Inter-organ cross-talk in human cancer cachexia revealed by spatial metabolomics.

BACKGROUND: Cancer cachexia (CCx) presents a multifaceted challenge characterized by negative protein and energy balance and systemic inflammatory response activation. While previous CCx studies predominantly focused on mouse models or human body fluids, there's an unmet need to elucidate the molecular inter-organ cross-talk underlying the pathophysiology of human CCx. METHODS: Spatial metabolomics were conducted on liver, skeletal muscle, subcutaneous and visceral adipose tissue, and serum from cachectic and control cancer patients. Organ-wise comparisons were performed using component, pathway enrichment and correlation network analyses. Inter-organ correlations in CCx altered pathways were assessed using Circos. Machine learning on tissues and serum established classifiers as potential diagnostic biomarkers for CCx. RESULTS: Distinct metabolic pathway alteration was detected in CCx, with adipose tissues and liver displaying the most significant (P ≤ 0.05) metabolic disturbances. CCx patients exhibited increased metabolic activity in visceral and subcutaneous adipose tissues and liver, contrasting with decreased activity in muscle and serum compared to control patients. Carbohydrate, lipid, amino acid, and vitamin metabolism emerged as highly interacting pathways across different organ systems in CCx. Muscle tissue showed decreased (P ≤ 0.001) energy charge in CCx patients, while liver and adipose tissues displayed increased energy charge (P ≤ 0.001). We stratified CCx patients by severity and metabolic changes, finding that visceral adipose tissue is most affected, especially in cases of severe cachexia. Morphometric analysis showed smaller (P ≤ 0.05) adipocyte size in visceral adipose tissue, indicating catabolic processes. We developed tissue-based classifiers for cancer cachexia specific to individual organs, facilitating the transfer of patient serum as minimally invasive diagnostic markers of CCx in the constitution of the organs. CONCLUSIONS: These findings support the concept of CCx as a multi-organ syndrome with diverse metabolic alterations, providing insights into the pathophysiology and organ cross-talk of human CCx. This study pioneers spatial metabolomics for CCx, demonstrating the feasibility of distinguishing cachexia status at the organ level using serum.

A custom tailored, evidence-based, theory-informed intervention for healthcare professionals to prevent burnout (LAGOM): study protocol for a pragmatic randomized controlled trial.

BACKGROUND: Healthcare professionals in hospitals are exposed to a high level of professional stress, time pressure, workload, and often times poor organizational support. This makes them especially susceptible to burnout. In this pragmatic randomized controlled trial, we test the hypothesis that participation in a 9-week program (LAGOM) that was designed in close collaboration with healthcare professionals, incorporating both individual and organizational aspects reduces emotional exhaustion in healthcare professionals (primary outcome). METHODS: Eighty four nurses and physicians working at the Charité - Universitätsmedizin Berlin and the Immanuel Hospital Berlin are automatically randomized to the LAGOM program (n = 42) or to usual care (n = 42) in a one-to-one allocation rate. The primary outcome emotional exhaustion is measured by the Maslach Burnout Inventory-Human Services Survey at baseline, post-intervention, and 1-month follow-up via an online survey. Secondary outcomes include depersonalization, personal accomplishment, subjective stress, mental well-being, self-care, self-efficacy, working conditions, mindfulness, and adverse events. Electrophysiological measures for heart rate variation analysis are captured. The PRECIS-2 tool is used to characterize the degree of pragmatism in our trial. Data analysis and primary intention-to-treat analysis using repeated measures analysis of variance are performed blind to intervention allocation. Per-protocol, subgroup, and secondary outcome analyses are conducted exploratively. An advisory board consisting of various stakeholders accompanies the study process. DISCUSSION: If LAGOM proves to be effective in reducing symptoms of burnout, the program could make an important contribution to tackling the problem of the very high burnout rates among healthcare professionals and become an integral part of preventive services offered by hospitals. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00034060. Registered 31 May 2024.

Cost Analysis of a Hand Hygiene Improvement Strategy in Long-Term Care Facilities.

