Association of nociplastic and neuropathic pain components with the presence of residual symptoms in patients with axial spondyloarthritis receiving biological disease-modifying antirheumatic drugs.

OBJECTIVE: To evaluate the association of nociplastic (NoP) and neuropathic pain (NP) components with residual symptoms in patients with radiographic axial spondyloarthritis (r-axSpA) receiving biological disease-modifying antirheumatic drugs (bDMARDs). METHODS: 78 patients with r-axSpA from the GErman SPondyloarthritis Inception Cohort receiving a bDMARD for at least 3 months were included in this analysis. The Widespread Pain Index (WPI) and the PainDETECT (PD) questionnaire were used to quantify the NoP and the NP components, respectively. Axial Spondyloarthritis Disease Activity Score (ASDAS) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) were used as measures of residual symptoms. C reactive protein (CRP) was used as a measure of systemic inflammatory activity. Univariable and multivariable regression analyses of disease activity were performed. The regions of the WPI score and items of the PD score were used for cluster analyses. RESULTS: Linear multivariable regression analysis showed that WPI and PD were independently associated with ASDAS (b=0.1, 95% CI 0.04 to 0.17, and b=0.05, 95% CI 0.02 to 0.08, respectively) and BASDAI (b=0.24, 95% CI 0.08 to 0.39, and b=0.17, 95% CI 0.1 to 0.25, respectively) in r-axSpA patients receiving stable treatment with bDMARDs. Furthermore, WPI and PD were found to be significantly associated with the presence of relevant residual symptoms as defined by BASDAI ≥4 (OR 1.93, 95% CI 1.09 to 4.15, and OR 1.32, 95% CI 1.04 to 1.85, respectively). The effects were present also in patients with normal level of CRP. Cluster analysis revealed three distinct pain distribution profiles and four specific sensory symptom constellations allowing differentiation of different pain subtypes. CONCLUSION: Both NoP and NP components seem to be associated with residual symptoms in patients with r-axSpA receiving treatment with bDMARDs.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial.

OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.

Difficult-to-treat psoriatic arthritis (D2T PsA): a scoping literature review informing a GRAPPA research project.

BACKGROUND: Psoriatic arthritis (PsA) is a multifaceted condition with a broad spectrum of manifestations and a range of associated comorbidities. A notable segment of patients with PsA remains resistant to even advanced therapeutic interventions. This resistance stems from myriad causes, including inflammatory and non-inflammatory factors. OBJECTIVES: To collate and critically assess the various definitions and criteria of difficult-to-treat (D2T PsA present in the literature. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines, we conducted a scoping review in July 2023, searching PubMed, American College of Rheumatology Convergence 2022, European Alliance of Associations for Rheumatology Congress 2023, Google Scholar and cited articles. Selection was made by two independent authors using Rayyan software, and conflicts were adjudicated by a third author. Eligibility criteria for PubMed focused on all article designs that were written in English, with full-text available, from the past decade, excluding only those not defining D2T PsA or targeting other populations. RESULTS: From the 565 references sourced, 15 studies were analysed, revealing considerable variations in defining both 'active disease' and 'resistant PsA', which was most often termed 'D2T' PsA. CONCLUSION: The definitions and criteria for D2T PsA and for 'active disease' are notably heterogeneous, with considerable variation across sources. The ongoing Group for Research and Assessment of Psoriasis and Psoriatic Arthritis initiative stands to bridge these definitional gaps and aims to provide guidance for clinicians and illuminate a path for pharmaceuticals and regulatory agencies to follow.

Evaluation of the Disease Activity index for PSoriatic Arthritis (DAPSA) with a quick quantitative C reactive protein assay (Q-DAPSA) in patients with psoriatic arthritis: a prospective multicentre cross-sectional study.

