The Impact of Educational Status on the Occurrence of Colonic Diverticula: Insights from an Austrian Cohort Study.

OBJECTIVE: Education often reflects socioeconomic status. Research indicates that lower socioeconomic status may increase the risk of diverticulosis, and according to data from the USA, diverticular disease is a significant and costly health problem. Our study explores the link between educational level and colonic diverticula occurrence. SUBJECT AND METHODS: We conducted a cohort study on 5,532 asymptomatic Austrian patients who underwent colonoscopy, categorizing them by education level using the updated Generalized International Standard Classification of Education (GISCED). Logistic regression models, adjusting for age, gender, metabolic syndrome, diet, and activity, were used to determine the association between education and diverticulosis. RESULTS: Overall, 39% of the patients had low educational status, while 53% had medium, and 8% had high educational status. Colon diverticula were less frequent in patients with medium (OR 0.73) and high (aOR 0.62) educational status. Medium educational level remained associated with lower rates of diverticulosis after adjustment for age and sex (aOR 0.85) and further metabolic syndrome, dietary habits, and physical activity (aOR 0.84). In higher education status, this phenomenon was only seen by trend. CONCLUSION: Low education correlated with higher colon diverticula risk, while medium education showed lower rates even after adjustments. This trend persisted at higher education levels, highlighting the potential for strategies for cost reduction tailored to socioeconomic conditions.

Association of cardiovascular health and educational status in a screening cohort.

INTRODUCTION: The global burden of chronic diseases, including cardiovascular disease, remains a significant public health challenge. The Life's Simple 7 (LS7) score was developed as a tool to evaluate cardiovascular health behaviours and habits and identify high-risk individuals. The present study aimed to assess the distribution of LS7 scores among educational strata. METHODS: The study population consisted of 3,383 asymptomatic individuals screened for colorectal cancer at a single centre in Austria. We split patients into lower (n = 1,055), medium (n = 1,997), and higher (n = 331) education, based on the International Standard Classification of Education (ISCED). Cox regression models were utilized to determine the association between education and mortality over a median follow-up period of 7 years. RESULTS: Individuals with higher educational status had a significantly higher prevalence of ideal cardiovascular health metrics, as defined by the LS7 score, compared to those with medium and lower educational status: n = 94 (28%) vs. n = 347 (17%) and n = 84 (8%), respectively, (p < 0.001). In the Cox regression analysis, both medium (HR = 0.61, 95% CI: 0.43-0.84, p < 0.001) and higher educational status (HR = 0.44, 95% CI: 0.19-1.01, p = 0.06) were associated with all-cause mortality, as was the LS7. CONCLUSION: Our findings highlight a significant association between lower educational status and poorer cardiovascular health, as assessed by LS7, which persisted even after multivariable adjustment. Additionally, both educational status and LS7 were associated with increased mortality, underscoring the significance of our results. These findings have important implications for public health, as screening and prevention strategies may need to be tailored to meet the diverse educational backgrounds of individuals, given the higher prevalence of unhealthy lifestyle behaviours among those with lower educational status.

Diabetes mellitus is associated with 90-day mortality in old critically ill COVID-19 patients: a multicenter prospective observational cohort study.

BACKGROUND: Several studies have found an association between diabetes mellitus, disease severity and outcome in COVID-19 patients. Old critically ill patients are particularly at risk. This study aimed to investigate the impact of diabetes mellitus on 90-day mortality in a high-risk cohort of critically ill patients over 70 years of age. METHODS: This multicentre international prospective cohort study was performed in 151 ICUs across 26 countries. We included patients ≥ 70 years of age with a confirmed SARS-CoV-2 infection admitted to the intensive care unit from 19th March 2020 through 15th July 2021. Patients were categorized into two groups according to the presence of diabetes mellitus. Primary outcome was 90-day mortality. Kaplan-Meier overall survival curves until day 90 were analysed and compared using the log-rank test. Mixed-effect Weibull regression models were computed to investigate the influence of diabetes mellitus on 90-day mortality. RESULTS: This study included 3420 patients with a median age of 76 years were included. Among these, 37.3% (n = 1277) had a history of diabetes mellitus. Patients with diabetes showed higher rates of frailty (32% vs. 18%) and several comorbidities including chronic heart failure (20% vs. 11%), hypertension (79% vs. 59%) and chronic kidney disease (25% vs. 11%), but not of pulmonary comorbidities (22% vs. 22%). The 90-day mortality was significantly higher in patients with diabetes than those without diabetes (64% vs. 56%, p < 0.001). The association of diabetes and 90-day mortality remained significant (HR 1.18 [1.06-1.31], p = 0.003) after adjustment for age, sex, SOFA-score and other comorbidities in a Weibull regression analysis. CONCLUSION: Diabetes mellitus was a relevant risk factor for 90-day mortality in old critically ill patients with COVID-19. STUDY REGISTRATION: NCT04321265, registered March 19th, 2020.

