Herpes Simplex Virus Bronchopneumonitis in Critically Ill Patients with Acute on Chronic Liver Failure: A Retrospective Analysis.

(1) Background: Critically ill patients are frequently diagnosed with pulmonary Herpes simplex virus-1 (HSV) reactivation, which then can lead to HSV bronchopneumonitis and is associated with higher mortality and longer mechanical ventilation. For the particular subgroup of critically ill patients with acute on chronic liver failure (ACLF), however, the impact of HSV reactivation is unknown. We investigated the impact of HSV reactivation in these patients. (2) Methods: We conducted a retrospective analysis, evaluating data from 136 mechanically ventilated patients with ACLF between January 2016 and August 2023. Clinical parameters were compared between patients with and without HSV bronchopneumonitis. (3) Results: 10.3% were diagnosed with HSV bronchopneumonitis (HSV group). Mortality did not differ between the HSV and non-HSV group (85.7% vs. 75.4%, p = 0.52). However, the clinical course in the HSV group was more complicated as patients required significantly longer mechanical ventilation (14 vs. 21 days, p = 0.04). Furthermore, fungal superinfections were significantly more frequent in the HSV group (28.6% vs. 6.6%, p = 0.006). (4) Conclusions: Mortality of critically ill patients with ACLF with HSV bronchopneumonitis was not increased in spite of the cirrhosis-associated immune dysfunction. Their clinical course, however, was more complicated with significantly longer mechanical ventilation.

Postmortem Minimally Invasive Autopsy in Critically Ill COVID-19 Patients at the Bedside: A Proof-of-Concept Study at the ICU.

BACKGROUND: Economic restrictions and workforce cuts have continually challenged conventional autopsies. Recently, the COVID-19 pandemic has added tissue quality and safety requirements to the investigation of this disease, thereby launching efforts to upgrade autopsy strategies. METHODS: In this proof-of-concept study, we performed bedside ultrasound-guided minimally invasive autopsy (US-MIA) in the ICU of critically ill COVID-19 patients using a structured protocol to obtain non-autolyzed tissue. Biopsies were assessed for their quality (vitality) and length of biopsy (mm) and for diagnosis. The efficiency of the procedure was monitored in five cases by recording the time of each step and safety issues by swabbing personal protective equipment and devices for viral contamination. FINDINGS: Ultrasound examination and tissue procurement required a mean time period of 13 min and 54 min, respectively. A total of 318 multiorgan biopsies were obtained from five patients. Quality and vitality standards were fulfilled, which not only allowed for specific histopathological diagnosis but also the reliable detection of SARS-CoV-2 virions in unexpected organs using electronic microscopy and RNA-expressing techniques. INTERPRETATION: Bedside multidisciplinary US-MIA allows for the fast and efficient acquisition of autolytic-free tissue and offers unappreciated potential to overcome the limitations of research in postmortem studies.

Systematic Evaluation of Clinical, Nutritional, and Fecal Microbial Factors for Their Association With Colorectal Polyps.

INTRODUCTION: The identification of risk factors for precursor lesions of colorectal cancer (CRC) holds great promise in the context of prevention. With this study, we aimed to identify patient characteristics associated with colorectal polyps (CPs) and polyp features of potential malignant progression. Furthermore, a potential association with gut microbiota in this context was investigated. METHODS: In this single-center study, a total of 162 patients with CPs and 91 control patients were included. Multiple variables including information on lifestyle, diet, serum parameters, and gut microbiota, analyzed by 16S-rRNA gene amplicon sequencing and functional imputations (Picrust2), were related to different aspects of CPs. RESULTS: We observed that elevated serum alkaline phosphatase (AP) levels were significantly associated with the presence of high-grade dysplastic polyps. This association was further seen for patients with CRC. Thereby, AP correlated with other parameters of liver function. We did not observe significant changes in the gut microbiota between patients with CP and their respective controls. However, a trend toward a lower alpha-diversity was seen in patients with CRC. Interestingly, AP was identified as a possible clinical effect modifier of stool sample beta diversity. DISCUSSION: We show for the first time an increased AP in premalignant CP. Furthermore, AP showed a significant influence on the microbial composition of the intestine. Relatively elevated liver enzymes, especially AP, may contribute to the detection of precancerous dysplastic or neoplastic changes in colorectal lesions. The association between elevated AP, premalignant CP, and the microbiome merits further study.

Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Platelet aggregates detected using quantitative phase imaging associate with COVID-19 severity.

BACKGROUND: The clinical spectrum of acute SARS-CoV-2 infection ranges from an asymptomatic to life-threatening disease. Considering the broad spectrum of severity, reliable biomarkers are required for early risk stratification and prediction of clinical outcomes. Despite numerous efforts, no COVID-19-specific biomarker has been established to guide further diagnostic or even therapeutic approaches, most likely due to insufficient validation, methodical complexity, or economic factors. COVID-19-associated coagulopathy is a hallmark of the disease and is mainly attributed to dysregulated immunothrombosis. This process describes an intricate interplay of platelets, innate immune cells, the coagulation cascade, and the vascular endothelium leading to both micro- and macrothrombotic complications. In this context, increased levels of immunothrombotic components, including platelet and platelet-leukocyte aggregates, have been described and linked to COVID-19 severity. METHODS: Here, we describe a label-free quantitative phase imaging approach, allowing the identification of cell-aggregates and their components at single-cell resolution within 30 min, which prospectively qualifies the method as point-of-care (POC) testing. RESULTS: We find a significant association between the severity of COVID-19 and the amount of platelet and platelet-leukocyte aggregates. Additionally, we observe a linkage between severity, aggregate composition, and size distribution of platelets in aggregates. CONCLUSIONS: This study presents a POC-compatible method for rapid quantitative analysis of blood cell aggregates in patients with COVID-19.

The human body produces a series of immune responses when it gets infected with SARS-CoV-2, the virus that causes COVID-19. One of these responses involves platelets, the blood clotting factor sticking to immune cells to form cell aggregates in the bloodstream. We aimed to understand the significance of these cell aggregates in COVID-19 disease progression. A quantitative imaging approach was used to investigate the number and components of these cell aggregates in SARS-CoV-2 infected patient blood. We observed blood from severe COVID-19 patients was associated with higher numbers and specific composition of cell aggregates. Our method can potentially support the risk stratification of severe patients to prevent complications in COVID-19 and other medical disorders, where immune cells are shown to aggregate.

Evaluation of a questionnaire to assess the indication for screening colonoscopy for asymptomatic patients.

INTRODUCTION: Colorectal cancer is the second most common cause of cancer death worldwide. Screening colonoscopy is a very effective measure to prevent colorectal cancer and can reduce mortality at the population level. However, the participation rates of screening programs are low.To provide easily accessible information on screening colonoscopy and to increase the participation rates of screening programs, we developed a questionnaire for asymptomatic patients based on the German guidelines to assess the indication for screening colonoscopy. We evaluated the questionnaire with reference to the indications given by specialists in gastroenterology. METHODS: Patients who visited a specialist in gastroenterology in an outpatient clinic of a tertiary hospital for other reasons than a colonoscopy were eligible for the study. A maximum of seven questions to assess the indication for screening colonoscopy were answered by the patients. Afterward, the indication for screening colonoscopy was given or not by a specialist in gastroenterology. The accuracy of the questionnaire was measured in terms of sensitivity, specificity, and predictive values. RESULTS: In total, 335 patients were included in the analyses, of whom 50 and 285 patients were given and were not given an indication for screening colonoscopy by the specialists, respectively. In 0/50 patients, the questionnaire was false negative and in 8/285 patients false positive. Thus, the questionnaire had a sensitivity of 100% (95% confidence interval: 93-100%), a specificity of 97% (95-99%), a negative predictive value of 100% (99-100%), and a positive predictive value of 86% (75-94%).A subgroup analysis including patients who had never had a colonoscopy (n=109) showed comparable results: sensitivity of 100% (92-100%), specificity of 92% (83-97%), negative predictive value of 100% (94-100%), and positive predictive value of 90% (87-97%). CONCLUSION: The self-assessment questionnaire for asymptomatic individuals to assess the recommendation for screening colonoscopy is very sensitive and specific compared to a specialist in gastroenterology.The questionnaire can be found at: https://www.interdisziplinaere-endoskopie.mri.tum.de/de/infos-patienten/index.php.

