Cases of Crimean-Congo haemorrhagic fever in North Macedonia, July to August 2023.

The last report of Crimean-Congo haemorrhagic fever (CCHF) in North Macedonia was more than 50 years ago in the northwest. We report on a fatal CCHF case following a Hyalomma tick bite in the east of the country in July 2023. Tracing of 67 contacts identified CCHF in one healthcare worker (HCW) providing care for the patient. Monitoring of contacts is concluded (including further 11 HCW contacts), thus far 28 days after the death of the case no additional cases were identified.

Outcome Evaluation of Arthroscopic Resection of Dorsal Wrist Ganglia.

Goals: Arthroscopic ganglionectomy has become an increasingly popular surgical option for dorsal wrist ganglia. The aim of this study was to describe our technique for the arthroscopic treatment of dorsal wrist ganglia and to evaluate the clinical results as well as the recurrence rate in our patients. Methods: In a prospective study, 48 patients who underwent arthroscopic treatment of dorsal ganglion of the wrist were included. Patients were evaluated preoperatively and 3 and 24 months post arthroscopy. A presence of recurrence at 24 months was recorded. The subjective outcome was evaluated with The Patient-Rated Wrist Evaluation (PRWE) and the Visual analog scale (VAS). Objective outcomes included grip strength and range of movement measurements. Results: The mean age was 36 years; the majority were women (36/48). Mean grip strength and the average flexion and extension in the wrist showed improvement after 3 months. The total PRWE score improved from 26.7 preoperatively to 10.2 at three months and 2.4 two years after surgery. After 24 months follow-up, there were only two patients with recurrence (4.2%). Conclusion: The arthroscopic resection of the dorsal wrist ganglia is a procedure with a low recurrence rate and lowest scaring and stiffness; it should be considered as a golden standard for operative treatment of the dorsal wrist ganglia.

Effect of Supplemental Antioxidant-Based Therapy on the Oxidative Stress Level in COVID-19 Patients.

Background: COVID-19 is a disease in several stages starting with virus replication to dysregulation in immune system response, organ failure and recovery/death. Our aim was to determine the effect of Ganoderma lucidum, lycopene, sulforaphane, royal jelly and resveratrol extract on markers of oxidative stress, inflammation, routine laboratory analyses and duration of symptoms in COVID-19 patients. Methods: The oxidative stress parameters and interleukines 6 and 8 (IL-6, IL-8), tumor necrosis factor alpha (TNF-α) were determined in order to estimate the antioxidant and the anti-inflammatory effect of the product using a spectrophotometric and a magnetic bead-based multiplex assay in serum of 30 patients with mild form of COVID-19. Results: Statistically significant differences were obtained for all investigated parameters between the treated patients and the control group. Moreover, significant differences were observed for leukocytes, neutrophil to leukocyte ratio and iron. The average duration of the symptoms was 9.4±0.487 days versus 13.1±0.483 days in the treatment and the control group, respectively (p=0.0003). Conclusion: Our results demonstrated the promising effect of Ge132+NaturalTM on reducing the oxidative stress and the IL-6, IL-8 and TNF-α levels, and symptoms duration in COVID-19 patients. The evidence presented herein suggest that the combination of Ganoderma lucidum extract, lycopene, sulforaphane, royal jelly and resveratrol could be used as a potent an adjuvant therapy in diseases accompanied by increased oxidative stress and inflammation.

Hematological Findings and Alteration of Oxidative Stress Markers in Hospitalized Patients with SARS-COV-2.

