Investigation of a Camera-Based Contactless Pulse Oximeter with Time-Division Multiplex Illumination Applied on Piglets for Neonatological Applications.

(1) Objective: This study aims to lay a foundation for noncontact intensive care monitoring of premature babies. (2) Methods: Arterial oxygen saturation and heart rate were measured using a monochrome camera and time-division multiplex controlled lighting at three different wavelengths (660 nm, 810 nm and 940 nm) on a piglet model. (3) Results: Using this camera system and our newly designed algorithm for further analysis, the detection of a heartbeat and the calculation of oxygen saturation were evaluated. In motionless individuals, heartbeat and respiration were separated clearly during light breathing and with only minor intervention. In this case, the mean difference between noncontact and contact saturation measurements was 0.7% (RMSE = 3.8%, MAE = 2.93%). (4) Conclusions: The new sensor was proven effective under ideal animal experimental conditions. The results allow a systematic improvement for the further development of contactless vital sign monitoring systems. The results presented here are a major step towards the development of an incubator with noncontact sensor systems for use in the neonatal intensive care unit.

Bifidobacterium and Lactobacillus Probiotics and Gut Dysbiosis in Preterm Infants: The PRIMAL Randomized Clinical Trial.

Importance: The effects of probiotic interventions on colonization with resistant bacteria and early microbiome development in preterm infants remain to be clarified. Objective: To examine the efficacy of Bifidobacterium longum subsp infantis, Bifidobacterium animalis subsp lactis (BB-12), and Lactobacillus acidophilus (La-5) probiotics to prevent colonization with multidrug-resistant organisms or highly epidemic bacteria (MDRO+) and to shape the microbiome of preterm infants toward the eubiotic state of healthy full-term infants. Design, Setting, and Participants: The multicenter, double-blinded, placebo-controlled, group sequential, phase 3 Priming Immunity at the Beginning of Life (PRIMAL) randomized clinical trial, conducted from April 2018 to June 2020, included infants with gestational age of 28 to 32 weeks at 18 German neonatal units. Data analyses were conducted from March 2020 to August 2023. Intervention: A total of 28 days of multistrain probiotics diluted in human milk/formula starting within the first 72 hours of life. Main Outcomes and Measures: Colonization with MDRO+ at day 30 of life (primary end point), late-onset sepsis and severe gastrointestinal complication (safety end points), and gut dysbiosis, ie, deviations from the microbiome of healthy, term infants (eubiosis score) based on 16-subunit ribosomal RNA and metagenomic sequencing. Results: Among the 643 infants randomized until the stop of recruitment based on interim results, 618 (median [IQR] gestational age, 31.0 [29.7-32.1] weeks; 333 male [53.9%]; mean [SD] birth weight, 1502 [369] g) had follow-up at day 30. The interim analysis with all available data from 219 infants revealed MDRO+ colonization in 43 of 115 infants (37.4%) in the probiotics group and in 39 of 104 infants (37.5%) in the control group (adjusted risk ratio, 0.99; 95% CI, 0.54-1.81; P = .97). Safety outcomes were similar in both groups, ie, late-onset sepsis (probiotics group: 8 of 316 infants [2.5%]; control group: 12 of 322 infants [3.7%]) and severe gastrointestinal complications (probiotics group: 6 of 316 infants [1.9%]; control group: 7 of 322 infants [2.2%]). The probiotics group had higher eubiosis scores than the control group at the genus level (254 vs 258 infants; median scores, 0.47 vs 0.41; odds ratio [OR], 1.07; 95% CI, 1.02-1.13) and species level (96 vs 83 infants; median scores, 0.87 vs 0.59; OR, 1.28; 95% CI, 1.19-1.38). Environmental uptake of the B infantis probiotic strain in the control group was common (41 of 84 [49%]), which was highly variable across sites and particularly occurred in infants with a sibling who was treated with probiotics. Conclusions and Relevance: Multistrain probiotics did not reduce the incidence of MDRO+ colonization at day 30 of life in preterm infants but modulated their microbiome toward eubiosis. Trial Registration: German Clinical Trials Register: DRKS00013197.

A Plea for Monitoring Serum Selenium Levels in Breast Cancer Patients: Selenium Deficiency Is Rare during the First Year of Therapy, and Selenium Supplementation Is Associated with Elevated Risk of Overdosing.

