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[LANGUAGE= \"English\"] Objective: Ankylosing spondylitis (AS) is a chronic systemic inflammatory disease that leads to structural and functional impairments and reduced quality of life, with heterogeneous manifestations. The origin and possible role of extracellular vesicles represented by exosomes (EVexo) in the pathogenesis of AS were examined in this study.Materials and Methods: Extracellular vesicles (EVs) were isolated from serum from ten AS patients and ten healthy controls through Izon qEV2/35 nm columns. After assessing the isolate purity by bicinchoninic acid assay (BCA) and Enzyme-Linked ImmunoSorbent Assay (ELISA), the relationship between EVexo concentration and AS was tested by the BCA method. The EVexo surface markers were analyzed by flow cytometry (FC) to verify EVexo presence and reveal its origin.Results: In FC analysis, CD86+TSG101+ and CD3+TSG101+ exosome percentages of AS group were significantly higher than the control group (p<0.05). A significant difference was found between the AS and control groups in terms of CD3+IL17+ and CD3+IFNg+ and CD86+TNFα+ and CD86+IL12(p35)+ exosome percentages (p<0.01).Conclusion: The exosomes whose ratio increased in the AS process were derived from T cells expressing increased levels of IL-17A and IFNg in their membranes, and macrophages expressing increased levels of TNFα and IL-12(p35) in their membranes. The EVexo profile did not change according to the AS course.

Objective: The aim of this study was to investigate the effects of anti-tumor necrosis factor (anti-TNF) agents on myocardial function and cardiovascular risk factors in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients receiving anti-TNF agents for inflammatory arthritis for six months by using standard and speckle tracking echocardiography. Methods: The study was conducted on a group of 30 patients composed of 12 with RA and 18 with AS. Demographic, standard and speckle tracking echocardiographic data, disease activities, laboratory results related to our research were prospectively assessed. Results: In the study, there was a statistically significant decrease in disease activity score, Bath Ankylosing Spondylitis Disease Activity index, Health Assessment Questionnaire, and Bath Ankylosing Spondylitis Functional Index scores and erythrocyte sedimentation rate, C-reactive protein values of patients with RA and AS in the sixth month of anti-TNF treatment. There was a decrease in left ventricular global longitudinal strain values assessed with speckle tracking echocardiography in the sixth month compared to the baseline and this difference was statistically significant. Conclusion: Myocardial strain imaging might be useful in assessing the early development of cardiac failure in patients with high cardiovascular risk, such as patients with RA and AS.

[LANGUAGE=”English”]Objective:To assess the frequency and related factors of hypogammaglobulinemia (HGG) and severe infections in patients who received rituximab (RTX) for rheumatic diseases during routine followup.Methods:Patients who were followed in Marmara University Rheumatology Clinic and received RTX are evaluated retrospectively. The immunoglobulin (Ig) G, IgM, IgA levels and clinical manifestations were obtained from patient files. The HGG frequency and related factors were assessed. Severe infections were also analysed.Results:A total of 144 patients were included (F/M: 105/39, mean age 52.8±13.8). In the majority of the patients (67%) the diagnosis was rheumatoid arthritis (RA). At least one subgroup of HGG was observed in 30% (43/144) of the patients. During follow-up 17 (11.8%) patients had low IgG, 37 (26%) low IgM, and 7 (4%) had low IgA levels. HGG rate was similar between RA, connective tissue diseases and anti-neutrophil cytoplasmic antibody associated vasculitis patients (25%, 30%, 47%, respectively, p=0.13). HGG was more frequent in men (p=0.028), in patients with higher accumulated RTX dose (p=0.006) and with hypertension (p=0.033). Concomitant use of disease-modifying anti-rheumatic drugs, glucocorticoid use and prior cyclophosphamide was not associated with higher HGG. Methotrexate use with RTX was a protective factor for HGG (HGG rate methotrexate + vs -: 12% vs 33%, p=0.032). Two patients with HGG (5%) received intravenous immunoglobulin replacement. Twenty-seven patients (18%) had severe infections. Lower IgG levels [IgG levels odds rato (OR) (95% confidence interval [CI]) 0.82 (0.70-0.96), p=0.018] and chronic lung disease (CLD) [CLD present OR (95% CI) 3.7 (1.2-10.8), p=0.017] were associated with severe infections in multivariate analysis. A total of 38 patients died during follow-up. Mortality was more frequent in patients with HGG [mortality rate HGG+ vs HGG -: 40% (17/43) vs 21% (20/101), p=0.02].Conclusion:While male gender, increased number of RTX courses and hypertension were found to be risk factors for HGG, CLD and lower IgG levels were associated with severe infections. Therefore, measuring Ig levels and assessing risk factors for HGG and severe infections during RTX treatment may provide information to prevent both conditions.[LANGUAGE=”Turkish”]ÖZETAmaç:Bu çalışmanın amacı rutin takip sırasında romatizmal hastalığı için rituksimab (RTX) alan hastalarda hipogamaglobulinemi (HGG) ve ciddi enfeksiyon sıklığı ve ilişkili faktörleri değerlendirmektir.Yöntem:Marmara Üniversitesi Romatoloji Kliniği’nde takip edilen ve RTX tedavisi alan hastalar retrospektif olarak değerlendirildi. İmmünoglobulin (Ig) G, IgM, IgA seviyeleri ve klinik bulgular hasta dosyalarından elde edildi. HGG sıklığı ve ilişkili faktörler değerlendirildi. Ciddi enfeksiyonlar da ayrıca analiz edildi.Bulgular:Çalışmaya toplam 144 hasta dahil edildi (K/E: 105/39, ortalama yaş 52,8±13,8). Hastaların çoğunluğunda (%67) tanı romatoid artrit (RA) idi. Herhangi bir subgrup HGG %30 (43/144) hastada gözlendi. İzlem sırasında 17 (%11,8) hasta düşük IgG, 37 (%26) hasta düşük IgM, 7 (%4) hasta ise düşük IgA seviyelerine sahipti. RA, bağ doku hastalıkları ve anti-nötrofil sitoplazmik antikor ilişkili vaskülitlerde HGG oranı benzerdi (sırasıyla %25, %30, %47, p=0,13). HGG erkeklerde (p=0,028), kümülatif RTX dozu yüksek olan hastalarda (p=0,006) ve hipertansiyonu olan hastalarda (p=0,033) daha sık idi. Eşlik eden hastalık modifiye edici anti-romatizmal ilaç kullanımı, glukokortikoid ve siklofosfamid kullanım öyküsü HGG ile ilişkili değildi. RTX ile metotreksat kullanımı HGG gelişimi için koruyucu bir faktördü (HGG oranı metotreksat +vs -: %12 vs %33, p=0,032). HGG gelişen 2 (%5) hastaya intravenöz immünoglobulin verildi. Yirmi yedi (%18) hastada ciddi enfeksiyon geliştiği görüldü. Çok değişkenli analizde düşük IgG seviyeleri [IgG düzeyi risk oranı (RO) (%95 güven aralığı [GA]) 0,82 (0,70-0,96), p=0,018] ve kronik akciğer hastalığı (KAH) [KAHv arlığı RO (%95 GA) 3,7 (1,2-10,8), p=0,017] ciddi enfeksiyonda artış ile ilişkili idi. İzlem sırasında 38 hastada ölüm görüldü. Mortalite HGG gelişen hastalarda daha sık idi [mortalite oranı HGG+ vs HGG -: %40 (17/43) vs %21 (20/101), p=0,02].Sonuç:Erkek cinsiyet, RTX doz artışı ve hipertansiyon HGG için risk faktörü iken, kronik akciğer hastalığı ve düşük IgG düzeyi ciddi enfeksiyon ile ilişkiliydi. Bu nedenle RTX tedavisi sırasında Ig düzeylerinin ölçümü ve HGG ve ciddi enfeksiyon için risk faktörlerinin değerlendirilmesi her iki durumun önlenmesinde yarar sağlayabilir.