The impact of ethnic background on ICU care and outcome in sepsis and septic shock - A retrospective multicenter analysis on 17,949 patients.

BACKGROUND: Previous studies have been inconclusive about racial disparities in sepsis. This study evaluated the impact of ethnic background on management and outcome in sepsis and septic shock. METHODS: This analysis included 17,146 patients suffering from sepsis and septic shock from the multicenter eICU Collaborative Research Database. Generalized estimated equation (GEE) population-averaged models were used to fit three sequential regression models for the binary primary outcome of hospital mortality. RESULTS: Non-Hispanic whites were the predominant group (n = 14,124), followed by African Americans (n = 1,852), Hispanics (n = 717), Asian Americans (n = 280), Native Americans (n = 146) and others (n = 830). Overall, the intensive care treatment and hospital mortality were similar between all ethnic groups. This finding was concordant in patients with septic shock and persisted after adjusting for patient-level variables (age, sex, mechanical ventilation, vasopressor use and comorbidities) and hospital variables (teaching hospital status, number of beds in the hospital). CONCLUSION: We could not detect ethnic disparities in the management and outcomes of critically ill septic patients and patients suffering from septic shock. Disparate outcomes among critically ill septic patients of different ethnicities are a public health, rather than a critical care challenge.

The association between educational status and colorectal neoplasia: results from a screening cohort.

INTRODUCTION: Educational status is used as a proxy for socioeconomic status. While lower levels of education are generally associated with poorer health, the data on the relationship between educational status and colorectal neoplasia is heterogenous. The aim of our study was to examine this relationship and to adjust the association between educational status and colorectal neoplasia for other health parameters. METHODS: We included 5977 participants undergoing a screening colonoscopy in Austria. We split the cohort into patients with lower (n = 2156), medium (n = 2933), and higher (n = 459) educational status. Multivariable multilevel logistic regression models were fitted to evaluate the association between educational status and the occurrence of any or advanced colorectal neoplasia. We adjusted for age, sex, metabolic syndrome, family history, physical activity, alcohol consumption, and smoking status. RESULTS: We found that the rates of any neoplasia (32%) were similar between the educational strata. However, patients with higher (10%) educational status evidenced significantly higher rates of advanced colorectal neoplasia compared to medium (8%) and lower (7%) education. This association remained statistically significant after multivariable adjustment. The difference was entirely driven by neoplasia in the proximal colon. CONCLUSION: Our study found that higher educational status was associated with a higher prevalence of advanced colorectal neoplasia compared to medium and lower educational status. This finding remained significant even after adjusting for other health parameters. Further research is needed to understand the underlying reasons for the observed difference, especially with regard to the specific anatomical distribution of the observed difference.

Diverticulosis and cardiometabolic risk factors: a systematic literature review.

BACKGROUND: There is a hypothesis of an association between diverticulosis and metabolic syndrome (MS) or its components, but data on this topic are inconsistent, and a systematic review has not been performed. We conducted a systematic review to investigate the possible association between cardiometabolic risk factors and diverticulosis. METHODS: A systematic literature search was conducted via PubMed, Cochrane Library, and Web of Science in December 2022 to collect the necessary data. Studies that examined the association between MS or individual metabolic factors and asymptomatic diverticulosis were included in the review. RESULTS: Of the potentially relevant articles identified via PubMed (477), Cochrane Library (224), and Web of Science (296), 29 articles met the inclusion criteria and were used for this work. These studies were assessed for study quality using GRADE. Overall, 6 studies were rated as "very low," 19 studies as "low," and 4 studies as "moderate." The data suggest an association between arterial hypertension, obesity, and fatty liver disease in younger patients and diverticulosis. Patient age appears to play an important role in diverticular formation. Data on diabetes mellitus is inconclusive and may require further investigation depending on the location of the diverticula. CONCLUSION: Based on the synthesized data, there is an association between arterial hypertension, obesity, and fatty liver disease in younger patients. The formation of diverticula seems to be influenced by age and genetic factors. The study suggests a connection with cardiometabolic risk factors. To gain a better understanding of the role of metabolic risk factors in asymptomatic diverticulosis, targeted studies are necessary based on these findings.

sST2 Levels Show No Association with Helicobacter pylori Infection in Asymptomatic Patients: Implications for Biomarker Research.

