A Toolchain for Privacy-Preserving Distributed Aggregation on Edge-Devices

Valuable insights, such as frequently visited environments in the wake of the COVID-19 pandemic, can oftentimes only be gained by analyzing sensitive data spread across edge-devices like smartphones. To facilitate such an analysis, we present a toolchain for a distributed, privacy-preserving aggregation of local data by taking the limited resources of edge-devices into account. The distributed aggregation is based on secure summation and simultaneously satisfies the notion of differential privacy. In this way, other parties can neither learn the sensitive data of single clients nor a single client's influence on the final result. We perform an evaluation of the power consumption, the running time and the bandwidth overhead on real as well as simulated devices and demonstrate the flexibility of our toolchain by presenting an extension of the summation of histograms to distributed clustering

Growth of Chlamydia pneumoniae Is Enhanced in Cells with Impaired Mitochondrial Function

Effective growth and replication of obligate intracellular pathogens depend on host cell metabolism. How this is connected to host cell mitochondrial function has not been studied so far. Recent studies suggest that growth of intracellular bacteria such as Chlamydia pneumoniae is enhanced in a low oxygen environment, arguing for a particular mechanistic role of the mitochondrial respiration in controlling intracellular progeny. Metabolic changes in C. pneumoniae infected epithelial cells were analyzed under normoxic (O2 ≈ 20%) and hypoxic conditions (O2 < 3%). We observed that infection of epithelial cells with C. pneumoniae under normoxia impaired mitochondrial function characterized by an enhanced mitochondrial membrane potential and ROS generation. Knockdown and mutation of the host cell ATP synthase resulted in an increased chlamydial replication already under normoxic conditions. As expected, mitochondrial hyperpolarization was observed in non-infected control cells cultured under hypoxic conditions, which was beneficial for C. pneumoniae growth. Taken together, functional and genetically encoded mitochondrial dysfunction strongly promotes intracellular growth of C. pneumoniae

Development and validation of BLOOMY prediction scores for 14-day and 6-month mortality in hospitalised adults with bloodstream infections: a multicentre, prospective, cohort study

Background: The burden of bloodstream infections remains high worldwide and cannot be confined to short-term in-hospital mortality. We aimed to develop scores to predict short-term and long-term mortality in patients with bloodstream infections. Methods: The Bloodstream Infection due to Multidrug-resistant Organisms: Multicenter Study on Risk Factors and Clinical Outcomes (BLOOMY) study is a prospective, multicentre cohort study at six German tertiary care university hospitals to develop and validate two scores assessing 14-day and 6-month mortality in patients with bloodstream infections. We excluded patients younger than 18 years or who were admitted to an ophthalmology or psychiatry ward. Microbiological, clinical, laboratory, treatment, and survival data were prospectively collected on day 0 and day 3 and then from day 7 onwards, weekly. Participants were followed up for 6 months. All patients in the derivation cohort who were alive on day 3 were included in the analysis. Predictive scores were developed using logistic regression and Cox proportional hazards models with a machine-learning approach. Validation was completed using the C statistic and predictive accuracy was assessed using sensitivity, specificity, and predictive values. Findings: Between Feb 1, 2017, and Jan 31, 2019, 2568 (61·5%) of 4179 eligible patients were recruited into the derivation cohort. The in-hospital mortality rate was 23·75% (95% CI 22·15-25·44; 610 of 2568 patients) and the 6-month mortality rate was 41·55% (39·54-43·59; 949 of 2284). The model predictors for 14-day mortality (C statistic 0·873, 95% CI 0·849-0·896) and 6-month mortality (0·807, 0·784-0·831) included age, body-mass index, platelet and leukocyte counts, C-reactive protein concentrations, malignancy (ie, comorbidity), in-hospital acquisition, and pathogen. Additional predictors were, for 14-day mortality, mental status, hypotension, and the need for mechanical ventilation on day 3 and, for 6-month mortality, focus of infection, in-hospital complications, and glomerular filtration rate at the end of treatment. The scores were validated in a cohort of 1023 patients with bloodstream infections, recruited between Oct 9, 2019, and Dec 31, 2020. The BLOOMY 14-day score showed a sensitivity of 61·32% (95% CI 51·81-70·04), a specificity of 86·36% (83·80-88·58), a positive predictive value (PPV) of 37·57% (30·70-44·99), and a negative predictive value (NPV) of 94·35% (92·42-95·80). The BLOOMY 6-month score showed a sensitivity of 69·93% (61·97-76·84), a specificity of 66·44% (61·86-70·73), a PPV of 40·82% (34·85-47·07), and a NPV of 86·97% (82·91-90·18). Interpretation: The BLOOMY scores showed good discrimination and predictive values and could support the development of protocols to manage bloodstream infections and also help to estimate the short-term and long-term burdens of bloodstream infections. Funding: DZIF German Center for Infection Research. Translation: For the German translation of the abstract see Supplementary Materials section

Increasing numbers and complexity of Staphylococcus aureus bloodstream infection - 14 years of prospective evaluation at a German tertiary care center with multi-center validation of findings

