Neurological and neuromuscular manifestations in patients with West Nile neuroinvasive disease, Belgrade area, Serbia, season 2022.

INTRODUCTION: We aimed to describe neurological manifestations and functional outcome at discharge in patients with West Nile neuroinvasive disease. METHODS: This retrospective study enrolled inpatients treated in the University Clinic for Infectious and Tropical Diseases in Belgrade, Serbia, from 1 June until 31 October 2022. Functional outcome at discharge was assessed using modified Rankin scale. RESULTS: Among the 135 analyzed patients, encephalitis, meningitis and acute flaccid paralysis (AFP) were present in 114 (84.6%), 20 (14.8%), and 21 (15.6%), respectively. Quadriparesis/quadriplegia and monoparesis were the most frequent forms of AFP, present in 9 (6.7%) and 6 (4.4%) patients, respectively. Fourty-five (33.3%) patients had cerebellitis, 80 (59.3%) had rhombencephalitis, and 5 (3.7%) exhibited Parkinsonism. Ataxia and wide-based gait were present in 79 (58.5%) patients each. Fifty-one (37.8%) patients had tremor (41 (30.3%) had postural and/or kinetic tremor, 10 (7.4%) had resting tremor). Glasgow coma score (GCS) ≤ 8 and respiratory failure requiring mechanical ventilation developed in 39 (28.9%), and 33 (24.4%) patients, respectively. Quadriparesis was a risk factor for prolonged ventilator support (29.5 ± 16.8 vs. 12.4 ± 8.7 days, p = 0.001). At discharge, one patient with monoparesis recovered full muscle strength, whereas 8 patients with AFP were functionally dependent. Twenty-nine (21.5%) patients died. All of the succumbed had encephalitis, and 7 had quadriparesis. Ataxia, tremor and cognitive deficit persisted in 18 (16.9%), 15 (14.2%), and 22 (16.3%) patients at discharge, respectively. Age, malignancy, coronary disease, quadriparesis, mechanical ventilation, GCS ≤ 8 and healthcare-associated infections were risk factors for death (p = 0.001; p = 0.019; p = 0.004; p = 0.001; p < 0.001; p < 0.001, and p < 0.001, respectively).

IL-23/IL-17 Axis in Chronic Hepatitis C and Non-Alcoholic Steatohepatitis-New Insight into Immunohepatotoxicity of Different Chronic Liver Diseases.

Considering the relevance of the research of pathogenesis of different liver diseases, we investigated the possible activity of the IL-23/IL-17 axis on the immunohepatotoxicity of two etiologically different chronic liver diseases. A total of 36 chronic hepatitis C (CHC) patients, 16 with (CHC-SF) and 20 without significant fibrosis (CHC-NSF), 19 patients with non-alcoholic steatohepatitis (NASH), and 20 healthy controls (CG) were recruited. Anthropometric, biochemical, and immunological cytokines (IL-6, IL-10, IL-17 and IL-23) tests were performed in accordance with standard procedure. Our analysis revealed that a higher concentration of plasma IL-23 was associated with NASH (p = 0.005), and a higher concentration of plasma IL-17A but a lower concentration of plasma IL-10 was associated with CHC in comparison with CG. A lower concentration of plasma IL-10 was specific for CHC-NSF, while a higher concentration of plasma IL-17A was specific for CHC-SF in comparison with CG. CHC-NSF and CHC-SF groups were distinguished from NASH according to a lower concentration of plasma IL-17A. Liver tissue levels of IL-17A and IL-23 in CHC-NSF were significantly lower in comparison with NASH, regardless of the same stage of the liver fibrosis, whereas only IL-17A tissue levels showed a difference between the CHC-NSF and CHC-SF groups, namely, a lower concentration in CHC-NSF in comparison with CHC-SF. In CHC-SF and NASH liver tissue, IL17-A and IL-23 were significantly higher in comparison with plasma. Diagnostic accuracy analysis showed significance only in the concentration of plasma cytokines. Plasma IL-6, IL-17A and IL-23 could be possible markers that could differentiate CHC patients from controls. Plasma IL-23 could be considered a possible biomarker of CHC-NSF patients in comparison with controls, while plasma IL-6 and IL-17-A could be biomarkers of CHC-SF patients in comparison with controls. The most sophisticated difference was between the CHC-SF and CHC-NSF groups in the plasma levels of IL-10, which could make this cytokine a useful biomarker of liver fibrosis.