INTRODUCTION: Helicobacter pylori (H. pylori) is a prevalent stomach bacterium that can cause a range of clinical outcomes, including gastric cancer. In recent years, soluble suppression of tumorigenicity-2 (sST2) has gained attention as a biomarker associated with various diseases, such as gastric cancer. The purpose of this study was to explore the possible connection between H. pylori infection and sST2 levels in patients who do not exhibit symptoms. METHODS: A total of 694 patients from the Salzburg Colon Cancer Prevention Initiative (Sakkopi) were included in the study. The prevalence of H. pylori infection was determined by histology, and sST2 levels were measured in serum samples. Clinical and laboratory parameters, such as age, sex, BMI, smoking status, hypertension, and metabolic syndrome, were also collected. RESULTS: The median sST2 concentration was similar between patients with (9.62; 7.18-13.44 ng/mL; p = 0.66) and without (9.67; 7.08-13.06 ng/mL) H. pylori. Logistic regression analysis did not show any association (OR 1.00; 95%CI 0.97-1.04; p = 0.93) between sST2 levels and H. pylori infection, which remained so (aOR 0.99; 95%CI 0.95-1.03; p = 0.60) after adjustment for age, sex, educational status, and metabolic syndrome. In addition, sensitivity analyses stratified by age, sex, BMI, smoking status, educational status, and the concomitant diagnosis of metabolic syndrome could not show any association between sST2 levels and H. pylori infection. CONCLUSION: The results indicate that sST2 may not serve as a valuable biomarker in the diagnosis and treatment of H. pylori infection. Our findings are of relevance for further research investigating sST2, as we could not find an influence of asymptomatic H. pylori infection on sST2 concentration. WHAT IS ALREADY KNOWN?: Soluble suppression of tumorigenicity-2 (sST2) has gained attention as a biomarker associated with various diseases, such as gastric cancer. WHAT IS NEW IN THIS STUDY?: The median sST2 concentration was similar between patients with (9.62; 7.18-13.44 ng/mL; p = 0.66) and without (9.67; 7.08-13.06 ng/mL) H. pylori. WHAT ARE THE FUTURE CLINICAL AND RESEARCH IMPLICATIONS OF THE STUDY FINDINGS?: The results indicate that sST2 may not serve as a valuable biomarker in the diagnosis and treatment of H. pylori infection.

The Association between Helicobacter pylori and Colorectal Neoplasia.

OBJECTIVES: Helicobacter pylori (H. pylori) and colorectal neoplasia (CRN) are frequent entities. Epidemiological data suggest an association between H. pylori positivity (H. pylori +) and CRN, whereas pathophysiologic considerations substantiate a possible causal relationship. However, the relationship between CRN and H. pylori + may also be mediated by shared risk factors. Therefore, the aim of this cross-sectional study was to evaluate a possible independent relationship between H. pylori and CRN in a Central European cohort. METHODS: We included 5,707 asymptomatic patients. All patients underwent screening colonoscopy and upper gastrointestinal endoscopy. We assessed the association between any CRN and advanced CRN with H. pylori + using multilevel logistic regression. We adjusted for age, sex, a positive family history of colorectal cancer, and cardiovascular risk. RESULTS: 1,082 patients (19%) were H. pylori + and 4,625 (81%) H. pylori -. Patients with both CRN and H. pylori had more cardiometabolic risk factors. In univariate (aOR 1.20; 1.10-1.31) and multivariable analysis (aOR 1.20; 1.08-1.32), H. pylori + was associated with the diagnosis of any CRN. However, H. pylori + was associated with the presence of advanced CRN (aOR 1.26; 0.96-1.64) only in trend. CONCLUSIONS: We found a clustered co-occurrence of CRN and H. pylori. This association persisted after correction for shared cardiometabolic risk factors. We suggest that our analysis emphasizes the clinical value of H. pylori eradication. Whether "test and treat" H. pylori is warranted to prevent CRN remains unclear but is at least a possibility given the simplicity of "test and treat."

Prevalence of Subclinical Cardiovascular Disease in Patients with Non-Alcoholic-Fatty Liver Disease: Analysis of the Paracelsus 10.000 Cohort Study.