(1) Background: The role of selenium in cancer biology remains poorly understood. Our aim was to study the course of selenium serum levels and the use of selenium supplements during breast cancer therapy. (2) Methods: Serum selenium levels, clinical-pathological data, selenium supplementation, and lifestyle factors were monitored quarterly over one year. (3) Results: A total of 110 non-metastatic breast cancer patients were enrolled in the prospective observational "BEGYN-1" study. At baseline, 2.9% of patients were selenium-deficient (<50 ng/mL), 1.9% were overdosed (>120 ng/mL), and 6.4% received substitution. The median selenium level was 81.5 ng/mL and ranged between 78.7 and 84.5 ng/mL within the year. A total of 25.3% of the patients received supplementation, resulting in significantly higher selenium levels (p < 0.05). A total of 8.7-28.6% of the patients using supplements were overdosed. Selenium levels strongly correlated with mushroom consumption (p = 0.003), but no association was found with therapy or clinical characteristics. (4) Conclusions: Although selenium deficiency is rare, serum selenium levels should be assessed in breast cancer patients. Mushrooms and nuts should be preferred over supplements to correct selenium deficiency. Ruling out selenium deficiency helps prevent the risk of selenosis and avoid unnecessary, costly supplementation in patients who are often financially burdened due to their disease.

Ultrasound-guided determination demonstrates influence of age, sex and type of sport on medial femoral condyle cartilage thickness in children and adolescents.

PURPOSE: To analyse the reliability of ultrasound-guided measurement of the cartilage thickness at the medial femoral condyle in athletically active children and adolescents before and after mechanical load in relation to age, sex and type of sport. METHODS: Three successive measurements were performed in 157 participants (median/min-max age: 13.1/6.0-18.0 years, 106 males) before and after mechanical load by squats at the same site of the medial femoral condyle by defined transducer positioning. Test-retest reliability was examined using Cronbach's α $\alpha $ calculation. Differences in cartilage thickness were analysed with respect to age, sex and type of practiced sports, respectively. RESULTS: Excellent reliability was achieved both before and after mechanical load by 30 squats with a median cartilage thickness of 1.9 mm (range: 0.5-4.8 mm) before and 1.9 mm (0.4-4.6 mm) after mechanical load. Male cartilages were thicker (p < 0.01) before (median: 2.0 mm) and after (2.0 mm) load when compared to female cartilage (before: 1.6 mm; after: 1.7 mm). Median cartilage thickness was about three times higher in karate athletes (before: 2.3 mm; after: 2.4 mm) than in sports shooters (0.7; 0.7 mm). Cartilage thickness in track and field athletes, handball players and soccer players were found to lay in-between. Sport type related thickness changes after mechanical load were not significant. CONCLUSION: Medial femoral condyle cartilage thickness in childhood correlates with age, sex and practiced type of sports. Ultrasound is a reliable and simple, pain-free approach to evaluate the cartilage thickness in children and adolescents. LEVEL OF EVIDENCE: Level III.

Course of Vitamin D Levels in Newly Diagnosed Non-Metastatic Breast Cancer Patients over One Year with Quarterly Controls and Substitution.

(1) Background: Vitamin D levels in patients remain inadequately understood, with research yielding inconsistent findings. Breast cancer patients, particularly due to oncological therapies, face an increased risk of osteopenia, which can be exacerbated by a vitamin D deficiency. (2) Methods: The prospective observational "BEGYN-1" study assessed serum 25(OH)D levels at baseline and quarterly thereafter. Clinical, pathological, nutritional, vitamin supplementation, and lifestyle data were recorded. (3) Results: Before treatment, 68.5% of patients were vitamin D deficient (<30 ng/mL), with 4.6% experiencing severe deficiency (<10 ng/mL). The median baseline 25(OH)D levels were 24 ng/mL (range: 4.8 to 64.7 ng/mL). Throughout the study, the median vitamin D levels increased to 48 ng/mL (range: 22.0 to 76.7 ng/mL). Before diagnosis, 16.7% received vitamin D substitution, and 97.8% received vitamin D substitution throughout the year with a median weekly dose of 20,000 IU. It took at least three quarterly assessments for 95% of patients to reach the normal range. A multiple GEE analysis identified associations between 25(OH)D levels and supplementation, season, age, VLDL, magnesium levels, and endocrine therapy. (4) Conclusions: Physicians should monitor 25(OH)D levels before, during, and after oncological therapy to prevent vitamin D deficiency and to adjust substitution individually. While variables such as seasons, age, VLDL, magnesium, diet, and oncological interventions affect 25(OH)D levels, supplementation has the greatest impact.

