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.

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.

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.

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.

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.

Identification of risk factors for upper gastrointestinal bleeding in intensive care unit patients (GIBICU study).

BACKGROUND AND GOALS: Risk stratification for the need for therapeutic endoscopy and prediction of mortality in patients with upper gastrointestinal bleeding (UGIB) can be assessed by several scores. However, current scores are not validated for variceal bleeding and Intensive Care Unit (ICU) patients. The aim of this study was to evaluate potential parameters for the prediction of UGIB and patient outcomes. PATIENTS AND STUDY METHODS: In this monocenter retrospective observational study, data from all esophagogastroduodenoscopies (EGD) between November 2014 and February 2020 with suspected hemorrhage in our ICU were evaluated. RESULTS: Out of 345 included EGD, 42.3% of UGIB was diagnosed. 51.9% needed endoscopic intervention. Overall, 52.3% of included patients with UGIB died. Logistic regression showed that preceding variceal or non-variceal UGIB (p < .001), serum lactate (p = .001), heart rate (HR) (p = .005), and blood transfusions (p = .001) were significant predictors of UGIB. Previous UGIB (p < .001), male sex (p = .015), known varices (p < .001), serum albumin (p = .19) and use of catecholamines (p = .040) were significant predictors for the need of endoscopic intervention. Higher mortality was significantly associated with the usage of steroids (p < .001), malignant preconditions (p = .021), serum albumin (p = .020) and prolonged PTT (partial thromboplastin time) (p = .001). CONCLUSIONS: We were able to identify additional parameters that had previously not been included in existing scores to predict the risk of UGIB, the need for therapeutic endoscopy and mortality in ICU patients. Therefore, an extension of these scores is necessary. Further validation of identified parameters in multicenter trials is needed to improve risk scores for ICU patients.

B-Lines Scores Derived From Lung Ultrasound Provide Accurate Prediction of Extravascular Lung Water Index: An Observational Study in Critically Ill Patients.

INTRODUCTION: Visualization of B-lines via lung ultrasound provides a non-invasive estimation of pulmonary hydration. Extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) assessed by transpulmonary thermodilution (TPTD) represent the most validated parameters of lung water and alveolocapillary permeability, but measurement is invasive and expensive. This study aimed to compare the correlations of B-lines scores from extensive 28-sector and simplified 4-sector chest scan with EVLWI and PVPI derived from TPTD in the setting of intensive care unit (primary endpoint). METHODS: We performed scoring of 28-sector and 4-sector B-Lines in 50 critically ill patients. TPTD was carried out with the PiCCO-2-device (Pulsion Medical Systems SE, Maquet Getinge Group). Median time exposure for ultrasound procedure was 12 minutes for 28-sector and 4 minutes for 4-sector scan. RESULTS: Primarily, we found close correlations of 28-sector as well as 4-sector B-Lines scores with EVLWI (R2 = 0.895 vs. R2 = 0.880) and PVPI (R2 = 0.760 vs. R2 = 0.742). Both B-lines scores showed high accuracy to identify patients with specific levels of EVLWI and PVPI. The extensive 28-sector B-lines score revealed a moderate advantage compared to simplified 4-sector scan in detecting a normal EVLWI ≤ 7 (28-sector scan: sensitivity = 81.8%, specificity = 94.9%, AUC = 0.939 versus 4-sector scan: sensitivity = 81.8%, specificity = 82.1%, AUC = 0.902). Both protocols were approximately equivalent in prediction of lung edema with EVLWI ≥ 10 (28-sector scan: sensitivity = 88.9%, specificity = 95.7%, AUC = 0.977 versus 4-sector scan: sensitivity = 81.5%, specificity = 91.3%, AUC = 0.958) or severe pulmonary edema with EVLWI ≥ 15 (28-sector scan: sensitivity = 91.7%, specificity = 97.4%, AUC = 0.995 versus 4-sector scan: sensitivity = 91.7%, specificity = 92.1%, AUC = 0.978). As secondary endpoints, our evaluations resulted in significant associations of 28-sector as well as simplified 4-sector B-Lines score with parameters of respiratory function. CONCLUSION: Both B-line protocols provide accurate non-invasive evaluation of lung water in critically ill patients. The 28-sector scan offers a marginal advantage in prediction of pulmonary edema, but needs substantially more time than 4-sector scan.

Prediction of Outcome in Acute Pancreatitis by the qSOFA and the New ERAP Score.

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.

Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: Results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study.