OBJECTIVES: To evaluate whether the costs of a successful tailored multifaceted strategy to improve hand hygiene compliance outweighed the savings by reducing infection costs in Dutch long-term care facilities (LTCFs). DESIGN: A retrospective cost analysis alongside a stepped-wedge cluster-randomized controlled trial. SETTING AND PARTICIPANTS: The study included 14 LTCFs (23 wards) in the Netherlands. METHODS: The cost analysis was based on the costs of the intervention vs the savings from avoided infections and associated treatment costs. Infection-related costs of the "usual-care" period were compared with the combined infection-related costs and intervention costs from the "intervention" period and the costs in the "post-intervention period." Multilevel analyses, with a linear model with periods as fixed effects, random effects for cluster LTCFs, and fixed effects for each step, were completed. RESULTS: There are no significant differences in total costs considering the 3 periods. When adjusting for time and clustering, the mean infection-related costs per week per LTCF for all the infections combined were highest during "usual-care" before the hand hygiene intervention was performed, namely 680 euros per week. Assuming the effect of the improvement strategy would be present for 12 months, the costs per week in the "intervention" and "post-intervention" periods were 627 euros (95% CI, 383-871) and 731 euros (95% CI, 508-954), respectively. Assuming the effect of the improvement strategy will last longer than 1 year (ie, 18 and 24 months), the average cost for the "intervention period" and the "post-intervention" period decreased to 615 euros and 719 euros during the intervention and 609 euros and 715 euros after the intervention, respectively. CONCLUSIONS AND IMPLICATIONS: Our multifaceted hand hygiene improvement strategy achieves cost savings. The results of our study are the first of an economic analysis of a hand hygiene improvement strategy in LTCFs. The results need to be confirmed by further economic evaluations.

The complete genome sequence of unculturable Mycoplasma faucium obtained through clinical metagenomic next-generation sequencing.

Introduction: Diagnosing Mycoplasma faucium poses challenges, and it's unclear if its rare isolation is due to infrequent occurrence or its fastidious nutritional requirements. Methods: This study analyzes the complete genome sequence of M. faucium, obtained directly from the pus of a sternum infection in a lung transplant patient using metagenomic sequencing. Results: Genome analysis revealed limited therapeutic options for the M. faucium infection, primarily susceptibility to tetracyclines. Three classes of mobile genetic elements were identified: two new insertion sequences, a new prophage (phiUMCG-1), and a species-specific variant of a mycoplasma integrative and conjugative element (MICE). Additionally, a Type I Restriction-Modification system was identified, featuring 5'-terminally truncated hsdS pseudogenes with overlapping repeats, indicating the potential for forming alternative hsdS variants through recombination. Conclusion: This study represents the first-ever acquisition of a complete circularized bacterial genome directly from a patient sample obtained from invasive infection of a primary sterile site using culture-independent, PCR-free clinical metagenomics.

Molecular epidemiology of a Parainfluenza Type 3 virus outbreak: Informing infection control measures on adult hematology wards.

OBJECTIVES: Parainfluenza virus type 3 (PIV3) outbreaks among hematology patients are associated with high morbidity and mortality. Prompt implementation of infection prevention (IP) measures has proven to be the most efficacious approach for controlling PIV3 outbreaks within this patient population. The most suitable IP measures can vary depending on the mode of virus transmission, which remains unidentified in most outbreaks. We describe the molecular epidemiology of an outbreak of PIV3 among hematology patients and the development of a new method that allows for the differentiation of outbreak and community strains, from which a closed outbreak could be inferred. METHODS: Patients were screened for respiratory viruses using multiplex-PCR. PIV3 positive samples with a cycle threshold (Ct)-value of <31 underwent a retrospective characterization via an in-house developed sequence analysis of the hemagglutinin-neuraminidase (HN) gene. RESULTS: Between July and September 2022, 31 hematology patients were identified with PIV3. Although infection control measures were implemented, the outbreak persisted for nine weeks. Sequencing the HN gene of 27 PIV3 strains from 27 patients revealed that all outbreak strains formed a distinct cluster separate from the control strains, suggestive of a nosocomial transmission route. CONCLUSIONS: Sequencing the HN gene of PIV3 strains in an outbreak setting enables outbreak strains to be distinguished from community strains. Early molecular characterization of PIV3 strains during an outbreak can serve as a tool in determining potential transmission routes. This, in turn, enables rapid implementation of targeted infection prevention measures, with the goal of minimizing the outbreak's duration and reducing associated morbidity and mortality.

