Bedside Hyperspectral Imaging and Organ Dysfunction Severity in Critically Ill COVID-19 Patients-A Prospective, Monocentric Observational Study.

Hyperspectral imaging (HSI) is a non-invasive technology that provides information on biochemical tissue properties, including skin oxygenation and perfusion quality. Microcirculatory alterations are associated with organ dysfunction in septic COVID-19 patients. This prospective observational study investigated associations between skin HSI and organ dysfunction severity in critically ill COVID-19 patients. During the first seven days in the ICU, palmar HSI measurements were carried out with the TIVITA® tissue system. We report data from 52 critically ill COVID-19 patients, of whom 40 required extracorporeal membrane oxygenation (ECMO). HSI parameters for superficial tissue oxygenation (StO2) and oxygenation and perfusion quality (NPI) were persistently decreased. Hemoglobin tissue content (THI) increased, and tissue water content (TWI) was persistently elevated. Regression analysis showed strong indications for an association of NPI and weaker indications for associations of StO2, THI, and TWI with sequential organ failure assessment (SOFA) scoring. StO2 and NPI demonstrated negative associations with vasopressor support and lactate levels as well as positive associations with arterial oxygen saturation. These results suggest that skin HSI provides clinically relevant information, opening new perspectives for microcirculatory monitoring in critical care.

Virtual reality-assisted distraction during transcatheter aortic valve implantation under local anaesthesia: A randomised study.

BACKGROUND: A minimal approach, using local anaesthesia alone, has been advocated to promote faster transcatheter aortic valve replacement (TAVR) procedures in intermediate-risk patients. Pre- and periprocedural anxiety and pain remain a concern. Virtual reality (VR) is a form of non-pharmacological distraction that can potentially modulate pain and anxiety. This randomised study explored whether VR reduces pain and anxiety during TAVR without sedation and compared the effects of VR with those of standard care. METHODS AND RESULTS: Between June 2022 and March 2023, 207 patients underwent transfemoral TAVR (TF-TAVR). Of these, 117 (56.5%) patients were willing to participate in the study and met the educational background and mental status criteria for assessment. Fifty-nine patients underwent TF-TAVR with VR glasses (VR group). Fifty-eight patients underwent standard TF-TAVR without VR (control group; CG). Post-interventional anxiety scores (STAI-S) (31.5 ± 13.4 vs. 38.5 ± 19.2, p = 0.02) and the perceived duration of the procedure (60.1 ± 32.3 vs. 73.0 ± 32.4, p = 0.04) were lower in the VR than in the CG. Procedure time, pain, and anxiety scores (visual analogue scale) were similar between the groups. The complication rate was low and not associated with VR. Post-interventional delirium occurred in nine patients, and was similar between the groups (VR: 4 [6.8%] vs. CG: 5 [8.6%], p = 0.71). No periprocedural strokes were observed. CONCLUSION: VR for TAVR is feasible and safe and expands the non-drug spectrum of therapy for anxiety and pain in patients undergoing TAVR with a minimalistic approach.

Effect of Dexamethasone on the Incidence and Outcome of COVID-19 Associated Pulmonary Aspergillosis (CAPA) in Critically Ill Patients during First- and Second Pandemic Wave-A Single Center Experience.