BACKGROUND: In patients with non-alcoholic fatty liver disease (NAFLD) cardiovascular diseases are more often the cause of death than the liver disease itself. However, the prevalence of atherosclerotic manifestations in individuals with NAFLD is still uncertain. This study aimed to explore the association between NAFLD and coronary artery calcification (CAC) in a Central European population. METHODS: A total of 1,743 participants from the Paracelsus 10,000 study were included. The participants underwent CAC scoring and were assessed for fatty liver index (FLI), fibrosing non-alcoholic steatohepatitis Index (FNI) and fibrosis-4 index (FIB-4 score), which are indicators for steatosis and fibrosis. Multivariable logistic regression models were calculated. RESULTS: Results revealed an association between liver steatosis/fibrosis and CAC. A FLI > 60 was associated with higher odds of NAFLD (OR 3.38, 95% CI: 2.61-4.39, p < 0.01) and increased prevalence of CAC-Score >300 compared to FLI <30 (9% vs. 3%, p < 0.01), even after adjusting for traditional cardiometabolic risk factors. While the crude odds ratios of the FIB-4 scores ≥ 1.3 and FNI score were significantly associated with increased odds of CAC, they became non-significant after adjusting for age, sex, and MetS. CONCLUSION: This study reveals a significant association between NAFLD and CAC. The findings suggest that assessing liver fat and fibrosis could enhance assessment of cardiovascular risk, but further research is needed to determine whether hepatic fat plays an independent role in the development of atherosclerosis and whether targeting liver steatosis can mitigate vascular risk.

Variations in end-of-life care practices in older critically ill patients with COVID-19 in Europe.

BACKGROUND: Previous studies reported regional differences in end-of-life care (EoLC) for critically ill patients in Europe. OBJECTIVES: The purpose of this post-hoc analysis of the prospective multicentre COVIP study was to investigate variations in EoLC practices among older patients in intensive care units during the coronavirus disease 2019 pandemic. METHODS: A total of 3105 critically ill patients aged 70 years and older were enrolled in this study (Central Europe: n = 1573; Northern Europe: n = 821; Southern Europe: n = 711). Generalised estimation equations were used to calculate adjusted odds ratios (aORs) to population averages. Data were adjusted for patient-specific variables (demographic, disease-specific) and health economic data (gross domestic product, health expenditure per capita). The primary outcome was any treatment limitation, and 90-day mortality was a secondary outcome. RESULTS: The frequency of the primary endpoint (treatment limitation) was highest in Northern Europe (48%), intermediate in Central Europe (39%) and lowest in Southern Europe (24%). The likelihood for treatment limitations was lower in Southern than in Central Europe (aOR 0.39; 95% confidence interval [CI] 0.21-0.73; p = 0.004), even after multivariable adjustment, whereas no statistically significant differences were observed between Northern and Central Europe (aOR 0.57; 95%CI 0.27-1.22; p = 0.15). After multivariable adjustment, no statistically relevant mortality differences were found between Northern and Central Europe (aOR 1.29; 95%CI 0.80-2.09; p = 0.30) or between Southern and Central Europe (aOR 1.07; 95%CI 0.66-1.73; p = 0.78). CONCLUSION: This study shows a north-to-south gradient in rates of treatment limitation in Europe, highlighting the heterogeneity of EoLC practices across countries. However, mortality rates were not affected by these results.

Helicobacter pylori and cardiovascular risk: Only a dead Helicobacter is a good Helicobacter?

OBJECTIVES: Helicobacter pylori (H. pylori) and cardiovascular (CV) disease share common symptoms and underlie many general medical complaints. Preliminary studies suggest an association between H. pylori positivity and CV risk, and gastroenterological guidelines recommend eradication of H. pylori in patients with manifest atherosclerosis. Therefore, the aim of this study was to examine the reciprocal association of H. pylori positivity and CV risk for their independence of shared risk factors. METHODS: We included 3284 asymptomatic participants of a colorectal cancer screening cohort who were offered and underwent upper gastrointestinal endoscopy. We calculated the 10-year risk for a CV event using the novel SCORE2 for each patient. We evaluated the association between H. pylori positivity and CV risk assessed by SCORE2 using both multilevel logistic and linear regression. We adjusted for age, sex and the concomitant diagnosis of metabolic syndrome. Lastly, we assessed the association between H. pylori status and mortality using proportional hazard Cox regression. RESULTS: In total, 2659 patients were H. pylori negative and 625 H. pylori positive. Helicobacter pylori positivity was associated with SCORE2 and remained so (r = .33; 95% CI 0.09-0.57; p = .006) after adjustment for age, sex, and the diagnosis of metabolic syndrome. Also, SCORE2 was associated with higher odds for H. pylori positivity (aOR 1.03 95% CI 1.01-1.05; p = .02) even after multivariable adjustment. Helicobacter pylori positivity was associated with neither CV (HR 0.60 95% CI 0.14-2.63; p = .50) nor all-cause (HR 1.20 95% CI 0.77-1.87; p = .43) mortality during a median follow-up of 9 years. CONCLUSIONS: In our study, H. pylori positivity and CV risk were independently associated. This did not translate into a dissimilar CV mortality between H. pylori positive and H. pylori negative patients. However, the overwhelming majority of our patients underwent H. pylori eradication. We, therefore, think that H. pylori eradication is at least safe from a cardiovascular perspective and warranted from gastrointestinal standpoint.