BACKGROUND: Outcome of severe acute pancreatitis (SAP) highly depends on the degree of systemic inflammation and organ failure. Although treatment approaches targeting the inflammatory cascade have failed in pancreatitis, recent studies suggest that extracorporeal cytokine adsorption effectively reduces concentrations of pro-inflammatory cytokines and potentially improves the outcome of sepsis. METHODS: Sixteen patients with SAP, presenting within 7 days upon onset of pain, an APACHE-II score of ≥10 and ≥1 marker of poor prognosis, received 2 consecutive 24-h treatments with CytoSorb® extracorporeal cytokine adsorption (intervention group). Hemodynamics, organ failure, and mortality were compared with an APACHE-II score-matched retrospective control group of 32 patients. RESULTS: The primary objective (20% decrease in the vasopressor dependency index or 20% increase in the cardiac index) was reached in 68.8% of the intervention and 28.1% of the control patients (p = 0.007), respectively. The cytokine adsorption significantly reduced IL-6 (-1998 pg/ml, p = 0.005) serum levels and resulted in stable CRP (p = 0.101) and decreased PCT (p = 0.003) levels in contrast to increased CRP (p = 0.014) and stable PCT levels (p = 0.695) in the control group. While mortality and improvement of respiratory failure were similar in both groups, renal failure significantly improved (change of KDIGO classification 72 h postcytokine adsorption [-1 vs. 0, p = 0.005]) and the SOFA score significantly decreased (day 5: -1.8 ± 2.0 vs. 1 ± 3.8, p = 0.013) in the intervention group. CONCLUSION: Cytokine adsorption might be an effective treatment option to stabilize hemodynamics in SAP. It decreases levels of the pro-inflammatory marker IL-6 and stabilizes organ function according to serial SOFA score assessments.

SARS-CoV-2 serology increases diagnostic accuracy in CT-suspected, PCR-negative COVID-19 patients during pandemic.

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.

High lipasemia is frequent in Covid-19 associated acute respiratory distress syndrome.

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).

Aspergillus fumigatus cholangitis in a patient with cholangiocarcinoma: case report and review of the literature.

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.

Convalescent plasma therapy in B-cell-depleted and B-cell sufficient patients with life-threatening COVID-19 - A case series.

OBJECTIVE: 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. PATIENTS AND METHODS: 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). RESULTS: 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. PO2/FiO2 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. CONCLUSION: 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.

Extracorporeal carbon dioxide removal with the Advanced Organ Support system in critically ill COVID-19 patients.

Disturbed oxygenation is foremost the leading clinical presentation in COVID-19 patients. However, a small proportion also develop carbon dioxide removal problems. The Advanced Organ Support (ADVOS) therapy (ADVITOS GmbH, Munich, Germany) uses a less invasive approach by combining extracorporeal CO2 -removal and multiple organ support for the liver and the kidneys in a single hemodialysis device. The aim of our study is to evaluate the ADVOS system as treatment option in-COVID-19 patients with multi-organ failure and carbon dioxide removal problems. COVID-19 patients suffering from severe respiratory insufficiency, receiving at least two treatments with the ADVOS multi system (ADVITOS GmbH, Munich, Germany), were eligible for study inclusion. Briefly, these included patients with acute kidney injury (AKI) according to KDIGO guidelines, and moderate or severe ARDS according to the Berlin definition, who were on invasive mechanical ventilation for more than 72 hours. In total, nine COVID-19 patients (137 ADVOS treatment sessions with a median of 10 treatments per patient) with moderate to severe ARDS and carbon dioxide removal problems were analyzed. During the ADVOS treatments, a rapid correction of acid-base balance and a continuous CO2 removal could be observed. We observed a median continuous CO2 removal of 49.2 mL/min (IQR: 26.9-72.3 mL/min) with some treatments achieving up to 160 mL/min. The CO2 removal significantly correlated with blood flow (Pearson 0.421; P < .001), PaCO2 (0.341, P < .001) and HCO 3 - levels (0.568, P < .001) at the start of the treatment. The continuous treatment led to a significant reduction in PaCO2 from baseline to the last ADVOS treatment. In conclusion, it was feasible to remove CO2 using the ADVOS system in our cohort of COVID-19 patients with acute respiratory distress syndrome and multiorgan failure. This efficient removal of CO2 was achieved at blood flows up to 300 mL/min using a conventional hemodialysis catheter and without a membrane lung or a gas phase.

Serum levels of advanced glycation end products and their receptors sRAGE and Galectin-3 in chronic pancreatitis.

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.

Vitamin D Deficiency Is Highly Prevalent in Critically Ill Patients and a Risk Factor for Mortality: A Prospective Observational Study Comparing Noncirrhotic Patients and Patients With Cirrhosis.