HCV and HCC Tango-Deciphering the Intricate Dance of Disease: A Review Article.

Hepatitis C virus (HCV) is a major cause of hepatocellular carcinoma (HCC) accounting for around one-third of all HCC cases. Prolonged inflammation in chronic hepatitis C (CHC), maintained through a variety of pro- and anti-inflammatory mediators, is one of the aspects of carcinogenesis, followed by mitochondrial dysfunction and oxidative stress. Immune response dysfunction including the innate and adaptive immunity also plays a role in the development, as well as in the recurrence of HCC after treatment. Some of the tumor suppressor genes inhibited by the HCV proteins are p53, p73, and retinoblastoma 1. Mutations in the telomerase reverse transcriptase promoter and the oncogene catenin beta 1 are two more important carcinogenic signaling pathways in HCC associated with HCV. Furthermore, in HCV-related HCC, numerous tumor suppressor and seven oncogenic genes are dysregulated by epigenetic changes. Epigenetic regulation of gene expression is considered as a lasting "epigenetic memory", suggesting that HCV-induced changes persist and are associated with liver carcinogenesis even after cure. Epigenetic changes and immune response dysfunction are recognized targets for potential therapy of HCC.

Antioxidant Genetic Variants Modify Echocardiography Indices in Long COVID.

Although disturbance of redox homeostasis might be responsible for COVID-19 cardiac complications, this molecular mechanism has not been addressed yet. We have proposed modifying the effects of antioxidant proteins polymorphisms (superoxide dismutase 2 (SOD2), glutathione peroxidase 1 (GPX1), glutathione peroxidase 3 (GPX3) and nuclear factor erythroid 2-related factor 2, (Nrf2)) in individual susceptibility towards the development of cardiac manifestations of long COVID-19. The presence of subclinical cardiac dysfunction was assessed via echocardiography and cardiac magnetic resonance imaging in 174 convalescent COVID-19 patients. SOD2, GPX1, GPX3 and Nrf2 polymorphisms were determined via the appropriate PCR methods. No significant association of the investigated polymorphisms with the risk of arrhythmia development was found. However, the carriers of variant GPX1*T, GPX3*C or Nrf2*A alleles were more than twice less prone for dyspnea development in comparison with the carriers of the referent ones. These findings were even more potentiated in the carriers of any two variant alleles of these genes (OR = 0.273, and p = 0.016). The variant GPX alleles were significantly associated with left atrial and right ventricular echocardiographic parameters, specifically LAVI, RFAC and RV-EF (p = 0.025, p = 0.009, and p = 0.007, respectively). Based on the relation between the variant SOD2*T allele and higher levels of LV echocardiographic parameters, EDD, LVMI and GLS, as well as troponin T (p = 0.038), it can be proposed that recovered COVID-19 patients, who are the carriers of this genetic variant, might have subtle left ventricular systolic dysfunction. No significant association between the investigated polymorphisms and cardiac disfunction was observed when cardiac magnetic resonance imaging was performed. Our results on the association between antioxidant genetic variants and long COVID cardiological manifestations highlight the involvement of genetic propensity in both acute and long COVID clinical manifestations.

GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19.

In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently and complemented with laboratory markers, modulates COVID-19 severity. The study included 265 COVID-19 patients. Polymorphism of GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 and GPX1 rs1050450 genes was determined with appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) and organ damage (urea, creatinine, transaminases and LDH) markers, complete blood count and coagulation status (d-dimer, fibrinogen) were measured. We found significant association for COVID-19 progression for patients with lymphocytes below 1.0 × 109/L (OR = 2.97, p = 0.002). Increased IL-6 and CRP were also associated with disease progression (OR = 8.52, p = 0.001, and OR = 10.97, p < 0.001, respectively), as well as elevated plasma AST and LDH (OR = 2.25, p = 0.021, and OR = 4.76, p < 0.001, respectively). Of all the examined polymorphisms, we found significant association with the risk of developing severe forms of COVID-19 for GPX3 rs8177412 variant genotype (OR = 2.42, p = 0.032). This finding could be of particular importance in the future, complementing other diagnostic tools for prediction of COVID-19 disease course.

