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Journal Article
Gheita, T., H. Gheita, and S. Kenawy, "The potential of genetically guided treatment in Behçet's disease.", Pharmacogenomics, vol. 17, issue 10, pp. 1165-74, 2016.
Gheita, A. A., T. A. Gheita, and S. A. Kenawy, "The potential role of B5: A stitch in time and switch in cytokine.", Phytotherapy research : PTR, vol. 34, issue 2, pp. 306-314, 2020. Abstract

The wound healing process is a multifaceted sequence of activities associated with tissue restoration. Novel approaches for the perfection of wound healing have been determined as a stitch in time saves nine. Dysregulation of the immune response is a key element in the pathogenesis of rheumatic diseases and serves as a potential target for novel therapeutic strategies. Vitamin B5 (VB5), also known as pantothenate or "anti-stress vitamin," is the precursor of coenzyme A, which is essential in every micro-organism. Many pantothenic acid amides acquire persuasive antimicrobial activity. Pantothenic acid improves surgical wounds healing with moisturizing and skin barrier enhancing potential. Its deficiency leads to reduced cortisol production, increased arthritic pain, myalgia, fatigue, headache, depression, insomnia, and widespread "proinflammatory" effects on the immune-system. VB5 triggers immune cells to produce cytokines and is multifunctional. The paradoxical effect of VB5 on the switch of anti-inflammatory and proinflammatory cytokines has been revealed. This review aims to present the long research journey of B5 as it is becoming a forerunner in the healing of wounds and in enhancing the immune function, thus providing potentially important therapeutic implications. As its role in healing a wound stitch is promising, amending the immune system damage too is a hopeful target.

Fathi, H. M., I. E. I. Gazzar, M. A. I. Elazeem, E. AboulKheir, N. M. Gamal, F. Ismail, R. E. R. Shereef, S. Tharwat, S. Elwan, N. Samy, et al., "Rheumatologists' knowledge and perception of COVID-19 and related vaccines: the vaXurvey2 online survey.", Rheumatology international, 2022. Abstract

The study aimed to explore the experience of coronavirus disease-2019 (COVID-19) infection and vaccine adverse events (AEs) among rheumatologists. A validated questionnaire was distributed as a Google form to rheumatologists across the country via social networking sites from late December 2021 till early January 2022. The questionnaire included questions regarding participants' socio-demographic details, COVID-19 infection and vaccination details with special emphasis on AEs. Out of 246 responses, 228 were valid. 200 (81.3%) responders had received the vaccine. The mean age of the 228 participants was 37.9 ± 8.5 years, 196 were females and 32 males (F:M 6.1:1) from 18 governorates across the country. Comorbidities were present in 54 subjects (27%). There was a history of highly suspicious or confirmed COVID-19 infection in 66.7% that were all managed at home. The COVID-19 vaccine was received by 200 and a booster dose of 18.5%. Obesity and musculoskeletal involvement co-morbidities were present only in those with AEs (9.1% and 5.5% respectively). AEs were present in 82%; 66.7% had injection-site tenderness, 50% fatigue, 35.5% fever, 15% chills, 42.5% myalgia, 14.5% arthralgia, 8% low back pain, headache 31%, dizziness 10%, sleepliness 16% and 15% developed post-vaccine. There were no differences according to the geolocation regarding the occurrence of COVID-19 infection (p = 0.19) or AEs post-vaccine (p = 0.58). The adverse events were mostly mild to moderate and tolerable which makes this work in agreement with other studies that support the broad safety of the vaccine in favor of the global benefit from mass vaccination.

Gheita, T. A., M. N. Salem, N. N. Eesa, N. M. Khalil, N. M. Gamal, R. A. Noor, A. H. Moshrif, R. E. Shereef, F. Ismail, N. Noshy, et al., "Rheumatologists' practice during the Coronavirus disease 2019 (COVID-19) pandemic: a survey in Egypt.", Rheumatology international, vol. 40, issue 10, pp. 1599-1611, 2020. Abstract

The aim of this work is to trace how rheumatologists all over Egypt are approaching the COVID-19 pandemic and what changes it has brought about in the patients' care with special attention to its effect on vulnerable rheumatic disease (RD) patients. This survey further aims to help inform the rheumatology community about the changes in practice during the COVID-19 pandemic. The survey included 26 questions distributed to University staff members across Egypt members of the Egyptian College of Rheumatology (ECR). It takes 5-10 min to fill out. The practice setting of participating rheumatologists included University Teaching Hospitals that are the main rheumatology and clinical immunology service providers for adults and children RD patients. There was an overall agreement across the country in the responses to the survey that took a median time of 7 min to fill in. Potential changes in rheumatology outpatient practice by staff members evolved since the COVID-19 pandemic. None of the university rheumatology staff members has prescribed chloroquine or HCQ to prevent or treat COVID-19 in a non-hospitalized patient who was not previously on it. Twenty-three recommended decrease/avoid NSAIDs if the RD patient had confirmed COVID-19 or symptoms. There is an agreement to the key emerging frontline role of rheumatologists in treating COVID-19. During the pandemic, RD cases requiring admission were dealt with by several modified strategies. The overall agreement among the different university rheumatology departments during such critical situation has provoked the ECR to consider providing provisional guidelines for dealing with RD patients during this global catastrophe.

