Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

A national, multicenter, retrospective study evaluating retention rate and efficacy of tocilizumab treatment in patients with active rheumatoid arthritis who had an inadequate response to csDMARDs and/or TNF inhibitors.

BACKGROUND: To describe the disease activity and retention rate in rheumatoid arthritis (RA) patients with inadequate response (IR) to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and/or tumor necrosis factor inhibitors (TNFis) who were prescribed tocilizumab (TCZ) as first-line or second-line biologic treatment in real-world setting. METHODS: Data gathered from patients' files was used in a multicenter and retrospective context. Retention rates and the Disease Activity Score in 28 joints with CRP (DAS28-CRP) were evaluated at time points. The relationship of drug efficacy with factors such as smoking, obesity, and previous use of TNFis was also examined. RESULTS: One hundred and twenty-four patients with a median (IQR) RA duration of 3.7 (7.4) years were included. Mean (SD) age was52.9 (12.9) and 75% of the patients were female. TCZ retention rates in the 6th and 12th months were 94.1% and 86.6%, respectively. In all patients, DAS28-CRP level decreased significantly from baseline to Months 3 and 6. There was an increase in patients with remission and/or low disease activity and a decrease in patients with high disease activity at Month 3 and Month 6 (p < 0.001 for both). Disease activity was similar between subgroups based on body mass index, smoking status, and previous use of TNFis at any time point. Regression analysis showed that absence of concomitant corticosteroid treatment independently was associated with remission/LDA achievement at Month 6 [OR = 0.31, 95% CI (0.14- 0.72), p = 0.006], and Month 12 [OR = 0.35, 95% CI (0.13-0.94), p = 0.037]. Overall, 25 mild adverse events were reported. DISCUSSION: TCZ was found to be effective and safe in RA patients with IR to csDMARDs and/or TNFis. The drug retention rate was considered satisfactory with more than half of the patients continuing TCZ treatment at Month 12.

EGFR blocker lapatinib inhibits the synthesis of matrix metalloproteinases from synovial fibroblasts.

BACKGROUND: Epidermal growth factor receptor (EGFR) family members and their associated ligands may be related to bone and joint destruction in rheumatoid arthritis. Matrix metalloproteinases are responsible for joint and bone tissue degradation. This study is intended to investigate the effect of epidermal growth factor receptor inhibition by lapatinib on the synthesis of matrix metalloproteinases in in vitro. METHODS: Synovial fibroblast cell culture was obtained from a patient with rheumatoid arthritis who underwent knee arthroplasty. Interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) were added to the cell culture to stimulate synovial fibroblast cells and create an inflammatory character. Understimulated and nonstimulated conditions, lapatinib was applied to the culture in four different concentrations of 25, 50, 100, and 200 µmol. Then, matrix metalloproteinase -1, -3, and, -13 levels were assessed. RESULTS: When stimulated with IL-1ß and TNF-α, the synthesis of matrix metalloproteinases from synovial fibroblast was increased significantly. When lapatinib is added to the stimulated synovial fibroblasts, matrix metalloproteinases synthesis is significantly suppressed. DISCUSSION: Inhibition of the EGFR pathway with lapatinib suppresses matrix metalloproteinases synthesis. Our results suggest EGFR pathway inhibition may be a promising option to prevent joint destruction in the treatment of rheumatoid arthritis.

The receptor for advanced glycation end product (RAGE) pathway in COVID-19.

INTRODUCTION: Coronavirus disease-2019 (COVID-19) with lung involvement frequently causes morbidity and mortality. Advanced age appears to be the most important risk factor. The receptor for advanced glycation end-product (RAGE) pathway is considered to play important roles in the physiological aging and pathogenesis of lung diseases. This study aimed to investigate the possible relationship between COVID-19 and RAGE pathway. MATERIALS AND METHODS: This study included 23 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed tomography. Serum soluble-RAGE (sRAGE) levels were determined using enzyme-linked immunosorbent assay. RESULTS: The sRAGE levels were significantly higher in the asymptomatic group than in the control group. Age, fibrinogen, C-reactive protein, and ferritin levels were higher and the sRAGE level was lower in the patients with lung involvement than in the asymptomatic patients. CONCLUSIONS: In this study, patients with high sRAGE levels were younger and had asymptomatic COVID-19. Patients with low sRAGE levels were elderly patients with lung involvement, which indicates that the RAGE pathway plays an important role in the aggravation of COVID-19.

