Two vicious circles associated with the aging of the immune system in the development of severe forms of COVID-19.

Background: The immune-inflammatory response is the basis of the pathophysiology of SARS-Cov-2 infection. In severe cases of COVID-19 uncontrolled systemic inflammatory response causes multiorgan dysfunction (MODS), as the most common immediate cause of death. Unfavorable outcome of the COVID-19 most often occurs in elderly patients. The aim of the study was to establish parameters with prognostic significance in severe cases of COVID-19 according to life years, laboratory markers of sepsis and MODS, as well as the number of peripheral CD4+ and CD8+T lymphocytes in 20 consecutively selected critically ill patients. Results: Eleven subjects were male, 9 female, mean age 73.45 ± 11.59, among which the oldest patient was 94 and the youngest 43 years. All the patients met the sepsis and MODS criteria. Increased age and low CD4+ and CD8+T cell counts were identified as independent predictors of death. Only the two youngest patients (43 and 50 years old) survived 28 days, and they are the only ones with a CD4 lymphocyte count above 500 cells/mm3. Conclusion: Senescence of the immune system is mostly characterized by reduced regenerative capacity of adaptive immunity with diminished ability to respond to new antigens and a manifested proinflammatory phenotype. Additional reduction of protective capacity by further deterioration of T cell quantity and quality due to sepsis itself and mutual interaction of senescent T cells and vascular endothelial cells in the induction of cytokine storm represent two complementary vicious cycles in the development of sepsis-related multiorgan dysfunction.

Fatal Case of Imported Tick-Borne Encephalitis in South Serbia.

Tick-borne encephalitis (TBE) is vaccine-preventable neglected zoonotic neuroinvasive disease, caused by tick-borne encephalitis virus (TBEV). Many of the Central and Eastern European countries are affected by TBE, which is often poorly perceived by tourists visiting endemic territories. Here we are reporting a fatal case of imported TBE in Serbian resident who was exposed to a tick bite during a visit to Switzerland.

The Occurrence of Acute Pancreatitis in Adult Patients during a Measles Outbreak from November 2017 to May 2018 in Southeastern Serbia.

Background and Objectives: Although it is believed that measles infections are under control, there is a global reappearance, and their treatment has become more complex as the disease is followed by a relatively high incidence of complications. This study, conducted on patients during a measles outbreak from November 2017 to May 2018, aims to evaluate a rarely reported complication of measles, acute morbilous pancreatitis (AMP), which has been reported in several cases to date. Materials and Methods: A total of 207 patients admitted and treated at the Clinic for Infectious Diseases, Clinical Center Nis, for measles infection were included in the analysis. The data collected from the patient's medical records included the demographic characteristics, disease duration, full blood, serum, and urine biochemical analysis, general measles-associated symptoms, and disease outcome. Results: According to the serum and urine amylase activity, and some clinical symptoms AMP were diagnosed in 14% (29/207) of the studied patients. These patients had significantly higher levels of ALT and vomited more frequently than the patients without AMP. Only slight differences in measles duration, changes in RBC count, and CRP levels were found between the males and females with AMP. Conclusions: Acute morbillous pancreatitis should not be underestimated as a complication, even though according to the results of our survey, it was not associated with a fatal outcome or disease severity as the course of it can be frequently rapid and fatal.

Two-Year Complete Remission of Diffuse Large B-Cell Lymphoma in an Immunological Nonresponder HIV-Infected Patient: Case Report.

INTRODUCTION: HIV-infected patients are affected significantly more frequently by all types of lymphoma, with diffuse large B-cell lymphoma (DLBCL) as the most prevalent histological type. Since the introduction of combination antiretroviral therapy (cART) morbidity and mortality of DLBCL has been markedly reduced, which is primarily interpreted as a result of the drug-mediated immune reconstitution. CASE REPORT: We present a previously healthy, 44-year-old HIV-infected man with DLBCL of the oral cavity, treated with immunochemotherapy and cART. During HIV-directed treatment, despite the successful virologic response, a satisfactory immunological response was not achieved. However, the patient had a 2-year complete remission after first-line treatment of DLBCL. CONCLUSION: Response to cART strongly predicts outcome in patients with DLBCL. Close monitoring of HIV-directed therapy efficacy, especially as to achievement of successful virologic response, independently associated with prolonged survival, is essential for estimating future DLBCL treatment strategies.

SUSCEPTIBILITY OF RESPIRATORY ISOLATES OF STREPTOCOCCUS PNEUMONIAE ISOLATED FROM CHILDREN HOSPITALIZED IN THE CLINICAL CENTER NIS.

