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    Unrecognized Wernicke's encephalopathy during pregnancy induced by hyperemesis gravidarum
    (Termedia Publishing House Ltd., 2025)
    Trpchevska, Emilija Nikolovska
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    Hyperemesis gravidarum (HG) is the most common indication for hospitalization in the first half of pregnancy. Although 70—90% of pregnant women experience nausea and vomiting, few develop HG. Maternal complications include malnutrition and vitamin deficiencies, peripheral neuropathy, and serious neurological complications, including central pontine myelinolysis and Wernicke’s encephalopathy (WE).
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    Upper gastrointestinal bleeding from primary aortoesophageal fistula in a patient with aneurism of the thoracoabdominal aorta: Case report and literature review
    (Wiley, 2024-08)
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    Andov, Mishel
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    Kolev, Aleksandar
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    Bundovski, Kristijan
    Upper gastrointestinal bleeding due to primary aortoesophageal fistula is a rare clinical condition burdened with high mortality rate. However, the outcomes are closely related to the level of clinical awareness, the complementary and multidisciplinary approach during the diagnostic workup, and the selected treatment option. We present an atypical case of an aneurysm of the thoracoabdominal aorta complicated with primary aortoesophageal fistula (AEF). A 55‐year‐old male with no previous diseases, presented with prolonged and intense back pain and upper gastrointestinal bleeding. The gastroscopy detected an unusual culprit lesion in the distal esophagus resembling an esophageal wall defect, and the computed tomography revealed an aneurysm of the thoracoabdominal aorta, remarkable surrounding hematoma, and active contrast extravasation. Despite the urgent surgical repair, a lethal outcome occurred. AEF patients require high clinical awareness and complementary multidisciplinary approach in order to provide a rapid diagnosis and optimal treatment.
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    АSSESSMENT OF OSTEOPOROSIS AND OCCURRENCE OF VERTEBRAL FRACTURES IN POSTMENOPAUSAL PATIENTS WITH RHEUMATOID ARTHRITIS TREATED WITH SMALL DOSES OF GLUCOCORTICOIDS
    (Институт за јавното здравје на Република Македонија = Institute of public health of the Republic of Macedonia, 2020-12-11)
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    Nikolovska-Kotevska, Mimoza
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    Karadzova-Stojanoska, Andzelika
    <jats:p>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.</jats:p>
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    Polymorphism IL 28B and response to therapy in chronic hepatitis C
    (2016)
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    INTRODUCTION: Chronic hepatitis C is still a majgor cause for developing cirrhosis and hepatocellular carcinoma which often results in liver failure and thus in liver transplantation. According to the World Health Organisation 180 million people are infected worldwide and 3-4 million new infections per year were estimated (1). The current standard of care (SOC) for chronic HCV infection is a combination of pegylated interferon (PegINF -2a or PegINF -2b) plus body-weighted ribavirin (RBV) for the duration of 24 weeks or 48 weeks depending on the HCV viral genotypes (2). The primary goal of the treatment is HCV eradication, which is actally sustained viral response (SVR). The SVR is defined as undetectable HCV RNA in serum, 24 weeks after the completion of the antiviral treatment (3). However, only about 40-50% genotype 1 or 4 patients treated and 80% genotype 2 or 3 patients treated could respond completely and achive sustained virological response (4,5). Moreover, side effects from the therapy such as influenza-like symptoms, psychiatric symptoms and hematological abnormalities, could result in the dose reduction or even the premature discontinuation of the treatment (6). To avoid these potential adverse events in patients who do not benefit from the treatment and to reduce the cost of therapy, it is necessary to predict an individual’s response before at the early stage of the treatment. Virus-specific characteristic (viral load, genotype, viral variants as mutations of interferon sensitivity determining region- ISDR) may be responsible for virologic response but also clinical parametars (age, gender, BMI, fibrosis stage, liver enzymes) (7,8). Investigations on genetic determinants of chronic hepatis C established that a single nucleotide polymorphism (SNP) in the interleukin (IL)-28B gene promoter region affected the spontaneous and induced clearance of hepatitis C virus (9). Among 500 000 genetic variants which were analyzed genome-wide, a few associated with virologic response were identified, and showed variable frequency and importance across human ethnic groups (10). The mechanism by which SNPs influence the outcome of HCV infection and its treatment is not clear. It is suggested that regulation of the promoter region of IL28B in antiviral activity may also affect two other genes belonging to interferon (INF)- family encoded in this region (10, 11). INF- possess antiviral activities agains hepatitis C virus (12). The genome-wide associated studies (GWAS) showed that SNPs near IL28B gene (CC for rs12979860, TT for rs8099917 and AA for rs12980275) were associated significantly with treatment outcome in patient with chronic hepatitis C. However, about 50% of patients with a sustained virological response do not carry favorable IL28B alleles (13). The factors which increase the chance of a therapeutic response in these patient are not yet known. A