Clinical decision making is improved by BioFire Pneumonia Plus in suspected lower respiratory tract infection after lung transplantation: Results of the prospective DBATE‐IT * study

Background: Lower respiratory tract infections (LRTIs) are a significant cause of morbidity and mortality in lung transplant (LTx) recipients. Timely and precise pathogen detection is vital to successful treatment. Multiplex PCR kits with short turnover times like the BioFire Pneumonia Plus (BFPPp) (manufactured by bioMérieux) may be a valuable addition to conventional tests. Methods: We performed a prospective observational cohort study in 60 LTx recipients with suspected LRTI. All patients received BFPPp testing of bronchoalveolar lavage fluid in addition to conventional tests including microbiological cultures and conventional diagnostics for respiratory viruses. Primary outcome was time‐to‐test‐result; secondary outcomes included time‐to‐clinical‐decision and BFPPp test accuracy compared to conventional tests. Results: BFPPp provided results faster than conventional tests (2.3 h [2–2.8] vs. 23.4 h [21–62], p < 0.001), allowing for faster clinical decisions (2.8 [2.2–44] vs. virology 28.1 h [23.1–70.6] and microbiology 32.6 h [4.6–70.9], both p < 0.001). Based on all available diagnostic modalities, 26 (43%) patients were diagnosed with viral LRTI, nine (15 %) with non‐viral LRTI, and five (8 %) with combined viral and non‐viral LRTI. These diagnoses were established by BFPPp in 92%, 78%, and 100%, respectively. The remaining 20 patients (33 %) received a diagnosis other than LRTI. Preliminary therapies based on BFPPp results were upheld in 90% of cases. There were six treatment modifications based on pathogen‐isolation by conventional testing missed by BFPPp, including three due to fungal pathogens not covered by the BFPPp. Conclusion: BFPPp offered faster test results compared to conventional tests with good concordance. The absence of fungal pathogens from the panel is a potential weakness in a severely immunosuppressed population

Wochenende — modular and flexible alignment-based shotgun metagenome analysis

Background: Shotgun metagenome analysis provides a robust and verifiable method for comprehensive microbiome analysis of fungal, viral, archaeal and bacterial taxonomy, particularly with regard to visualization of read mapping location, normalization options, growth dynamics and functional gene repertoires. Current read classification tools use non-standard output formats, or do not fully show information on mapping location. As reference datasets are not perfect, portrayal of mapping information is critical for judging results effectively. Results: Our alignment-based pipeline, Wochenende, incorporates flexible quality control, trimming, mapping, various filters and normalization. Results are completely transparent and filters can be adjusted by the user. We observe stringent filtering of mismatches and use of mapping quality sharply reduces the number of false positives. Further modules allow genomic visualization and the calculation of growth rates, as well as integration and subsequent plotting of pipeline results as heatmaps or heat trees. Our novel normalization approach additionally allows calculation of absolute abundance profiles by comparison with reads assigned to the human host genome. Conclusion: Wochenende has the ability to find and filter alignments to all kingdoms of life using both short and long reads, and requires only good quality reference genomes. Wochenende automatically combines multiple available modules ranging from quality control and normalization to taxonomic visualization. Wochenende is available at https://github.com/MHH-RCUG/nf_wochenende

BaiCD gene cluster abundance is negatively correlated with Clostridium difficile infection

Background Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea. Secondary bile acids were shown to confer resistance to colonization by C. difficile. 7 alpha-dehydroxylation is a key step in transformation of primary to secondary bile acids and required genes have been located in a single bile acid-inducible (bai) operon in C. scindens as well as in C. hiranonis, two Clostridium sp. recently reported to protect against C. difficile colonization. Aim To analyze baiCD gene abundance in C. difficile positive and negative fecal samples. Material & methods A species-specific qPCR for detecting baiCD genes was established. Fecal samples of patients with CDI, asymptomatic toxigenic C. difficile colonization (TCD), non-toxigenic C. difficile colonization (NTCD), of C. difficile negative (NC) patients, and of two patients before and after fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) were tested for the presence of the baiCD genes. Results The prevalence of the baiCD gene cluster was significantly higher in C. difficile negative fecal samples than in samples of patients diagnosed with CDI (72.5% (100/138) vs. 35.9% (23/64;p<0.0001). No differences in baiCD gene cluster prevalence were seen between NC and NTCD or NC and TCD samples. Both rCDI patients were baiCD-negative at baseline, but one of the two patients turned positive after successful FMT from a baiCD-positive donor. Conclusion Fecal samples of CDI patients are less frequently baiCD-positive than samples from asymptomatic carriers or C. difficile-negative individuals. Furthermore, we present a case of baiCD positivity observed after successful FMT for rCDI

