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Chronic inflammation has been identified as an important risk factor for the development of malignancy, and knowledge about its molecular and cellular mechanisms is increasing. Several chronic inflammatory diseases of the gastrointestinal tract are important as risk factors for malignancy and have been studied in detail. In this review, we summarize important molecular mechanisms in chronic inflammation and highlight established and potential links between chronic inflammation and gastrointestinal cancer. In addition, we present the role of chronic inflammation in numerous tumors within the gastrointestinal tract as well as the relevant pathways or epidemiologic observations linking the pathogenesis of these tumors to inflammation. [ABSTRACT FROM AUTHOR]

(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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Mucormycosis is associated with high mortality rates in critically ill patients. • Diagnostic strategies are needed. • Aggressive antifungal therapy is essential for intensive care patients with mucormycosis. Mucormycosis is a rare invasive fungal infection with high mortality in patients with severe underlying predisposing factors causing immunosuppression. The exact incidence of mucormycosis and the optimal therapeutic approach is difficult to determine, especially in severe cases, due to the rarity of the disease. The new second-generation triazole isavuconazole provides an alternative treatment option which may represent a potential benefit in severe cases. A retrospective case series was conducted of patients with a positive laboratory culture for Mucorales and consistent clinical findings who required intensive care treatment. Patient characteristics including demographics, comorbidities, microbiological analysis, specific antifungal therapy and clinical outcome were analysed. Fifteen critically ill patients with Mucorales detected between 2016 and 2019 were included in this study; the crude mortality rate was 100%. At the time of diagnosis of mucormycosis, 80% of subjects had relevant medical immunosuppression and 53.3% of subjects had neutropenia. Manifestation of mucormycosis was pulmonary in 53.3% of subjects, rhino-orbital in 20% of subjects and disseminated in 26.7% of subjects. Notably, 40% of all patients had received antifungal prophylaxis prior to mucormycosis, mainly with posaconazole due to underlying haematological malignancy, thus possibly representing break-through infections. Antifungal therapy for invasive mucormycosis was administered in 80% of subjects for a median duration of 16 days. In this retrospective cohort analysis of intensive care patients, the prognosis of mucormycosis was extremely poor. An aggressive strategy for diagnosis and treatment is essential for intensive care patients with mucormycosis. There is a need for further research to determine if combination therapy in higher dosages or prompt surgery is beneficial in severe critically ill patients. [ABSTRACT FROM AUTHOR]

Background: In the absence of PCR detection of SARS-CoV-2 RNA, accurate diagnosis of COVID-19 is challenging. Low-dose computed tomography (CT) detects pulmonary infiltrates with high sensitivity, but findings may be non-specific. This study assesses the diagnostic value of SARS-CoV-2 serology for patients with distinct CT features but negative PCR.Methods: IgM/IgG chemiluminescent immunoassay was performed for 107 patients with confirmed (group A: PCR + ; CT ±) and 46 patients with suspected (group B: repetitive PCR-; CT +) COVID-19, admitted to a German university hospital during the pandemic's first wave. A standardized, in-house CT classification of radiological signs of a viral pneumonia was used to assess the probability of COVID-19.Results: Seroconversion rates (SR) determined on day 5, 10, 15, 20 and 25 after symptom onset (SO) were 8%, 25%, 65%, 76% and 91% for group A, and 0%, 10%, 19%, 37% and 46% for group B, respectively; (p < 0.01). Compared to hospitalized patients with a non-complicated course (non-ICU patients), seroconversion tended to occur at lower frequency and delayed in patients on intensive care units. SR of patients with CT findings classified as high certainty for COVID-19 were 8%, 22%, 68%, 79% and 93% in group A, compared with 0%, 15%, 28%, 50% and 50% in group B (p < 0.01). SARS-CoV-2 serology established a definite diagnosis in 12/46 group B patients. In 88% (8/9) of patients with negative serology > 14 days after symptom onset (group B), clinico-radiological consensus reassessment revealed probable diagnoses other than COVID-19. Sensitivity of SARS-CoV-2 serology was superior to PCR > 17d after symptom onset.Conclusions: Approximately one-third of patients with distinct COVID-19 CT findings are tested negative for SARS-CoV-2 RNA by PCR rendering correct diagnosis difficult. Implementation of SARS-CoV-2 serology testing alongside current CT/PCR-based diagnostic algorithms improves discrimination between COVID-19-related and non-related pulmonary infiltrates in PCR negative patients. However, sensitivity of SARS-CoV-2 serology strongly depends on the time of testing and becomes superior to PCR after the 2nd week following symptom onset. [ABSTRACT FROM AUTHOR]

Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in critically ill patients with endstage liver disease. Therefore, aim of this study is to predict the prevalence and outcome of IPA in critically ill patients with underlying liver cirrhosis and evaluation of the necessity Glactomannan (GM) screening in serum and bronchoalveolar lavage (BAL) in this cohort. In total 12 out of 84 patients (14%) had probable IPA. The mean optical density index (ODI) bronchoalveolar lavage (BAL) GM index was 3.6 ± 1.5 (Range: 1.7–5.7). An overall sensitivity of 90% (95% CI 86–96%) and specificity of 85% (95% CI 81–88%) was found for the BAL GM in IPA. Acute Physiology And Chronic Health Evaluation (APACHE II), sequential organ failure assessment (SOFA) as well the model of endstage liver disease (MELD) score were significantly higher in the probable IPA group as compared to the No IPA group (26 versus 21, p < 0.001 and 14 versus 10, p < 0.044). Length of intensive care unit (ICU) stay was significantly longer in probable IPA patients (16 versus 10 days, p < 0.027) and mortality rate was significantly higher in probable IPA patients (100% versus 65%, p < 0.001) as compared to No IPA patients. APACHE II and MELD score were independently associated with higher mortality rate using multivariate logistic regression (p = 0.025 and p = 0.034). In conclusion, IPA has a relevant impact on outcome. Screening for IPA is indicated, easy to perform and a necessity to improve outcome. [ABSTRACT FROM AUTHOR]

In the past decades, social-ecological systems (SESs) worldwide have undergone dramatic transformations with often detrimental consequences for livelihoods. Although resilience thinking offers promising conceptual frameworks to understand SES transformations, empirical resilience assessments of real-world SESs are still rare because SES complexity requires integrating knowledge, theories, and approaches from different disciplines. Taking up this challenge, we empirically assess the resilience of a South African pastoral SES to drought using various methods from natural and social sciences. In the ecological subsystem, we analyze rangelands' ability to buffer drought effects on forage provision, using soil and vegetation indicators. In the social subsystem, we assess households' and communities' capacities to mitigate drought effects, applying agronomic and institutional indicators and benchmarking against practices and institutions in traditional pastoral SESs. Our results indicate that a decoupling of livelihoods from livestockgenerated income was initiated by government interventions in the 1930s. In the post-apartheid phase, minimum-input strategies of herd management were adopted, leading to a recovery of rangeland vegetation due to unintentionally reduced stocking densities. Because current livelihood security is mainly based on external monetary resources (pensions, child grants, and disability grants), household resilience to drought is higher than in historical phases. Our study is one of the first to use a truly multidisciplinary resilience assessment. Conflicting results from partial assessments underline that measuring narrow indicator sets may impede a deeper understanding of SES transformations. The results also imply that the resilience of contemporary, open SESs cannot be explained by an inward-looking approach because essential connections and drivers at other scales have become relevant in the globalized world. Our study thus has helped to identify pitfalls in empirical resilience assessment and to improve the conceptualization of SES dynamics. [ABSTRACT FROM AUTHOR]

To investigate the effect of convalescent plasma therapy (CPT) on clinical courses of B-cell-sufficient and B-cell-depleted patients with life-threatening COVID-19. In this case series, we retrospectively analysed clinical, laboratory and cardiopulmonary parameters of six patients with life-threatening COVID-19 receiving convalescent plasma (CP) as rescue therapy between April 11, 2020 to October 10, 2020. Clinical and laboratory parameters before and after transfusion were compared in two B-cell-depleted patients and four B-cell sufficient patients (control group). Both B-cell-depleted patients cleared SARS-CoV-2 virus and survived, while all other patients died within 14 days from intervention despite maximal therapeutic efforts. D-dimer levels increased in both cohorts subsequent to CPT. In control patients, mean Interleukin-6 increased and platelet levels decreased as opposed to decreasing and stable levels in B-cell-depleted patients, respectively. Control patients required increased doses of vasopressor compared to decreasing doses in B-cell depleted patients subsequent to CPT. PO 2 /FiO 2 decrease was more pronounced and respiratory deterioration required postinterventional extracorporeal membrane oxygenation in two control patients. Transpulmonary thermodilution revealed a further increase of the Extravascular Lung Water Index upon CPT in control patients. Use of CP in late stages of life-threatening COVID-19 should be used with caution but may be beneficial in B-cell-depleted patients. Further studies are necessary to assess factors predicting potential therapeutic benefits as well as possible hazards. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background & Aims: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens., Methods: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP., Results: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose., Conclusions: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