Influence of a Structured Microbiological Endotracheal Monitoring Program on the Outcome of Critically Ill COVID-19 Patients: An Observational Study.

BACKGROUND: In past influenza pandemics and the current COVID-19 pandemic, bacterial endotracheal superinfections are a well-known risk factor for higher morbidity and mortality. The goal of this study was to investigate the influence of a structured, objective, microbiological monitoring program on the prognosis of COVID-19 patients with mechanical ventilation. METHODS: A structured microbiological monitoring program (at intubation, then every 3 days) included collection of endotracheal material. Data analysis focused on the spectrum of bacterial pathogens, mortality, as well as intensive care unit (ICU), hospital, and mechanical ventilation duration. RESULTS: A total of 29% of the patients showed bacterial coinfection at the time of intubation, and within 48 h, 56% developed ventilator-associated pneumonia (VAP). Even though patients with VAP had significantly longer ICU, hospital, and mechanical ventilation durations, there was no significant difference in mortality between patients with VAP pneumonia and patients without bacterial infection. CONCLUSION: VAP is a common complication in COVID-19 patients. In contrast to already published studies, in our study implementing a structured microbiological monitoring program, COVID-19 patients with bacterial coinfection or VAP did not show higher mortality. Thus, a standardized, objective, microbiological screening can help detect coinfection and ventilator-associated infections, refining anti-infective therapy and positively influencing patient outcomes.

Fulminant Liver Failure after Treatment with a Checkpoint Inhibitor for Gastric Cancer: A Case Report and Review of the Literature.

Nivolumab is a promising monoclonal antibody inhibitor of programmed death-1, a protein on the surface of T-cells. As such, it is approved for use in patients with multiple advanced malignancies and can significantly elongate progression-free survival. However, monoclonal antibody inhibitors can lead to adverse hepatic reactions, which in rare cases result in further hepatic damage. Herein, we present a case of a patient with locally advanced gastric carcinoma treated with fluorouracil, oxaliplatin, docetaxel and the checkpoint inhibitor nivolumab. Five months after her first dosage of nivolumab and without a preexisting liver disease, she presented with transaminitis. During the course of her stay, the patient developed status epilepticus, which required mechanical ventilation followed by fulminant hepatic failure. A subsequent liver biopsy revealed severe liver damage with extensive confluent parenchymal necrosis corresponding to checkpoint-inhibitor-induced hepatitis. Alternative reasons for this hepatic failure were ruled out. Despite aggressive therapeutic interventions including corticosteroids and plasma exchange, the patient died due to liver failure. Although hepatic failure is rarely seen in patients with checkpoint inhibitor therapy, it requires early awareness and rapid intervention.

How much can farmers pay for weeding robots? A Monte Carlo simulation study.

This paper investigates the Maximum Acquisition Values (MAVs) of weeding robots and their determinants in both organic and conventional sugar beet farming in Germany. The MAV is defined in this paper as the price of the weeding robot that renders the same net profit as the current weeding methods. For our analysis, a Monte Carlo simulation approach is used, combined with empirical data and data collected from weeding robot companies. The results show that the MAVs of mechanical weeding robots for organic farming are substantially higher than that of spot spraying robots for conventional farming. Technology attributes are more influential than labour cost in determining the MAVs of weeding robots: in organic farming, technology attributes such as area capacity and weeding efficiency impact the MAVs of mechanical weeding robots the most; in conventional farming, supervision intensity and the robot's ability to save herbicides are the most influential factors. The wage rate of unskilled labour, relevant for manual weeding, plays a more important role in determining the MAVs than that of skilled labour, relevant for supervision of the robot. This implies that a shortage of seasonal workers and hence increases in the wage of low-skilled labour could be important drivers of the adoption of mechanical weeding robots. Plot characteristics such as plot size and mechanisation level only have limited impacts on the MAVs. Supplementary Information: The online version contains supplementary material available at 10.1007/s11119-023-10015-x.

