Compensated Advanced Chronic Liver Disease and Steatosis in Patients with Type 2 Diabetes as Assessed through Shear Wave Measurements and Attenuation Measurements.

Patients with type 2 diabetes (T2D) are at risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the prevalence of compensated advanced chronic liver disease (cACLD) and steatosis in patients with T2D using the new non-invasive diagnostic methods of shear wave measurements (SWMs) and attenuation (ATT) measurements in comparison with those of vibration-controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), which served as the reference methods. Among 214 T2D patients, steatosis at any grade and cACLD were revealed in 134 (62.6%) and 19 (8.9%) patients, respectively. SWMs showed a high correlation with VCTE (Spearman's ρ = 0.641), whereas SWMs produced lower (mean of -0.7 kPa) liver stiffness measurements (LSMs) overall. At a LSM of >11.0 kPa (Youden), SWMs had an AUROC of 0.951 that was used to diagnose cACLD (defined as a LSM of >15 kPa through VCTE) with 84.2% sensitivity and 96.4% specificity. The performance of ATT measurements in diagnosing liver steatosis at any grade (defined as the CAP of ≥274 dB/m) was suboptimal (AUROC of 0.744 at the ATT measurement cut-off of >0.63 dB/cm/MHz (Youden) with 59% sensitivity and 81.2% specificity). In conclusion, the prevalence of liver steatosis and previously unrecognized cACLD in patients with T2D is high and SWMs appear to be a reliable diagnostic method for this purpose, whereas further investigation is needed to optimize the diagnostic performance of ATT measurements.

Estimated plasma volume status in COVID-19 patients and its relation to comorbidities and clinical outcomes.

Blood plasma is a large reservoir of circulating mediators of inflammation and its expansion has been associated with unfavorable outcomes in patients with inflammatory and cardiovascular diseases. The aim of this study was to determine clinical and prognostic value of estimated plasma volume status (ePVS) in hospitalized patients with COVID-19. We retrospectively investigated 5871 consecutive COVID-19 patient hospitalized in our tertiary-level institution in period 3/2020-6/2021. ePVS was determined using the Strauss-derived Duarte formula and was correlated with clinical characteristics and unwanted outcomes. Median ePVS was 4.77 dl/g with interquartile range 4.11-5.74. Higher ePVS was significantly associated with older age, female sex, higher comorbidity burden, worse functional status, less severe COVID-19 clinical presentation with lower severity and longer duration of symptoms, but more pronounced inflammatory profile with higher C-reactive protein, interleukin-6 and D-dimer levels (P < 0.05 for all analyses). In the multivariate regression analysis U shaped relationship of ePVS with mortality was revealed, present independently of age, sex, COVID-19 severity and comorbidity burden. In addition, higher ePVS was independently associated with higher tendency for mechanical ventilation, intensive care unit treatment, venous thromboembolism, major bleeding and bacteriemia and lower ePVS was independently associated with tendency for arterial thrombotic events. Higher ePVS, indicative of plasma volume expansion and inflammatory cytokine accumulation, may predispose respiratory deterioration and venous thromboembolism, despite less severe initial clinical presentation. Lower ePVS, indicative of hemoconcentration, may predispose arterial thrombotic events. Both may be associated with higher mortality in hospitalized COVID-19 patients.

The Intestinal Microbiota in the Development of Chronic Liver Disease: Current Status.

Chronic liver disease (CLD) is a significant global health burden, leading to millions of deaths annually. The gut-liver axis plays a pivotal role in this context, allowing the transport of gut-derived products directly to the liver, as well as biological compounds from the liver to the intestine. The gut microbiota plays a significant role in maintaining the health of the digestive system. A change in gut microbiome composition as seen in dysbiosis is associated with immune dysregulation, altered energy and gut hormone regulation, and increased intestinal permeability, contributing to inflammatory mechanisms and damage to the liver, irrespective of the underlying etiology of CLD. The aim of this review is to present the current knowledge about the composition of the intestinal microbiome in healthy individuals and those with CLD, including the factors that affect this composition, the impact of the altered microbiome on the liver, and the mechanisms by which it occurs. Furthermore, this review analyzes the effects of gut microbiome modulation on the course of CLD, by using pharmacotherapy, nutrition, fecal microbiota transplantation, supplements, and probiotics. This review opens avenues for the translation of knowledge about gut-liver interplay into clinical practice as an additional tool to fight CLD and its complications.

