Academic Medical Journal

CLINICAL AND LABORATORY CHARACTERISTICS OF PATIENTS WITH ACUTE ISCHEMIC STROKE AND COVID-19: CASE SERIES AND OF LITERATURE REVIEW

Arbana Rexhepi — 2022-06-15

Introduction: COVID-19 is closely linked to coagulopathy and consequently thromboembolism, thus increasing the probability for development of ischemic strokes.

Aim: The purpose of our study was to evaluate the clinical, laboratory and neuroimaging characteristics as well as outcome in patients with COVID-19 who developed acute ischemic stroke (AIS), hospitalized at the COVID Center at the University Clinic for Neurology in Skopje, N. Macedonia during the period of November 2020 - March 2021.

Material and methods: We conducted a retrospective analysis of ten patients with acute ischemic stroke, out of 566 COVID-19 patients hospitalized at the COVID Center at the University Clinic for Neurology in Skopje, N. Macedonia. during the period of November 2020 - March 2021 Demographic characteristics, level of consciousness, stroke type, region and volume, presence of hemorrhagic transformation and mass effect, comorbidities, level of D-dimer and inflammatory markers, presence of pneumonia and outcome of the patients were analyzed.

Results: Majority of patients developed ischemic strokes secondary to large-vessel occlusion in the anterior circulation and only one patient had posterior circulation stroke. Three patients developed massive stroke with hemorrhagic transformation and mass effect. Seven patients developed COVID-19 associated pneumonia.

Conclusion: Acute ischemic stroke in patients with COVID-19 is more likely to occur in elderly patients with cardiovascular comorbidities. Aging, comorbidities, impaired level of consciousness and increased level of D-dimer and CRP on admission along with COVID-19 pneumonia contribute to the fatal outcome.

PERFORMANCE CHARACTERISTICS OF SNIBE SARS-COV-2 IgM/IgG AND SARS-COV-2 S-RBD IgG SEROLOGICAL ASSAYS

Jasna Bogdanska — 2022-06-15

Since corona virus emerged, few tests for diagnosis and follow-up of the disease were approved for urgent use by FDA. Serological tests for the presence of SARS-Cov-2-specific M/G and RBD IgG antibodies manufactured by SNIBE were introduced to the market at the beginning of 2020, with a primary recommendation for monitoring and responding to SARS-Cov-2 infection or vaccines.

According to the Standard ISO 15189, each laboratory should take special actions before implementation of any new analyses as routine ones. Bearing this in mind, a verification of the chemiluminescence method for antibody detection according to the CLSI EP 15-A2 and CLSI EP 15-A3 protocol was done in our laboratory.

Pooled control samples for IgG, IgM and RBG IgG with two levels, as well as serum samples for positive IgG antibodies were used for method verification. As part of the verification procedure, the precision of the method was estimated.

The results of the repeatability and coefficients of variation for SARS-Cov-2 IgM/IgG and SARS-Cov-2 S-RBD IgG were equal or less than the manufacturer’s claims, except for negative control RBD IgG samples. Estimated results for within-laboratory precision (reproducibility) as well as coefficients of variation were less or equal to the manufacturer’s claims, except for positive control samples for IgM.

We can conclude that the estimated performance characteristics of SNIBE SARS-Cov-2 IgM/IgG and SARS-Cov-2 S-RBD IgG serological assays are consistent with the manufacturer’s claim’ and that they can be introduced in our laboratory.

PREDICTABILITY OF D-DIMER LEVEL ON ADMISSION FOR HOSPITAL OUTCOMES IN HOSPITALIZED PATIENTS WITH COVID-19 PNEUMONIA

Zorica Markovska — 2022-06-15

The aim of this study was to evaluate the role of D-dimer as a biomarker in the assessment of COVID-19 prognosis in hospitalized patients.

Material and methods: A total of 117 patients with confirmed COVID-19 pneumonia between the age of 19 and 89 years were admitted to the City General Hospital 8th September, Skopje, Macedonia. In all patients, a D-dimer test for coagulation profile and lactate dehydrogenase (LDH) for disease progression were performed on the day of admission. Patient demographic data, presence of comorbidities, severe symptoms, and radiological findings were determined for each patient. We calculated the National Early Warning Score (NEWS 2) for assessment of acute illness severity. The level of oxygen saturation (SpO₂) was also determined. Length of hospital stay and length of stay at home were filled later after hospitalization using medical records.

