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Objective. After the beginning of the COVID-19 pandemic caused by the SARS-CoV -2 virus, enormous pressure fell on the entire health system. Since there is no adequate cure for this disease, "off-label" use of several drugs (azithromycin, chloroquine, hydroxychloroquine, etc.) was resorted to. The aim of this study was to analyse QTc interval dynamics and its relationship with other factors which could influence outcome in patients with COVID-19. Methods. Study has observational, case-control design with retrospective data collection from medical files of adult patients, with RT-PCR confirmed COVID-19. The cases (n=30) were subjects with fatal outcome and the controls (n=169) were the survivors. The QTc interval was calculated on admission, during and after initial drug treatments with presumed activity against SARS-CoV-2, mostly antimalarials. Primary independent and outcome variables were QTc interval prolongation and all-cause mortality, respectively. Results. Study population included 120 males (60.3%), the mean patients age was 57.3+-15.8 years (+-SD). The most common comorbid illnesses were hypertension (98 patients), pre-existing arrhythmias (32) and diabetes mellitus (29). The most frequently prescribed QTc prolonging drugs were azithromycin (69.8% of patients), chloroquine (50.3%) and hydroxychloroquine (42.7%). Total of 131 patients (65.8%) had QTc interval increase >60 ms from baseline, of whom 5 had QTc prolongation >500 ms (2.5%). De novo ventricular tachyarrhythmias were registered at 14 patients (7%) and 13 (92.8%) of them died. Pre-existing arrhythmias (odds ratio 9.30, 95% confidence interval 2.91-29.73, p480 ms) did not (1.02, 0.22-4.67, p=0.974). Case fatality rate was 15.1%, as 30 patients died during hospitalization. Conclusion. Clinical importance of drug-induced QTc interval prolongation of hospitalized patients with COVID-19 should be considered primarily within the context of other risks, particularly older age, pre-existing cardiovascular disorders and major electrolyte disturbances.

The Special Hospital for Addiction Diseases (SBBZ) received the status of a secondary level health care institution and reference center for addiction diseases in 2007. The turning points in the development of the pharmacy service in SBBZ in the previous 60 years are presented, by applying the method of historical analysis for the period from 1958 until today. The dispensary for the treatment of alcoholics and the fight against alcoholism was founded in 1958 in Belgrade, and a hospital pharmacy within the Clinical Department for Alcoholism started operating there. For the next four decades, it grew into the Institute for Alcoholism (1968), the Institute for Alcoholism and Drug Addiction in 1973, and in 1980 changed its name to the Institute for Addiction Diseases. This health institution is part of the OOUR Clinic for Psychiatry and Neurology (1987), which was one of the working organizations of the Clinical Hospital Center "Dr Dragisa Misovic-Dedinje". The Institute for Addiction Diseases was founded in 1992, separated from the KBC and has been operating as the SBBZ since 2007 (1). With the independence of the hospital, the hospital pharmacy organizationally belonged to the laboratory and the hospital pharmaceutical activity was performed by only one pharmacist (2). It can be concluded that the transformation of the health institution had little impact on the work of the hospital pharmacy service because at all turning points there was always a pharmacist as the only professional, a holder of a job in a hospital pharmacy. Specijalna bolnica za bolesti zavisnosti (SBBZ) dobija status ustanove sekundarnog nivoa zdravstvene zaštite i referentnog centra za bolesti zavisnosti 2007. godine. Obavlja delatnosti iz oblasti: psihijatrije, neurologije, interne medicine, biohemijsko-toksikološke dijagnostike, farmaceutske delatnosti, psihologije, specijalne pedagogije, socijalne zaštite. Prikazane su prelomne tačke u razvoju apotekarske službe u SBBZ u prethodnih 60 godina, primenom metode istorijske analize za period od 1958.godine do danas. Dispanzer za lečenje alkoholičara i borbu protiv alkoholizma osnovan je 1958. godine u Beogradu i u njemu počinje sa radom bolnička apoteka u sklopu Kliničkog odeljenja za alkoholizam. Narednih četiri decenije prerasta u Institut za alkoholizam (1968. god.), “Institut za alkoholizam i narkomaniju” 1973. godine, a 1980. godine menja naziv u Zavod za bolesti zavisnosti. Ova zdravstvena ustanova ulazi u sastav OOUR-a Klinika za psihijatriju i neurologiju (1987.god.), koja je bila jedna od radnih organizacija Kliničko-bolničkog centra “Dr Dragiša Mišović- Dedinje”. Zavod za bolesti zavisnosti je osnovan 1992. godine, izdvojio se