Short-term outcomes of patients with chronic liver disease hospitalised with COVID-19.

BACKGROUND: Patients with chronic liver disease (CLD) might have an aggravated course after acquisition of coronavirus disease 2019 (COVID-19). AIMS: To analyse the outcomes of patients with CLD who were hospitalised due to COVID-19. METHODS: The medical records of 4014 patients hospitalised because of COVID-19 in a regional referral hospital over a 12-month period were analysed. Patients with CLD were identified based on discharge diagnoses according to the International Classification of Diseases-10th Revision. Patients were followed for 30 days from admission and their outcomes (intensive care unit (ICU) admission, mechanical ventilation (MV) or death) were analysed. RESULTS: Of the 4014 patients, 110 (2.7%) had CLD and 49 (1.2%) had cirrhosis. The median age of CLD patients was 67.5 years, 79 (71.8%) were males, 224 (23.5%) were obese, 56 (50.9%) reported alcohol abuse, 24 (21.8%) had non-alcoholic fatty liver disease, 11 (10%) had viral hepatitis and 98 (89.1%) had pneumonia. The median length of hospitalisation was 12 days; 32 (29.1%) patients required ICU admission and 23 (20.9%) patients required MV, while 43 (39.1%) died. In univariate analysis, patients with cirrhosis (45% vs 73%, hazard ratio (HR) = 2.95; P < 0.001), but not those with non-cirrhotic CLD (74% vs 73%; P > 0.05), experienced worse 30-day survival when compared with age, sex and COVID-19 duration-matched cohorts. In a logistic regression analysis conducted on the overall and matched cohorts, liver cirrhosis, but not CLD, predicted inferior survival independently of age, comorbidities and severity of COVID-19, with a fourfold higher adjusted risk of 30-day mortality. CONCLUSION: Cirrhosis is independently associated with higher 30-day mortality of hospitalised patients with COVID-19.

Experiences and attitudes of medical professionals on treatment of end-of-life patients in intensive care units in the Republic of Croatia: a cross-sectional study.

BACKGROUND: Decisions about limitations of life sustaining treatments (LST) are made for end-of-life patients in intensive care units (ICUs). The aim of this research was to explore the professional and ethical attitudes and experiences of medical professionals on treatment of end-of-life patients in ICUs in the Republic of Croatia. METHODS: A cross-sectional study was conducted among physicians and nurses working in surgical, medical, neurological, and multidisciplinary ICUs in the total of 9 hospitals throughout Croatia using a questionnaire with closed and open type questions. Exploratory factor analysis was conducted to reduce data to a smaller set of summary variables. Mann-Whitney U test was used to analyse the differences between two groups and Kruskal-Wallis tests were used to analyse the differences between more than two groups. RESULTS: Less than third of participants (29.2%) stated they were included in the decision-making process, and physicians are much more included than nurses (p < 0.001). Sixty two percent of participants stated that the decision-making process took place between physicians. Eighteen percent of participants stated that 'do-not-attempt cardiopulmonary resuscitations' orders were frequently made in their ICUs. A decision to withdraw inotropes and antibiotics was frequently made as stated by 22.4% and 19.9% of participants, respectively. Withholding/withdrawing of LST were ethically acceptable to 64.2% of participants. Thirty seven percent of participants thought there was a significant difference between withholding and withdrawing LST from an ethical standpoint. Seventy-nine percent of participants stated that a verbal or written decision made by a capable patient should be respected. Physicians were more inclined to respect patient's wishes then nurses with high school education (p = 0.038). Nurses were more included in the decision-making process in neurological than in surgical, medical, or multidisciplinary ICUs (p < 0.001, p = 0.005, p = 0.023 respectively). Male participants in comparison to female (p = 0.002), and physicians in comparison to nurses with high school and college education (p < 0.001) displayed more liberal attitudes about LST limitation. CONCLUSIONS: DNACPR orders are not commonly made in Croatian ICUs, even though limitations of LST were found ethically acceptable by most of the participants. Attitudes of paternalistic and conservative nature were expected considering Croatia's geographical location in Southern Europe.