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., (© 2023. The Author(s).)

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., (© 2023. The Author(s).)

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.

Background: Early identification of patients with acute severe pancreatitis is important for prompt and adequate treatment. Existing scores for pancreatitis are often laborious or require serial patient evaluation, whereas the qSOFA score, that was established to predict outcome in patients with suspected infection, is simple to perform., Aims and Methods: In this cohort study, we analyse the potential of the qSOFA score to predict outcome of patients with acute pancreatitis and refine the qSOFA score by rapid available laboratory parameters to the emergency room assessment of acute pancreatitis (ERAP) score. Validation was performed in a separate patient cohort., Results: In total 203 patients with acute pancreatitis were recruited. The qSOFA score has the potential to predict ICU admission (AUC = 0.730, p = 0.002) and organ failure (AUC = 0.799, p = 0.013) in acute pancreatitis. Respiratory rate, mental status, blood urea nitrogen and C-reactive protein are the rapid available parameters with the highest individual impact in binary logistic regression analyses. Their combination to the ERAP score can predict severity of acute pancreatitis according to the revised Atlanta classification (AUC = 0.689 ± 0.041, p < 0.001), ICU admission (AUC = 0.789 ± 0.067, p < 0.001), multi-organ dysfunction syndrome (AUC = 0.963 ± 0.024, p < 0.001) and mortality (AUC = 0.952 ± 0.028, p = 0.001). The performance and prognostic validity for organ failure and mortality were validated in an independent patient cohort., Conclusion: The qSOFA is a rapidly available prognostic score in acute pancreatitis with limited prognostic validity. A combination with the laboratory parameters BUN and CRP results in the new ERAP score with outstanding prognostic validity for multi-organ dysfunction syndrome and mortality., (© 2021. The Author(s).)

Nearly 5% of patients suffering from COVID-19 develop acute respiratory distress syndrome (ARDS). Extravascular lung water index (EVLWI) is a marker of pulmonary oedema which is associated with mortality in ARDS. In this study, we evaluate whether EVLWI is higher in patients with COVID-19 associated ARDS as compared to COVID-19 negative, ventilated patients with ARDS and whether EVLWI has the potential to monitor disease progression. EVLWI and cardiac function were monitored by transpulmonary thermodilution in 25 patients with COVID-19 ARDS subsequent to intubation and compared to a control group of 49 non-COVID-19 ARDS patients. At intubation, EVLWI was noticeably elevated and significantly higher in COVID-19 patients than in the control group (17 (11-38) vs. 11 (6-26) mL/kg; p < 0.001). High pulmonary vascular permeability index values (2.9 (1.0-5.2) versus 1.9 (1.0-5.2); p = 0.003) suggested a non-cardiogenic pulmonary oedema. By contrast, the cardiac parameters SVI, GEF and GEDVI were comparable in both cohorts. High EVLWI values were associated with viral persistence, prolonged intensive care treatment and in-hospital mortality (23.2 ± 6.7% vs. 30.3 ± 6.0%, p = 0.025). Also, EVLWI showed a significant between-subjects (r = - 0.60; p = 0.001) and within-subjects correlation (r = - 0.27; p = 0.028) to Horowitz index. Compared to non COVID-19 ARDS, COVID-19 results in markedly elevated EVLWI-values in patients with ARDS. High EVLWI reflects a non-cardiogenic pulmonary oedema in COVID-19 ARDS and could serve as parameter to monitor ARDS progression on ICU.

