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Background: Campylobacter infections are typically self-limited, but in cases with severe enteritis, immuno-compromised system and bacteremia, an appropriate antimicrobial treatment is demanding. Our study aim was to determine the isolation rate of Campylobacter among patients with acute enteritis in the capital of North Macedonia and its antimicrobial susceptibility. Material and methods: A total number of 3820 patients clinically diagnosed as acute enteritis, were included in the study. Stool samples were collected and Campylobacter was isolated and identified by classical microbiological methods. Antimicrobial susceptibility of all isolates to Ceftriaxone, Amoxicillin-clavulonic acid, Erythromycin, Ciprofloxacin, Tetracycline and Gentamicin was determined by disc-diffusion technique. Additionally, minimal inhibitory concentrations of all Campylobacter isolates against erythromycin, ciprofloxacin and tetracycline were determined by Epsilon gradient tests. Results: Campylobacter species was isolated in 97 patients. Although the mean isolation rate of Campylobacter spp. during the whole study period was 2.53%, a statistically significant increase was detected in 2016 and 2017, in comparison with the data from previous four years of the study. The isolation rate of Campylobacter spp. didn’t reveal statistically significant difference between males and females (p > 0.05). 46.4 % of patients with Campylobacter enteritis were children at the age under 15 years. Forty-three C. jejuni isolates were susceptible to all six antibiotics, but the remaining 44 isolates revealed resistance to at least one antibiotic. C. coli isolates were resistant to 3 antibiotics simultaneously. Two C. coli isolates only, were susceptible to all 6 antibiotics. 40.90% of C. jejuni and 50% of C. coli isolates were resistant to beta-lactams, fluoroquinolones and tetracyclines, simultaneously. Conclusion: The increase of the isolation rate of Campylobacter from patients with acute enteritis indicates the need for permanent isolation and identification of Campylobacter from every clinically diagnosed patient, as acute enteritis. Erythromicin is the most effective antibiotic for treatment of Campylobacter enteritis in our patients. The high level of Campylobacter resistance to beta-lactams, fluoroquinolones and tetracyclines requires more rational approach in the treatment of Campylobacter enteritis

