Joksimovikj, Nenad
Preferred name
Joksimovikj, Nenad
Official Name
Joksimovikj, Nenad
Main Affiliation
Email
nenad.joksimovikj@medf.ukim.edu.mk
37 results
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Item type:Publication, Diagnostic Potential of Calprotectin for Spontaneous Bacterial Peritonitis in Patients Withliver Cirrhosis and Ascites(Walter de Gruyter GmbH / Macedonian Academy of Sciences and Arts, 2021-12-30); ; ; ; The development of spontaneous bacterial peritonitis (SBP) is a serious and life-threatening condition in patients with cirrhosis and ascites. The aim of this study was to determine the diagnostic potential of calprotectin in ascites, for SBP in patients with liver cirrhosis and ascites before and after antibiotic treatment and to compare the mean values of calprotectin in ascites in patients with and without SBP. This prospective-observational study was comprised of 70 patients with cirrhosis and ascites, divided into two groups, the SBP and the non-SBP group. Quantitative measurements of calprotectin in ascites was completed with the Quantum Blue Calprotectin Ascites test (LF-ASC25), using the Quantum Blue Reader. The average value of calprotectin in the SBP group was 1.5 ± 0.40 μg / mL, and in the non-SBP group it was lower (0.4 ± 0.30). The difference between the mean values was statistically significant with p <0.05. The mean value of calprotectin in ascites before therapy among the SBP group was 1.5 ± 0.4, and after antibiotic therapy, the value decreased significantly to 1.0 ± 0.6; the difference between the mean values was statistically significant with p <0.05. ROC analysis indicated that calprotectin contributed to the diagnosis of SBP with a 94.3% sensitivity rating (to correctly identify positives), and the specificity was 62.5%, which corresponded to the value of 0.275. Our research confirmed that ascitic calprotectin was a good predictor, and is significantly associated with the occurrence of SBP in patients with liver cirrhosis. By monitoring the value of calprotectin in ascites on the 7th day of antibiotic treatment, the effectiveness of antibiotic treatment in patients with SBP can be determined. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, The Onset and Prognosis of Hepatorenal Syndrome - Three Year Single Center Experience(BANTAO Association, 2010-12); ; Introduction: The hepatorenal syndrome (HRS) refers to the development of acute renal failure in the setting of advanced liver disease. It can occur in a substantial proportion of patients with fulminate hepatic failure from any cause. The aim of our study was to investigate the onset, outcome and prognosis of patients with hepatorenal syndrome hospitalized at our unit. Methods: This is a cross-sectional retrospective study in a cohort of 543 cirrhotic patients, during a period of 3 years (January, 2008 - December, 2010). Hepatorenal syndrome was detected in 20 (3.7%) patients and in all of them a few variables such as: age, gender, history of cirrhosis or other liver disease, etiology of cirrhosis, Child-Pugh classification, other complications of the cirrhosis except for HRS, treatment and survival were analyzed. Results: The average preceding time up to the occurrence of HRS was around 3 years (36.8±47.8 months), although there were 4 patients who developed HRS only a month after the onset of cirrhotic symptoms. A group of seven patients with HRS diagnosed during the first year of the onset of symptoms. The mean age of patients was 55.5±13.3 years. There was a significant difference in the gender distribution, three quarters of patients being males. With regard to the etiology, 12 patients had alcoholic abuse, and a half of them (50%) were with mixed etiology (Hepatitis B plus alcohol abuse). Two patients had a pure chronic hepatitis B virus (HBV) infection as a cause of cirrhosis. Four were with chronic liver disease of unknown etiology (2 of them with confirmed histology of chronic hepatitis). All of the cirrhotic patients were scored as grade C according to the Child – Pugh classification. Hepatic encephalopathy was the most predominant concomitant complication present in 17 (85%) patients with HRS. Only 2 showed signs of malignancy with suspected hepatocellular carcinoma (HCC). The estimated average hospital stay was 6.15 days, ranging from 1-14 days. The applied treatment was generally unsuccessful. Majority of cases (14) were supported