OBJECTIVES: This study aimed to evaluate the Disease Activity index for PSoriatic Arthritis (DAPSA) based on a quick quantitative C reactive protein (qCRP) assay (Q-DAPSA) in a multicentre, prospective, cross-sectional study in patients with psoriatic arthritis (PsA). METHODS: The assessment of prospectively recruited study patients included joint examination and patient reported outcome (PRO) measures (patient global assessment, patient pain assessment). Following, the DAPSA based on a routine laboratory CRP measurement, Q-DAPSA and clinical DAPSA (cDAPSA) were calculated. Cross-tabulations and weighted Cohen's kappa were performed to analyse the agreement of disease activity categories. Bland-Altman plots and intraclass correlation coefficients were used to determine the agreement of numerical values regarding CRP and qCRP as well as different disease activity scores. RESULTS: Altogether, 104 patients with PsA could be included in the statistical analysis. With Q-DAPSA, 102 of 104 (98.1%) patients achieved identical disease activity categories in comparison to DAPSA with a weighted Cohen's kappa of 0.980 (95% CI: 0.952 to 1.000). The agreement between DAPSA and cDAPSA was slightly lower with identical disease activity categories seen in 97 of 104 (93.3%) of patients and with a weighted Cohen's kappa of 0.932 (95% CI 0.885 to 0.980). CONCLUSIONS: The Q-DAPSA showed an almost perfect agreement with the conventional DAPSA regarding identical disease activity categories. Thus, the Q-DAPSA can be used as a timely available disease activity score in patients with PsA with the additional benefit of CRP involvement. Consequently, the Q-DAPSA could facilitate the implementation of the treat-to-target concept in clinical routine and clinical trials.

Treatment with tumour necrosis factor inhibitors is associated with a time-shifted retardation of radiographic spinal progression in patients with axial spondyloarthritis.

OBJECTIVE: The objective of the current study was to analyse the association between treatment with tumour necrosis factor inhibitors (TNFi) and radiographic spinal progression in patients with axial spondyloarthritis (axSpA) from a long-term inception cohort. METHODS: A total of 243 patients with axSpA from the German Spondyloarthritis Inception Cohort with at least two sets of spinal radiographs obtained at least 2 years apart during a 10-year follow-up were included. Spinal radiographs were evaluated by three trained and calibrated readers according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). The association between the current TNFi, previous TNFi and radiographic spinal progression defined as the absolute mSASSS change score over 2 years was analysed using longitudinal generalised estimating equations analysis. RESULTS: TNFi treatment in the current 2-year interval was not associated with retardation of radiographic spinal progression (ß=-0.02 (95% CI -0.37 to 0.34) and -0.17 (95% CI -0.54 to 0.20) for any and ≥12 months treatment duration, respectively, adjusted for sex, the Ankylosing Spondylitis Disease Activity Score, smoking, presence of definite radiographic sacroiliitis, mSASSS at baseline and non-steroidal anti-inflammatory drug intake). TNFi treatment in the previous 2-year interval, was, however, significantly associated with reduction of mSASSS progression, which was especially evident in patients who received TNFi in the previous and in the current intervals: ß=-0.58 (95% CI -1.02 to -0.13), adjusted for the same variables. CONCLUSION: TNFi treatment was associated with a time-shifted effect on radiographic spinal progression in axSpA that became evident between years 2 and 4 after treatment initiation.

Treatment With Tumor Necrosis Factor Inhibitors Is Associated With a Time-Shifted Retardation of Radiographic Sacroiliitis Progression in Patients With Axial Spondyloarthritis: 10-Year Results From the German Spondyloarthritis Inception Cohort.

OBJECTIVE: To investigate the longitudinal association between radiographic sacroiliitis progression and treatment with tumor necrosis factor inhibitors (TNFi) in patients with early axial spondyloarthritis (SpA) in a long-term inception cohort. METHODS: We included patients from the German Spondyloarthritis Inception Cohort who underwent radiographic assessment of the sacroiliac joints at baseline and at least once more during the 10-year follow-up. Two central readers scored the radiographs according to the modified New York criteria for ankylosing spondylitis. The sacroiliac sum score was calculated as a mean of the scores determined by both readers. TNFi use was assessed according to exposure in the current and/or previous 2-year radiographic interval. The association between TNFi use and radiographic sacroiliitis progression was examined by longitudinal generalized estimating equation analysis with adjustment for potential confounders. RESULTS: In this long-term inception cohort, 10-year follow-up data on 737 radiographic intervals assessed in 301 patients with axial SpA (166 patients with nonradiographic axial SpA and 135 patients with radiographic axial SpA) were obtained. Having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was associated with a significant decrease in the sacroiliitis sum score (ß = -0.09 [95% confidence interval (95% CI) -0.18, -0.003]; analyses adjusted for age, sex, symptom duration, HLA-B27 status, Bath Ankylosing Spondylitis Disease Activity Index score, C-reactive protein, and nonsteroidal antiinflammatory drug intake). In contrast, among patients receiving TNFi in the current radiographic interval, there was no significant association with change in the sacroiliitis sum score (ß = 0.05 [95% CI -0.05, 0.14]). This effect of having received ≥12 months of treatment with TNFi in the previous 2-year radiographic interval was stronger in patients with nonradiographic axial SpA as compared to patients with radiographic axial SpA (ß = -0.16 [95% CI -0.28, -0.03] versus ß = -0.04 [95% CI -0.15, 0.07]). CONCLUSION: Treatment with TNFi was associated with the reduction in radiographic sacroiliitis progression in patients with axial SpA. This effect became evident between 2 and 4 years after treatment was initiated.

