Targeting the Granulocytic Defense against A. fumigatus in Healthy Volunteers and Septic Patients.

Neutrophil granulocytes (NGs) are among the key players in the defense against Aspergillus fumigatus (A. fumigatus). To better elucidate a pathophysiological understanding of their role and functions, we applied a human cell model using NGs from healthy participants and septic patients to evaluate their inhibitory effects on the growth of A. fumigatus ex vivo. Conidia of A. fumigatus (ATCC® 204305) were co-incubated with NGs from healthy volunteers or septic patients for 16 h. A. fumigatus growth was measured by XTT assays with a plate reader. The inhibitory effect of NGs on 18 healthy volunteers revealed great heterogeneity. Additionally, growth inhibition was significantly stronger in the afternoon than the morning, due to potentially different cortisol levels. It is particularly interesting that the inhibitory effect of NGs was reduced in patients with sepsis compared to healthy controls. In addition, the magnitude of the NG-driven defense against A. fumigatus was highly variable among healthy volunteers. Moreover, daytime and corresponding cortisol levels also seem to have a strong influence. Most interestingly, preliminary experiments with NGs from septic patients point to a strongly diminished granulocytic defense against Aspergillus spp.

Incidence and outcome of invasive candidiasis in intensive care units (ICUs) in Europe: results of the EUCANDICU project.

BACKGROUND: The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe. METHODS: A multinational, multicenter, retrospective study was conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU). RESULTS: During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio [OR] 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis. CONCLUSIONS: The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.

Impact of Invasive Pulmonary Aspergillosis in Critically Ill Surgical Patients with or without Solid Organ Transplantation.

BACKGROUND: Critically ill patients, especially those who have undergone solid organ transplantation (SOT), are at risk of invasive pulmonary aspergillosis (IPA). The outcome relevance of adequately treated putative IPA (pIPA) is a matter of debate. The aim of this study is to assess the outcome relevance of pIPA in a cohort of critically ill patients with and without SOT. METHODS: Data from 121 surgical critically ill patients with pIPA (n = 30) or non-pIPA (n = 91) were included. Cox regression analysis was used to identify risk factors for mortality and unfavourable outcomes after 28 and 90 days. RESULTS: Mortality rates at 28 days were similar across the whole cohort of patients (pIPA: 31% vs. non-pIPA: 27%) and did not differ in the subgroup of patients after SOT (pIPA: 17% vs. non-pIPA: 22%). A higher Sequential Organ Failure Assessment (SOFA) score and evidence of bacteraemia were identified as risk factors for mortality and unfavourable outcome, whereas pIPA itself was not identified as an independent predictor for poor outcomes. CONCLUSIONS: Adequately treated pIPA did not increase the risk of death or an unfavourable outcome in this mixed cohort of critically ill patients with or without SOT, whereas higher disease severity and bacteraemia negatively affected the outcome.

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.

Risk Factors for Intra-Abdominal Candidiasis in Intensive Care Units: Results from EUCANDICU Study.

INTRODUCTION: Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%. Candida spp. may be responsible for up to 10-30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU. METHODS: We performed a case-control study in 26 European ICUs during the period January 2015-December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study. RESULTS: During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65-72.82, p = 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98-21.99, p = 0.002), abdominal drain (OR 6.58; 95% CI 1.73-25.06, p = 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04-17.46, p = 0.04) or antibiotics (OR 3.78; 95% CI 1.32-10.52, p = 0.01) were independently associated with IAC. CONCLUSIONS: Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.

Next-Generation Sequencing-Based Decision Support for Intensivists in Difficult-to-Diagnose Disease States: A Case Report of Invasive Cerebral Aspergillosis.

Aspergillus spp. are widespread environmental pathogens that can induce invasive aspergillosis, especially in immunocompromised patients. An 86-year-old female patient presented with a rare case of invasive cerebral aspergillosis. The aspergilloma invaded the intracranial region originating from the ethmoidal sinus and the orbital apex. In contrast to routine diagnostic procedures, next-generation sequencing (NGS) was able to identify the fungal pathogen in the cerebrospinal fluid as well as in plasma samples, supporting the biopsy-based diagnosis of invasive cerebral aspergillosis. Therefore, NGS-based diagnostics may be of particular importance for difficult-to-diagnose disease states, when conventional diagnostic procedures fail.

Are there risk factors for snowboard injuries? A case-control multicentre study of 559 snowboarders.

OBJECTIVE: To analyse risk factors leading to injuries during snowboarding. DESIGN: A case-control multicentre survey of injured and non-injured snowboarders. SETTING: One tertiary and two secondary trauma centres in Bern, Switzerland. METHODS: All snowboard injuries admitted to our tertiary and two affiliated secondary trauma centres from 1 November 2007 to 15 April 2008 were analysed on the basis of a completed questionnaire incorporating 15 variables. The same questionnaire was applied in non-injured controls at valley stations after a snowboarding day during the same period. A multiple logistic regression was performed (dichotomous variables). Patterns of combined risk factors were calculated by inference trees. RESULTS: 306 patients and 253 controls were interviewed. The following variables were statistically significant for the injured PATIENTS: low readiness for speed (OR 0.20, 95% CI 0.06 to 0.64, p=0.0037), bad weather/visibility (OR 19.06, 95% CI 2.70 to 134.73, p=0.0031) and old snow (OR 0.11, 95% CI 0.02 to 0.68, p=0.0323). Not wearing a helmet and riding on icy slopes emerged as a combination of risk factors associated with injury. CONCLUSIONS: Several risk factors and combinations exist, and different risk profiles were identified. Future research should be aimed at more precise identification of groups at risk and developing specific recommendations for each group-for example, a snow-weather conditions index at valley stations.