Transpulmonary thermodilution: A revised correction formula for global end-diastolic volume index derived after femoral indicator injection.

PURPOSE: Transpulmonary thermodilution (TPTD) is usually performed by jugular indicator injection. In clinical practice, femoral venous access is often used instead, resulting in substantial overestimation of global end-diastolic volume index (GEDVI). A correction formula compensates for that. The objective of this study is to first evaluate the efficacy of the currently implemented correction function and then further improve this formula. METHODS: The performance of the established correction formula was investigated in our prospectively collected dataset of 98 TPTD measurements from 38 patients with both, jugular and femoral venous access. Subsequently, a new correction formula was developed: cross validation revealed the favourite covariate combination and a general estimating equation provided the final version, which was tested in a retrospective validation on an external dataset. RESULTS: Investigating the current correction function revealed a considerable reduction of bias compared to no correction. Concerning the objective of formula development, the covariate combination of GEDVI obtained after femoral indicator injection, age and body surface area is even favoured, when compared to the parameters of the previously published correction formula, as a further reduction of mean absolute error (68 vs. 61 ml/m2), a better correlation (0.90 vs. 0.91) and an increased adjusted R2 (0.72 vs 0.78) is noticed in the cross validation results. Of particular clinical importance is, that more measurements were correctly assigned to the same GEDVI category (decreased / normal / increased) using the revised formula, compared with the gold standard of jugular indicator injection (72.4 vs. 74.5%). In a retrospective validation, the newly developed formula showed a greater reduction of bias (to 2 vs. 6 %) than the currently implemented formula. CONCLUSIONS: The currently implemented correction function partly compensates for GEDVI overestimation. Applying the new correction formula on GEDVI measured after femoral indicator administration enhances the informative value and reliability of this preload parameter.

A deep learning model enables accurate prediction and quantification of pulmonary edema from chest X-rays.

BACKGROUND: A quantitative assessment of pulmonary edema is important because the clinical severity can range from mild impairment to life threatening. A quantitative surrogate measure, although invasive, for pulmonary edema is the extravascular lung water index (EVLWI) extracted from the transpulmonary thermodilution (TPTD). Severity of edema from chest X-rays, to date is based on the subjective classification of radiologists. In this work, we use machine learning to quantitatively predict the severity of pulmonary edema from chest radiography. METHODS: We retrospectively included 471 X-rays from 431 patients who underwent chest radiography and TPTD measurement within 24 h at our intensive care unit. The EVLWI extracted from the TPTD was used as a quantitative measure for pulmonary edema. We used a deep learning approach and binned the data into two, three, four and five classes increasing the resolution of the EVLWI prediction from the X-rays. RESULTS: The accuracy, area under the receiver operating characteristic curve (AUROC) and Mathews correlation coefficient (MCC) in the binary classification models (EVLWI < 15, ≥ 15) were 0.93 (accuracy), 0.98 (AUROC) and 0.86(MCC). In the three multiclass models, the accuracy ranged between 0.90 and 0.95, the AUROC between 0.97 and 0.99 and the MCC between 0.86 and 0.92. CONCLUSION: Deep learning can quantify pulmonary edema as measured by EVLWI with high accuracy.

Age and Comorbidity Burden of Patients Critically Ill with COVID-19 Affect Both Access to and Outcome of Ventilation Therapy in Intensive Care Units.

During the COVID-19 pandemic, large numbers of elderly, multimorbid people required treatment in intensive care units. This study investigated how the inherent patient factors age and comorbidity burden affected the treatment strategy and the outcome achieved. Retrospective analysis of data from intensive care patients enrolled in the Lean European Open Survey on SARS-CoV2-Infected Patients (LEOSS) cohort found that a patient's age and comorbidity burden in fact influenced their mortality rate and the use of ventilation therapy. Evidence showed that advanced age and multimorbidity were associated with the restrictive use of invasive ventilation therapies, particularly ECMO. Geriatric patients with a high comorbidity burden were clustered in the sub-cohort of non-ventilated ICU patients characterized by a high mortality rate. The risk of death generally increased with older age and accumulating comorbidity burden. Here, the more aggressive an applied procedure, the younger the age in which a majority of patients died. Clearly, geriatric, multimorbid COVID-19 patients benefit less from invasive ventilation therapies. This implies the need for a holistic approach to therapy decisions, taking into account the patient's wishes.