Results: Patients were classified according to D-dimer level into a low group (D-dimer ≤ 2 mcg/ml) and a high group (D-dimer ≥ 2 mcg/ml). Elevated D-dimer level was associated with severity, hypoxia, and lethal outcome. Patients with a high level of D-dimer had a higher NEWS 2 score, worsen radiological findings, and higher LDH. Patients with low levels of D-dimer stayed at home longer than those with higher D-dimer levels.

Conclusion: The D-dimer level is a useful marker in assessing the coagulation profile of patients with COVID-19 pneumonia regardless of the type of disease. Implementation of screening tools like the NEWS 2 score is also needed for better risk stratification on hospital admission.

COPD IN A SAMPLE OF GENERAL ADULT POPULATION FROM THE SKOPJE REGION

Jordan Minov — 2022-06-15

Aim of the study. To determine the COPD prevalence in a sample of general adult population from the Skopje region and its distribution by sex, age, smoking status, working status, family history of chronic bronchitis/asthma, and mode of household heating and cooking.

Methods. A cross-sectional study including 2,348 participants from the Skopje region was performed in the period 2018-2021. The study protocol included completion of a questionnaire and spirometric measurements (pre- and post-bronchodilator spirometry). COPD was defined by spirometric finding of persistent airflow limitation in symptomatic study subjects.

Results. COPD prevalence in the whole study sample was 4.6%, being non-significantly higher in men (5.1%) than in women (4.1%). Fourfold higher prevalence of COPD was registered in the study subjects aged over 45 years as compared to the younger ones (6.7% vs. 1.6%; P = 0.000). COPD prevalence was significantly higher in active smokers as compared to non-smoking study subjects (9.4% vs. 1.9%; P = 0.000). In regard to working status, COPD prevalence among active workers was 3.9%, in the group of retired persons 8.7%, while in the group of students there was not any subject with COPD. In addition, COPD prevalence in the workers occupationally exposed to noxious particles or gases was significantly higher than in unexposed workers (4.7% vs. 2.4%; P = 0.021).

Conclusion. Our findings indicate age, active smoking and occupational exposures to noxious particles or gases as the factors significantly related to COPD prevalence in the examined sample of general adult population from the Skopje region.

KNOWLEDGE AND PRACTICE OF PREVENTION OF HEPATITIS B AMONG HEALTHY POPULATION IN COMMUNITY

Monika Neloska — 2022-06-15

Introduction: This study aims to evaluate Knowledge of transmission and practice (KAP) towards Hepatitis B (HBV) among healthy population of R.N. Macedonia.

Methods: A cross sectional study was undertaken. 600 healthy individuals (aged 18 years and above) were approached for the study. Descriptive statistics were conducted using frequencies and proportions. Unadjusted odds ratios (OR) and their 95% confidence intervals (CI) were used as indicators of the strength of association. A p-value of 0.05 or less was used as cut off level for statistical significance. All analyses were performed using SPSS 20.0. Internal consistency was assessed by using Cronbach’s alpha (α = 0.78) and was found to be in acceptable ranges.

Results: Majority of participants (39.7%) were from the age group 40–49 and 65.3% of the respondents were female, 46.8% were with university degree; 72.2% of the study participants were married; 92.2%of the respondents came from urban area; 76.7% were employed and 67.7% with moderate monthly income. In terms of knowledge about the mode of transmission, the majority of respondents, i.e. participants in the study showed a moderate level of knowledge - 56.6% points (50% -75% points). Poor knowledge was evident in the answers to the questions related to the transmission piercing-48.3% and the question related to the transmission question cocaine sniffing - 21.0%) Correct answer in the study that showed a good level of knowledge i.v. drug use 87.2%

Conclusion: The positive linear correlations reaffirms that better knowledge of transmission can lead to positive prevention and subsequently in good practices.

CORRELATION OF SERUM LEVELS OF INFLAMMATORY CYTOKINES WITH SEVERE FORM OF CHOLECYSTITIS

Zarko Spasovski — 2022-06-15

Introduction: Cholecystitis is an inflammatory response of the body triggered by a number of mutually supporting biological mechanisms, which by creating and releasing inflammatory mediators - cytokines activate the innate or acquired immune system.

