Browsing by Author "Ostojic, Predrag (8503557700)"

The aim of this study was to estimate prevalence and severity of renal insufficiency in systemic sclerosis (SSc) and to assess risk factors associated with reduced glomerular filtration rate (GFR) in SSc patients. Seventy-three consecutive patients with SSc (67 women and 6 men), mean age 56.2 years, mean disease duration 6.7 years, were included in this cross-sectional study. GFR was measured by creatinine clearance (CCr) in all patients, as well as 24-h proteinuria. We assessed frequency and severity of renal insufficiency in our patients with SSc and estimated the association of renal insufficiency with age, disease duration, subtype of the disease, earlier diagnosed arterial hypertension, and medications for which we assumed to affect renal function—cytostatics, nonsteroidal anti-inflammatory drugs, glucocorticoids, ACE inhibitors, diuretics, and calcium channel blockers (CCB). Fifty-six out of 73 patients with SSc (76.7%) had reduced GFR (CCr lower than 90 ml/min), compared to 17/73 (23.3%) of patients with normal renal function. Mild renal insufficiency was noticed in 28/73 (38.4%), moderate in 21/73 (28.8%) and severe renal insufficiency in 5/73 (6.8%). End-stage renal disease (CCr < 15 ml/min) was found in 2/73 (2.7%) of patients. Using the univariate general linear statistical model, we have found that previously diagnosed arterial hypertension and treatment with glucocorticoids are independent risk factors for reduced GFR. On the other hand, age, disease duration, disease form, as well as antibodies (anticentromere antibodies—ACA and anti-topoisomerase I antibodies—ATA) were excluded as independent risk factors. Patients with SSc and arterial hypertension treated with CCB had significantly higher mean CCr than patients treated with diuretics (90.4 vs 53.5 ml/min, p = 0.03), or patients treated with ACE inhibitors (90.4 vs 41.7 ml/min, p = 0.001). Decreased GFR is common in SSc. Most of patients have mild or moderate renal insufficiency. Previously diagnosed arterial hypertension, especially when treated with ACE inhibitors or diuretics, and glucocorticoids are independent risk factors associated with reduced GFR in SSc. These medications should be therefore used with caution in SSc patients. © 2016, Springer-Verlag Berlin Heidelberg.

The aim of this study was to estimate prevalence and severity of renal insufficiency in systemic sclerosis (SSc) and to assess risk factors associated with reduced glomerular filtration rate (GFR) in SSc patients. Seventy-three consecutive patients with SSc (67 women and 6 men), mean age 56.2 years, mean disease duration 6.7 years, were included in this cross-sectional study. GFR was measured by creatinine clearance (CCr) in all patients, as well as 24-h proteinuria. We assessed frequency and severity of renal insufficiency in our patients with SSc and estimated the association of renal insufficiency with age, disease duration, subtype of the disease, earlier diagnosed arterial hypertension, and medications for which we assumed to affect renal function—cytostatics, nonsteroidal anti-inflammatory drugs, glucocorticoids, ACE inhibitors, diuretics, and calcium channel blockers (CCB). Fifty-six out of 73 patients with SSc (76.7%) had reduced GFR (CCr lower than 90 ml/min), compared to 17/73 (23.3%) of patients with normal renal function. Mild renal insufficiency was noticed in 28/73 (38.4%), moderate in 21/73 (28.8%) and severe renal insufficiency in 5/73 (6.8%). End-stage renal disease (CCr < 15 ml/min) was found in 2/73 (2.7%) of patients. Using the univariate general linear statistical model, we have found that previously diagnosed arterial hypertension and treatment with glucocorticoids are independent risk factors for reduced GFR. On the other hand, age, disease duration, disease form, as well as antibodies (anticentromere antibodies—ACA and anti-topoisomerase I antibodies—ATA) were excluded as independent risk factors. Patients with SSc and arterial hypertension treated with CCB had significantly higher mean CCr than patients treated with diuretics (90.4 vs 53.5 ml/min, p = 0.03), or patients treated with ACE inhibitors (90.4 vs 41.7 ml/min, p = 0.001). Decreased GFR is common in SSc. Most of patients have mild or moderate renal insufficiency. Previously diagnosed arterial hypertension, especially when treated with ACE inhibitors or diuretics, and glucocorticoids are independent risk factors associated with reduced GFR in SSc. These medications should be therefore used with caution in SSc patients. © 2016, Springer-Verlag Berlin Heidelberg.