Presence of spondyloarthritis associated to higher disease activity and HLA-B27 positivity in patients with early Crohn's disease: Clinical and MRI results from a prospective inception cohort.

OBJECTIVE: To determine the SpA prevalence and identify its associated factors in Crohn's disease (CD) patients receiving a systematically rheumatological and imaging assessment, including magnetic resonance imaging (MRI) of the sacroiliac joints and spine. METHODS: CD patients either naive to biologics or without them for three months prior enrollment were recruited in a subgroup of the German Spondyloarthritis Inception Cohort (GESPIC-Crohn). A structured assessment of SpA manifestations was performed by a rheumatologist, including MRI of sacroiliac joints and spine. Demographic and clinical parameters including disease activity in CD (Harvey Bradshaw Index-HBI) and SpA (C-reactive protein - CRP, Bath Ankylosing Spondylitis Disease Activity Index, and Ankylosing Spondylitis Disease Activity Score) were collected. Univariable and multivariable logistic regression analyses were performed to identify factors associated with the presence of SpA. RESULTS: A total of 103 patients with CD were included in the cohort. The mean CD disease duration was 1.3±2.4years and 95.1% were naïve to biologics. The most frequent musculoskeletal manifestation was back pain (65.0%), followed by chronic back pain (50.5%), and arthralgia (43.7%). Prevalence of SpA was 19.4% with slightly higher proportion of axial SpA than peripheral SpA, and higher proportion of radiographic axial SpA (7.4%) than non-radiographic axial SpA (2.8%). Changes in MRI compatible with axial SpA were found in 15 (14.7%) patients, of which 9 (81.1%) patients had the clinical diagnosis of axial SpA. HLA-B27 positivity (OR 9.02, CI 95% 2.29-35.55) and higher disease activity of CD as reflected by the HBI (OR 1.14, 95%CI 1.01-1.30) were significant and independently associated with the presence of SpA. CONCLUSION: SpA was present in nearly one out of five patients with CD and it was associated with the expression of HLA-B27 and a higher clinical activity of CD. Our findings raise awareness to rheumatologists and gastroenterologists on the high concomitance between both diseases and may help to reduce the delay in SpA diagnosis.

Efficacy of tofacitinib in reduction of inflammation detected on MRI in patients with Psoriatic ArthritiS presenTing with axial involvement (PASTOR): protocol of a randomised, double-blind, placebo-controlled, multicentre trial.

INTRODUCTION: Psoriatic arthritis (PsA) is an inflammatory disease characterised by synovitis, enthesitis, dactylitis and axial involvement. The prevalence of axial involvement ranges from 25% to 70% in this patient group. Treatment recommendations for axial PsA were mainly extrapolated from guidelines for axial spondyloarthritis, and the main treatment options are non-steroidal anti-inflammatory drugs and biological disease-modifying antirheumatic drugs (tumour necrosis factor, IL-17 and IL-23 inhibitors). Tofacitinib was approved for the treatment of PsA and its efficacy on axial inflammation has been demonstrated in a phase II study of ankylosing spondylitis (AS). This prospective study aims to evaluate the efficacy of tofacitinib in reducing inflammation in the sacroiliac joints (SIJs) and spine on MRI in patients with axial disease of their PsA presenting with active axial involvement compatible with axial PsA. METHODS AND ANALYSES: This is a randomised, double-blind, placebo-controlled, multicentre clinical trial in patients with axial PsA who have evidence of axial involvement, active disease as defined by a Bath AS Disease Activity Index score of ≥4 and active inflammation on MRI of the SIJs and/or spine as assessed by and independent central reader. The study includes a 6-week screening period, a 24-week treatment period, which consist of a 12-week placebo-controlled double-blind treatment period followed by a 12-week active treatment period with tofacitinib for all participants, and a safety follow-up period of 4 weeks. At baseline, 80 subjects shall be randomised (1:1) to receive either tofacitinib or matching placebo for a 12-week double-blind treatment period. At week 12, an MRI of the whole spine and SIJs will be performed to evaluate the primary study endpoint. ETHICS AND DISSEMINATION: The study will be performed according to the ethical principles of the Declaration of Helsinki and the German drug law. The independent ethics committees of each centre approved the ethical, scientific and medical appropriateness of the study before it was conducted. TRIAL REGISTRATION NUMBER: NCT04062695; ClinicalTrials.gov and EudraCT No: 2018-004254-22; European Union Clinical Trials Register.

Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

BACKGROUND: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research. DESIGN: Prospective, multicenter, multinational, cross-sectional study. METHODS AND ANALYSES: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information. ETHICS: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885.

Extrahepatic autoimmune diseases in primary biliary cholangitis: Prevalence and significance for clinical presentation and disease outcome.

BACKGROUND AND AIM: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). METHODS: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. RESULTS: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti-mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high-risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event-free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjögren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. CONCLUSIONS: Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome.

Two decades of research on autoimmune liver disease in Turkey.

BACKGROUND/AIMS: Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) are the 3 main autoimmune liver diseases (AILDs). The epidemiology of AILD in Turkey is not known. To determine the scientific status, we performed a scientometric analysis of AILD-related original articles that originated from Turkey. MATERIALS AND METHODS: We searched the Web of Science database, the Science Citation Index Expanded (SCI-E), and the Social Sciences Citation Index (SSCI) by using the keywords "autoimmune hepatitis," "primary biliary cholangitis/primary biliary cirrhosis," and "primary sclerosing cholangitis" in conjunction with "Turkey." A scientometric analysis was done on the search results. RESULTS: We identified 117 AILD-related papers that were published in Turkey from 1997 to 2019. Among these, 70 case reports, letters, and reviews and 2 original articles that were not cited in SCI-E/SSCI were excluded. The remaining 45 original articles were further analyzed. These studies were related to AIH (n=22), PBC (n=7), PSC (n=9), PBC-AIH overlap (n=5), and others (n=2). Four of the publications originated in pediatric settings; 9 of 45 papers were published from 1997 to 2008 and 36 papers were published from 2009 to 2019. Most papers (75%) were reported from 5 centers; 9 papers (20%) were published in journals with an impact factor of 3 or higher. CONCLUSION: The overall number and quality of AILD-related papers in Turkey are unexpectedly low, although a number of papers have received considerable international recognition. More epidemiologic, prospective, and multicenter research projects are warranted to advance AILD knowledge and to produce high-quality research from Turkey.

The importance of complete blood count parameters in the screening of gastric cancer.

INTRODUCTION: Gastric cancer is ranked fourth among all cancers in the world and second in cancer-related deaths. Gastritis leads to the activation of neutrophils, lymphocytes, macrophages, and platelets. Long-term inflammation leads to multistage histopathologic changes called Correa tract, which includes gastritis, atrophy, intestinal metaplasia (IM), dysplasia, and cancer stages. AIM: To determine if there is any difference in haematological parameters between gastric cancer (GC) patients, patients with IM, and healthy controls (HC). MATERIAL AND METHODS: Seventy-three GC patients, 79 patients with IM, and 70 HCs were included in the study. Demographics and laboratory parameters of complete blood count were extracted from the hospital medical database records. RESULTS: The mean Hb levels were statistically significant between all three groups. Mean red cell distribution width (RDW), white blood cells (WBC), mean platelet volume (MPV), platelet distribution width (PDW), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and monocyte-to-lymphocyte (MLR) levels were statistically significantly different between gastric cancer and healthy controls. Mean RDW, MPV, and PDW levels were statistically significantly different between the IM and healthy control groups. Mean WBC, NLR, PLR, and MLR levels were statistically significantly different between the gastric cancer and IM groups. CONCLUSIONS: RDW, platelet count, NLR, MLR, and PLR have diagnostic value and can help to distinguish patients with GC from those with IM. These parameters are accessible easily, the cost is not high, and it may help patients not to delay endoscopic screening.

Primary Hypertrophic Osteoarthropathy Mimicking Juvenile Idiopathic Arthritis: A Novel SLCO2A1 Mutation and Imaging Findings.

Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis, is a rare, multisystemic, autosomal recessive condition typically presenting with digital clubbing, osteoarthropathy, and various skin manifestations. Radiographs show distinctive periosteal reaction and thickening along the long bones. PHO is caused by homozygous mutations in the HPGD gene in chromosome 4q34.1 or the SLCO2A1 gene in 3q22.1q22.2. Here, we report on a 20-year-old male with enlarged and swollen joints with arthralgia, palmoplantar hyperhidrosis, and large hands and feet with marked digital clubbing. We also present radiographic, MRI, and ultrasonographic features of the case. These clinical and imaging findings were compatible with the diagnosis of PHO, and a novel homozygous mutation, c.576C>G, p.Ile192Met, was found in SLCO2A1.