Material and methods: The study was conducted at the General City Hospital (GCH) "8^th September" in Skopje and the Institute of Immunology and Human Genetics in Skopje, in the period of 2020-2022. Statistical analysis of the data was performed with the statistical package SPSS for Windows 26.0.

Results: The study included 165 subjects with gallbladder inflammation divided into 3 groups: mild, moderate and severe inflammation grade. Patients with mild, moderate, and severe inflammatory processes differed significantly in IgG levels (p = 0.049), IgA (p = 0.021), and IgM (p = 0.016) and insignificantly in IgE1 levels (p = 0.16). Patients with a severe inflammatory process had a higher prevalence of IL-2R and IL-8 than patients with a mild grade (p = 0.035; p = 0.26, respectively). The intensity of inflammatory process had a non-significant effect on the levels of TNF-alpha (p = 0.078), and a significant effect on the levels of fibrinogen (p = 0.001), with significantly higher levels of fibrinogen in the group of patients with severe inflammatory process compared to the group with mild grade (p = 0.0009).

Conclusion: The intensity of inflammatory process affects the serum levels of inflammatory cytokines with presence of strong correlation between the severe form of cholecystitis and elevated serum levels of certain inflammatory cytokines.

ASSOCIATION OF CCNG1 AND FDXR GENE EXPRESSION DURING RADIOTHERAPY WITH BIOCHEMICAL- AND LIFESTYLE-RELATED CONFOUNDING FACTORS IN BREAST CANCER PATIENTS

Katerina Trenceva — 2022-06-15

Introduction: CCNG1 and FDXR are well-established gene expression biomarkers of IR exposure. Expression alterations during radiotherapy (RT) in patients with different types of cancer has seldom been investigated, along with their potential associations with biochemical- and lifestyle-related confounding factors, that would help elucidate specific changes in RT response and individualize RT in breast cancer patients.

Materials and methods: A non-randomized, controlled, open-trial clinical study was performed in 57 breast cancer patients (intervention group, IG) and 56 healthy individuals (control group, CG). Gene expression was analyzed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in leukocytes of peripheral blood samples.

Results: A significant up-regulation of FDXR was observed up to 48 h after the first RT fraction, with no significant expression alterations of CCNG1 at 24 h and 48 h. Fold changes of CCNG1 were slightly lower (1.13-1.23) compared to FDXR (1.49-2.08). RT-induced FDXR and CCNG1 expression alterations could not be significantly associated with patient age, increased WBC count (> 9x10⁹/L), increased C-reactive protein (CRP) during RT (> 5 mg/L) and decrease of increased CRP values during RT. Patients with diabetes mellitus had lower CCNG1 fold changes 24 h post-RT (0.89 ± 0.3 vs. 1.23 ± 0.6); identical was the finding for smokers and non-smokers (1.06 ± 0.5 vs. 1.22 ± 0.7).

Conclusion: RT-induced CCNG1 and FDXR changes could not be significantly associated with the examined biochemical- and lifestyle confounding factors, except for diabetes mellitus and smoking.

POSTOPERATIVE ADJUVANT INTENSITY-MODULATED RADIOTHERAPY FOR RADICALLY RESECTED RECTAL ADENOCARCINOMA: DATA FROM EVERYDAY PRACTICE

Nenad Mitreski — 2022-06-15

Introduction: Adjuvant radiochemotherapy is a standard treatment in patients with surgically treated stage II or III rectal adenocarcinoma who did not undergo neoadjuvant radiotherapy. Intensity-modulated radiation therapy (IMRT) was only marginally investigated in postoperative setting.

Material and methods: A longitudinal observational analysis was conducted in patients with radically resected stage II or III rectal adenocarcinoma treated with IMRT at the University Clinic for Radiotherapy and Oncology as part of the adjuvant postoperative treatment. The dose-volume parameters of the radiotherapy plans, as well as acute side effects of 40 patients were analyzed.

Results: The average dose received by the target volume was 49.95 Gy (range 27-54 Gy). The mean volume of peritoneal cavity receiving 45 Gy (V45) was 102.73 cm3 (±52.10), V30 for pelvic bones was 38.3% (±5.48), V40 for bladder 52.48% (±10.9). The most frequent acute side effects were diarrhea in 17 (42.5%), lymphopenia in 34 (85%) and thrombocytopenia in 26 patients (65%). Most of the side effects were self-limiting and caused disruption of the radiation treatment only in 3 patients (7.5%).