Patterns of corticosteroid use among remdesivir and matched patients and associated clinical outcomes in hospitalized COVID-19 patients.

INTRODUCTION: We aimed to investigate patterns of corticosteroid use and their relationship with remdesivir use and clinical outcomes in a large real-life cohort of COVID-19 patients treated in a tertiary-level institution. METHODS: We retrospectively analyzed a total of 1558 severe and critical COVID-19 patients, including 779 patients treated with remdesivir and 779 matched control patients. RESULTS: A total of 167 (10.7%) patients received none, 710 (45.6%) low, 539 (34.6%) high, and 142 (9.1%) very high corticosteroid doses. Patients treated with remdesivir had significantly longer exposure to corticosteroids, received higher average and maximal daily doses, and cumulative corticosteroid doses. In the multivariate analysis remdesivir use, lower cumulative comorbidity burden, higher severity of COVID-19 symptoms, and mechanical ventilation were recognized as mutually independent predictors of the use of higher corticosteroid doses. Higher corticosteroid doses were associated with significantly increased mortality.Among non-remdesivir treated patients, there was a U-shaped relationship between maximal daily corticosteroid dose and mortality. Among remdesivir treated patients gradual increase in mortality with increasing corticosteroid doses was observed. CONCLUSION: Patterns of corticosteroid use differ regarding the use of remdesivir and may moderate its association with survival among severe and critical COVID-19 patients.

Corticosteroid Dosing Level, Incidence and Profile of Bacterial Blood Stream Infections in Hospitalized COVID-19 Patients.

COVID-19 patients with severe or critical symptoms are often treated with corticosteroids, per contemporary guidelines. Due to their immunosuppressive and immunomodulatory properties, corticosteroids are associated with the development of superinfections. We aimed to retrospectively assess patterns of corticosteroid use and the profiles of bacterial blood stream infections associated with exposure to different dosing levels, in a cohort of 1558 real-life adult COVID-19 patients. A total of 1391 (89.3%) patients were treated with corticosteroids, with 710 (45.6%) patients receiving low, 539 (34.6%) high and 142 (9.1%) very high corticosteroid doses. Bacteremia developed in a total of 178 (11.4%) patients. The risk of bacteremia was of similar magnitude between the no and low-dose corticosteroid treatments (p = 0.352), whereas it progressively increased with high (OR 6.18, 95% CI (2.66-14.38), p < 0.001) and very high corticosteroid doses (OR 8.12, 95% CI (3.29-20.05), p < 0.001), compared to no corticosteroid treatment. These associations persisted after multivariate adjustments and were present independently of sex, comorbidity burden, and mechanical ventilation. The profiles of individual bacterial pathogens differed depending on the used corticosteroid doses. High and very high corticosteroid doses are frequently used for real-life COVID-19 patients with severe and critical clinical presentations and are associated with a higher risk of bacteremia independently of sex, comorbidity burden, and mechanical ventilation use.

Comparison of vitamin K and non-vitamin K oral anticoagulants and the bleeding frequency in the emergency department.

INTRODUCTION: Safety studies of anticoagulant therapy have so far been conducted on many subjects in controlled conditions (i.e., clinically monitored) and demonstrated the noninferiority of new ones over old anticoagulant drugs. Data on the propositions for the presence of symptoms and signs of bleeding among various anticoagulants in the emergency department indicate that these data do not match the data published so far. AIM: The aim of the study was to investigate the differences in the frequency of bleeding and bleeding-related symptoms as a reason for emergency department attendance in patients on anticoagulant therapy. METHODS: The study included patients from the emergency department of University Hospital for one year, who were on anticoagulant therapy and who met the inclusion criteria. Out of a total of 595 patients, 409 were on warfarin (68.74%), and the rest were taking direct oral anticoagulants (DOAC): dabigatran 71 (11.93%), rivaroxaban 66 (11.09%) and apixaban 49 (8.23%). RESULTS: Out of 409 patients taking warfarin, 34.4% were adequately anticoagulated with the frequency of bleeding 13.7%, while in 57.2% of patients, PT INR was higher than the reference values with the frequency of bleeding 15.0%. A comparison between all DOAC groups and adequately anticoagulated warfarin patients in the frequency of bleeding and bleeding-related symptoms as a reason for emergency attendance yielded a difference that was marginally statistically significant (Pearson Chi-Square = 7.554, p = 0.052). CONCLUSION: Monitoring the frequency of bleeding and bleeding-related symptoms in patients on oral anticoagulant therapy as a reason for emergency department attendance may be a new safety and efficacy factor in real-life patient scenarios.

