Lacrimal gland ultrasonography and elastography as a diagnostic and activity tool for primary Sjögren's syndrome.

OBJECTIVE: To investigate the effectiveness of 2-dimensional shear wave elastography (2D-SWE) in the assessment of lacrimal gland involvement in primary Sjögren's syndrome (pSS) and to determine the association between ultrasonographic findings and clinical activity measures. METHOD: Forty-six patients who fulfilled the 2016 American College of Rheumatology/European League Against Rheumatism (EULAR) classification criteria of pSS and 23 age and gender-matched healthy control subjects were enrolled. Clinical, laboratory and labial biopsy histopathologic characteristics of patients were recorded. Disease activity of pSS and severity of ocular dryness were evaluated with EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) and Ocular Surface Disease Index (OSDI), respectively. Parotid and lacrimal gland architectures were assessed by B-mode ultrasound and 2D-SWE techniques. RESULTS: Mean shear wave elastography measurements, reflecting loss of elasticity, were remarkably higher in pSS patients compared to healthy subjects both in the lacrimal and parotid glands (8.99 ± 3.45 vs 3.68 ± 1.76 in lacrimal glands and 14.14 ± 4.39 vs 7.83 ± 1.69 in parotid glands, all P < 0.001). Shear wave elasticity of lacrimal glands was correlated with OSDI and ESSPRI scores (r = 0.69; P = 0.001 and r = 0.58; P = 0.001, respectively). A cut-off value of 4.6 kPa in the lacrimal gland elasticity discriminated pSS patients from healthy subjects with a sensitivity of 94% and specificity of 87%. CONCLUSION: Results of our study suggest that lacrimal glands lose elasticity in patients with pSS and the assessment of elasticity with 2D-SWE might help to classify patients as having pSS. Further studies are needed to validate the diagnostic utility of lacrimal 2D-SWE by including diseases other than pSS.

COVID-19 in familial Mediterranean fever: Clinical course and complications related to primary disease.

OBJECTIVES: To evaluate the impact of familial Mediterranean fever (FMF) features on the clinical course and outcomes of coronavirus disease 2019 (COVID-19) and clinical course of FMF after COVID-19. METHODS: Consecutive FMF patients with COVID-19 were enrolled from three referral hospitals. Clinical features of FMF and detailed COVID-19 information were obtained from patient interviews and medical records. RESULTS: Seventy-three FMF patients were included in the study. 94.5% of patients had clinical symptoms of COVID-19. We found 24.7% hospitalization, 12.3% respiratory support, 4.1% intensive care unit admission, 6.8% complication, and 1.4% mortality rate in patients. The risk factors of hospitalization for respiratory support were male gender [OR: 7.167 (95% CI: 1.368-37.535)], greater age [OR: 1.067 (95% CI: 1.016-1.121)], and non-adherence to colchicine treatment before the infection [OR: 7.5 (95% CI: 1.348-41.722)]. One-third of patients had reported attacks after COVID-19. The patterns of triggered attacks were fever, peritonitis, pleuritis, transient arthritis, chronic knee mono-arthritis, and protracted febrile myalgia. CONCLUSIONS: FMF characteristics were not associated with worse outcomes of COVID-19. Colchicine non-adherence was the risk factor of hospitalization for oxygen support. The rate of FMF attacks after COVID-19 is prominently increased, with some of them being protracted and destructive.

Treatment with biologic DMARDs may not adversely affect lung nodules in rheumatoid arthritis patients.

OBJECTIVE: Lung nodules (LNs) impose diagnostic and therapeutic challenges in patients with rheuma- toid arthritis (RA) due to unpredictable outcomes. Potential induction of nodulosis with the use of con- ventional synthetic DMARDs (csDMARD) and lack of knowledge regarding the effect of biologic disease-modifying anti-rheumatic drugs (bDMARDs)/tofacitinib on the LN raise concerns and have an impact on treatment decisions. This study aims to evaluate the possible effects of the bDMARDs/tofa- citinib and csDMARDS on LNs observed in RA patients. METHODS: Electronic health records of RA patients who had LNs detected on computed tomography (CT) between January 2015 and December 2020 were evaluated retrospectively. Patients with follow- up CT images were included in the study. Baseline and follow-up images were meticulously examined for the number, size, attenuation, and cavity formation. Clinical, histopathologic, and laboratory find- ings were analyzed. RESULTS: Forty-two RA patients with LNs were studied, 21 were on bDMARDs/tofacitinib (11 females, mean age: 59.7 6 8.4) and 21 were on csDMARDs (12 females, mean age: 71.4 6 8.3). The proportion of patients with progressed nodules during follow-up was comparable between groups (six patients in bDMARDs/tofacitinib vs seven patients in csDMARDs). Progression of LNs was observed in six patients in the bDMARDs/tofacitinib group: three in anti-TNFa, two in rituximab, and one in abatacept users and none in tofacitinib users. CONCLUSION: Our results suggest that the risk of progression in LNs in RA patients with use of bDMARDs/tofacitinib might not impose a higher risk compared to csDMARDs. Moreover, bDMARDs/ tofacitinib might result in regression in LNs.