Aim: The aim of our study was to determine the most common bacteria isolated from wound samples and tо compare the frequency of the resistant bacteria isolated over a 3-year period. Material and methods: During a three years period (2017-2019) a total of 11 863 wound samples (wound swabs, punctuates, exudates, tissue, etc.) were obtained from the hospitalized patients in the University Clinics of the ,,Mother Theresa” campus, the City hospital ,,8th September” and the University Clinic for surgical diseases ,,St. Naum Ohridski” in Skopje. All samples were processed at the Institute of Microbiology and Parasitology, Faculty of Medicine, Skopje. They were examined by standard microbiology techniques. Identification and susceptibility of microorganisms were done by both standard methods and automatized Vitek 2 system. Results: Out of a total number of samples, which was 3 463 in 2017, 4 127 in 2018 and 4 273 in 2019, positive were 2 068 (60%), 2 302 (55.8%) and 2 387 (55.9%), respectively. From the total of aerobes/facultative anaerobes (2 758, 2 949 and 3 279 in three consecutive years, 2017, 2018 and 2019, respectively), Staphylococcus aureus was the most predominant isolate (19.5%, 16.6%, 16.9%) followed by Enterococcus spp (16%, 16%, 16.7%), Pseudomonas aeruginosa (12%, 13%, 12.7%) and E. coli (10%, 10.4%, 10.7%). Considering anaerobic bacteria, the percentage of Gram positive anaerobes (Peptostreptococcus) has decreased from 33% to 18% out of a total number of anaerobes, unlike Gram negative anaerobes in which the increasing percentage was mostly observed in bacteria of the genus Bacteroides (from 39% to 45%). The percentage of the resistant strains of MRSA, CNS-MR and VRE was almost the same in that period. In Gram-negatives the percentage of ESBL-positive isolates of E. coli and Enterobacter spp. increased consecutively from 2017 to 2019. The increase in the percentage of resistant strains was more noticeable in ESBL-positive isolates of Klebsiella pneumonia between 2017 and 2018, but in 2019 a percentage decrease can be observed. Considering carbapenem-resistant (CR) Enterobacterales, an increase in the resistance was noticeable in K. pneumonia. The increase in the percentage of resistant strains in Enterobacter spp. between 2017 and 2018, as well as the decrease between 2018 and 2019 was statistically significant. The percentage of CR-isolates of Pseudomonas aeruginosa was from 30% to 38% and for Acinetobacter spp. this percentage was from 81% to 85%. Conclusion: The knowledge of the most commonly isolated bacterial pathogens, especially the presence of resistant bacteria, is crucial and should be continuously monitored in order to understand, construct and update effective treatment algorithms and guidelines., Цел: Цел на студијата е да се детектираат најчестите бактерии изолирани од примероци од рани и да се спореди процентот на резистентни бактерии во тригодишниот период. Материјал и методи: Во период од три години (2017-2019) беа земени вкупно 11 863 примероци од рани (брисеви, пунктати, ексудати, ткиво и др.) од пациенти хоспитализирани во Универзитетските клиники во кампусот ,,Мајка Тереза”, Градската болница ,,8. Септември” Универзитетската клиника за хируршки болести ,,Св. Наум Охридски” во Скопје. Сите примероци беа обработени на Институтот за микробиологија и паразитологија, Медицински факултет, Скопје. За обработка беа користени стандардни микробиолошки техники. Идентификацијата на бактериите, како и одредување на нивната осетливост кон антимикробни средства беше направена со стандардни и автоматизирани методи (Vitek 2- систем). Резултати: Од вкупниот број на примероци кој изнесуваше 3 463 во 2017, 4 127 во 2018 и 4 273 во 2019 год., позитивни беа 2 068 (60%), 2 302 (55,8%) и 2 387 (55,9%), последователно. Од вкупниот број аероби/факултативно анаероби (2 758, 2 949 и 3 279 во три последователни години, 2017, 2018 и 2019 год.), најчесто изолирана беше бактеријата Staphylococcus aureus (19,5%, 16,6% и 16,9%), потоа Enterococcus spp (16%, 16% и 16,7%), Pseudomonas aeruginosa (12%, 13% и 12,7%) и E. coli (10%, 10,4% и 10,7%). Од анаеробните бактерии, беше детектирано намалување на процентот на Грам-позитивните анаероби (Peptostreptococcus) од 33% на 18%, од вкупиот број на анаероби, за разлика од Грам-негативните анаероби каде беше детектирано зголемување на тој процент, особено кај бактериите од родот Bacteroides (од 39% на 45%). Процентот на резистентни соеви (MRSA, CNS-MR и VRE) беше речиси идентичен во испитуваниот период. Кај Грам-негативните бактерии, беше детектирано зголемување на процентот на ESBL-позитивни изолати на E. coli и Enterobacter spp. во периодот од 2017 до 2019, а кај Klebsiella pneumoniaе во периодот од 2017 и 2018 имаше зголемување, а во 2019 намалување на тој процент. Во однос на карбапенем-резистентните (CR) ентеробактерии, кај К. pneumoniae беше детектирано зголемување на процентот на резистентни изолати во сите три години, додека, пак, кај Enterobacter spp. тој процентот беше повисок меѓу 2017 и 2018, а во 2019 год. статистички значајно понизок. Процентот на CR- изолати на Pseudomonas aeruginosa беше помеѓу 30% и 38%, а за Acinetobacter spp. овој процент беше меѓу 81% и 85%. Заклучок: Потребно е континуирано мониторирање на најчесто изолираните бактерии од примероците од рани, особено присуството на резистентни бактерии, со цел примена на соодветни алгоритми и водичи за ефективен третман на инфекциите на рани. &nbsp

Acquired lymphangiectasia of the vulva is very uncommon. Owing to the non-specific papillomatous manifestation and the vast array of possible differential diagnoses, lymphangioma circumscriptum (LC) still presents a diagnostic challenge. In this report, we present a very rare form of acquired vulvar LC in a 71-year-old patient with a longstanding history of asymptomatic lesions over the labia majora that had been previously treated as genital warts. On examination, the patient had multiple clustered translucent papules up to 15mm in diameter, morphologically reminiscent of vesicles, that oozed clear fluid throughout her groin and swollen labia majora. The patient also suffered concomitant bilateral lower-extremity lymphedema. A skin biopsy showed multiple, irregular-shaped lumina containing eosinophilic material in the upper dermis. Dilated lymphatic channels were lined by a single layer of flattened endothelial cells and the overlying epidermis showed acanthosis, hyperkeratosis, focal mild pseudoepitheliomatous hyperplasia. There is still no consensus on the optimal management of LC. Our patient was referred to a plastic surgeon for further evaluation and treatment. Although there are a variety of therapeutic modalities for LC, positive results are few and relapses are observed.