iz KBC i od 2007. godine radi kao SBBZ (1). Osamostaljivanjem bolnice, bolnička apoteka je organizaciono pripala laboratoriji i bolničku farmaceutsku delatnost je obavljao samo jedan farmaceut (2). Broj zaposlenih se menjao ali ne u srazmeri sa obimom poslova u bolničkoj apoteci, da bi mnogo kasnije, 2020. godine bolnička apoteka postala izdvojena, samostalna organizaciona jedinica sa zaposlenim 1 specijalistom farmacije i 1 farmaceutskim tehničarom. Može se zaključiti da je transformacija zdravstvene ustanove imala malog uticaja na rad bolničke apotekarske službe jer je u svim prelomnim tačkama uvek postojao farmaceut kao jedino stručno lice, nosilac poslova u bolničkoj apoteci. VIII Kongres farmaceuta Srbije sa međunarodnim učešćem, 12-15.10.2022. Beograd

The use of artificial intelligence, especially machine learning methods in creating models that will be applied in clinical practice has reached its peak with the appearance of the COVID-19 pandemic. This study aims to determine the severity of the clinical condition of COVID-19 patients based on blood marker analysis. The study used data from 60 COVID- 19 patients treated at the Clinical Center Kragujevac. The research methodology includes the selection of the most important laboratory parameters as well as the classification of patients depending on them using methods of supervised learning, regression and classification. With an accuracy of 90%, three parameters were selected that can mostly indicate the severity of the patient's condition, which are: lactate dehydrogenase (LDH), C-reactive protein (CRP), white blood cells (WBC). Laboratory biomarkers such as LDH, CRP and WBC may have an impact on predicting outcomes and help classify patients into an appropriate group based on symptoms.

4. kongres socijalne medicine Srbije sa međunarodnim ućešćem, 2-3.12.2021.

Progresija od inflamacijske bolesti creva do kolorektalnog karcinoma je višestepeni proces, koji uključuje alteraciju tumor-supresorskih gena, kao što su r53 i r16. Cilj ove studije bio je da ispita obrasce ekspresije r16, r53 i VEGF u ciljanom tkivu, kao i serumske vrednosti citokina (TNF-α, TGF-β, IL-4, IL-6, IL-10, IL-17, IL-27 i IFN-γ) i tumorskih markera (AFP, CA 19-9, CEA) kod ispitanika sa inflamacijskom bolešću creva i kolorektalnim karcinomom. Serumske vrednosti citokina kod ispitanika sa ulceroznim kolitisom (n=24), Kronovom bolešću (n=5) i kolorektalnim karcinomom (n=75), kao i zdravih kontrola (n=37) analizirane su ELISA tehnikom. Endoskopske biopsije uzoraka ciljanog tkiva (ulcerozni kolitis, Kronova bolest, kolorektalni karcinom) analizirane su imunohistohemijskim bojenjem na r16, r53 i VEGF. Ispitanici sa ulceroznim kolitisom i postojanjam ekstraintestinalnih manifestacija, komplikacija i pozitivne ekspresije r16, r53 i VEGF (pojedinačno) imali su više serumske vrednosti proinflamatornih citokina. Značajno veći procenat ispitanika sa kolorektalnim karcinomom imao je pozitivnu ekspresiju r16, r53 i VEGF, u odnosu na ispitanike sa inflamacijskom bolešću creva. Ispitanici sa kolorektalnim karcinomom i pozitivnom ekspresijom VEGF imali su snižene sistemske vrednosti proinflamatornog citokina IFN-γ i povišene vrednosti imunosupresivnog citokina IL-10. Relativno niske vrednosti IL-10 kod ispitanika. Progression from ulcerative colitis (UC) toward colorectal carcinoma (CRC) is multistep process that includes gene alterations of tumor suppressor genes, such as p53 and p16. The aim of this study was to investigate the expression patterns of p16, p53 and VEGF in affected tissue and serum levels of cytokines TNF-α, IFN-γ, IL-4, IL-6, IL-10 and IL-17 in patients with UC and CRC, respectively. Serum levels of cytokine in patients with UC (n=24) and CRC (n=75) and in a healthy group (n=37) were analyzed by ELISA. Endoscopic biopsies specimens of UC and CRC were studied by immunohistochemical staining for p16, p53 and VEGF. Patients with UC with presence of extraintestinal manifestations, complications, and positive staining of p16, p53 and VEGF respectively had higher serum levels of pro-inflammatory cytokines. Higher percentage of CRC patients had positive staining of p16, p53 and VEGF. CRC patients with positive staining of VEGF had decreased systemic values of proinflammatory IFN-γ and increased values of immunosuppressive IL-10. Relatively low IL-10 in patients with severe UC is insufficient to compensate IL-6 secretion and subsequently enhanced type 1/17 immune response. In UC patients, p16 and p53 induce enhanced VEGF expression and subsequent production of pro-inflammatory TNF-α and IL-6. In CRC patients VEGF seems to have immunosuppressive role. It appears that tumor suppressor gene-VEGF axis have dual role on immune response in inflammation of UC and tumor growth and progression of CRC.