Hypoosmolar and hyperosmolar COVID-19 patients are predisposed to dismal clinical outcomes.

We aimed to investigate the associations of hypo- and hyperosmolarity at hospital admission with clinical characteristics and outcomes in 5645 consecutive hospitalized COVID-19 patients treated at a tertiary-level institution. Serum osmolarity was calculated as 2x Na (mmol/L) + urea (mmol/L) + glucose (mmol/L), with normal range from 275 to 295 mOsm/L. Median serum osmolarity was 292.9 mOsm/L with 51.8% normoosmolar, 5.3% hypoosmolar and 42.9% hyperosmolar patients present at the time of hospital admission. Hypoosmolarity was driven by hyponatremia, and was associated with the presence of chronic liver disease, liver cirrhosis, active malignancy and epilepsy. Hyperosmolarity was driven by an increase in urea and glucose and was associated with the presence of chronic metabolic and cardiovascular comorbidities. Both hypo- and hyperosmolar patients presented with more severe COVID-19 symptoms, higher inflammatory status, and experienced higher mortality in comparison to normoosmolar patients. In multivariate analysis, hypoosmolarity (adjusted odds ratio (aOR)=1.39, p = 0.024) and hyperosmolarity (aOR = 1.9, p < 0.001) remained significantly associated with higher mortality independently of older age, male sex, higher Charlson Comorbidity Index and more severe COVID-19. Disruptions in serum osmolarity are frequent in COVID-19 patients, may be easy to detect and target therapeutically, and thus potentially moderate associateds poor prognosis.

Proton pump inhibitors use prior to COVID-19 hospitalization is associated with higher Clostridioides difficile infection rate.

BACKGROUND: There are uncertainties regarding associations of prior proton pump inhibitor (PPI) use with susceptibility for COVID-19 and risks associated with SARS-CoV-2 infection. We aimed to evaluate the associations of prior PPI use with outcomes in hospitalized patients with COVID-19. RESEARCH DESIGN AND METHODS: We have retrospectively evaluated a total of 5959 consecutively hospitalized patients with COVID-19 from a tertiary-level institution in the period 3/2020-6/2021. Associations of prior PPI use with outcomes of in-hospital mortality, mechanical ventilation, intensive care unit stay, venous thromboembolism, arterial thrombosis, major bleeding, bacteremia, and Clostridioides difficile infection (C. diff.) were evaluated in entire and case-matched cohorts. RESULTS: Among 5959 evaluated patients, there were 1967 (33%) PPI users. In an entire cohort, prior PPI use was associated with higher in-hospital mortality and higher occurrence of C. diff. Association of prior PPI use with mortality diminished, whereas association with C. diff. persisted after multivariable adjustments. In a matched cohort, prior PPI use was associated only with higher risk of C. diff. but not other outcomes in line with multivariable analysis. CONCLUSIONS: Although prior PPI use might not have a significant impact on clinical course and mortality of SARS-CoV-2 infection, it may predispose patients to the development of complications like higher occurrence of C. diff. and thus substantially impact the course of treatment.

Predictors of prolonged hospitalization of COVID-19 patients.

PURPOSE: Despite the importance of hospital bed network during the pandemic, there are scarce data available regarding factors predictive of prolonged length of hospitalization of COVID-19 patients. METHODS: We retrospectively analyzed a total of 5959 consecutive hospitalized COVID-19 patients in period 3/2020-6/2021 from a single tertiary-level institution. Prolonged hospitalization was defined as hospital stay > 21 days to account for mandatory isolation period in immunocompromised patients. RESULTS: Median length of hospital stay was 10 days. A total of 799 (13.4%) patients required prolonged hospitalization. Factors that remained independently associated with prolonged hospitalization in multivariate analysis were severe or critical COVID-19 and worse functional status at the time of hospital admission, referral from other institutions, acute neurological, acute surgical and social indications for admission vs admission indication of COVID-19 pneumonia, obesity, chronic liver disease, hematological malignancy, transplanted organ, occurrence of venous thromboembolism, occurrence of bacterial sepsis and occurrence of Clostridioides difficile infection during hospitalization. Patients requiring prolonged hospitalization experienced higher post-hospital discharge mortality (HR = 2.87, P < 0.001). CONCLUSIONS: Not only severity of COVID-19 clinical presentation but also worse functional status, referral from other hospitals, certain indications for admission, certain chronic comorbidities, and complications that arise during hospital stay independently reflect on the need of prolonged hospitalization. Development of specific measures aimed at improvement of functional status and prevention of complications might reduce the length of hospitalization.