Serum levels of fetuin-A as a novel biomarker for disease activity in patients with Takayasu arteritis and granulomatous polyangiitis.

OBJECTIVE: The aim of the present study was to investigate serum fetuin-A (Fet-A) levels in patients with Takayasu arteritis (TA) and granulomatous polyangiitis (GPA) and to analyze the relationship between serum Fet-A levels and disease activity scores. METHOD: Thirty-two TA and 28 GPA patients presented to the rheumatology clinic at Gazi University and met the criteria of American College of Rheumatology 1990 and 2012 International Chapell Hill meeting, respectively, and 20 healthy control subjects were included in the present study. We collected data on serum C-reactive protein (CRP), albumin, calcium, and phosphate levels as well as erythrocyte sedimentation rates. Calcification risk index (CRI) was calculated for each patient. The Birmingham Vasculitis Activity Score (BVAS) and Indian Takayasu Clinical Activity Score (ITAS), were used to assess disease activity in GPA and TA patients respectively. RESULTS: Serum Fet-A levels were significantly lower in the overall vasculitis group compared to control group (p = 0.015). In subgroup analysis, Fet-A levels were significantly lower in those with active disease, compared to control group (p = 0.001, for active TA (n = 18) and GPA (n = 17), respectively). However, there was no significant difference in serum Fet-A levels in inactive cases versus control subjects (p = 0.061, for inactive TA (n = 14) and GPA (n = 11), respectively). Serum Fet-A levels negatively correlated with BVAS (r = - 0.675) and ITAS scores (r = - 0.385), as well as with CRP and CRI. CONCLUSION: Our results suggest that serum Fet-A level could be a novel biomarker for assessment of activity status in patients with GPA or TA. Key Points • Serum Fetuin-A is negative acute phase protein and systemic calcification inhibitor synthesized in hepatocytes and secreted by various inflammation. • Serum Fetuin-A was negatively correlated with CRP, BVAS, and ITAS scores and significantly decreased in vasculitis patients with high disease activity. • Serum Fetuin-A could be a promising and useful biomarker for the assessment of disease activity for vasculitis, also that it might also be a predictor of long-term cardiovascular progression.

Efficacy and safety of tofacitinib in rheumatoid arthritis-associated interstitial lung disease: TReasure real-life data.

OBJECTIVES: Rheumatoid arthritis associated interstitial lung disease (RA-ILD) is a major concern in RA. These patients have been included in clinical trials and in the post-marketing setting of RA patients using tofacitinib. We aimed to assess the real-life efficacy and safety of tofacitinib in patients with RA-ILD. METHODS: RA patients with ILD diagnosis based on the HRCT images of the lungs from eight different centres recruited to study. As a control group, RA patients without ILD under tofacitinib were included. Demographic data, patients' characteristics, available pulmonary function tests regarding RA and RA-ILD at the visit in which tofacitinib was initiated and for the last follow-up visit under tofacitinib were recorded. Reasons for tofacitinib discontinuation were also recorded. Drug retention rates were compared by log-rank test. p-value <0.05 was considered statistically significant. RESULTS: A total of 47(42.6% male) RA patients with RA-ILD and a control group of 387 (17.8% male) patients without RA-ILD were included in analysis. After the median of 12 (9-19) months follow-up, mean FEV1%; 82.1 vs. 82.8 (pre/post-treatment, respectively, p=0.08), mean FVC%; 79.8 vs. 82.8 (pre/post-treatment, respectively, p=0.014) were stable and worsening was observed in 2/18 (11.1%) patients. Retention rates were similar (p=0.21, log-rank). In RA-ILD group, most common cause of drug discontinuation was infections (6.3 vs. 2.4 per 100 patient-years). CONCLUSIONS: Treatment strategy of RA-ILD patients is still based on small observational studies. A high rate of discontinuation due to infections was observed in RA-ILD patients under tofacitinib; however, RA-ILD patients were older than RA patients without ILD.

The impact of anti-TNF treatment on Wnt signaling, noggin, and cytokine levels in axial spondyloarthritis.

