Function of s100 protein in coronary atherosclerosis / Función de la proteína s100 en aterosclerosis coronaria

SUMMARY: Atherosclerosis is a complex disease whose pathogenesis includes endothelial activation, accumulation of lipids in the subendothelium, formation of foam cells, fat bands and formation of atherosclerotic plaque. These complex mechanisms involve different cell populations in the intimate sub-endothelium, and the S-100 protein family plays a role in a number of extracellular and intracellular processes during the development of atherosclerotic lesions. The aim of this study was to determine the phenotypic characteristics of smooth muscle cells and the consequent expression of S100 protein in atherosclerotic altered coronary arteries in advanced stages of atherosclerosis. 19 samples of right atherosclerotic coronary arteries in stages of fibro atheroma (type V lesion) and complicated lesions (type VI lesion) have been analyzed. According to the standard protocol, the following primary antibodies have been used in the immunohistochemical analysis: a-smooth muscle actin (α-SMA), vimentin and S-100 protein. All analyzed samples have been in advanced stages of atherosclerosis, fibro atheroma (stage V lesions) and complicated lesions (type VI lesions). Most of them have had the structure of a complicated lesion with atheroma or fibro atheroma as a basis, subsequently complicated by disruption (subtype VI a), hemorrhage (subtype VI b) or thrombosis (subtype VI c), as well as by the presence of several complications on the same sample. Marked hypocellularity is present in the subendothelium of plaques. Cell population at plaque margins is characterized by immunoreactivity to α-SMA, vimentin, and S100 protein. Some of these cells accumulate lipids and look like foam cells. In the cell population at the margins of the plaques, smooth muscle cells of the synthetic phenotype are present, some of which accumulate lipids and demonstrate S100 immunoreactivity. Summarizing numerous literature data and our results, we could assume that smooth muscle cells, due to their synthetic and proliferative activity in the earlier stages of pathogenesis, as well as the consequent expression of S100 protein, could accumulate lipids in the earlier stages of atherosclerosis which, in advanced stages analyzed in this study, result in immunoreactivity of foam cells of smooth muscle origin to S100 protein.

RESUMEN: La aterosclerosis es una enfermedad compleja cuya patogenia incluye activación endotelial, acumulación de lípidos en el subendotelio, formación de células espumosas, bandas grasas y formación de placa aterosclerótica. Estos complejos mecanismos involucran diferentes poblaciones celulares en el subendotelio íntimo, y la familia de proteínas S-100 juega un papel en varios procesos extracelulares e intracelulares durante el desarrollo de lesiones ateroscleróticas. El objetivo de este estudio fue determinar las características fenotípicas de las células de músculo liso y la consecuente expresión de la proteína S100 en arterias coronarias alteradas ateroscleróticas en estadios avanzados de aterosclerosis. Se analizaron 19 muestras de arterias coronarias ateroscleróticas derechas en estadios de fibroateroma (lesión tipo V) y lesiones complicadas (lesión tipo VI). Según el protocolo estándar, en el análisis inmunohistoquímico se utilizaron los siguientes anticuerpos primarios: α-actina de músculo liso (α-SMA), vimentina y proteína S-100. Todas las muestras analizadas han estado en estadios avanzados de aterosclerosis, fibroateroma (lesiones estadio V) y lesiones complicadas (lesiones tipo VI). La mayoría de ellos han tenido la estructura de una lesión complicada con ateroma o fibroateroma como base, complicada posteriormente por disrupción (subtipo VI a), hemorragia (subtipo VI b) o trombosis (subtipo VI c), así como por la presencia de varias complicaciones en la misma muestra. La hipocelularidad marcada estaba presente en el subendotelio de las placas. La población celular en los márgenes de la placa se caracterizaba por inmunorreactividad a α-SMA, vimentina y proteína S100. Algunas de estas células acumulan lípidos y parecen células espumosas. En la población celular en los márgenes de las placas, estaban presentes las células de músculo liso de fenotipo sintético, algunas de las cuales acumulaban lípidos y mostraban inmunorreactividad S100. Resumiendo numerosos datos de la literatura y nuestros resultados, podríamos suponer que las células del músculo liso, debido a su actividad sintética y proliferativa en las primeras etapas de la patogénesis, así como la consecuente expresión de la proteína S100, podrían acumular lípidos en las primeras etapas de la aterosclerosis que, en estadios avanzados analizados en este estudio, dan como resultado inmunorreactividad de células espumosas de origen muscular liso a la proteína S100.