Objective: The aim of this study was to investigate the effects of antitumor necrosis factor (anti-TNF) agents on myocardial function and cardiovascular risk factors in rheumatoid arthritis (RA) and ankylosing spondylitis (AS) patients receiving anti-TNF agents for inflammatory arthritis for six months by using standard and speckle tracking echocardiography. Methods: The study was conducted on a group of 30 patients composed of 12 with RA and 18 with AS. Demographic, standard and speckle tracking echocardiographic data, disease activities, laboratory results related to our research were prospectively assessed. Results: In the study, there was a statistically significant decrease in disease activity score, Bath Ankylosing Spondylitis Disease Activity index, Health Assessment Questionnaire, and Bath Ankylosing Spondylitis Functional Index scores and erythrocyte sedimentation rate, C-reactive protein values of patients with RA and AS in the sixth month of anti-TNF treatment. There was a decrease in left ventricular global longitudinal strain values assessed with speckle tracking echocardiography in the sixth month compared to the baseline and this difference was statistically significant. Conclusion: Myocardial strain imaging might be useful in assessing the early development of cardiac failure in patients with high cardiovascular risk, such as patients with RA and AS. Keywords: Tumor necrosis factor antagonist, cardiovascular risk, rheumatoid arthritis, ankylosing spondylitis Amac: Calismanin amaci, romatoid artrit (RA) ve ankilozan spondilit (AS) hastalarinda, alti ay sureyle anti-tumor nekroz faktoru (anti-TNF) ku llanim in in miyokard fonksiyonu ve kardiyovaskuler risk faktorleri uzerindeki etkilerini standart ve speckle tracking ekokardiyografi kullanarak arastirmaktir. Yontem: Calismaya 12 RA ve 18 AS olmak uzere toplam 30 hasta dahil edildi. Arastirmamizla ilgili demografik, standart ve speckle tracking ekokardiyografik veriler, hastalik aktiviteleri, laboratuvar sonuclari prospektif olarak degerlendirildi. Bulgular: Calismada anti-TNF tedavisinin altinci ayinda RA ve AS'li hastalarin hastalik aktivite skoru, Bath Ankilozan Spondilit Hastalik Aktivite indeksi, Saglik Degerlendirme Anketi ve Bath Ankilozan Spondilit Fonksiyonel indeksi skorlarinda ve eritrosit sedimentasyon hizinda, C-reaktif protein degerlerinde istatistiksel olarak anlamli dusus saptandi. Speckle tracking ekokardiyografi ile degerlendirilen sol ventrikul global longitudinal strain degerlerinde baslangica kiyasla altinci ayda istatistiksel olarak anlamli azalma oldugu saptandi. Sonuc: Miyokardiyal strain goruntulemesi RA ve AS'li hastalar gibi yuksek kardiyovaskuler riski olan hastalarda kalp yetmezliginin erken gelisimini degerlendirmede yararli olabilir. Anahtar Kelimeler: Tumor nekroz faktor antagonist, kardiyovaskuler risk, romatoid artrit, ankilozan spondilit

Objective: To assess the frequency and related factors of hypogammaglobulinemia (HGG) and severe infections in patients who received rituximab (RTX) for rheumatic diseases during routine follow-up. Methods: Patients who were followed in Marmara University Rheumatology Clinic and received RTX are evaluated retrospectively. The immunoglobulin (Ig) G, IgM, IgA levels and clinical manifestations were obtained from patient files. The HGG frequency and related factors were assessed. Severe infections were also analysed. Results: A total of 144 patients were included (F/M: 105/39, mean age 52.8[+ or -]13.8). In the majority of the patients (67%) the diagnosis was rheumatoid arthritis (RA). At least one subgroup of HGG was observed in 30% (43/144) of the patients. During follow-up 17 (11.8%) patients had low IgG, 37 (26%) low IgM, and 7 (4%) had low IgA levels. HGG rate was similar between RA, connective tissue diseases and anti-neutrophil cytoplasmic antibody associated vasculitis patients (25%, 30%, 47%, respectively, p=0.13). HGG was more frequent in men (p=0.028), in patients with higher accumulated RTX dose (p=0.006) and with hypertension (p=0.033). Concomitant use of disease-modifying anti-rheumatic drugs, glucocorticoid use and prior cyclophosphamide was not associated with higher HGG. Methotrexate use with RTX was a protective factor for HGG (HGG rate methotrexate + vs -: 12% vs 33%, p=0.032). Two patients with HGG (5%) received intravenous immunoglobulin replacement. Twenty-seven patients (18%) had severe infections. Lower IgG levels [IgG levels odds rato (OR) (95% confidence interval [CI]) 0.82 (0.70-0.96), p=0.018] and chronic lung disease (CLD) [CLD present OR (95% CI) 3.7 (1.2-10.8), p=0.017] were associated with severe