Expression of CYP2B6 Enzyme in Human Liver Tissue of HIV and HCV Patients.

Background and Objectives: Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections present significant public health challenges worldwide. The management of these infections is complicated by the need for antiviral and antiretroviral therapies, which are influenced by drug metabolism mediated by metabolic enzymes and transporters. This study focuses on the gene expression of CYP2B6, CYP3A4, and ABCB1 transporters in patients with HIV, HCV, and HIV/HCV co-infection, aiming to assess their potential association with the choice of therapy, patohistological and clinical parameters of liver damage such as the stage of liver fibrosis, serum levels of ALT and AST, as well as the grade of liver inflammation and other available biochemical parameters. Materials and Methods: The study included 54 patients who underwent liver biopsy, divided into HIV-infected, HCV-infected, and co-infected groups. The mRNA levels of CYP2B6, CYP3A4, and ABCB1 was quantified and compared between the groups, along with the analysis of liver fibrosis and inflammation levels. Results: The results indicated a significant increase in CYP2B6 mRNA levels in co-infected patients, a significant association with the presence of HIV infection with an increase in CYP3A4 mRNA levels. A trend towards downregulation of ABCB1 expression was observed in patients using lamivudine. Conclusions: This study provides insight into gene expression of CYP2B6 CYP3A4, and ABCB1 in HIV, HCV, and HIV/HCV co-infected patients. The absence of correlation with liver damage, inflammation, and specific treatment interventions emphasises the need for additional research to elucidate the complex interplay between gene expression, viral co-infection, liver pathology, and therapeutic responses in these particular patients population.

Rotational thromboelastometry (ROTEM) profiling of COVID-19 patients.

We evaluated coagulation abnormalities via traditional tests and rotational thromboelastometry (ROTEM) in a group of 94 patients with confirmed SARS-CoV-2 infection and different severity of pneumonia (34 moderate, 25 severe, 35 critical) with the hypothesis that ROTEM parameters differed by coronavirus disease 2019 (COVID-19) severity. Shorter than normal clotting time (CT) and higher than normal maximum clot firmness (MCF) in extrinsic rotational thromboelastometry (EXTEM) and fibrinogen rotational thromboelastometry (FIBTEM), shorter than normal EXTEM clot formation time (CFT), and higher than normal α-angle were classified as markers of hypercoagulable state. Increment in the number of patients with ≥2 hypercoagulable parameters, higher EXTEM (P = .0001), FIBTEM MCF (P = .0001) and maximum lysis decrement (P = .002) with increment in disease severity was observed (P = .0001). Significant positive correlations between IL6 and CT EXTEM (P = .003), MCF EXTEM (P = .033), MCF FIBTEM (P = .01), and negative with ML EXTEM (P = .006) were seen. Our findings based on analysis of different disease severity groups confirmed that a hypercoagulable ROTEM pattern characterized by clot formation acceleration, high clot strength, and reduced fibrinolysis was more frequent in advanced disease groups and patients with high IL6. These results supported the need for different thromboprophylaxis approaches for different severity groups.

Immunomodulatory effects of galectin-1 in patients with chronic lymphocytic leukemia.

Galectin-1 (Gal-1) has been implicated in the progression of chronic lymphocytic leukemia (CLL) but also the development of immunodeficiency, which commonly accompany this malignancy. In this in vitro study, we investigated the effects of Gal-1 inhibition in the sera of immunocompromised CLL patients on immunomodulating properties of dendritic cells (DCs). DCs derived from peripheral blood mononuclear cells were treated with a healthy serum, CLL serum as well as the combination of CLL serum and Gal-1 inhibitor (OTX008). Following the treatment, the expression levels of DC maturation markers (CD80, CD83, CD86 and IDO-1) were determined as well as their cytokine profile and the ability to polarize the immune response in co-cultures with CD4+ T cells. After treatment with CLL serum, an increase in interleukin (IL)-10 production was observed in both DC cultures and co-cultures with CD4+ T cells. OTX008 caused a reduction in IL-10 production as well as IL-2, but no significant alteration in the expression of DC maturation markers or T regulatory cell (Treg) frequency was observed. The results of our study suggest that Gal-1 from CLL serum give rise to a specific IL-10+ CD4+ T cell phenotype, other than Treg, that could mediate immunodeficiency development in CLL patients.