Teaching breaking bad news in a gyneco-oncological setting: a feasibility study implementing the SPIKES framework for undergraduate medical students.

BACKGROUND: It is a crucial task for physicians to deliver life threatening information to patients (breaking bad news; BBN). Many aspects influence these conversations on both sides, patients, and doctors. BBN affects the patient-physician relationship, patients' outcome, and physicians' health. Many physicians are still untrained for this multi-facetted task and feel unprepared and overburdened when facing situations of BBN. Therefore, any faculties should aim to integrate communication skills into their medical curricula as early as possible. The SPIKES protocol is an effective framework to deliver BBN. Aim of this study is to evaluate the feasibility and obstacles of a BBN seminar and its acceptance and learning curve among undergraduate medical students. METHODS: 158 2nd year undergraduate medical students attended a compulsory BBN seminar. The task was to deliver a cancer diagnosis to the patient within a patient - physician role-play in a gyneco-oncological setting before and after a presentation of the SPIKES protocol by the lecturer. The students evaluated important communication skills during these role-plays respectively. Self-assessment questionnaires were obtained at the beginning and end of the seminar. RESULTS: Most students indicated that their confidence in BBN improved after the seminar (p < 0.001). They like the topic BBN to be part of lectures (76%) and electives (90%). Communication skills improved. Lecturer and seminar were positively evaluated (4.57/5). CONCLUSION: The seminar significantly increased confidence and self-awareness in delivering life-threatening news to patients among undergraduate medical students. Important learning aspects of BBN and communication skills could be delivered successfully to the participants within a short time at low costs. The integration of communication skills should be implemented longitudinally into medical curricula starting before clinical education to increase the awareness of the importance of communication skills, to decrease anxiety, stress, and workload for future doctors and- most importantly- to the benefit of our patients.

Detection of volatile organic compounds in headspace of Klebsiella pneumoniae and Klebsiella oxytoca colonies.

Introduction: Early diagnosis of infections and sepsis is essential as adequate therapy improves the outcome. Unfortunately, current diagnostics are invasive and time-consuming, making diagnosis difficult, especially in neonatology. Novel non-invasive analytical methods might be suitable to detect an infection at an early stage and might even allow identification of the pathogen. Our aim is to identify specific profiles of volatile organic compounds (VOCs) of bacterial species. Methods: Using multicapillary column-coupled ion mobility spectrometry (MCC/IMS), we performed headspace measurements of bacterial cultures from skin and anal swabs of premature infants obtained during weekly screening for bacterial colonization according to KRINKO. We analyzed 25 Klebsiella pneumoniae (KP) cultures on MacConkey (MC) agar plates, 25 Klebsiella oxytoca (KO) cultures on MC agar and 25 bare MC agar plates as a control group. Results: Using MCC/IMS, we identified a total of 159 VOC peaks. 85 peaks allowed discriminating KP and bare MC agar plates, and 51 peaks comparing KO and bare MC agar plates and 6 peaks between KP and KO (significance level of p < 0.05 after Bonferroni post hoc analysis), respectively. Peaks P51 (n-Decane) and P158 (Phenylethyl Alcohol), showed the best sensitivity/specificity/ positive predictive value/negative predictive value of 99.9% each (p < 0.001) for KP. P158 showed the best sensitivity/specificity/positive predictive value/negative predictive value of 99.9% each (p < 0.001) for KO. Comparing KP and KO, best differentiation was enabled using peaks P72, P97 and P16 with sensitivity/specificity/positive predictive value/negative predictive value of 76.0%, 84.0%, 82.6%, 77.8%, respectively (p < 0.05). Discussion: We developed a method for the analysis of VOC profiles of bacteria. Using MCC/IMS, we demonstrated that VOCs derived from bacteria are clearly distinguishable from a bare agar plate. Characteristic peaks obtained by MCC/IMS are particularly suitable for the species-specific identification and differentiation of KP and KO. Thus, MCC/IMS might be a useful tool for in vitro diagnostics. Future studies must clarify whether similar patterns of VOCs can be detected in vivo in patients that are colonized or infected with KP or KO to enable rapid and accurate diagnosis of bacterial colonization.