infections in multivariate analysis. A total of 38 patients died during follow-up. Mortality was more frequent in patients with HGG [mortality rate HGG+ vs HGG -: 40% (17/43) vs 21% (20/101), p=0.02]. Conclusion: While male gender, increased number of RTX courses and hypertension were found to be risk factors for HGG, CLD and lower IgG levels were associated with severe infections. Therefore, measuring Ig levels and assessing risk factors for HGG and severe infections during RTX treatment may provide information to prevent both conditions. Keywords: Rituximab, hypogammaglobulinemia, severe infection, rheumatic diseases Amac: Bu calismanin amaci rutin takip sirasinda romatizmal hastaligi icin rituksimab (RTX) alan hastalarda hipogamaglobulinemi (HGG) ve ciddi enfeksiyon sikligi ve iliskili faktorleri degerlendirmektir. Yontem: Marmara Universitesi Romatoloji Klinigi'nde takip edilen ve RTX tedavisi alan hastalar retrospektif olarak degerlendirildi. Immunoglobulin (Ig) G, IgM, IgA seviyeleri ve klinik bulgular hasta dosyalarindan elde edildi. HGG sikligi ve iliskili faktorler degerlendirildi. Ciddi enfeksiyonlar da ayrica analiz edildi. Bulgular: Calismaya toplam 144 hasta dahil edildi (K/E: 105/39, ortalama yas 52,8[+ or -]13,8). Hastalarin cogunlugunda (%67) tani romatoid artrit (RA) idi. Herhangi bir subgrup HGG %30 (43/144) hastada gozlendi. Izlem sirasinda 17 (%11,8) hasta dusuk IgG, 37 (%26) hasta dusuk IgM, 7 (%4) hasta ise dusuk IgA seviyelerine sahipti. RA, bag doku hastaliklari ve anti-notrofil sitoplazmik antikor iliskili vaskulitlerde HGG orani benzerdi (sirasiyla %25, %30, %47, p=0,13). HGG erkeklerde (p=0,028), kumulatif RTX dozu yuksek olan hastalarda (p=0,006) ve hipertansiyonu olan hastalarda (p=0,033) daha sik idi. Eslik eden hastalik modifiye edici anti-romatizmal ilac kullanimi, glukokortikoid ve siklofosfamid kullanim oykusu HGG ile iliskili degildi. RTX ile metotreksat kullanimi HGG gelisimi icin koruyucu bir faktordu (HGG orani metotreksat +vs -: %12 vs %33, p=0,032). HGG gelisen 2 (%5) hastaya intravenoz immunoglobulin verildi. Yirmi yedi (%18) hastada ciddi enfeksiyon gelistigi goruldu. Cok degiskenli analizde dusuk IgG seviyeleri [IgG duzeyi risk orani (RO) (%95 guven araligi [GA]) 0,82 (0,70-0,96), p=0,018] ve kronik akciger hastaligi (KAH) [KAHv arligi RO (%95 GA) 3,7 (1,2-10,8), p=0,017] ciddi enfeksiyonda artis ile iliskili idi. Izlem sirasinda 38 hastada olum goruldu. Mortalite HGG gelisen hastalarda daha sik idi [mortalite orani HGG+ vs HGG-: %40 (17/43) vs %21 (20/101), p=0,02]. Sonuc: Erkek cinsiyet, RTX doz artisi ve hipertansiyon HGG icin risk faktoru iken, kronik akciger hastaligi ve dusuk IgG duzeyi ciddi enfeksiyon ile iliskiliydi. Bu nedenle RTX tedavisi sirasinda Ig duzeylerinin olcumu ve HGG ve ciddi enfeksiyon icin risk faktorlerinin degerlendirilmesi her iki durumun onlenmesinde yarar saglayabilir. Anahtar Kelimeler: Rituksimab, hipogamaglobulinemi, ciddi enfeksiyon, romatolojik hastaliklar

To evaluate the static and dynamic balances in psoriatic arthritis (PsA) and to investigate their relationship with clinical and functional parameters. Patients diagnosed with PsA and healthy controls were recruited consecutively into the study. The demographic variables such as age, sex, body mass index of the subjects were noted. Radiographic images were examined for the detection of foot deformities. ‘Foot and Ankle Outcome Score’ (FAOS) was used to assess foot function. The dynamic and static balance of the patients was evaluated by ‘Berg Balance Scale’ (BBS) and ‘Neurocom Balance Master’ device. The fatigue (Multidimensional Assessment of Fatigue: MAF), depression (Beck Depression Inventory: BDI) and sleep disorders (Pittsburgh Sleep Quality Index: PSQI) of all patients were evaluated. This study included 50 PsA patients and 50 healthy controls with mean ages of 45.02 (SD 12.81) and 45.12 (SD 10.56), respectively. Demographic data of both groups were similar. Concerning the balance tests, there were significant differences (p < 0.05) between patient and control groups about the all tests of sway velocity (except on foam surface eyes closed test), end sway of tandem walk test, movement time of bilateral step up over test and lift up index of left step up over test. There was no significant correlation between static and dynamic balance parameters with MAF, BDI, PSQI, foot deformities and FAOS. The static and dynamic balance impairments are seen in PsA. As the balance parameters had no significant correlation with functional and clinical data, they are acceptable as independent parameters during the course of the disease.

