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Gheita, T. A., S. Sayed, and H. A. Gheita, "Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome. ", Intl J Rheum Dis, issue doi: 10.1111/1756-185X.12426. [Epub ahead of print], 2014.
Gheita, T., S. Sayed, H. Gheita, and S. Kenawy, "Vitamin D status in rheumatoid arthritis patients: relation to clinical manifestations, disease activity, quality of life and fibromyalgia syndrome.", Int J Rheum Dis, vol. 19, issue 3, pp. 294-9, 2016.
Elgengehy, F. T., S. M. Gamal, N. Sobhy, I. Siam, A. M. Soliman, G. W. Elhady, and T. A. Gheita, "Vasculitis damage index in Behçet's disease.", Advances in rheumatology (London, England), vol. 61, issue 1, pp. 33, 2021. Abstract

BACKGROUND: Vasculitis damage index (VDI) is a validated damage index for systemic vasculitis, and as Behçet's disease is considered one of systemic vascular disease we aimed to study the relationship of the vasculitis damage index to clinical manifestations and comorbidity in patients with Behçet's disease (BD) to determine if VDI could be used to assess damage in patients with BD.

METHODS: A total of 109 patients with BD were recruited from the Rheumatology Department (outpatient and inpatient clinic), Cairo University Hospitals. All patients were subjected to full history taking, clinical examination, and routine laboratory investigations. Disease activity was assessed by the BD current activity form, and the VDI was calculated in all patients. The relationship of the VDI to the disease clinical manifestations was studied. Mann-Whitney and Kruskal Wallis tests were used to estimate differences in quantitative variables. Spearman correlation test was used to test for correlation between quantitative variables.

RESULTS: In the current study, the VDI ranged from 1 to 10, with a mean of 3.5 ± 1.8. It was significantly associated with total thrombosis (P = 0.022); total neurological manifestations (P = 0.000), especially stroke and cranial nerve affection; uveitis (P = 0.005); avascular necrosis (AVN) (P = 0.015); osteoporosis (P = 0.01); impaired vision (P < 0.0001); cataract (P < 0.0001); and diabetes (P = 0.012). Generally, immunosuppressive treatment was significantly associated with VDI (P = 0.039), especially cyclophosphamide (P < 0.0001), biological agent (P = 0.008), chlorambucil (P = 0.003), and anticoagulant (P = 0.02). VDI was also significantly correlated with age (P = 0.033), disease duration (P = 0.029), and duration of eye involvement (P = 0.003).

CONCLUSION: VDI is significantly associated with most disease parameters of BD, except for parameters such as mucocutaneous manifestations and uncomplicated venous thrombosis; however, further studies may be needed to establish BD-specific damage index.

Gheita, T. A., B. R. Sakr, R. E. Rabea, and S. M. Abdel Hamid, "Value of hematological indices versus VEGF as biomarkers of activity in Behçet's disease.", Clinical rheumatology, vol. 38, issue 8, pp. 2201-2210, 2019. Abstract

OBJECTIVE: The aim of this study is to investigate the value of several hematological indices, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), red blood cell distribution width (RDW), and mean platelet volume (MPV), versus vascular endothelial growth factor (VEGF) as biomarkers of activity in Behçet's disease (BD).

METHODS: This study included 96 adult BD patients recruited from the Rheumatology Outpatient Clinic, Kasr Al-Ainy Hospital, Cairo University, and 60 healthy subjects as controls. Assessment of BD activity was done using the Behçet's Disease Current Activity Form (BDCAF). The CBC was measured by COULTER LH 750 assay analyzer with special consideration to the NLR, PLR, MPV, and RDW. Serum VEGF level was measured by enzyme-linked immunosorbent assay (ELISA) technique.

RESULTS: The NLR, RDW, and PLR were significantly higher in BD patients when compared with healthy controls (p = 0.011, < 0.001, < 0.001, respectively), while there was no statistical difference in MPV or VEGF between patients and controls (p = 0.82, 0.46). NLR and PLR were significantly higher in BD patients with vascular activity (p = 0.03, 0.01). RDW was significantly higher, while MPV was significantly lower in patients with vascular manifestations (p = 0.04, 0.004). NLR and PLR were the most valuable predictors of vascular activity (p = 0.033, 0.018). PLR was more powerful as a predictor of vascular activity, but it had a lower specificity than NLR.

CONCLUSION: The NLR, PLR, and RDW are significantly higher in BD patients, suggesting their value as promising inflammatory biomarkers in BD. NLR and PLR are the most valuable predictors of vascular activity, while RDW and MPV were not valuable predictors of BD activity, rather implicated in the ongoing vascular inflammatory process in BD. The VEGF was neither a surrogate biomarker of BD activity nor reflecting the ongoing inflammatory process in BD.

