Clinical laboratories in the era of the COVID-19 pandemic: An analysis of experiences in Serbia

The COVID-19 pandemic represents one of the most serious public health threats that our world has faced in recent history. Clinical laboratories play a significant role in the global fight against this pandemic. This paper is based on the experiences of the Center for Medical Biochemistry of the University Clinical Center of Serbia. Using mixed methods research, the study sheds light on the many challenges that the Center has been facing during the pandemic, it outlines the implementation of change, and makes recommendations for functioning during the COVID-19 pandemic and in the post-COVID era.

SARS-Cov-2: Epidemiological characteristics, clinical characteristics, diagnosis and prevention: A review of current knowledge

The SARS-Cov-2 disease appeared in December 2019, when the new coronavirus was confirmed to be the cause of the disease. The objective of this article is to summarize previous research on the epidemiological characteristics, etiology, clinical characteristics, diagnosis, prevention, and control of the new SARS-Cov-2 infection. The SARS-Cov-2 virus belongs to the group of betacoronaviruses, which are single-stranded RNA viruses. The envelope has a crucial role in the pathogenicity of the virus. A viral infection can cause an excessive immune response in the patient, which is labeled as a "cytokine storm," and whose effect is extensive tissue damage. Three main routes of the transmission of the virus are: droplets, direct contact, aerosol. The incubation period is considered to be 1-14 days. The clinical manifestation ranges from asymptomatic, mild, to severe, and some cases end in death. The main clinical manifestations include fever, cough, and shortness of breath. Nasal congestion, a runny nose, a sore throat, headache, myalgia, diarrhea, loss of the sense of taste and/or smell have also been reported. The diagnostic procedures are the following: clinical manifestation, chest X-rays, biochemical analyses, epidemiological anamnesis. A positive nasopharyngeal or oropharyngeal swab (Ag test, and/or reverse transcription polymerase chain reaction (RT-PCR)) is used for etiological diagnosis. The SARS-Cov-2 infection has affected a large number of people and countries around the world. The application of preventive measures, early identification of infected persons, their isolation , and vaccination are currently the most effective mode in the battle against this virus. After the conclusion of the pandemic, it will be possible to estimate the health, social and economic impact of the virus.

Osteoarthritis, osteoarthrosis and osteoarthropathy: What is the difference?

Osteoarthritis, osteoarthrosis, and osteoarthropathy are diseases that doctors encounter daily in their practice. The use of all three terms is customary, often without a clear justification as to why a particular term is used for a particular case. In the past several decades, doctors mainly differentiated among these diseases based on clinical presentation and radiography. In the past several years, however, significant progress has been made in the field of biochemical, immunological, and cytohistological research, which has provided explanations for the pathogenesis of these conditions, enabled defining differences amongst them and facilitated the use of appropriate terms for each one of these diseases. The term arthritis (osteoarthritis) should be used exclusively for primarily inflammatory joint diseases-rheumatoid arthritis, juvenile arthritis, reactive arthritis (Reiter's syndrome). If the etiology is infectious, this must also be emphasized-septic (purulent) arthritis, tuberculous arthritis. Arthrosis (osteoarthrosis) relates to changes in the joints occurring due to pathological processes within the joint itself, but which, in their basis, are not inflammatory. Arthropathy is a term for joint disease stemming from another diseased organ or system of organs.

Preimplantation genetic testing

The application of preimplantation genetic testing (PGT) began in the late 1980s. Pre-implantation genetic testing, as the earliest possible method of prenatal diagnosis, enables the selection of embryos with a normal karyotype for embryo transfer. The use of preimplantation genetic testing has proven to be a useful method in the following three groups of inherited diseases: monogenic disorders (single gene defects), trinucleotide repeat disorders, and chromosomal abnormalities. The success rate of in vitro fertilization (IVF) has increased significantly since the introduction of PGT into clinical practice. This paper presents a literature review with the aim of clearly determining the role of PGT in embryo selection before embryo transfer, as well as the role of this type of testing in increasing the success rate of IVF. One of the goals of the paper is also to review the development of molecular genetic methods that are currently, or have once been, in routine use when performing PGT. The current literature is an indicator of the development and progress of molecular genetics techniques applied in PGT. At the same time, it provides an opportunity and an incentive for further extensive research that will lead to the improvement of preimplantation genetic testing and thus increase the success rate of in vitro fertilization.