Conclusion: Integrating IMRT in the adjuvant treatment of locally advanced rectal cancer provides a good dose distribution and organs at risk sparing. The treatment is well tolerated, the side effects are mainly of lesser degrees and easily managed. A prospective trial comparing IMRT with 3-dimensional conformal radiotherapy is needed to assess whether IMRT offers a better perspective for adjuvant treatment.

FREQUENCY OF GENETIC VARIANTS ASSOCIATED WITH CORONARY ARTERY DISEASE AND VENOUS THROMBOEMBOLISM IN YOUNG PATIENTS IN REPUBLIC OF N. MACEDONIA

Ivica Bojovski — 2022-06-15

Introduction: Coronary artery disease - CAD and venous thromboembolism - VTE are two major manifestations of cardiovascular diseases. Genetic mutations responsible for the occurrence of CAD and VTE in young population are subject of numerous researches and studies.

Aim: To determine the allelic and genotypic frequencies of the analyzed gene variants and to examine whether there is overlap of the most common genetic mutations between the two groups.

Material and methods: This clinical study analyzed the demographic, clinical, and genetic data of a group of 36 patients up to 50 years of age with CAD and a second group of 32 patients up to 50 years of age with VTE. The selection of subjects was according to previously established inclusion and exclusion criteria. Genetic testing was performed on each patient to determine the presence of certain genetic mutations.

Results: The occurrence of CAD and VTE in young population is significantly more common in men. In terms of risk factors, overweight and obesity were found to be the most common in both groups, while hypertension and smoking being more prevalent in the CAD group. Heterozygous mutations for: MTHFR C677T, eNOS 786 T>C, e NOS 894T and B-fibrinogen were most common in group 1, while in group 2 heterozygous mutations for: eNOS -786 T>C, MTHFR C677T, MTHFR a1298C and B-fibrinogen.

Conclusion: Genetic polymorphisms in MTHFR, B-fibrinogen and eNOS genes should be tested in patients with CAD and VTE under 50 years of age as additional risk factors.

DEAN’S ADDRESS ON THE OCCASION OF THE 75TH ANNIVERSARY OF THE FACULTY OF MEDICINE, Ss. CYRIL AND METHODIUS UNIVERSITY IN SKOPJE

Sonja Topuzovska — 2022-06-15

NEW SURGICAL TECHNIQUE FOR TREATMENT OF SUPERFICIAL VARICOSE VEINS

Vlatko Cvetanovski — 2022-06-15

In this article we have described our combination of few proven surgical techniques in treatment of superficial venous disease.

Superficial venous disease and complications that are a consequence from their presence represent an increasingly common problem observed in different medical specialties.

Many patients consult their family physician for the first time when they have experienced some of the complications from superficial venous disease.

Availability of Color-Doppler sonography (CDS) enables timely diagnosis in early phase when only few symptoms are present.

Most patients require a combination of treatment methods depending on the point of the highest venous reflux, the presence of bulging varicosities, the presence of incompetent perforator veins and the depth of subcutaneous tissue overlying the muscle fascia.

ABNORMAL T WAVE INVERSIONS AND EXTREME QT PROLONGATION

Antonio Georgiev — 2022-06-15

Introduction: Cardiovascular diseases are the cause of sudden cardiac arrest. One of the leading causes of death is the occurrence of ventricular arrhythmias. Prompt evaluation, diagnosis and management of ventricular arrhythmias are life-saving for these patients.

Case report: We present the case of a 70-year-old female patient with neurological sensorimotor polyneuropathy with quadriparesis and verified chronic renal failure (CRF) gr. IV admitted at the University Clinic for Nephrology for acute renal failure. After hemodialysis treatment, she developed arrhythmogenic disability such as episodes of ventricular fibrillation (VF) and ventricular tachycardia (VT). The onset of VT/VF required pharmacologic and shock therapy treatment. Electrocardiogram (ECG) at presentation upon admission to the cardiology clinic was with abnormal T wave and QT inversions. We did not find any electrolytic disturbances or echocardiographic abnormalities in search for ischemia segment wall changes. Coronary angiography showed no significant lesions of the coronary arteries. Our strategy for treating this long QT interval was temporary pacing with high doses of b-blockers. According to the good response to the therapy, the patient got permanent pacing therapy (AAIàDDD mode) and till this day she is still safe from occurrence of ventricular arrhythmias.

