Microbial cell-free DNA-sequencing as an addition to conventional diagnostics in neonatal sepsis.

BACKGROUND: Bloodstream infections remain a challenge for neonatologists, as traditional culture-based methods are time-consuming and rely on adequate blood volume. Next-generation sequencing (NGS) offers an alternative, as it can identify microbial cell-free DNA (mcfDNA) in a small blood sample, providing rapid pathogen detection. This study aimed to assess the diagnostic performance of DISQVER®-NGS compared to blood cultures in neonatal patients with suspected sepsis. METHODS: In neonates with suspected sepsis, blood cultures and samples for NGS were prospectively collected. Patients were divided into four categories: 1) sepsis, blood culture positive, 2) clinical sepsis, culture negative, 3) suspected sepsis, 4) validation cohort. RESULTS: NGS detected bacterial, viral or fungal mcfDNA in 24 of 82 samples. Blood cultures were collected in 46 of 84 patients (15/46 positive). DISQVER® correctly identified pathogens in 9/15 patients with a positive blood culture, two with intrinsic resistance to their antibiotic regimen. In seven samples NGS reported the mcfDNA of bacteria that could have theoretically grown in culture but did not. CONCLUSIONS: NGS may enhance sensitivity in sepsis diagnostics by detecting mcfDNA in neonates with suspected sepsis. Interpreting NGS results requires correlation with clinical data, laboratory values, and routine microbiological tests for a comprehensive understanding of the patient's condition. IMPACT: Conventional blood culture methods have limitations in accuracy and turnaround time. The study aimed to investigate the diagnostic performance of the Next-Generation Sequencing method DISQVER® compared to traditional blood cultures in neonatal patients with suspected sepsis. Our findings suggest that NGS has the potential to augment the precision of conventional diagnostic techniques, can lead to improved detection of pathogens and targeted treatment approaches in neonatal sepsis. It is emphasized that further validation and integration with clinical and microbiological data are required to ensure optimal clinical utility.

Biodynamic lighting conditions preserve nocturnal melatonin production in pregnant women during hospitalization: A randomized prospective pilot study.

Background and purpose: Maternal circadian rhythms are important for maintaining maternal and fetal homeostasis. The maternal circadian system coordinates the internal clock of the fetus with environmental lighting conditions via the melatonin signal. The intensity and wavelength of daylight influence nocturnal melatonin production. This study aims to evaluate the effect of environmental lighting conditions on melatonin production in pregnant women with reduced mobility during hospitalization. Methods: We installed a human-centric lighting system with biodynamic effects (BDL, biodynamic lighting) in the patient rooms. The pregnant women in the patient rooms with standard indoor conditions served as a control group. The illuminance (lux) and dose of effective circadian irradiation (Hec) were recorded every 10 seconds by light dosimeters (Lucerne University, Switzerland) attached to the patients` clothing. Results: We analyzed the illuminance status of 47 pregnant women with a median (IQR) gestational age of 29.9 (25.4-32.3) weeks of gestation. The median illuminance in the control group was significantly lower (p<0.05) than in the BDL group in the morning and afternoon from day 1 to 5. BDL patients had a significantly higher effective circadian irradiation in the morning. The effective circadian irradiation showed a significant daily rhythm only in the BDL group. The BDL group had a significantly higher melatonin production on day 3 (p=0.006) and day 5 (p=0.012) than the control group median (IQR) nocturnal 6-Sulfatoxymelatonin excretion 15840 (10140-22160) ng/12h vs. 6141 (2080-11328) ng/12h on day 3 and 18780 (11320-23562) ng/12h vs. 6380 (3500-17600) ng/12h on day 5). Conclusion: We have demonstrated that dramatically altered lighting conditions of hospitalized pregnant women may be optimized by installing biodynamic lighting systems in the patient rooms resulting in the maintenance of nocturnal melatonin production in pregnant women.

Prediction of ECMO and Mortality in Neonates with Congenital Diaphragmatic Hernia Using the SNAP-II Score.

BACKGROUND: The mortality of neonates with congenital diaphragmatic hernia (CDH) ranges between 20 and 40% even in specialized high-volume centers. The Score for Neonatal Acute Physiology-II (SNAP-II Score) could facilitate the decision about supportive therapies in CDH newborns. METHODS: The SNAP-II score consists of the variables arterial blood pressure, pH, PaO2:FiO2, body temperature, diuresis, and seizure activity and was calculated at an age of 12 h. RESULTS: 101 CDH newborns treated in our institution between 2009 and 2017 were included in the study. A SNAP-II score ≥ 28 was calculated as cutoff for predicting mortality (AUC 0.876; 95% CI: 0.795-0.957). The mortality rate was 52.9% with a SNAP-II score ≥ 28, and 5.9% with a SNAP-II score<28. Sensitivity and specificity for predicting mortality was 81.8 and 79.7%, the negative predicting value (NPV) was 94.0%, the positive predicting value (PPV) 52.9%. The optimal cutoff for predicting ECMO was ≥ 22 (AUC 0.895; 95% CI: 0.836-0.954). Sensitivity and specificity for predicting ECMO therapy was 90.7, and 63.8%, the NPV was 90.2%, and the PPV was 65% respectively. The SNAP-II score was independently associated with mortality [OR 1.126 (95% CI: 1.050-1.207)] and the need for ECMO therapy [OR 1.243 (95% CI: 1.106-1.397)]. CONCLUSION: The SNAP-II score is strongly associated with mortality and the need for ECMO therapy in CDH newborns and should be implemented in the risk stratification of these infants.