EASIX Is an Accurate and Easily Available Prognostic Score in Critically Ill Patients with Advanced Liver Disease.

Acute-on-chronic liver failure (ACLF) is associated with high mortality. Objective prognostic scores are important for treatment decisions. EASIX (Endothelial Activation and Stress Index) is a simple biomarker consisting of LDH, platelets, and creatinine, reflecting endothelial dysfunction after allogeneic stem cell transplantation. Considering endothelial dysfunction in the pathogenesis of ACLF, this study aimed to test the discriminative ability of EASIX in advanced liver disease. We retrospectively analysed the prognostic potential of EASIX to predict 28-day and 3-month mortality in a total of 188 liver cirrhotic patients requiring treatment at the intensive care unit. We evaluated the ability of EASIX to rule out early infections and predict the need for hemodialysis. EASIX performed moderately better than established scores in predicting 28-day mortality (AUC = 0.771) and was nearly equivalent (AUC = 0.791) to SOFA and APACHE-II in the prediction of 3-month mortality. Importantly, EASIX showed better diagnostic potential in ruling out clinically apparent infections than common proinflammatory markers (AUC = 0.861, p < 0.001) and showed suitable accuracy in predicting the need for hemodialysis (AUC = 0.833). EASIX is an accurate, objective and easily assessable biomarker for predicting mortality and complications in patients with advanced liver disease.

Accuracy of hemodynamic parameters derived by GE E-PiCCO in comparison with PiCCO® in patients admitted to the intensive care unit.

To evaluate the agreement and accuracy of a novel advanced hemodynamic monitoring (AHM) device, the GE E-PiCCO module, with the well-established PiCCO® device in intensive care patients using pulse contour analysis (PCA) and transpulmonary thermodilution (TPTD). A total of 108 measurements were performed in 15 patients with AHM. Each of the 27 measurement sequences (one to four per patient) consisted of a femoral and a jugular indicator injection via central venous catheters (CVC) and measurement using both PiCCO (PiCCO® Jug and Fem) and GE E-PiCCO (GE E-PiCCO Jug and Fem) devices. For statistical analysis, Bland-Altman plots were used to compare the estimated values derived from both devices. The cardiac index measured via PCA (CIpc) and TPTD (CItd) was the only parameter that fulfilled all a priori-defined criteria based on bias and the limits of agreement (LoA) by the Bland-Altman method as well as the percentage error by Critchley and Critchley for all three comparison pairs (GE E-PiCCO Jug vs. PiCCO® Jug, GE E-PiCCO Fem vs. PiCCO® Fem, and GE E-PiCCO Fem vs. GE E-PiCCO Jug), while the GE E-PiCCO did not accurately estimate EVLWI, SVRI, SVV, and PPV values measured via the jugular and femoral CVC compared with values assessed by PiCCO®. Consequently, measurement discrepancy should be considered on evaluation and interpretation of the hemodynamic status of patients admitted to the ICU when using the GE E-PiCCO module instead of the PiCCO® device.

Adjunctive Hydrocortisone Improves Hemodynamics in Critically Ill Patients with Septic Shock: An Observational Study Using Transpulmonary Thermodilution.