Conclusion: Prolongation of ventricular repolarization in patients with long QT interval must be registered as a predictor of occurrence of ventricular arrhythmias.

TESSIER No. 7 CLEFT WITH MACROSTOMIA: CASE REPORT AND LITERATURE REVIEW

Alekasndar Iliev — 2022-06-15

Craniofacial clefts are rare conditions with an incidence of 2-7 per 100,000 births. Because of the limited experience with such cases, they pose a great challenge for the head and neck reconstructive surgeon. The Tessier no. 7 cleft is the most common and is found in various clinical presentations starting from a small notch in the oral commissure to a significantly disfiguring entity, sometimes as a part of Hemifacial microsomia or Goldenhar’s Syndrome. We present a case of a young girl with a unilateral Tessier no. 7 cleft with macrostomia and bilateral facial skin tags, the surgical options, as well as the follow-up results of the repair.

OPEN ESOPHAGECTOMY AS A TREATMENT OF CHOICE FOR ESOPHAGEAL CANCER AND A SUCCESSFUL OUTCOME AT THE UNIVERSITY CLINIC IN SKOPJE, NORTH MACEDONIA: A CASE REPORT

Borislav Kondov — 2022-06-15

Esophageal cancer is one of the least studied cancers and has high mortality rates, mainly because it is diagnosed at rather late stage. It requires urgent attention and in patients where surgery is feasible, it is immediately performed. There is a considerable variation in terms of the surgical approach in different countries, but open esophagectomy is a treatment of choice.

This study describes a case of esophageal squamous cell carcinoma that was successfully treated with open esophagectomy and therefore provides information about the present state of esophageal cancer surgery at the University Clinic in Skopje, North Macedonia. The patient underwent clinical examination after which she was admitted to our department for surgical treatment. Esophagography and CT imaging were done pre- and postoperatively and no complications were noted after surgery. The patient was discharged and a written informed consent was obtained for publication of this case and any accompanying images.

SMALL INTESTINE INTUSSUSCEPTION DUE TO GASTROINTESTINAL STROMAL TUMOR IN PREGNANCY: A CASE REPORT

Igor Samardjiski — 2022-06-15

Gastrointestinal stromal tumour (GIST) is very rare in pregnancy and only a few cases have been described in the literature. We present a case of a 38-year-old primigravida, presented with non-specific symptoms for the first time in the second trimester. Due to the non-specificity of the symptoms on one hand and the rarity of the tumour on the other, it took a long time for the final diagnosis to be made.

Accidentally, on a routine obstetric ultrasound examination, a solid tumour formation was observed, localized under the lower pole of the left kidney. On MRI of the abdomen, in front of the left kidney there was a tubular structure, in close relation with small intestine, suspected for intussusception. At 28 weeks of gestation, an exploratory laparotomy was performed with resection of the involved part of the jejunum and TT anastomosis. Pregnancy was terminated electively, by caesarean section, in 38+6 gestational weeks.

The clinical presentation of the GIST depends on the primary location of the tumour. Due to the extremely rare occurrence of these tumours in pregnancy, there is no solid scientific evidence for the most appropriate time of their treatment and the time of termination of pregnancy. The biggest challenge in pregnancy is timely diagnosis and treatment, without impact on the foetus. A multidisciplinary approach is needed. In our case, the severity of the mother’s symptoms outweighed the danger to the foetus from general anaesthesia and surgery itself.

SURGICAL TREATMENT OF CONGENITAL CENTRAL DEFICIENCY OF THE HAND (CLEFT HAND) IN AN ADULT PATIENT - CASE REPORT

Marta Foteva — 2022-06-15

Cleft hand is a congenital hand anomaly, which is characterized by the absence of one or more central digits (II, III and/or IV) of the hand and/or foot. The clinical appearance is very irregular, and treatment of cleft hand involves cosmetic and functional considerations. Due to the great clinical variability, the choice of the appropriate surgical procedure is difficult as there is no single surgical procedure to treat all cleft hands.

