Effects of Hypoxia and Inflammation on Hepcidin Concentration in Non-Anaemic COVID-19 Patients.

Background/Objectives: This study aimed to explore the influence of hypoxia, inflammation, and erythropoiesis on hepcidin and other iron status parameters in non-anaemic COVID-19 patients admitted to the emergency unit before the introduction of therapeutic interventions. Methods: Ninety-six COVID-19 patients and 47 healthy subjects were recruited. Patients were subdivided into hypoxic or normoxic groups and, after follow-up, into mild and moderate, severe or critical disease severity groups. Iron, unsaturated iron-binding capacity (UIBC), ferritin, C-reactive protein (CRP), and interleukin 6 (IL-6) were measured on automatic analysers. ELISA kits were used for hepcidin and erythropoietin (EPO) determination. We calculated total iron-binding capacity (TIBC) and ratios of hepcidin with parameters of iron metabolism (ferritin/hepcidin, hepcidin/iron), inflammation (hepcidin/CRP, hepcidin/IL-6), and erythropoietic activity (hepcidin/EPO). Results: Hepcidin, ferritin, EPO, CRP, IL-6, ferritin/hepcidin, and hepcidin/iron were increased, while UIBC, TIBC, hepcidin/CRP, and hepcidin/IL-6 were decreased in hypoxic compared to normoxic patients as well as in patients with severe or critical disease compared to those with mild and moderate COVID-19. Regarding predictive parameters of critical COVID-19 occurrence, in multivariable logistic regression analysis, a combination of EPO and ferritin/hepcidin showed very good diagnostic performances and correctly classified 88% of cases, with an AUC of 0.838 (0.749-0.906). Conclusions: The hypoxic signal in our group of patients was not strong enough to overcome the stimulating effect of inflammation on hepcidin expression. EPO and ferritin/hepcidin might help to identify on-admission COVID-19 patients at risk of developing a critical form of the disease.

Acute Liver Failure after Treatment with Rivaroxaban for Aortic Thrombosis Associated with COVID-19 Infection and Methylenetetrahydrofolate Reductase Gene Polymorphism (C677T).

Coronavirus disease-2019 (COVID-19) has become associated with prothrombotic state that could lead to severe arterial thrombotic complications. In the case of severe COVID-19 infection, hepatic dysfunction has been observed in more than 50% of patients. In this article, we present a case of aortic thrombosis associated with COVID-19 infection and methylenetetrahydrofolate reductase gene polymorphism (C677T) treated with rivaroxaban resulting in acute liver failure with fatal outcome.

Can Lung Imaging Scores and Clinical Variables Predict Severe Course and Fatal Outcome in COVID-19 Pneumonia Patients? A Single-Center Observational Study.

COVID-19 prediction models mostly consist of combined clinical features, laboratory parameters, and, less often, chest X-ray (CXR) findings. Our main goal was to propose a prediction model involving imaging methods, specifically ultrasound. This was a single-center, retrospective cohort observational study of patients admitted to the University Hospital Split from November 2020 to May 2021. Imaging protocols were based on the assessment of 14 lung zones for both lung ultrasound (LUS) and computed tomography (CT), correlated to a CXR score assessing 6 lung zones. Prediction models for the necessity of mechanical ventilation (MV) or a lethal outcome were developed by combining imaging, biometric, and biochemical parameters. A total of 255 patients with COVID-19 pneumonia were included in the study. Four independent predictors were added to the regression model for the necessity of MV: LUS score, day of the illness, leukocyte count, and cardiovascular disease (χ2 = 29.16, p < 0.001). The model accurately classified 89.9% of cases. For the lethal outcome, only two independent predictors contributed to the regression model: LUS score and patient's age (χ2 = 48.56, p < 0.001, 93.2% correctly classified). The predictive model identified four key parameters at patient admission which could predict an adverse outcome.

Acute Arterial Thrombosis of Lower Extremities in COVID-19 Patients.

