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Introduction: Neonatal hypothermia in low-resource settings is prevalent and closely associated with high morbidity and mortality. We examined if an easy-to-read temperature detector device improves health outcomes., Methods: In a descriptive study, 1009 admissions to a neonatal ward in a tertiary care hospital in Lilongwe, Malawi, were analysed and divided into a baseline and a trial group. The data of 531 newborns with standard care (SC) before the trial were compared with 478 newborns during the implementation of the device (device care=DC). Staff and caregivers were trained on using the device and how to react in case of hypothermia. Data were collected from patient files, device documentation sheets, interviews and focus group discussions. Hypothermia was defined as a body temperature <36.5°C., Results: During the trial, body temperatures throughout the hospital stay were significantly more often obtained (p<0.0001). The median temperature measurements per newborn per day were 1.3 times with SC and 1.6 times with DC, and mild hypothermia was more frequently detected. Moderate hypothermia was avoided in the lightest weight group possibly contributing to significantly shorter hospital stays of surviving newborns (p=0.007). Many caregivers had difficulties using and interpreting the device correctly, and 47% of the reported colours did not match the registered temperatures. Contrary to the above, a questionnaire and focus group discussions with caregivers and health workers showed a high acceptance and the overall opinion that the device was beneficial., Conclusion: With more frequent temperature checks, infants with lower birth weight possibly benefited from implementing an easy-to-read continuous temperature indicator, but hypothermia rates remained high. Our data and experiences reveal structural, communicational and consistency/interpretation deficits. Although specifically designed for low-resource settings, the implementation of the device needs a well-working and structured environment, especially regarding staff and caregiver communication., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form and declare that the study received financial support from Else-Kröner-Fresenius Stiftung and that JG received financial support from LMU, as explained under 'Funding'., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2024 The Authors. The Clinical Teacher published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

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.

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.

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., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Puchwein-Schwepcke, Genzel-Boroviczény and Nussbaum.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

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., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

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.

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.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

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.

Objective: Perturbation of the endothelial glycocalyx is discussed in the pathogenesis of complications related to cardiopulmonary bypass. We evaluated the effects of cardiopulmonary bypass on the microcirculation and the microvascular endothelial glycocalyx of infants undergoing surgery for congenital cardiac defects., Methods: The microcirculation was visualized at the ear conch using Sidestream dark field imaging before surgery (T0), after admission to the intensive care unit (T1), 24 hours postsurgery (T2), and 7 days postsurgery (T3). Glycocalyx thickness was assessed by measurement of the perfused boundary region. Microcirculatory parameters included total and perfused vessel density, vessel diameters, and microcirculatory flow index., Results: A total of 40 infants undergoing cardiac surgery (36 with cardiopulmonary bypass, 4 without cardiopulmonary bypass) were examined. As controls, measurements before and after cardiac catheterization (n = 6) and before and after surgery for cleft palate (n = 9) were performed. After surgery with cardiopulmonary bypass, the perfused boundary region was significantly increased, indicating reduced glycocalyx thickness at T1 compared with preoperative values with a stepwise return to baseline by T3. In the control groups, no significant perfused boundary region changes were noted. Furthermore, after cardiopulmonary bypass, a transient, significant reduction of the microcirculatory flow index and the perfused vessel density was seen at T1. Similar changes were observed after cardiac surgery without cardiopulmonary bypass, but not in the other controls., Conclusions: Our study reveals for the first time local perturbations of the endothelial glycocalyx and microvascular perfusion in infants after surgery with cardiopulmonary bypass. Microcirculatory monitoring might be a useful tool to evaluate interventions aiming at reduction of bypass-related complications., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Pathology is a discipline that provides the basis of the understanding of disease in medicine. The past decades have seen a decline in the emphasis laid on pathology teaching in medical schools and outdated pathology curricula have worsened the situation. Student opinions and thoughts are central to the questions of whether and how such curricula should be modernized., Methods: A survey was conducted among 1018 German medical students regarding their preferences in pathology teaching modalities and their satisfaction with lecture-based courses. A qualitative analysis was performed comparing a recently modernized pathology curriculum with a traditional lecture-based curriculum. The differences in modalities of teaching used were investigated., Results: Student satisfaction with the lecture-based curriculum positively correlated with student grades (spearman's correlation coefficient 0.24). Additionally, students with lower grades supported changing the curriculum (spearman's correlation coefficient 0.47). The majority supported virtual microscopy, autopsies, seminars and podcasts as preferred didactic methods., Conclusions: The data supports the implementation of a pathology curriculum where tutorials, autopsies and supplementary computer-based learning tools play important roles.

The pros and cons of home monitoring especially for premature infants with continuing apneic episodes and/or chronic lung disease are an ongoing discussion. The controversy spans socio-economic requirements, medical indication as well as patient and family needs. Here, the costs of home monitoring and follow-up care on the one hand and longer hospitalization times on the other need to be considered. This article aims to create a basis for this discussion by summarizing current evidence for the indications and considerations for differential diagnoses while also outlining the established follow-up program for these patients at the Dr. v. Hauner Children's Hospital at the Ludwig-Maximilians-University Munich, Germany., (© Georg Thieme Verlag KG Stuttgart · New York.)

Unlabelled: Neonatal blue light phototherapy (NBLP) is an effective treatment for hyperbilirubinaemia. Concerning the influence on melanocytic nevi, conflicting studies have been published. To assess the role of NBLP according to the incidence of melanocytic nevi in preschool children, a cohort of 104 5- to 6-year-old children were included. The case group consisted of 52 NBLP-exposed children, while the control group (n = 52) never had NBLP and was matched regarding age, gender, gestational age and skin phototype. Six dizygotic twins were included with one twin having received NBLP, respectively. The following parameters were recorded: nevi count, presence of freckles, café-au-lait macules, skin phototype and previous history of sun exposure. There was no significant association between nevi count and exposure to NBLP (median nevi count 17.0 compared to 18.5 in controls). No significant difference was also found in the dizygotic twin pairs with a median nevi count of 10.0 (with NBLP) compared to 14.5 (without NBLP). However, a significantly higher prevalence of café-au-lait macules was found in children with NBLP (mean count 0.5) than in children without NBLP (mean count 0.2; p = 0.001). Significant predictors for the number of melanocytic nevi included skin phototype, sun exposure and vacations in the South., Conclusion: In this study, NBLP had no significant influence on the development of melanocytic nevi, but on café-au-lait macules which was a new finding. Differences with comparable studies regarding age, differentiation between nevi and other pigmented lesions as well as dose and type of NBLP need to be taken into account for further investigations.