Cilj rada je korelativna analiza imunohistohemijske ekspresije Stathmina 1, Ki67, Ecadherina, Bcl-2 i p53 u intestinalnom i difuznom karcinomu želuca sa klasičnim prognostičkim parametrima tumora. Korišćen je biopsijski operativni materijal Hirurške klinike KBC Zemun. Prvu ispitivanu grupu (n =45) su činile operativne biopsije sa intestinalnim adenokarcinomom želuca, a drugu (n =45) su činile operativne biopsije difuznog adenokarcinoma želuca. Kontrolnu grupu obje ispitivane grupe, predstavljaju operativne biopsije netumorskog tkiva želuca, iz okoline tumora. Nakon rutinske obrade tkiva i kalupljenja u parafin, na presjecima debljine 4μm su primjenjene klasična HE i imunohistohemijska ABC metoda sa anti – Stathmin 1, Ki67, E-cadherin, p53 i Bcl-2 antitijelima . U intestinalnom adenokarcinomu ni jedan od ispitivanih onkoproteina ne zavisi od pola i lokalizacije tumora. Stathmin 1 je u značajnoj vezi sa ekspresijom p53 i invazijom krvnih sudova. Ekspresija p53 je značajno povezana sa starosnom dobi i histološkim gradusom, a ekspresija Ki67 je u značajnoj vezi sa ekspresijom Bcl-2, histološkim gradusom, invazijom limfnih sudova, pT statusom, metastazama u limfnim čvorovima i stadijumom tumorske bolesti. E-cadherin je u značajnoj inverznoj korelaciji sa ekspresijom Bcl-2, invazijom limfnih i krvnih sudova, metastazama u limfnim čvorovima, udaljenim metastazama i stadijumom tumorske bolesti. Bcl-2 je značajno povezan sa makroskopskim tipom tumora, histološkim gradusom, invazijom limfnih i krvnih sudova, metastazama u limfnim čvorovima i stadijumom bolesti. U difuznom adenokarcinomu je Stathmin 1 povezan visokim koeficijentima korelacije sa ekspresijom Ki67, p53, E-cadherin, Bcl-2, histološkim gradusom, invazijom limfnih i krvnih sudova, metastazama u limfnim čvorovima, udaljenim metastazama, pT statusom i stadijumom bolesti. ROC analiza je pokazala da senzitivnost za Stathmin 1, za difuzni adenokarcinom iznosi 72.9%, a specifičnost 67.6%, dok je senzitivnost za Ki67 66.7%, a specifičnost 65.6%. U difuznom adenokarcinomu je porast indeksa ekspresije Stathmina 1 praćen povećanim proliferativnim indeksom, redukcijom ćelijske adhezije, redukcijom apoptoze i porastom metastatskog potencijala, zbog čega ovaj onkoprotein može biti atratkivna terapijska meta u ciljanoj terapiji ovog tipa karcinoma želuca. Comparative analysis of immunohistochemical expression of Stathmin 1, Ki67, Ecadherin, p53 and Bcl2 in intestinal and diffuse gastric cancer. The aim of this study was to correlate the immunohistochemical expression of Stathmin 1, Ki67, E-cadherin, Bcl-2 and p53 in intestinal and diffuse gastric cancer with classical tumor prognostic parameters. Biopsy operative material from the Surgical Clinic of KBC Zemun was used. The first examined group (n = 45) consisted of operative biopsies with intestinal gastric adenocarcinoma, and the second (n = 45) consisted of operative biopsies of diffuse gastric adenocarcinoma. The control group of both the first (n = 45) and second (n = 45) examined groups are operative biopsies of adjacent non-tumor gastric tissue. After routine tissue processing and paraffin molding, classical HE and immunohistochemical ABC methods with anti - Stathmin 1, Ki67, Ecadherin, p53 and Bcl-2 antibodies were applied on 4μm thick sections. In intestinal adenocarcinoma, none of the examined oncoproteins depends on the sex and localization of the tumor. Stathmin 1 is significantly associated with p53 expression and vascular invasion. P53 expression is significantly associated with age and histological grade, and Ki67 expression is significantly associated with Bcl-2 expression, histological grade, lymph vessel invasion, pT status, lymph node metastases, and disease stage. E-cadherin is significantly inversely correlated with Bcl-2 expression, lymph and blood vessel invasion, lymph node metastases, distant metastases, and disease stage. Bcl-2 is significantly associated with macroscopic tumor type, histological grade, lymph and blood vessel invasion, lymph node metastases, and disease stage. In diffuse adenocarcinoma, Stathmin 1 is associated with high correlation coefficients