The illusory certainty: Information repetition and impressions of truth enhance subjective confidence in validity judgments independently of the factual truth.

People not only judge repeatedly perceived information as more likely being true (the so-called truth effect) they also tend to be more confident after judging the validity of repeated information. These phenomena are assumed to be caused by a higher subjective feeling of ease (i.e., fluency) when processing repeated (vs. new) information. Based on the suggestion that a higher number of coherent mental activations is promoting a fluency experience, we argue that besides repetition an already existing information network, that is (nonspecific) prior knowledge, can enhance fluency. Following this argumentation, information repetition as well as the act of judging incoming information as being true (vs. false) should feed into subjective confidence - independently of the factual truth (when judging under uncertainty). To test this, we reanalyzed two published data sets and conducted a new study. In total, participants (N = 247) gave 29,490 truth judgments and corresponding ratings of subjective confidence while attending two judgement phases (i.e., 10 min and 1 week after the exposure phase in each experiment). Results showed that (a) repetition (in 3 of 3 data sets) and (b) impressions of truth (in 2 of 3 data sets) were systematically related to higher subjective confidence. Moreover, we found (c) a significant positive interaction between repetition and impressions of truth after both intervals in all data sets. Our analyses further underline the moderating effect of time: Influences of repetition significantly decreased with increasing time interval. Notably, the factual truth did not systematically affect any of the above reported effects.

Uncovering the spread of drug-resistant bacteria through next-generation sequencing based surveillance: transmission of extended-spectrum ß-lactamase-producing Enterobacterales by a contaminated duodenoscope.

Contamination of duodenoscopes is a significant concern due to the transmission of multidrug-resistant organisms (MDROs) among patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), resulting in outbreaks worldwide. In July 2020, it was determined that three different patients, all had undergone ERCP with the same duodenoscope, were infected. Two patients were infected with blaCTX-M-15 encoding Citrobacter freundii, one experiencing a bloodstream infection and the other a urinary tract infection, while another patient had a bloodstream infection caused by blaSHV-12 encoding Klebsiella pneumoniae. Molecular characterization of isolates was available as every ESBL-producing isolate undergoes Next-Generation Sequencing (NGS) for comprehensive genomic analysis in our center. After withdrawing the suspected duodenoscope, we initiated comprehensive epidemiological research, encompassing case investigations, along with a thorough duodenoscope investigation. Screening of patients who had undergone ERCP with the implicated duodenoscope, as well as a selection of hospitalized patients who had ERCP with a different duodenoscope during the outbreak period, led to the discovery of three additional cases of colonization in addition to the three infections initially detected. No microorganisms were detected in eight routine culture samples retrieved from the suspected duodenoscope. Only after destructive dismantling of the duodenoscope, the forceps elevator was found to be positive for blaSHV-12 encoding K. pneumoniae which was identical to the isolates detected in three patients. This study highlights the importance of using NGS to monitor the transmission of MDROs and demonstrates that standard cultures may fail to detect contaminated medical equipment such as duodenoscopes.

Anconeus-sparing minimally invasive approach for lateral ulnar collateral ligament reconstruction using a triceps tendon autograft is an effective and safe treatment for chronic posterolateral instability of the elbow.