Hemophagocytic syndrome (HPS) or hemophagocytic lymphohistiocytosis (HLH) is an acute and rapidly progressive systemic inflammatory disorder characterized by cytopenia, excessive cytokine production, and hyperferritinemia. Common clinical manifestations of HLH are acute unremitting fever, lymphadenopathy, hepatosplenomegaly, and multiorgan failure. Due to a massive cytokine release, this clinical condition is considered as a cytokine storm syndrome. HPS has primary and acquired (secondary, reactive) forms. Its primary form is mostly seen in childhood and caused by various mutations with genetic inheritance and, therefore, is called familial HLH. Secondary HLH may be caused in the presence of an underlying disorder, that is, secondary to a malignant, infectious, or autoimmune/autoinflammatory stimulus. This paper aims to review the pathogenesis and the clinical picture of HLH, and its severe complication, the cytokine storm, with a special emphasis on the developed classification criteria sets for rheumatologists, since COVID-19 infection has clinical symptoms resembling those of the common rheumatologic conditions and possibly triggers HLH. MED-LINE/Pubmed was searched from inception to April 2020, and the following terms were used for data searching: “hemophagocytic syndrome” OR “macrophage activation syndrome” OR “hemophagocytic lymphohistiocytosis”, OR “cytokine storm”. Finally, AND “COVID-19” was included in this algorithm. The selection is restricted to the past 5 years and limited numbers of earlier key references were manually selected. Only full-text manuscripts, published in an English language peer-reviewed journal were included. Manuscript selection procedure and numbers are given in Fig. 2. Briefly, the database search with the following terms of “Hemophagocytic syndrome” OR “Macrophage activation syndrome” OR “Hemophagocytic lymphohistiocytosis” OR “Cytokine storm” yielded 6744 results from inception to April 2020. The selection is restricted to the past 5 years and only limited numbers of earlier key references were selected, and this algorithm resulted in 3080 manuscripts. The addition of (AND “COVID-19”) resulted in 115 publications of which 47 studies, together with four sections of an online book were used in the final review. No statistical method was used. HLH is triggered by genetic conditions, infections, malignancies, autoimmune-autoinflammatory diseases, and some drugs. In COVID-19 patients, secondary HLH and cytokine storm may be responsible for unexplained progressive fever, cytopenia, ARDS, neurological and renal impairment. Differentiation between the primary and secondary forms of HLH is utterly important, since primary form of HLH requires complicated treatments such as hematopoietic stem cell transplantation. Further studies addressing the performance of HScore and other recommendations in the classification of these patients is necessary.

COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.

Newly emerging variants of coronavirus 2 (SARS-CoV-2) raise concerns about the spread of the disease, and with the rising case numbers, the Coronavirus disease 2019 (COVID-19) remains a challenging medical emergency towards the end of the year 2021. Swiftly developed novel vaccines aid in the prevention of the spread, and it seems that a specific cure will not be at hand soon. The prognosis of COVID-19 in patients with autoimmune/autoinflammatory rheumatic diseases (AIIRD) is more severe when compared to the otherwise healthy population, and vaccination is essential. Evidence for both the efficacy and safety of COVID-19 vaccination in AIIRD under immunosuppression is accumulating, but the effect of Interleukin-1 on vaccination in general and in AIIRD patients is rarely addressed in the current literature. In light of the current literature, it seems that the level of agreement on the timing of COVID-19 vaccination is moderate in patients using IL-1 blockers, and expert opinions may vary. Generally, it may be recommended that patients under IL-1 blockade can be vaccinated without interrupting the anti-cytokine therapy, especially in patients with ongoing high disease activity to avoid disease relapses. However, in selected cases, after balancing for disease activity and risk of relapses, vaccination may be given seven days after the drug levels have returned to baseline, especially for IL-1 blocking agents with long half-lives such as canakinumab and rilonacept. This may help to ensure an ideal vaccine response in the face of the possibility that AIIRD patients may develop a more pronounced and severe COVID-19 disease course.