with the expression of Ki67, p53, E-cadherin, Bcl-2, histological grade, lymph and blood vessel invasion, lymph node metastases, distant metastases, pT status and stage. ROC analysis showed that the sensitivity for Stathmin 1, for diffuse adenocarcinoma is 72.9% and the specificity is 67.6%, while the sensitivity for Ki67 is 66.7% and the specificity is 65.6%. In diffuse adenocarcinoma, the increase in Stathmin 1 expression index is accompanied by increased proliferative index, reduction of cell adhesion, reduction of apoptosis and increase of metastatic potential, due to which this oncoprotein can be an attractive therapeutic target in targeted therapy of this type of gastric cancer.

Uvod Prema podacima Svetske zdravstvene organizacije i bazi podataka GLOBOCAN, kolorektalni karcinom (KRK) je treći karcinom po učestalosti kod muškaraca a drugi kod žena, i drugi karcinom po smrtnosti u svetu. Oko 70% obolelih biva dijagnostikovano sa lokalizovanom bolešću i potom radikalno operisano. Nažalost, kod oko 1/3 ovih pacijenata se javlja relaps bolesti, a 73% njih umre. Zbog toga je pojava relapsa jedan od najvažnijih faktora preživljavanja obolelih od KRK. Uprkos opsežnom znanju o faktorima rizika za pojavu relapsa, ona se ne može u potpunosti predvideti. Sve je više dokaza da ekspresije ERα, ERβ i PR mogu biti faktori koji utiču na prognozu KRK. Postoje dokazi da je gubitak ekpresije ERβ u tumorskom tkivu povezan je sa višim stadijumima bolesti i predstavlja loš prognostički znak. Prisustvo ERα je otkriveno u debelom crevu najpre na nivou mRNK, ali su nedavne studije potvrdile i njegovu merljivu imunohistohemijsku ekspresiju i prognostiki potencijal. Istraživanja koja su se bavila ekpresijom i ulogom ciklina D1 u patogenezi i prognozi KRK dala su potpuno kontradiktorne rezultate. Prema nekim autorima. povećana ekspresija ciklina D1 je dobar, a prema drugima loš prognostički znak. S druge strane, neki autori su pokazali da se prognostička vrednost ovog markera razlikuje kod muškaraca i žena. Slično je i sa rezultatima studija koje su se bavile značajem ekspresije Bcl-2 u prognozi KRK-a. Neki autori sugerišu da je visoka ekspresija Bcl-2 povezana sa povoljnom prognozom kod pacijenata sa KRK iz Evrope i Amerike, ali su razlike u ekspresiji bile povezane sa primenom neoadjuvantne terapije. Studije koje su ispitivale ekspresiju gore pomenutih markera na tkivu KRK dale su kontradiktorne rezultate u pogledu velikih varijacija nivoa ekspresije i korelacije sa kliničkim ishodom. Cilj naše studije je bio da ispita nivoe ekspresije ERα, ERβ, PR, ciklina D1 i Bcl-2 na tkivu KRK u "visoko rizičnom" Dukes B i Dukes C stadijumu i utvrdi da li postoji njihova korelacija sa ranim relapsom KRK u periodu od dve godine nakon radikalnog hirurškog lečenja. Materijali i metode Dizajn studije i populacija koja se istražuje Ova retrospektivna studija obuhvatila je 101 pacijenta sa dijagnozom kolorektalnog karcinoma. U studiju su bili uključeni pacijenti sa potvrđenim Dukes C i „visoko rizičnom“ Dukes B stadijumom (stadijum pT4 i/ili N2; slabo diferencirani tumor; perforacija; limfovaskularna invazija; perineuralna invazija; 50% bila je statistički češća u grupi DFS ≤ 24 nego u grupi DFS ≥ 48 (p = 0.021). Nivoi hemoglobina bili su slični među grupama. CRP je bio značajno veći u grupi sa DFS ≤ 24 (p < 0.001). Nije bilo razlike u NLR i PLR između grupa. Nivo albumina bio je značajno veći u grupi DFS ≥ 48. Pacijenti sa ekspresijom ciklina D1 > 50% su imali 5.2 a sa odmaklim T stadijumom 11.3 puta veću šansu da imaju relaps u toku prve dve godine od radikalne operacije. Umerena ekspresija ERβ je bila udružena sa 79.2% manjom šansom za pojavu relapsa u ovom periodu. Povišene vrednosti CRP, iznad referentnih, bile su udružene sa 5.9 puta većom šansom za kraće vreme do pojave relapsa. Zaključak Pojava ranog relapsa KRK u prve dve godine nakon radikalnog operativnog lečenja u "visoko rizičnom" Dukes B i Dukes C stadijumu povezana je sa smanjenom ekspresijom ERβ i visokom ekspresijom ciklina D1. Ekspresija ERα, PR i Bcl-2 na tkivu kolorektalnog karcinoma nije u korelaciji sa ranim relapsima. Rezultati naše