A pilot study in Serbia by European Clostridium difficile Infection Surveillance Network.

Clostridium (Clostridioides) difficile infections (CDIs) are among the most frequent healthcare-associated infections in Serbia. In 2013, Serbia participated in the European Clostridium difficile Infection Surveillance Network (ECDIS-Net) who launched a pilot study to enhance laboratory capacity and standardize surveillance for CDI. Two clinics of Clinical Center of Serbia [Clinic for Infectious and Tropical Diseases (CITD) and Clinic of Orthopedic Surgery and Traumatology (COT)] from Belgrade and one general hospital from another metropolitan area of Serbia, Uzice, participated. During a period of 3 months in 2013, all patients with diagnosed CDI were included. The CDI incidence rates in CITD, COT, and General Hospital Uzice were 19.0, 12.2, and 3.9 per 10,000 patient-days, respectively. In total, 49 patients were enrolled in the study with average age of 72 years. A complicated course of CDI was found in 14.3% of all patients. Six (12.2%) of 49 patients died, but not attributable to CDI. Of 39 C. difficile isolates, available for ribotyping, 78.9% belonged to ribotype 027; other PCR ribotypes were 001, 015, 002, 005, 010, 014, and 276. Antimicrobial susceptibility testing revealed low levels of MIC50 and MIC90 for metronidazole (0.5 µg/ml both) and vancomycin (0.25 and 0.5 µg/ml), while 28 strains of ribotype 027 were resistant to moxifloxacin with MIC ≥4 µg/ml. National surveillance is important to obtain more insight in the epidemiology of CDI and to compare the results with other European countries. This study by ECDIS-Net gives bases for a national surveillance of CDI in Serbia.

Gut-Liver Axis, Gut Microbiota, and Its Modulation in the Management of Liver Diseases: A Review of the Literature.

The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called "the new virtual metabolic organ", makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of "ancient" microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.

Oral teicoplanin versus oral vancomycin for the treatment of severe Clostridium difficile infection: a prospective observational study.

The aim of this study was to compare clinical cure rate, recurrence rate and time to resolution of diarrhea in patients with severe and severe-complicated Clostridium difficile infection (CDI) treated with teicoplanin or vancomycin. This two-year prospective observational study included patients with first episode or first recurrence of CDI who had severe or severe-complicated CDI and were treated with teicoplanin or vancomycin. Primary outcomes of interest were clinical cure rate at discharge and recurrence rate after eight weeks follow up, and secondary outcomes were all-cause mortality and time to resolution of diarrhea. Among 287 study patients, 107 were treated with teicoplanin and 180 with vancomycin. The mean age of patients was 73.5 ± 10.6 years. One hundred eighty six patients (64.8%) had prior CDI episode. Severe complicated disease was detected in 23/107 (21.5%) and 42/180 (23.3%) patients treated with teicoplanin and vancomycin, respectively. There was no statistically significant difference in time to resolution of diarrhea between two treatment arms (6.0 ± 3.4 vs 6.2 ± 3.1 days, p = 0.672). Treatment with teicoplanin resulted in significantly higher clinical cure rate compared to vancomycin [90.7% vs 79.4%, p = 0.013, odds ratio (OR) (95% confidence interval (CI)) 2.51 (1.19-5.28)]. Recurrence rates were significantly lower in patients treated with teicoplanin [9/97 (9.3%) vs 49/143 (34.3%), p < 0.001, OR (95%CI) 0.20 (0.09-0.42)]. There was no statistically significant difference in overall mortality rate. Teicoplanin might be a good treatment option for patients with severe CDI. Patients treated with teicoplanin experienced remarkably lower recurrence rates compared to vancomycin-treated patients.

Single-Walled Carbon Nanotube-Modified Gold Leaf Immunosensor for Escherichia coli Detection.