Objectives: Staphylococcus aureus bloodstream infection (SAB) is a common and severe infection. This study aims to describe temporal trends in numbers, epidemiological characteristics, clinical manifestations, and outcomes of SAB. Methods: We performed a post-hoc analysis of three prospective SAB cohorts at the University Medical Center Freiburg between 2006 and 2019. We validated our findings in a large German multi-center cohort of five tertiary care centers (R-Net consortium, 2017-2019). Time-dependent trends were estimated using Poisson or beta regression models. Results: We included 1,797 patients in the mono-centric and 2,336 patients in the multi-centric analysis. Overall, we observed an increasing number of SAB cases over 14 years (+6.4%/year and 1,000 patient days, 95%-CI: +5.1%-7.7%), paralleled by an increase in the proportion of community-acquired SAB (+4.9%/year (95%-CI: +2.1-7.8%), CA-SAB) and a decrease in the rate of methicillin-resistant-SAB (-8.5%/year (95%-CI: -11.2-(-5.6%)), MRSA-SAB). All of these findings were confirmed in the multi-center validation cohort (+6.2% cases per 1000 patient cases/year (95%-CI: -0.6-+12.6%), CA-SAB +8.7% (95%-CI: -1.2-+19.6%), MRSA-SAB -18.6% (95%-CI: -30.6-(-5.8%))). Moreover, we found an increasing proportion of patients with multiple risk factors for complicated/difficult-to-treat SAB (+8.5%/year, 95%-CI: +3.6-13.5%, p<0.001), alongside an overall higher level of comorbidities (Charlson comorbidity score +0.23 points/year, 95%-CI: +0.09-0.37, p=0.005). At the same time, the rate of deep-seated foci like osteomyelitis or deep-seated abscesses significantly increased (+6.7%, 95%-CI: +3.9-9.6%, p<0.001). A reduction of in-hospital mortality by 0.6% per year (95%-CI: 0.08-1%) was observed in the subgroup of patients with infectious diseases (ID) consultations. Conclusions: We found an increasing number of SAB combined with a significant increase in comorbidities and complicating factors in tertiary care centers. The resulting challenges in securing adequate SAB management in the face of high patient turnover will become an important task for physicians

Surveillance and Genomic Analysis of Third-Generation Cephalosporin-Resistant and Carbapenem-Resistant Klebsiella pneumoniae Complex in Germany

To analyse the epidemiology and population structure of third-generation cephalosporin-resistant (3GCR) and carbapenem-resistant (CR) Klebsiella pneumoniae complex isolates, patients were screened for rectal colonisation with 3GCR/CR K. pneumoniae complex on admission to six German university hospitals (2016-2019). Also collected were 3GCR/CR and susceptible K. pneumoniae isolates from patients with bloodstream infections (2016-2018). Whole-genome sequencing was performed followed by multilocus sequencing typing (MLST), core-genome MLST, and resistome and virulome analysis. The admission prevalence of 3GCR K. pneumoniae complex isolates during the 4-year study period was 0.8%, and 1.0 bloodstream infection per 1000 patient admissions was caused by K. pneumoniae complex (3GCR prevalence, 15.1%). A total of seven K. pneumoniae complex bloodstream isolates were CR (0.8%). The majority of colonising and bloodstream 3GCR isolates were identified as K. pneumoniae, 96.7% and 98.8%, respectively; the remainder were K. variicola and K. quasipneumoniae. cgMLST showed a polyclonal population of colonising and bloodstream isolates, which was also reflected by MLST and virulome analysis. CTX-M-15 was the most prevalent extended-spectrum beta-lactamase, and 29.7% of the colonising and 48.8% of the bloodstream isolates were high-risk clones. The present study provides an insight into the polyclonal 3GCR K. pneumoniae population in German hospitals

Resolving colistin resistance and heteroresistance in Enterobacter species

Taxonomical complexity has muddled the classification of clinically relevant Enterobacter species. Authors carry out a genome-based study on clinical isolates to investigate colistin resistance and heteroresistance in Enterobacter

Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19

Immune perturbation is a hallmark of Coronavirus Disease 2019 (COVID-19) with ambiguous roles of various immune cell compartments. Plasma cells, responsible for antibody production, have a two-pronged response while mounting an immune defence with 1) physiological immune response producing neutralizing antibodies against protein structures of SARS-CoV-2 and 2) potentially deleterious autoantibody generation. Growing evidence hints towards broad activation of plasma cells and the presence of pathologic autoantibodies (abs) that mediate immune perturbation in acute COVID-19 [1]. Recently, a systematic screening for abs confirmed induction of diverse functional abs in SARS-CoV-2 infection, targeting several immunomodulatory proteins, including cytokines/chemokines and their respective G-protein coupled receptors (GPCR) [1]. Abs against GPCR act as agonistic and allosteric receptor modulators and are linked to chronic inflammatory diseases [2] and, as we recently demonstrated, disease severity in acute COVID-19 [3]