To assess the effects of alpha-tocopherol and ascorbic acid on skin thickening and lung function in patients with early diffuse systemic sclerosis (SSc), thirteen patients with early diffuse SSc, with positive anti-topoisomerase-I antibody, high skin thickening progression rate (STPR < 12/year) and decreased lung diffusing capacity (DLCO ≤ 75%) were included in this study. Patients were randomized into two subgroups: Subgroup A-six patients, treated with intravenous cyclophosphamide (CyP) (500 mg/m 2 of body surface monthly) and antioxidants (alpha-tocopherol 400 IU/day and ascorbic acid 1,000 mg/day), and Subgroup B-seven patients, who received CyP without antioxidants. In both subgroups, effects of treatment on skin thickening and lung function were evaluated by comparison of the modified Rodnan skin score (MRSS), STPR, forced vital capacity (FVC), transfer-factor (DLCO) and diffusing coefficient for carbon monoxide (DLCO/VA) at baseline and 1 month after the sixth pulse of CyP. The mean MRSS did not change from baseline to the end of the follow-up in subgroup A (15.7 vs. 16.4, P = 0.50), but it increased significantly in subgroup B (17.9 vs. 23.6, P = 0.03). Although the mean STPR decreased notably in both subgroups of patients (in subgroup A-from 18.9/year to 2.2/year, P = 0.03, and in subgroup B-from 17.5/year to 8.6/year, P = 0.03), the mean STPR at the end of the treatment period was significantly lower in subgroup A (2.2/year vs. 8.6/year, P = 0.04). The mean value of FVC did not change either in subgroup A (91.0-87%, P = 0.2) or in subgroup B (from 101.2 to 99.7%, P = 0.7). Parameters of lung diffusing capacity improved somewhat in subgroup A (DLCO from 55.7 to 62.0% and DLCO/VA from 68.7 to 74.2%) and decreased in subgroup B (DLCO from 66.2 to 60.6% and DLCO/VA from 76.9 to 71.6%), but differences were not statistically significant. After 6 months of therapy, patients treated with CyP and antioxidants had a significantly lower STPR, compared to patients treated with CyP only. Lung function parameters remained stable in both subgroups. However, lung diffusing capacity improved slightly, without statistical significance, in patients treated with CyP and antioxidants, and it deteriorated in patients without antioxidants. © 2010 Springer-Verlag.

To assess the effects of alpha-tocopherol and ascorbic acid on skin thickening and lung function in patients with early diffuse systemic sclerosis (SSc), thirteen patients with early diffuse SSc, with positive anti-topoisomerase-I antibody, high skin thickening progression rate (STPR < 12/year) and decreased lung diffusing capacity (DLCO ≤ 75%) were included in this study. Patients were randomized into two subgroups: Subgroup A-six patients, treated with intravenous cyclophosphamide (CyP) (500 mg/m 2 of body surface monthly) and antioxidants (alpha-tocopherol 400 IU/day and ascorbic acid 1,000 mg/day), and Subgroup B-seven patients, who received CyP without antioxidants. In both subgroups, effects of treatment on skin thickening and lung function were evaluated by comparison of the modified Rodnan skin score (MRSS), STPR, forced vital capacity (FVC), transfer-factor (DLCO) and diffusing coefficient for carbon monoxide (DLCO/VA) at baseline and 1 month after the sixth pulse of CyP. The mean MRSS did not change from baseline to the end of the follow-up in subgroup A (15.7 vs. 16.4, P = 0.50), but it increased significantly in subgroup B (17.9 vs. 23.6, P = 0.03). Although the mean STPR decreased notably in both subgroups of patients (in subgroup A-from 18.9/year to 2.2/year, P = 0.03, and in subgroup B-from 17.5/year to 8.6/year, P = 0.03), the mean STPR at the end of the treatment period was significantly lower in subgroup A (2.2/year vs. 8.6/year, P = 0.04). The mean value of FVC did not change either in subgroup A (91.0-87%, P = 0.2) or in subgroup B (from 101.2 to 99.7%, P = 0.7). Parameters of lung diffusing capacity improved somewhat in subgroup A (DLCO from 55.7 to 62.0% and DLCO/VA from 68.7 to 74.2%) and decreased in subgroup B (DLCO from 66.2 to 60.6% and DLCO/VA from 76.9 to 71.6%), but differences were not statistically significant. After 6 months of therapy, patients treated with CyP and antioxidants had a significantly lower STPR, compared to patients treated with CyP only. Lung function parameters remained stable in both subgroups. However, lung diffusing capacity improved slightly, without statistical significance, in patients treated with CyP and antioxidants, and it deteriorated in patients without antioxidants. © 2010 Springer-Verlag.