The requirement to prevent foodborne illnesses underscores the need for reliable detection tools, stimulating biosensor technology with practical solutions for in-field applications. This study introduces a low-cost immunosensor based on a single-walled carbon nanotube (SWCNT)-modified gold leaf electrode (GLE) for the sensitive detection of Escherichia coli. The immunosensor is realized with a layer-by-layer (LbL) assembly technique, creating an electrostatic bond between positively charged polyethylenimine (PEI) and negatively charged carboxyl-functionalized SWCNTs on the GLE. The structural and functional characterization of the PEI-SWCNT film was performed with Raman spectroscopy, high-resolution scanning electron microscopy (HRSEM), and electrical measurements. The PEI-SWCNT film was used as a substrate for antibody immobilization, and the electrochemical sensing potential was validated using electrochemical impedance spectroscopy (EIS). The results showed a wide dynamic range of E. coli detection, 101-108 cfu/mL, with a limit of detection (LOD) of 1.6 cfu/mL in buffer and 15 cfu/mL in the aqueous solution used for cleansing fresh lettuce leaves, affirming its efficiency as a practical and affordable tool in enhancing food safety.

Molnupiravir's real-world effectiveness in COVID-19 outpatients at high risk of severe disease: a single-center study.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic started in March 2020. Since then, there has been an urgent need for effective therapeutic methods to manage the disease. We aimed to assess the effectiveness of molnupiravir in reducing the need for hospitalization in at-risk, non-hospitalized COVID-19 patients. METHODOLOGY: This was a single-center, non-randomized, observational retrospective study of non-hospitalized patients with confirmed COVID-19, treated at the Clinic for Infectious and Tropical Diseases, University Clinical Center in Belgrade, Serbia. RESULTS: The study was conducted between 15 December 2021 and 15 February 2022 and included 320 patients. Of these, 165 (51.6%) received treatment with molnupiravir. The study and control groups were similar in gender and age distribution. The study group had a higher proportion of vaccination (75.2% vs. 51%, p < 0.001). There was no statistically significant difference in presence of comorbidity within the groups. Majority of the patients who received molnupiravir did not require hospitalization; and this was statistically significant in comparison to control group (92.7 vs. 24.5%, p < 0.001). Oxygen supplementation was less frequently required in the study group compared to the control group (0.6% vs. 31%, p < 0.001). During the follow-up period of 12.12 ± 3.5 days, significantly less patients from the study group were admitted to the intensive care unit (p < 0.001). Molnupiravir significantly reduced the risk of hospitalization by 97.9% (HR 0.021; 95% CI 0.005-0.089; p < 0.001). CONCLUSIONS: Molnupiravir is an effective therapy in preventing the development of severe forms of COVID-19 and hospitalization.

Is There a Role for Growth and Differentiation Factor-15 in B-Cell Lymphoproliferative Neoplasms?

Growth and differentiation factor-15 (GDF-15) correlates with worse outcome of many tumours and any cause mortality. Data about its role in lymphoproliferative neoplasms (LPN) are scarce. Our research aimed to reveal the correlation between GDF-15 and standard laboratory parameters of LPN activity, and to get insight into the possible value of this cytokine assessment in lymphoma patients. Prospective research included 40 patients treated for aggressive or indolent LPN, and 31 with indolent LPN on "watch and wait" regimen. Analyses were performed before and after treatment in treated patients and on two separate occasions in the "watch and wait" group. ELISA technique with R&D assays according to the manufacturer manual, from stored sera at - 70 °C was used for GDF-15 level measurement. Statistical analyses were performed by IBM SPSS Statistics 22 using descriptive and inferential statistics. As appropriate, differences between groups were assessed by two tailed t-test, Mann-Whitney or x2 test. Spearman Rank Order Correlation was done to correlate GDF-15 with standard laboratory markers of disease activity. All tests are two-tailed with significance level p < 0. 05. GDF-15 (p = 0.028) and fibrinogen (p = 0.001) concentrations increased after treatment in indolent lymphoma patients while ß2 microglobulin decreased (p < 0.001). GDF-15 positively correlated with ß2microglobulin before (p < 0.001) and after (p = 0.031) therapy. There were no differences in any of the aforementioned parameters in the "watch and wait" group during observation. A positive correlation between GDF-15 and ß2 microglobulin in patients with indolent LPN who need treatment suggests potential value in risk assessment. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01695-6.

The Interplay of Conflicting and Complementing Institutional Logics in Sustainability Practices.

