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    SAPS 2 score valid parameter for outcome in severe influenza
    (Faculty of Medicine, Ss. Cyril and Methodius University, Skopje, R Macedonia, 2021)
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    Cvetanovski, Vlatko
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    Insight in the Current Progress in the Largest Clinical Trials for Covid-19 Drug Management (As of January 2021)
    (Macedonian Academy of Sciences and Arts/Sciendo, 2021-04-23)
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    Ridova Nevenka
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    Stojanoska, Tatjana
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    Abstract The outbreak of the COVID-19 pandemic has generated the largest global health crisis of the 21st century, evolving into accelerating socioeconomic disruption. In spite of all rapidly and widely emerging scientific data on epidemiology, diagnosis, prevention and treatment of the COVID-19 disease, severe acute respiratory coronavirus 2 (SARS-CoV-2) is continuing to propagate in lack of definitive and specific therapeutic agents. Current therapeutic strategies are mainly focused on viral inhibition by antiviral drugs and hampering the exuberant immune response of the host by immunomodulatory drugs. In this review, we have studied the reports of the largest clinical trials intended to COVID-19 treatment published during the first year of the pandemics. In general, these results concentrate on seven therapeutic options: remdesivir, chloroguine/hydroxychloroquine, lopinavir-ritonavir combination, corticosteroids, tocilizumab, convalescent plasma and monoclonal antibodies. In line with the reviewed data, as of January 2021, most of the evidence support the use of remdesivir in hospitalized patients with moderate and severe forms of the disease and provide reliable data on the substantial beneficial effect of corticosteroids in patients requiring supplemental oxygen. Moreover, preliminary RECOVERY trial results have demonstrated the efficacy of tociluzumab in the treatment of critically ill patients. The reports presenting the outcomes of the other immune-based therapies under investigation are enthusiastically awaited.
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    Relationship Between Azithromycin and Cardiovascular Outcomes in Unvaccinated Patients With COVID-19 and Preexisting Cardiovascular Disease
    (American Heart Association, 2023-07)
    Bergami M
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    Manfrini O
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    Nava S
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    Caramori G
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    Yoon J
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    Procalcitonin values as prognostic marker in patients with sepsis and septic shock.
    (Македонско лекарско друштво = Macedonian Medical Association, 2018)
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    Seasonal influenza-factors associated with a severe clinical form of the illness.
    (Македонско лекарско друштво = Macedonian Medical Association, 2016)
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    Kirova Urosevic V
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    Acute bacterial meningitis – challenges and conclusions
    (IMAB Peytchinski Publishing Ltd., 2024-10)
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    Cana, Fadil
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    Acute bacterial meningitis is an urgent condition characterized by significant morbidity and mortality. In the last decades, epidemiology of the most common etiologic agents as well as the age limit has changed significantly, with dominant involvement of the adult population and population at risk. Streptococcus pneumoniae remains the most common bacteria causing bacterial meningitis. The aim of this study is to observe the changes in the prevalence of etiologic agents and their dominance, the most commonly affected age groups, as well as comorbidities and complications in patients with acute bacterial meningitis treated at the University Clinic for Infectious Diseases in Skopje, R.N. Macedonia. In the last seven-year period, 194 patients with acute bacterial meningitis were treated. The etiologic agent in cerebrospinal fluid was confirmed in 94 (48.45%) patients, with the predominance of S. pneumoniae in 74 (78.72%). L. monocytogenes with 10 (10.63%) and N. meningitides with 6 (6.38%) were less represented. Male sex is dominant with 111 (57.21%) and older age groups as well. More than half of the patients, from the study, belonged to the at risk population with the highest percentage of them presenting with more than two comorbidities, as well as complications. In our study group, 41 (21.13%) of the patients died. Because of the substantial mortality and morbidity, it remains an urgent need to optimally deploy existing vaccines worldwide and develop new prevention strategies and treatment options.