Virtual and augmented reality in critical care medicine: the patient's, clinician's, and researcher's perspective.

Virtual reality (VR) and augmented reality (AR) are aspiring, new technologies with increasing use in critical care medicine. While VR fully immerses the user into a virtual three-dimensional space, AR adds overlaid virtual elements into a real-world environment. VR and AR offer great potential to improve critical care medicine for patients, relatives and health care providers. VR may help to ameliorate anxiety, stress, fear, and pain for the patient. It may assist patients in mobilisation and rehabilitation and can improve communication between all those involved in the patient's care. AR can be an effective tool to support continuous education of intensive care medicine providers, and may complement traditional learning methods to acquire key practical competences such as central venous line placement, cardiopulmonary resuscitation, extracorporeal membrane oxygenation device management or endotracheal intubation. Currently, technical, human, and ethical challenges remain. The adaptation and integration of VR/AR modalities into useful clinical applications that can be used routinely on the ICU is challenging. Users may experience unwanted side effects (so-called "cybersickness") during VR/AR sessions, which may limit its applicability. Furthermore, critically ill patients are one of the most vulnerable patient groups and warrant special ethical considerations if new technologies are to be introduced into their daily care. To date, most studies involving AR/VR in critical care medicine provide only a low level of evidence due to their research design. Here we summarise background information, current developments, and key considerations that should be taken into account for future scientific investigations in this field.

Noninvasive ventilation in COVID-19 patients aged ≥ 70 years-a prospective multicentre cohort study.

BACKGROUND: Noninvasive ventilation (NIV) is a promising alternative to invasive mechanical ventilation (IMV) with a particular importance amidst the shortage of intensive care unit (ICU) beds during the COVID-19 pandemic. We aimed to evaluate the use of NIV in Europe and factors associated with outcomes of patients treated with NIV. METHODS: This is a substudy of COVIP study-an international prospective observational study enrolling patients aged ≥ 70 years with confirmed COVID-19 treated in ICU. We enrolled patients in 156 ICUs across 15 European countries between March 2020 and April 2021.The primary endpoint was 30-day mortality. RESULTS: Cohort included 3074 patients, most of whom were male (2197/3074, 71.4%) at the mean age of 75.7 years (SD 4.6). NIV frequency was 25.7% and varied from 1.1 to 62.0% between participating countries. Primary NIV failure, defined as need for endotracheal intubation or death within 30 days since ICU admission, occurred in 470/629 (74.7%) of patients. Factors associated with increased NIV failure risk were higher Sequential Organ Failure Assessment (SOFA) score (OR 3.73, 95% CI 2.36-5.90) and Clinical Frailty Scale (CFS) on admission (OR 1.46, 95% CI 1.06-2.00). Patients initially treated with NIV (n = 630) lived for 1.36 fewer days (95% CI - 2.27 to - 0.46 days) compared to primary IMV group (n = 1876). CONCLUSIONS: Frequency of NIV use varies across European countries. Higher severity of illness and more severe frailty were associated with a risk of NIV failure among critically ill older adults with COVID-19. Primary IMV was associated with better outcomes than primary NIV. Clinical Trial Registration NCT04321265 , registered 19 March 2020, https://clinicaltrials.gov .

Association between tracheostomy timing and outcomes for older critically ill COVID-19 patients: prospective observational study in European intensive care units.

