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.

Pneumomediastinum, pneumatosis intestinalis and pneumoperitoneum in a patient with polymyositis: case-based review.

Pneumomediastinum (PnM), pneumatosis intestinalis (PI), and pneumoperitoneum (PP) are rare complications of inflammatory myositis. We present a 59-year-old polymyositis (PM) patient who experienced all three complications simultaneously. The patient who presented with proximal muscle weakness, dysphagia, and weight loss was diagnosed with PM due to elevated muscle enzymes and consistent electromyography and muscle biopsy with inflammatory myopathy. On the 45th day of her immunosuppressive treatment, PnM, PI, and PP were detected incidentally in 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan performed for severe weight loss and treatment-resistant severe disease. Since the patient had no symptoms or signs of PnM and PP, no additional intervention was applied to the current treatment, and spontaneous regression was observed in the follow-up. In addition to this case, we reviewed patients with PM who developed PBM, PP, and PI in the literature.

The risk of cancer in patients with primary Sjögren syndrome: a single-center study from Turkey.

BACKGROUND: The aim of this study is to determine the risk of cancer in patients with primary Sjögren syndrome (pSS) from a single center in Turkey. METHODS: Clinical data of the subjects with pSS were retrospectively analyzed. The incidence of cancer for general population was obtained from GLOBOCAN 2018. Age- and sex-specific standardized incidence ratios (SIR) of solid and hematological cancers were calculated compared with the general population. RESULTS: Four hundred thirty patients with pSS were included in the study. The majority of the patients were female (n = 396, 92.1%), and the mean age was 58.6 ± 12.0 years. Thirty-four patients (7.9 %) were diagnosed with cancer (26 solid and 8 hematological) during follow-up. The SIR for all cancers was 2.45 (95% CI, 1.625-3.275). The SIR was 2.42 (95% CI, 1.542-3.298) for solid cancers and 8.42 (95% CI, 2.394 - 14.446) for hematological cancers. The most diagnosed malignancies were breast cancer (n = 6), ovarian cancer (n = 6), and non-Hodgkin lymphoma (NHL) (n = 4). There was an increased risk for ovarian cancer (SIR 12.76, 95% CI, 2.545-22.975). The SIR values were 2.08 (95% CI, 0.419-3.741) and 10.81 (95% CI, 0.216-21.404) for breast cancer and NHL, respectively. DISCUSSION: The risk of hematological and solid cancers was higher in the patients with pSS when compared to general population. In our pSS cohort, the risk for ovarian cancer was found to be increased, which has not been previously reported in the literature.

Characterization of Some Microorganisms from Human Stool Samples and Determination of Their Effects on CT26 Colorectal Carcinoma Cell Line.

The present study aimed to isolate and identify the potential probiotic, pathobiont, and pathogenic microorganisms in the stool samples of 12 healthy individuals and evaluate their in vitro effects on cancer formation. A total of 83 strains were isolated from the stool samples and identified using MALDI-Biotyper. Fourteen of the isolates were identified as Candida spp., three isolates were identified as Cryptococcus neoformans, 55 isolates were identified as lactic acid bacteria, and the remaining isolates belonged to different 11 bacterial genera. Important microbial properties for cancer prevention and some probiotic properties were examined. All strains maintained their viability under acidic conditions and in media containing bile salts. Of the bacterial strains, 62.5% were resistant to ampicillin, chloramphenicol, gentamicin, erythromycin, kanamycin, penicillin, streptomycin, tetracycline, and vancomycin. All yeast strains were resistant to ketoconazole and susceptible to nystatin. The susceptibility of the strains to fluconazole, voriconazole, amphotericin B, and itraconazole varied. Fifty-nine percent of the strains produced EPS and 21.7% showed proteolytic activity (PA). Of the strains, 15.7% both produced exopolysaccharides (EPS) and had PA. The antioxidant activity (AOA) varied depending on the strains. The pathobiont and pathogenic microorganisms promoted tumor formation, while potential probiotic microorganisms had a suppressive effect on tumor formation (P > 0.01). One yeast (Candida kefyr MK17) and three lactic acid bacteria strains (Lacticaseibacillus paracasei MK73, Lactiplantibacillus plantarum MK55, Limosilactobacillus mucosae MK45) have superior potential thanks to their anticarcinogenic properties as well as tolerance to gastrointestinal tract conditions. Stool samples of each individual contain various potential probiotic, pathobiont, and pathogenic microorganisms.