Superinfections with Aspergillus spp. in patients with Coronavirus disease 2019 (CAPA: COVID-19-associated pulmonary aspergillosis) are increasing. Dexamethasone has shown beneficial effects in critically ill COVID-19 patients. Whether dexamethasone increases the risk of CAPA has not been studied exclusively. Moreover, this retrospective study aimed to identify risk factors for a worse outcome in critically ill COVID-19 patients. Data from 231 critically ill COVID-19 patients with or without dexamethasone treatment from March 2020 and March 2021 were retrospectively analysed. Only 4/169 (6.5%) in the DEXA-group and 13/62 (7.7%) in the Non-DEXA group were diagnosed with probable CAPA (p = 0.749). Accordingly, dexamethasone was not identified as a risk factor for CAPA. Moreover, CAPA was not identified as an independent risk factor for death in multivariable analysis (p = 0.361). In contrast, elevated disease severity (as assessed by Sequential Organ Failure Assessment [SOFA]-score) and the need for organ support (kidney replacement therapy and extracorporeal membrane oxygenation [ECMO]) were significantly associated with a worse outcome. Therefore, COVID-19 treatment with dexamethasone did not increase the risk for CAPA. Moreover, adequately treated CAPA did not represent an independent risk factor for mortality. Accordingly, CAPA might reflect patients' severe disease state instead of directly influencing outcome.

Critically Ill COVID-19 Patients Show Reduced Point of Care-Measured Butyrylcholinesterase Activity-A Prospective, Monocentric Observational Study.

A biomarker for risk stratification and disease severity assessment in SARS-CoV-2 infections has not yet been established. Point of care testing (POCT) of butyrylcholinesterase (BChE) enables early detection of systemic inflammatory responses and correlates with disease severity in sepsis and burns. In acute care or resource-limited settings, POCT facilitates rapid clinical decision making, a particularly beneficial aspect in the management of pandemic situations. In this prospective observational study, POCT-measured BChE activity was assessed in 52 critically ill COVID-19 patients within 24 h of ICU admission and on the third and seventh day after ICU admission. Forty (77%) of these patients required venovenous extracorporeal membrane oxygenation (vvECMO). In critically ill COVID-19 patients, BChE activity is significantly decreased compared with healthy subjects, but also compared with other inflammatory conditions such as sepsis, burns, or trauma. POCT BChE activity reflects the severity of organ dysfunction and allows prediction of 28-day mortality in critically ill COVID-19 patients. Implementing early POCT BChE measurement could facilitate risk stratification and support admission and transfer decisions in resource-limited settings.

Optimization of sepsis therapy based on patient-specific digital precision diagnostics using next generation sequencing (DigiSep-Trial)-study protocol for a randomized, controlled, interventional, open-label, multicenter trial.

BACKGROUND: Sepsis is triggered by an infection and represents one of the greatest challenges of modern intensive care medicine. With regard to a targeted antimicrobial treatment strategy, the earliest possible pathogen detection is of crucial importance. Until now, culture-based detection methods represent the diagnostic gold standard, although they are characterized by numerous limitations. Culture-independent molecular diagnostic procedures represent a promising alternative. In particular, the plasmatic detection of circulating, cell-free DNA by next-generation sequencing (NGS) has shown to be suitable for identifying disease-causing pathogens in patients with bloodstream infections. METHODS: The DigiSep-Trial is a randomized, controlled, interventional, open-label, multicenter trial characterizing the effect of the combination of NGS-based digital precision diagnostics with standard-of-care microbiological analyses compared to solely standard-of-care microbiological analyses in the clinical picture of sepsis/septic shock. Additional anti-infective expert consultations are provided for both study groups. In 410 patients (n = 205 per arm) with sepsis/septic shock, the study examines whether the so-called DOOR-RADAR (Desirability of Outcome Ranking/Response Adjusted for Duration of Antibiotic Risk) score (representing a combined endpoint including the criteria (1) intensive/intermediate care unit length of stay, (2) consumption of antibiotics, (3) mortality, and (4) acute kidney injury (AKI)) can be improved by an additional NGS-based diagnostic concept. We also aim to investigate the cost-effectiveness of this new diagnostic procedure. It is postulated that intensive/intermediate care unit length of stay, mortality rate, incidence of AKI, the duration of antimicrobial therapy as well as the costs caused by complications and outpatient aftercare can be reduced. Moreover, a significant improvement in patient's quality of life is expected. DISCUSSION: The authors´ previous work suggests that NGS-based diagnostics have a higher specificity and sensitivity compared to standard-of-care microbiological analyses for detecting bloodstream infections. In combination with the here presented DigiSep-Trial, this work provides the optimal basis to establish a new NGS-driven concept as part of the national standard based on the best possible evidence. TRIAL REGISTRATIONS: DRKS-ID DRKS00022782 . Registered on August 25, 2020 ClinicalTrials.gov NCT04571801 . Registered October 1, 2020.