Introduction: Septic shock is associated with high mortality and hemodynamic impairment. The use of corticoids is a common therapeutic tool in critically ill patients. However, data on the mechanisms and prognostic ability of hemodynamic improvement by adjunctive steroids are rare. This study primarily aimed to evaluate short-term effects of hydrocortisone therapy on catecholamine requirement and hemodynamics derived from transpulmonary thermodilution (TPTD) in 30 critically ill patients with septic shock and a 28 days mortality rate of 50%. Methods: Hydrocortisone was administered with an intravenous bolus of 200 mg, followed by a continuous infusion of 200 mg per 24 h. Hemodynamic assessment was performed immediately before as well as 2, 8, 16, and 24 h after the initiation of corticoids. For primary endpoint analysis, we evaluated the impact of hydrocortisone on vasopressor dependency index (VDI) and cardiac power index (CPI). Results: Adjunctive hydrocortisone induced significant decreases of VDI from 0.41 (0.29-0.49) mmHg-1 at baseline to 0.35 (0.25-0.46) after 2 h (P < .001), 0.24 (0.12-0.35) after 8 h (P < .001), 0.18 (0.09-0.24) after 16 h (P < .001) and 0.11 (0.06-0.20) mmHg-1 after 24 h (P < .001). In parallel, we found an improvement in CPI from 0.63 (0.50-0.83) W/m2 at baseline to 0.68 (0.54-0.85) after 2 h (P = .208), 0.71 (0.60-0.90) after 8 h (P = .033), 0.82 (0.6-0.98) after 16 h (P = .004) and 0.90 (0.67-1.07) W/m2 after 24 h (P < .001). Our analyses revealed a significant reduction in noradrenaline requirement in parallel with a moderate increase in mean arterial pressure, systemic vascular resistance index, and cardiac index. As a secondary endpoint, our results showed a significant decrease in lung water parameters. Moreover, changes in CPI (ΔCPI) and VDI (ΔVDI) after 24 h of hydrocortisone therapy revealed accurate prognostic ability to predict 28 days mortality (AUC = 0.802 vs 0.769). Conclusion: Adjunctive hydrocortisone leads to a rapid decrease in catecholamine requirement and a substantial circulatory improvement in critically ill patients with septic shock.

Differentiation of Spontaneous Bacterial Peritonitis from Secondary Peritonitis in Patients with Liver Cirrhosis: Retrospective Multicentre Study.

Ascitic fluid infection is a serious complication of liver cirrhosis. The distinction between the more common spontaneous bacterial peritonitis (SBP) and the less common secondary peritonitis in patients with liver cirrhosis is crucial due to the varying treatment approaches. This retrospective multicentre study was conducted in three German hospitals and analysed 532 SBP episodes and 37 secondary peritonitis episodes. Overall, >30 clinical, microbiological, and laboratory parameters were evaluated to identify key differentiation criteria. Microbiological characteristics in ascites followed by severity of illness and clinicopathological parameters in ascites were the most important predictors identified by a random forest model to distinguish between SBP and secondary peritonitis. To establish a point-score model, a least absolute shrinkage and selection operator (LASSO) regression model selected the ten most promising discriminatory features. By aiming at a sensitivity of 95% either to rule out or rule in SBP episodes, two cut-off scores were defined, dividing patients with infected ascites into a low-risk (score ≥ 45) and high-risk group (score < 25) for secondary peritonitis. Overall, the discrimination of secondary peritonitis from SBP remains challenging. Our univariable analyses, random forest model, and LASSO point score may help clinicians with the crucial differentiation between SBP and secondary peritonitis.

Galactomannan-Antigen Testing from Non-Directed Bronchial Lavage for Rapid Detection of Invasive Pulmonary Aspergillosis in Critically Ill Patients: A Proof-of-Concept Study.

Invasive pulmonary aspergillosis is associated with high mortality. For diagnosis, galactomannan-antigen in serum and bronchoalveolar lavage fluid is recommended, with higher sensitivity in bronchoalveolar lavage fluid. Because of invasiveness, bronchoalveolar lavage might be withheld due to patients' or technical limitations, leading to a delay in diagnosis while early diagnosis is crucial for patient outcome. To address this problem, we performed an analysis of patient characteristics of intubated patients with invasive pulmonary aspergillosis with comparison of galactomannan-antigen testing between non-directed bronchial lavage (NBL) and bronchoalveolar lavage fluid. A total of 32 intubated ICU patients with suspected invasive pulmonary aspergillosis could be identified. Mycological cultures were positive in 37.5% for A. fumigatus. Galactomannan-antigen in NBL (ODI 4.3 ± 2.4) and bronchoalveolar lavage fluid (ODI 3.6 ± 2.2) showed consistent results (p-value 0.697). Galactomannan-antigen testing for detection of invasive pulmonary aspergillosis using deep tracheal secretion showed comparable results to bronchoalveolar lavage fluid. Because of widespread availability in intubated patients, galactomannan-antigen from NBL can be used as a screening parameter in critical risk groups with high pretest probability for invasive aspergillosis to accelerate diagnosis and initiation of treatment. Bronchoalveolar lavage remains the gold standard for diagnosis of invasive aspergillosis to be completed to confirm diagnosis, but results from NBL remove time sensitivity.

