Validating genetic variants in innate immunity linked to infectious events in acute myeloid leukemia post-induction chemotherapy.

Infectious events, such as sepsis and invasive fungal disease (IFD), pose significant risks in patients with acute myeloid leukemia (AML). Previous studies, including our own, have suggested a potential role of single nucleotide polymorphisms (SNPs) within the innate immune system in influencing individual infection susceptibility. However, many of these associations lack validation in independent cohorts. This study sought to validate the impact of 11 candidate SNPs across 6 genes (TLR2, TLR4, Dectin-1, DC-SIGN, PTX3, L-Ficolin) in an independent cohort of patients. Two cohorts with newly diagnosed AML patients receiving intensive induction chemotherapy were analyzed: a stratification cohort comprising 186 patients and a validation cohort consisting of 138 patients. Multiple SNPs in each cohort were found to be associated to infectious complications, notably the DC-SIGN SNP rs4804800 demonstrated a significant association with sepsis in both cohorts. SNPs within the PTX3 and Dectin-1 genes were linked to IFD development in one cohort each. This study represents the first validation study of candidate genes associated with infectious events in AML patients after intensive induction chemotherapy. Identifying genetic predispositions to infections could significantly impact the management of antimicrobial prophylaxis and treatment in AML patients.

[INTERPOLAR-prospective, interventional studies as part of the Medical Informatics Initiative to improve medication therapy safety in healthcare]. / INTERPOLAR ­ prospektive, interventionelle Studien im Rahmen der Medizininformatik-Initiative zur Verbesserung der Arzneimitteltherapiesicherheit in der Krankenversorgung.

Medication analyses by ward pharmacists are an important measure of drug therapy safety (DTS). Medication-related problems (MRPs) are identified and resolved with the attending clinicians. However, staff resources for extended medication analyses and complete documentation are often limited. Until now, data required for the identification of risk patients and for an extended medication analysis often had to be collected from various parts of the institution's internal electronic medical record (EMR). This error-prone and time-consuming process is to be improved in the INTERPOLAR (INTERventional POLypharmacy-Drug interActions-Risks) project using an IT tool provided by the data integration centers (DIC).INTERPOLAR is a use case of the Medical Informatics Initiative (MII) that focuses on the topic of DTS. The planning phase took place in 2023, with routine implementation planned from 2024. DTS-relevant data from the EMR is to be presented and the documentation of MRPs in routine care is to be facilitated. The prospective multicenter, cluster-randomized INTERPOLAR­1 study serves to evaluate the benefits of IT support in routine care. The aim is to show that more MRPs can be detected and resolved with the help of IT support. For this purpose, six normal wards will be selected at each of eight university hospitals, so that 48 clusters (with a total of at least 70,000 cases) are available for randomization.

[Automated surveillance and risk prediction with the aim of risk-stratified infection control and prevention (RISK PRINCIPE)]. / Automatisierte Surveillance und Risikovorhersage mit dem Ziel einer risikostratifizierten Infektionskontrolle und -prävention (RISK Prediction for Risk-stratified Infection Control and Prevention).

Healthcare-associated infections (HCAIs) represent an enormous burden for patients, healthcare workers, relatives and society worldwide, including Germany. The central tasks of infection prevention are recording and evaluating infections with the aim of identifying prevention potential and risk factors, taking appropriate measures and finally evaluating them. From an infection prevention perspective, it would be of great value if (i) the recording of infection cases was automated and (ii) if it were possible to identify particularly vulnerable patients and patient groups in advance, who would benefit from specific and/or additional interventions.To achieve this risk-adapted, individualized infection prevention, the RISK PRINCIPE research project develops algorithms and computer-based applications based on standardised, large datasets and incorporates expertise in the field of infection prevention.The project has two objectives: a) to develop and validate a semi-automated surveillance system for hospital-acquired bloodstream infections, prototypically for HCAI, and b) to use comprehensive patient data from different sources to create an individual or group-specific infection risk profile.RISK PRINCIPE is based on bringing together the expertise of medical informatics and infection medicine with a focus on hygiene and draws on information and experience from two consortia (HiGHmed and SMITH) of the German Medical Informatics Initiative (MII), which have been working on use cases in infection medicine for more than five years.

Persistent neurocognitive deficits in cognitively impaired survivors of sepsis are explained by reductions in working memory capacity.

Introduction: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Mounting evidence suggests that many cognitively impaired sepsis survivors show long-term neurocognitive deficits in neuropsychological tasks. To date, the underlying mechanisms of these deficits are insufficiently understood. Based on previous evaluations we hypothesized that visual attention and working memory may be affected in a sample of cognitively impaired sepsis survivors. Methods: We utilized psychophysical whole-and partial-report paradigms based on the computational theory of visual attention (TVA) to determine (i) whether sepsis survivors show changes in basic parameters of visual attention and working memory, (ii) whether the affected parameters are related to neuropsychological test results in a standard battery in sepsis survivors and matched healthy control participants, (iii) whether between-group differences in these basic parameters of visual attention could account for underperformance of sepsis survivors in neuropsychological tests when adjusting for potentially relevant clinical variables. Results: We showed that, in sepsis survivors, the maximum number of elements consciously maintained in an instant, i.e. the working memory storage capacity K, is reduced (sepsis survivors: M = 3.0; healthy controls: M = 3.4). Moreover, K explained variance in neurocognitive outcomes -17% in attentional and 16 % in executive functions - in a standard neuropsychological battery. The association remained stable when adjusting for clinical variables. Discussion: Thus, in our sample of cognitively impaired sepsis survivors, a reduction in working memory capacity seems to be a critical determinant of the neurocognitive sequelae. It should be the subject of future work on mechanisms but may also serve as surrogate outcome measure in interventional studies.