Adult-onset still's disease and treatment results with tocilizumab.

AIMS: Adult-onset Still's disease (AOSD) is a rare and non-familial auto-inflammatory disorder. Increased levels of IL-6 and other pro-inflammatory cytokines have been shown in AOSD. To evaluate the efficacy and safety profile of tocilizumab (TCZ), an IL-6 receptor antagonist monoclonal antibody, in AOSD. METHODS: Thirty-nine patients followed up with the diagnosis of AOSD between 2013 and 2019 were retrospectively evaluated and the 16 patients (10 Female/6 Male) treated with TCZ for refractory AOSD were included in the study group. Among the remaining 23 patients 16 had non-biological treatments and had no important complications at the presentation. TCZ was given to patients at a dose of 4-8 mg/kg every 4 weeks. Patients were evaluated after 3-6 months of TCZ treatment for side effects, inflammatory and clinical response and concomitant treatments. RESULTS: In TCZ (+) patients, the majority were female (62.5%), the mean age at disease onset was 38.5 ± 17.9 (20-81) years, and the most common symptoms and signs were myalgia (81.3%), fever (81.3%) and skin eruptions (75%). There was no difference between TCZ (+) and TCZ (-) groups for age, sex and clinical presentations. There was a significant decrease in dose of prednisolone, sedimentation rate, leucocyte count, C-reactive protein and ferritin levels and improvement in all clinical complaints after TCZ treatment. There were no relapses during the treatment. Three patients are in remission and under follow-up without any treatment after cessation of TCZ (4 months-3 years). No exacerbation of disease yet seen in those patients. CONCLUSIONS: TCZ is an effective and well-tolerated treatment option for treatment resistant AOSD and contributes to the glucocorticoid-sparing. Since TCZ is a new drug in the treatment of AOSD, further studies are needed to assess whether the complications reported during the treatment are because of TCZ or natural course of the disease or coincidental findings.

The inhibition of Src kinase suppresses the production of matrix metalloproteinases in from synovial fibroblasts and inhibits MAPK and STATs pathways

Background/aim: The purpose of this study was to investigate the antiarthritic potentials of the inhibition of Src kinase in vivo and in vitro settings. Materials and methods: Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund's adjuvant (collagen induced arthritis [CIA] model) in Wistar albino rats. One day after the onset of arthritis, dasatinib, a potent Src kinase inhibitor, (5 mg/kg/day) was given via oral gavage. Tissue Src, Fyn, MAPK and STAT mRNA expressions were determined by real-time polymerase chain reaction. On the other hand, fibroblast like synoviocytes (FLSs) were harvested patients with rheumatoid arthritis (RA) undergoing surgical knee joint replacement. FLSs were stimulated with cytokines and dasatinib was added in different concentrations. MMP ­1, ­3, and ­13 levels in FLSs culture were determined by ELISA. Results: The tissue mRNA expressions of Src, Fyn, MAPK and STATs were increased in the arthritis CIA group compared to the control group. Their mRNA expressions in the CIA + dasatinib group were decreased and similar in the control group. In in vitro setting, MMP ­1, ­3, and ­13 expressions from FLSs induced by IL-1ß and TNF-α were increased, while dasatinib suppressed their productions from FLSs. Conclusion: The present study shows that the inhibition of Src kinase has antiarthritic potentials in both in vivo and in vitro settings. Src kinase inhibition may be candidate to further research in human RA.

Epigallocatechin 3-gallate attenuates arthritis by regulating Nrf2, HO-1, and cytokine levels in an experimental arthritis model.