Aspergillus spp. cholangitis is an uncommon presentation of invasive aspergillosis. Only few cases are described in the literature affecting severely immunocompromised patients or patients following biliary surgery. Especially, invasive aspergillosis in non-haematological patients is associated with high mortality rates, caused by atypical presentations, which is associated with a delay in diagnosis and therapy. We report a 72-year-old man with primary diagnosis of cholangiocarcinoma and stent implantation by endoscopic retrograde cholangiopancreatography (ERCP) for biliary decompression who developed severe cholangitis with invasive aspergillosis. The patient had no history of prior hospitalisation, no immunosuppressive therapy and no preceding biliary surgery. Furthermore, in this exceptional case of extrapulmonary aspergillosis, there were no signs of pulmonary involvement. From the literature review, only three cases of Aspergillus cholangitis could be identified. Clinical manifestations of invasive aspergillosis can be variable and classical risk factors such as immunosuppression are not mandatorily present. Clinical awareness of these rare cases is of vital importance for initiation of correct therapy.

Background: Covid-19 is a rapidly spreading viral disease that can cause severe acute respiratory distress syndrome (ARDS). Besides the lungs it can also affect other organs like the heart or the liver. Whether there is a pancreatic manifestation as well is currently unclear., Methods: and aims: We prospectively collected patient information of patients with Covid-19 associated ARDS in a registry (COvid Registry REChts der Isar intensive care Trial - CORRECT) and analyzed this patient cohort for signs of acute pancreatitis (e.g. lipase activity >3 times the upper limit)., Results: 12/38 (31.6%) patients with Covid-19 associated ARDS had a serum lipase activity >180 U/l. Median lipase activity was 422 U/l (186-1127). No patient showed typical findings of acute pancreatitis on imaging studies. On hemodynamic monitoring no patient had signs of intravascular fluid demand regarding MAP, GEDVI and therapy with vasopressors. To avoid worsening respiratory function no treatment with crystalloids was initiated. Lipasemia was not explained by gastroenteritis or renal insufficiency, occurred before as well as after viral clearance and 16.1 ± 6.0 days after the first symptoms. No patient developed severe acute pancreatitis during the follow up period of 35.8 ± 8.3 days., Conclusion: High lipasemia without typical signs of acute pancreatitis is a frequent finding in severe Covid-19 associated ARDS. Considering the markedly high levels of serum lipase activity, we think impaired microcirculation in severely ill patients can explain this finding rather than extra-pancreatic co-morbidities (UTN: DRKS00021612)., Competing Interests: Declaration of competing interest Tobias Lahmer received travel grants from Gilead, Pfizer and MSD. Sebastian Rasch received travel grants from Gilead. Wolfgang Huber collaborated with Pulsion Medical Systems SE, Feldkirchen, Germany as member of the Medical Advisory Board. All other authors declare that there is no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Haemodynamic monitoring before extra-corporeal membrane oxygenation (ECMO) might help to optimize the effectiveness of ECMO. However, there are concerns that pulmonary arterial and trans-pulmonary thermodilution (TPTD) might be confounded by a loss of indicator into the ECMO-circuit, resulting in an overestimation of volumetric parameters. Since there is a lack of data on indicator dilution techniques during ECMO, we compared TPTD-measurements before and during ECMO. TPTD-derived parameters before and after initiation of ECMO were compared in 14 intensive care unit-patients with veno-venous ECMO and TPTD-monitoring (PiCCO ® ). Eight patients had a jugular and six patients a femoral central venous catheter (CVC). Cardiac index, global end-diastolic volume index (GEDVI) and extra-vascular lung water index (EVLWI) before ECMO as well as the ECMO-flow were comparable in patients with jugular and femoral CVC. Pre-ECMO, cardiac index (CI) was not significantly different compared to values during ECMO (4.5 ± 1.7 vs. 4.4 ± 2.1 L/min/m 2 ; p = 0.43). By contrast, GEDVI (791 ± 179 vs. 974 ± 384 mL/m 2 ; p = 0.04) and EVLWI (21 ± 9 vs. 28 ± 11 mL/kg; p < 0.01) were higher during ECMO than before. Increases in GEDVI (36 ± 210 vs. 378 ± 247 mL/m 2 ; p = 0.02) and EVLWI (3 ± 2 vs. 11 ± 8 mL/kg; p = 0.06) were substantially more pronounced in patients with femoral compared to jugular indicator injection. In multivariate analysis, femoral indicator injection was independently associated with larger increases in GEDVI (p < 0.01) and EVLWI (p = 0.04) during ECMO. However, CI and haemodynamic parameters not derived from TPTD, but from pulse contour analysis (systolic and diastolic arterial pressure, stroke volume variation and pulse pressure variation) were not affected by the start of ECMO. Our study demonstrates marked increases in GEDVI and EVLWI after the onset of ECMO. These increases were more pronounced for femoral compared to jugular indicator injection. CI and haemodynamic parameters not derived from TPTD were not affected by the extra-corporeal circuit.