The performance of the WHO COVID-19 severity classification, COVID-GRAM, VACO Index, 4C Mortality, and CURB-65 prognostic scores in hospitalized COVID-19 patients: data on 4014 patients from a tertiary center registry.

AIM: To evaluate the predictive properties of several common prognostic scores regarding survival outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively reviewed the medical records of 4014 consecutive COVID-19 patients hospitalized in our tertiary level institution from March 2020 to March 2021. Prognostic properties of the WHO COVID-19 severity classification, COVID-GRAM, Veterans Health Administration COVID-19 (VACO) Index, 4C Mortality Score, and CURB-65 score regarding 30-day mortality, in-hospital mortality, presence of severe or critical disease on admission, need for an intensive care unit treatment, and mechanical ventilation during hospitalization were evaluated. RESULTS: All of the investigated prognostic scores significantly distinguished between groups of patients with different 30-day mortality. The CURB-65 and 4C Mortality Score had the best prognostic properties for prediction of 30-day mortality (area under the curve [AUC] 0.761 for both) and in-hospital mortality (AUC 0.757 and 0.762, respectively). The 4C Mortality Score and COVID-GRAM best predicted the presence of severe or critical disease (AUC 0.785 and 0.717, respectively). In the multivariate analysis evaluating 30-day mortality, all scores mutually independently provided additional prognostic information, except the VACO Index, whose prognostic properties were redundant. CONCLUSION: Complex prognostic scores based on many parameters and comorbid conditions did not have better prognostic properties regarding survival outcomes than a simple CURB-65 prognostic score. CURB-65 also provides the largest number of prognostic categories (five), allowing more precise risk stratification than other prognostic scores.

The attitude and knowledge of medical students regarding dementia.

OBJECTIVE: Due to the growing number of older people with dementia (PWD) worldwide, there is an urgent need to improve undergraduate medical education on dementia and skills of future health professionals to provide the best quality care for PWD. The study aimed to determine attitudes and knowledge regarding dementia among medical students. METHODS: This cross-sectional, survey-based study included 231 final-year medical students who completed the paper-and-pencil questionnaire with seven categories of questions including two dementia knowledge tests. RESULTS: Students have relatively neutral attitudes towards working with PWD and a rather poor theoretical knowledge in the dementia knowledge exam. Students showed the best theoretical knowledge about the symptoms of Alzheimer's disease, while their knowledge was poor in the field of differential diagnoses, epidemiology, and pathogenesis of Alzheimer's disease. One in 11 sixth-year medical students has never had contact with a person with dementia. The opinion of most students was that they should have spent more time with PWD during their medical education and that there are too few classes in the field of dementia at the School of Medicine. The dementia knowledge test with 23 Multiple-Choice Questions showed a higher internal consistency compared to the Alzheimer's Disease Knowledge Scale. CONCLUSION: There is an urgent need to increase the interest and improve attitudes and knowledge towards dementia for all future health care professionals from the earliest student days to provide the best care for PWD.

The effect of outpatient antibiotic treatment of coronavirus disease 2019 on the outcomes in the emergency department: a propensity score matching study.