Clinical signs and symptoms of COVID-19 varied from asymptomatic forms to severe, life-threatening conditions that required treatment in intensive care units. These severe forms of illness are connected with a hypercoagulable state due to excessive inflammation, hypoxia, immobilisation, and altered angiotensin-converting enzyme 2 (ACE-2). In total, 17 COVID-19 positive patients were diagnosed with peripheral arterial thrombosis (AT), 13 of them had COVID-19 pneumonia. Laboratory findings in patients with X-ray confirmed pneumonia showed a four times higher neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) and three times higher lactate dehydrogenase level (LDH) than patients without confirmed pneumonia. Patients with pneumonia had significantly more bilateral occlusions of the lower extremities and a significantly higher percentage with complete occlusion of the arteries than patients without pneumonia. The rate of limb loss was 35.3%. They were all from the group with COVID-19 pneumonia. Ten out of thirteen patients with pneumonia died due to acute respiratory distress syndrome (ARDS). All patients without pneumonia were discharged from the hospital. The aim of this retrospective study was to report the incidence of arterial thrombosis of lower extremities and their complications in the acute phase of the infection among COVID-19 patients admitted to the hospital for treatment.

Case of Acute Disseminated Encephalomyelitis Associated with Cytomegalovirus Reactivation in an Immunocompromised Systemic Lupus Erythematosus Patient.

We present a case of an immunocompromised systemic lupus erythematosus female patient admitted to our hospital for general impairment, monoparesis, and temporary cognitive disability. The case represented a significant diagnostic and therapeutic challenge primarily because of a wide range of differential diagnosis options (CNS lupus, ischemic cerebrovascular disease, viral meningoencephalitis, progressive multifocal leukoencephalopathy, limbic encephalitis, and acute disseminated encephalomyelitis-ADEM). Brain MRI findings were compatible with ADEM, and microbiological tests showed a cytomegalovirus infection (CMV) which is rarely associated with ADEM despite the increasing number of immunocompromised patients prone to symptomatic CMV reactivation. Our patient was treated with intravenous methylprednisolone, immunoglobulin (IVIG), along with antiviral therapy resulting in a favorable therapeutic effect. In conclusion, only a few described ADEM cases have been associated with CMV, and none of them, to the best of our knowledge, in an immunocompromised patient. In this case, a multidisciplinary approach and broad diagnostic considerations were decisive for successful treatment and outcome.

In-Hospital Mortality of COVID-19 Patients Treated with High-Flow Nasal Oxygen: Evaluation of Biomarkers and Development of the Novel Risk Score Model CROW-65.

To replace mechanical ventilation (MV), which represents the cornerstone therapy in severe COVID-19 cases, high-flow nasal oxygen (HFNO) therapy has recently emerged as a less-invasive therapeutic possibility for those patients. Respecting the risk of MV delay as a result of HFNO use, we aimed to evaluate which parameters could determine the risk of in-hospital mortality in HFNO-treated COVID-19 patients. This single-center cohort study included 102 COVID-19-positive patients treated with HFNO. Standard therapeutic methods and up-to-date protocols were used. Patients who underwent a fatal event (41.2%) were significantly older, mostly male patients, and had higher comorbidity burdens measured by CCI. In a univariate analysis, older age, shorter HFNO duration, ventilator initiation, higher CCI and lower ROX index all emerged as significant predictors of adverse events (p < 0.05). Variables were dichotomized and included in the multivariate analysis to define their relative weights in the computed risk score model. Based on this, a risk score model for the prediction of in-hospital mortality in COVID-19 patients treated with HFNO consisting of four variables was defined: CCI > 4, ROX index ≤ 4.11, LDH-to-WBC ratio, age > 65 years (CROW-65). The main purpose of CROW-65 is to address whether HFNO should be initiated in the subgroup of patients with a high risk of in-hospital mortality.

Blood markers of endothelial dysfunction and their correlation to cerebrovascular reactivity in patients with chronic hepatitis C infection.

Although liver cirrhosis and hepatocellular carcinoma are major consequences of hepatitis C (HCV), there has been an increasing number of studies examining extrahepatic manifestations, especially those caused by systemic chronic inflammation and metabolic complications that might predispose HCV patients to atherosclerosis and ischemic cerebrovascular disease (CVD). The aim of our study was to assess E-selectin, VCAM-1, ICAM-1 and VEGF-A serum levels in patients with chronic HCV infection and to correlate them with cerebrovascular reactivity. A blood sample was taken from eighteen patients with chronic hepatitis C infection and from the same number of healthy blood donors in the control group. The aim was to analyse markers of endothelial dysfunction and to correlate them with cerebrovascular reactivity expressed as breath-holding index (BHI) determined using transcranial color Doppler. The obtained results revealed significant differences between the groups in all endothelial markers except for the E selectin. While the ICAM-1 and sVCAM-1 were significantly increased in the hepatitis group, VEGF-A was significantly decreased. A significant reduction of 0.5 (95% CI 0.2, 0.8) in the mean BHI was found in the hepatitis group (mean BHI 0.64) compared to controls (mean BHI 1.10). No significant association between the BHI and any of the endothelial markers was found in the control group, while in the hepatitis group, the scatter plot of ICAM-1 vs BHI suggested that the association might be present. In conclusion, the results of this study confirm an association between a chronic HCV infection and altered cerebrovascular reactivity as well as higher levels of markers of endothelial activation (ICAM-1, VCAM-1) as possible indicators of an increased CVD risk.