Validation of the fractional exhaled breath temperature measurement: reference values.

Exhaled breath temperature (EBT) is a known biomarker of inflammation and airways blood flow. As opposed to previous studies, we were able to measure temperature of separate fractions of exhaled breath (fEBT) (those from the peripheral and central airways). The aim was to validate the fEBT measurement method to determine the reference values and the influence of endogenous and exogenous factors on fEBT in healthy subjects. This cross-sectional study included 55 healthy adults in whom fEBT was repeatedly measured, two days in a row, using a FractAir®device. Also, basal metabolic rate, level of physical activity, distance from the main road, outdoor and ambient temperature, air pressure and humidity, haematology and inflammation markers, lung function, cumulative EBT and body temperature at characteristic points on the body were measured. The results showed that fEBT from central airways was lower compared to fEBT from the periphery and that fEBTs were not related to body temperature (p> 0.05 for all). We also showed repeatability of fEBT measurements for two consecutive days. All EBT fractions correlated significantly with ambient temperature (<0.01). No associations of fEBT with other personal and external factors were found using multivariate analysis. At room temperature of 22 °C, the physiological temperature values of the first fraction were 23.481 ± 3.150 °C, the second fraction 26.114 ± 4.024 °C and the third fraction 28.216 ± 3.321 °C. The proposed reference values represent the first part of validation of fEBT as the method for the use in clinical practice.

Risks associated with prior oral anticoagulation use in hospitalized COVID-19 patients - A retrospective cohort study on 5392 patients from a tertiary centre.

INTRODUCTION: There are conflicting data on prior oral-anticoagulant (OAC) use and outcomes of hospitalized COVID-19 patients. Due to uncertainties regarding associated risks with the prior OAC use, we have investigated this issue in a large cohort of hospitalized COVID-19 patients from our institution. METHODS: We have retrospectively evaluated a total of 5392 consecutive COVID-19 patients hospitalized in our tertiary center institution in period 3/2020 to 6/2021. Majority of patients received low-molecular-weight-heparin thromboprophylaxis and corticosteroids during hospitalization. Patients' characteristics and clinical outcomes were documented as a part of a hospital registry project and were evaluated according to the prior non-OAC, warfarin and direct oral anticoagulants (DOAC) use. RESULTS: Median age was 72 years, median Charlson comorbidity index (CCI) was 4 points. There were 56.2% male patients. Majority of patients had severe (70.5%) or critical (15.8%) COVID-19 on admission. A total of 84.8% patients did not receive prior OAC, 9% were previously anticoagulated with warfarin and 6.2% were previously anticoagulated with DOACs. In the multivariate regression analyses, prior warfarin use was associated increased in-hospital mortality (OR 1.24, P = 0.048) independently of older age (OR 2.12, P < 0.001), male sex (OR 1.27, P < 0.001), higher CCI (OR 1.26, P < 0.001) and severe or critical COVID-19 on admission (OR 22.66, P < 0.001). Prior DOAC use was associated with higher occurrence of major bleeding (OR 1.72, P = 0.045) independently of higher CCI (OR 1.08, P = 0.017). CONCLUSION: Prior OAC use could be associated with worse clinical outcomes during COVID-19 hospitalization. These phenomena might be OAC type specific and persist after multivariate adjustments.

Prevalence of ABO and RhD blood group phenotypes in the Croatian population and in patients with severe COVID-19 in Croatia.