Gheita, T. A., and N. N. Easa, "Rheumatology in Egypt: back to the future.", Rheumatology International , vol. 39, issue 1, pp. 1-12, 2019.
Hammam, N., S. Tharwat, R. E. R. Shereef, A. M. Elsaman, N. M. Khalil, H. M. Fathi, M. N. Salem, H. M. El-Saadany, N. Samy, A. S. El-Bahnasawy, et al., "Rheumatology university faculty opinion on coronavirus disease-19 (COVID-19) vaccines: the vaXurvey study from Egypt.", Rheumatology international, vol. 41, issue 9, pp. 1607-1616, 2021. Abstract

OBJECTIVES: The aim of the present work was to explore the perspectives of Egyptian Rheumatology staff members as regards the coronavirus disease-19 (COVID-19) vaccine.

METHODS: The survey is composed of 25 questions. Some questions were adapted from the global rheumatology alliance COVID-19 survey for patients.

RESULTS: 187 rheumatology staff members across Egypt from 18 universities and authorizations actively participated with a valid response. The mean time needed to complete the survey was 17.7 ± 13 min. Participants were 159 (85%) females (F:M 5.7:1). One-third agreed that they will be vaccinated once available, 24.6% have already received at least one dose, 29.4% are unsure while 16% will not take it. Furthermore, 70.1% agreed that they will recommend it to the rheumatic diseases (RD) patients once available, 24.1% are not sure while 5.9% will not recommend it. RD priority to be vaccinated against COVID-19 in descending order include SLE (82.9%), RA (55.1%), vasculitis (51.3%), systemic sclerosis (39.6%), MCTD (31.6%), Behcet's disease (28.3%). The most common drugs to be avoided before vaccination included biologics (71.7%), DMARDs (44.4%), biosimilars (26.7%), IVIg (17.1%) and NSAIDs (9.1%).

CONCLUSIONS: The results of the study and specifically the low rate of acceptability are alarming to Egyptian health authorities and should stir further interventions to reduce the levels of vaccine hesitancy. As rheumatic disease patients in Egypt were not systematically provided with the vaccine till present, making the vaccine available could as well enhance vaccine acceptance. Further studies to investigate any possible side effects, on a large scale of RD patients are warranted.

Hammam, N., N. M. Gamal, M. H. Elzohri, A. M. Elsonbaty, A. M. Rashed, Z. H. Eldaly, D. Tarik, and T. A. Gheita, "Serum 14-3-3η protein is associated with clinical and serologic features of Sjögren's syndrome in patients with systemic lupus erythematosus: a cross-sectional analysis.", Clinical rheumatology, vol. 39, issue 9, pp. 2603-2610, 2020. Abstract

INTRODUCTION/OBJECTIVES: Systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) may coexist and carry a higher risk for future comorbidities. Although 14-3-3η protein is recently a known diagnostic marker in rheumatoid arthritis (RA), its role has not been investigated in SLE. The aim of this study was to compare serum 14-3-3η protein level in SLE and RA patients and to examine its association with clinical and laboratory features in SLE patients.

METHODS: Eighty-four SLE patients and 39 RA patients were included. Sociodemographic, SLE disease activity index (SLEDAI), and damage index were assessed for SLE patients. Data about secondary SS were collected. 14-3-3η was measured by ELISA; titres above 0.19 ng/ml were considered positive.

RESULTS: Serum 14-3-3η protein in SLE was significantly lower than in RA (0.37 ± 0.09 vs 1.5 ± 0.51; p < 0.001). 14-3-3η protein level was comparable between SLE patients with and without arthritis (0.29 ± 0.8 vs 0.15 ± 0.08 respectively; p = 0.20). Serum 14-3-3η protein level was higher in SLE with secondary SS features compared to those without (0.22 ± 0.10 IU/ml vs 0.11 ± 0.04 IU/ml; respectively, p < 0.001). There were no differences in 14-3-3η positivity for other lupus criteria or correlation of 14-3-3η titer with SLEDAI. 14-3-3η protein at 1.11 ng/mL yield a secondary SS diagnostic accuracy of 71%.

CONCLUSIONS: Serum 14-3-3η protein level is high in SLE-associated SS. The 14-3-3η protein level was able to distinguish patients with secondary SS among patients with SLE. Studying the role of 14-3-3η protein in Sjögren's syndrome would be considered in further larger scale studies to confirm the impact of any association. Key Points • Serum 14-3-3η protein level is significantly higher in systemic lupus patients with secondary Sjögren's syndrome (SS) in comparison to those without. • Serum 14-3-3η protein can be used as a useful marker to distinguish patients with secondary SS among patients with systemic lupus. • 14-3-3η protein level shows no difference between systemic lupus patients with and without arthritis.

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.
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.
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., 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., 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, GS Azkalany, and et al, "Subclinical sacroiliitis in brucellosis: Clinical presentation and MRI findings. ", Z Rheumatol., vol. 74, issue 3, pp. 240-245, 2014.
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.

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.

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.

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.
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.