IL-17 inhibition in axial spondyloarthritis: current and future perspectives.

INTRODUCTION: Interleukin (IL)-17 is a proinflammatory cytokine considered to play a significant role in the immunopathogenesis of ankylosing spondylitis (AS)/axial spondyloarthritis (axSpA) as well as of other spondyloarthritides. There is a number of substances targeting IL-17, which are at different stages of development in the axSpA indication. AREAS COVERED: This review summarizes the current evidence on the role of IL-17 in the pathophysiology of axSpA and provided a comprehensive review of clinical and radiographic outcomes as well as of safety data from studies with IL-17A inhibitors secukinumab and ixekizumab. Ongoing studies on other IL-17 inhibitors (bimekizumab, brodalumab and BCD-085) that are being developed are also summarized. EXPERT OPINION: The development of the IL-17 inhibitors has expanded AS treatment with effective options and confirmed the pathophysiological role of IL-17 in axSpA. IL-17 inhibition showed sufficient efficacy against signs and symptoms of the disease even after the failure of tumor necrosis factor inhibitors, being at the same time reasonably safe.

Stratifying the risk factors for hypoparathyroidism after total thyroidectomy. A single Center study.

BACKGROUND: Post-operative hypoparathyroidism is a complication in patients who undergo thyroid surgery. Our study aimed to evaluate the incidence and causes of post-operative transient and permanent hypoparathyroidism in patients undergoing thyroid surgery. MATERIALS AND METHODS: The data of 933 consecutive patients who underwent total thyroidectomy in a single center were retrospectively evaluated. The rate of post-operative hypoparathyroidism, clinicopathological features, and laboratory parameters during the post-operative first day, first month, and first year of patients with and without hypoparathyroidism were analyzed. Patients with hypoparathyroidism were classified as transient or permanent cases. RESULTS: The incidence of post-operative hypoparathyroidism was 22.7%, including transient (20.6%) and permanent (2.1%). In multivariable analysis, independent predictors of permanent hypoparathyroidism were as follows: surgery due to malignant thyroid disease, tumor multifocality, and pre-operative vitamin-D deficiency (VDD) (p<0.001, 0.047, and 0.002, respectively). During the post-operative first month, the mean serum PTH levels were found to be 7.58 pg/mL, and they remained low on the post-operative first year in patients with permanent hypoparathyroidism. CONCLUSION: Surgery due to thyroid malignancy and VDD should be considered risk factors for permanent hypoparathyroidism in patients who undergo thyroid surgery. The post-operative first month is important in the prediction of permanent hypoparathyroidism. KEY WORDS: Hypoparathyroidism, Permanent, Transient.

Acute long-distance trail running increases serum IL-6, IL-15, and Hsp72 levels.

Interleukin-6 (IL-6), IL-15, and heat shock protein 72 (Hsp72) are molecules that have significant metabolic effects on glucose and fat metabolism and a cell's stress response. The aim of this study is to determine serum levels of these molecules in runners after a long-distance trail run. Serum IL-15 levels after such endurance events have not been investigated yet. Blood samples were collected from 37 athletes (11 female, 26 male) before and after a 35-km trail run, with a total climb of 940 m. Serum was obtained from the samples, and IL-6, IL-15, and Hsp72 levels were measured from using the sandwich ELISA method. The athletes completed the race in 308.3 ± 37.4 min on average. After the race, the mean serum IL-6, IL-15, and Hsp72 concentrations increased 13.2-fold, 2.22-fold, and 1.6-fold, respectively (p < 0.001, p < 0.001, and p = 0.039, respectively). This is the first study to demonstrate the increase in serum IL-15 levels following an acute endurance exercise. In addition to IL-15, we report that IL-6 and soluble Hsp72 levels also increased significantly following a 35-km trail run. Since these molecules are involved in regulating glucose and fat metabolism, significant increases of IL-6, IL-15, and soluble Hsp72 may have health benefits that may be associated with long-distance trail runs, which are becoming more popular worldwide.