D-dimer, CRP, PCT, and IL-6 Levels at Admission to ICU Can Predict In-Hospital Mortality in Patients with COVID-19 Pneumonia.

INTRODUCTION: Health care workers have had a challenging task since the COVID-19 outbreak. Prompt and effective predictors of clinical outcomes are crucial to recognize potentially critically ill patients and improve the management of COVID-19 patients. The aim of this study was to identify potential predictors of clinical outcomes in critically ill COVID-19 patients. METHODS: The study was designed as a retrospective cohort study, which included 318 patients treated from June 2020 to January 2021 in the Intensive Care Unit (ICU) of the Clinical Hospital Center "Bezanijska Kosa" in Belgrade, Serbia. The verified diagnosis of COVID-19 disease, patients over 18 years of age, and the hospitalization in ICU were the criteria for inclusion in the study. The optimal cutoff value of D-dimer, CRP, IL-6, and PCT for predicting hospital mortality was determined using the ROC curve, while the Kaplan-Meier method and log-rank test were used to assess survival. RESULTS: The study included 318 patients: 219 (68.9%) were male and 99 (31.1%) female. The median age of patients was 69 (60-77) years. During the treatment, 195 (61.3%) patients died, thereof 130 male (66.7%) and 65 female (33.3%). 123 (38.7%) patients were discharged from hospital treatment. The cutoff value of IL-6 for in-hospital death prediction was 74.98 pg/mL (Sn 69.7%, Sp 62.7%); cutoff value of CRP was 81 mg/L (Sn 60.7%, Sp 60%); cutoff value of procalcitonin was 0.56 ng/mL (Sn 81.1%, Sp 76%); and cutoff value of D-dimer was 760 ng/mL FEU (Sn 63.4%, Sp 57.1%). IL-6 ≥ 74.98 pg/mL, CRP ≥ 81 mg/L, PCT ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL were statistically significant predictors of in-hospital mortality. CONCLUSION: IL-6 ≥ 74.98 pg/mL, CRP values ≥ 81 mg/L, procalcitonin ≥ 0.56 ng/mL, and D-dimer ≥ 760 ng/mL could effectively predict in-hospital mortality in COVID-19 patients.

Development and Validation of a Multivariable Predictive Model for Mortality of COVID-19 Patients Demanding High Oxygen Flow at Admission to ICU: AIDA Score.

INTRODUCTION: Risk stratification is an important aspect of COVID-19 management, especially in patients admitted to ICU as it can provide more useful consumption of health resources, as well as prioritize critical care services in situations of overwhelming number of patients. MATERIALS AND METHODS: A multivariable predictive model for mortality was developed using data solely from a derivation cohort of 160 COVID-19 patients with moderate to severe ARDS admitted to ICU. The regression coefficients from the final multivariate model of the derivation study were used to assign points for the risk model, consisted of all significant variables from the multivariate analysis and age as a known risk factor for COVID-19 patient mortality. The newly developed AIDA score was arrived at by assigning 5 points for serum albumin and 1 point for IL-6, D dimer, and age. The score was further validated on a cohort of 304 patients admitted to ICU due to the severe form of COVID-19. RESULTS: The study population included 160 COVID-19 patients admitted to ICU in the derivation and 304 in the validation cohort. The mean patient age was 66.7 years (range, 20-93 years), with 68.1% men and 31.9% women. Most patients (76.8%) had comorbidities with hypertension (67.7%), diabetes (31.7), and coronary artery disease (19.3) as the most frequent. A total of 316 patients (68.3%) were treated with mechanical ventilation. Ninety-six (60.0%) in the derivation cohort and 221 (72.7%) patients in the validation cohort had a lethal outcome. The population was divided into the following risk categories for mortality based on the risk model score: low risk (score 0-1) and at-risk (score > 1). In addition, patients were considered at high risk with a risk score > 2. By applying the risk model to the validation cohort (n = 304), the positive predictive value was 78.8% (95% CI 75.5% to 81.8%); the negative predictive value was 46.6% (95% CI 37.3% to 56.2%); the sensitivity was 82.4% (95% CI 76.7% to 87.1%), and the specificity was 41.0% (95% CI 30.3% to 52.3%). The C statistic was 0.863 (95% CI 0.805-0.921) and 0.665 (95% CI 0.598-0.732) in the derivation and validation cohorts, respectively, indicating a high discriminative value of the proposed score. CONCLUSION: In the present study, AIDA score showed a valuable significance in estimating the mortality risk in patients with the severe form of COVID-19 disease at admission to ICU. Further external validation on a larger group of patients is needed to provide more insights into the utility of this score in everyday practice.