studije ukazuju su povećana ekspresija ciklina D1 i smanjena ekspresija ERβ pokazatelji loše prognoze obolelih od kolorektalnog karcinoma, posebno kod pacijenata sa uznapredovalim T stadijumom. Stoga bi se ciklin D1 i ERβ mogli smatrati značajnim, nezavisnim prognostičkim faktorima za pacijente obolele od ove bolesti i potencijalnim terapijskim metama. Ključne reči: kolorektalni karcinom, relaps, ERα, ERβ, PR, ciklin D1, Bcl-2 Introduction According to the World Health Organization and the GLOBOCAN database, colorectal cancer (CRC) is the third most common cancer in men and the second in women. It is the second most deadly cancer worldwide. About 70% of the patients undergo surgery with curative intent. Unfortunately, around 1/3 of these patients experience disease recurrence, and approximately 73% of them die. Therefore, CRC recurrence is one of the most important factors influencing patient survival. Despite the extensive knowledge about the risk factors for CRC recurrence, its occurrence cannot be fully predicted. There has been growing evidence that the expression of ERα and ERβ, as well as PR, may be factors that influence CRC prognosis. The loss of ERβ expression in tumor tissue is associated with advanced cancer stages and is a poor prognostic sign. ERα was found in the colon at the mRNA level, but recent studies also confirm its measurable immunohistochemical expression and prognostic potential. Researches that have addressed the role of cyclin D1 in the pathogenesis of CRC and its value as a prognostic marker has yielded entirely contradictory results. According to some authors, increased cyclin D1 expression is a good, and according to others, a poor prognostic sign. On the other hand, some authors showed that this marker's prognostic value differs between men and women. The similar is with the results of studies on the importance of Bcl-2 expression in CRC prognosis. Some of them suggest that high expression of Bcl-2 is associated with favorable prognosis in CRC patients from Europe and America, but differences in expression depended on neoadjuvant therapy. The studies examining the expression of the receptors mentioned above on CRC tissue are contradictory in terms of large variations in expression levels and correlations with the clinical outcome. This study aimed to examine the expression levels of ERα, ERβ, PR, Cyclin D1 and Bcl2 on the tissue of CRC in "high risk" Dukes’ B and Dukes’ C stages and determine whether the expression correlates with early CRC recurrence within two years after surgery. Material and methods Study design and study population This retrospective study included 101 patients diagnosed with colorectal cancer in Dukes’ C and "high-risk" Dukes’ B stages (stage pT4 and/or N2; a poorly differentiated tumor; perforation; lymphovascular invasion; perineural invasion; 50% was statistically more often in DFS ≤ 24 group than in the DFS ≥ 48 group (p = 0.021). Levels of hemoglobin were similar between groups. CRP was significantly higher in the DFS ≤ 24 group (p < 0.001). There was no difference in NLR and PLR between groups. The level of albumins was significantly higher in the DFS ≥ 48 group. Patients with an expression of cyclin D1 > 50% had 5.2, and an advanced T stadium had 11, 3 times higher odds of having a DFS ≤ 24 months. Moderate expression of ERβ was joined with 79.2 % smaller odds for DFS ≤ 24 months. Higher levels of CRP (above referent range) were joined with 5,9 higher odds for DFS ≤ 24 months. Conclusion The occurrence of early relapse of CRC in the first two years after radical surgical treatment in the “high-risk” Dukes’ B and Dukes’ C stages is associated with decreased ERβ expression and high cyclin D1 expression. The expression of ERα, PR, and Bcl-2 on colorectal cancer tissue is not correlated with early recurrences. Our findings indicate the increased expression of cyclin D1 and reduced expression of ERβ are indicators of poor prognosis in CRC, especially in patients with advanced T stage. Therefore, cyclin D1 and ERβ may be considered significant, independent prognostic factors in CRC patients and possible therapeutic targets.