The impact of institutional environments on sustainability is well documented in the international business literature. However, how multiple and occasionally conflicting institutional logics shape sustainability as it is practiced by individuals across countries remains undertheorized. Our study contributes to this line of research by examining how multiple institutional logics inform the comprehension of sustainability practices in two high-hazard organizations in the Republic of Serbia and Canada. In doing so, our findings explicate three multi-level mechanisms - pulling down (1st level), relating (2nd level), and aligning (2nd level) - through which individuals in these organizations across two countries construct a localized understanding of sustainability. In both countries, individuals pull down elements of the state and organizational logics to construct meso-level logics they use to comprehend sustainability practices, albeit differently. In Serbia, due to the conflict between the current state logic and dominant high-hazard organizational logic, individuals pull down elements of the high-hazard organizational logic and the enduring legacy state logic to construct a community logic and align sustainability practices with it. In Canada, the state logic complements the high-hazard organizational logic, resulting in individuals pulling down elements of both logics to construct the professional logic and aligning their practice with it. In both countries, due to the dominance of the high-hazard organizational logic, individuals relate their practices to the well-being of others. Based on our comparative case analysis, we create a general model and a country-specific model depicting how individuals embed multiple institutional logics into their sustainability practices.

The emergence of a value transformation strategic initiative in the healthcare context.

How do strategic initiatives emerge? Despite rich tradition in the emergent strategy literature-focused on significant organizational change-surprisingly little insight exists on the dynamics of a new initiative's emergence. This is particularly relevant in healthcare because of the increasing pressure to implement value transformation models focused on maximizing value at the point of care. The value transformation model prioritizes the decisions of the frontline providers and thus requires their expertise and commitment for the model's implementation and success. In our case study of a dental organization, "OptiPlex," we trace the emergence of a value transformation strategic initiative from its origination at the point of care to its formalization into the organization's strategic plan. Using qualitative methods, we identify three phases in the emergence of the value transformation strategic initiative, each embodying different championing behaviors necessary for the initiative's emergence. In doing so, we explicate the nature of these behaviors and how they link up across the organizational hierarchy to drive the value transformation strategic initiative's emergence and implementation.

A single-center experience of early administration of tocilizumab and corticosteroids in patients with COVID-19 pneumonia.

BACKGROUND: We investigated the therapeutic response of tocilizumab (TCZ) therapy in patients with coronavirus disease 2019 (COVID-19) pneumonia. METHODS: This observational retrospective study included 205 patients with confirmed COVID-19 pneumonia with SpO2˂93% and a markedly increased level of at least two biomarkers of inflammation. The TCZ was given in combination with corticosteroids. Clinical and laboratory results were analyzed and compared before TCZ therapy and 7 d after. RESULTS: The mean value of C-reactive protein (CRP) was significantly lower (p=0.001) on the seventh day after administration of TCZ compared with before (10.7 and 173.6 mg/L, respectively). Only in 9/205 (4.3%) patients, the CRP level did not decrease during the week-long period, and this was related to disease progression. The mean level of interleukin-6 before TCZ administration was 88±113 pg/mL, while after it was 32.7±21.7 pg/mL (p=0.01). After 7 d of TCZ therapy, almost 50% of patients who needed high-flow oxygen or ventilation support started to receive low-flow oxygen, while 73/205 (35.6%) patients who received low-flow oxygen before TCZ administration did not receive further oxygen support anymore (p=0.001). Although they received TCZ treatment, 38/205 (18.5%) severely sick patients died. CONCLUSIONS: Tocilizumab improves clinical outcomes in hospitalized COVID-19 patients. These advantages were evident independent of the patient's comorbidities and were in addition to the advantages of systemic corticosteroids. In COVID-19 patients at risk of cytokine storms, TCZ appears to be an effective therapy choice.

Influence of chronic liver diseases on the course and outcome of COVID-19.