INTRODUCTION: A 25-hydroxyvitamin D, 25(OH)D, deficiency is common among critically ill patients and correlated with increased mortality. Furthermore, deficiency is associated with advanced liver disease. However, there are no studies available comparing the dimensions and consequences of a 25(OH)D deficiency between patients with and without liver cirrhosis in the setting of intensive care units (ICUs). This study focuses on differences in 25(OH)D status between critically ill noncirrhosis patients and patients with cirrhosis (primary end point), hypothesizing that deficiency and its impact on mortality risk are even more pronounced in patients with cirrhosis. METHODS: We performed a prospective observational study of 176 patients (noncirrhosis patients, N = 114; patients with cirrhosis, N = 62) with a laboratory assessment of 25(OH)D on ICU admission and survival analyses after 180 days. RESULTS: On admission, 55% of patients showed a severe deficiency, 25(OH)D <10 ng/mL, and a further 23% moderate deficiency (10-19 ng/mL). The overall median level of 25(OH)D was 8.0 (5.0-18.0) ng/mL (10.5 [6.0-21.3] in noncirrhosis patients vs 7.0 [4.8-10.0] in patients with cirrhosis; P < .001). We found extremely low levels particularly in patients without prior vitamin D supplementation (6.0 [4.0-7.5] in patients with cirrhosis vs 8.0 [5.0-12.0] ng/mL in noncirrhosis patients; P = .004). Vitamin D status correlated inversely with the sequential organ failure assessment, acute and physiology chronic health evaluation, model of end-stage liver disease, and Child-Pugh scores. Survival analyses categorized 25(OH)D levels <10 ng/mL as a high-risk factor for mortality 180 days after admission (hazard ratio [HR]: 2.45, 95% confidence interval [CI] = 1.60-3.70; P < .001). In patients with cirrhosis, a severe deficiency (<10 ng/mL) involved a significantly higher mortality risk than in noncirrhosis patients (HR: 2.30, 95% CI = 1.39-3.82; P = .001). In cases of admission levels ≥10 ng/mL, however, mortality risk was similar between patients with cirrhosis and noncirrhosis patients (HR: 1.08, 95% CI = 0.43-2.73; P = .873). CONCLUSIONS: Hypovitaminosis D is a highly frequent disorder in critically ill patients admitted to ICU. A severe deficiency with levels <10 ng/mL is a high risk factor for increased mortality, especially in patients with cirrhosis.

Transpulmonary thermodilution before and during veno-venous extra-corporeal membrane oxygenation ECMO: an observational study on a potential loss of indicator into the extra-corporeal circuit.

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/m2; p = 0.43). By contrast, GEDVI (791 ± 179 vs. 974 ± 384 mL/m2; 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/m2; 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.

Influence of Sustained Low-Efficiency Dialysis Treatment on Isavuconazole Plasma Levels in Critically Ill Patients.

Isavuconazole plasma concentrations were measured before and after sustained low-efficiency dialysis (SLED) treatment in 22 critically ill adult patients with probable invasive aspergillosis and underlying hematological malignancies. Isavuconazole levels were significantly lower after SLED treatment (5.73 versus 3.36 µg/ml; P < 0.001). However, even after SLED treatment, isavuconazole concentrations exceeded the in vivo MICs for several relevant Aspergillus species.

Changes in pathogen spectrum and antimicrobial resistance development in the time-course of acute necrotizing pancreatitis.

BACKGROUND AND AIM: In contrast to the first peak of multi-organ failure in acute pancreatitis, the second peak is mostly triggered by septic complications. Our aim was to analyze the spectrum of pathogens and antimicrobial resistance development in relation to the time-course of the disease and its clinical outcome. METHODS: One hundred twenty-two patients with acute necrotizing pancreatitis undergoing pancreas puncture at two tertiary academic medical centers in Germany were retrospectively analyzed. RESULTS: At species level, there was a change in spectrum from Enterococcus faecalis (∆d150 - d1 = 14.6% - 16.7% = -2.1%) to Enterococcus faecium (∆d150 - d1 = 93.1% - 16.3% = 76.8%) (P < 0.001) and from Candida albicans (∆d150 - d1 = 39.7% - 23.6% = 16.1%) to non-albicans Candida spp. (∆d150 - d1 = 43.5% - 6.4% = 37.1%) (P = 0.005). Time-to-event analysis of acquired antimicrobial resistance showed that the overall number of patients with Enterobacteriaceae presented an antimicrobial susceptibility decrease by 59.7% (∆d1 - d100 = 87.0% - 27.3% = 59.7%). The cumulative incidence of multi-resistant bacteria increased with length of hospital stay (∆d150 - d1 = 49.1% - 3.1% = 46.0%) (P = 0.004). Multivariable logistic regression analysis in relation to the pathogen spectrum and antimicrobial resistance development showed a significantly higher mortality for non-albicans Candida spp. (P = 0.039, odds ratio [OR] = 3.32 [95% confidence interval [CI]: 1.07-10.35]), E. faecium (P = 0.009, OR = 3.73 [95% CI: 1.38-10.05]), and multi-resistant bacteria (P = 0.007, OR = 5.08 [95% CI: 1.55-16.66]). CONCLUSIONS: Antimicrobial treatment of infected pancreatic necrosis becomes more challenging over time, owing to a change in spectrum favoring difficult-to-treat pathogens and an increase in multi-resistant bacteria associated with worse clinical outcomes (World Health Organization trial registration number: DRKS00014785).

Increased risk of candidemia in patients with necrotising pancreatitis infected with candida species.

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.