The aim of this study was to analyze the relative frequency, clinical characteristics, disease onset and progression in f-IPF vs. sporadic IPF (s-IPF). Familial IPF index patients and their family members were recruited into the European IPF registry/biobank (eurIPFreg) at the Universities of Giessen and Marburg (UGMLC). Initially, we employed wide range criteria of f-IPF (e.g. relatives who presumably died of some kind of parenchymal lung disease). After narrowing down the search to occurrence of idiopathic interstitial pneumonia (IIP) in at least one first grade relative, 28 index patients were finally identified, prospectively interviewed and examined. Their family members were phenotyped with establishment of pedigree charts. Within the 28 IPF families, overall 79 patients with f-IPF were identified. In the same observation period, 286 f-IIP and s-IIP patients were recruited into the eurIPFreg at our UGMLC sites, corresponding to a familial versus s-IPF of 9.8%. The both groups showed no difference in demographics (61 vs. 79% males), smoking history, and exposure to any environmental triggers known to cause lung fibrosis. The f-IPF group differed by an earlier age at the onset of the disease (55.4 vs. 63.2 years; p < 0.001). On average, the f-IPF patients presented a significantly milder extent of functional impairment at the time point of inclusion vs. the s-IPF group (FVC 75% pred. vs. FVC 62% pred., p = 0.011). In contrast, the decline in FVC was found to be faster in the f-IPF vs. the s-IPF group (4.94% decline in 6 months in f-IPF vs. 2.48% in s-IPF, p = 0.12). The average age of death in f-IPF group was 67 years vs. 71.8 years in s-IPF group (p = 0.059). The f-IIP group displayed diverse inheritance patterns, mostly autosomal-dominant with variable penetrance. In the f-IPF, the younger generations showed a tendency for earlier manifestation of IPF vs. the older generation (58 vs. 66 years, p = 0.013). The 28 f-IPF index patients presented an earlier onset and more aggressive natural course of the disease. The disease seems to affect consecutive generations at a younger age. Nr. NCT02951416 http://www.www.clinicaltrials.gov

Listeria monocytogenes is a bacterial pathogen and causative agent for the foodborne infection listeriosis, which is mainly a threat for pregnant, elderly, or immunocompromised individuals. Due to its ability to invade and colonize diverse eukaryotic cell types including cells from invertebrates, L. monocytogenes has become a well-established model organism for intracellular growth. Almost 10 years ago, we and others presented the first whole-genome microarray-based intracellular transcriptome of L. monocytogenes. With the advent of newer technologies addressing transcriptomes in greater detail, we revisit this work, and analyze the intracellular transcriptome of L. monocytogenes during growth in murine macrophages using a deep sequencing based approach. We detected 656 differentially expressed genes of which 367 were upregulated during intracellular growth in macrophages compared to extracellular growth in Brain Heart Infusion broth. This study confirmed ∼64% of all regulated genes previously identified by microarray analysis. Many of the regulated genes that were detected in the current study involve transporters for various metals, ions as well as complex sugars such as mannose. We also report changes in antisense transcription, especially upregulations during intracellular bacterial survival. A notable finding was the detection of regulatory changes for a subset of temperate A118-like prophage genes, thereby shedding light on the transcriptional profile of this bacteriophage during intracellular growth. In total, our study provides an updated genome-wide view of the transcriptional landscape of L. monocytogenes during intracellular growth and represents a rich resource for future detailed analysis.

Aim: To evaluate safety and clinical outcome of rapid enteral feeding advances in preterm infants <1500 g birthweight (BW).Methods: In this single‐center retrospective cohort study, 293 preterm infants born during 2015–2018 were comparatively analyzed before (n = 145) and after (n = 148) the implementation of a rapid enteral feeding protocol with daily milk increments of 20–30 ml/kg of body weight. Major outcome parameters were focused toward pulmonary morbidities and nutritional variables.Results: Preterm infants in the rapid feeding advancement group were more successfully stabilized on noninvasive ventilation (p < 0.001) never requiring mechanical ventilation. Duration of respiratory support (0.465) and frequency of bronchopulmonary dysplasia (BPD) (p = 0.341) and severe BPD (0.273) did not differ between both groups. Furthermore, patients in the rapid feeding group achieved full volume feedings faster (p < 0.001), regained BW earlier (p = 0.009), and displayed significantly improved somatic growth at 36 weeks gestational age (p < 0.001). There was no increased risk for further morbidities of prematurity including feeding intolerance, necrotizing enterocolitis (NEC), and focal intestinal perforation.Conclusion: Rapid enteral feeding advancements in preterm infants <1500 g BW are safe and do not impede stabilization on noninvasive ventilation.