U studiji su ispitivane sistemske koncentracije imunomodulacijskih proteina/interleukina i kliničko-patohistološke karakteristike bolesti i povezane su sa anemijom/trombocitozom kod obolelih od kolorektalnog karcinoma (CRC). Ispitanici sa CRC-om, su razvrstani u grupu sa anemijom, odnosno sa trombocitozom (eksperimentalne grupe) i grupu bez anemije, odnosno bez trombocitoze (kontrolne grupe). U ovako determinisanim skupovima ispitanika analizirane su kliničke (kompletna krvna slika sa brojem krvnih ćelija, vrednost hemoglobina, preocena aktivnosti bolesti, kompletan radiološki pregled, prisustvo komplikacija i pojava bolesti van gastrointestinalnog trakta) i patohistološke karakteristike bolesti (tip tumora, nuklearni i histološki gradus, TNM klasifikacija), kao i koncentracija citokina i imunomodulacijskih proteina (IL-1, IL-4, IL-10, IL-17, IL-33, galektina-1, galektina-3, TNF-α i INF-γ) i biohemijskih belega maligne bolesti (AFP,.CEA,.CA.19-9) u serumu bolesnika. Bolesnici sa CRCom i anemijom, odnosno trombocitozom imaju teži kliničko-patohistološki oblik bolesti (viši nuklearni i histološki gradus tumora, veći stepen invazije limfnih i krvnih sudova, viši TNM stadijum bolesti, više otkrivenih metastaza u plućima, jetri ili peritoneumu), u poređenju sa bolesnicima sa CRC-om bez anemije, odnosno bez trombocitoze. Takođe, utvrđena je pozitivna korelacija anemije, odnosno trombocitoze i sistemskih vrednosti interleukina, imunomodulacijskih proteina i biohemijskih belega maligne bolesti (AFP,.CEA,.CA.19-9) uhserumu bolesnika. Postoji pozitivna korelacija između sistemskih vrednosti imunomodulacijskih proteina i težeg kliničko-patohistološkog oblika bolesti, u odnosu na prisustvo anemije, odnosno trombocitoze kod bolesnika sa kolorektalnim karcinomom. We investigated systemic concentrations of immunomodulatory proteins/interleukins, as well as clinical and histopathological characteristics of the disease and correlated them with anemia/thrombocytosis in patients with colorectal cancer (CRC). The study included patients with colorectal cancer, divided into a group with anemia and a group with thrombocytosis (experimental groups) and a group without anemia, or without thrombocytosis (control groups). In such determined groups, clinical (complete blood count with blood cell count, hemoglobin value, disease activity, complete radiological examination, complications and occurrence of diseases outside the gastrointestinal tract) and pathohistological characteristics of the disease (tumor type, nuclear and histologic grade, TNM classification), as well as concentrations of cytokines and immunomodulatory proteins (IL-1, IL-4, IL-10, IL-17, IL-33, galectin-1, galectin-3, TNF-α and INF-γ) and biochemical indicators of malignant disease (AFP,.CEA,.CA.19-9) in the patients’ serum were analyzed. Patients with CRC and anemia/thrombocytosis, have a more severe clinical-pathohistological form of the disease (higher nuclear and histological grade of tumor, higher lymph and blood vessels invasion, higher TNM stage of the disease, more detectable lung, liver or peritoneum metastasis) compared to CRC patients without anemia or thrombocytosis. Moreover, a positive correlation between anemia/thrombocytosis, and cytokines, AFP,.CEA and.CA.19-9 values in the patients’ serum was determined. There is a positive correlation between the systemic values of immunomodulatory proteins and severe clinical-pathohistological form of the disease, based on the presence of anemia or thrombocytosis in CRC patients.