This study aims to analyze the effects of cyclophosphamide pulse therapy on parameters of lung function in patients with systemic sclerosis. Nineteen patients with systemic sclerosis (15 women and four men, aged 25-67 years, mean disease duration 5 years and 9 months) were included in this study. The main reason for the beginning of cyclophosphamide therapy was the decrease of transfer-factor (DLCO) or diffusing coefficient for carbon monoxide (DLCO/VA) under 70% of predictive value. Intravenous cyclophosphamide was administered monthly in a dose of 500 mg/m 2 body surface. The efficacy was evaluated by comparison of forced vital capacity (FVC), DLCO, and DLCO/VA at the baseline and 1 month after the sixth pulse. Statistical analyses were performed using Student's T test and Wilcoxon's test. The difference between FVC at the baseline (86.6%) and at the end of the follow-up period (89.2%) was not statistically significant (t=-1.25, p>0.05). However, a significant increase of DLCO (from 61.2% to 70.5%, z=-2.04, p=0.04) and DLCO/VA (from 57.8% to 72.5%, z=2.67, p=0.008) was observed. Minor side effects were noticed in some patients. Two patients had nausea after cyclophosphamide infusion, two patients had insignificant decrease of creatinine clearance, and two patients had temporary and mild leukopenia. In patients with systemic sclerosis and lung involvement, an improvement of lung-diffusing capacity was noticed 6 months after the beginning of cyclophosphamide pulse therapy, with only minor side effects. © Clinical Rheumatology 2006.

The study aims to analyze the effects of induction treatment with cyclophosphamide (CYC) pulse therapy followed by maintenance treatment with other mild immunosuppressive agents on lung function in scleroderma (SSc) patients. Thirty patients with SSc (mean age 52 years, mean disease duration < 2 years) with forced vital capacity (FVC) ≤ 80% and/or diffusing capacity of carbon monoxide (DLco) ≤ 70% were included. Monthly CYC pulses were given for 6 months (induction treatment), followed by 3-monthly maintenance pulses for the next 18 months, and during the next 5 years patients received other mild immunosupressive therapy brought by the competent rheumatologist. The efficacy was evaluated by comparing FVC% and DLco% after 6, 24, and 84 months from the baseline. All patients completed induction and maintenance treatment with CYC. Three patients were lost to follow-up. The rest of 27 patients, during the next 5 years, received other immunosupressive agents (14 azathioprine, 9 methotrexate, and 4 mycophenolate mofetil). Three patients died in the 4 years of follow-up. By 6, 24, and 84 months, the mean FVC and DLco changes were + 0.47 and + 2.10, + 3.30 and − 2.49, and + 1.53 and − 3.76%, respectively. These changes were not significantly different from the baseline values. CYC does not appear to result in clinically significant improvement of pulmonary function but fulfilled criteria of stable disease. Maintenance treatment with other mild immunosupressive agents preserves the benefits achieved during CYC treatment. © 2018, International League of Associations for Rheumatology (ILAR).