The Diagnostic Value of Fluoro-18 Fluorodeoxyglucose (F-18 FDG) PET/CT in Fever or Inflammation of Unknown Origin: A Retrospective Study at a Rheumatology Clinic.

Introduction Further diagnostic procedures are necessary for patients with fever of unknown origin (FUO) and unknown cause of inflammation (inflammation of unknown origin - IUO) for the identification of the definitive diagnosis. The aim of this study was to evaluate the contribution and roles of F-18 FDG PET/CT (fluoro-18 fluorodeoxyglucose-positron emission tomography/computed tomography) in the diagnostic process of patients with FUO/IUO. Methods The data of 58 patients who had F-18 FDG PET/CT scans for FUO/IUO were re-evaluated retrospectively. The relationships between definitive diagnosis and fluorodeoxyglucose uptake and SUVmax (maximum standardized uptake value) were examined. Results  Rheumatic disease was diagnosed in 26 patients (44.5%), malignancy in 20 patients (34.5%), and infectious diseases in six patients (10.3%). The most prevalent rheumatic disease in patients with FUO/IUO was systemic vasculitis (n:10, 17.2%), especially large vessel vasculitis. There were 37 patients (63.7%) with clinically significant true positive fluorodeoxyglucose uptake. True positive fluorodeoxyglucose uptake was significantly higher in patients diagnosed with malignancy (85%, 17/20 patients) compared to other diagnoses. Fluorodeoxyglucose uptake above physiological levels was determined in 15 of the 26 patients (57.6%) diagnosed with rheumatic diseases. Conclusion The results of this study showed that F-18 FDG PET/CT is a useful imaging modality in FUO/IUO patients, who present a challenging diagnostic process for clinicians. In addition to malignancies, the presence of chronic inflammatory diseases, especially early period systemic vasculitis, were diagnosed in these patients.

Real-world data on change in work productivity, activity impairment, and quality of life in patients with psoriatic arthritis under anti-TNF therapy: a postmarketing, noninterventional, observational study.

OBJECTIVES: To understand change in work productivity, activity impairment, quality of life (QoL), and disease activity in patients with psoriatic arthritis (PsA) receiving anti-tumor necrosis factor (anti-TNF) treatment. METHOD: One hundred twenty patients with PsA receiving anti-TNF therapy were recruited to this noninterventional, observational study. Work disability was assessed via the Work Productivity and Activity Impairment (WPAI) questionnaire and disease activity was calculated via the 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP) and Disease Activity Index for Psoriatic Arthritis with 28 joints (DAPSA28) score. Patient-reported outcomes (PROs), from visual analog scores and Health Assessment Questionnaire-Disability Index scores, were evaluated to understand the clinical effectiveness at baseline and every 3 months until the month-9 final visit. The American College of Rheumatology (ACR)20/50/70 response criteria were assessed at month 9. RESULTS: A total of 120 patients (females, n = 73) were enrolled in the study. Mean (SD) age and disease duration were 41.6 ± 11.1 years and 6.9 ± 6.5 years, respectively. The most commonly used TNFα inhibitor was adalimumab (42.4%), followed by etanercept (25.8%). All WPAI questionnaire parameters were reduced at the follow-up visits compared with baseline (p < 0.001 for all). PROs and disease activity indicators (DAS28-CRP and DAPSA28) significantly improved during the course of anti-TNF treatments (p < 0.001 for all). Additionally, ACR20/50/70 responses were determined as 86.8%, 63.7%, and 41.8% of patients at the month-9 visit. CONCLUSIONS: The real-world data in PsA patients receiving anti-TNF treatment showed improvement in WPAI, QoL, and disease activity over 9 months of treatment. TRIAL REGISTRATION: NCT02028169 Key Points • Psoriatic arthritis (PsA), with debilitating effects on quality of life, occurs mostly in young adults and has negative impacts on employment status and work productivity. • Early PsA diagnosis and treat-to-target treatment strategies aim to reduce pain and joint damage, as well as improve work productivity. • Real-world data on the impact of treatment with anti-tumor necrosis factor (anti-TNF) agents on work productivity in PsA in the literature is scarce. • Our study of real-world data in patients with PsA receiving anti-TNF treatment showed improvement in work productivity, as well as in clinical and patient-reported outcomes.

The risk of cancer in patients with primary Sjögren syndrome; A single-center study from Turkey.