INTRODUCTION: Coronavirus disease of 2019 (COVID-19) is a global health problem. The impact of chronic liver diseases on the course and outcome of COVID-19 is still the subject of research. The aim of this study was to show the characteristics of COVID-19 patients with chronic liver diseases, and to establish the risk factors for unfavourable outcome. METHODS: A retrospective observational study was conducted at the Infectious Disease Clinic in Belgrade, Serbia, and included 80 patients with chronic liver diseases and COVID-19 within a time frame of two years (between 15 March 2020 and 15 March 2022). Characteristics of the affected persons, as well as the risk factors for a fatal outcome, were analyzed. RESULTS: Of the 80 subjects in the study, 23.8% had chronic viral hepatitis, 12.5% autoimmune liver diseases and alcoholic liver disease respectively, 30% had non-alcoholic fatty liver disease, while 11.2% had chronic liver diseases of unknown aetiology. A total of 33.7% had cirrhosis, 6.3% hepatocellular carcinoma and 5% had liver transplants. A total of 92.5% of respondents had pneumonia (21.2% were critically ill). A deterioration of chronic liver disease was registered among 33.7% of patients, and decompensation in 3.8%; 76.3% patients recovered, while 23.7% had a lethal outcome. Risk factors for lethal outcome by univariate analysis were: alcoholic liver disease, cirrhosis, increased transaminases values prior to COVID-19, malignancy, severe pneumonia and dyspnea. In a multivariate analysis, the presence of liver cirrhosis (OR = 69.1, p = 0.001) and severe pneumonia (OR = 22.3, p = 0.006) remained independently predictive for lethal outcome. CONCLUSION: These findings will help with the evaluation of COVID-19 patients who have chronic liver diseases and will improve their risk stratification.

Shared accountability in distributed leadership for improved healthcare access: a study of a US dental institution.

PURPOSE: Accountability within distributed leadership (DL) is critical for DL to drive positive outcomes in health services organizations. Despite this, how accountability emerges in DL is less clear. This study aims to understand how accountability emerges in DL so that distributed leaders can drive improvements in healthcare access - an increasingly important outcome in today's health services environment. DESIGN/METHODOLOGY/APPROACH: The authors use an instrumental case study of a dental institution in the USA, "Environ," as it underwent a strategic change to improve healthcare access to rural populations. The authors focused on DL occurring within the strategic change and collected interview, observation and archival data. FINDINGS: The findings demonstrate accountability in DL emerged as shared accountability and has three elements: personal ownership, agentic actions and a shared belief system. Each of these was necessary for DL to advance the strategic change for improved healthcare access. PRACTICAL IMPLICATIONS: Top managers should be cognizant of the emergence processes driven by DL. This includes enabling pockets of employees to connect, align and link up so that ideas, processes and practices can emerge and allow for shared accountability in DL. ORIGINALITY/VALUE: The overarching contribution of this research is identifying shared accountability in DL and its three elements: personal ownership, agentic actions and a shared belief system. These elements serve as a platform to demonstrate "how DL works" in a healthcare organization.

Antioxidant Genetic Profile Modifies Probability of Developing Neurological Sequelae in Long-COVID.

Understanding the sequelae of COVID-19 is of utmost importance. Neuroinflammation and disturbed redox homeostasis are suggested as prevailing underlying mechanisms in neurological sequelae propagation in long-COVID. We aimed to investigate whether variations in antioxidant genetic profile might be associated with neurological sequelae in long-COVID. Neurological examination and antioxidant genetic profile (SOD2, GPXs and GSTs) determination, as well as, genotype analysis of Nrf2 and ACE2, were conducted on 167 COVID-19 patients. Polymorphisms were determined by the appropriate PCR methods. Only polymorphisms in GSTP1AB and GSTO1 were independently associated with long-COVID manifestations. Indeed, individuals carrying GSTP1 Val or GSTO1 Asp allele exhibited lower odds of long-COVID myalgia development, both independently and in combination. Furthermore, the combined presence of GSTP1 Ile and GSTO1 Ala alleles exhibited cumulative risk regarding long-COVID myalgia in carriers of the combined GPX1 LeuLeu/GPX3 CC genotype. Moreover, individuals carrying combined GSTM1-null/GPX1LeuLeu genotype were more prone to developing long-COVID "brain fog", while this probability further enlarged if the Nrf2 A allele was also present. The fact that certain genetic variants of antioxidant enzymes, independently or in combination, affect the probability of long-COVID manifestations, further emphasizes the involvement of genetic susceptibility when SARS-CoV-2 infection is initiated in the host cells, and also months after.