Cryoglobulinemia is thought to be a rare condition. It may be an isolated disorder or secondary to a particular disease. According to immunoglobulin composition, cryoglobulinemia is classified into three types. In mixed cryoglobulinemia (types II and III), vascular deposition of cryoglobulin-containing immune complexes and complement may induce a clinical syndrome, characterized by systemic vasculitis and inflammation – cryoglobulinemic vasculitis (CryoVas). Most common clinical manifestations in CryoVas are skin lesions (orthostatic purpura and ulcers), weakness, peripheral neuropathy, Raynaud’s phenomenon, sicca syndrome, membranoproliferative glomerulonephritis, and arthralgia and seldom arthritis. In patients with mixed cryoglobulinemia, prevalence of anti-hepatitis C virus (HCV) antibodies and/or HCV RNA, detected by polymerase chain reaction (PCR), is reported to be up to 90%, indicating a significant role of HCV in the development of this condition. The goals of therapy for mixed cryoglobulinemia include immunoglobulin level reduction and antigen elimination. CryoVas not associated with HCV infection should be treated according to treatment recommendations for small-vessel vasculitides. CryoVas associated with chronic HCV infection should be treated with antivirals along with immunosuppressive drugs, with or without plasmapheresis, depending on disease severity and organ involvement. Patients who do not respond to first-line therapy may achieve remission when treatment with rituximab is started as second-line therapy. In HCVrelated CryoVas, antiviral therapy should be given along with rituximab in order to achieve complete or partial remission. Moreover, rituximab has proven to be a glucocorticoid-sparing medication. Other potential therapies for refractory CryoVas include mycophenolate mofetil and belimumab, while tumor necrosis factor (TNF) inhibitors are not effective. © 2017 Ostojic and Jeremic.

Cryoglobulinemia is thought to be a rare condition. It may be an isolated disorder or secondary to a particular disease. According to immunoglobulin composition, cryoglobulinemia is classified into three types. In mixed cryoglobulinemia (types II and III), vascular deposition of cryoglobulin-containing immune complexes and complement may induce a clinical syndrome, characterized by systemic vasculitis and inflammation – cryoglobulinemic vasculitis (CryoVas). Most common clinical manifestations in CryoVas are skin lesions (orthostatic purpura and ulcers), weakness, peripheral neuropathy, Raynaud’s phenomenon, sicca syndrome, membranoproliferative glomerulonephritis, and arthralgia and seldom arthritis. In patients with mixed cryoglobulinemia, prevalence of anti-hepatitis C virus (HCV) antibodies and/or HCV RNA, detected by polymerase chain reaction (PCR), is reported to be up to 90%, indicating a significant role of HCV in the development of this condition. The goals of therapy for mixed cryoglobulinemia include immunoglobulin level reduction and antigen elimination. CryoVas not associated with HCV infection should be treated according to treatment recommendations for small-vessel vasculitides. CryoVas associated with chronic HCV infection should be treated with antivirals along with immunosuppressive drugs, with or without plasmapheresis, depending on disease severity and organ involvement. Patients who do not respond to first-line therapy may achieve remission when treatment with rituximab is started as second-line therapy. In HCVrelated CryoVas, antiviral therapy should be given along with rituximab in order to achieve complete or partial remission. Moreover, rituximab has proven to be a glucocorticoid-sparing medication. Other potential therapies for refractory CryoVas include mycophenolate mofetil and belimumab, while tumor necrosis factor (TNF) inhibitors are not effective. © 2017 Ostojic and Jeremic.