Ulcerozni kolitis (engl. Ulcerative colitis- UC) je hronično oboljenje koje karakteriše zapaljenje sluznice digestivnog trakta, prvenstveno debelog creva. Metabolički sindrom je čest poremećaj značajno povezan sa UC. Veliki broj studija je pokazao značajan komorbiditet ovih poremećaja i njihovu genetsku povezanost. Cilj studije bio je da se ispita povezanost razvojnih faza metaboličkog sindroma sa težinom bolesti, te lokalnim i sistemskim imunskim odgovorom kod pacijenata sa ulceroznim kolitisom. Kod ispitanika sa ulceroznim kolitisom i metaboličkim sindromom zabeležena je klinički i patohistološki blaža bolest sa sistemskom i lokalnom predominacijom galektina 1, galektina 3 i imunosupresivnog citokina IL-10, uz sniženu koncentraciju proinflamacijskih citokina TNF-α, IL-6 i IL-17. Takođe je registrovana manja zastupljenost CD8+ T limfocita, a veća zastupljenost regulatornih CD4+Foxp3+ limfocita, kao i veća ekspresija galektina-3 na limfocitima i veća produkcija imunosupresivnog IL-10 u lamina propria-i obolelih od ulceroznog kolitisa sa metaboličkim sindromom. Kod ispitanika u terminalnoj fazi metaboličkog sindomoma zabeležena je klinički i patohistološki teža forma ulceroznog kolitisa. U ovoj grupi ispitanika nađena je sistemska i lokalna predominacija proinflamacijskih citokina TNF-α, IL-6 i IL-17 nad galektinom-1, galektina-3 nad proinflamacijskim medijatorima TNF-α i IL-17 kao i povećana ekspresija galektina-3 na imunokompetentnim ćelijama koje infiltrišu lamina propria-u. Lokalna i sistemska predominacija Gal-1 i Gal-3 nad proinflamacijskim citokinima kod obolelih sa metaboličkim sindromom može predstavljati mehanizam zaustavljanja i ograničavanja proinflamacijskog procesa i sprečiti oštećenje tkiva, ukazujući na imunosupresivnu ulogu Gal-1 i Gal-3 u biologiji ulceroznog kolitisa kod bolesnika sa metaboličkim sindromom. Sistemska i lokalna predominacija proinflamacijskih citokina TNF-α, IL-6 i IL-17 nad Gal-1 i Gal-3 u terminalnoj fazi metaboličkog sindroma pojačava zapaljenje i sledstveno oštećenje tkiva. Ulcerative colitis (UC) is a chronic disease characterized by inflammation of intestinal epithelium, primarily of the colon. Metabolic syndrome is a common disorder significantly associated with UC. A large number of studies have shown significant comorbidity of these disorders and their genetic linkage. The aim of the study was to examine the relationship between the developmental stages of the metabolic syndrome with the severity of the disease, and the local and systemic immune response in patients with ulcerative colitis. Clinical and pathohystologically mild disease with systemic and local prevalence of galectin 1, galectin 3 and immunosuppressive cytokine IL-10 was observed in subjects with ulcerative colitis and metabolic syndrome, with reduced concentration of proinflammatory cytokines TNF-α, IL-6, and IL-17. Further, we detected lower incidence of CD8+ T lymphocytes and enhanced accumulation of regulatory CD4+ Foxp3+ T cells, as well as increased expression of galectin-3 on lymphocytes and higher production of immunosuppressive IL-10 in lamina propria derived from UC patients with metabolic syndrome. Clinical and pathohystologically severe disease was observed in the patients with terminal phase of the metabolic syndrome. In this group of subjects, we found systemic and local prevalence of proinflammatory cytokines TNF-α, IL-6, and IL-17 over galectin-1; galectin-3 over TNF-α and IL-17; as well as increased expression of galectin-3 on immunocompetent cells infiltrating the lamina propria. Local and systemic dominance of Gal-1 and Gal-3 over proinflammatory cytokines in patients with metabolic syndrome may present a mechanism for stopping and limiting the proinflammatory process and preventing tissue damage, indicating the immunosuppressive role of Gal-1 and Gal-3 in the ulcerative colitis biology of patients with metabolic syndrome. Systemic and local prevalence of proinflammatory cytokines TNF-α, IL-6, and IL-17 over Gal-1 and Gal-3 in the terminal phase of the metabolic syndrome enhances inflammation and consequent tissue damage.