Background/aim: Hematological parameters are the starting point in COVID-19 severity classification. The aim of this study was to analyze oxidative stress in hospitalized COVID-19 patients and to determine its association with D-dimer, neutrophil to lymphocyte ratio (NLR), and platelets to lymphocyte ratio (PLR) as markers for disease progression. Materials and methods: 52 patients with moderate and severe forms of COVID-19 were enrolled. A hematological and coagulation profile was performed for each patient. PAT (total antioxidant power, iron-reducing) and d-ROMs (plasma peroxides) were determined in serum at admission and 7 days after hospitalization. Results: The severe group presented parameters that indicated a poor prognosis. Patients that recovered had a significant reduction in d-ROM (t-test, p<0.01) and improvement in oxidative stress index (t-test, p<0.05). Patients that died had significantly decreased PAT (p<0.01) resulting in an increase in oxidative stress. Except for d-ROM vs PLR in both groups and d-ROM vs D-dimer in the severe group, a good correlation between oxidative stress parameters and D-dimer, PLR, and NLR was demonstrated (p<0.01). Conclusion: Our results show that oxidative stress markers can be used as a tool for disease progression in COVID-19. This analysis is easily accessible and affordable in addition to conventional hematological parameters performed for severity classification.

Presentation of cytokine profile in relation to oxidative stress parameters in patients with severe COVID-19: a case-control pilot study.

Introduction: COVID-19 can be worsened by hyper-production of cytokines accompanied by increased level of oxidative stress. The aim of this study was to investigate the correlation between a set of cytokines and the markers of the oxidative stress. Methods: The levels of cytokines IL-2, IL-4, IL-6, IL8, IL-10, VEGF, IFN-γ, TNF-α, IL-1α, MCP-1 and EGF were determined by using High Sensitivity Evidence Investigator™ Biochip Array technology. The oxidative stress parameters (d-ROM, PAT, OS index) were measured in serum on FRAS5 analytical photometric system. Results: IL-6, IL-8, IL-10, VEGF, MCP-1 and EGF were significantly higher (p<0.05) in the patients with severe COVID-19 with increased levels of IL-2, IFN-g, TNF-a and IL-1α. The d-ROM, OS index, and PAT were significantly higher (p<0.05) in severe COVID-19 patients. IL-6 demonstrated the strongest correlation with all of the markers of the oxidative stress, d-ROM (r=0.9725, p=0.0001), PAT (r=0.5000, p=0.0001) and OS index (r=0.9593, p=0.012). Similar behavior was evidenced between IFN-g and d-ROM (r=0.4006, p=0.0001), PAT (r=0.6030, p=0.0001) and OS index (r=0.4298, p=0.012). Conclusion: The oxidative stress markers show good correlation with the tested cytokines which can be measured at the beginning of the disease in a primary care setting to predict the course of COVID-19.

Vitamin D levels and oxidative stress markers in patients hospitalized with COVID-19.

BACKGROUND: COVID-19 is characterized by the presence of oxidative stress. Vitamin D status has been reviewed as one of the factors that may affect disease severity. The aim of this study was to assess the relationship between serum vitamin D levels, oxidative stress markers and disease severity in hospitalized COVID-19 patients. METHODS: Vitamin D levels were measured in 33 patients with COVID-19. The total antioxidant power and plasma peroxides were determined in serum. RESULTS: Severe COVID-19 patients have lower vitamin D levels (18.39 ± 2.29 ng/mL vs. 28.47 ± 3.05 ng/mL, p < .05) and higher oxidative stress compared to the moderate group. When divided according to serum vitamin D levels, significantly higher values of LDH (604.8 ± 76.98 IU/mL vs. 261.57 ± 47.33 IU/mL) and D-dimer (5978 ± 2028ng/mL vs. 977.7 ± 172 ng/mL) were obtained in the group with vitamin D below 30 ng/mL, followed with significantly higher levels of plasma peroxides (d-ROMs: 414.9 ± 15.82 U.Carr vs. 352.4 ± 18.77 U.Carr; p < .05) and oxidative stress index (OSI: 92.25 ± 6.60 vs. 51.89 ± 6.45; p < .001). CONCLUSION: The presented data provide a justification to consider vitamin D as an important factor that could ameliorate disease severity through its anti-inflammatory and antioxidant effects.

Evaluation of severity scoring systems in patients with severe community acquired pneumonia.

