Growing Prevalence and Incidence of Diabetes in Republic of Macedonia in the Past 5 Years Based on Data from the National System for Electronic Health Records

Introduction. Diabetes is a chronic metabolic disease characterized with a rapid progression of prevalence in last 3 decades, especially in countries with low and middle income. Next three decades this number of diabetes in the world is expected to be doubled. Early diagnosis and appropriate management of diabetes is the primary way to prevent and delay cardiovascular complications. Patients and methods. In this retrospective study, we used the data from National electronic system e-health which was performed in late 2014, wich gives us nearly precise data, and we made statistical analysis for diabetes in last 5 years (2015-2019). Results. In 2015 we have registered 103480 patients with DM, in 2016 108130 patients, in 2017 114408, in 2018 119999 and in 2019 124450 patients with DM. 95% of patients are with T2DM and 4, 1% with T1DM. According the data from State statistical office for population of Republic of Macedonia, the prevalence of T2DM for the years 2015-2019 is as follows: 5,66% in 2015, 6.13% In 2016, 6.55% I 2017, 7,06% in 2018 and 7,2% in 2019.   Conclusions. The number of registered  patients with diabetes in last 5 years has grown up for 20970 or 20%, in the last 5 years the number of patients with  type 2 diabetes has grown up for 18272 patients or 11%. The prevalence of T2DM has increased for 1.54%. Involvement of primary health care professionals has improved the early diagnosis of type 2 diabetes

Gastroesophageal Reflux Symptoms in Patients with Chronic Obstructive Pulmonary Disease

BACKGROUND: It is known that there is some relation between airways obstruction and gastroesophageal reflux symptoms (GER) symptoms in patients with chronic obstructive pulmonary disease (COPD).AIM: The aim was to determine frequency of GER symptoms and correlation with pulmonary function tests in patients with COPD.MATERIAL AND METHODS: The study included 58 patients. First group had 20 patients with mild COPD, second group had 18 patients with moderate COPD and third group had 20 patients with severe COPD. We had also a control group with 12 healthy subjects. All subjects completed their self-reported questionnaire about symptoms like: acid-regurgitation, heartburn, dysphagia, dyspnea and chronic cough.RESULTS: COPD patients with airways obstruction and significant GER symptoms had their respiratory symptoms associated with reflux events. More of COPD patients had significant GER symptoms defined as regurgitation and dysphagia once or more per week. Patients with FEV1 less than 50% showed more prevalent GER symptoms compared to those with values of FEV1 grater then 50%.CONCLUSION: GER symptoms are more prevalent in patients with severe airways obstruction when compared to less airways obstructed group and controls. We could suggest an association between the degree of airways obstruction in patients with COPD and the increased rate of GER symptoms

Spatial patterns of diatom diversity and community structure in ancient Lake Ohrid

[EN] The extraordinary diversity in long-lived lakes is largely driven by distinct eco-evolutionary processes. With their unique biota and numerous endemic taxa, these lakes are key settings for fundamental studies related to ecology, diversity, and evolution. Here, we test how the environment shapes diatom diversity and community patterns over space in ancient Lake Ohrid. By applying Bray–Curtis similarity analyses of diatom community data, including widespread and endemic taxa, we identified two major zones: littoral and sublittoral. The latter one is being characterized with higher endemic diversity. The a and b diatom diversity and community distribution in the northern and eastern part of the lake are influenced by the presence of vertical (bathymetrical) and horizontal barriers. The zonation of the diatom communities appears driven by two large-scale factors: (i) water depth, and (ii) water chemistry, primarily, the concentration of total phosphorus, nitrogen ammonia, and conductivity. Both drivers appear to equally influence diatom diversity and community patterns. We present initial data on diatom–environment relations, where the results support earlier ecological studies emphasizing the relevance of ongoing human-induced eutrophication in the northern lake area. This study provides background information on the role of the environment in structuring contemporary diatom diversity. However, future research needs to focus on the biotic component including species competition in order to reveal the mechanisms driving spatial community dynamics in Lake OhridSIThe presented study would not have been possible without the support of the Western Balkan Environmental Network project (www.newenproject.org