Predictors of Mortality in Critically Ill COVID-19 Patients Demanding High Oxygen Flow: A Thin Line between Inflammation, Cytokine Storm, and Coagulopathy.

INTRODUCTION: Mortality among critically ill COVID-19 patients remains relatively high despite different potential therapeutic modalities being introduced recently. The treatment of critically ill patients is a challenging task, without identified credible predictors of mortality. METHODS: We performed an analysis of 160 consecutive patients with confirmed COVID-19 infection admitted to the Respiratory Intensive Care Unit between June 23, 2020, and October 2, 2020, in University Hospital Center Bezanijska kosa, Belgrade, Serbia. Patients on invasive, noninvasive ventilation and high flow oxygen therapy with moderate to severe ARDS, according to the Berlin definition of ARDS, were selected for the study. Demographic data, past medical history, laboratory values, and CT severity score were analyzed to identify predictors of mortality. Univariate and multivariate logistic regression models were used to assess potential predictors of mortality in critically ill COVID-19 patients. RESULTS: The mean patient age was 65.6 years (range, 29-92 years), predominantly men, 68.8%. 107 (66.9%) patients were on invasive mechanical ventilation, 31 (19.3%) on noninvasive, and 22 (13.8%) on high flow oxygen therapy machine. The median total number of ICU days was 10 (25th to 75th percentile: 6-18), while the median total number of hospital stay was 18 (25th to 75th percentile: 12-28). The mortality rate was 60% (96/160). Univariate logistic regression analysis confirmed the significance of age, CRP, and lymphocytes at admission to hospital, serum albumin, D-dimer, and IL-6 at admission to ICU, and CT score. Serum albumin, D-dimer, and IL-6 at admission to ICU were independently associated with mortality in the final multivariate analysis. CONCLUSION: In the present study of 160 consecutive critically ill COVID-19 patients with moderate to severe ARDS, IL-6, serum albumin, and D-dimer at admission to ICU, accompanied by chest CT severity score, were marked as independent predictors of mortality.

Disfunção de múltiplos órgãos causada por corpo estranho no esôfago / Multiple organ dysfunction caused by a foreign body in the esophagus

RESUMO Apresentamos o caso de uma paciente de 71 anos de idade admitida à unidade de terapia intensiva clínica em condição de falência de múltiplos órgãos. Após o quarto dia, com aplicação de todas as modalidades de suporte à vida (estímulo com vasopressores, ventilação mecânica, terapia com diálise contínua, terapia com antibióticos de amplo espectro e outras medidas de suporte), dados inespecíficos fornecidos por acompanhante revelaram que a paciente vinha apresentando dificuldade persistente para deglutir líquidos e alimentos sólidos por alguns dias antes da admissão ao hospital. Após a realização de procedimentos adicionais de diagnóstico radiológico e endoscópico, detectou-se a presença de um corpo estranho no esôfago: um fragmento de fio de aço com cerca de 6 cm de comprimento e dobrado ao meio, que havia penetrado a parede do esôfago e se projetava ao nível da sétima vértebra cervical. Conseguimos remover o corpo estranho por via endoscópica sem maiores complicações e, a seguir, estabilizar nossa paciente, com utilização de medidas terapêuticas adicionais, conforme necessário.

ABSTRACT We present the case of a 71-year-old patient who was admitted to the medical intensive care unit in a state of multiple organ dysfunction. After the fourth day of applying all needed life-saving measures (vasopressor stimulation, mechanical ventilation, continuous dialysis treatment, broad spectrum antibiotic therapy, and other supportive measures), nonspecific heteroanamnestic data revealed that the patient had been having a persistent difficulty in swallowing liquids and food for a few days prior to hospital admission. After performing additional radiological and endoscopic diagnostic procedures, a foreign body was detected; a steel wire that had a length of approximately 6cm and was bent in a half had penetrated the esophagus and was projected into the seventh neckline. We managed to evacuate the foreign body endoscopically without further complications, and we stabilized our patient using additional therapeutic measures as needed.