Background: /Objectives: AGE and their receptors like RAGE and Galectin-3 can activate inflammatory pathways and have been associated with chronic inflammatory diseases. Several studies investigated the role of AGE, Galectin-3 and sRAGE in pancreatic diseases, whereas no comprehensive data for chronic pancreatitis (CP) are available., Methods: Serum samples from CP patients without an active inflammatory process (85 ACP; 26 NACP patients) and 40 healthy controls were collected. Levels of AGE, sRAGE and Galectin-3 were measured by ELISA. To exclude potential influences of previously described RAGE SNPs on detected serum levels, we analyzed variants rs207128, rs207060, rs1800625, and rs1800624 by melting curve technique in 378 CP patients and 338 controls., Results: AGE and Galectin-3 serum levels were significantly elevated in both ACP and NACP patients compared to controls (AGE: 56.61 ± 3.043 vs. 31.71 ± 2.308 ng/mL; p < 0.001; Galectin-3: 16.63 ± 0.6297 vs. 10.81 ± 0.4835 ng/mL; p < 0.001). In contrast, mean serum sRAGE levels were significantly reduced in CP patients compared to controls (sRAGE: 829.7 ± 37.10 vs. 1135 ± 55.74 ng/mL; p < 0.001). All results were consistent after correction for gender, age and diabetes mellitus. No genetic association with CP was found., Conclusions: Our extensive analysis demonstrated the importance of aging related pathways in the pathogenesis of CP. As the results were consistent in ACP and NACP, both entities most likely share common pathomechanisms. Most probably the involved pathways are a general hallmark of an inflammatory state in CP that is even present in symptom-free intervals., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Chronic pancreatitis (CP) is a fibrotic disorder of the pancreas leading to clinical sequelae like pain and an excess of comorbidity including cardiovascular disease and cancers. The aim of this study was to determine the relationship between systemic inflammation and quality of life in patients with CP. Patients were prospectively recruited and underwent a quality of life assessment (EORTC QLQ-C30 and PAN 28). The serum inflammatory profile was assessed using an MSD 30-plex array. The relationship between clinical variables, inflammatory cytokines and quality of life was determined by a GLM-MANOVA and the individual impact of significant variables evaluated by a second ANOVA. In total, 211 patients with a median age of 53 years were recruited across 5 European centres. Gender, age, nicotine and alcohol abuse were clinical variables associated with altered quality of life. Systemic inflammation with high levels of pro-inflammatory cytokines (Eotaxin, IL-1β, IL-7, IL-8, IL-12/IL-23p40, IL-12p70, IL-13, IL-16, IP-10, MCP-1, MCP-4, MDC, MIP-1a, TARC, TNFß) was associated with diminished quality of life in general and specific domains including pain, physical and cognitive functioning. As conclusion, CP is associated with a systemic inflammatory response that has a negative impact on quality of life and accelerates aging.