Epigallocatechin 3-gallate (EGCG) is a polyphenol that has been shown to have antioxidant and anti-inflammatory effects. In this study, collagen-induced arthritis (CIA) model, in Wistar albino rats, was used to elucidate the effect of EGCG on pathogenetic pathways in inflammatory arthritis. The levels of serum TNF-α, IL-17, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx); the expression levels of tissue heme oxygenase-1 (HO-1) and nuclear factor erythroid 2-related factor 2 (Nrf2); histopathologically, perisynovial inflammation and cartilage-bone destruction were examined. In the sham group, serum TNF-α, IL-17, and MDA levels increased, while SOD, CAT, GPx levels, and the expressions of Nrf2 and HO-1 decreased. On the other hand, in the EGCG administered groups, serum TNF-α, IL-17, and MDA levels improved, while SOD, CAT, GPx levels and the expressions of Nrf2 and HO-1 increased. Moreover, histopathological analysis has shown that perisynovial inflammation and cartilage-bone destruction decreased in the EGCG administered groups. These results suggest that EGCG has an antiarthritic effect by regulating the oxidative-antioxidant balance and cytokine levels in the CIA model, which is a surrogate experimental model of rheumatoid arthritis.

Infliximab treatment in refractory vascular Behcet's disease: A single-center experience.

OBJECTIVE: This study aims to investigate the efficacy and reliability of infliximab treatment in Behcet's disease with vascular involvement. METHODS: This single-center retrospective study included a total of 18 patients diagnosed with Behcet's disease with vascular involvement who were initiated infliximab treatment after exhibiting resistance to conventional immunosuppressive treatments. RESULTS: Seventeen patients achieved remission with infliximab treatment. While 18 patients were receiving a median of 50 (IQR: 20-61) mg/day equivalent of methylprednisolone before infliximab treatment, after infliximab treatment, only four patients were receiving 4 mg/day equivalent of methylprednisolone (p < 0.001). Only 4 patients were receiving oral anticoagulant treatment during infliximab treatment, and compared to the patients who were not receiving oral anticoagulants, there was no significant difference between the two groups according to occurrence of new vascular events. CONCLUSION: Infliximab seems to be an effective and reliable treatment in Behcet's disease with vascular involvement and may also allow reduced dosage or even the discontinuation of corticosteroids. The results of our study suggest that oral anticoagulant use is unnecessary in Behcet's disease with vascular involvement. However, further long-term randomized controlled studies are needed to investigate the length of infliximab regimen, whether or not it should be discontinued, and if so, whether or not immunosuppressants should be given as maintenance after discontinuation.

The assessment of the serum levels of TWEAK and prostaglandin F2α in COVID ­ 19

Background/aim: It is claimed that aberrant immune response has a more important role than the cytopathic effect of the virus in the morbidity and mortality of the coronavirus disease 2019 (COVID-19). We aimed to investigate the possible roles of tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/Fn14 pathway and leukotrienes (LT) in uncontrolled immune response that occurs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Materials and methods: This study included 25 asymptomatic patients and 35 patients with lung involvement who were diagnosed with COVID-19 as well as 22 healthy volunteers. Lung involvement was determined using computed-tomography. Serum TWEAK, LTE4, and prostaglandin F2α (PGF2α) levels were determined. Results: Compared with the healthy control group, TWEAK, LTE4, and PGF2α levels were higher in the group of SARS-CoV-2 infection without lung involvement. In the group of SARS-CoV-2 infection with lung involvement, age, fibrinogen, sedimentation, C-reactive protein and ferritin, TWEAK, LTE4, and PGF2α levels were higher, and lymphocyte levels were lower compared with the asymptomatic group. Conclusions: In the study, TWEAK and LTE4 levels increased in cases with COVID-19. These results support that TWEAK/Fn14 pathway and LT may involved in the pathology of aberrant immune response against SARS-CoV-2. Inhibition of each of these pathways may be a potential target in the treatment of COVID-19.

Sleep quality, sleeping postures, and sleeping equipment in patients with ankylosing spondylitis

Background/aim: Inflammatory back pain, spinal stiffness, and limited spinal mobility are characteristic features of ankylosing spondylitis (AS). Sleeping postures can affect and/or reflect sleeping disturbances. The aim of the study was to evaluate sleeping postures and sleep disturbances in patients with AS. Materials and methods: Seventy-seven patients with AS and 49 healthy controls were enrolled. The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) were applied to both groups. The most common sleeping postures were noted. Results: There was no significant difference between the groups in terms of sleeping postures. Total PSQI and ISI scores were higher in the AS group than in the controls (P = 0.004 and P = 0.038, respectively). The selection of sleeping postures of active and inactive patients were similar. The number of pillows used was not the same in the AS and control groups (P = 0.016). The frequency of customized bed use was higher in the AS group compared to the control group (P = 0.004). Conclusion: Sleep disturbances are more of a problem in patients with AS compared to healthy patients and in active AS patients compared to inactive ones. However, sleeping postures do not seem to affect either sleep disturbances or disease activity in patients with AS.