Multiple organ dysfunction caused by a foreign body in the esophagus. / Disfunção de múltiplos órgãos causada por corpo estranho no esôfago.

We present the case of a 71-year-old patient who was admitted to the medical intensive care unit in a state of multiple organ dysfunction. After the fourth day of applying all needed life-saving measures (vasopressor stimulation, mechanical ventilation, continuous dialysis treatment, broad spectrum antibiotic therapy, and other supportive measures), nonspecific heteroanamnestic data revealed that the patient had been having a persistent difficulty in swallowing liquids and food for a few days prior to hospital admission. After performing additional radiological and endoscopic diagnostic procedures, a foreign body was detected; a steel wire that had a length of approximately 6cm and was bent in a half had penetrated the esophagus and was projected into the seventh neckline. We managed to evacuate the foreign body endoscopically without further complications, and we stabilized our patient using additional therapeutic measures as needed.

Apresentamos o caso de uma paciente de 71 anos de idade admitida à unidade de terapia intensiva clínica em condição de falência de múltiplos órgãos. Após o quarto dia, com aplicação de todas as modalidades de suporte à vida (estímulo com vasopressores, ventilação mecânica, terapia com diálise contínua, terapia com antibióticos de amplo espectro e outras medidas de suporte), dados inespecíficos fornecidos por acompanhante revelaram que a paciente vinha apresentando dificuldade persistente para deglutir líquidos e alimentos sólidos por alguns dias antes da admissão ao hospital. Após a realização de procedimentos adicionais de diagnóstico radiológico e endoscópico, detectou-se a presença de um corpo estranho no esôfago: um fragmento de fio de aço com cerca de 6 cm de comprimento e dobrado ao meio, que havia penetrado a parede do esôfago e se projetava ao nível da sétima vértebra cervical. Conseguimos remover o corpo estranho por via endoscópica sem maiores complicações e, a seguir, estabilizar nossa paciente, com utilização de medidas terapêuticas adicionais, conforme necessário.

Histochemical, immunohistochemical and ultrastructural analysis of aortic wall in neonatal coarctation.

The neonatal type of coarctation is characterized by the presence of the ductal sling and coarctational shelf placed proximally in relation to the ductal orifice. Those morphological features are not described in detail yet from immunohistochemical and transmission electron microscopy (TEM) aspects, so the aim of this study was to investigate the smooth muscle cells (SMCs) phenotype in aortic intimal thickening, presence of inflammatory cells and contents of intimal and medial, and adventitial connective tissue. We examined samples of coarctation segments excised at surgery after end-to-end anastomosis from 30 patients, ages from 14 days to three months, histochemicaly, immunocytochemically and by TEM. In all samples, it is noticed focal intimal thickening on the posterior aortic wall, with accumulation of SMCs, which show immunoreactivity on alpha-smooth muscle actin (α-SMA) and vimentin (but not on desmin) and also expressed proliferating cell nuclear antigen (PCNA) and S-100 protein. At TEM analysis, those SMCs show a fibroblast-like morphology, so their functions could be to proliferate and secrete extracellular matrix (ECM) components (a synthetic phenotype). In all studied samples of the coarctation, on the posterior wall, the immunocytochemical and TEM examination revealed the presence of SMCs of the synthetic phenotype. Results also showed an increase of the cell number in intima of this part of aortic wall, followed by proliferated SMCs in inner media and absence of inflammatory cells. This finding suggests that proliferation of the SMCs, their synthetic activity and increase of the cell number could lead to formation of the intimal thickening on the posterior wall.

Matrix Metalloproteinase-9 and Tissue Inhibitor of Matrix Metalloproteinase-1 in Sepsis after Major Abdominal Surgery.