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    Pneumonia impact on the flow and the outcome at patients with seasonal influenza
    (European Respiratory Society, 2020-09)
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    Abstract Seasonal influenza complications are the cause of development of severe clinical picture as well as death. The most common are the respiratory ones, and the leading one that stands out is the secondary bacterial pneumonia. The aim of this study is determining the pneumonia impact on the severity of the clinical picture as well as the outcome for the patients with influenza. The research is prospectively compared in groups, carried out at University Clinic for Infectious Diseases during a 3-year period. 122 adult patients with clinical and laboratory confirmed influenza have been analyzed. Based on the severity of the clinical picture, patients were divided into two groups, a severe (n=87) and a mild (n=35) form of the disease. During the study demographic, general data, clinical symptoms and signs as well as complications have been recorded. Out of 122 patients with influenza, there were registered complications at 108 (88.52%), with significant appearance in the group with severe influenza 93.1% vs 77.14% (p=0.012). The most common one in percentage is pneumonia 98(80.33%) which also significantly influenced the severity of the disease (p=0.002). Complications such as ABI 8(6.56%), ARDS 7(5.74%), sepsis 5(4.1%), DIC 4(3.28%), and otitis 2(1.64%) have been registered only in the group with severe influenza. At 5(4.1%) patients acute meningoencephalitis has been registered, gastroenterocolitis at 3(2.46%), an hepatic damage at 14(11.47%) of the patients. Pneumonia as the most common complication for patients with severe influenza has significant impact on the clinical flow ant the outcome of the disease.
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    Evaluation of oxidative stress markers in hospitalized patients with moderate and severe COVID-19
    (Walter de Gruyter GmbH/Sciendo, 2021-12-01)
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    Background. Clinical evidence suggests increased oxidative stress in COVID-19 patients and this worsened redox status could potentially contribute to the progression of the disease. Objectives. To investigate the oxidative stress we have measured oxidative stress parameters, namely, PAT (total antioxidant power, iron reducing) and d-ROMs (plasma peroxides). Additionally we have investigated their correlation with the most frequently used clinical parameters CRP, LDH, and NLR in serum from moderate and severe COVID-19 patients hospitalized in a tertiary hospital. Methods. PAT and d-ROMs were determined by analytical photometric metric method in serum from 50 hospitalized patients. For each of them, two samples were collected and analyzed immediately after collection seven days apart. Results. All patients at admission had a much higher value for plasma peroxides and a significant correlation between oxidative stress parameters and CRP, LDH, and NLR. (p<0.05), except for OS index (OSI) vs CRP in the severe group. At discharge, plasma peroxides were reduced and OSI was improved in the moderate group. Conclusion. We consider that using OSI at the beginning of COVID-19 disease presents a valuable starting point for the general assessment of oxidative stress and hence enabling a better triage of the patients in terms of disease severity.
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    Epidemiology of Community-Acquired Sepsis in Adult Patients: A Six Year Observational Study
    (Macedonian Academy of Sciences and Arts/Sciendo, 2018-07-01)
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    Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection and it is a major cause of morbidity and mortality worldwide. The aim of this study is to describe epidemiology of community-acquired sepsis in the Intensive care unit (ICU) of the Macedonian tertiary care University Clinic for Infectious Diseases. A prospective observational study was conducted over a 6-year period from January, 2011 to December, 2016. All consecutive adults with community-acquired sepsis or septic shock were included in the study. Variables measured were incidence of sepsis, age, gender, comorbidities, season, source of infection, complications, interventions, severity indexes, length of stay, laboratory findings, blood cultures, 28-day and in hospital mortality. Of 1348 admissions, 277 (20.5%) had sepsis and septic shock. The most common chronic condition was heart failure (26.4%), and the most frequent site of infection was the respiratory tract (57.4%). Median Simplified Acute Physiology Score (SAPS II) was 50.0, and median Sequential Organ Failure Assessment (SOFA) score was 8.0. Blood cultures were positive in 22% of the cases. Gram-positive bacteria were isolated in 13% and Gram-negatives in 9.7% of patients with sepsis. The overall 28-day and in hospital mortality was 50.5% and 56.3% respectively. The presence of chronic heart failure, occurrence of ARDS, septic shock and the winter period may influence an unfavorable outcome. Mortality compared to previous years is unchanged but patients that we have been treating these last 6 years have had more severe illnesses. Better adherence to the Surviving Sepsis guidelines will reduce mortality in this group of severely ill patients.