detailed analysis if the course of therapy of chronic hepatitis C with pegylated INF and ribavirin in the presence of a hazardous IL28B allele might better delineate the clinical characteristics of the difficult-to-treat group of patients. The aim of the study was to evaluate the effects of IL28B polymorphism on response to treatment with peginterferon and ribavirin in patients with chronic hepatitis C. MATERIAL AND METHODS: Twenty-five adult Caucasians previous assessed with chronic hepatitis C due to HCV genotupe 1 and 3 were included in the study. The study protocol was approved by the institutional ethics committee and written informed consent was obtained from each study participant. Patients were treated with standard antiviral therapy with pegylated INF alfa and ribavirin. Pegylated interferon alfa 2a 180 μg was administered subcutaneously once a week. Body-weighted ribavirin was administered daily. The treatment duration was 48 weeks for patients with HCV genotype 1 and 24 weeks for patients infected with HCV genotype 3. SVR was used for the assessment of the antiviral treatment effectiveness. SVR is defined by undetectable viral RNA 24 weeks after the end of treatment. Finaly eighteen patients were analysed, because two premature discontinuated the treatment and for five there are no available data for SVR. Sample od peripheral blood were collected from each patient enrolled in the study for HCV quatntification and IL28B polymorphism genotyping. Reverse transcriptase-polymerase chain reaction assay for HCV quantification was done with One-tube real time PCR HCV amplification with lower detection limit 70 IU/ml. Polymorphisms rs12979860 (C>T) and rs8099917 (T>G) in gene IL28B were genotyed by PCR. Each polymorphism assay contained one pair of primers and one pair of probes, and each allele of the polymorphisms was labeled. For statistical analysis mean and standard deviation were used for parametric variables. Considering the small sample difference test (percentage of structure) was used to determinate the genetic predictors of the SVR. A p<0.05 was consideded statistically significant. RESULTS: The study population included 9 genotype 1 and 9 genotype 3 HCV infected patients. Their median age was 31.4±4.4 years and 88.88% were males. SVR were achived in 83.3% patients. The distribution of the frequencies od rs12979860 genotypes in the analyzed sample was: 10 (55.55%) patients with CC genotype and 8 (44.44%) patients with CT genotype. The distribution of the frequencies od rs8099917 genotypes was: 15 (83.33%) patients with TT genotype and 3 (16.66%) patients with TG genotype. The difference test showed that difference in persentage which is registered between SVR in CC and CT is not statistically significant (p=0,6714). There is no association in achievement SVR in CC and non-CC genotypes of rs12979860. There also no significance in achieving SVR in patients with TT genotype of rs8099917 and in patients with TG genotypes (p=0.3961). Futhermore there was no association with the achivment od SVR as compared with genotype (p=0.0579). DISCUSION: In this study, no significant difference was found in the response to treatment and allele proportions of SNPs rs12979860 and rs8099917 possibly due to the small size of the sample. The study of Silva Conde et al. confirmed similar effect of IL28B polymorphism on SVR in infected HCV patients (14). In another study from Norway and Denmark involving genotype 3 HCV-infected patients, RVR was achived by a significantly greater number of patients who had CC and TT genotypes at rs 12979860 and rs8099917, respectively, but these genotypes showed no association with SVR (15). Consistent to our findings were results of the study of Sarrazin et al.which present no significant association of SNPa rs8099917 with virologic treatment response (16). Investigation of a comparable number of genotype 2/3 infected patients in study by Rauch et al. also showed no correlation between the rs8099917 genotype and virologic response to pegylated interferon/ribavirin combination therapy (17). In contrast, the GWAS identified that homozygosis for C allele of rs12979860 and homozygosis for the T allele of rs8099917 were favorable genotypes of the IL28B gene polymorphisms which predicted the SVR in patients with chronic hepatitis C treated with peginterferon and ribavirin (18,19). The distribution of frequencies of rs12979860 genotypes in our study group was : CC 55.55% and CT in 44.44% . The distribution of frequencies of rs8099917 genotypes in our study sample was TT 83.33% and TG 16.66%. Sticchi et al. reported distribution of rs8099917 genotypes TT in 55%, TG in 40% and GG in 5% of the study participants (20). Results of other studies reported bigger percentage of CT than CC for distribution of the frequencies of rs12979860 (21.22). However, about 50% of patients with a sustained virological response do not carry favorable IL28B alleles (13). The factors which increase the chance of a therapeutic response in these patient are not yet known. Other factors, such as HCV genotype, viral-load, ethnicity should be used together with IL28B genotype as predictors of response on antiviral therapy. CONCLUSION: We did not find a significant association of SNPs rs12979860 and rs8099917 with SVR thus disagreeing with studies that found an association between genotype CC (rs12979860) and SVR in individuals with genotype 1, 2 and 3 as well as between genotype TT (rs 8099917) and SVR in individuals with genotype 3. Our study is limited by its sample size. And possibly results due to this fact. Nevertheless genotyping of this polymorphism on a large HCV population will aid clinical decision making for both current standard care and potentially for the integration of other agents in future, providing an opportunity for clinicians to individualize treatment regimens for hepatitis C patients.