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El-Gazzar, I. I., H. M. Fathy, T. A. Gheita, and S. A. Kenawy, "Tumor necrosis factor-α -308 A/G gene polymorphism in children with juvenile idiopathic arthritis: relation to disease activity, damage, and functional status.", Clin Rheumatol, vol. 36, issue 8, pp. 1757-1763, 2017.
Gheita, T. A., S. Sayed, G. S. Azkalany, N. Abaza, N. Hammam, and A. H. Eisa, "Toll-like receptor 9 in systemic sclerosis patients: relation to modified Rodnan skin score, disease severity, and functional status.", Clinical Rheumatology, vol. 37, issue 3, pp. 757-763, 2017.
Elessawi, D. F., H. Gabr, M. M. M. Badawy, and T. A. Gheita, "Therapeutic potential of mesenchymal stem cells for scleroderma induced in mouse model.", Tissue & cell, vol. 73, pp. 101671, 2021. Abstract

OBJECTIVE: To examine the potential therapeutic effect of mesenchymal stem cells (MSCs) for experimental scleroderma.

MATERIALS AND METHODS: Fifty-four mice six-week-old (30-35 g) were studied. Hypochlorous acid (HOCl) induced scleroderma was considered. Mice were divided into 3 groups: (I) Control: Six mice did not receive any treatment and were sacrificed at the end of the experiment; (II) HOCl mice (induced scleroderma as a positive control): (III) MSCs-treated HOCl mice: Thirty six HOCl-induced mice were injected with MSCs (7.5 × 105) intravenous every week for 3 weeks. Skin pieces were taken from the backs of mice and lung tissue pieces. a smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β1) were analysed or fixed in 10 % formalin for skin and lung tissue histopathological analysis. Plasma nitric oxide (NO) was also assayed.

RESULTS: There was a significant rise in the NO level and of the cutaneous and lung tissue α-SMA and TGF-β1 in untreated scleroderma-induced mice. The values significantly normalized after MSC therapy over the 7 weeks duration of the study. The altered histopathology of the skin and lung tissues in the scleroderma-induced mice showed a remarkable tendency to normalization of the skin and lung parenchyma and vasculature.

CONCLUSION: There was a significant rise in the level of NO and skin and lung tissue α-SMA and TGF-β1 in untreated scleroderma-induced mice and values were significantly normalized after MSC therapy over the 7 weeks duration of the study. Altered histopathology of the skin and lung appeared nearly normal after MSC therapy.

Gheita, T. A., "Targeted gene therapy in the management of osteoarthritis: back to the future with great expectations. ", Int. J. Clin. Rheumatol. , vol. 12, issue 4, pp. 105-107, 2017.
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Acar-Denizli, N., I. - F. Horváth, T. Mandl, R. Priori, A. Vissink, G. Hernandez-Molina, B. Armagan, S. PRAPROTNIK, A. Sebastian, E. Bartoloni, et al., "Systemic phenotype related to primary Sjögren's syndrome in 279 patients carrying isolated anti-La/SSB antibodies.", Clinical and experimental rheumatology, vol. 38 Suppl 126, issue 4, pp. 85-94, 2020. Abstract

OBJECTIVES: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria.

METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative.

RESULTS: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group.

CONCLUSIONS: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.

Retamozo, S., N. Acar-Denizli, A. Rasmussen, I. F. Horváth, C. Baldini, R. Priori, P. Sandhya, G. Hernandez-Molina, B. Armagan, S. PRAPROTNIK, et al., "Systemic manifestations of primary Sjögren's syndrome out of the ESSDAI classification: prevalence and clinical relevance in a large international, multi-ethnic cohort of patients.", Clinical and experimental rheumatology, vol. 37 Suppl 118, issue 3, pp. 97-106, 2019. Abstract

OBJECTIVES: To analyse the frequency and characterise the systemic presentation of primary Sjögren's syndrome (SS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients.

METHODS: The Big Data Sjögren Project Consortium is an international, multicentre registry based on world-wide data-sharing and cooperative merging of pre-existing clinical SS databases from leading centres in clinical research in SS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded.

RESULTS: Information about non-ESSDAI features was available in 6331 patients [5,917 female, mean age at diagnosis 52 years, mainly White (86.3%)]. A total of 1641 (26%) patients had at least one of the ESSDAI systemic features. Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud's phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs. 94.1%, p<0.001) and positive minor salivary gland biopsy (86.7% vs. 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs. 68.7%, p<0.001), anti-La/SSB antibodies (44.5% vs. 40.4%, p=0.004), ANA (82.7% vs. 79.5%, p=0.006), low C3 levels (17.4% vs. 9.7%, p<0.001), low C4 levels (14.4% vs. 9.6%, p<0.001), and positive serum cryoglobulins (8.6% vs. 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p<0.001 for all comparisons).

