence of adverse neurodevelopment was associated with birth weight (p < 0.001) and intraventricular hemorrhage (IVH; p < 0.01). CONCLUSIONS: Birth weight and respiratory morbidity, as measured by MAP × FiO2, were the most predictive of death or BPD and NEC, whereas poor neurodevelopmental outcome was associated with low birth weight and IVH. Univariate models also identified PCO2. Thus, hypercapnia seems to reflect greater disease severity, a likely contributor to differences in outcomes.

Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study.

BACKGROUND: Tolerating higher partial pressures of carbon dioxide (PCO2) in mechanically ventilated extremely low birthweight infants to reduce ventilator-induced lung injury may have long-term neurodevelopmental side effects. This study analyses the results of neurodevelopmental follow-up of infants enrolled in a randomised multicentre trial. METHODS: Infants (n=359) between 400 and 1000 g birth weight and 23 0/7-28 6/7 weeks gestational age who required endotracheal intubation and mechanical ventilation within 24 hours of birth were randomly assigned to high PCO2 or to a control group with mildly elevated PCO2 targets. Neurodevelopmental follow-up examinations were available for 85% of enrolled infants using the Bayley Scales of Infant Development II, the Gross Motor Function Classification System (GMFCS) and the Child Development Inventory (CDI). RESULTS: There were no differences in body weight, length and head circumference between the two PCO2 target groups. Median Mental Developmental Index (MDI) values were 82 (60-96, high target) and 84 (58-96, p=0.79). Psychomotor Developmental Index (PDI) values were 84 (57-100) and 84 (65-96, p=0.73), respectively. Moreover, there was no difference in the number of infants with MDI or PDI <70 or <85 and the number of infants with a combined outcome of death or MDI<70 and death or PDI<70. No differences were found between results for GMFCS and CDI. The risk factors for MDI<70 or PDI<70 were intracranial haemorrhage, bronchopulmonary dysplasia, periventricular leukomalacia, necrotising enterocolitis and hydrocortisone treatment. CONCLUSIONS: A higher PCO2 target did not influence neurodevelopmental outcomes in mechanically ventilated extremely preterm infants. Adjusting PCO2 targets to optimise short-term outcomes is a safe option. TRIAL REGISTRATION NUMBER: ISRCTN56143743.

The effect of red blood cell transfusion on the microcirculation of anemic children.

UNLABELLED: Red blood cell transfusion can improve but also might temporarily reduce the microcirculation. The buccal microcirculation was visualized and total vessel density (TVD) determined with sidestream dark field imaging in 19 pediatric anemic (Hb 7.2 g/dL, 95 % CI 6.5-7.9) oncology or hematology patients receiving red blood cell transfusions (Tx) and in 18 age-matched healthy non-anemic controls. After transfusion, Hb (8.0 g/dL, 95 % CI 7.3-8.6) and TVD increased (14.7 ± 1.7 versus 16.6 ± 2.0 mm/mm(2)) significantly with a concomitant decrease in RBC velocity in medium-sized vessels (pre-Tx 711 ± 199 versus post-Tx 627 ± 163 µm/s). Compared to the controls, pre-Tx TVD (17.5 ± 1.3 mm/mm(2)) was lower and RBC velocity (476 ± 77 µm/s) was significantly higher. After transfusion, TVD and RBC velocity remained significantly lower and higher, respectively. In a subgroup, analysis of the transfused children with infection of TVD at baseline was lower with a larger increase after transfusion compared to anemic children without infection (ΔTVD 3.4 ± 2.6 versus ΔTVD 1.3 ± 1.5 mm/mm(2)). CONCLUSION: With the rise of hemoglobin after transfusion, significant improvements of tissue perfusion were demonstrated but differences to non-anemic controls persisted. In particular, the microcirculation of anemic oncology patients with infection improved after transfusion. WHAT IS KNOWN: • Transfusions can improve but also temporarily reduce the microcirculation. • In neonates, transfusion significantly increases total vessel density. What is New: • Pretransfusion, the microcirculation of the anemic children differed significantly from the controls. • After transfusion, the microcirculation improved but still differed from the controls. • These changes were most profound in anemic patients with concurrent infection, therefore transfusion threshholds might need to be higher.