Background. The aim of this study was to evaluate the ability of severity scoring systems to predict 30-day mortality in patients with severe community-acquired pneumonia. Methods. The study included 98 patients aged ≥18 years with community acquired pneumonia hospitalized at the Intensive Care Unit of the University Clinic for Infectious Diseases in Skopje, Republic of North Macedonia, during a 3-year period. We recorded demographic, clinical and common biochemical parameters. Five severity scores were calculated at admission: CURB 65 (Confusion, Urea, Respiratory Rate, Blood pressure, Age ≥65 years), SCAP (Severe Community Acquired Pneumonia score), SAPS II (Simplified Acute Physiology Score), SOFA (Sequential Organ Failure Assessment Score) and MPM (Mortality Prediction Model). Primary outcome variable was 30-day in-hospital mortality. Results. The mean age of the patients was 59.08 ± 15.76 years, predominantly males (68%). The overall 30-day mortality was 52%. Charlson Comorbidity index was increased in non-survivors (3.72 ± 2.33) and was associated with the outcome. All severity indexes had higher values in patients who died, that showed statistical significance between the analysed groups. The areas under curve (AUC) values of the five scores for 30-day mortality were 0.670, 0.732, 0,726, 0.785 and 0.777, respectively. Conclusion. Widely used severity scores accurately detected patients with pneumonia that had increased risk for poor outcome, but none of them individually demonstrated any advantage over the others.

Evaluation of oxidative stress markers in hospitalized patients with moderate and severe COVID-19.

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.

The Impact of Pneumonia on the Course and Outcome in Patients with Seasonal Influzenza.

INTRODUCTION: Seasonal influenza, although often presented as a mild, self-limiting disease, is frequently accompanied by complications that lead to the development of a severe clinical presentation and a fatal outcome. The most common are respiratory complications, with secondary bacterial pneumonia being the leading cause. AIM: The aim of this study is to determine the impact of pneumonia on the severity of the clinical presentation and outcome in patients with seasonal influenza. MATERIALS AND METHODS: This research is comparatively group-based and has been conducted at the University Clinic for Infectious Diseases and Febrile Conditions during a three-year period. The analysis consists of 122 adult patients with clinically and laboratory-confirmed influenza. Based on the severity of the clinical picture, the patients are divided into two groups, severe (n=87) and mild (n=35) forms of the disease. The study included demographic, general data, clinical symptoms, and signs as well as complications. RESULTS: Of 122 patients with seasonal influenza, complications were registered among 108(88.52%), with a significantly more frequent emergence among the group with severe influenza 93.1% vs 77.14% (p=0.012). Pneumonia was the most common 98(80.33%) and had a significant effect on disease severity (p=0.002). Complications from the types of ABI 8(6.56%), ARDS 7(5.74%), sepsis 5(4.1%), DIC 4 (3.28%) and otitis 2(1.64%) were reported only in the group with severe influenza. Acute meningoencephalitis was registered among 5(4.1%), gastroenterocolitis among 3(2.46%), and hepatic damage among 14(11.47%) of patients. CONCLUSION: Pneumonia as the most common complication among patients with seasonal influenza significantly impacts the clinical course and outcome of the illness.

Prevalence of Rotaviruses in the Etiology of Acute Diarrhea in Young Children, Clinical forms, Extraintestinal Manifestations and Complications.

Rotavirus is highly contagious factor with dominant feces-oral transmission. Because it is stable in external environment, transmission clusters are possible by close contact, ingestion of contaminated water or food or contact with contaminated surfaces. It survives within hours and days on hands and contaminated surfaces. This makes it the most common enteric and nosocomial pathogen in the world, especially in early childhood. In addition to the rapid dehydration with pronounced electrolyte disturbances, numerous extraintestinal possibilities have been recorded in the clinical picture, which emphasizes the need for prevention of this disease.In the period from 1.02.2018 to 31.01.2020 at the Clinic for Infectious diseases were treated 1060 patients with diarrheal disease, of which 502 children (47.36%). Rotavirus etiology was confirmed in 23.30% of the children. According to the protocols, laboratory and biochemical investigations were done to all 117 children, with tracking parameters and their dynamics of admission and discharge from the hospital. Most of the children, 84 (82.0 6%) are from urban areas, with a more confirmed epidemiological survey of 59 (42.00%). The average age of the children was 8 months, with a small percentage of children on maternal food (breastfed 25, i.e. 21.37%), with high febrile admission in 99% of children with an average temperature of 38.5oC and an average febrile duration of 4 days, with an average of 7 (+ 2.49) of stools and 5 (+ 2.12) of vomiting. There was a significant difference in hematocrit, leukocyte, electrolyte, glycaemia, and CRP values on admission and discharge. There was predominant isonatremic dehydration, and the compensatory mechanisms followed by the values of the electrolytes ABS, Ph, BE showed a tendency to maintain within the physiological limits. The clinical picture of extraintestinal manifestations included bronchitis, mesenteric lymphadenitis, upper respiratory infections and rash.Rotavirus infection is a serious health and economic problem in our country, so it needs continuous prevention and monitoring in order to reduce the incidence, and thus the need for hospitalization and cure of rotavirus disease.