INTRODUCTION: Streptococcus pneumoniae is one of the most common causes of respiratory infections. The aim was to study the susceptibility to antimicrobial agents of respiratory isolates ofStreptococcus pneumoniae obtained from hospitalized children. MATERIAL AND METHODS: A total of 190 respiratory pneumococcal isolates obtained from children aged from 0 to 14 years were isolated and identified by using standard microbiological methods. Susceptibility to oxacillin, erythromycin, clindamycin, tetracycline, cotrimoxazole, ofloxacin and rifampicin was tested by disc diffusion method. Minimal inhibitory concentrations for amoxicillin and ceftriaxone were determined by means of E test. The macrolide-resistant phenotype was detected by double disc diffusion test. RESULTS: All tested isolates were susceptible to amoxicillin and ceftriaxone. The minimal amoxicillin concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.50 microg/ml and 1.0 microg/ml, respectively and the minimal ceftriaxone concentration inhibiting the growth of 50% of isolates and of 90% of isolates was 0.25 microg/ml and 0.50 microg/ml, respectively. Susceptibility to erythromycin and clindamycin was observed in 21.6% and 29.47% of isolates, respectively. The resistence to macrolides-M phenotype was detected in 10.07% of isolates and constitutive macrolide-lincosamide-streptogramin phenotype (constitutive MLS phenotype) was found in 89.93% of isolates. All tested isolates were susceptible to ofloxacin and rifampicin. CONCLUSION: Amoxicillin could be the therapy of choice in pediatric practice. The macrolides should not be recommended for the empirical therapy of pneumococcal respiratory tract infection in our local area.

Anaphylactic shock due to unruptured hepatic hydatid cyst complicated by multiple intrahospital infections.

Anaphylactic shock due to unruptured hydatid cyst is a rare complication of hepatic echinococcosis. Here, we present an unusual case of unruptured hydatid cyst causing anaphylactic shock followed by appendicitis, ileus, and complicated by septic condition due to multiple intrahospital infections. Decision of the surgical cyst removal at the right moment and appropriate antimicrobial treatment are key factors for a positive outcome.

Listeria monocytogenes meningitis in an immunocompetent 18-year-old patient as a possible diagnostic and therapeutical problem.

INTRODUCTION: Listeria monoytogenes is the third most frequent cause of bacterial meningitis in adults. It commonly affects persons with defective cell-mediated immunity or advanced age, and only a few patiens with no underlying predisposition have been reported. CASE REPORT: We presented an previously healthy, 18-year-old man with typical clinical features of meningitis. On the account of earlier treatment with ceftriaxone and cerebrospinal fluid finding, an assumption of partially treated bacterial meningitis was made. The initial treatment with vancomycin and ceftriaxone, substituted on day 4 with meropenem, did not produce any clinical effect. On day 6 Listeria monocytogenes was isolated and, even as late as that, the administration of ampicillin was followed by complete recovery of the patient. CONCLUSION: In younger, immunocompetent individuals, in spite of the existent diagnostic and therapeutic problems, the subacute course of Listeria monocytogenes meningitis provides enough time for appropriate treatment and favorable disease outcome.

Antioxidant defense and oxidative stress in children with acute hepatitis A.

BACKGROUND AND OBJECTIVES: Published data on oxidative stress in children with acute hepatitis A are still very scarce. This study aims to evaluate the oxidant/antioxidant status of these patients. DESIGN AND SETTING: Prospective, case-control study, over 2.5 years in patients under hospitalized and ambulatory care. PATIENTS AND METHODS: The levels of a whole-blood antioxidant, reduced glutathione; and plasma antioxidants, ß-carotene, retinol, ascorbic acid, α-tocopherol; and the biomarker of oxidative stress, malondialdehyde, were evaluated in 50 pediatric patients (age range, 5-16 years; 29 males and 21 females) with acute hepatitis A and in 50 healthy children as control subjects (age range, 5-16 years; 25 males and 25 females). RESULTS: Plasma levels of reduced glutathione, ß-carotene, retinol, α-tocopherol and ascorbic acid were significantly lower, while malondialdehyde plasma levels were significantly increased in the patient group when compared to the controls (P<.0001 for all parameters). CONCLUSIONS: Our findings show that pediatric patients with acute hepatitis A were influenced by oxidative stress, resulting in significantly lower levels of plasma antioxidants and increased lipid peroxidation. In the absence of other therapeutic options, antioxidant vitamin supplements could be added to the therapy for these patients to help reestablish the oxidant status balance. Further investigations to confirm this suggestion are recommended.

Characteristics of chronic hepatitis C among intravenous drug users: a comparative analysis.

Hepatitis C virus (HCV) usually evades the host's immune system and persists as a chronic infection. Intravenous drug users (IVDU) represent the majority of patients infected with HCV. Combined therapy of chronic hepatitis C (CHC) with peginterferon alpha-2a and ribavirin can be successful even when patients continue the intravenous drug use. In this study, we compared the characteristics of age, gender, genotype, and stage of fibrosis and the therapy outcome among IVDU and patients with no history of drug use. The study included 69 patients diagnosed with chronic hepatitis C, evaluated and treated at the Clinic for infectious diseases in Nis from 2005 to 2009. HCV RNA was detected by a polymerase chain reaction and the determination of genotypes was undertaken. Liver biopsies were examined histopathologically. Patients received a combined treatment of peginterferon alfa-2a and ribavirin. Therapy efficiency was evaluated based on the achievement of the sustained virological response (SVR). A comparison of characteristics was performed with the use of Mann-Whitney U test, chi-square (chi2) test and logistic regression. IVDU were significantly younger than patients in the control group. Prevalence of stage 1 fibrosis was significantly higher among IVDU. The therapy outcome is influenced by the patient's age and HCV genotypes. Each year added to one patient decreased the therapy efficiency by 8.1%, while genotypes 2 and 3 experienced a therapy which was 2.08 times more efficient than in other cases. IVDU represent a specific population different from non-using patients. However, they can be treated effectively if an adequate patient-doctor relationship is established.