Investigation of the association between Rho/Rho-kinase gene polymorphisms and systemic sclerosis.

Systemic sclerosis (SSc) is a disease characterized by inflammation, vascular abnormalities and fibrosis. The role of Rho/Rho-kinase pathway was demonstrated in the pathogenesis of fibrosis, inflammation and vascular abnormalities. This study was aimed to investigate the relation between SSc and Rho/Rho-kinase gene polymorphisms. The study included 339 patients with SSc and 302 healthy subjects who were apparently healthy and at similar age and gender. Genotype distributions and allele frequencies were detected by using Chi-square test or Fisher's exact Chi-square test between groups, and the haplotype analysis was applied using online program (SHEsis). Significant association was found in a polymorphism in the ROCK1 gene (rs35996865), a polymorphism in ROCK2 gene (rs10178332), a polymorphism in RhoA gene (rs2177268) and two polymorphisms in RhoC gene (rs11102522 and rs11538960) with SSc disease (p < 0.0022). In this study, association between SSc disease and Rho/Rho-kinase gene polymorphisms was investigated for the first time; significant associations between ROCK1, ROCK2, RhoA and RhoC gene polymorphisms and SSc disease were demonstrated. The results strongly suggest that this SNP may be an important risk factor for development of SSc. However, further validation of these findings in an independent cohort is necessary.

The IL-33 gene is related to increased susceptibility to systemic sclerosis.

Systemic sclerosis (SSc) is a chronic inflammatory disease characterized by widespread fibrosis of the skin and several visceral organs. The pro-fibrotic potential of interleukin (IL)-33 has been demonstrated by in both in vitro and in vivo settings; moreover, increased level of IL-33 has also been reported in patients with SSc. Therefore, the aim of the present study was to detect the potential association of IL-33 gene polymorphisms on the susceptibility of SSc. A total of 300 SSc patients and 280 healthy controls (HC) were enrolled in this multicentric preliminary candidate gene study. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms (SNPs) of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. There was no significant difference in terms of the allelic distributions and minor allele frequencies of evaluated four IL-33 polymorphisms between the SSc and HC groups (P > 0.05 for all). Moreover, the genotypic distributions of rs1157505, rs11792633 and rs1929992 polymorphisms were not significantly different (P > 0.05 for all). However, CC genotype of rs7044343 SNP was significantly higher in the SSc group compared to the HC group (P = 0.013, OR 1.75, 95 % CI 1.12-2.72). This preliminary candidate gene study demonstrates that rs7044343 polymorphism of IL-33 gene is associated with the susceptibility to the SSc in Turkish population. It may be suggested that IL-33 gene may be a candidate gene to research in SSc.

Serum IL-33 level and IL-33 gene polymorphisms in Behçet's disease.

Behçet's disease (BD) is a chronic inflammatory disease. Increased productions of cytokines including interleukin (IL)-1ß and IL-18 are documented, and IL-1α and ß gene polymorphisms are associated with susceptibility to the disease. IL-33 is a recently discovered member of IL-1 cytokine family. The aim of the study was to detect serum IL-33 level and IL-33 gene polymorphisms in a cohort of BD. Unrelated 117 patients with BD and 149 healthy controls (HC) were enrolled. Serum IL-33 levels were analyzed by enzyme-linked immunosorbent assay method. DNA samples were harvested using an appropriate commercial DNA isolation kit. Four single nucleotide polymorphisms of IL-33 gene (rs7044343, rs1157505, rs11792633 and rs1929992) were genotyped using the appropriate commercial primer/probe sets on real-time PCR. Serum IL-33 level was not significantly different in the BD and HC groups (p > 0.05). However, its level was lower in the active BD patients compared to the inactive ones and HC group (p = 0.044 and p = 0.037, respectively). There was no significant difference in terms of the genotypic and allelic distributions of rs1157505 and rs1929992 polymorphisms (p > 0.05 for all). However, the TT variants of rs7044343 and rs11792633 polymorphisms were very rare, and the T allele frequencies of these polymorphisms were lower, in the BD group compared to the HC group (p < 0.0001 for all). The rs7044343 and rs11792633 variants of IL-33 gene are associated with the decreased risk of BD in our cohort. Therefore, it may be concluded that IL-33 acts a protective role on the pathogenesis of BD.