Objective: To analyze neurological and electroneurography (ENG) findings in patients with systemic sclerosis (SSc) and symptoms of neuropathic pain in upper and lower extremities. Patients and methods: Using the PainDetect questionnaire, 42 consecutive patients with SSc (38 women and 4 men) were screened for the presence of neuropathic pain in upper and/or lower extremities. Patients with previously diagnosed diabetes or other metabolic diseases, malignancy, other autoimmune disorders, or any neurological or psychiatric disease, were not included. Neurological examination, ENG, and laboratory analyses (glycated hemoglobin—HbA1C, and vitamin B12) were performed in SSc patients with neuropathic pain in extremities. Methods of descriptive statistics were used to summarize the data. Results: Eleven patients (26.2%) had significant symptoms of neuropathic pain in extremities. Neurological examination indicated polyneuropathy in 10/11 (90.9%) of patients. Symmetrical hyperesthesia in the lower and/or upper extremities was found in ten patients. Symmetrical hyporeflexia was found in 7/11 (63.6%) of patients in the arms, and 6/11 (54.4%) of patients in the legs. Proprioception was diminished in 3/11 (27.3%), whilst pallhypesthesia was present in all patients. However, polyneuropathy could be confirmed by ENG only in four out of ten SSc patients, who had typical neurological findings for polyneuropathy. Hypoesthesia in a specific lumbar root dermatome, suggesting radiculopathy, was found in 6/11 (54.5%) of patients. Asymmetrical hyporeflexia was noticed in 2/11 (18.1%) of patients in the lower limbs. Seven patients (63.6%) had signs of radiculopathy in at least one root dermatome on ENG. Conclusion: A significant number of SSc patients with neuropathic pain in the upper and/or lower extremities have symptoms and signs of polyneuropathy undetectable by ENG, which indirectly suggests the presence of small-fiber polyneuropathy in these patients. In some patients, radiculopathy cannot be excluded as possible co-morbid non-scleroderma condition associated with neuropathic pain. © 2018, Belgian Neurological Society.

Objectives: This study aims to assess the prevalence and clinical correlates of small airway obstruction (SAO) in patients with systemic sclerosis (SSc). Methods: Sixty-nine consecutive patients with SSc (63 women and 6 men) were included. Lung function tests, including assessment of lung diffusing capacity, were performed in all patients. Patients were considered to have SAO when the maximal expiratory flow at 25% of the forced vital capacity (MEF25) was lower than 60% as predicted. High-resolution computed tomography (HRCT) of the lung was performed in all patients with MEF25 < 60%. We assessed the relationship of SAO in our patients with large airway obstruction, decreased lung diffusing capacity, HRCT findings, disease duration, disease subtype, scleroderma-specific antibodies, and smoking. Results: SAO was noticed in 46/69 (66.6%) of patients with SSc. Restrictive lung disease was found in 4/69 (5.8%), obstruction of large airways in 18/69 (26.1%), and decreased lung diffusing capacity in 47/69 (68.1%) of patients. No difference in gender, age, disease duration, disease subtype, and scleroderma-specific antibodies was found between patients with and without SAO. Eighteen out of forty-six (39.1%) patients with SAO had decreased forced expiratory volume in 1 sec (FEV1) and the Tiffeneau-Pinelli index, indicating presence of coexistent large airway obstruction. Twenty out of forty-six (43.5%) patients with SAO had associated decreased lung diffusing capacity, while 8/46 (17.4%) of patients had isolated SAO. HRCT patterns of interstitial lung disease (ILD) were found more frequently in patients with SAO and decreased lung diffusing capacity, compared with patients with SAO and normal diffusing capacity (75% vs 11.5%, p = 0.008). We have noticed that tobacco smokers among SSc patients with SAO have more common associated obstructive lung disease on spirometry (58.8% vs 15.4%, p = 0.004). On the other hand, isolated SAO and SAO associated with impaired diffusing capacity were equally frequent among smokers and non-smokers. Conclusion: Patients with SSc have commonly SAO. It can be considered clinical feature of undiagnosed asthma or chronic obstructive pulmonary disease (COPD), if isolated or associated with large airway obstruction, especially in tobacco smokers. On the other hand, SAO associated with decreased lung diffusing capacity was found to be not related to smoking, and may indicate a possible prominent bronchiolar involvement within SSc-related interstitial lung diseaseKey Points• Small airway obstruction in patients with systemic sclerosis can be considered a clinical feature of undiagnosed obstructive lung disease, if isolated or associated with large airway obstruction, especially in tobacco smokers.• Obstruction of small airways, associated with decreased lung diffusing capacity, may indicate a possible prominent bronchiolar involvement within systemic sclerosis–related interstitial lung disease. © 2020, International League of Associations for Rheumatology (ILAR).