BACKGROUND: Surgical treatment helps to restore stability of the elbow in patients with posterolateral rotatory instability (PLRI). The anconeus muscle is one of the most important active stabilizers against PLRI. A minimally invasive anconeus-sparing approach for lateral ulnar collateral ligament (LUCL) reconstruction using a triceps tendon autograft has been previously described. The purpose of this study was to evaluate the outcome of this intervention and identify risk factors that influenced the clinical and patient-reported outcomes. METHODS: Sixty-one patients with chronic PLRI and no previous elbow surgery who underwent surgical reconstruction of the LUCL using a triceps tendon autograft in a minimally invasive anconeus-sparing approach during 2012 and 2018 were evaluated. Outcome measures included a clinical examination and the Oxford Elbow Score (OES) and the Mayo Elbow Performance Score (MEPS) questionnaires. Subjective patient outcomes were evaluated with the visual analog scale (VAS) for pain and the Subjective Elbow Value (SEV). Integrity of the common extensor tendons and centering of the radial head were assessed preoperatively on standardized magnetic resonance images (MRIs). RESULTS: Fifty-two patients were available at final follow-up. The mean age of patients was 51 ± 12 years with a mean follow-up of 53 ± 14 months (range 20-76). Clinical examination after surgery (n = 41) showed no clinical signs of instability in 98% of the patients (P < .001) and a nonsignificant improvement in range of motion. OES, MEPS, and VAS scores averaged 40 ± 10 of 48 points, 92 ± 12 of 100 points, and 1 ± 2 points, respectively, all corresponding with good or excellent outcomes. The SEV was 88%, indicating very high satisfaction with the surgery. Only 1 patient had revision surgery due to pain, and there were no reported postoperative complications in this cohort. A radial head subluxation in the MRI correlated significantly with worse postoperative outcomes. CONCLUSIONS: The anconeus-sparing minimally invasive technique for posterolateral stabilization of the elbow using a triceps tendon autograft is an effective and safe treatment for chronic posterolateral instability of the elbow with substantial improvements in elbow function and pain relief with a very low rate of persistent clinical instability.

Effect and Process Evaluation of an Intervention to Improve Hand Hygiene Compliance in Long-Term Care Facilities.

OBJECTIVES: This study evaluated the effect of a tailored, multifaceted improvement strategy on hand hygiene compliance in long-term care facilities (LTCFs). We also performed a process evaluation to explore the mechanisms through which our strategy brought about change. DESIGN: We conducted a stepped-wedge cluster-randomized controlled trial with a sequential rollout of the improvement strategy to all participating LTCFs. The strategy consisted of education, training, reminders, observation sessions (including feedback), and team meetings (including feedback). SETTING AND PARTICIPANTS: The study included nursing professionals from 14 LTCFs (23 wards) in the Netherlands. METHODS: Hand hygiene compliance was observed during 5 measurement periods using WHO's "Five Moments for Hand Hygiene." Multilevel analyses and corresponding tests were completed on an intention-to-treat basis. RESULTS: The absolute intervention effect of overall hand hygiene compliance (primary outcome measure) was 13% (95% CI 9.3-16.7, P < .001), adjusted for time and clustering. The adjusted absolute effect was 23% (95% CI 7-39, P < .002) before a clean and aseptic procedure, 18% (95% CI 10-26, P < .001) after touching a resident, 14% (95% CI 7-22, P < .003) before touching a resident, 10% (95% CI 5-15, P < .001) after contact with body fluid, and 1% (95% CI -11 to 13, P = .8) after touching a resident's surroundings. With the exception of leadership, participants at LTCFs with more exposure to the intervention components showed statistically significantly more improvement than those at facilities with lower exposure scores. CONCLUSIONS AND IMPLICATIONS: Our strategy was successful in improving hand hygiene compliance. LTCFs with more team members exposed to the different intervention components, demonstrated a greater effect from the intervention. To strengthen the impact of our intervention, we recommend that future improvement strategies provide more support to managers to ensure they are better equipped to take on their leadership roles and enable their teams to improve and maintain hand hygiene compliance.

A practice guide on antimicrobial stewardship in nursing homes.