Role and Significance of Markers of Inflammation in the Asthmatic Disease

BACKGROUND: Asthma is characterized by airway inflammation which can be reversible.AIM: Investigation the importance of eosinophils, ECP and IL-5 in asthmatics versus patients with obstructive bronchitis and healthy subjects. We investigated the values before and after the treatment in asthmatics.MATERIAL AND METHODS: We studied 77 subjects divided in three groups as follows: 1) asthma patients; 2) patients with obstructive bronchitis and 3) control group of healthy subjects. In all the subjects there were determined: Total number of eosinophils (Eo), eosinophilic cationic protein (ECP), Interleukin 5 (IL-5) and allergy tests. RESULTS: The total number of eosinophils was significantly increased in the group of asthma patients versus second and third group. We found that the presence of ECP demonstrate an ongoing inflammation, with or without clinical symptoms of asthma patients. There was significant difference between the values of ECP of asthma patients versus second and third group. Our results have shown that IL-5 was significantly increased versus second group and controls (p < 0.01). We also found the decrease of the values of inflammatory markers after the treatment with corticosteroids. CONCLUSIONS: Eosinophils, ECP and IL-5 could be useful markers for selecting allergic patients and could be the monitors of treatment effects

Ц-реактивен протеин и cоодносот на неутрофили-лимфоцити како фактори за предиктивност на тежината на клиничката слика кај COVID-19

COVID-19 is an infectious disease that can manifest quite differently. In this study we examined the relationship between the value of serum CRP(C-reactive protein) andneutrophil-lymphocyte ratio (NLR) as predictor factors for the development of a severe clinical manifestation in COVID19 patients. Materials and methods: We followed 95 COVID-19 positive patients who were hospitalized at the University Clinic for Eye Diseases - COVID Center. We analyzed the initial laboratory parameters of white blood cells and CRP on admission of the patients and the results of laboratory analyses performed before they left the Clinic, or the last parameters before the lethal outcome in those patients who died. Several models of logistic regression were tested to analyze the predictive value of these markers of inflammation for lethal outcome in patients hospitalized for COVID-19. Results: Bivariate analysis demonstrated that the length of hospital stay was significantly shorter in patients with lethal outcome (p=0.001). The NLR was significantly higher in patients with lethal outcome at both times (p=0.005; and p=0.017). Leukocyte’s count (p=0.046, and p<0.001) and CRP (p=0.013,and p=0.005) were also significantly higher in patients with lethal outcome at both times. The increase on the NLR scale both at hospitalization and at discharge (or the last analysis before death) leads to increase in the odds of lethal outcome (T1:40.4% increased odds; T2:36% increased odds). Conclusion: CRP and NLR are laboratory parameters that can predict the severity of the clinical manifestation in patients with COVID-19.COVID-19 е инфективно заболување кое може да се манифестира доста различно. Во оваа студија ние ја испитувавме поврзаноста помеѓу вредностите на CRP (Ц-реактивен протеин) и соодносот неутрофили-лимфоцити (NLR) како предиктивни фактори за развој на тешка клиничка слика кај пацентите со COVID-19. Материјали и методи:Следевме 95 COVID-19 позитивни пациенти кои беа хоспитализирани во УК за очни болести - COVID центар во Скопје. Ги анализиравме лабораториските параметри на леукоцитите и CRP при прием на пациентите во Клиниката и резултатите од лабораториските анализи изведени пред пациентите да ја напуштат Клиниката или пред нивниот летален исход, кај оние што починаа. Беа тестирани неколку модели на логистичка регресија со цел да се утврди предиктивната вредност на овие маркери на инфламација за летален исход кај пациенти хоспитализирани од COVID-19. Резултати: Анализата покажа дека должината на престој во болница беше значително пократка кај пациентите со летален исход (=0,001). NLR беше значително повисок кај пациенти со летален исход и во двете времиња (p = 0,005; и p = 0,017). Бројот на леукоцитите (p = 0,046, и p <0.001) и CRP (p = 0,013, и p = 0,005), исто така, беа значително повисоки кај пациенти со летален исход во двете времиња. Повисоки вредности на NLR и при хоспитализација и при отпуштање (или последна анализа пред настапување на смртта) доведува до зголемување на шансите за летален исход (Т1: 40,4% зголемени шанси; Т2: 36% зголемени шанси). Заклучок: CRP и NLR се лабораториски параметри кои можат да ја предвидат сериозноста на клиничката слика кај пациенти со COVID-19.