BACKGROUND: The aim of this study was to determine the distribution of ABO and RhD blood group phenotypes in the general population in the Republic of Croatia and among hospitalized patients with severe COVID-19. MATERIALS AND METHODS: Data on ABO and RhD blood groups of all blood donors in Croatia (who donated blood during the period 2015-2020) and patients and pregnant women tested at the Croatian Institute of Transfusion Medicine during the 2-year period, 2019-2020, were obtained from the e-Delphyn blood bank information system. A total of 614,673 results were analyzed in this group. The other group consisted of 780 COVID-19 patients hospitalized with severe COVID-19. Data are presented as total number and percentages and a comparison of proportions test was performed. RESULTS: The most frequent ABO phenotype in the general population is A (38%), followed by O (37%), B (18%) and AB (7%). RhD positive individuals accounted for 81% of the general population and RhD negative for the other 19%. Among COVID-19 patients, phenotype A was the most frequent (42%), followed by phenotypes O (32%), B (17%) and AB (9%). Thus blood group A was significantly more common among COVID-19 patients than among the general population, whereas blood group O was significantly less frequent. DISCUSSION: This study provides the first official results of the distribution of ABO and RhD blood group phenotypes in the general population in Croatia. Moreover, this study confirms other researchers' observations about the predominance of the A blood group phenotype among COVID-19 patients.

A1B and BB blood group genotypes are risk factors for pulmonary embolism.

BACKGROUND: Pulmonary embolism (PE) is a potentially life-threatening condition that mainly affects the people of advanced age. While certain blood group phenotypes (non­O blood group) are known risk factors for the development of venous thromboembolism (VTE), there is no research which investigated the association of blood group genotypes with severity of PE. The aim of this study was to investigate the frequency of ABO blood group genotypes among the population of patients with PE and to investigate the correlation of the pulmonary embolism severity index (PESI) score to specific ABO blood group genotypes. MATERIAL AND METHODS: In this cross-sectional study 74 patients with PE diagnosed using CT pulmonary angiography were included and 303 blood donors without VTE or congenital thrombophilia participated as a control group. After isolation of genomic DNA ABO blood group genotype was determined using the polymerase chain reaction sequence-specific amplification (PCR-SSP) method. RESULTS: We observed a significantly higher frequency of A1B and BB genotypes in patients with PE compared to healthy individuals (A1B 14.9% vs. 4.3%, P < 0.001; BB 5.4% vs. 0.7%, P = 0.004), while the O1O1 genotype was significantly less frequent in patients (24.3% vs. 37.3%, P = 0.036). Analyzing the severity of the clinical presentation according to the PESI score, we did not find a correlation between the severity of the clinical presentation and a certain blood type genotype. CONCLUSION: Patients with A1B and BB blood type genotype were at increased risk for developing pulmonary embolism, while patients with O1O1 genotype had a significantly lower risk of developing PE.

Prevalence and Prognostic Impact of Deranged Liver Blood Tests in COVID-19: Experience from the Regional COVID-19 Center over the Cohort of 3812 Hospitalized Patients.

BACKGROUND: Derangement of liver blood tests (LBT) is frequent in patients with Coronavirus disease 2019 (COVID-19). We aimed to evaluate (a) the prevalence of deranged LBT as well as their association with (b) clinical severity at admission and (c) 30-day outcomes among the hospitalized patients with COVID-19. METHODS: Consecutive patients with COVID-19 hospitalized in the regional referral center over the 12-month period were included. Clinical severity of COVID-19 at hospital admission and 30-day outcomes (need for intensive care, mechanical ventilation, or death) were analyzed. RESULTS: Derangement of LBT occurred in 2854/3812 (74.9%) of patients, most frequently due to elevation of AST (61.6%), GGT (46.1%) and ALT (33.4%). Elevated AST, ALT, GGT and low albumin were associated with more severe disease at admission. However, in multivariate Cox regression analysis, when adjusted for age, sex, obesity and presence of chronic liver disease, only AST remained associated with the risk of dying (HR 1.5081 and 2.1315, for elevations 1-3 × ULN and >3 × ULN, respectively) independently of comorbidity burden and COVID-19 severity at admission. Patients with more severe liver injury more frequently experienced defined adverse outcomes. CONCLUSIONS: Deranged LBTs are common among patients hospitalized with COVID-19 and might be used as predictors of adverse clinical outcomes.