BACKGROUND: Tracheostomy is performed in patients expected to require prolonged mechanical ventilation, but to date optimal timing of tracheostomy has not been established. The evidence concerning tracheostomy in COVID-19 patients is particularly scarce. We aimed to describe the relationship between early tracheostomy (≤10 days since intubation) and outcomes for patients with COVID-19. METHODS: This was a prospective cohort study performed in 152 centres across 16 European countries from February to December 2020. We included patients aged ≥70 yr with confirmed COVID-19 infection admitted to an intensive care unit, requiring invasive mechanical ventilation. Multivariable analyses were performed to evaluate the association between early tracheostomy and clinical outcomes including 3-month mortality, intensive care length of stay, and duration of mechanical ventilation. RESULTS: The final analysis included 1740 patients with a mean age of 74 yr. Tracheostomy was performed in 461 (26.5%) patients. The tracheostomy rate varied across countries, from 8.3% to 52.9%. Early tracheostomy was performed in 135 (29.3%) patients. There was no difference in 3-month mortality between early and late tracheostomy in either our primary analysis (hazard ratio [HR]=0.96; 95% confidence interval [CI], 0.70-1.33) or a secondary landmark analysis (HR=0.78; 95% CI, 0.57-1.06). CONCLUSIONS: There is a wide variation across Europe in the timing of tracheostomy for critically ill patients with COVID-19. However, we found no evidence that early tracheostomy is associated with any effect on survival amongst older critically ill patients with COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04321265.

Health-related quality of life in older patients surviving ICU treatment for COVID-19: results from an international observational study of patients older than 70 years.

BACKGROUND: health-related quality of life (HRQoL) is an important patient-centred outcome in patients surviving ICU admission for COVID-19. It is currently not clear which domains of the HRQoL are most affected. OBJECTIVE: to quantify HRQoL in order to identify areas of interventions. DESIGN: prospective observation study. SETTING: admissions to European ICUs between March 2020 and February 2021. SUBJECTS: patients aged 70 years or older admitted with COVID-19 disease. METHODS: collected determinants include SOFA-score, Clinical Frailty Scale (CFS), number and timing of ICU procedures and limitation of care, Katz Activities of Daily Living (ADL) dependence score. HRQoL was assessed at 3 months after ICU admission with the Euro-QoL-5D-5L questionnaire. An outcome of ≥4 on any of Euro-QoL-5D-5L domains was considered unfavourable. RESULTS: in total 3,140 patients from 14 European countries were included in this study. Three months after inclusion, 1,224 patients (39.0%) were alive and the EQ-5D-5L from was obtained. The CFS was associated with an increased odds ratio for an unfavourable HRQoL outcome after 3 months; OR 1.15 (95% confidence interval (CI): 0.71-1.87) for CFS 2 to OR 4.33 (95% CI: 1.57-11.9) for CFS ≧ 7. The Katz ADL was not statistically significantly associated with HRQoL after 3 months. CONCLUSIONS: in critically ill old intensive care patients suffering from COVID-19, the CFS is associated with the subjectively perceived quality of life. The CFS on admission can be used to inform patients and relatives on the risk of an unfavourable qualitative outcome if such patients survive.

The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial.

BACKGROUND: In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients. METHODS: This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day- and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression. RESULTS: 44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p < 0.001), arterial hypertension (70% versus 65%, p = 0.006) and had a higher score on Clinical Frailty Scale (CFS; IQR 2-5 versus IQR 2-4, p < 0.001). Patients under prior paracetamol treatment were less often subjected to intubation and vasopressor use, compared to patients without paracetamol intake (65 versus 71%, p < 0.001; 63 versus 69%, p = 0.007). Paracetamol intake was not associated with ICU-, 30-day- and 3-month-mortality, remaining true after multivariate adjusted analysis. CONCLUSION: Paracetamol intake prior to ICU admission was not associated with short-term and 3-month mortality in old, critically ill intensive care patients suffering from COVID-19. TRIAL REGISTRATION: This prospective international multicentre study was registered on ClinicalTrials.gov with the identifier "NCT04321265" on March 25, 2020.

Therapeutic Potential of Sunitinib in Ameliorating Endothelial Dysfunction in Type 2 Diabetic Rats.