Patient with Antineutrophil Cytoplasmic Antibody Associated Small Vessel Vasculitis, Acute Renal Failure, and Coronavirus Disease-19 Pneumonia: A Diagnostic and Therapeutic Challenge

BACKGROUND: Antineutrophil cytoplasmatic antibody (ANCA)-associated vasculitis (AAV) has a predilection for the kidney and more than three quarters of patients have renal involvement with rapidly progressive glomerulonephritis. Small-vessel systemic vasculitis may present as pulmonary-renal syndrome and is characterized by necrotizing glomerulonephritis and pulmonary hemorrhage. Diagnosis and therapy for AAV in coronavirus disease (COVID) COVID-19 pandemic require multi-disciplinary collaboration due to the affection of multiple systems and risks associated with immunosuppressive medications. CASE REPORT: A 69-year-old non-smoker, non-diabetic female presented in the outpatient unit at the department of pulmonology with dry cough, malaise, and sub-febrile temperature, lasting for 1 month. The patient had a high suspicion of severe pulmonary-renal syndrome, ANCA-AAV, and acute renal failure requiring hemodialysis. She was treated with corticosteroids, cyclophosphamide, and plasma exchange. The treatment led to temporary improvement. Infections with COVID-19, Enterococcus in the urine, and Acinetobacter in the tracheal aspirate further complicated the clinical picture and despite antibiotic treatment, use of tocilizumab and convalescent plasma, the outcome was lethal. CONCLUSION: It is important to establish the diagnosis and distinguish accurately between vasculitis and infection to provide adequate and timely therapy

Улогата на некои инфламаторни маркери, цитокини и тумор маркери во дијагноза на ендометриозата