Association of Systemic Inflammatory Response Syndrome with Bacteremia in Patients with Sepsis.

The aim of this study was to evaluate the usability of systemic inflammatory response syndrome (SIRS) and commonly used biochemical parameters as predictors for positive blood culture in patients with sepsis. The study included 313 patients aged ≥18 years with severe sepsis and septic shock consecutively admitted in the Intensive Care Unit (ICU) of the University Clinic for Infectious Diseases in Skopje, Republic of North Macedonia. The study took place from January 1, 2011 to December 31, 2017. We recorded demographic variables, common laboratory tests, SIRS parameters, site of infection, comorbidities and Sequential Organ Failure Assessment (SOFA) score. Blood cultures were positive in 65 (20.8%) patients with sepsis. Gram-positive bacteria were isolated from 35 (53.8%) patients. From the evaluated variables in this study, only the presence of four SIRS parameters was associated with bacteremia, finding that will help to predict bacteremia and initiate early appropriate therapy in septic patients.

The influence of illness duration before diagnosis on clinical characteristics and outcome in human brucellosis.

Our study assesses the influence of illness duration before establishing the diagnosis of brucellosis and initiating therapy on patients' main clinical characteristics and outcome in an endemic area. The medical files of 297 patients with brucellosis were retrospectively analysed. They were divided into four groups according to illness duration before initiating therapy: <10 days; 11-30 days; 31-90 days; and >90 days. There were significant differences in the occurrences of fever (P = 0.019), focal forms (P = 0.026), spondylitis (P = 0.034) and therapeutic failures (P = 0.006) between the groups. Duration of >30 days before treatment initiation is responsible for more serious clinical presentation and outcome, whereas illness duration of >90 days further worsens the clinical progression in human brucellosis.

The changing pattern of fever of unknown origin in the Republic of North Macedonia.

INTRODUCTION: The study aimed to compare the etiologic spectrum of diseases causing fever of unknown origin (FUO) and methods for definitive diagnosis in a tertiary care hospital in the Republic of North Macedonia during two different time periods. PATIENTS AND METHODS: There were analysed retrospectively the causes for FUO and final diagnostic approaches in 185 patients with classic FUO that were treated at the University Hospital for Infectious Diseases in Skopje during two time periods. Seventy nine patients were treated during 1991 to 1995 and 106 patients during 2011 to 2015. RESULTS: When comparing these two periods, infections were present in 46.8% and 29.2% (p = 0.014), non-infective inflammatory disorders in 22.8% and 25.5% (p = 0.674), neoplasms in 10.1% and 13.2% (p = 0.522), miscellaneous in 8.9% and 12.3% (p = 0.461) and undiagnosed cases in 11.4% and 19.8% (p = 0.124), respectively. The most common causes for FUO during the first period were abscesses (8.9%), tuberculosis and systemic lupus erythematosus (7.6% each), whereas in the second period the commonest causes were adult onset Still disease and solid organ neoplasm (7.6% each), polymyalgia rheumatica, abscesses and visceral leishmaniasis (5.7% each). The newer imaging techniques and clinical course evaluation had superior diagnostic significance during the second period. CONCLUSION: A changing pattern of diseases causing FUO during the examined periods was evident. Infections continue to be the most common cause but with decreasing incidence when compared to 20 years ago. Even nowadays clinical evaluation and follow-up still remain the vital diagnostic tools in determining the etiology of FUO.