Pacijenti koji su inficirani virusom humane imunodeficijencije (HIV), tokom svoje bolesti, imaju različite gastrointestinalne simptome koji uključuju i dispepsiju. Gastrointestinalni simptomi mogu biti posledica dejstva samog HIV-a, različitih oportunističkih i ne-oportunističkih infekcija uključujući i infekciju sa Helicobacter pylori (H. pylori), kao i negativne efekte visoko aktivne antiretrovirusne terapije (HAART). H. pylori ima glavnu ulogu u patogenezi hroničnog gastritisa, peptičke ulkusne bolesti, karcinoma želuca, MALT limfoma i nekoliko ekstra-gastričnih manifestacija. Ona je jedan od najznačajnijih bakterijskih patogena u opštoj populaciji, a prevalencija ove infekcije se procenjuje na više od 50% u svetskoj populaciji. Faktori rizika i putevi prenosa ove infekcije su još uvek nedovoljno jasni. Prevalencija H. pylori infekcije kod ljudi koji su inficirani HIV-om (PLHIV) varira od 10 do 76%, zavisno od vremenskog perioda kada je rađeno istraživanje, geografske lokalizacije i populacije. Studije koje su rađene ranije, prijavile su nižu prevalenciju ove koinfekcije kod PLHIV u poređenju sa HIV negativnim kontrolama, suprotno novijim podacima, u modernoj - sadašnjoj HAART eri, u kojoj se prevalenija H. pylori infekcije kod PLHIV približava prevalenciji koja postoji u opštoj populaciji. Cilj: Procena učestalosti H. pylori infekcije u populaciji HIV-om inficiranih u odnosu na kontrolnu grupu sa H. pylori monoinfekcijom, povezanosti imunskog statusa sa dispeptičnim simptomima, endoskopskim i patohistološkim nalazima sluznica želuca i dvanaestopalačnog creva, zatim procena uticaja antiretrovirusne terapije (ART) na učestalost H. pylori koinfekcije i patohistološki nalaz sluznice želuca i ispitivanje faktora rizika za H. pylori infekciju kod inficiranih HIV-om u odnosu na kontrolnu grupu. Materijali i metode: Istraživanje je sprovedeno kao studija slučajeva i kontrola u periodu od 01.01.1993. godine do 31.12.2015. godine u Beogradskoj Klinici za infektivne i tropske bolesti Kliničkog centra Srbije... People living with HIV infection (PLHIV), during their lifetime of illness, suffer from a variety of gastrointestinal (GI) symptoms, including dyspepsia. GI symptoms may occur due to HIV itself, adverse effects of highly active antiretroviral therapy (HAART), or due to a variety of opportunistic and non – opportunistic infections. H. pylori has a key role in pathogenesis of chronic gastritis, peptic ulcer disease, gastric cancer, MALT lymphoma and a few extra - gastric manifestations. It’s one of the most important bacterial pathogens in the general population worldwide, with the estimated prevalence of more than 50%. The risk factors and transmission pathways for this infection have not yet been fully clarified. The prevalence of H. pylori infection in PLHIV varies between 10 and 76%, depending on the period in which different research was conducted, geographical position and population. Research that was done earlier reported lower prevalence of H. pylori and HIV co-infection compared to HIV negative control groups, contrary to newer data in modern HAART era, in which the prevalence of H. pylori infection in PLHIV approaches the prevalence in general population. Goal: Estimating the frequency of H. pylori co-infection in PLHIV compared to control group, assessing the correlation between immune status and dyspeptic symptoms, endoscopic and pathohistological findings of ventricular and duodenal mucous membranes, estimating effects of HAART on the frequency of H. pylori and HIV co-infection and pathohistological findings of ventricular mucous membrane and revealing the risk factors for H. pylori and HIV co-infection in comparison to the control group. Methods: This case – control study was conducted for the period between 1st January 1993 and 31st December 2015 at University Hospital for Infectious and Tropical Diseases, Clinical Centre of Serbia, Belgrade. The study included all the patients who were, for the aforecited period of time, due to dyspeptic symptoms, subjected to esophagogastroduodenoscopy (EGDS) with gastric and duodenal tissue biopsy and histological examination of sampled material...