[Collateral damage and hospital infections].

COLLATERAL DAMAGE: Implies negative ecological effects of antibiotic therapy, characterized by the selection of resistant microorganisms and adverse colonization or injections with their multi-resistant species. MICROBIAL RESISTANCE: Is mediated by various mechanisms, the presence of which is determined by the nature of antibiotic effects and origin of the agent. Its most important aspect is multiple resistance, most commonly conditioned by the presence of several different resistance genes localized in the form of common units on gene transport elements (integrons, transposons, plasmids). It is further developed by way of mutation-guided alterations in the environments with a strong, selective antibiotic pressure, such as hospital conditions. HOSPITAL INFECTIONS: Bacteremias and pneumonias, above all, are nowadays the principal cause of hospital morbidity and mortality. More than 70% of agents causing them are resistant to at least one of the antibiotics to which they were sensitive once, and multi-resistance is their very common feature as well. Currently valid recommendations for the treatment of nosocomial bacteremias and pneumonias are the empirical application of broad spectrum antibiotics, de-escalation treatment, short therapy course. use of bactericidal antibiotics, and optimization of their pharmacodynamics. in that regard, a combined treatment with carbapenems and glycopeptides reduces the probability of inadequate onset of treatment and the risk of further development of microbial resistance (in some cases it also mediates the establishment of earlier sensitivity), it shortens treatment time, and reduces treatment costs. Further improvement of such a treatment involves a possible adjustment to the well known and regularly monitored local incidence and resistance of microbial agents.

[Efficiency of a combined peginterferon alpha-2a and ribavarin therapy in intravenous opiate substances abusers with chronic hepatitis C].

BACKGROUND/AIM: The most important ethiology factor of chronic liver disease that progresses into terminal insufficiency is hepatitis C virus (HCV) infection. Intravenous (iv) drug abuse is the main cause for spreading HCV. Thus the therapy for such patients is of extreme importance in reducing the incidence of the disease. The aim of the study was to establish efficacy of a combined therapy with peginterferon alpha-2a and ribavirin in iv opiate substances abusers having chronic HCV infection in relation to sex, age, genotype and level of fibrosis and duration of HCV infection before the treatment. METHODS: Thirty one iv opiate substances abusers with chronic hepatitis C (HHC) were enrolled in the examination. The patients were divided according to the genotype into two groups. The patients with genotypes 1 and 4 (n = 18) were treated for 48 weeks, while those with genotypes 2 and 3 (n = 13) for 24 weeks. PCR HCV RNA, genotype determination and liver biopsy were done to each patient. RESULTS: A stabile virological response was achieved in 93.5% of the patients, so the therapy demonstrated statistically significant efficacy i. v. opiate substances abusers with HHC (p < 0.001). There was no statistically significant difference in therapeutic response among patient groups formed according to the genotype, sex, duration of the disease and level of fibrosis (p > 0.05). CONCLUSION: Therapy of of iv opiate substances abusers with HHC has its specificities, and these patients need special treatment. Efficacy of the therapy was equivalent in patient groups formed according to the sex, genotype, level of fibrosis and duration of HCV infection. A combined therapy with peginterferon alfa 2a and ribavirin has high level of success in the treatment of these patients.

[Soluble CD4 antigens in the cerebrospinal fluid as a marker of lymphocytic infiltration of the central nervous system]. / Solubilni CD4 antigeni u cerebrospinslnoj tecnosti kao marker limfocitne infiltracije centralnog nervnog sistema.

Early diagnosis of the central nervous system (CNS) infections is a precondition of their successful treatment. However, the essential standard examination of the cerebrospinal fluid (CSF) is sometimes neither specific enough to define their basic nature, nor sufficient to differentiate them from processes of non-infectious origin. Supposing that the released surface molecules of activated immunocompetent cells could better define the character of inflammatory reaction, the levels of soluble CD4 antigens (sCD4) were determined with enzyme-immunosorbent test in the CSF of the patients with various CNS diseases. In contrast to cerebrovascular insults, toxic-metabolic, and other conditions in control group, detectable sCD4 concentrations in acute encephalitis (24 +/- 11 U/ml) were verified at the beginning of the disease, being also present in cytologically diagnosed normal CSF findings. They were significantly higher (p<0.05) compared to acute serous meningitis (13.5 +/- 8 U/ml), while in purulent meningitis they were measurable only after the disease progression--in correlation with the disturbed brain system function. The obtained results suggested the significance of CD4 antigen levels in CSF as a sensitive and specific marker of lymphocytic infiltration of the brain parenchyma, the measurement of which could contribute to early identification of the CNS infections, better understanding of their pathogenesis, and the assessment of the actual level of the destruction of neurons.