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    Insulin resistance in patients with chronic hepatitis C
    (Македонско лекарско друштво = Macedonian Medical Association, 2016)
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    Introduction: Insulin resistance is the most common extrahepatic manifestation associated with hepatitis C virus, which leads to developing more pronounced fibrosis and liver steatosis. The aim of the study was to assess the prevalence of insulin resistance in non-diabetic, treatment naive patients with chronic hepatitis C and to analyze the relation of insulin resistance with genotype, viral load, gender, age, laboratory parameters, inflammatory and fibrotic changes in the liver, body mass index (BMI) and the presence of steatosis. Material and methods: In this cross sectional study, 224 patients with hepatitis C viral infection were included. The patients were divided into two groups. The first group was with no insulin resistance and the second one with present insulin resistance. They were compared in terms of genotype, viral load, gender, age, inflammatory and fibrotic changes in the liver, BMI and liver steatosis. Results: Insulin resistance was present in 45.5% of patients. The following factors were associated with insulin resistance: age (p = 0.0022), inflammatory and fibrotic changes in the liver (p = 0.001, p = 0.006, respectively), steatosis (p = 0.015) and transaminase activities (for AST, p = 0,002, for ALT, p = 0.001). Conclusion: In the Republic of Macedonia, high percentage of 45.5% among non-diabetic and treatment naïve patients with chronic viral hepatitis C, had insulin resistance. Insulin resistance was more prevalent in older patients, in those with more pronounced inflammatory and fibrotic changes in the liver, in patients with steatosis and in those with higher transaminase activity.
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    MODEL FOR END-STAGE LIVER DISEASE (MELD) IN STRATIFIACATION OF IN HOSPITAL PATIENTS WITH TERMINAL LIVER DISEASE
    (2012)
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    Serafimovski V
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    Syardelova K
    INTRODUCTION: Liver cirrhosis is end stage of liver disease where liver transplantation is the only curative treatment. MELD score system is relatively newer system (the last ten years) used as assesment tool for liver disease severity as well as for creating of liver transplantation priority lists. In the contrary of already used system - Child-Turcotte-Pugh, where posibility for subjective assesment of variables as ascites and encephalopathy is existing, this system avoids such posibility. MELD includes another very important variable – renal function assesment as serious prognostic factor. Well-defined formula calculating natural logarithms of bilrubin, creatinin and international normalized ratio (INR) of prothrombin time determined MELD-'s set of points. The aim of this study is to stratify in hospital patients in Clinic of Gastroenterohepatology, Skopje with terminal liver disease using MELD scoring system and easy recognize the real need for transplantation in these patients. MATERIAL AND METHODS: This retrospective study is analyzing medical discharge summary among 192 patients hospitalized at our clinic in the period from 01.01.2011 to 31.12.2011 with diagnosis of liver cirrhosis, who have all the necessary parameters available to calculate the MELD score (patients with the same diagnosis without the necessary parameters were excluded from the study). Patients were aged between 20 and 90 years (average age 55.7 years) with predominance of males (147 males and 45 females). They were analyzed in accordance to cirrhosis etiology, indication for hospitalization, MELD score and the risk of lethal outcome. Descriptive statistics to analyze data was used. RESULTS: Total of 192 patients are analyzed, 76.6% are male, while 23.4% are women. From the etiological point of view the alcohol as cause of cirrhosis dominates in 73 patients (38%), followed by HBV infection in 49 patients (25.5%), undefined etiology has in 24 patients (12.5%), mixed etiology of ethyl and viral origin of hepatitis B in 11 patients (6%), HCV infection in 9 patients (4.7%), immunogenic etiology in 8 patients (4.1%), portal vein thrombosis in 4 patients (2.1%), secondary biliary cirrhosis in 4 patients (2.1%), alcohol and HCV infection in 3 patients (1.5%), mixed HBV and HCV infection in 2 patients (1%), primary biliary cirrhosis in 2 patients (1%), Wilson disease in 2 patients (1%) and nonalcoholic steatohepatitis as a cause of cirrhosis in 1 patient (0.5%). The most common reason for hospitalization is