A practice guide to help nursing homes set up an antimicrobial stewardship (AMS) program was developed based on experiences gained during a project at one of the largest providers of elderly care in the South-east of the Netherlands. The guideline for the implementation of AMS in Dutch hospitals served as a starting point and were tailored to the unique characteristics of a nursing home setting. This practice guide offers recommendations and practical tools while emphasizing the importance of establishing a multidisciplinary approach to oversee AMS efforts. The recommendations and practical tools address various elements of AMS, including the basic conditions to initiate an AMS program and a comprehensive approach to embed an AMS program. This approach involves educating nurses and caregivers, informing volunteers and residents/their representatives, and the activities of an antibiotic team (A-team). The practice guide also highlights a feasible work process for the A-team. This process aims to achieve a culture of continuous learning and improvement that can enhance the overall quality of antibiotic prescribing rather than making individual adjustments to client prescriptions. Overall, this practice guide aims to help nursing homes establish an AMS program through collaborative efforts between involved physicians, pharmacists, clinical microbiologists, and infection control practitioners. The involved physician plays a crucial role in instilling a sense of urgency and developing a stepwise strategy.

Seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Dutch hospitals after the 2020 first wave: a multicentre cross-sectional study with prospective follow-up.

BACKGROUND: We aimed to estimate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seroprevalence and describe its determinants and associated symptoms among unvaccinated healthcare workers (HCWs) after the first wave of the pandemic. METHODS: HCWs from 13 Dutch hospitals were screened for antibodies against the spike protein of SARS-CoV-2 in June-July 2020 and after three months. Participants completed a retrospective questionnaire on determinants for occupational and community exposure to SARS-CoV-2 and symptoms suggestive of COVID-19 experienced since January 2020. The seroprevalence was calculated per baseline characteristic and symptom at baseline and after follow-up. Adjusted odds ratios (aOR) for seropositivity were determined using logistic regression. RESULTS: Among 2328 HCWs, 323 (13.9%) were seropositive at enrolment, 49 of whom (15%) reported no previous symptoms suggestive of COVID-19. During follow-up, only 1% of the tested participants seroconverted. Seroprevalence was higher in younger HCWs compared to the mid-age category (aOR 1.53, 95% CI 1.07-2.18). Nurses (aOR 2.21, 95% CI 1.34-3.64) and administrative staff (aOR 1.87, 95% CI 1.02-3.43) had a higher seroprevalence than physicians. The highest seroprevalence was observed in HCWs in the emergency department (ED) (aOR 1.79, 95% CI 1.10-2.91), the lowest in HCWs in the intensive, high, or medium care units (aOR 0.47, 95% CI 0.31-0.71). Chronic respiratory disease, smoking, and having a dog were independently associated with a lower seroprevalence, while HCWs with diabetes mellitus had a higher seroprevalence. In a multivariable model containing all self-reported symptoms since January 2020, altered smell and taste, fever, general malaise/fatigue, and muscle aches were positively associated with developing antibodies, while sore throat and chills were negatively associated. CONCLUSIONS: The SARS-CoV-2 seroprevalence in unvaccinated HCWs of 13 Dutch hospitals was 14% in June-July 2020 and remained stable after three months. A higher seroprevalence was observed in the ED and among nurses, administrative and young staff, and those with diabetes mellitus, while a lower seroprevalence was found in HCWs in intensive, high, or medium care, and those with self-reported lung disease, smokers, and dog owners. A history of altered smell or taste, fever, muscle aches and fatigue were independently associated with the presence of SARS-CoV-2 antibodies in unvaccinated HCWs.

Environmental monitoring for filamentous fungal pathogens in hematopoietic cell transplant units.

The incidence of invasive fungal disease (IFD) is on the rise due to increasing numbers of highly immunocompromized patients. Nosocomial IFD remains common despite our better understanding of its risk factors and pathophysiology. High-efficiency particulate air filtration with or without laminar air flow, frequent air exchanges, a positive pressure care environment, and environmental hygiene, amongst other measures, have been shown to reduce the mould burden in the patient environment. Environmental monitoring for moulds in areas where high-risk patients are cared for, such as hematopoietic cell transplant units, has been considered an adjunct to other routine environmental precautions. As a collaborative effort between authors affiliated to the Infection Prevention and Control Working Group and the Fungal Infection Working Group of the International Society of Antimicrobial Chemotherapy (ISAC), we reviewed the English language literature and international guidance to describe the evidence behind the need for environmental monitoring for filamentous fungi as a quality assurance approach with an emphasis on required additional precautions during periods of construction. Many different clinical sampling approaches have been described for air, water, and surface sampling with significant variation in laboratory methodologies between reports. Importantly, there are no agreed-upon thresholds that correlate with an increase in the clinical risk of mould infections. We highlight important areas for future research to assure a safe environment for highly immunocompromized patients.