Background and Objectives: Candida infections are frequent in necrotising pancreatitis. Candidemia is associated with very high mortality and its risk due to infected pancreatic necrosis is unknown. So we aimed to assess potential risk factors and the risk of candidemia in necrotising pancreatitis., Methods: We retrospectively searched our clinical database for the diagnosis necrotising pancreatitis from 2007 till March 2017 and entered relevant information in a database for statistical analysis., Results: in total, 136 patients met the inclusion criteria. Candida infected pancreatic necrosis were found in 54 patients and 7 patients developed candidemia. Patients with Candida infected necrosis had a significantly higher in hospital mortality (35.2% versus 13.4%, p = 0.003). The highest mortality was observed in patients with candidemia (57.1% versus 20.2%, p = 0.042). Male gender (OR 0.32, CI 0.13-0.78, p = 0.013) and post-ERCP pancreatitis (OR 4.32, CI 1.01-18.36, p = 0.048) had a significant impact on the risk of Candida infections of pancreatic necrosis. Candidemia was significantly more frequent in patients with Candida infected necrosis (11.1% versus 1.2%, p = 0.016). Candida albicans was the most common species followed by Candida glabrata., Conclusion: Candidemia is a relevant complication of necrotising pancreatitis and associated with high mortality. If patients do not respond to antibiotic therapy empiric antifungal therapy should be discussed., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Purpose: Invasive pulmonary aspergillosis (IPA) is an important cause of morbidity/mortality in immunocompromised critically ill patients. New diagnostic strategies for early detection of IPA include the noninvasive biomarkers 1,3-β-d-glucan (BDG), serum, and bronchoalveolar (BAL) fluid galactomannan (GM). The aim of this study was to compare these markers for early detection of IPA in immunosuppressed critically ill patients., Methods: Between December 2014 and December 2015, 49 immunosuppressed patients with respiratory failure were treated at our intensive care unit (ICU). We compared the BDG Fungitell assay with GM Platelia assay in serum and BAL for early detection of IPA. All tests were performed initially after admission at the ICU., Results: In our study with 49 patients, 13 (26%) had probable IPA. These patients had a higher Acute Physiology And Chronic Health Evaluation II score (28 vs 23, P<.001), Sequential Organ Failure Assessment score (16 vs 14, P<.001), more neutropenia (77% vs 30%, P<.001), worse Horowitz Index (99 vs 73 P<.020), a longer ICU stay (26 vs 17 days, P<.044), and a higher mortality rate (77% vs 58%, P<.001) as compared with patients without probable IPA. The used biomarker BDG presented in patients with probable IPA showed significantly higher levels as compared with patients without probable IPA (375 [103-1000 pg/mL; P<.001] vs 64 [30-105 pg/mL; P < .001]). Comparison of BDG with GM showed that positive serum GM could be detected in only 4 (30%), whereas positive BAL GM could be detected in 12 (92%; mean optical density index, 3.7) of 13 probable IPA cases. These results can be expressed as an overall sensitivity of 88% and a specificity of 82% for probable IPA using the BDG Fungitell assay, a sensitivity of 35% and a specificity of 70% using the serum GM Platelia assay, and a sensitivity of 70% and a specificity of 94% using the BAL GM Platelia assay. The negative predictive values of the used tests were 94% for the BDG Fungitell assay, 94% for the serum GM Platelia assay, and 90% for the BAL GM Platelia assay., Conclusion: 1,3-β-d-Glucan may be a useful marker for patients under surveillance at risk for IPA. In critically ill patients with immunosuppression, early diagnosis of IPA may be improved by BDG as compared with serum GM. However, diagnostic performance and accuracy increase when BDG is run in parallel with GM from BAL; moreover, the association of the 2 parameters has also the advantage of detecting early and reliable IPA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Chronic pancreatitis is an inflammatory disorder of the pancreas that is associated with accelerated mortality for patients suffering from this disease. The association between chronic inflammation and accelerated biological ageing has been well described and is often referred to as "inflammageing". In this review we seek to determine how systemic inflammation in chronic pancreatitis may contribute to an accelerated ageing phenotype., Methods: A systematic literature search with a predefined search protocol was performed on Medline, Embase and Cochrane libraries according to the PRISMA guidelines., Results: The initial search identified 499 studies. After title, abstract and full text screen of the search results, 20 were included for further evaluation. In the 20 remaining articles 41 inflammatory mediators were identified - mainly involved in chronic inflammation, fibrosis and particularly cardinal features of inflammageing such as sarcopenia and osteoporosis., Conclusion: Chronic pancreatitis is associated with elevated levels of inflammatory mediators many of which are associated with an accelerated ageing phenotype and may explain some of the clinical sequelae of this disease., (Copyright © 2016 IAP and EPC. All rights reserved.)