Prediction of outcome from community-acquired severe sepsis and septic shock in tertiary-care university hospital in a developing country.

Our aim was to determine the risk factors on mortality in adult patients with community-acquired severe sepsis and septic shock. The main outcome measure was hospital mortality. This prospective single centre study was conducted from January 1, 2008 to December 31, 2010, and included 184 patients, of whom 135 (73.4%) were with severe sepsis and 49 (26.6%) had septic shock. Overall, ninety-five (51.6%) patients have died, 60 (44.4%) in severe sepsis and 35 (71.4%) patients with septic shock. The lung was the most common site of infection 121 (65.8%), and chronic heart failure was the most frequent comorbidity 65 (35.3%). Logistic multivariate analysis identified three independent risk factors for mortality in patients with severe sepsis: positive blood culture (odds ratio, 2.39; 95% confidence interval, 1.13-5.06; P = 0.02), three or more organ dysfunctions (odds ratio, 3.93; 95% confidence interval, 1.62-9.53; P = 0.002), and Simplified Acute Physiology Score (SAPS) II (odds ratio, 1.02; 95% confidence interval, 1.00-1.04; P = 0.01). In addition to SAPS II, positive blood culture, and three or more organ dysfunctions are important independent risk factors for mortality in patients with severe sepsis and septic shock.

Human brucellosis in Macedonia - 10 years of clinical experience in endemic region.

AIM: To present our 10-year clinical experience with brucellosis patients at the University Clinic for Infectious Diseases and Febrile Conditions in Skopje, Republic of Macedonia. METHODS: A total of 550 patients with brucellosis treated between 1998 and 2007 were retrospectively assessed for their demographic, epidemiological, and clinical characteristics and outcomes. RESULTS: Of the 550 patients, 395 (72%) were male. The median age was 34.5 years (range, 1-82). Direct contact with infected animals was recorded in 333 (61%) patients and positive family history in 310 (56%). The most frequently seen symptoms were arthralgia (438, 80%), fever (419, 76%), and sweating (394, 72%). The most common signs were fever and hepatomegaly, which were verified in 357 (65%) and 273 (50%) patients, respectively. Focal brucellosis was found in 362 patients (66%) and osteoarticular in 299 (54%). Therapeutic failures were registered in 37 (6.7%) patients. Of the 453 (82%) patients who completed a follow-up period of at least 6 months, relapses occurred in 60 (13%). CONCLUSION: Due to non-specific clinical manifestation and laboratory parameters, brucellosis should be considered one of the differential diagnoses of any patient suffering from obscure involvement of various organs in a brucellosis-endemic region. High percentage of relapses and therapeutic failures in spite of the use of currently recommended therapeutic regimens indicates the seriousness of this zoonosis and the need to control it.

Wide-field digital imaging based telemedicine for screening for acute retinopathy of prematurity (ROP). Six-year results of a multicentre field study.

OBJECTIVE: To report on a 6-year experience with wide-field digital imaging based telemedicine (WFDI telemedicine) to reduce the risk for blindness from retinopathy of prematurity (ROP). METHODS: Wide-angle digital fundus cameras (RetCam 120, Massie Lab, Pleasanton, CA, USA) were installed in five neonatal intensive care units (NICUs) in Germany. All prematures at risk were screened with WFDI, and the local ophthalmologists were asked to continue binocular indirect ophthalmoscopy (BIO) according to the German guidelines. Image data were coded and transferred to the Reading Centre in Regensburg. Image evaluation and additional BIO of infants with suspected treatment-requiring ROP (STR-ROP i.e. threshold ROP zone II, prethreshold ROP zone I (type-1 ROP according to ETROP), and ROP possibly requiring treatment but not reliably classifiable from the images) were performed by paediatric ophthalmologists at the Reading Centre. ROP was classified following ICROP, ETROP, and revised ICROP criteria. Outcome measures were incidence of clinically relevant ROP (CR-ROP, i.e. any ROP up to mid-peripheral zone III,