CONCLUSIONS: More than a quarter of patients with primary SS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT (ear, nose, and throat), cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud's phenomenon.

Eesa, N. N., H. Abdel Nabi, R. E. Owaidy, I. Khalifa, A. R. Radwan, A. M. NourEl-Din, M. A. Amer, R. R. El Shereef, E. Hassan, F. Ismail, et al., "Systemic lupus erythematosus children in Egypt: Homeland spectrum amid the global situation.", Lupus, vol. 30, issue 13, pp. 2135-2143, 2021. Abstract

OBJECTIVES: This study aims to present the manifestations of juvenile systemic lupus erythematosus (JSLE) across Egypt, to focus on age at onset and gender-driven influence on disease characteristics, and to compare findings to other countries.

METHODS: The study included 404 Egyptian children with systemic lupus erythematosus (SLE) presenting to one of the specialized rheumatology centers corresponding to 13 major governorates. Juvenile cases age was ≤ 16°years at the time of recruitment. The SLE Disease Activity Index (SLEDAI) and damage index (DI) were assessed.

RESULTS: The mean age was 13.2 ± 2.4°years; 355 females and 49 males (7.2:1), and the disease duration was 2.3 ± 1.6 years, while age at disease onset was 11.1 ± 2.5°years. Their SLEDAI was 13.5 ± 12.3, and DI, 0.36 ± 0.78. The overall estimated prevalence of childhood-SLE patients in the recruited cohort in Egypt was 1/100,000 population (0.24/100000 males and 1.8/100000 females). 7.4% developed pre-pubertal SLE (≤ 7 years); 73.3%, peri-pubertal; and 19.3% during early adolescence. The differences according to age group were equal for gender and clinical manifestations except skin lesions present in 59.3% of pre-pubertal onset, 74.6% of peri-pubertal, and 84.2% of adolescents ( = 0.029), and renal involvement in 73.8% of peripubertal, 62.1% of pre-pubertal and 58.9% of adolescents ( = 0.03). Laboratory investigations, SLEDAI, and DI were similar among age categories. Lupus nephritis was more common in Egypt compared to JSLE from other countries.

CONCLUSION: Our large multicenter study identified that female gender influenced disease characteristics with more frequent skin involvement. Skin lesions were significantly higher in adolescents, while renal involvement in peri-pubertal children.

Gheita, T. A., S. Sayed, GS Azkalany, and et al, "Subclinical sacroiliitis in brucellosis: Clinical presentation and MRI findings. ", Z Rheumatol., vol. 74, issue 3, pp. 240-245, 2014.
Gheita, T. A., S. A. Kenawy, R. W. El-Sisi, and et al, "Subclinical reduced G6PD activity in RA and SS patients: relation to clinical characteristics, disease activity and MetS. ", Modern Rheum,, vol. 24, issue 4, pp. 612-617, 2014.
Gheita, T. A., S. Sayed, W. Hammam, and G. A. Hegazy, "Subclinical hypovitaminosis D and osteoporosis in breast cancer patients. ", 7th Int’l Conf. on Osteoporosis and Bone Research (COBR), , Xiamen, China, 2014.
Gheita, T. A., S. Sayed, W. Hammam, and G. A. Hegazy, "Subclinical hypovitaminosis D and osteoporosis in breast cancer patients", Middle East J of Internal Medicine, vol. 8, issue 2, pp. 12-17, 2015.
Gheita, T. A., H. Raafat, H. Khalil, and et al, "Serum level of APRIL/BLyS in Behҫet’s disease patients: clinical significance in uveitis and disease activity. Modern Rheumatology", Mod Rheumatol,, vol. 23, issue 3, pp. 542-546, 2013.
Gheita, T. A., A. M. N. Abdel-Baky, H. S. Assal, and et al, "Serum Cystatin C, UNGAL and NAG in juvenile and adult SLE; relation to clinical manifestations, disease activity and damage.", Saudi J Kidney Dis Transpl., issue Accepted fort publication, 2015.
Eldefrawy, A., T. Gheita, H. Raslan, and M. El-Ansary-etal, "Serum and synovial cartilage oligomeric matrix protein levels in early and established rheumatoid arthritis", Z Rheumatol, vol. 75, issue 9, pp. 917-923, 2016.
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