The rs3768777-G allele of ITGAV gene is associated with rheumatoid arthritis.

Integrin αvß3 (vitronectin receptor) plays a prominent role in angiogenesis, a key pathogenic feature of rheumatoid arthritis (RA). Moreover, integrin αV (ITGAV) subunit gene has been associated with a susceptibility to RA. The aim of the present study was to detect the potential association between ITGAV gene polymorphisms and a susceptibility to RA in a Turkish cohort. DNA samples were harvested from 160 patients with RA and 144 healthy controls (HC). Three single-nucleotide polymorphisms of ITGAV gene (rs3738919, rs3768777, and rs10174098) were genotyped using real-time PCR. Serum vitronectin levels were analyzed in 30 RA patients, 28 Behçet's disease (BD) patients, and 30 HC subjects. There was no significant difference between the RA and HC groups in terms of the genotypic and allelic distributions of rs3738919 and rs10174098 polymorphisms. However, the prevalence of rs3768777-G allele was higher in the RA group than in the HC group (OR 2.3, 95 % CI 1.6-3.2, p < 0.0001). Moreover, there was a significant association between RA and the genotypic distribution of rs3768777 (GG + AG vs. AA: OR 2.1, 95 % CI 1.3-3.4; GG vs. AG + AA: OR 4.1, 95 % CI 2.1-7.8). Serum vitronectin levels were lower in the RA and BD groups than in the HC group (p ANOVA = 0.002). The rs3738919 and rs10174098 polymorphisms of the ITGAV gene seem not to be associated with susceptibility to RA in Turkish patients. However, rs3768777 increases the risk of RA in this group. These results suggest that the ITGAV gene may be a candidate gene for the etiopathogenesis of RA.

An investigation of the relationship between Behçet's disease and tenascin-C.

Objectives: The study aimed to investigate serum tenascin-C levels and its relationship with pathogenesis of Behçet's disease (BD) with inflammatory processes. Patients and methods: This prospective and analytical study included 34 BD patients (19 males, 15 females; mean age: 31.5±8.2 years; range, 18 to 48 years) who met the 2014 International Criteria for Behçet's Disease and had no comorbidities and 37 healthy volunteers (21 females, 16 males; mean age: 29.6±5.3 years; range, 21 to 45 years). Sex, age, age at diagnosis, clinical and laboratory data, medication use, and smoking history of the participants were recorded. Serum tenascin-C levels were measured using a commercially available tenascin-C enzyme-linked immunosorbent assay kit. Results: There was no significant difference between the groups in terms of age (p=0.262) and sex (p=0.287). Serum tenascin-C levels were significantly lower in the BD group (10,824±7,612 pg/mL) compared to the control group (27,574±14,533 pg/mL, p<0.001). In the receiver operating characteristic analysis performed for the diagnostic value of tenascin-C level in BD, the sensitivity was determined as 79.4% and the specificity as 82.5% (p<0.001). No statistically significant difference was observed in tenascin-C levels in correlation with clinical characteristics, laboratory values, medication use, and smoking in the BD group. Conclusion: In contrast to other chronic inflammatory diseases, lower levels of tenascin-C were observed in patients with BD than in the healthy individuals, which can be attributed to the absence of prolonged chronic inflammatory course in BD. The fact that tenascin-C levels are high in other rheumatic inflammatory diseases but low in BD may be useful in the differential diagnosis of BD.

The Role of Tenascin-C in the Physiopathology of Familial Mediterranean Fever.