We present a case of bilateral cleft hand in an adult male patient (24 years of age). The patient presented with cleft hand of both hands; the right hand more severely affected with missing middle metacarpal and finger, typical V cleft with wide interdigital space, normal first web space and incomplete syndactyly of IV-V finger. Since his main concern was the cosmetic appearance of the right hand and there was good function in the thumb and index finger, the logical choice was to close the central cleft and preserve the function he already had. Postoperatively, the patient gained useful grip with all fingers, a satisfactory range of motion and preserved useful pattern of pinch. The cosmetic appearance improved substantially, much to the patient’s satisfaction.

To the best of our knowledge, this is the first reported case of cleft hand in our country. For an adult patient to whom the aspect of cosmetic appearance is very important, surgery is indicated for cosmetic improvement, but care must be taken not to sacrifice the functionality of the hand.

PERCUTANEOUS AS A MINIMALLY INVASIVE TECHNIQUE FOR ACHILLES TENDON RUPTURE

Kornelija Gjorgjieska — 2022-06-15

The Achilles tendon is the strongest tendon in the human body. When the applied force exceeds the tensile capacity of this tendon, which occurs when the ankle bends abruptly under the action of a compressive force, the tendon is at risk of rupture. The incidence of rupture ranges from 18 per 100,000. Certain antibiotics, long-term steroid use, tendinopathy, and other degenerative disorders are known to increase the risk of rupture, yet the leading cause remains traumatic injury, with predominance in men aged 30 to 50 years. There are two types of treatment: conservative and surgical. Recent studies have shown a difference in outcome between non-surgical and surgical treatment. Meta-analyses have shown that non-surgical treatment increases the risk of re-rupture, while open surgery has a risk of early complications and infection. It is necessary to find a solution to minimize the postoperative complications of open surgery, and possible relapses after the application of conservative treatment, treated with plaster immobilization. Therefore, there is a need for the use of minimally invasive surgery, which has been adopted as a smart way to reduce the rate of postoperative infections. It is also clear that the treatment must be tailored to the needs of each patient individually.

PUNCTURE INJURY IN THORACOLUMBAR REGION

Goce Volcevski — 2022-06-15

Puncture injuries made by a knife are common injuries which occur during close interpersonal conflicts. We present a case of a 28-year-old patient with puncture injury made by a knife with long edge in the left thoracolumbar region, between the eighth and ninth rib.

CORTICAL VISION IMPAIRMENT - A CASE REPORT

Igor Isjanovski — 2022-06-15

Cortical visual impairment (CVI) is a brain-based visual impairment. The eyes can see, but the brain can’t interpret the visual world.

Cortical visual impairment (CVI) in children is most commonly caused by peri- or postnatal hypoxia-ischemia, but may also occur following other insults, e.g., trauma, epilepsy, infections, drugs or poisons, and certain neurologic diseases. Case report: A case of a 9-year-old child, girl who was referred with Dg. epilepsy et CVI by a specialist doctor, pediatric neurologist from the University Pediatric Clinic for fundus examination and ophthalmological investigation and evaluation. Children with CVI have different levels of severity of visual impairment. There is no one-size-fits-all model, and every child is unique.

CURRENT SITUATION IN CHEMOPROPHYLAXIS AND THERAPEUTIC TREATMENT OF COVID-19

Mile Bosilkovski — 2022-06-15

Two years have passed since the emergence of SARS-CoV-2 infection and even after all this time medical approach in prophylaxis and treatment of COVID-19 is still very relevant. The search for a magical drug which would be a game changer and which would significantly change the clinical course and the outcome of the disease continues with undiminished intensity but also with a great dose of reservation that this search can last for a long time. Until then, it is necessary to use the current knowledge based on conducted trials and gained experiences. Based on this premises, many relevant health organizations, institutions, universities and medical societies worldwide have developed appropriate guidelines for treatment of COVID-19, which are subjected to periodic updates based on the newest discoveries. Following these guidelines, the treatment of COVID-19 patients has been improved in many ways and very good results have been achieved at this time, which unfortunately is far from the best. This paper sublimates the current guidelines issued from respectable health authorities (organizations, institutions, universities and societies) based on the newest studies and meta-analyses which have been subjected to the most rigorous, strict, critical and competent review processes.