Early and Rapid Identification of COVID-19 Patients with Neutralizing Type I Interferon Auto-antibodies

Journal of Clinical Immunology - Six to 19% of critically ill COVID-19 patients display circulating auto-antibodies against type I interferons (IFN-AABs). Here, we establish a clinically applicable...     

Novel inhalational murine model of invasive pulmonary aspergillosis

We developed a novel model of invasive aspergillosis (IA) that recapitulates human disease. Mice were immunosuppressed with cyclophosphamide and cortisone acetate and then infected in an aerosol chamber. This procedure reproducibly delivered 1 x 10(3) to 3 x 10(3) conidia to the lungs. Lethal pulmonary IA developed over 2 weeks and was prevented by amphotericin B.     

Adherence to an antibiotic stewardship bundle targeting Staphylococcus aureus blood stream infections at a 200-bed community hospital

Purpose

Bacteremia with Staphylococcus aureus (SAB) is a serious clinical condition and is associated with a high mortality, ranging from 20 to 40 %. Different trials from tertiary referral hospitals demonstrate that infectious disease consultation and adherence to standard of care indicators reduce the high mortality. Data from <250-bed general hospitals are lacking in this context.

Methods

Patient cases at a community 200-bed general hospital with documented SAB were retrospectively analyzed from January 2010 to March 2013 regarding defined standard of care indicators. In April 2013, an antibiotic stewardship bundle approach was implemented targeting SAB. Follow-up was available until December 2013. Adherence to the different components of the bundle was analyzed.

Results

There were 64 cases of SAB reported. After exclusion of five cases, 39 cases were included in the pre-intervention period and 20 patients in the post-intervention period. Mean average bundle adherence increased from a baseline score of 0.8–3.7 (p < 0.001) in the post-intervention period, whereas in-hospital mortality decreased significantly (44 vs. 10 %, p < 0.001) despite or even because the absolute number of detected cases of SAB increased substantially after the intervention was initiated.

Conclusion

Although we were unable to identify whether the bundle, one of its components, or procedural improvements are responsible for the success of the intervention, our study indicates that the applied approach is feasible and is accompanied by a significant reduction of in-hospital mortality in the secondary care setting. The intervention may serve as a model for other hospitals with similar structures and baseline situations.     

Combining Structural Optimization and Process Assurance in Implicit Modelling for Casting Parts

The structural optimization of manufacturable casting parts is still a challenging and time-consuming task. Today, topology optimization is followed by a manual reconstruction of the design proposal and a process assurance simulation to endorse the design proposal. Consequently, this process is iteratively repeated until it reaches a satisfying compromise. This article shows a method to combine structural optimization and process assurance results to generate automatically structure- and process-optimized die casting parts using implicit geometry modeling. Therefore, evaluation criteria are developed to evaluate the current design proposal and qualitatively measure the improvement of manufacturability between two iterations. For testing the proposed method, we use a cantilever beam as an example of proof. The combined iterative method is compared to manual designed parts and a direct optimization approach and evaluated for mechanical performance and manufacturability. The combination of topology optimization (TO) and process assurance (PA) results is automated and shows a significant enhancement to the manual reconstruction of the design proposals. Further, the improvement of manufacturability is better or equivalent to previous work in the field while using less computational effort, which emphasizes the need for suitable metamodels to significantly reduce the effort for process assurance and enable much shorter iteration times.     

Infectious diseases consultations can make the difference: a brief review and a plea for more infectious diseases specialists in Germany

Trained infectious diseases (ID) specialists are an integral part of inpatient and outpatient care in many countries, however, these specialized services are established only in selected tertiary care hospitals in Germany. This review summarises studies that addressed the impact of ID consultation services on patient care and outcome. Extensive data for a clinical benefit is available in the context of Staphylococcus aureus bacteremia (SAB), in which in-hospital or 30-day mortality was significantly reduced by 40–50 % in patients evaluated and treated in cooperation with ID consultants. This effect was associated with improved adherence to quality-of-care standards. Moreover, newer studies show a reduced length of hospital stay due to ID consultations, especially if patients are evaluated early in the course of their hospital stay. Of note, informal consultations do not seem to be equivalent to a formal ID consultation with bedside patient evaluation. Studies in other patient groups (solid organ transplant recipients or intensive care unit patients) or in the context of other infections (infective endocarditis, pneumonia, other bloodstream infections) also revealed positive effects of ID consultations.Higher rates of appropriate empirical and targeted antimicrobial treatments and de-escalation strategies due to successful pathogen identification were documented. These modifications resulted in lower treatment costs and decreased antimicrobial resistance development. Although there are methodological limitations in single studies, we consider the consistent and reproducible positive effects of ID consultations shown in studies in different countries and health care systems as convincing evidence for improved quality-of-care and treatment outcomes in patients with infectious diseases. Thus, we strongly recommend efforts to establish significantly more ID consultation services in hospitals in Germany.     