OBJECTIVE: Familial Mediterranean fever (FMF) is an autoinflammatory disease common in the Mediterranean basin. It has been determined that tenascin-C level is increased in rheumatic inflammatory diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus, and systemic sclerosis. However, the role of tenascin-C has not been investigated in FMF. This study aimed to investigate serum tenascin-C levels in FMF patients and to investigate possible relationships between them. MATERIALS AND METHODS: About 38 patients diagnosed with FMF and 40 healthy controls were included in the study. The patient's sex, age, clinical symptoms, physical examination, and laboratory results were recorded. Serum tenascin-C levels were determined by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: The serum tenascin-C levels were significantly lower in the FMF patients (10297 ± 8107 pg/ml) compared to the healthy control group (29461 ± 13252 pg/ml) (p < 0.001). In receiver operating characteristic (ROC) analysis, when the cut-off point was chosen as 11076 pg/ml, sensitivity was 77.1% and specificity was 91.9%. When the cut-off point was chosen as 19974 pg/ml, sensitivity was 91.4% and specificity was 75.7%. It was determined that the serum tenascin-C levels did not correlate with age, gender, and laboratory parameters in the healthy control group and FMF patients (p > 0.05). CONCLUSION: This is the first study investigating tenascin-C levels in FMF. Tenascin-C levels in FMF patients were lower than in healthy controls. Low tenascin-C levels in FMF, which are high in other chronic rheumatic diseases, may be a valuable indicator. Therefore, serum tenascin-C level seems to be a useful marker in distinguishing FMF patients from healthy individuals.

The comparison of the impact of ghrelin and tacrolimus on vitreous cytokine levels in an experimental uveitis model.

BACKGROUND: We aimed to compare the effects of intraperitoneal ghrelin and tacrolimus on vitreous levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6) in an experimental autoimmune uveitis model. METHODS: Twenty-four male rats, each weighing 300 g, were assigned into four groups, six rats in each. All the rats, except for those in group 1, were injected intravitreally with concanavalin a to induce experimental uveitis. The development of uveitis was confirmed by the histopathologic examination of two rat globes from each group. The rats in group 2 were not given any treatment after uveitis was induced. The rats in group 3 were administered 1 mg/kg/day of intraperitoneal tacrolimus on days 0, 1, 3, 5 and 7 following the induction of uveitis (on the 14th day of study). The rats in group 4 were given 10 ng/kg/day of intraperitoneal ghrelin for 7 days following the induction of uveitis. On the 21st day of the study, all rats were sacrificed, and the eyes enucleated were subjected to histopathologic examination. Vitreous levels of TNF-α, IL-1 and IL-6 were measured by the enzyme-linked immunosorbent assay method. RESULTS: The histopathologic evaluation carried out to confirm the development of uveitis revealed destruction in the retinae and ciliary bodies of the immunized rats. The mean vitreous levels of TNF-α, IL-1 and IL-6 were significantly higher in the sham group than in the control group (p < 0.05). The levels of these three cytokines showed a significant decrease in the tacrolimus treatment group (p < 0.05). Cytokine levels decreased in the ghrelin treatment group relative to the control group; however, the decrease was not found statistically significant (p > 0.05). CONCLUSIONS: Tacrolimus could be effective in uveitis treatment by neutralizing or decreasing the levels of cytokines such as TNF-α, IL-1 and IL-6 that have a critical part in the pathogenesis of uveitis. However, ghrelin failed to produce the desired effect. Further studies using different doses and different ways of administration are needed to determine the effective dose of ghrelin in uveitis.

Ovarian Reserve and Pelvic Ultrasound Assessment in Familial Mediterranean Fever.