BACKGROUND: The role of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in sepsis after major abdominal surgery and sepsis-associated organ dysfunction is unexplored. MATERIALS AND METHODS: Fifty-three patients with sepsis after major abdominal surgery were compared to 50 operated and 50 nonoperated controls. MMP-9, TIMP-1, biomarkers of inflammation, kidney and liver injury, coagulation, and metabolic disorders were measured daily during 96 h following diagnosis of sepsis and once in controls. MMP-9/TIMP-1 ratios and disease severity scores were calculated. Use of vasopressors/inotropes, mechanical ventilation, and survival were recorded. RESULTS: Septic patients had lower MMP-9 and MMP-9/TIMP-1 ratios but higher TIMP-1 levels compared to controls. AUC-ROC for diagnosis of sepsis was 0.940 and 0.854 for TIMP-1 and 0.924 and 0.788 for MMP-9/TIMP-1 ratio (sepsis versus nonoperated and sepsis versus operated controls, resp.). Lower MMP-9 and MMP-9/TIMP-1 ratio and higher TIMP-1 levels were associated with shorter survival. MMP-9, TIMP-1, and MMP-9/TIMP-1 ratio correlated with biomarkers of inflammation, kidney and liver injury, coagulation, metabolic disorders, and disease severity scores. Use of vasopressors/inotropes was associated with higher TIMP-1 levels. CONCLUSIONS: MMP-9, TIMP-1, and MMP-9/TIMP ratio were good diagnostic or prognostic biomarkers of sepsis after major abdominal surgery and were linked to sepsis-associated organ dysfunction.

Melanoma of the sinonasal mucosa: A report on the two cases and a review of the literature.

INTRODUCTION: Primary mucosal melanoma of the sinonasal tract is a rare neoplasm, accounting for less than 1% of all melanomas. It has an aggressive and unpredictable biologic behavior characterized by frequent incidence of local recurrence, local and distant metastasis of the disease. CASE REPORT: This report summarizes the results of the previous research concerning sinonasal mucosal melanoma, and by the example of the two patients suffering from mucosal melanoma, we described clinical and histopathological features of this rare neoplasm and our experience in its diagnosis and treatment. CONCLUSION: Only histopathological analysis complemented by immunobistochemical analysis contributes to early and accurate diagnosis of the disease.

[Pathophysiology, Clinical Manifestation and Management of Angioedema - Our Experience].

INTRODUCTION: Angioedema is characterized by subcutaneous and/or submucosal swelling usually localized to the lips, eyelids, tongue, oral cavity, larynx and pharynx. Various types of angioedema, caused by different pathophysiologic mechanisms, can have the same or very similar clinical picture and require different diagnostic and therapeutic procedures. The immediate threat to life as a result of rapidly developed edema of the pharynx and larynx with airway obstruction requires endotracheal intubation or emergency tracheotomy. Standard therapy, which includes epinephrine, second-generation antihistamines and steroids, is not effective in the treatment of all types of angioedema. OBJECTIVE: On the basis of the clinical presentation and course of angioedema, this retrospective study was aimed at contributing to a better understanding of the etiopathogenesis of the disease and at helping determine the most effective available treatment modalities. METHODS: This retrospective study included patients treated under the diagnosis of angioedema of the upper aerodigestive tract between 2000 and 2012 in the Department of Otorhinolaryngology, Clinical Center of Banja Luka. RESULTS: A total of 76 subjects were included in the study. The average age was 62.8 years. There were 40 (52.6%) male and 36 (47.4%) female patients. The largest number of patients (44.7%) had type II angioedema. Almost half of the patients or 36 patients (47.4%) were on treatment with an angiotensin-converting enzyme inhibitor (ACEi), but there was no statistically significant difference under the total number of patients (p=0.678). CONCLUSION: Better understanding of pathophysiologic mechanisms and the adoption of diagnostic protocols contributes to more effective treatment of angioedema.

Effects of changes in dynamic characteristics of the middle ear on transient-evoked otoacoustic emissions.

Transient-evoked otoacoustic emissions are transmitted through the middle ear. The purpose of this study was to investigate the effects of dynamic properties of the transmission system on the measurability of transient otoacoustic emissions. The authors analyzed the presence of transient otoacoustic emissions in 48 children with serous otitis media regarding the tympanogram, presence and type of effusion and pure tone average findings. The results obtained in this research show the predominant absence of transient otoacoustic emissions in patients with type B tympanogram (69.1%) especially if the effusion is mucoid (77.5%) with the hearing loss of 15 decibel hearing level. This research shows that disorders in dynamic characteristics of the middle ear in patients with serous otitis obstruct the transmission of acoustic energy and affect the measurability of transient otoacoustic emissions, especially if the effusion is mucoid and hearing loss of 15 decibel hearing level.

[Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall].

BACKGROUND/AIM: The main complication of the atherosclerotic abdominal aortic aneurysm (AAA) is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. METHOD: During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 microm thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff--PAS stain) and immunocytochemically using a DAKO LSAB+/HRP technique to identify alpha-smooth muscle actin (alpha-SMA), vimentin, myosin heavy chains (MHC), desmin, S-100 protein, CD45 and CD68 (DAKO specification). RESULTS: The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs) are present, which express a alpha-SMA and vimentin (but without MHC or desmin expression), as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68- immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection). CONCLUSION: Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the lesion.

Cost-effectiveness of four immunomodulatory therapies for relapsing-remitting multiple sclerosis: a Markov model based on data a Balkan country in socioeconomic transition.

BACKGROUND/AIM: A cost-effectiveness analyses of immunomodulatory treatments for relapsing-remitting multiple sclerosis (RRMS) in developed countries have shown that any benefit from these drugs is achieved at very high cost. The aim of our study was to compare the cost-effectiveness of five treatment strategies in patients diagnosed with RRMS (symptom management alone and in combination with subcutaneous glatiramer acetate, intramuscular interferon beta-1a, subcutaneous interferon beta-1a, or intramuscular interferon [beta-1b) in a Balkan country in socio-economic transition. METHODS: The Markov model was developed based on the literature about effectiveness and on local Serbian cost calculations. The duration of a cycle in the model was set to a month. The baseline time horizon was 480 months (40 years). The societal perspective was used for costs and outcomes, and they were discounted for 3% annually. Monte Carlo micro simulation with 1000 virtual patients was done. RESULTS: Significant gain with immunomodulatory therapy was achieved only in relapse-free years, while the time spent in health states EDSS 0.0-5.5 was longer with symptomatic therapy only, and gains in life years and QALYs were only marginal. One QALY gained costs more than a billion of Serbian dinars (more than 20 million US dollars), making each of the four immunomodulatory therapies cost-ineffective. CONCLUSION: Our study suggests that immunomodulatory therapy of RRMS in a Balkan country in socioeconomic transition is not cost-effective, regardless of the type of the therapy. Moderate gain in relapse-free years does not translate to gain in QALYs, probably due to adverse effects of immunomodulatory therapy.

Nonsteroidal antiinflammatory drugs and risk of gastrointestinal bleeding among patients on hemodialysis.

BACKGROUND: Both use of nonsteroidal antiinflammatory drugs (NSAIDs) and chronic renal insufficiency are significant independent risk factors for gastrointestinal bleeding. OBJECTIVE: The aim of our study was to investigate whether regular use of NSAIDs further increases the risk of gastrointestinal bleeding among patients with end-stage renal insufficiency on hemodialysis. METHODS: This was a case-control study. Case and control patients were selected from the lists of patients on hemodialysis during the period of 4 months (n=650), at 3 secondary care general hospitals in Serbia. Cases (n=33) were chosen from the study population if they had experienced at least 1 episode of gastrointestinal bleeding during the last 3 years. For each case, at least 1 sex- and age-matched control patient (n=45) was randomly selected from the source population. RESULTS: Among patients on hemodialysis, NSAIDs users had approximately 3 times higher risk of developing gastrointestinal bleeding, than non-users (crude odds ratio = 3.29; 95% confidence interval [95% CI], 1.28-8.45). After adjustment for potential confounders (sex, age, use of erythropoietin or parenteral iron, frequency of NSAID use, smoking, drinking alcohol, heart failure, arterial hypertension, diabetes mellitus, chronic obstructive pulmonary disease, and use of anticoagulants, antiplatelet agents, beta-blockers, angiotensin-converting enzyme inhibitors or diuretics), the only significant association that remained was between gastrointestinal bleeding and use of NSAIDs (OR adjusted = 5.8; 95% CI, 1.3-26.9; p=0.024). CONCLUSION: There is a need for development of effective strategies to prevent gastrointestinal bleeding in patients on hemodialysis who use NSAIDs.