Endometriosis is a multifactorial disease which etiopathogenesis has not been elucidated. One of the theories of etiopathogenesis is the inflammatory theory. Aims of the study: To develop a practical non-invasive test for the diagnosis of endometriosis by examining some inflammatory markers and cytokines; to compare the highly sensitive C-reactive protein (hsCRP), cytokines (interleukin-6-IL-6 and tumor necrotizing factor alpha) and the tumor marker cancer antigen 125 (CA-125) among healthy patients and patients with endometriosis; to determine the sensitivity and specificity of each biomarker separately in the diagnosis of endometriosis and to determine their role in the diagnosis of endometriosis. Materials and methods: In a prospective study conducted at the University Clinic for Gynecology and Obstetrics, Ss. Cyril and Methodius University in Skopje, North Macedonia 138 patients were included of a reproductive age between 18-50 years (83 with diagnosis endometriosis operated laparoscopically or with laparotomy) and a control group of 55 healthy women, in a period between 01.09.2018 to 01.05.2021. Serum levels of IL-6, TNF-α, hs-CRP and tumor marker CA-125 were evaluated in both groups. Results: Serum levels of CA-125, IL-6 and TNF-α and hs-CRP were significantly higher in patients with endometriosis compared to the control group. The surface under the ROC curve (AUC) for IL-6, CA-125, hs-CRP, and TNF-α has shown that as individual markers they all have a discriminatory capacity to diagnose patients with endometriosis. Conclusions: Results obtained in our study showed statistically significantly higher serum concentrations of CA-125, IL-6 and TNF-α and hs-CRP in patients with endometriosis compared to the control group of patients. However, none of these biomarkers showed a high sensitivity for diagnosis of endometriosis. It is necessary to find a panel combination of biomarkers with a high sensitivity of about 100% that will enable early diagnosis of endometriosis.Ендометриозата е мултифакторно заболување, чија етиопатогенеза не е разјаснета. Една од теориите за етиопатогенезата е инфламаторната теорија. Цели на истражувањето: Да се развие практичен неинвазивен тест за дијагноза на ендометриозата со иследување нанекои инфламаторни маркери и цитокини; да се направи споредба на  високосензитивниот Ц-реактивен протеин  (hsCRP), цитокините (интерлеукин 6 –IL-6 и тумор-некротизирачки фактор алфа - TNF-α) и туморскиот маркер cancer antigen 125 (CA-125) кај здрави пациентки и пациентки со ендометриоза; да се утврди сензитивноста и специфичноста на секој биомаркер посебно во дијагнозата на ендометриозата и да се утврди нивната улога во дијагноза на ендометриозата. Материјал и методи: Во проспективна студија спроведена на Универзитетската клиника за гинекологија и акушерство, Универзитет „Св. Кирил и Методиј“ во Скопје, Северна Македонија беа вклучени 138 испитанички на репродуктивна возраст помеѓу 18-50 години (83 со дијагнозa ендометриоза, оперирани со лапароскопија или лапаротомија) и контролна група од 55 здрави жени, во период од 01.09.2018 година до 01.05.2021. Серумските вредности на интерлеукин 6 (IL-6), тумор-некротизирачки фактор алфа (TNF-α), високоспецифичен Ц-реактивен протеин (hsCRP) и туморскиот маркер CA-125 беа евалуирани во двете групи. Резултати: Серумските вредности на CA-125, IL-6 и TNF-α и hsCRP беа сигнификантно повисоки кај пациентките со ендометриоза во споредба со оние во контролната група. Површината под ROC кривата (AUC) за IL-6, CA-125, hs-CRP и TNF-α покажа дека како поединечни маркери сите имаат дискриминаторен капацитет за дијагноза на пациентки со ендометриоза. Заклучоци: Иследувањата во нашата студија покажаа статистички сигнификантно повисоки концентрации на CA-125, IL-6 и TNF-α и hs-CRP кај пациентките со ендометриоза во однос на контролната група пациентки. Меѓутоа, ниту еден од овие биомаркери не покажа висока сензитивност за дијагноза на ендометриозата. Потребно е да се најде панел комбинација на биомаркери со висока сензитивност од околу 100% кои ќе овозможат  рана дијагноза на ендометриозата

Analysis of Plasma Concentrations of Theophylline in Smoking and Nonsmoking Patients with Asthma

BACKGROUND: While dosing theophylline in asthmatics, we should consider that a lot of medicines, substances, conditions and diseases affect the clearance of theophylline, such as smoking, macrolide antibiotics, barbiturates, oral contraceptives, heart and liver insufficiency, alcohol, calcium-antagonists, pneumonia, viral infections, hypoxemia, etc.AIM: The aim of the study is to investigate the concentrations of theophylline during the day in smoking and nonsmoking patients with asthma.MATERIAL AND METHODS: We have estimated the concentrations of theophylline 6 times daily by the HPLC method (Keith Muir, J Chromatography) in 20 smoking and 20 nonsmoking asthmatic patients, who were treated with theophylline sustained-release tablets 175 mg twice daily.RESULTS: In the first group of 20 nonsmoking patients we obtained constant therapeutic and optimal concentrations of theophylline. In the second group of 20 smoking asthmatics the concentration of theophylline in plasma, in 8pm and 8am the next day was very low.CONCLUSION: Because in smokers we have increased clearance and the decreased half- life of theophylline, and in order to prevent the night time life-threatening attacks, it is necessary to recommend maximal doses of theophylline, especially in the evening. According to the study, dosage should be individualized in order to optimize the treatment based on the measurement of theophylline concentration in plasma

Проценка на остеопорозата и појава на вертебрални фрактури кај постменопаузни пациентки со ревматоиден артритис третирани со мали дози на гликокортикоиди