Mould infections have a high mortality in high-risk patients. Ventilation engineering significantly reduces the risk of acquiring such infections. Environmental sampling for moulds is carried out in many centers in addition to standard precautions. We review the literature on this subject.

Review on infection control strategies to minimize outbreaks of the emerging pathogen Elizabethkingia anophelis.

BACKGROUND: Elizabethkingia anophelis is a multi-drug resistant emerging opportunistic pathogen with a high mortality rate, causing healthcare-associated outbreaks worldwide. METHODS: We report a case of E. anophelis pleuritis, resulting from transmission through lung transplantation, followed by a literature review of outbreak reports and strategies to minimize E. anophelis transmission in healthcare settings. RESULTS: From 1990 to August 2022, 14 confirmed E. anophelis outbreak cohorts and 21 cohorts with suspected E. anophelis outbreaks were reported in literature. A total of 80 scientific reports with recommendations on diagnostics and infection control measures were included and summarized in our study. CONCLUSION: Strategies to prevent and reduce spread of E. anophelis include water-free patient rooms, adequate hygiene and disinfection practices, and optimized diagnostic techniques for screening, identification and molecular typing.

The Seven-parameter Diffusion Model: an Implementation in Stan for Bayesian Analyses.

Diffusion models have been widely used to obtain information about cognitive processes from the analysis of responses and response-time data in two-alternative forced-choice tasks. We present an implementation of the seven-parameter diffusion model, incorporating inter-trial variabilities in drift rate, non-decision time, and relative starting point, in the probabilistic programming language Stan. Stan is a free, open-source software that gives the user much flexibility in defining model properties such as the choice of priors and the model structure in a Bayesian framework. We explain the implementation of the new function and how it is used in Stan. We then evaluate its performance in a simulation study that addresses both parameter recovery and simulation-based calibration. The recovery study shows generally good recovery of the model parameters in line with previous findings. The simulation-based calibration study validates the Bayesian algorithm as implemented in Stan.

Vancomycin-resistant enterococci (VRE) in hospital settings across European borders: a scoping review comparing the epidemiology in the Netherlands and Germany.

The rising prevalence of vancomycin-resistant enterococci (VRE) is a matter of concern in hospital settings across Europe without a distinct geographical pattern. In this scoping review, we compared the epidemiology of vancomycin-resistant Enterococcus spp. in hospitals in the Netherlands and Germany, between 1991 and 2022. We searched PubMed and summarized the national antibiotic resistance surveillance data of the two countries. We included 46 studies and summarized national surveillance data from the NethMap in the Netherlands, the National Antimicrobial Resistance Surveillance database in Germany, and the EARS-Net data. In total, 12 studies were conducted in hospitals in the Netherlands, 32 were conducted in German hospitals, and an additional two studies were conducted in a cross-border setting. The most significant difference between the two countries was that studies in Germany showed an increasing trend in the prevalence of VRE in hospitals, and no such trend was observed in studies in the Netherlands. Furthermore, in both Dutch and German hospitals, it has been revealed that the molecular epidemiology of VREfm has shifted from a predominance of vanA towards vanB over the years. According to national surveillance reports, vancomycin resistance in Enterococcus faecium clinical isolates fluctuates below 1% in Dutch hospitals, whereas it follows an increasing trend in German hospitals (above 20%), as supported by individual studies. This review demonstrates that VRE is more frequently encountered in German than in Dutch hospitals and discusses the underlying factors for the difference in VRE occurrence in these two neighboring countries by comparing differences in healthcare systems, infection prevention control (IPC) guidelines, and antibiotic use in the Netherlands and Germany.