This study aimed to assess symptoms of depression and anxiety in Serbian patients with systemic sclerosis (SSc) and to estimate the impact of disease severity and socioeconomic factors on development of depression and anxiety in SSc. Thirty-five patients with SSc and 30 age- and gender-matched healthy individuals participated. Symptoms of depression and anxiety were evaluated using the Beck's depression inventory and Zung's anxiety self-assessment scale. We estimated the impact of gender, age, economic status, marital status, disease duration, disease subset (limited or diffuse), and some clinical features on development of depressive symptoms and anxiety in patients with SSc. Symptoms of depression were found in 68.6% of patients (compared with 23.3% in the control group), were more frequent in patients with longer disease duration and in female and older patients, and were more common in unemployed and retired patients than in employed individuals. No differences in anxiety and depressive symptoms was noticed between patients with limited and diffuse SSc or those with or without restrictive lung disease, pulmonary hypertension, finger-tip ulcers, and heart involvement. Symptoms of depression were associated with severe pain. Symptoms of anxiety were found in 80% of patients compared with 13.3% of healthy individuals and were equally as frequent in patients of different gender, age, socioeconomic status, and disease duration and severity. Symptoms of depression and anxiety are common in Serbian patients with SSc. Depressive symptoms depended mostly on socioeconomic factors, disease duration, and pain intensity, whereas disease severity had no significant impact on development of depressive symptoms and anxiety.

Objectives: Osteoarthritis (OA), a prevalent and disabling condition, significantly burdens individuals and healthcare systems worldwide. It is characterized by joint pain, stiffness, and structural changes in cartilage, bone, and synovium. The clinical manifestations of OA vary widely, reflecting complex interactions among genetic, metabolic, biomechanical, and environmental factors. Despite progress in identifying OA clinical phenotypes, inconsistent terminology, including “phenotypes,” “subtypes,” and “subgroups,” hinders effective communication and research translation. This review aims to synthesize existing literature on clinical OA phenotypes, terminology, and definitions and propose a research agenda. Method: This scoping review followed PRISMA-ScR guidelines, focusing on publications from 2010 to 2023 investigating clinical phenotypes in adult OA patients. Searches were conducted in MEDLINE, SCOPUS, and EBSCOhost using combinations of terms related to clinical phenotypes in OA. Studies were screened, duplicates removed, and relevant data were charted and analyzed by two independent reviewers. Results: From 196 identified studies, 50 were included in the final analysis. Eight clinical phenotypes were categorized, including inflammatory, biomechanical, metabolic, and pain-sensitization. minimal joint disease, psychologically driven, menopause, severe radiographic. Most studies focused on knee OA, with limited exploration of hand, midfoot, and hip OA. Phenotype-based management strategies demonstrated potential for improving treatment outcomes and guiding research. Conclusion: Standardizing terminology and leveraging phenotype-based frameworks hold promise for advancing personalized OA care and research. Future efforts should focus on validating criteria, developing accessible diagnostic tools, and addressing understudied OA phenotypes. This work highlights the value of tailoring interventions to specific OA phenotypes for improved patient outcomes. Clinical trial number: Not applicable © The Author(s) 2025.

This article is a small case series that aims to discuss the impact of depression, vascular, and fibrotic changes on development of erectile dysfunction (ED) in patients with systemic sclerosis (SSc). In this paper, we present five male patients with SSc, aged 30-48 years. All patients are nonsmokers, and their past medical history does not reveal any other diseases or treatment procedures (drugs) that may have influence on erectile function. We used a five-item questionnaire, the International Index of Erectile Function (IIEF-5), to assess ED in our patients. Microvascular abnormalities (estimated by nailfold capillaroscopy), fibrotic changes (assessed by skin score, chest X-ray and reduction in forced vital capacity), and presence of depression (estimated using the Beck's Depression Inventory) were evaluated. To assess efficacy of sildenafil citrate (25-50 mg 1 h before each sexual activity), patients with ED filled up the IIEF-5 before and after 1-month therapy. We concluded that ED is a frequent and early clinical feature in men with SSc. Microvascular abnormalities are similar in patients with and without ED. Although patients with ED had higher depression indices, an unsatisfactory response to sildenafil citrate indicates that psychoneurogenic factors are not crucial in development of ED in SSc. Patients with ED had more extended fibrotic changes, which indirectly suggests that fibrosis of the corporal body may play the main role in the pathogenesis of ED in SSc. © 2007 Clinical Rheumatology.