Influence of antifungal prophylaxis on the occurrence of fungal infections in patients undergoing allogeneic transplantation

Introduction: Patients with hematologic malignancies, such as acute myeloid leukemia and acute lymphoblastic leukemia (AML/ALL), myelodysplastic syndrome (MDS), and those undergoing allergenic stem cell transplantation (alloSCT) are at the highest risk of invasive fungal infections (IFI). The most common causative agents are Candida spp. and Aspergillus spp. Among the strategies for preventing IFIs is the adequate implementation of antifungal prophylaxis recommended by the NCCN (National Comprehensive Cancer Network). Aim: The aim of the study was to analyze the occurrence of IFIs in these patients, as well as to analyze the impact and importance of timely antifungal prophylaxis with regards to the development of these infections. Materials and methods: The retrospective study included 42 patients, of the average age of 35 years, who underwent the allo-SCT program, between 2017 to 2019, and received antifungal prophylaxis at the Clinic for Hematology of the Clinical Center of Serbia (CCS). Based on information obtained from medical histories, databases were formed. Statistical analysis included descriptive statistical methods that were performed in the SPSS program. Results: Nineteen (45.2%) patients presented with the clinical manifestation of oral candidiasis. Invasive pulmonary aspergillosis developed in only 3 (7.1%) patients. There was a statistically significant association between clinically manifest aspergillosis (7.1%) and the presence of antigens (Galactomannan) in these patients (p <0.001). There was also a statistically significant association between clinically manifest aspergillosis and graft weakness: 2 (66.6%) vs. 1 (33.3%), (p = 0.016). Conclusion: The use of adequate antifungal prophylaxis significantly reduces the incidence of IFIs in patients undergoing the allo-SCT program, and this contributes to the reduction of morbidity and mortality.

Esophageal, gastric, colorectal, pancreatic, hepatocellular carcinomas and cholangiocarcinomas in Northern Macedonia: A series of patients treated at the University Clinic, between 2015 and 2019

Introduction: The global burden of gastrointestinal cancer (GIC) is growing. Stomach, colon and liver are among the five most common sites for GIC in men and women worldwide. The incidence of GIC shows significant variation in Europe and North America. Aim: The aim of this paper is to describe hospital morbidity from GI cancer at the University Clinic in Northern Macedonia. Materials and methods: A retrospective longitudinal analysis included a series of cases with GIC, at the University Clinic of Gastroenterohepatology (UCG) in Skopje, in the period 2015-2019. Descriptive statistical methods were used to describe hospital morbidity from GIC, and its distribution by age, sex, and cancer site. Results: In a five-year period, a total of 2,831 patients with GIC were treated at the UCG, of which 1,484 patients had colorectal cancer, 763 patients had gastric cancer and 88 patients had esophageal cancer. Although liver cancers were less common, as many as one eighth of such patients (355 or 13%) had nonspecific liver malignancy. Most patients were in the 60-69 age group, with the exception of esophageal cancer. An increase in the incidence of pancreatic cancer was observed, almost equal, when considering the distribution by sex, and mainly in the age groups 60-69 and 70-79 years. Conclusion: Hospital morbidity due to GIC in North Macedonia shows an increasing trend, so it is important to determine how much screening has contributed to the early detection of these cancers and to ensure access to and availability of therapy for hepatitis B and C.

COVID-19 mortality in Belgrade

Introduction: Mortality data are the most reliable indicators of the number of lives that a community has lost due to COVID-19 and represent the minimum data necessary for public health decision-making. Aim: The aim of the study is to describe the basic characteristics of population mortality from COVID-19 in Belgrade in 2020. Methods: The unit of observation in this cross-sectional study for the description of mortality from COVID-19 in 2020 was the population of Belgrade (total, by sex, and by age intervals). COVID-19 was analyzed as the main cause of death (ICD-10: U071, U072). The number and the structure of deaths (%), the crude death rate (per 1,000 population) and the specific death rate (per 100,000 population) were analyzed. The data sources for the study were official statistics on vital events of the Statistical Office of the Republic of Serbia. Results: In 2020, 10.5% of the total number of deaths were due to COVID-19, and the majority of deaths was from the male contingent of Belgrade residents. The mortality rate due to COVID-19 was 158.78 per 100,000 population (211.7 for males and 111.4 for females). COVID-19 was the second leading cause of death in Belgrade. Conclusion: The results of this study indicate the existence of premature mortality in Belgrade. In 2020, COVID-19 was the second leading cause of death among the male residents of Belgrade, while in female residents, it was the third leading cause of mortality. This research provides evidence that can contribute to the international discussion about societal losses caused by the COVID-19 pandemic.