BACKGROUND: The aim of this study is to determine the risk of cancer in the patients with primary Sjögren syndrome (pSS) from a single-center in Turkey. METHODS: Clinical data of the subjects with pSS were retrospectively analyzed. The incidence of cancer for general population was obtained from GLOBOCAN 2018. Age- and sex-specific Standardized Incidence Ratios (SIR) of solid and hematological cancers were calculated compared with the general population. RESULTS: Four hundred thirty patients with pSS were included in the study. The majority of the patients were female (n=396, 92.1%), and the mean age was 58.6 ±12.0 years. Thirty-four patients (7.9 %) were diagnosed with cancer (26 solid and 8 hematological) during follow-up. The SIR for all cancers was 2.45 (95% CI, 1.625- 3.275). The SIR was 2.42 (95% CI, 1.542-3.298) for solid cancers and 8.42 (95% CI, 2.394 - 14.446) for hematological cancers. The most diagnosed malignancies were breast cancer (n=6), ovarian cancer (n=6), and non-Hodgkin lymphoma (NHL) (n=4). There was an increased risk for ovarian cancer (SIR 12.76; 95% CI, 2.545-22.975). The SIR values were 2.08 (95% CI, 0.419-3.741) and 10.81 (95% CI, 0.216-21.404) for breast cancer and NHL, respectively. CONCLUSION: The risk of hematological and solid cancers was higher in the patients with pSS when compared to general population. In our pSS cohort, the risk for ovarian cancer was found to be increased, which has not been previously reported in the literature.

The effects of biological agents on vascular structural lesions in Takayasu's arteritis.

OBJECTIVES: The aim of the present study was to evaluate the effects of biological disease-modifying antirheumatic drugs (bDMARDs) administered to patients with Takayasu's arteritis (TAK) on disease activity and vascular damage. METHODS: This study included TAK patients who were receiving bDMARDs for at least six months. Disease activity (National Institutes of Health [NIH]), vascular lesions, and vascular damage (Combined Arteritis Damage Score [CARDS]) scores were determined. RESULTS: There were 21 TAK patients who received infliximab (INF) and/or tocilizumab (TCZ) (mean age = 38.6±11.8 years; female proportion = 20 [95.2%]). The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and NIH disease activity score were found to significantly decrease with bDMARD treatments. There were also significant decreases in the mean CARDS and the total number of vascular lesions after treatment (p<0.05). Unlike occlusions, an important decrease was observed in the occurrences of stenosis and aneurysms with bDMARD treatments. Regression was detected in the vascular lesions of 15 (71.4%) patients compared to the last image before bDMARD therapies. CONCLUSIONS: Our study results indicate that biological agents, such as INF and/or TCZ, that are used in the treatmentof TAK are capable of remedying certain vascular lesions and may provide additional benefits to patients with TAK who do not sufficiently respond to conventional synthetic disease-modifying antirheumatic drug (DMARD) treatment.

Clinical and serological characteristics of seronegative primary Sjögren's syndrome: a comparative study.

OBJECTIVES: This study compared the clinical and serological characteristics of seronegative and seropositive primary Sjögren syndrome (pSS) and examined whether current classification criteria for pSS cover seronegative pSS. METHODS: The study group comprised 375 patients (341 women and 34 men) diagnosed with pSS. A clinical diagnosis by an expert rheumatologist was considered the "gold standard" for the diagnosis of pSS. The clinical and serological characteristics of the patients were retrospectively collected from hospital medical files. RESULTS: Fifty-eight of the 375 pSS patients (15.5%) were seronegative for ANA, RF, anti-Ro, and anti-La autoantibodies. Seronegative pSS was diagnosed based on lymphocytic infiltrations in lip biopsy samples. There were no statistically significant differences in terms of patient age, age at diagnosis, sex distribution, clinical features, and laboratory findings between seronegative and seropositive pSS. The frequency of hypergammaglobulinemia was higher in seropositive pSS. The 2016 ACR/ULAR criteria best covered most seronegative pSS cases (84.5%). For seronegative pSS, the agreement between the 2002 AECG, 2012 ACR, and 2016 ACR/EULAR criteria was relatively low. CONCLUSIONS: The clinical features of seronegative pSS (i.e., a lack of four autoantibodies in serum) were similar to those of seropositive pSS. The current classification criteria for pSS should not be used in the diagnosis of seronegative pSS, as the agreement between the different sets of criteria was low, and some patients fell outside the classification. Further clinical and laboratory studies are needed to identify the features that distinguish seronegative pSS. Key Points • Approximately 15% of the pSS patients were seronegative for ANA, RF, anti-Ro, and anti-La autoantibodies. • Seronegative pSS was diagnosed based on lymphocytic infiltrations in lip biopsy samples. • The clinical features of seronegative pSS were similar to those of seropositive pSS. • The current classification criteria for pSS should not be used in the diagnosis of seronegative patients, as the agreement between the different sets of criteria was low, and some patients fell outside the classification.