Surface water in Lower Saxony: A reservoir for multidrug-resistant Enterobacterales.

The emergence of extended-spectrum ß-lactamase and carbapenemase-producing Enterobacterales (ESBL-E and CPE, respectively) is a threat to modern medicine, as infections become increasingly difficult to treat. These bacteria have been detected in aquatic environments, which raises concerns about the potential spread of antibiotic resistance through water. Therefore, we investigated the occurrence of ESBL-E and CPE in surface water in Lower Saxony, Germany, using phenotypic and genotypic methods. Water samples were collected from two rivers, five water canals near farms, and 18 swimming lakes. ESBL-E and CPE were isolated from these samples using filters and selective agars. All isolates were analyzed by whole genome sequencing. Multidrug-resistant Enterobacterales were detected in 4/25 (16%) water bodies, including 1/2 rivers, 2/5 water canals and 1/18 lakes. Among all samples, isolates belonging to five different species/species complexes were detected: Escherichia coli (n = 10), Enterobacter cloacae complex (n = 4), Citrobacter freundii (n = 3), Citrobacter braakii (n = 2), and Klebsiella pneumoniae (n = 2). Of the 21 isolates, 13 (62%) were resistant at least to 3rd generation cephalosporins and eight (38%) additionally to carbapenems. CPE isolates harbored blaKPC-2 (n = 5), blaKPC-2 and blaVIM-1 (n = 2), or blaOXA-181 (n = 1); additionally, mcr-9 was detected in one isolate. Two out of eight CPE isolates were resistant to cefiderocol and two to colistin. Resistance to 3rd generation cephalosporins was mediated by ESBL (n = 10) or AmpC (n = 3). The presence of AmpC-producing Enterobacterales, ESBL-E and CPE in northern German surface water samples is alarming and highlights the importance of aquatic environments as a potential source of MDR bacteria.

Baroreflex activity through the analysis of the cardio-respiratory variability influence over blood pressure in cardiomyopathy patients.

A large portion of the elderly population are affected by cardiovascular diseases. Early prognosis of cardiomyopathies remains a challenge. The aim of this study was to classify cardiomyopathy patients by their etiology based on significant indexes extracted from the characterization of the baroreflex mechanism in function of the influence of the cardio-respiratory activity over the blood pressure. Forty-one cardiomyopathy patients (CMP) classified as ischemic (ICM-24 patients) and dilated (DCM-17 patients) were considered. In addition, thirty-nine control (CON) subjects were used as reference. The beat-to-beat (BBI) time series, from the electrocardiographic (ECG) signal, the systolic (SBP), and diastolic (DBP) time series, from the blood pressure signal (BP), and the respiratory time (TT), from the respiratory flow (RF) signal, were extracted. The three-dimensional representation of the cardiorespiratory and vascular activities was characterized geometrically, by fitting a polygon that contains 95% of data, and by statistical descriptive indices. DCM patients presented specific patterns in the respiratory response to decreasing blood pressure activity. ICM patients presented more stable cardiorespiratory activity in comparison with DCM patients. In general, CMP shown limited ability to regulate changes in blood pressure. In addition, patients also shown a limited ability of their cardiac and respiratory systems response to regulate incremental changes of the vascular variability and a lower heart rate variability. The best classifiers were used to build support vector machine models. The optimal model to classify ICM versus DCM patients achieved 92.7% accuracy, 94.1% sensitivity, and 91.7% specificity. When comparing CMP patients and CON subjects, the best model achieved 86.2% accuracy, 82.9% sensitivity, and 89.7% specificity. When comparing ICM patients and CON subjects, the best model achieved 88.9% accuracy, 87.5% sensitivity, and 89.7% specificity. When comparing DCM patients and CON subjects, the best model achieved 87.5% accuracy, 76.5% sensitivity, and 92.3% specificity. In conclusion, this study introduced a new method for the classification of patients by their etiology based on new indices from the analysis of the baroreflex mechanism.