Ulrich H. Thome's research while affiliated with University Hospital Leipzig and other places

Background Respiratory tract colonisation with Ureaplasma species has been associated with the development of acute and long-term pulmonary morbidity in preterm infants. Apart from inflammation, the underlying mechanisms of Ureaplasma-driven lung disease are mainly unknown. The present investigation is the first to examine the influence of acute Ureaplasma infection on critical mechanisms of alveolar fluid clearance in the immature lung. Methods Primary rat fetal distal lung epithelial (FDLE) cells were incubated with viable Ureaplasma in the absence or presence of the urease inhibitor flurofamide. Na+ transport and activity of the epithelial Na+ channel (ENaC) and the Na,K-ATPase were determined in Ussing chambers. Barrier integrity, metabolic activity, gene expression, and kinase signalling were also assessed. Results We found a 30-90% decrease of epithelial Na+ transport upon 24 hours of Ureaplasma infection resulting from significant inhibition of ENaC and Na,K-ATPase activities. Notably, Ureaplasma induced phosphorylation of Erk1/2, a well-known inhibitor of ENaC activity. Moreover, Ureaplasma-driven NH3 production - and not the accompanying pH shift - inhibited the epithelial Na+ transport. Co-incubation with flurofamide entirely restored Na+ transport in Ureaplasma-infected FDLE cells. Conclusion Our data demonstrate that Ureaplasma infection significantly impairs epithelial Na+ transport and subsequent fluid clearance in fetal alveolar cells, most likely by Erk1/2 phosphorylation. We identified NH3 as the mediating virulence factor and were able to restore Na+ transport by inhibiting the Ureaplasma-specific urease. This is the first study to show a functional impairment of pulmonary epithelial cells upon Ureaplasma infection, revealing a potential mechanism of Ureaplasma-driven preterm lung disease.

Background Despite therapeutic hypothermia (TH) and neonatal intensive care, 45–50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol — a xanthine oxidase inhibitor — reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. Methods/design The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. Results The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and .”will be stratified for the two treatment groups. Discussion The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. Trial registration ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

Purpose This study assesses whether peripherally inserted central venous catheters (PICC), impregnated with anti-infective drugs, reduce the rate of infections in neonates compared with unimpregnated catheters. Methods A retrospective analysis was conducted on electronic patient records of neonates born between August 2014 and May 2020, who had PICCs inserted, either standard (S-PICC) or with anti-infective drugs (A-PICC). Catheter-related bloodstream infections (CRBSI) were diagnosed based on clinical symptoms, laboratory results, and mentioning of infection in the patient record. Data on dwell time, mechanical ventilation, insertion site, maximum C-reactive protein (CRP) concentration, and anti-infective drug use were analyzed. Results A total of 223 PICCs were included. The infection rates were A-PICC (18.9%) and S-PICC (12.5%), which were not significantly different (p = 0.257). A-PICCs had significantly longer dwell times than S-PICCs (median 372 vs. 219 h, p = 0.004). The time to infection was not different between the groups (p = 0.3). There were also no significant differences in maximum CRP, insertion site abnormalities, or anti-infective drug use between the groups. Conclusion This retrospective study did not find a significant reduction in infection rates by using PICCs containing anti-infective drugs in neonates. Current antibiotic impregnations do not seem to be effective in preventing blood stream infections.

Background Human milk banking has become an important aspect of Nutritional medicine. It is not just about the provision of mother’s own milk (MOM) or donor human milk (DHM) in the hospital, but also a strategy to encourage breastfeeding in the clinical setting and beyond. Objective To describe the feeding patterns of hospitalised infants including human milk dispensed by the Leipzig Donor Human Milk Bank (LMB). Design A descriptive analysis of daily data on milk feeds dispensed by LMB for hospitalised infants distinguishing between MOM or DHM, either fresh or frozen, and raw/pasteurised milk from 2012–2019. Results We included 2,562 infants with median hospitalisation of 23 days, for whom human milk was dispensed on median 76% of those days and other nutrition on the remaining days. Raw MOM and raw DHM comprised 52% and 8% of the dispensed milk, respectively. Dispensing exclusive DHM instead of MOM for at least one full day was required for 55% of the infants, mostly at the beginning but also later during hospitalisation. Exclusive raw DHM was dispensed on at least 1 day for 37% of the infants, in different birthweight strata <1,000 g: 10%, 1,000-1500 g: 11%, 1,500-2500 g: 13% and > 2,500 g: 3%. At discharge, MOM was dispensed for more than 60% of the infants. Conclusion During an infant’s hospital stay, LMB dispenses various human milk feeds with interspersed DHM resulting in complex intra-individual and time-variant feeding patterns. LMB dispenses raw MOM and especially raw DHM with the intention to retain the properties of human milk unlike a diet containing pasteurised DHM and/or formula. Although raw DHM comprises a small percentage of all dispensed milk, raw DHM is dispensed for a substantial portion of infants. Our results document that dispensing raw DHM, is possible in routine settings.

Background Randomized controlled trials have indicated reduced mortality rates in very preterm infants assigned to high compared to low oxygen saturation (SpO 2 ) target levels, accompanied by higher rates of retinopathy of prematurity and bronchopulmonary dysplasia. However, the benefit-to-harm ratio may depend on the local background mortality risk. We therefore aimed to quantify the risk–benefit ratios of different SpO 2 target ranges in 10 tertiary newborn intensive care units (NICUs) in East Germany. Methods In a retrospective multicenter study, 1,399 infants born between 2008 and 2012 at a gestational age between 24 0/7 and 27 6/7 weeks and with a birthweight below 1,250 g were grouped according to the hospital's target SpO 2 range [high oxygen saturation group (HOSG) above 90%], low oxygen saturation group (LOSG) below 90%] and the compliance of units with their target SpO 2 range. The association between neonatal morbidities, neurodevelopmental outcomes, selected treatment strategies, and target SpO 2 ranges was calculated using chi-squared and Mann Whitney U tests. Results Nine of the ten participating NICUs met their SpO 2 target ranges. Five units were considered as HOSG, and five units were considered as LOSG. Necrotizing enterocolitis and intraventricular hemorrhage grade ≥ 2 occurred significantly more frequently in the HOSG than in the LOSG (8.4% vs. 5.1%, p = 0.02; and 26.6% vs. 17.7%, p < 0.001). No significant differences in the mortality rate and the rate of retinopathy of prematurity were found. Conclusion In our patient population, a lower SpO 2 target range was not associated with increased safety risks in extremely preterm infants. We cannot be sure that our outcome differences are associated with differences in oxygen saturations due to the retrospective study design and the differences in site practices.