Background: Obesity is the most common chronic metabolic disease in children and adolescents. It has reached epidemic ranges and is a significant global problem. Objective: This study aimed to investigate the possible metabolic disturbances in children and adolescents with obesity and severe obesity. Subjects and methods: This cross-sectional study included 158 (82 boys, 76 girls) obese children and adolescents between ages of 0 and 17years (10.43 ± 3.11 years). The obesity was defined according to the sex- and age-specific growth charts proposed by the Centers for Disease Control and Prevention as BMI ≥ 95th percentile. Severe obesity was classified as 120% of the 95th percentile for age and sex. Study participants underwent medical assessment and analysis of: ALT, AST, fasting serum triglycerides, total serum cholesterol, fasting plasma glucose and plasma glucose from oral glucose tolerance test. Results: The majority of study participants were severely obese (69.92%). The highest distribution of abnormal biochemical results was seen in elevated ALT (53.91%) followed by elevated triglycerides (34.75%). The prevalence of abnormal total cholesterol level was significantly higher (p=0.04) in the group of obese children compared to the severely obese children. The levels of total cholesterol were also statistically higher in the group of adolescents compared to preadolescents (p=0.02). An important number of obese patients (2.5%) and even higher number of severely obese patients (5.26%) had carbohydrate intolerance. Conclusion: There was a significant elevation of ALT, total serum cholesterol and triglycerides in all study participants. High serum lipids and high hepatic enzymes (as introduction in non-alcoholic fatty liver disease) are alarming. Strikingly, there was carbohydrate intolerance in an important number of patients. Treatment and education of patients and parents is mandatory. Preventive measures in the society concerning childhood obesity are necessary.

A 16-year-old girl with a history of nontraumatic swelling of both forearms, osteochondromas of the knees, heterotopic ossification of the neck and back, severe malformations of all digits with hypoplastic or absent nails, alopecia partialis of the scalp, and moderate cognitive impairment was seen for diagnostic evaluation. Whole exome sequencing identified an activating mutation of ACVR1 (c.983G > A; p.Gly328Glu) which confirmed a suspected FOP variant. The delayed diagnosis of an FOP variant in this patient could have been avoided if the significance of severe digital malformations had been recognized, especially in the setting of progressive heterotopic ossification.

BACKGROUND: Squamous cell carcinoma (SCC) of the lower lip is a relatively rare carcinoma, with the incidence of 1 to 2%, but it is the most common carcinoma in the oral cavity accounting for 25-30% of all malignant oral tumours. AIM: This study aimed to determine the role of neovascularisation in the process of tumour progression. METHODS: We analysed the surgical specimens obtained from 60 patients with squamous cell carcinoma (SCC) of the lower lip. The examined group consisted of 45 specimens of patients without metastasis and 15 specimens of patients with metastasis in the regional lymph nodes. Histopathological slides were immunohistochemically stained with an antibody against CD34 and by hematoxylin & eosin staining for routine histopathological examination. RESULTS: The results obtained showed a statistically significant difference in the density of neovascularisation between groups of the SCC with different grade of differentiation (Kruskal-Wallis test: H (2, N = 60) = 30.0943, p = 0.00001). Statistical analysis also showed a significant difference in the density of vascularisation of lower lip SCC between patients without metastasis and patients with neck metastasis (Mann-Whitney U test, p = 0.000198). Applying Pearson’s chi-square test, we found a highly significant statistical difference in grade of SCC differentiation in patients with and without neck metastasis (p = 0.0000). CONCLUSION: In conclusion, the density of neoangiogenesis is increased in tumours with poorer differentiation and in patients with neck metastasis. So, the density of neovascularisation of the primary lip SCC may predict the tumour progression.

Obesity and excess weight are a pandemic phenomenon in the modern world. Childhood and adolescent obesity often ends up in obesity in adults. The costs of obesity and its consequences are staggering for any society, crippling for countries in development. Childhood obesity is also widespread in Macedonia. Metabolic syndrome, dyslipidemia and carbohydrate intolerance are found in significant numbers. Parents and grandparents are often obese. Some of the children are either dysmorphic, or slightly retarded. We have already described patients with Prader-Willi syndrome, Bardet-Biedl syndrome or WAGR syndrome. A genetic screening for mutations in monogenic obesity in children with early, rapid-onset or severe obesity, severe hyperphagia, hypogonadism, intestinal dysfunction, hypopigmentation of hair and skin, postprandial hypoglycaemia, diabetes insipidus, abnormal leptin level and coexistence of lean and obese siblings in the family discovers many genetic forms of obesity. There are about 30 monogenic forms of obesity. In addition, obesity is different in ethnic groups, and the types of monogenic obesity differ. In brief, an increasing number of genes and genetic mechanisms in children continue to be discovered. This sheds new light on the molecular mechanisms of obesity and potentially gives a target for new forms of treatment.