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    Prevalence of Allelic Variants and Clonality of IGHV1-69 Expressing B-Cells in Patients with Different Severity of COVID 19 Disease
    (Elsevier, 2021-11-23)
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    Nevenka Ridova
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    Simona Stojanovska
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    Tatjana Stojanoska
    Abstract Introduction: Since the first months of the COVID-19 pandemic, efforts have been made to understand the importance of broadly neutralising natural antibodies in determining the response to SARS-CoV-2. Previous studies have shown that allelic variants of the IGHV1-69 gene play a dominant role in protective natural antibody responses to several other viral pathogens, including influenza virus, hepatitis C virus, human immunodeficiency virus and, most notably, the SARS-CoV-2-related viruses SARS-CoV and MERS-CoV. These allelic variants are commonly known as 51p1-related and differ from the other IGHV1-69 alleles (known as hv1263-related) in the presence of a Phe54 residue in the CDR2 region. Importantly, crystallographic studies have shown that the Phe54 residue is critical for the binding of IGHV1-69 antibodies to the SARS-CoV and MERS-CoV spike proteins. In this study, we evaluated the prevalence of 51p1 and hv1263 alleles and the clonality of 51p1- and hv1263-expressing B cells in a large cohort of healthy individuals and COVID-19 patients and correlated the findings with the severity of the disease. Мaterials and methods: A total of 419 samples were included in the study, of which 78 asymptomatic/mildly symptomatic individuals, 200 hospitalized patients with severe disease, 94 critically ill patients and 47 healthy donors. Peripheral blood was collected 8-20 days after the onset of symptoms and total cellular RNA was extracted from whole blood using an automated procedure. Аllelle-specific Ig-gene fingerprinting of IgM heavy chain transcripts was used to simultaneously analyse the clonality of the IgM+ B-cell population and the clonality of the 51p1- and hv1263-expressing B cell populations. The significance of the differences in the prevalence of clonal B-cell populations between healthy donors and patients and between patients with different severity of the disease was calculated with the Chi-Square test. Results: Analysis of the clonality of the IgM+ B-cell population showed a polyclonal pattern in most of the investigated healthy individuals (33/47, 70%) but in only 20% of all SARS-CoV-2 infected individuals (75/372, p<0.001). A significant difference was also observed between mildly affected and severely/critically ill patients [31/78 (39.7%) vs. 44/294 (15%), respectively) (p<0.001)], but not between severely and critically ill patients [28/200 (14,%) vs. 16/94 (17,1%), (p=n.s.)]. No 51p1 transcripts were detected in 74/372 (19.9%) of SARS-CoV-2 infected individuals and in 14/47 (29,8%) of the control group (p>0,01), while hv1263 transcripts were not detected in 155/289 (53,6%) and in 27/47 (68,6%) tasted patients and controls, respectively (p>0,05). We did not find a statistically significant difference in the prevalence of 51p1 and hv1263 alleles between patients with different disease severity. However, a significantly higher number of patients displayed clonal expansions of 51p1- or hv1263-expressing B cells (219/372(58.9%) and 118/244 (48,4%), respectively in comparison to healthy donors [5/47(10.6%) and 7/47(14.9%), respectively]. There was no statistically significant difference between mildly affected and severely/critically ill patients in the clonallity status of 51p1- 38/61 (62,3%) and 182/237 (76,7%) respectively or between hv1263- expressing B cells in the same two groups of patients [20/25 (80%) and 98/109 (89,9%), p>0.05]. Conclusions: Our results show that SARS-CoV-2 infection stimulates clonal expansions of IGHV1-69 -expressing B-cells, but this is independent of the severity of the disease. In addition, no difference in the prevalence of IGHV1-69 alleles was observed between patients at different stages of the disease, indicating that natural neutralizing antibodies encoded by this gene are not an important determinant of COVID-19 severity and progression. Disclosures No relevant conflicts of interest to declare.