INTRODUCTION: Sunitinib, a multi-targeted tyrosine kinase receptor inhibitor used to treat renal-cell carcinoma and gastrointestinal stromal tumor, was recently shown to have a beneficial effect on metabolism in type 2 diabetes (T2D). Endothelial dysfunction is a key factor behind macro- and microvascular complications in T2D. The effect of sunitinib on endothelial function in T2D remains, however, unclear. We therefore tested the hypothesis that sunitinib ameliorates endothelial dysfunction in T2D. METHODS: Sunitinib (2 mg/kg/day, by gavage) was administered to T2D Goto-Kakizaki (GK) rats for 6 weeks, while water was given to GK and Wistar rats as controls. Hemodynamic, inflammatory, and metabolic parameters as well as endothelial function were measured. RESULTS: Systolic, mean arterial blood pressures, plasma tumor necrosis factor α levels, kidney weight to body weight (BW) ratio, and glucose levels were higher, while BW was lower in GK rats than in Wistar rats. Six-week treatment with sunitinib in GK rats did not affect these parameters but suppressed the increase in glucose levels. Endothelium-dependent relaxations were reduced in both aortas and mesenteric arteries isolated from GK as compared to Wistar rats, which was markedly reversed in both types of arteries from GK rats treated with sunitinib. CONCLUSIONS: This study demonstrates that sunitinib has a glucose-lowering effect and ameliorates endothelial dysfunction in both conduit and resistance arteries of GK rats.

Sex-specific treatment characteristics and 30-day mortality outcomes of critically ill COVID-19 patients over 70 years of age-results from the prospective COVIP study.

PURPOSE: Older critically ill patients with COVID-19 have been the most vulnerable during the ongoing pandemic, with men being more prone to hospitalization and severe disease than women. We aimed to explore sex-specific differences in treatment and outcome after intensive care unit (ICU) admission in this cohort. METHODS: We performed a sex-specific analysis in critically ill patients ≥ 70 yr of age with COVID-19 who were included in the international prospective multicenter COVIP study. All patients were analyzed for ICU admission and treatment characteristics. We performed a multilevel adjusted regression analysis to elucidate associations of sex with 30-day mortality. RESULTS: A total of 3,159 patients (69.8% male, 30.2% female; median age, 75 yr) were included. Male patients were significantly fitter than female patients as determined by the Clinical Frailty Scale (fit, 67% vs 54%; vulnerable, 14% vs 19%; frail, 19% vs 27%; P < 0.001). Male patients more often underwent tracheostomy (20% vs 14%; odds ratio [OR], 1.57; P < 0.001), vasopressor therapy (69% vs 62%; OR, 1.25; P = 0.02), and renal replacement therapy (17% vs 11%; OR, 1.96; P < 0.001). There was no difference in mechanical ventilation, life-sustaining treatment limitations, and crude 30-day mortality (50% male vs 49% female; OR, 1.11; P = 0.19), which remained true after adjustment for disease severity, frailty, age and treatment limitations (OR, 1.17; 95% confidence interval, 0.94 to 1.45; P = 0.16). CONCLUSION: In this analysis of sex-specific treatment characteristics and 30-day mortality outcomes of critically ill patients with COVID-19 ≥ 70 yr of age, we found more tracheostomy and renal replacement therapy in male vs female patients, but no significant association of patient sex with 30-day mortality. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04321265); registered 25 March 2020).

RéSUMé: OBJECTIF: Les patients âgés gravement malades atteints de la COVID-19 ont été les plus vulnérables pendant la pandémie actuelle, les hommes étant plus sujets à l'hospitalisation et aux maladies graves que les femmes. Nous avons cherché à explorer les différences spécifiques au sexe dans le traitement et les devenirs après l'admission à l'unité de soins intensifs (USI) dans cette cohorte. MéTHODE: Nous avons effectué une analyse spécifique au sexe chez des patients gravement malades âgés de ≥ 70 ans atteints de COVID-19 qui ont été inclus dans l'étude prospective multicentrique internationale COVIP. Tous les patients ont été analysés pour connaître les détails de leur admission à l'USI et les caractéristiques de leur traitement. Nous avons réalisé une analyse de régression ajustée à plusieurs niveaux pour élucider les associations entre le sexe et la mortalité à 30 jours. RéSULTATS: Au total, 3159 patients (69,8 % d'hommes, 30,2 % de femmes; âge médian, 75 ans) ont été inclus. Les patients de sexe masculin étaient significativement plus en forme que les patientes, tel que déterminé par l'échelle de fragilité clinique (bonne santé, 67 % vs 54 %; vulnérables, 14 % vs 19 %; fragiles, 19 % vs 27 %; P < 0,001). Les patients de sexe masculin ont plus souvent bénéficié d'une trachéostomie (20 % vs 14 %; rapport de cotes [RC], 1,57; P < 0,001), d'un traitement vasopresseur (69 % vs 62 %; RC, 1,25; P = 0,02) et d'un traitement substitutif de l'insuffisance rénale (17 % vs 11 %; RC, 1,96; P < 0,001). Il n'y avait aucune différence en matière de ventilation mécanique, de limites des traitements de maintien en vie et de mortalité brute à 30 jours (50 % d'hommes vs 49 % de femmes; RC, 1,11; P = 0,19), ce qui est demeuré le cas après ajustement pour tenir compte de la gravité de la maladie, de la fragilité, de l'âge et des limites du traitement (RC, 1,17 ; intervalle de confiance à 95 %, 0,94 à 1,45; P = 0,16). CONCLUSION: Dans cette analyse des caractéristiques de traitement spécifiques au sexe et des résultats de mortalité à 30 jours des patients gravement malades atteints de COVID-19 de ≥ 70 ans, nous avons noté un nombre plus élevé de trachéotomies et de traitements substitutifs de l'insuffisance rénale chez les hommes vs les femmes, mais aucune association significative entre le sexe des patients et la mortalité à 30 jours. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04321265); enregistré le 25 mars 2020.