with albumin and fresh frozen plasma transfusion and haemodialysis was performed in 4 patients. The mortality rate was high, reaching 80% (16 patients) with an average time of death at 6.8±4.4 days after the hospital admission. Although the evaluation period was short, there is a clear raising trend in number of detected patients with HRS at our Clinical Center. Conclusion: Compared to other reports, our single centre experience shows lower occurrence rate. Despite the use of available conservative medical treatment, there was no recovery of the hepatic failure in any of HRS patients. The absence of liver transplantation or TIPS in our country is the second contributing factor related to the high mortality rate in our cohort. Finally, gastroenterohepatologists should be aware and try to prevent iatrogenic precipitants of HRS as an aggressive diuretic treatment or removal of large volumes of ascitic fluid by paracentesis without compensating for fluid depletion by intravenous replacement could additionally impair the renal failure. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, PREDICTIVE POTENTIAL OF BLOOD AND ASCITIC FLUID LABORATORY PARAMETERS FOR SPONTANEOUS BACTERIAL PERITONITIS IN PATIENTS WITH CIRRHOSIS(Georgian Association of Business Press, 2021-12); ; ; ; Patients with spontaneous bacterial peritonitis (SBP) usually have serious complications associated with deteriorating synthetic and excretory function of the liver cells, and require hospitalization and regular monitoring of biochemical parameters in blood and ascites.Aims - to determine the average values of laboratory parameters in blood and ascites in patients with SBP, to determine whether there is a difference in the average values between patients with SBP and non-SBP as well as their predictive power for the diagnosis of SBP.The study was designed as a prospective-analytical-observational and was conducted at the University Clinic for Gastroenterohepatology in Skopje for a period of one year. The study population included hospitalized patients with established liver cirrhosis, regardless of etiology; 70 patients, divided into two groups, 35 patients with SBP and 35 non-SBP. The selection of patients who were included in the study was conducted according to pre-determined inclusion and exclusion criteria. All diagnostic test specimens were immediately referred to the Central Clinical Laboratory. Five ml of a total of 10 ml of ascites were used for automatic counting of PMNC, and 5 ml for biochemical analysis of ascites (total sweat-WP). At the same time, for the needs of biochemical blood tests, a venipuncture of 10 ml of blood was performed.The univariate analysis showed that INR, albumin/s, creatinine/s, TP/ascites (p=0.039, p=0.035, p=0.013, p=0.000, p=0.030) were independent risk factors for the development of SBP. INR>1.2 significantly increased the chance of SBP by three times (Exp (B) = 3.222 (CI (1.063-9.768)). Serum albumin<35 g/L significantly increased the chance of SBP by five and a half times (Exp (B) = 5.712 (CI (1.135-28.748). Creatinine/s>115 µmol/L significantly increased the chance of SBP by four times (Exp (B) = 4.070 (CI (1.352-12.255)).TP in ascites ≤10 significantly increased the chance of SBP by five times (Exp (B) = 5.337 (CI (6.243-416.469). The multivariate logistic analysis confirmed that INR>1.2 and creatinine>115 µmol/L were statistical risk factors (predictors) that increased the chance of SBP.Low serum albumin values are independent risk factors for predicting SBP and significantly increase the risk of developing SBP by five and a half times. Patients with SBP have lower mean TP values in ascites than non-SBP. Low TP values in ascites<11g/L are independent risk factors for the development of SBP and significantly increase the risk of SBP by five times. Of course, additional and larger studies are necessary in order to confirm our conclusion in the future. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Functional outcome and quality of life after restorative proctocolectomy and ileal-pouch anal anastomosis in Elderely patients(2012); ; - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Polymorphism IL 28B and response to therapy in chronic hepatitis C(2016); ; ; ; 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. - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Имунолошки карактеристики на пациенти со различна клиничка манифестација на COVID-19 во корелација со SARS CoV-2 вакцинации(SHMSHM - AAMD, 2024); ; ; Вовед: Пандемијата на COVID-19 го смени животот на целата планета, однесе голем број на животи, многу луѓе останаа со трајни секвели. Во научната мисла перзистира енигмата за разноликоста во текот на болеста. Од особена важност е разбирањето на одбрамбените одговори од страна на имунолошкиот систем против инфекцијата со SARS-CoV-2, особено Т-лимфоцитните клетки кои го модулираат специфичниот имунолошки одговор, вклучувајки го целуларниот и хуморалниот дел. Цели: Да се одредат клиничките и патолошките карактеристики кај пациентите кои прележале тежок и лесен COVID 19, да се одредат разликите во хуморалниот имунолошки одговор кај различните групи пациентите и да се корелираат со вакциналниот статус на пациентите за SARS CoV- 2. Материјал и методи: Проспективна кохортна студија во времетраење од 3 месеци реализирана на ЈЗУ Универзитетска клиника за пулмологија и алергологија и Институтот за имунобиологија и хумана генетика при Медицински факултет – Скопје. Во студијата беа вклучени 50 пациенти со наполнети 18 години и постари, со прележан COVID 19 кои се поделени во две групи: лесна клиничка манифестација, или асимптоматски пациенти кои имале позитивен PCR за SARS-CoV-2 и пациенти со тешка клиничка манифестација и хоспитализација. Анализирани се параметрите од медицинската историја на болните, биохемиски анализи, параметри за хуморален имунолошки одговор, податок за вакцинација против SARS-CoV-2. Заклучок: Тежината на клиничката слика корелира правопропорционално со бројот на коморбидитетите, а обратнопропорционално со вакциналниот статус. Не се најде корелација со пушачкиот статус и тежината на клиничката слика. Пациентите со тежок COVID-19 имаа незначително повисок титар на IgG антитела. Студијата покажа дека 98% од сите испитаници имаа позитивни неутрализирачки антитела за SARS-CoV-2, со изразито висок титар над референтните вредности. - Some of the metrics are blocked by yourconsent settings
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Item type:Publication, Insulin resistance in patients with chronic hepatitis C(Македонско лекарско друштво = Macedonian Medical Association, 2016); ; ; ; 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. - Some of the metrics are blocked by yourconsent settings
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Item type:Publication, ИМУНОЛОШКИ КАРАКТЕРИСТИКИ НА ПАЦИЕНТИ СО РАЗЛИЧНА КЛИНИЧКА МАНИФЕСТАЦИЈА НА COVID-19 ВО КОРЕЛАЦИЈА СО SARS COV-2 ВАКЦИНАЦИИ И КОМОРБИДИТЕТИ(SHMSHM - AAMD, 2024); ; Вовед: Пандемијата на COVID-19 го смени животот на целата планета, однесе голем број на животи, многу луѓе останаа со трајни секвели. Во научната мисла перзистира енигмата за разноликоста во текот на болеста. Од особена важност е разбирањето на одбрамбените одговори од страна на имунолошкиот систем против инфекцијата со SARS-CoV-2, особено Т-лимфоцитните клетки кои го модулираат специфичниот имунолошки одговор, вклучувајки го целуларниот и хуморалниот дел. Цели: Да се одредат клиничките и патолошките карактеристики кај пациентите кои прележале тежок и лесен COVID 19, да се одредат разликите во хуморалниот имунолошки одговор кај различните групи пациентите и да се корелираат со вакциналниот статус на пациентите за SARS CoV- 2. Материјал и методи: Проспективна кохортна студија во времетраење од 3 месеци реализирана на ЈЗУ Универзитетска клиника за пулмологија и алергологија и Институтот за имунобиологија и хумана генетика при Медицински факултет – Скопје. Во студијата беа вклучени 50 пациенти со наполнети 18 години и постари, со прележан COVID 19 кои се поделени во две групи: лесна клиничка манифестација, или асимптоматски пациенти кои имале позитивен PCR за SARS-CoV-2 и пациенти со тешка клиничка манифестација и хоспитализација. Анализирани се параметрите од медицинската историја на болните, биохемиски анализи, параметри за хуморален имунолошки одговор, податок за вакцинација против SARS-CoV-2. Заклучок: Тежината на клиничката слика корелира правопропорционално со бројот на коморбидитетите, а обратнопропорционално со вакциналниот статус. Не се најде корелација со пушачкиот статус и тежината на клиничката слика. Пациентите со тежок COVID-19 имаа незначително повисок титар на IgG антитела. Студијата покажа дека 98% од сите испитаници имаа позитивни неутрализирачки антитела за SARS-CoV-2, со изразито висок титар над референтните вредности.