Background: Very low birth weight (VLBW) infants on noninvasive ventilation (NIV) experience frequent fluctuations in oxygen saturation (SpO2) that are associated with an increased risk for mortality and severe morbidities. Methods: In this randomized crossover trial, VLBW infants (n = 22) born 22+3 to 28+0 weeks on NIV with supplemental oxygen were allocated on two consecutive days in random order to synchronized nasal intermittent positive pressure ventilation (sNIPPV) and nasal high-frequency oscillatory ventilation (nHFOV) for 8 h. nHFOV and sNIPPV were set to equivalent mean airway pressure and transcutaneous pCO2. Primary outcome was the time spent within the SpO2 target (88–95%). Results: During sNIPPV, VLBW infants spent significantly more time within the SpO2 target (59.9%) than during nHFOV (54.6%). The proportion of time spent in hypoxemia (22.3% vs. 27.1%) and the mean fraction of supplemental oxygen (FiO2) (29.4% vs. 32.8%) were significantly reduced during sNIPPV, while the respiratory rate (50.1 vs. 42.6) was significantly higher. Mean SpO2, SpO2 above the target, number of prolonged (>1 min) and severe (SpO2 <80%) hypoxemic episodes, parameters of cerebral tissue oxygenation using NIRS, number of FiO2 adjustments, heart rate, number of bradycardias, abdominal distension and transcutaneous pCO2 did not differ between both interventions. Conclusions: In VLBW infants with frequent fluctuations in SpO2, sNIPPV is more efficient than nHFOV to retain the SpO2 target and to reduce FiO2 exposure. These results demand more detailed investigations into cumulative oxygen toxicities during different modes of NIV over the weaning period, particularly with regard to consequences for long-term outcomes.

Background and Aim: Obstructive urolithiasis is a common disease in small ruminants with fatal outcomes if left untreated. Many methods have been established; however, long-term success rates remain unsatisfactory. Four bibliographic databases (PubMed, HeBis, Medline (OvidSP), and Web of Science) were searched to evaluate the prevalence of urolithiasis in small ruminants and long-term outcomes after surgery using a systematic review. The study aimed to give evidence-based data concerning prevalence and success rates after surgery. Materials and Methods: The analysis included 24 (total 239) peer-reviewed journal articles dealing with the prevalence of urolithiasis and 16 (total 39) concerning long-term outcomes after surgery. Literature was included if it referred to species, language, availability, and relevant statements to the specific questions, including the presence of control groups. Heterogeneity tests included χ2, Ι2, and τ2, respectively. A 95% confidence interval was determined, and effects were estimated using the fixed effect model. Due to a feeding-associated bias, prevalence analysis was conducted for a sorghum-based and a corn-based feeding resulting in a weighted prevalence of 62% and 17%, respectively. Analysis of long-term outcomes after surgical interventions revealed long-term success rates of 15-77% after ultrasonographic tube cystotomy and marsupialization of the urinary bladder, respectively. Results: The prevalence of urolithiasis is strongly associated with feeding and may be calculated as 17% in corn-based rations and 62% in sorghum-based rations. Surgical interventions result in guarded to moderate long-term success rates of 15-66%. Urethral stoma and marsupialization of the bladder provide acceptable long-term success rates with 71-77% but are rather salvage techniques than accepted surgical methods, especially when used in companion animals. Conclusion: The development of urolithiasis is mainly influenced by nutrition. Effective prophylaxis of this disease should, therefore, always include advisory service for the owners. Existing surgical techniques should be critically re-evaluated concerning their long-term success rates.