Survival analysis of patients with Sjögren's syndrome in Turkey: a tertiary hospital-based study.

OBJECTIVES: This study was conducted to determine long-term survival rates and the factors associated with mortality in Turkish primary Sjögren syndrome (pSS) patients. METHODS: All patients diagnosed with pSS between 2004 and 2014 were included in this study. By January 2019, all subjects still living by the end of the study, as well as any death, were identified. Survival rates and standard mortality rates (SMRs) using general population mortality data were calculated. Mortality-related factors were determined by univariate and multivariate analysis. RESULTS: During follow-up, 33 cases of 372 pSS patients resulted in death (8.9%). Of those patients, they were typically older at disease onset, at recruitment, and had shorter follow-up times (p < 0.001 for all). The overall SMR of all pSS patients compared with the general population was 2.11 (95% confidence interval (CI) 1.39-2.83). Male pSS patients had a higher SMR than that of general male patients. Overall survival rates were 97.8% at five years, 90.2% at 10 years, and 87.1% at 15 years in patients with pSS. The survival rate of pSS patients was significantly lower than the general Turkish population (p = 0.011). Multivariate Cox regression analysis showed that older age at disease onset and the presence of interstitial lung disease (ILD) were independent risk factors for mortality. CONCLUSIONS: Based on these data, mortality rates of Turkish pSS patients are higher compared with the general population. Survival significantly decreased in the pSS patients with ILD, especially in older male patients at disease onset. Male gender and malignancy may also be associated with a worse prognosis in pSS patients.Key Point• Mortality in Sjögren's syndrome.

Primary Sjögren's syndrome in patients with celiac disease.

BACKGROUND/AIM: Many autoimmune diseases occur concomitantly with celiac disease (CD). We aimed to determine the frequency of Sjögren's syndrome (SS) in CD patients based on SS-specific serology verified by minor labial salivary biopsy. MATERIALS AND METHODS: Eight-two patients with CD were included in the study. After examination for objective evidence of sicca complex, all patients were tested for serological presence of rheumatoid factor (RF) and antinuclear antibodies (ANAs) and for ANA profile. Minor labial salivary biopsy was performed for patients with positive serology and/or clinical signs of SS. RESULTS: Of the patients included, 24 (29.3%) had dry eye symptoms while 20 (24.4%) had dry mouth symptoms. Dry eye was detected by Schirmer test in 10 patients (12.2%) and by ocular staining score in only 2 patients (2.4%). All samples were negative for RF while 12 (14.6%) samples were positive for ANAs. Of 82 patients with CD, the diagnosis of SS was established in only one patient (1.2%), while one patient (1.2%) was diagnosed with morphea and 4 patients (4.9%) were classified as having undifferentiated connective tissue disease. CONCLUSION: The prevalence of SS in CD is low, so there is no need for serologic screening of all patients with CD for SS.

Leptin and leptin receptors in salivary glands of primary Sjögren's syndrome.

BACKGROUND: The role of leptin in primary Sjögren's syndrome (SS) pathogenesis is unknown. The aim of this study was to investigate the expression of leptin and leptin receptor (LEPR) in minor salivary glands in patients with SS. MATERIALS AND METHODS: The expression of leptin and LEPR in minor salivary gland specimens obtained from patients with primary SS (n=50) and control subjects (n=50) were examined using immunohistochemical staining. RESULTS: Acinar cells, epithelial cells and adipocytes in salivary glands can express leptin and LEPR. It was observed that there was intense staining in the focal lymphocytic infiltration areas in SS patients. The intensity of leptin and LEPR staining under microscopy (400×) were graded semiquantitatively as negative, mild, moderate or strongly positive, and scored as 1, 2 or 3, respectively. The expression levels of leptin and LEPR in patients with primary SS were not higher than in controls. There was no significant difference in degrees of leptin and LEPR staining, staining intensity, and immunoreactive scores between groups. The expression of leptin and LEPR were not correlated with autoantibodies such as RF, ANA, anti-Ro, and/or anti-La positivity. CONCLUSIONS: These findings indicate that leptin and its receptors do not play an important role in primary SS pathophysiology.