Serum cytokines MCP-1 and GCS-F as potential biomarkers in pediatric inflammatory bowel disease.

BACKGROUND: Inflammatory bowel diseases (IBDs) with the subtypes ulcerative colitis (UC) and Crohn disease (CD), are chronic autoimmune inflammatory disorders of the gastrointestinal tract. Cytokines are associated with the development and progression in pediatric IBD. We measured cytokine levels in pediatric IBD patients to assess their potential function as biomarkers in disease assessment. METHOD: In this prospective cohort study, we enrolled 33 children with IBD. All patients were in stable remission for 3 months on enrollment. Patients who developed a relapse within six months after enrollment were classified as relapsers. Blood sampling was performed at enrolment and for relapsers in relapse and post-relapse. Serum concentrations of 14 cytokines, chemokines and growth factors (IL-1α, IL-1ß, IL-6, IL-12p40, IP-10, TNF-α, IFN-γ, IL-10, IL-8, MIP-1α, MCP-1, MCP-3, G-CSF, GM-CSF) were measured simultaneously using multiplex bead-based sandwich immunoassay on Luminex 100 system. RESULTS: MCP-1 was significantly higher in CD patients compared to UC patients at each disease stage: stable remission (P<0.048), unstable remission (P<0.013), relapse (P<0.026) and post-relapse (P<0.024). G-CSF was significantly increased in UC patients developing a relapse and in post-relapse stage compared to UC patients in remission (P<0.02 and p<0.03, respectively). CONCLUSION: MCP-1 showed potential as a diagnostic biomarker in CD patients independent of disease activity as it was able to discriminate between subtypes of pediatric IBD. In UC patients, G-CSF was significantly elevated in relapsers indicating its use and role as a potential prognostic biomarker.

Improved awareness of physical activities is associated with a gain of fitness and a stable body weight in breast cancer patients during the first year of antineoplastic therapy: the BEGYN-1 study.

Background: Breast cancer is the most frequent cancer in women. Reduced physical activity and overweight are associated with poor prognosis. Breast cancer patients have a high risk to gain weight, lose muscle mass and reduce physical activity during therapy. Concepts are urgently needed to motivate patients to engage in physical activity. Methods: 110 non-metastatic breast cancer patients were included in the prospective observational BEGYN-1 study. Physiological parameters and body composition were measured before the start of therapy and then quarterly for one year. Patients used a fitness tracker and documented their physical activity in a diary throughout the study. Results: Although the patients were not offered any guided exercise, and despite the restrictions during the COVID-19 pandemic, they increased their physical activity (metabolic equivalent of task (MET) -minutes): p<0.001), physical fitness (decreasing resting heart rate: p=0.001) and did not gain weight (median - 0.4kg) over the course of the study. Conclusion: Improved awareness of physical activity is associated with an increase in physical activity, fitness, and a stable weight during the first year of therapy in breast cancer patients. Counselling at diagnosis should motivate patients to engage in physical activity, wear a fitness tracker and document activities.

Sex Differences in the Frequencies of B and T Cell Subpopulations of Human Cord Blood.

Cord blood represents a link between intrauterine and early extrauterine development. Cord blood cells map an important time frame in human immune imprinting processes. It is unknown whether the sex of the newborn affects the lymphocyte subpopulations in the cord blood. Nine B and twenty-one T cell subpopulations were characterized using flow cytometry in human cord blood from sixteen male and twenty-one female newborns, respectively. Except for transitional B cells and naïve B cells, frequencies of B cell counts across all subsets was higher in the cord blood of male newborns than in female newborns. The frequency of naïve thymus-negative Th cells was significantly higher in male cord blood, whereas the remaining T cell subpopulations showed a higher count in the cord blood of female newborns. Our study is the first revealing sex differences in the B and T cell subpopulations of human cord blood. These results indicate that sex might have a higher impact for the developing immune system, urging the need to expand research in this area.

Prevalence and Relevance of Vitamin D Deficiency in Newly Diagnosed Breast Cancer Patients: A Pilot Study.