Triage at a non-covid hospital during the COVID-19 pandemic

At the time of the COVID-19 pandemic, the Emergency Center of the University Clinical Center of Serbia (EC-UCCS), although a non-covid hospital, had to adapt to taking care of a large number of critically ill and, at the same time, potentially contagious patients. In this paper, we present the ways that the EC-UCCS has adjusted to the conditions of the pandemic, where no precise protocols had previously been established for acting in these types of situations. In March 2019, the Admissions Triage Facility of Emergency Medicine (ATFEM) was established. The main task of this facility was to separate patients with epidemiological risk (ER) from patients without risk and to carry out their further isolated care. ER assessment involves completing an epidemiological questionnaire, a targeted brief history, body temperature measurement, and assessment of the patient's respiratory status. The complete triage process, initial diagnosis, and treatment of patients with ER is the task and responsibility of emergency medicine specialists. Between March 15, 2020 and March 15, 2021, about 155,000 patients were examined in triage, of whom 9,519 had ER and were taken care of in the ATFEM. This triage method minimizes the spread of infection while taking care of all critically ill patients, regardless of ER. However, both patients with low and high risk of COVID-19, were all admitted to the same facility, due to the shortage of available space. Also, triage relates only to "covid triage" and not to triage according to the degree of urgency of the patients, which is the primary task of every modern emergency center.

Prognostic significance of serum ferritin levels on initial diagnosis in patients with acute myeloid leukemia

Introduction/Aim: Acute myeloid leukemia (AML) is a heterogenous malignant disease whose course and outcome are influenced by a number of prognostic factors. Serum ferritin (SF) is often elevated in oncology patients, and it has been shown that it strongly influences an unfavorable outcome in various malignancies. The aim of this study is to assess the effect of high SF values on overall survival and disease-free survival, as well as to assess the correlation of SF values with other prognostic markers, such as clinical and laboratory parameters. Methods: Retrospective analysis included 108 patients diagnosed with AML at the Clinic for Hematology of the Clinical Center of Serbia (CCS), in Belgrade, in the period 2017 - 2019. Patients with acute promyelocytic leukemia, acute mixed lineage leukemia, secondary AML and patients treated with palliative therapy were excluded from the study. Patients were grouped based on the SF cutoff value of 800 µg/L. Results: Patients with higher SF values had a significantly higher incidence of early death (p = 0.020), sepsis in the induction phase of therapy (p < 0.010), and significantly lower initial hemoglobin levels (p = 0.040), as compared to patients with lower SF values. SF at diagnosis appeared to be a significant independent predictive factor of overall survival (p = 0.019) and of disease-free survival (p = 0.040). Conclusion: Our study showed a significant association of high SF values with sepsis in induction, early death, mean hemoglobin, overall survival, and disease-free survival. Identification of SF as an independent prognostic factor and a potential target site of the action of new drugs could contribute to a better prognosis of AML patients.

Limitations of rapid serological testing for SARS-CoV-2 in non-vaccinated patients in acute cardiac care

In December 2019 in the city of Wuhan, in China, the first cases of infection caused by the new SARS-CoV-2 virus appeared, and later on, the disease caused by this virus was named COVID-19. Shortly after this, on March 11 th , 2020, the WHO characterized COVID-19 as a global pandemic. The symptoms of COVID-19 and acute cardiovascular disorders (e.g., heart failure, pulmonary embolism or myocardial ischemia) frequently overlap, which poses a challenge for the establishing of a differential diagnosis in clinical practice. Rapid serological tests, which detect IgM and IgG classes of antibodies for SARS-CoV 2, have been developed with the primary purpose of screening the population's immunological response to the SARS-CoV-2 virus. However, rapid serological tests are often used outside their original purpose, i.e., for the triage of possibly infected, non-vaccinated individuals, because they offer quick results, which may be particularly relevant in emergency settings. If serological testing is used to guide the admission of non-vaccinated patients with acute cardiovascular disorders to either an isolation unit for suspected COVID-19 positive individuals, or to hospital facilities for non-infected patients, it is important to recognize its limitations, in order to reduce the risk of false-positive or false-negative results. Hence, appropriate patient selection and cautious test interpretation is necessary to avoid misdiagnosis. The aim of this paper is to illustrate how serological testing may be used as a screening tool to inform the management of non-vaccinated patients with acute cardiovascular disorders requiring urgent hospital admission. As an illustration, we describe two clinical situations, in which serological testing produced meaningful results.