Background/objectives: Angiogenesis plays a central role in tumor growth and metastasis and tyrosine kinases are crucial in the modulation of growth factor signaling. Several side effects of tyrosine kinase inhibitors have been reported, including diarrhea due to pancreatic insufficiency. The suspected mechanism is the anti-angiogenetic effect of the inhibited vascular endothelial growth factor (VEGF) causing a disturbance of the microvasculation. The aim of the present study was to determine the volume of the pancreas before and after a therapy both with the multi-tyrosine kinase inhibitor Sorafenib and Bevacizumab, which is a humanized monoclonal immunoglobulin G1 antibody against VEGF., Methods: Retrospective monocentric study including 42 patients who received either Sorafenib, Bevacizumab combined with Flourouracil and/or Irinotecan, or singly Flourouracil and Irinotecan for different non-pancreatic malignancies. The volume of the pancreas was measured before and after therapy by CT-scan based volumetry., Results: The pancreatic volume was statistically significantly lower after treatment with Sorafenib (75.4 mL vs. 71.0 mL; p = 0.006) or Bevacizumab and Fluorouracil ± Irinotecan (71.8 mL vs. 62.6 mL; p = 0.020). The pancreatic volume did not change statistically significantly after treatment with Fluorouracil ± Irinotecan only (51.1 mL vs. 49.9 mL; p = 0.142)., Conclusions: Pancreatic volume decreases statistically significantly under treatment with both the multi-tyrosine kinase inhibitor Sorafenib and the angiogenesis inhibitor Bevacizumab. This volume reduction is most likely due to a reduced microvasculation by inhibition of VEGF., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Most of the data about epidemiology, clinical presentation and treatment of autoimmune pancreatitis (AIP) is based on case series or small study groups. We therefore analyzed all cases of AIP treated at our clinic retrospectively., Methods: We searched our clinical database for the diagnosis pancreatitis between January 2007 and June 2014, selected patients with AIP and entered all relevant information in a database for statistical analysis., Results: In total 53 patients with AIP were treated at our institution, 62% with type 1 and 23% with type 2 AIP. Gender distribution was male/female 3.1:1 for type 1 and 1:1.2 for type 2 AIP. The median age was 63.0 and 32.5 years for type 1 and type 2 AIP, respectively. The most common symptom is abdominal pain particular in patients with type 2 AIP whereas jaundice was only apparent in patients with type 1 AIP. The international diagnostic criteria seem to facilitate diagnosis of AIP as unnecessary pancreatic surgery in patients with AIP decreases. In 62.6% of the patients therapy was indicated and 84.8% showed a response to initial therapy with steroids. Recurring disease occurred in 28.3% of the cases but only 3.8% suffered a second relapse. Permanent maintenance therapy with steroids or additional therapy with immunomodulatory drugs is successful in recurring disease., Conclusion: Our data further corroborate previous findings on epidemiology, clinical presentation and treatment of AIP. AIP is a well manageable autoimmune disease in most patients. Better biopsy techniques and simplified diagnostic criteria might further alleviate diagnosis of AIP., (Copyright © 2015 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.)

Purpose: Patients with liver failure requiring dialysis are at increased risk for citrate accumulation during sustained low-efficiency dialysis (SLED). The aim of this study was to evaluate the feasibilty of citrate SLED in critical ill patients with liver failure and investigate predictive parameters regarding citrate accumulation., Materials and Methods: This is a prospective study in 24 medical intensive care unit patients with liver failure and a total of 43 SLED runs (maximum of 3 runs per patient) using citrate anticoagulation. Liver function was characterized before SLED using not only laboratory parameters but also determination of the plasma disappearance rate of indocyanine green. In addition, blood gas parameters as well total calcium and citrate in serum were measured at baseline and defined time points during SLED., Results: Accumulation of citrate could be observed in all SLED runs, which were nearly normalized until the end of SLED and 24 hours after SLED, respectively. However, the critical threshold of total calcium/ionized calcium on ratio of greater than 2.5 was exceeded in only 1 patient. Equalization of initial metabolic acidosis was possible without major disturbances of acid base and electrolyte status. Liver function parameters showed poor predicitve capabilities regarding citrate accumulation., Conclusions: Despite substantial accumulation of citrate in serum, SLED is save and feasible in patients with liver failure using a citrate anticoagulation. Careful monitoring of electrolytes and acid base status is mandatory to ensure patient safety., (Copyright © 2015 Elsevier Inc. All rights reserved.)