Management of intoxicated patients - a descriptive outcome analysis of 4,267 ICU patients.

INTRODUCTION: Intoxications are common in intensive care units (ICUs). The number of causative substances is large, mortality usually low. This retrospective cohort study aims to characterize differences of intoxicated compared to general ICU patients, point out variations according to causative agents, as well as to highlight differences between survivors and non-survivors among intoxicated individuals in a large-scale multi-center analysis. METHODS: A total of 105,998 general ICU patients and 4,267 individuals with the admission diagnoses "overdose" and "drug toxicity" from the years 2014 and 2015 where included from the eICU Collaborative Research Database. In addition to comparing these groups with respect to baseline characteristics, intensive care measures and outcome parameters, differences between survivors and non-survivors from the intoxication group, as well as the individual groups of causative substances were investigated. RESULTS: Intoxicated patients were younger (median 41 vs. 66 years; p<0.001), more often female (55 vs. 45%; p<0.001), and normal weighted (36% vs. 30%; p<0.001), whereas more obese individuals where observed in the other group (37 vs. 31%; p<0.001). Intoxicated individuals had a significantly lower mortality compared to general ICU patients (1% vs. 10%; aOR 0.07 95%CI 0.05-0.11; p<0.001), a finding which persisted after multivariable adjustment (aOR 0.17 95%CI 0.12-0.24; p<0.001) and persisted in all subgroups. Markers of disease severity (SOFA-score: 3 (1-5) vs. 4 (2-6) pts.; p<0.001) and frequency of vasopressor use (5 vs. 15%; p<0.001) where lower, whereas rates of mechanical ventilation where higher (24 vs. 26%; p<0.001) in intoxicated individuals. There were no differences with regard to renal replacement therapy in the first three days (3 vs. 4%; p=0.26). In sensitivity analysis (interactions for age, sex, ethnicity, hospital category, maximum initial lactate, mechanical ventilation, and vasopressor use), a trend towards lower mortality in intoxicated patients persisted in all subgroups. CONCLUSION: This large-scale retrospective analysis indicates a significantly lower mortality of intoxicated individuals compared to general ICU patients.

The Association of Glucose Control with Circulating Levels of Red Blood Cell-Derived Vesicles in Type 2 Diabetes Mellitus Patients with Atrial Fibrillation.

Hyperglycemia is a trigger for structural alteration of red blood cells (RBCs) and their ability to release extracellular vesicles (EVs). The aim of the study was to elucidate whether glucose control in T2DM patients with concomitant HF and AF affects a circulating number of RBC-derived EVs. We prospectively included 417 T2DM patients with HF, 51 of them had atrial fibrillation and 25 healthy volunteers and 30 T2DM non-HF individuals. Clinical assessment, echocardiography examination and biomarker measures were performed at the baseline of the study. RBC-derived EVs were determined as CD235a+ PS+ particles by flow cytometry. NT-proBNP levels were measured by ELISA. AF patients with glycosylated hemoglobin (HbA1c) < 6.9% had lower levels of CD235a+ PS+ RBC-derived vesicles than those with HbA1c ≥ 7.0%. There were no significant differences in number of CD235a+ PS+ RBC-derived vesicles between patients in entire cohort and in non-AF sub-cohort with HbA1c < 6.9% and HbA1c ≥ 7.0%, respectively. Multivariate linear regression yielded that CD235a+ PS+ RBC-derived vesicles ≥ 545 particles in µL (OR = 1.06; 95% CI = 1.01−1.11, p = 0.044) independently predicted HbA1c ≥ 7.0%. Elevated levels of CD235a+ PS+ RBC-derived EVs independently predicted poor glycaemia control in T2DM patients with HF and AF.