Next-generation sequencing diagnostics of bacteremia in pediatric sepsis.

INTRODUCTION: Sepsis and septic shock are the most severe forms of infection affecting predominantly elderly people, preterm and term neonates, and young infants. Even in high-income countries sepsis causes about 8% of admissions to pediatric intensive care units (PICUs). Early diagnosis, rapid anti-infective treatment, and prompt hemodynamic stabilization are crucial for patient survival. In this context, it is essential to identify the causative pathogen as soon as possible to optimize antimicrobial treatment. To date, culture-based diagnostic procedures (e.g., blood cultures) represent the standard of care. However, they have 2 major problems: on the one hand, in the case of very small sample volumes (and thus usually in children), they are not sufficiently sensitive. On the other hand, with a time-to-result of 2 to 5 days, blood cultures need a relatively long time for the anti-infective therapy to be calculated. To overcome these problems, culture-independent molecular diagnostic procedures such as unbiased sequence analysis of circulating cell-free DNA (cfDNA) from plasma samples of septic patients by next-generation sequencing (NGS) have been tested successfully in adult septic patients. However, these results still need to be transferred to the pediatric setting. METHODS: The Next GeneSiPS-Trial is a prospective, observational, non-interventional, multicenter study used to assess the diagnostic performance of an NGS-based approach for the identification of causative pathogens in (preterm and term) neonates (d1-d28, n = 50), infants (d29 to <1 yr, n = 50), and toddlers (1 yr to <5 yr, n = 50) with suspected or proven severe sepsis or septic shock (according to the pediatric sepsis definition) by the use of the quantitative sepsis indicating quantifier (SIQ) score in comparison to standard of care (culture-based) microbiological diagnostics. Potential changes in anti-infective treatment regimens based on these NGS results will be estimated retrospectively by a panel of 3 independent clinical specialists. DISCUSSION: Neonates, infants, and young children are significantly affected by sepsis. Fast and more sensitive diagnostic approaches are urgently needed. This prospective, observational, non-interventional, multicenter study seeks to evaluate an NGS-based approach in critically ill children suffering from sepsis. TRIAL REGISTRATION: DRKS-ID: DRKS00015705 (registered October 24, 2018). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015705.

Characteristics of Critically Ill Patients with COVID-19 Compared to Patients with Influenza-A Single Center Experience.

Infections with SARS-CoV-2 spread worldwide early in 2020. In previous winters, we had been treating patients with seasonal influenza. While creating a larger impact on the health care systems, comparisons regarding the intensive care unit (ICU) courses of both diseases are lacking. We compared patients with influenza and SARS-CoV-2 infections treated at a tertiary care facility offering treatment for acute respiratory distress syndrome (ARDS) and being a high-volume facility for extracorporeal membrane oxygenation (ECMO). Patients with COVID-19 during the first wave of the pandemic (n = 64) were compared to 64 patients with severe influenza from 2016 to 2020 at our ICU. All patients were treated using a standardized protocol. ECMO was used in cases of severe ARDS. Both groups had similar comorbidities. Time in ICU and mortality were not significantly different, yet mortality with ECMO was high amongst COVID-19 patients with approximately two-thirds not surviving. This is in contrast to a mortality of less than 40% in influenza patients with ECMO. Mortality was higher than estimated by SAPSII score on admission in both groups. Patients with COVID-19 were more likely to be male and non-smokers than those with influenza. The outcomes for patients with severe disease were similar. The study helps to understand similarities and differences between patients treated for severe influenza infections and COVID-19.