AIM: To determine the effect of outpatient oral antibiotics on coronavirus disease 2019 (COVID-19) in patients presenting to the emergency department. METHODS: This retrospective cohort study with propensity score matching conducted at University Hospital Dubrava collected data on all emergency department visits due to COVID-19 in November 2020. The primary outcome was hospital admission. The secondary outcomes were pneumonia development, respiratory failure, and required level of respiratory support. RESULTS: Overall, 1217 visits were evaluated and 525 patients were included in the analysis. After propensity score matching, 126 pairs of treated patients and controls were identified. Patients and controls did not differ in physical examination findings, laboratory test results, radiographic findings, or defined outcomes before and after matching. CONCLUSION: This study suggests no benefit of empirical oral antibiotics for outpatient treatment of COVID-19. In patients presenting to the emergency department, prior oral antibiotic treatment did not affect hospital admission rates or the level of respiratory support required.

Red cell distribution width is a potent prognostic parameter for in-hospital and post-discharge mortality in hospitalized coronavirus disease 2019 patients: a registry-based cohort study on 3941 patients.

AIM: To investigate clinical and prognostic associations of red cell distribution width (RDW) in hospitalized coronavirus disease 2019 (COVID-19) patients. METHODS: We retrospectively analyzed the records of 3941 consecutive COVID-19 patients admitted to a tertiary-level institution from March 2020 to March 2021 who had available RDW on admission. RESULTS: The median age was 74 years. The median Charlson comorbidity index (CCI) was 4. The majority of patients (84.1%) on admission presented with severe or critical COVID-19. Patients with higher RDW were significantly more likely to be older and female, to present earlier during infection, and to have higher comorbidity burden, worse functional status, and critical presentation of COVID-19 on admission. RDW was not significantly associated with C-reactive protein, occurrence of pneumonia, or need for oxygen supplementation on admission. During hospital stay, patients with higher RDW were significantly more likely to require high-flow oxygen therapy, mechanical ventilation, intensive care unit, and to experience prolonged immobilization, venous thromboembolism, bleeding, and bacterial sepsis. Thirty-day and post-hospital discharge mortality gradually increased with each rising RDW percent-point. In a series of multivariate Cox-regression models, RDW demonstrated robust prognostic properties at >14% cut-off level. This cut-off was associated with inferior 30-day and post-discharge survival independently of COVID-19 severity, age, and CCI; and with 30-day survival independently of COVID severity and established prognostic scores (CURB-65, 4C-mortality, COVID-gram and VACO-index). CONCLUSION: RDW has a complex relationship with COVID-19-associated inflammatory state and is affected by prior comorbidities. RDW can improve the prognostication in hospitalized COVID-19 patients.

Clinical and prognostic significance of C-reactive protein to albumin ratio in hospitalized coronavirus disease 2019 (COVID-19) patients : Data on 2309 patients from a tertiary center and validation in an independent cohort.

C­reactive protein (CRP) and albumin are inflammation sensitive parameters that are regulated by interleukin­6 inflammatory pathways. The CRP to albumin ratio (CAR) integrates these two into a potent clinical parameter whose clinical and prognostic association in the context of coronavirus disease 2019 (COVID-19) have not been well defined. We aimed to investigate the clinical and prognostic significance of CAR in the context of COVID-19 infection.We retrospectively analyzed 2309 consecutive COVID-19 patients hospitalized at a tertiary level hospital in the period from March 2020 to March 2021 who had baseline data for a CAR assessment. Findings were validated in an independent cohort of 1155 patients hospitalized from March 2021 to June 2021.The majority of patients (85.8%) had severe or critical COVID-19 on admission. Median CRP, albumin and CAR levels were 91 mg/L, 32 g/L and 2.92, respectively. Higher CAR was associated with a tendency for respiratory deterioration during hospitalization, increased requirement of high-flow oxygen treatment and mechanical ventilation, higher occurrence of bacteriemia, higher occurrence of deep venous thrombosis, lower occurrence of myocardial infarction, higher 30-day mortality and higher postdischarge mortality rates. We defined and validated four CAR prognostic categories (< 1.0, 1.0-2.9, 3.0-5.9 and ≥ 6.0) with distinct 30-day survival. In the series of multivariate Cox regression models we could demonstrate robust prognostic properties of CAR that was associated with inferior 30-day survival independently of COVID-19 severity, age and comorbidities and additionally independently of COVID-19 severity, CURB-65 and VACO index in both development and validation cohorts.The CAR seems to have a good potential to improve prognostication of hospitalized COVID-19 patients.

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.