variceal bleeding in 51 patients (26.6%), followed by refractory ascites in 35 patients (18.2%), jaundice in 31 patients (16.1%), portal encephalopathy in 29 patients (15.1%), diagnostic differentiation (liver biopsy) in 28 patients (14.6%), and hepato-renal syndrome in 14 patients (7.3%). In accordance to the MELD score, patients are divided into 5 groups regarding to calculated percentage of three month mortality. Average MELD score for all 192 patients is 15. Under this scoring system 4 patients (2.1%) belong to the group with highest risk (71.3% is the rate of mortality within three months), 14 patients (7.3%) in group having 52.6% mortality rate within three months, 31 patients (16%) belong to a group with 19.6% mortality rate, and the remaining patients in the group with 6% mortality rate (69 patients - 36%) and the group with the lowest mortality of 1.9% (74 patients - 39.5%). The outcome of 20 from 192 patients analyzed was lethal. The reason for this outcome was hepato-renal syndrome in 11 patients (55%), variceal bleeding in 7 patients (35%) and in 2 patients (10%) hepatic coma. DISCUSSION: Liver cirrhosis as an indication for hospitalization is often seen in our daily practice. Especially common reason for hospitalization is the occurrence of complications of cirrhosis (variceal bleeding, refractory ascites, jaundice, portal encephalopathy or hepato-renal syndrome), which caused lethal outcome in some patients. According to our analysis, a significant percentage of patients (39/192 or 25.4%) with MELD score> 20, belong to the group with high short-term risk of lethal outcome (3 months mortality rate). Those patients in developed countries would find themselves on a priority list for liver transplantation. Our commitment (such as internal disease specialists and surgeons) should be to enable these patients equal access to treatment as in those patients with terminal liver failure in developed countries.
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    Rituximab in treatment of a patient with granulomatosis with polyangitis - a case report
    (Македонско лекарско друштво = Macedonian medical association, 2023-01)
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    Guchev, Filip
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    Antova, Dubravka
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    Karadzova Stojanovska, Anzhelika
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    Vidinikj, Sonja
    ANCA-associated vasculitis (AAV) is a necrotizing vasculitis with few or no immune deposits that can affect predominantly small vessels. It can affect vessels in every organ and tissue of the body; the clinical manifestations of the disease are extremely variable. B-cells are of major importance in the disease pathogenesis as precursors of ANCA-producing plasma cells and, possibly, also as antigen-presenting and cytokineproducing cells. Therefore, rituximab, a monoclonal antibody drug causing partial B-cell depletion, has emerged as a powerful option in the treatment of AAV such as granulomatosis with polyangiitis. We present the case of a 25-year-old female diagnosed with granulomatosis with polyangiitis and treated with rituximab and high-dose corticosteroids.
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    Rare presentation of gastric schwannoma: a case report.
    (2016)
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    Isahi U
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    Mishevski J
    Schwannomas or neurilemmomas are well-defined benign tumors arising from neural crest cells and surrounding the nerve sheath. These neoplasm’s are rare among the spindle cell mesenchymal tumors of the gastrointestinal tract, and develop most commonly in the stomach representing 0.2% of all gastric tumors. We present a case of 53-years-old female with a history of upper abdominal pain. The physical examination revealed palpable epigastric mass; serum biochemistry and tumor markers were in normal range. Abdominal ultrasound as a first imaging procedure detected 5 cm cystic tumor located between the body and the tail of the pancreas, while upper endoscopy showed sub mucosal mass in the region of cardia. Diagnostic dilemma was resolved by the means of endoscopic ultrasound (EUS), which defined the exact place of the tumor in the gastric wall. Since EUS biopsy was not available procedure, percutaneous biopsy was performed. Histological and immuno-histochemical findings of the biopsy specimen and surgically resected tumor were identical, establishing the diagnosis of schwannoma. Complete surgical resection of the tumor is the treatment of choice, and the prognosis after tumor resection is excellent.