Bile Acids Specifically Increase Hepatitis C Virus RNA-Replication

<div><h3>Background</h3><p>Hepatitis C virus (HCV) patients with high serum levels of bile acids (BAs) respond poorly to IFN therapy. BAs have been shown to increase RNA-replication of genotype 1 but not genotype 2a replicons. Since BAs modulate lipid metabolism including lipoprotein secretion and as HCV depends on lipids and lipoproteins during RNA-replication, virus production and cell entry, BAs may affect multiple steps of the HCV life cycle. Therefore, we analyzed the influence of BAs on individual steps of virus replication.</p> <h3>Methods</h3><p>We measured replication of subgenomic genotype (GT) 1b and 2a RNAs as well as full-length GT2a genomes in the presence of BAs using quantitative RT-PCR and luciferase assays. Cell entry was determined using HCV pseudoparticles (HCVpp). Virus assembly and release were quantified using a core-specific ELISA. Replicon chimeras were employed to characterize genotype-specific modulation of HCV by BAs. Lunet CD81/GFP-NLS-MAVS cells were used to determine infection of Con1 particles.</p> <h3>Results</h3><p>BAs increased RNA-replication of GT1b replicons up to 10-fold but had no effect on subgenomic GT2a replicons both in Huh-7 and HuH6 cells. They did not increase viral RNA translation, virus assembly and release or cell entry. Lowering replication efficiency of GT2a replicons rendered them susceptible to stimulation by BAs. Moreover, replication of full length GT1b with or without replication enhancing mutations and GT2a genomes were also stimulated by BAs.</p> <h3>Conclusions</h3><p>Bile acids specifically enhance RNA-replication. This is not limited to GT1, but also holds true for GT2a full length genomes and subgenomic replicons with low replication capacity. The increase of HCV replication by BAs may influence the efficacy of antiviral treatment in vivo and may improve replication of primary HCV genomes in cell culture.</p> </div

Globally, songs and instrumental melodies are slower, higher, and use more stable pitches than speech: a registered report

Both music and language are found in all known human societies, yet no studies have compared similarities and differences between song, speech, and instrumental music on a global scale. In this Registered Report, we analyzed two global datasets: (i) 300 annotated audio recordings representing matched sets of traditional songs, recited lyrics, conversational speech, and instrumental melodies from our 75 coauthors speaking 55 languages; and (ii) 418 previously published adult-directed song and speech recordings from 209 individuals speaking 16 languages. Of our six preregistered predictions, five were strongly supported: Relative to speech, songs use (i) higher pitch, (ii) slower temporal rate, and (iii) more stable pitches, while both songs and speech used similar (iv) pitch interval size and (v) timbral brightness. Exploratory analyses suggest that features vary along a “musi-linguistic” continuum when including instrumental melodies and recited lyrics. Our study provides strong empirical evidence of cross-cultural regularities in music and speech

Risikofaktoren für Schließungen von neonatologischen und pädiatrischen Stationen in nosokomialen Ausbrüchen