Osteoporosis (OP) is a serious extracorporeal manifestation that occurs in patients with rheumatoid arthritis (RA). One of the risk factors is long-term use of glucocorticoids (GC). Osteoporosis together with the increased risk of vertebral (VF) and non-vertebral fractures (non-VF) in particular has a negative impact on quality of life in patients with rheumatoid arthritis. The aim of the study was to detect the occurrence of OP and VF in postmenopausal patients with RA and their association with long-term use of small doses of glucocorticoids. Material and methods: A total of 46 patients were analyzed. All respondents underwent imaging for osteoporosis evaluation with a DXA scanner (Lunar iDXA, GE) and VF  with incorporated Vertebral Fracture Assessment (VFA). Results: The values of bone mineral densities (BMD) were significantly smaller in the group that received glucocorticoids. According to VFA, 37,0% of patients were registered to have a fracture of middle degree, a mild fracture was registered in 19.6% of patients, and severe fractures were registered in 3 patients (6.5%). Conclusion: In postmenopausal patients with RA receiving GC therapy, a more common occurrence of osteoporosis and vertebral fractures was reported compared with the remaining group of RA patients. All patients with RA in menopause need to be screened for timely detection and treatment of osteoporosis and prevention of its complications.Остеопорозата (OP) е сериозна вонзглобна манифестација која се јавува кај пацинетки со ревматоиден артритис (RA). Еден од ризик-факторите претставува долготрајната примена на гликокортикоиди (GC). Остеопорозата заедно со зголемениот ризик од вертебрални (VF) и невертебрални фрактури (non-VF) има негативно влијание врз квалитетот на живот кај пациентките со ревматоиден артритис.  Целта на трудот беше да се детектира  појавата на  OP и VF  кај постменопаузни пациентки со RА и нивната поврзаност со долготрајната примена на мали дози гликокортикоиди. Материјал и методи: Беа анализирани 46 пациентки. Кај сите беше направенo снимање за евалуација на остеопороза со апарат за двојно-енергетска x-зрачна aпсорпциометрија - DXA скен, “Lunar iDXA”, производство на GE, со вграден софтвер за проценка на VF, VFA (Vertebral Fracture Assessment). Резултати: Вредностите на коскениот минерален дензитет (BMD) беа сигнификантно помали во групата која примала гликокортикоиди. Според VFA, кај 37,0% од пациентките беше регистрирана фрактурa од среден степен, кај 19,6% леснa фрактурa, a  тешка фрактура беше регистрирана кај три пациентки (6,5%). Заклучок: Кај постменопаузните пациентки со RA кои примаа терапија со GC беше регистрирана  почеста појава на OP како и VF споредено со останатата група пациентки со ревматоиден артритис. Кај сите пациенки со RA во менопауза,  потребно е навремено детектирање и третман на остеопорозата и превенирање на нејзините компликации

The Effect of Combined Therapy ICS/LABA and ICS/LABA plus Montelukast in Patients with Uncontrolled Severe Persistent Asthma Based on the Serum IL-13 and FEV1

BACKGROUND: IL-13 is one of many cytokines responsible for the chronic inflammation of asthma.AIM: The aim of this study was to determine the effect of combined therapy ICS/LABA and ICS/LABA plus Montelukast in patients with uncontrolled severe persistent asthma by analyzing of serum IL-13 and FEV1 before the treatment and after 6 months of therapy.MATERIAL AND METHODS: In study we included two groups. First group with 27 patients were treated with ICS/LABA. Second group with 29 patients were treated with ICS/LABA plus Montelukast. In each of them were measured serum IL-13 levels by the ELISA method and FEV1 before and after 6 months of treatment. Results were statistically analyzed according to the Wilcoxon Pairs Test and T-test.RESULTS: The obtained results in both groups showed that the serum IL-13 before the start of therapy were much higher and after 6 months of treatment significantly reduces their value, which in the second group were more expressed. The difference in the average value of FEV1 in both groups before and after therapy was statistically significant.CONCLUSION: Treatment with ICS/LABA plus Montelukast proved superior compared to therapy of ICS/LABA in patients with uncontrolled severe persistent asthma and allows achievement of well controlled of asthma with subjective clinical improvement