Randomised clinical trial comparing concomitant and hybrid therapy for eradication of Helicobacter pylori infection.

BACKGROUND: The primary objective of this study was to compare concomitant and hybrid therapy in the first line eradication treatment of Helicobacter pylori infection in Split-Dalmatia County, Croatia, in which clarithromycin resistance is above 20%. The secondary objective of the study was to determine and compare compliance and adverse events rate between these therapeutic protocols. MATERIALS AND METHODS: In an open-label, randomised clinical trial 140 patients total with H. pylori infection were randomly assigned to either concomitant (esomeprazole 40 mg, amoxicillin 1 g, metronidazole 500 mg, clarithromycin 500 mg, twice daily for 14 days) or hybrid (esomeprazole 40 mg and amoxicillin 1 g twice daily during 14 days with adding metronidazole 500 mg and clarithromycin 500 mg twice daily, in the last 7 days,) treatment group. RESULTS: Eradication rates for concomitant group and hybrid therapy group were 84.1% (58/69) and 83.1% (59/71) respectively in the intention-to-treat analysis and 96.7% (58/60) and 95.2% (59/62) in per-protocol analysis. There was no significant difference between the groups (ITT analysis: P = 0.878; PP analysis: P = 0.675). Adverse events were more frequent in the concomitant group (33.3% vs 18.3%, P = 0.043). There was no difference among groups regarding compliance rate. CONCLUSION: Hybrid therapy has similar eradication rate as concomitant therapy, with lower adverse events rate. In the era of increasing antibiotic resistance, eradication regime with less antibiotic's usage, as hybrid therapy, should be reasonable first line treatment choice for H. pylori infection. Clinical Trials, gov: NCT03572777.

Evaluation of cerebrovascular reactivity in chronic hepatitis C patients using transcranial color Doppler.

Hepatitis C viral (HCV) infection is associated with systemic inflammation and metabolic complications that might predispose patients to atherosclerosis, including cerebrovascular atherosclerosis. The aim of this study was to assess cerebrovascular reactivity in patients with chronic hepatitis C. Seventeen patients with chronic hepatitis C infection, as well as 11 healthy blood donors in the control group, were assessed for cerebrovascular reactivity according to the well-established breath-holding test that uses the transcranial color Doppler for measurement of blood flow velocity. Results obtained during the breath-holding revealed significantly lower average peak systolic (AvPS start, P = 0.018), end-diastolic (AvED start, P = 0.031) and mean velocity values at the very beginning of the breath-holding procedure (AvmeanV start, P = 0.02), as well as a lower mean peak systolic velocity at the end of the breath-holding test (AvPS max, P = 0.02) in the hepatitis C group. Vascular reactivity values, calculated as the breath-holding index, were also significantly lower (P = 0.045) in the hepatitis C group. In conclusion, the results of this study suggest an association between chronic HCV infection and altered cerebrovascular reactivity which may ultimately have an unfavorable effect on cerebrovascular hemodynamics and lead to increased risk of cerebrovascular diseases.

CT perfusion and noncontrast CT in acute ischemic stroke diagnosing--is there influence on early thrombolytic therapy outcome?

The objective of this study was to compare noncontrast computed tomography (NCCT) and computed tomography perfusion (CTP) in early diagnosis of acute ischemic stroke and to define influence of these diagnostic procedures on early outcome of thrombolytic therapy (TLTH). The study included 45 patients, 35 patients submitted to NCCT and CTP and 10 patients who underwent only NCCT, before CTP was introduced. Based on the National Institute of Health Stroke Scale (NIHSS) score we compared early outcome of patients who received TLTH after NCCT only (group 1) with the early outcome of patients who received TLTH following NCCT and CTP (group 2). Statistically significant difference was found in acute stroke diagnosing between CTP and NCCT (p = 0.002). There were no statistically significant differences in TLTH early outcome between group 1 and group 2. In conclusion, CTP should be done regulary in patients presenting with acute ischemic stroke symptoms. More research needs to be done in defining exact influence of CTP implementation on the TLTH outcome.