Adenosine A1 receptors determine effects of caffeine on total fluid intake but not caffeine appetite

Adenosine A1 receptor wild-type (+/+) and knockout (-/-) mice were used to elucidate the role of adenosine A1 receptors in caffeine self-administration in a two-bottle choice test and in the effect of caffeine on total fluid intake and plasma renin concentration. With access to water only, adenosine A1 receptor -/- mice showed greater basal fluid intake and greater plasma renin concentration than +/+ mice. Free access to both water and a caffeinated solution (30 mg/100 ml) for 14 days increased total fluid intake only in adenosine A1 receptor +/+ mice (by 23+/-3%), and both total fluid intake and plasma renin concentration were no longer different between genotypes. Mean intake of water and caffeinated solution was not different between adenosine A1 receptor +/+ and -/- mice. These data reveal that adenosine A1 receptors do not contribute to caffeine consumption, but determine the effects of caffeine on fluid intake and plasma renin concentration.     

Unanticipated Heterogeneity in Growth Rate and Virulence among Candida albicans AAF1 Null Mutants

The disruption of a specific gene in Candida albicans is commonly used to determine the function of the gene product. We disrupted AAF1, a gene of C. albicans that causes Saccharomyces cerevisiae to flocculate and adhere to endothelial cells. We then characterized multiple heterozygous and homozygous mutants. These null mutants adhered to endothelial cells to the same extent as did the parent organism. However, mutants with presumably the same genotype revealed significant heterogeneity in their growth rates in vitro. This heterogeneity was not the result of the transformation procedure per se, nor was it caused by differences in the expression or function of URA3, a marker used in the process of gene disruption. The growth rate among the different heterozygous and homozygous null mutants was positively correlated with in vivo virulence in mice. It is possible that the variable phenotypes of C. albicans were due to mutations outside of the AAF1 coding region that were introduced during the gene disruption process. These results indicate that careful phenotypic characterization of mutants of C. albicans generated through targeted gene disruption should be performed to exclude the introduction of unexpected mutations that may influence pathogenicity in mice.     

Risk factors for abdominal wall defects

In the last decades, the prevalence of gastroschisis (GS) has increased worldwide. The purpose of this study was to identify maternal risk factors explaining the described gain and to identify differences between GS and omphalocele (OC). A case-control design was used to compare GS (n = 36) and OC (n = 18) mothers to control group (CG; n = 30) matched for maternal age. Specialized questionnaires and mothers' prenatal records were used, and participants completed a structured interview. Focus was on medical history, changing nutrition, drug consumption, and external risk factors. The local ethics committee approved this study. GS mothers were significantly younger (mean 23.00; median 24; SD ±5) than OC (P = 0.007; mean 28.61; median 28, 19-41; SD ±5.1) and CG (P = 0.001; mean 30.77; median 31, SD ±6.2). Mothers with abdominal wall defects (AWD) ingested antibiotics more often (P = 0.008) than CG. Socioeconomic characteristics, for example, level of profession, of GS mothers was significantly lower than OC (P = 0.039) and CG (P = 0.05) mothers, and their cohabitation time was shorter (P < 0.05; mean 35 month/median 24 month, SD ±35.8). Incidence of OC significantly increased after hormonal treatment (P = 0.022) and invasive prenatal diagnostics (P < 0.05) compared to GS. GS mothers took folic acid prophylaxis less often than OC (P = 0.02). Smoking, illicit drugs, and external risks like herbicides showed no influence, but GS mothers drink significantly more often alcohol (P = 0.05). We confirmed an increased risk for GS if several factors such as young maternal age, short cohabitation time, and usage of antibiotics coincide with alcohol consumption and associated immune diseases. OC increased after hormonal treatment and invasive prenatal diagnostics.