(1) Background: Vitamin D plays an important role in many types of cancer. It was the aim of this study to analyze serum 25-hydroxyvitamin D (25(OH)D) levels in newly diagnosed breast cancer patients, and the association with prognostic and lifestyle factors. (2) Methods: 110 non-metastatic breast cancer patients were included in the prospective observational "BEGYN" study at Saarland University Medical Center between September 2019 and January 2021. At the initiation visit, serum 25(OH)D levels were measured. Clinicopathological data on prognosis, nutrition, and lifestyle were extracted from data files and obtained using a questionnaire. (3) Results: Median serum 25(OH)D in breast cancer patients was 24 ng/mL (range 5-65 ng/mL), with 64.8% of patients being vitamin D deficient. 25(OH)D was higher among patients that reported the use of vitamin D supplements (43 ng/mL versus 22 ng/mL; p < 0.001), and in summer compared to other seasons (p = 0.03). Patients with moderate vitamin D deficiency were less likely to have triple negative breast cancer (p = 0.047). (4) Conclusions: Routinely measured vitamin D deficiency is common in breast cancer patients and needs to be detected and treated. However, our results do not support the hypothesis that vitamin D deficiency may be a main prognostic factor for breast cancer.

Patterns of volatile organic compounds in excrements of preterm neonates.

BACKGROUND: As neonates are susceptible for many diseases, establishing noninvasive diagnostic methods is desirable. We hypothesized that volatile organic compounds (VOCs) could be successfully measured in diaper samples. METHODS: We performed a feasibility study to investigate whether ambient air-independent headspace measurements of the VOC profiles of diapers from premature infants can be conducted using ion mobility spectrometer coupled with multi-capillary columns (B & S Analytik GmbH). RESULTS: We analysed 39 diapers filled with stool (n = 10) or urine (n = 20) respectively, using empty diapers as a control (n = 9). A total of 158 different VOCs were identified, and we classified the content of the diapers (urine or stool) according to their VOC profiles with a significance level of p < 0.05. CONCLUSIONS: We have developed a novel method to study headspace VOC profiles of biosamples using ion mobility spectrometry coupled with multi-capillary columns. Using this method, we have characterized the VOC profiles of stool and urine of preterm neonates. Future studies are warranted to characterize specific VOC profiles in infections and other diseases of the preterm neonate, thus establishing quick and noninvasive diagnostics in the routine care of the highly vulnerable preterm and term neonates.

Noise and Critical Sound Levels During Non-Invasive Ventilation of a Preterm Infant in the Incubator.

BACKGROUND: Preterm birth and the subsequent necessary treatment in neonatal intensive care units (NICU) subjects the preterm infant to non-physiological noise exposure with potentially adverse consequences for short- and long-term development. Adjusters to improve the acoustic environment for the preterm infant need to be defined. METHODS: Sound pressure level measurements during routine procedures in a NICU were performed by »" microphones placed inside and outside the incubator. The microphones need to be suitably positioned to measure sound pressure levels that are representative for the sound field inside and outside the incubator. The sound pressure level spectra generated by respiratory support and corresponding monitor alarms were compared. RESULTS: Inside the incubator, higher sound level pressures (in dBA) were generated primarily by the use of the system components of the incubator itself than outside, whereas when the incubator was closed, it had an insulating effect on sounds generated in the NICU. Non-invasive ventilation resulted in an increase in sound pressure levels from 50 to 60 dBA in the neonate's environment, with sound pressure levels increasing particularly in the frequency range above 1 kHz. CONCLUSION: Preterm infants are exposed to high sound levels, especially in the non-physiological high-frequency range, particularly during non-invasive ventilation. The continuous sound exposure could be further reduced to some extent by an optimized design of the incubator.

Immunization of preterm infants: current evidence and future strategies to individualized approaches.