Introduction Familial Mediterranean fever (FMF) is an inflammatory rheumatic disease that affects people in their reproductive period. The aim of this study was to investigate the number of gravida, ovarian reserve, and ovarian doppler characteristics in FMF patients. Methods The study design is cross-sectional. Between November 1, 2018, and October 31, 2019, 40 FMF patients, and 40 age-matched volunteers were included in the study. Early follicular phase follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), progesterone, and anti-Mullerian hormone (AMH) levels, as well as ovarian volume, antral follicle count (AFC), ovarian stromal artery doppler findings, and pelvic pathologies, were evaluated. Results The number of gravida, and the AFC was significantly higher in the control group (16.00 ± 5.22) compared to the patients with FMF (13.00 ± 4.09) (p = 0.026). LH values were significantly higher in the FMF group. Thirteen patients (32.5%) received anakinra and colchicine, and 27 patients (67.5%) received only colchicine. There was no significant difference between the patients receiving anakinra, and the patients receiving colchicine in terms of AMH, FSH, AFC, and E2 values. Conclusion FMF patients were found to have low gravida and AFC, and a significant portion was observed to have pelvic fluid and hydrosalpinx. In conclusion, the presence of pelvic fluid, hydrosalpinx, and low AFC persist in FMF patients despite colchicine and/or anti-interleukin-1 treatments. The low gravida may be related to these pathologies detected in patients with FMF.

Assessment of pulmonary arterial stiffness in patients with systemic sclerosis without overt pulmonary hypertension.

Pulmonary hypertension (PH) is a pathophysiological disorder that may involve multiple clinical conditions and complicate most systemic diseases. Systemic sclerosis (SSc), represents the leading cause of connective tissue disease (CTD) associated with PAH. Although SSc is a rare disease, it is associated with higher morbidity and early mortality than other rheumatological diseases due to developing SSc-associated interstitial pulmonary disease (ILD) and/or pulmonary arterial hypertension (PAH). The impact of the early diagnosis on the prognosis is evident. In this context, in our study, we aimed to investigate the early changes in pulmonary vascular bed by measuring pulmonary arterial stiffness (PAS) in SSc patients without overt PAH. Sixty-two SSc patients and fifty-eight gender and age-matched, healthy subjects enrolled in this cross-sectional observational study. SSc patients were evaluated in terms of disease duration and severity. Modified rodnan skin score (mRSS) was calculated as disease severity index. Echocardiographic parameters were assessed and compared to the control group. Right ventricular (RV) diameters, systolic pulmonary artery pressure (sPAP), and right ventricle myocardial performance index (RV-MPI) were significantly higher in the SSc group compared to the control group (p < 0.05). Tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) were significantly lower in the SSc group compared to the control group (p < 0.05). PAS value (25.5 ± 9.2 kHz/ms vs. 18.1 ± 7.4 kHz/ms, p < 0.001) was significantly higher in the SSc group than in the control group. A statistically significant positive correlation relationship was detected between the PAS value and CRP, ESR, disease duration, mRSS. According to these results, in SSc patients, PAS as an inexpensive and easily applicable echocardiographic method might serve as a marker of early detection of PAH.

The Relationship Between COVID-19 Disease Severity and Zonulin Levels.

Introduction Zonulin is a protein that plays a role in the reversible regulation of epithelial permeability. As zonulin is released in large amounts into the intestinal lumen, it disrupts the integrity of the tight junctions and causes continuous migration of antigens to the submucosa. Consequently, it can trigger inflammatory processes and severe immune reactions. In severe cases, SARS-CoV-2 may have a major impact on the clinical manifestations of the disease by directly or indirectly affecting intestinal cells and triggering systemic inflammation. Therefore, our study aimed to investigate the role of one of the possible mediators, zonulin, in the severity of the COVID-19 infection. Methods  Thirty COVID-19 patients and 35 healthy controls were included in the study. Blood samples were taken from the patients on the 1st, 4th, and 8th days of hospitalization. Serum zonulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Complete blood count (white blood cell [WBC], neutrophil, lymphocyte, and platelet), biochemical parameters (serum lactic acid dehydrogenase [LDH], erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], D-dimer, ferritin, fibrinogen levels) were determined and chronic systemic disease states of the patients were assessed. Results  Serum zonulin levels were notably higher in the healthy control group compared to the patient group (p=0.003). Although there was an increase in the zonulin values by time in hospitalization, this rising was not significant. Conversely, ESR and CRP levels were significantly higher in the patient group (p<0.001). There was no significant difference between the two groups regarding gender, age, and WBC counts. Conclusion  The serum zonulin levels of COVID-19 patients with the mild clinical course were lower than the healthy control group. Moreover, serum zonulin levels were not correlated with ESR, CRP, and other inflammation markers. Our results suggest that low serum zonulin levels in COVID-19 patients might represent a mild disease course.