Edler R, Chhatwal P, Albrecht U-V, Vonberg R-P. Risikofaktoren für Schließungen von neonatologischen und pädiatrischen Stationen in nosokomialen Ausbrüchen. Monatsschrift Kinderheilkunde. 2022.**Hintergrund** Im Fall eines nosokomialen Ausbruchs (NA) in der Pädiatrie und Neonatologie wird neben einer Vielzahl weiterer Maßnahmen mintunter die gesamte Station für Neuaufnahmen geschlossen. Dies ist infektionsprophylaktisch zwar oft effektiv, jedoch ökonomisch oft auch sehr nachteilig. Wichtig sind daher Kenntnisse darüber, wann eine solche Schließung sehr wahrscheinlich unvermeidbar ist, um diese dann frühestmöglich durchzuführen. **Ziel der Arbeit** Ermittlung von Charakteristika, die eine Schließung letztlich wahrscheinlich machen. **Material und Methoden** Systematische Literaturrecherche der Worldwide Outbreak Database und weiterer internationaler Datenbanken zu NA mit und ohne Schließung. **Ergebnisse** Es wurden 198 NA aus der Pädiatrie (darunter 25 NA mit und 173 NA ohne Schließung) sowie weitere 413 NA aus der Neonatologie (darunter 52 NA mit und 361 NA ohne Schließung) eingeschlossen. In 446 dieser 611 NA waren auch Intensivstationen (ITS) betroffen. Insgesamt waren 16.107 Patienten betroffen und es ereigneten sich 3155 Infektionen mit 1542 Todesfällen. Die Gesamtdauer der NA betrug dabei 2 bis 4380 Tage; sofern erfolgt, betrug die Dauer der Schließung 2 bis 210 Tage. Die am häufigsten nachgewiesenen Erreger in Ausbrüchen mit Schließung warenS. marcescens, E. cloacaeundK. pneumoniae. Die Beteiligung einer ITS sowie hohe Fallzahlen korrelierten signifikant mit der Wahrscheinlichkeit für eine spätere Schließung. **Diskussion** Insbesondere für die Neonatologie wird bei der Beteiligung einer ITS an einem NA empfohlen, eine Schließung des Bereiches frühzeitig zu erwägen. Zudem kann in NA die Definition lokal festgelegter Schwellenwerte für Patientenzahlen, bei deren Überschreiten bestimmte Hygienemaßnahmen, wie z. B. die Schließung der Station, initiiert werden, sinnvoll sein.**Background** A bundle of infection control measures are implemented in the case of a nosocomial outbreak (NO) in pediatrics and neonatology, including the total closure of the ward for new admissions. This represents a very effective but unfortunately also cost-intensive decision. Thus, knowledge on certain outbreak characteristics that will very probably result in such a closure is important in order to carry this out as early as possible to minimize nosocomial transmissions and subsequent infections as well as financial loss. **Objective** To determine the characteristics that are highly associated with a need for closure of the ward or unit. **Material and methods** A systematic review of the medical literature on NO in pediatrics and neonatology was carried out in the Worldwide Outbreak Database, which represents the largest collection of literature on NO, and additional international databases on NO with closure were then statistically compared to NO without closure. **Results** Overall, 198 NO in pediatrics (including 25 NO with and 173 NO without closure) and a further 413 NO in neonatology (including 52 NO with and 361 NO without closure) were included in the analysis. Intensive care units (ICUs) were involved in 446 of these 611 NO (73.0%). The source of the NO remained unknown in 299 of the 611 NO (48.9%). Among the 16,107 affected patients there were 3155 infections and 1542 fatal cases. The duration of the NOs ranged from 2 to 4380 days. The duration of closure (if applicable) ranged from 2 to 210 days. The most frequently reported pathogens in NO with subsequent closure wereSerratia marcescens,Enterobacter cloacae, andKlebsiella pneumoniae. The involvement of an ICU was significantly associated with the decision to finally close the affected location (pediatric ICU:p = 0.026; neonatological ICU:p < 0.001). The same observation was made when a large number of patients were involved in the NO. The top 5 measures in NO in pediatrics and neonatology were screening of patients (387 NO), enforcement of hand hygiene (302 NO), screening of staff (291 NO), isolation precautions in single rooms or cohorts (270 NO) and modification of the antimicrobial treatment (249 NO). **Conclusion** Based on these findings one should consider closure of the ward early in the course of events when experiencing a NO on an ICU in pediatrics and especially in neonatology. Furthermore, it would be useful to define a locally established threshold for the number of patients involved in such a NO, which could then trigger the enforcement of new implementation of infection control measures, such as a closure of the entire unit. Finally, we would like to encourage everybody experiencing an NO to share the observations in detail with others. Data from NO are crucial in order to generate infection control recommendations in guidelines, that are appropriate for education of all kinds of medical staff, and it can be very helpful to rely on previous experiences during a new ongoing outbreak investigation