Preterm infants are at particularly high risk for infectious diseases. As this vulnerability extends beyond the neonatal period into childhood and adolescence, preterm infants benefit greatly from infection-preventive measures such as immunizations. However, there is an ongoing discussion about vaccine safety and efficacy due to preterm infants' distinct immunological features. A significant proportion of infants remains un- or under-immunized when discharged from primary hospital stay. Educating health care professionals and parents, promoting maternal immunization and evaluating the potential of new vaccination tools are important means to reduce the overall burden from infectious diseases in preterm infants. In this narrative review, we summarize the current knowledge about vaccinations in premature infants. We discuss the specificities of early life immunity and memory function, including the role of polyreactive B cells, restricted B cell receptor diversity and heterologous immunity mediated by a cross-reactive T cell repertoire. Recently, mechanistic studies indicated that tissue-resident memory (Trm) cell populations including T cells, B cells and macrophages are already established in the fetus. Their role in human early life immunity, however, is not yet understood. Tissue-resident memory T cells, for example, are diminished in airway tissues in neonates as compared to older children or adults. Hence, the ability to make specific recall responses after secondary infectious stimulus is hampered, a phenomenon that is transcriptionally regulated by enhanced expression of T-bet. Furthermore, the microbiome establishment is a dominant factor to shape resident immunity at mucosal surfaces, but it is often disturbed in the context of preterm birth. The proposed function of Trm T cells to remember benign interactions with the microbiome might therefore be reduced which would contribute to an increased risk for sustained inflammation. An improved understanding of Trm interactions may determine novel targets of vaccination, e.g., modulation of T-bet responses and facilitate more individualized approaches to protect preterm babies in the future.

Contactless radar-based breathing monitoring of premature infants in the neonatal intensive care unit.

Vital sign monitoring systems are essential in the care of hospitalized neonates. Due to the immaturity of their organs and immune system, premature infants require continuous monitoring of their vital parameters and sensors need to be directly attached to their fragile skin. Besides mobility restrictions and stress, these sensors often cause skin irritation and may lead to pressure necrosis. In this work, we show that a contactless radar-based approach is viable for breathing monitoring in the Neonatal intensive care unit (NICU). For the first time, different scenarios common to the NICU daily routine are investigated, and the challenges of monitoring in a real clinical setup are addressed through different contributions in the signal processing framework. Rather than just discarding measurements under strong interference, we present a novel random body movement mitigation technique based on the time-frequency decomposition of the recovered signal. In addition, we propose a simple and accurate frequency estimator which explores the harmonic structure of the breathing signal. As a result, the proposed radar-based solution is able to provide reliable breathing frequency estimation, which is close to the reference cabled device values most of the time. Our findings shed light on the strengths and limitations of this technology and lay the foundation for future studies toward a completely contactless solution for vital signs monitoring.

Longitudinal Assessment of Physical Activity, Fitness, Body Composition, Immunological Biomarkers, and Psychological Parameters During the First Year After Diagnosis in Women With Non-Metastatic Breast Cancer: The BEGYN Study Protocol.

BACKGROUND: Moderate physical activity is associated with an improved prognosis and psychosocial outcome in breast cancer patients. Although exercise and physical activity are associated with multiple physiological and psychological effects, many of the underlying mechanisms remain obscure. The BEGYN study (Influence of physical activity in breast cancer patients on physiological and psychological parameters and on biomarkers) aims at identifying potential associations between the extent of physical activity, fitness, body composition, immunological biomarkers, psycho-emotional parameters, and the course of treatment during the first year after diagnosis of breast cancer. METHODS: The prospective observational BEGYN study will include 110 non-metastatic breast cancer patients. The patients will be assessed during a base line visit prior to the initiation of the antineoplastic therapy and after 3, 6, 9 and 12 months. The physical activity will be measured using a fitness tracker and a self-assessment diary during the entire study. Each visit will include the assessment of (i) cardiorespiratory fitness measured by spiroergometry, (ii) body composition, (iii) psycho-emotional parameters (quality of life, mental health, fatigue, depression, distress, anxiety, well-being), and (iv) extensive blood tests including routine laboratory, vitamin D, selenium and immunologically relevant biomarkers (e.g., leukocyte subpopulations and cytokine profiles). DISCUSSION: Whereas most studies investigating the influence of physical activity in breast cancer patients focus on specific activities for three months or less, the BEGYN study will quantify the daily physical activity and cardiorespiratory fitness of breast cancer patients based on objective measurements in the context of the oncological therapy for 12 months after diagnosis. The study will reveal potential associations between exercise, immune status and physical as well as psycho-emotional outcome and the clinical course of the disease. Moreover, complementary therapies such as Vit D and Selenium supplementation and parameters investigating the motivation of the patients are part of the study. Due to this holistic approach, the BEGYN study will guide towards confirmatory studies on the role of physical activity in breast cancer patients to develop individualized counselling regarding the recommended type and extent of exercise. TRIAL REGISTRATION: This study has been registered at the German Clinical Trials Register DRKS00024829.

Detection of Volatile Organic Compounds as Potential Novel Biomarkers for Chorioamnionitis - Proof of Experimental Models.