Expression of M30 and M65 in celiac disease. Analytical cross-sectional study

ABSTRACT BACKGROUND: The role of villous atrophy in apoptosis, a distinctive feature of celiac disease, is a matter of controversy. The aim of this study was to determine the apoptosis rate through immunohistochemical staining for M30 and M65 in celiac disease cases. DESIGN AND SETTING: Analytical cross-sectional study in a tertiary-level center. METHODS: Duodenal biopsies from 28 treatment-naive patients with celiac disease, 16 patients with potential celiac disease, 10 patients with a gluten-free diet and 8 controls were subjected to immunohistochemical staining for the end-apoptotic marker M30 and the total cell death marker M65. H-scores were compared. Several laboratory parameters were recorded concomitantly, and at the one-year follow-up for celiac disease and potential celiac disease patients. RESULTS: There was a significant difference in H-score for M30 expression between the celiac disease, potential celiac disease and gluten-free diet groups (P = 0.009). There was no significant difference in H-score for M65 expression. There was a positive correlation between the H-score for M30 expression and the anti-tissue transglutaminase immunoglobulin A (anti-tTgIgA) and anti-tissue transglutaminase immunoglobulin G (anti-tTgIgG) levels (R = 0.285, P = 0.036; and R = 0.307, P = 0.024, respectively); and between the H-score for M65 expression and the anti-tTgIgA and anti-tTgIgG levels (R = 0.265, P = 0.053; and R=0.314, P = 0.021, respectively). There was no difference between celiac disease and potential celiac disease patients regarding the laboratory parameters selected. CONCLUSION: The rates of apoptosis and nutritional deficiencies in patients with potential celiac disease were similar to those in patients with celiac disease.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Expression of M30 and M65 in celiac disease. Analytical cross-sectional study.

BACKGROUND: The role of villous atrophy in apoptosis, a distinctive feature of celiac disease, is a matter of controversy. The aim of this study was to determine the apoptosis rate through immunohistochemical staining for M30 and M65 in celiac disease cases. DESIGN AND SETTING: Analytical cross-sectional study in a tertiary-level center. METHODS: Duodenal biopsies from 28 treatment-naive patients with celiac disease, 16 patients with potential celiac disease, 10 patients with a gluten-free diet and 8 controls were subjected to immunohistochemical staining for the end-apoptotic marker M30 and the total cell death marker M65. H-scores were compared. Several laboratory parameters were recorded concomitantly, and at the one-year follow-up for celiac disease and potential celiac disease patients. RESULTS: There was a significant difference in H-score for M30 expression between the celiac disease, potential celiac disease and gluten-free diet groups (P = 0.009). There was no significant difference in H-score for M65 expression. There was a positive correlation between the H-score for M30 expression and the anti-tissue transglutaminase immunoglobulin A (anti-tTgIgA) and anti-tissue transglutaminase immunoglobulin G (anti-tTgIgG) levels (R = 0.285, P = 0.036; and R = 0.307, P = 0.024, respectively); and between the H-score for M65 expression and the anti-tTgIgA and anti-tTgIgG levels (R = 0.265, P = 0.053; and R=0.314, P = 0.021, respectively). There was no difference between celiac disease and potential celiac disease patients regarding the laboratory parameters selected. CONCLUSION: The rates of apoptosis and nutritional deficiencies in patients with potential celiac disease were similar to those in patients with celiac disease.

Emerging treatment options for spondyloarthritis.

The management of spondyloarthritis (SpA) has substantially changed as a consequence of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs). However, the treatment options in patients with axial SpA (axSpA) not responding to nonsteroidal anti-inflammatory drugs (NSAIDs) had been restricted to tumor necrosis factor alpha (TNFα) inhibitors for almost 15 years. With the approval of secukinumab, an interleukin (IL)-17A inhibitor, there is a new alternative in the treatment of axial SpA. In patients with psoriatic arthritis (PsA) not responding to conventional therapy with NSAIDs and conventional synthetic DMARDs, therapeutic options are more diverse. In addition to TNFα inhibitors and secukinumab, another IL-17A inhibitor ixekizumab, IL-12/23 blocker ustekinumab, phosphodiesterase-4 inhibitor apremilast, T-cell-mediated pathway inhibitor abatacept, and Janus kinase (JAK) inhibitor tofacitinib are the approved treatment. Nevertheless, there is still an unmet need for further treatment options in both axSpA and PsA. Further therapeutics, such as the dual IL-17A and F inhibitor bimekizumab, IL-17 receptor blocker brodalumab, and JAK inhibitors baricitinib, filgotinib and upadacitinib are in development for these indications. IL-23 inhibitors risankizumab, tildrakizumab, and guselkumab are further emerging drugs for PsA. Thus, the number of treatment options in SpA is likely to be increased over the next few years that make identification of optimal treatment strategies essential.