Therapy limitation in octogenarians in German intensive care units is associated with a longer length of stay and increased 30 days mortality: A prospective multicenter study.

PURPOSE: The approach to limit therapy in very old intensive care unit patients (VIPs) significantly differs between regions. The focus of this multicenter analysis is to illuminate, whether the Clinical Frailty Scale (CFS) is a suitable tool for risk stratification in VIPs admitted to intensive care units (ICUs) in Germany. Furthermore, this investigation elucidates the impact of therapeutic limitation on the length of stay and mortality in this setting. METHODS: German cohorts' data from two multinational studies (VIP-1, VIP-2) were combined. Univariate and multivariate logistic regression were used to evaluate associations with mortality. RESULTS: 415 acute VIPs were included. Frail VIPs (CFS > 4) were older (85 [IQR 82-88] vs. 83 [IQR 81-86] years p < .001) and suffered from an increased 30-day-mortality (43.4% versus 23.9%, p < .0001). CFS was an independent predictor of 30-day-mortality in a multivariate logistic regression model (aOR 1.23 95%CI 1.04-1.46 p = .02). Patients with any limitation of life-sustaining therapy had a significantly increased 30-day mortality (86% versus 16%, p < .001) and length of stay (144 [IQR 72-293] versus 96 [IQR 47.25-231.5] hours, p = .026). CONCLUSION: In German ICUs, any limitation of life-sustaining therapy in VIPs is associated with a significantly increased ICU length of stay and mortality. CFS reliably predicts the outcome.

Accuracy of prehospital diagnosis and triage of a Swiss helicopter emergency medical service.

BACKGROUND: Helicopter emergency medical services (HEMSs) have become a standard element of modern prehospital emergency medicine. This study determines the percentage of injured HEMS patients whose injuries were correctly recognized by HEMS physicians. METHODS: A retrospective level III evidence prognostic study using data from the largest Swiss HEMS, REGA (Rettungsflugwacht/Guarde Aérienne), on adult patients with trauma transported to a Level I trauma center (January 2006-December 2007). National Advisory Committee on Aeronautics (NACA) scores and the Injury Severity Score (ISS) were assessed to identify severely injured patients. Injured body regions diagnosed by REGA physicians were compared with emergency department discharge diagnoses. RESULTS: Four hundred thirty-three patients were analyzed. Median age was 42.1 years (interquartile range, 25.5-57.9). Three hundred twenty-three (74.6%) were men. Patients were severely injured, with an in-hospital NACA score of 4 or higher in 88.7% of patients and median ISS of 13. REGA physicians correctly recognized injuries to the head in 92.9%, to the femur in 90.5%, and to the tibia/fibula in 83.8% of patients. Injuries to these body regions were overdiagnosed in less than 30%. Abdominal injuries were missed in 56.1%, pelvic injuries in 51.8%, spinal injuries in 40.1%, and chest injuries in 31.2% of patients. CONCLUSION: This study shows that patients are adequately triaged by REGA physicians reflected by a NACA score 4 or higher in 88.7% of patients and a median ISS of 13. However, recognition of injured body regions seems to be challenging in the prehospital setting. Prospective studies on specific training of HEMS physicians for recognition of these injuries (e.g., portable ultrasonography, telemedicine) might help in the future. LEVEL OF EVIDENCE: Prognostic study, level III.

Do alpine skiers and snowboarders wear protective equipment more often after an accident?

QUESTIONS UNDER STUDY/PRINCIPLES: Analysis of changes in the behaviour of wearing protective equipment by alpine skiers and snowboarders after injury, performed at a level I trauma centre in Switzerland. METHODS: We present a study, using a standardised questionnaire, assessing behaviour on ski slopes by adult patients admitted between Oct 2007 and April 2008. Patients were re-interviewed after the 2008/2009 season. McNemar tests were used to analyse differences in protective clothing wearing rates between the two seasons. Multiple logistic regression with age, gender and injury severity score (ISS) as predictors, was used to compare findings in those who started wearing protective equipment and those who did not. RESULTS: A total of 104/132 patients from the 2007/2008 season were questioned about wearing protective equipment in 2008/2009. 20 patients could not be reassessed (7 declined, 13 had abandoned winter sports). A total of 84 patients were reassessed (61 alpine skiers and 23 snowboarders). The median age of participants was 39 years and 70.2% were male. Helmet and back protector wearing rates increased from 40.5% to 78.6% (p <0.001) and from 14.3% to 23.8% (p = 0.021), respectively. Snowboarders more than doubled their helmet wearing rate (39.1% to 82.6%, p = 0.002). Skiers showed a trend towards doubling their back protector wearing rate (6.6% to 14.8%, p = 0.063). Younger skiers started wearing back protectors more often than older skiers. CONCLUSIONS: Sustained injury might provide skiers and snowboards with a potent trigger to change their attitude towards the use of protective equipment. The psychological processes influencing the use of protective equipment require further investigation.