BACKGROUND: In the past several decades, the increasing frequency of overweight and obese children and adolescents in the world has become a public health problem. It has contributed significantly to the already high tide of diabetes, cardiovascular and cerebrovascular diseases.AIM: To investigate the frequency of insulin resistance and to evaluate the metabolic profile of insulin resistant and non-insulin resistant obese children and adolescents.SUBJECTS AND METHODS: The study included 96 (45 boys, 51 girls) obese children and adolescents aged 4-17 years old (10.50 ± 2.87 years). Only participants with Body Mass Index ≥ 95 percentile were included. We analysed sera for fasting insulin levels (FI), fasting serum triglycerides (TG), total serum cholesterol (TC), fasting plasma glucose (FPG) and plasma glucose 2 hours after the performance of the oral glucose tolerance test (2-h G). Homeostatic model assessment for insulin resistance (HOMA-IR) index was calculated as fasting insulin concentration (microunits per millilitre) x fasting glucose concentration (millimolar)/22.5. The value of HOMA-IR above 3.16 was used as a cut-off value for both genders.RESULTS: Insulin resistance was determined in 58.33% of study participants. Insulin resistant participants had significantly higher level of 2-h G (p = 0.02), FI level (p = 0.000) as well as TG levels (p = 0.01), compared to non-insulin resistant group. Strikingly, 70.73% of the pubertal adolescents were insulin resistant in comparison to 49.09% of the preadolescents (p = 0.03). Significantly higher percentage of insulin-resistant participants were girls (p = 0.009). Moreover, a higher percentage of the girls (70.59%) than boys (44.44%) had HOMA-IR above 3.16 and had elevated FI levels (70.59% vs 48.89%). The difference in the frequency of insulin resistance among obese versus severely obese children and adolescents was not significant (p = 0.73, p > 0.05). Our study results also showed positive, but weak, correlation of HOMA-IR with age, FPG, TG and BMI of the participants (p < 0.05).CONCLUSION: Higher percentage of insulin-resistant participants was of female gender and was adolescents. In general, insulin resistant obese children and adolescents tend to have a worse metabolic profile in comparison to individuals without insulin resistance. It is of note that the highest insulin resistance was also linked with the highest concentrations of triglycerides.

Background Diabetic nephropaty (DN) occurs in approximately 40% of patients with diabetes mellitus, and is the most common cause of end-stage renal disease. The mechanisms of DN are not very clear more recently, but the renin-angiotensin system (RAS) plays an important role. It has been known that rennin-angiotensin system blockers have a renal protective effect. The present study was undertaken to evaluate the effects of the candesartan on functional renal tests in streptozotocin (STZ) induced DN in rats. Methods DM was induced by a single intraperitoneal injection (ip) injection of STZ (60 mg/kg). In order to develop DN the animals were left in diabetic condition during 4 weeks. The DM rats were randomly assigned to the two experimental groups (STZ and STZ+CAN). To estimate the symptoms and signs of DN, the STZ group of rats was left without treatment. For assessment of the effects of the AT1 antagonist, candesartan (CAN) (5 mg/kg/day) was administered from week 4 to week 12. Renal function was assessed by determination of serum creatinine, blood urea nitrogen (BUN) test, 24-hour urine volume and urine albumin. Results The administration of STZ have caused diabetes mellitus (DM) with symptoms and signs of DN including poor general condition, body weight loss, as well as abnormalities of serum and urinary renal function tests. In STZ group of rats, these symptoms have been more distinctly 8 and 12 weeks after administration of STZ. Conclusion The candesartan treatment, although not completely but to a great extent ameliorates the functional renal disorder induced by STZ and may be used as a first line drug in preventing DN.

Immunohistochemistry (IHC), as such, can be used in routine pathology in order to make correct diagnosis of lung carcinomas. Consequently, more detailed analyses are needed in this field in order to make a wide spectrum of unique combinations for such pulmonary neoplasms. Our aim was to apply an antibody panel, and examine and confirm its utility in the differential diagnosis of lung cancer. Twenty-one cases (both bioptic and surgical material) of diagnosed lung cancer were investigated. An immunohistochemical analysis--(RTU FLEX Immunoperoxidase system) was made using Dako monoclonal antibodies (Cytokeratin 7, CK7; Cytokeratin 20, CK20; Neuron specific enolase, NSE, Thyroid transcription factor-1, TTF1 and Leucocyte common antigen, LCA). LCA expression was not expressed in any of our cases. Most adenocarcinoma were CK7(+)--83.3% and TTF1(±)--50%. The CK20(+) expression showed a metastatic pulmonary deposit of adenocarcinoma in the lung. TTF1(+)--100%, NSE(+)--100% and CK7(-)--66.66% expression was found in most cases of SCLC. NSE(+)--100% had the highest expression in carcionoid tumour, while TTF1(+) expression was highest in SCLC. For squamous cell carcinoma (SqCC), immunostaining was negative for this antibody panel, except focal and weak expression of NSE--60%, so we did some extra IHC using CKHMW antibody, which showed the highest expression. The essential antibody panel that we have confirmed and suggest for routine basic differential diagnosis of pulmonary neoplasms is: TTF1, CK7, CK20 and NSE. Due to the high number of co-occurrunces IHC should not be performed alone, but integrated in conjunction with morphological diagnosis.