Gut Microbial Disruption in Critically Ill Patients with COVID-19-Associated Pulmonary Aspergillosis.

OBJECTIVES: COVID-19 disease can be exacerbated by Aspergillus superinfection (CAPA). However, the causes of CAPA are not yet fully understood. Recently, alterations in the gut microbiome have been associated with a more complicated and severe disease course in COVID-19 patients, most likely due to immunological mechanisms. The aim of this study was to investigate a potential association between severe CAPA and alterations in the gut and bronchial microbial composition. METHODS: We performed 16S rRNA gene amplicon sequencing of stool and bronchial samples from a total of 16 COVID-19 patients with CAPA and 26 patients without CAPA. All patients were admitted to the intensive care unit. Results were carefully tested for potentially confounding influences on the microbiome during hospitalization. RESULTS: We found that late in COVID-19 disease, CAPA patients exhibited a trend towards reduced gut microbial diversity. Furthermore, late-stage patients with CAPA superinfection exhibited an increased abundance of Staphylococcus epidermidis in the gut which was not found in late non-CAPA cases or early in the disease. The analysis of bronchial samples did not yield significant results. CONCLUSIONS: This is the first study showing that alterations in the gut microbiome accompany severe CAPA and possibly influence the host's immunological response. In particular, an increase in Staphylococcus epidermidis in the intestine could be of importance.

A Novel Machine Learning-Based Point-Score Model as a Non-Invasive Decision-Making Tool for Identifying Infected Ascites in Patients with Hydropic Decompensated Liver Cirrhosis: A Retrospective Multicentre Study.

This study is aimed at assessing the distinctive features of patients with infected ascites and liver cirrhosis and developing a scoring system to allow for the accurate identification of patients not requiring abdominocentesis to rule out infected ascites. A total of 700 episodes of patients with decompensated liver cirrhosis undergoing abdominocentesis between 2006 and 2020 were included. Overall, 34 clinical, drug, and laboratory features were evaluated using machine learning to identify key differentiation criteria and integrate them into a point-score model. In total, 11 discriminatory features were selected using a Lasso regression model to establish a point-score model. Considering pre-test probabilities for infected ascites of 10%, 15%, and 25%, the negative and positive predictive values of the point-score model for infected ascites were 98.1%, 97.0%, 94.6% and 14.9%, 21.8%, and 34.5%, respectively. Besides the main model, a simplified model was generated, containing only features that are fast to collect, which revealed similar predictive values. Our point-score model appears to be a promising non-invasive approach to rule out infected ascites in clinical routine with high negative predictive values in patients with hydropic decompensated liver cirrhosis, but further external validation in a prospective study is needed.

Fulminant Adenoviral-Induced Hepatitis in Immunosuppressed Patients.

Human adenovirus (HAdV) can often lead to fulminant hepatitis in immunocompromised patients, mostly after reactivation of HAdV. Different risk factors, e.g., transplantation and chemotherapy, increase the risk of developing a HAdV hepatitis. We retrospectively analyzed three patients who showed the characteristics of a HAdV hepatitis observed in disseminated disease. In addition to PCR, diagnosis could be proven by pathology, CT scan, and markedly elevated transaminases. All patients had a hemato-oncologic underlying disease. Two had received a stem-cell transplant, and one was under chemotherapy including rituximab. Despite therapy with cidofovir, all patients died. As the incidence of HAdV hepatitis is low, diagnosis may be easily overlooked. No treatment approaches have yet been established. HAdV hepatitis should be considered as a differential diagnosis, especially when risk factors are present. To avoid dissemination, treatment should be initiated as soon as possible.