Background: Histologic chorioamnionitis is only diagnosed postnatally which prevents interventions. We hypothesized that volatile organic compounds (VOCs) in the amniotic fluid might be useful biomarkers for chorioamnionitis and that VOC profiles differ between amnionitis of different origins. Methods: Time-mated ewes received intra-amniotic injections of media or saline (controls), or live Ureaplasma parvum serovar 3 (Up) 14, 7 or 3d prior to c-section at day 124 gestational age (GA). 100 µg recombinant ovine IL-1α was instilled at 7, 3 or 1d prior to delivery. Headspace VOC profiles were measured from amniotic fluids at birth using ion mobility spectrometer coupled with multi-capillary columns. Results: 127 VOC peaks were identified. 27 VOCs differed between samples from controls and Up- or IL-1α induced amnionitis. The best discrimination between amnionitis by Up vs. IL-1α was reached by 2-methylpentane, with a sensitivity/specificity of 96/95% and a positive predictive value/negative predictive values of 96 and 95%. The concentration of 2-methylpentane in VOCs peaked 7d after intra-amniotic instillation of Up. Discussion: We established a novel method to study headspace VOC profiles of amniotic fluids. VOC profiles may be a useful tool to detect and to assess the duration of amnionitis induced by Up. 2-methylpentane was previously described in the exhalate of women with pre-eclampsia and might be a volatile biomarker for amnionitis. Amniotic fluids analyzed by ion mobility spectrometry coupled with multi-capillary columns may provide bedside diagnosis of amnionitis and understanding inflammatory mechanisms during pregnancy.

Attenuated asthma phenotype in mice with a fetal-like antigen receptor repertoire.

We hypothesized that the scarcity of N-nucleotides might contribute to the inability of the neonate to mount a robust allergic immune response. To test this, we used terminal deoxyribunucleotidyl Transferase deficient (TdT-/-) mice, which express "fetal-like" T cell receptor and immunoglobulin repertoires with largely germline-encoded CDR3 regions. Intraperitoneal sensitization was followed by aerosol provocation with either PBS or the allergen OVA in both TdT-/- mice and wild-type mice to develop allergic respiratory inflammation. The effects of this procedure were investigated by lung function test, immunological analysis of serum and brochoalveolar lavage. The local TH2 cytokine milieu was significantly attenuated in TdT-/- mice. Within this group, the induction of total IgE levels was also significantly reduced after sensitization. TdT-/- mice showed a tendency toward reduced eosinophilic inflow into the bronchial tubes, which was associated with the elimination of respiratory hyperreactivity. In conclusion, in a murine model of allergic airway inflammation, the expression of fetal-like antigen receptors was associated with potent indications of a reduced ability to mount an asthma phenotype. This underlines the importance of somatically-generated antigen-receptor repertoire diversity in type one allergic immune responses and suggests that the fetus may be protected from allergic responses, at least in part, by controlling N addition.

Five Year Follow Up of Extremely Low Gestational Age Infants after Timely or Delayed Administration of Routine Vaccinations.

This study is aimed at detecting the rate of untimely immunization in a large cohort of extremely low gestational age neonates (ELGANs) of the German Neonatal Network (GNN) and at addressing risk factors for delayed vaccination and associated long-term consequences. We performed an observational study of the GNN between 1st January 2010 and 31st December 2019. The immunization status for the hexavalent and pneumococcal immunization was evaluated in n = 8401 preterm infants <29 weeks of gestation. Univariate analysis and logistic/linear regression models were used to identify risk factors for vaccination delay and outcomes at a 5-year follow-up. In our cohort n = 824 (9.8%) ELGANs did not receive a timely first immunization with the hexavalent and pneumococcal vaccine. Risk factors for delayed vaccination were SGA status (18.1% vs. 13.5%; OR 1.3; 95% CI: 1.1-1.7), impaired growth and surrogates for complicated clinical courses (i.e., need for inotropes, necrotizing enterocolitis). At 5 years of age, timely immunized children had a lower risk of bronchitis (episodes within last year: 27.3% vs. 37.7%; OR 0.60, 95% CI: 0.42-0.86) but spirometry measures were unaffected. In conclusion, a significant proportion of ELGANs are untimely immunized, specifically those with increased vulnerability, even though they might particularly benefit from the immune-promoting effects of a timely vaccination.