INTRODUCTION: Anti-tumor necrosis factor (anti-TNF) agents are commonly used in treatment of axial spondyloarthritis (axSpA), but clinical and radiological improvement is not achieved in all patients. We aimed to investigate the impact of anti-TNFs on inflammatory and noninflammatory parameters in patients with axSpA. METHODS: In this longitudinal study, 30 biologic naïve axSpA patients with high disease activity and 30 healthy controls were enrolled. All patients were treated with anti-TNF agents for 6 months. ASDAS-CRP, BASDAI, BASFI, BASMI, patient and physician global assessments were evaluated. C-reactive protein, COX2, TNF-α IL-6, IL-17, IL-22, IL-23, IL-33, sclerostin, dickkopf-1, and noggin levels were evaluated at baseline and at 6 months of anti-TNF treatment. RESULTS: At baseline, axSpA patients had significantly higher median (IQR) TNF-α levels, 34.4 (31.4-37.03) vs. 18.1 (12.1-28.4) pg/ml (p < 0.001), and lower DKK1, 446.7 (356.9-529.3) vs. 1088.7 (951.7-1244.4) pg/ml, and sclerostin, 312.4 (140.8-412.7) vs. 412.3 (295.4-512.8) pg/ml, compared to healthy controls (all p < 0.001). The median (IQR) serum levels of IL-17, IL-22, and IL-33 increased significantly after 6 months of anti-TNF treatment, from 93.3 (85.1-104.8) to 102.1 (86.6-114.6) pg/ml (p = 0.026), 159.2 (151.9-178.4) to 183.5 (156.3-304.6) pg/ml (p = 0.033), and 127.8 (106.6-186.1) to 147.06 (128.5-213.4) pg/ml (p = 0.016), respectively. Sclerostin and DKK-1 levels increased significantly after anti-TNF treatment from 312.4 (140.8-412.7) to 405.1 (276.3-452.5) pg/ml (p = 0.018) and 446.7 (356.9-529.3) to 881.3 (663.1-972.2) pg/ml (p < 0.001), while there was no significant change in noggin level. CONCLUSIONS: Many inflammatory cytokines increase after anti-TNF treatment and noggin is not affected by anti-TNF treatment in AxSpA. Noggin might be a therapeutic target in patients with axSpA. KEY POINTS: • Anti-TNF therapy is not sufficient for complete blockage of the inflammatory process in axial spondyloarthritis. • The increase in IL-17, IL-22, and IL-33 may decrease the efficiency of anti-TNF therapy. • Noggin might be a therapeutic target as a complementary or alternative approach to anti-TNF therapy in axial spondyloarthritis.

Diagnostic utility of serum biomarkers in large vessel vasculitis and their correlation with positron emission tomography.

OBJECTIVES: To investigate the association between vascular inflammation, as detected by positron emission tomography (PET) imaging and interleukin-6 (IL-6), pentraxin3, and B-cell-activating factor (BAFF) in subjects with LVV. METHODS: The study included newly diagnosed giant cell arteritis (GCA, n = 27) or Takayasu arteritis (n = 9) patients and healthy control (HC, n = 31) subjects. PET scan and blood samples were obtained before the introduction of treatments. IL-6, PTX3, and BAFF levels were determined quantitatively by enzyme-linked immunosorbent assay kits. RESULTS: Thirty-six patients with LVV (20 females, 16 males; age 64.5 ± 16.6 years) and 31 HC (14 females, 17 males; age 37.1 ± 9.6 years) were included. Serum levels of IL-6, PTX3, and BAFF were increased in patients with newly diagnosed LVV compared with healthy control subjects. In receiver operating characteristics (ROC) analysis, serum IL-6 and BAFF provided excellent discrimination of newly diagnosed LVV patients from HC (area under the ROC curve of >0.90 and >0.80, respectively). None of the inflammatory markers correlated with vascular inflammatory activity determined by PET scanning. CONCLUSIONS: Our results suggest that IL-6 and BAFF may serve as markers of large vessel vasculitis, while PTX3 is not useful. None of the inflammatory markers correlated with PET assessed vasculitis activity.

Compliance of Familial Mediterranean Fever Patients With Regular Follow-up Visits and Associated Factors.

BACKGROUND: Follow-up is crucial to detect asymptomatic complications of familial Mediterranean fever (FMF). The current European League Against Rheumatism recommendations state that patients with FMF should be evaluated at least every 6 months to monitor attacks, acute phase response, and proteinuria. OBJECTIVES: This study aimed to assess compliance of FMF patients with regular follow-up visits and the associated factors. METHODS: Adult patients with a diagnosis of FMF who had their initial visit at least over 1 year ago were included. Demographic and socioeconomic data, family history, and comorbid diseases were obtained from medical records. The International Severity Score for FMF and the Autoinflammatory Disease Damage Index scores were calculated. We defined patients as "compliant with follow-up visits" both if they had at least 2 visits during the previous year and a compatible physician's assessment. The characteristics of the compliant and noncompliant patients were compared, and multivariable logistic regression analysis was used to determine the factors influencing visit compliance. RESULTS: Four hundred seventy-four patients with FMF were included. Two hundred thirty (48.5%) were compliant, and 244 (51.5%) were noncompliant with follow-up visits. A family history of FMF in parents, the absence of a family history of FMF in siblings, treatment with biologic agents, concomitant medication use, multisite involvement during FMF attacks, and treatment satisfaction were independent predictors of visit compliance. CONCLUSIONS: Only half of the patients with FMF were compliant with follow-up visits. Better strategies should be implemented to increase the compliance of FMF patients. Identifying independent predictors would help to build one.

Long-term safety and efficacy of anakinra and canakinumab in patients with familial Mediterranean fever: a single-centre real-life study with 101 patients.

OBJECTIVES: Anakinra and canakinumab are the most commonly used agents in colchicine resistant/intolerant patients. In this study we investigated long-term efficacy and safety of anakinra and canakinumab. METHODS: In this retrospective study, we enrolled 101 adult patients with familial Mediterranean fever (FMF). Clinical and laboratory parameters before and after treatment with anakinra/canakinumab and the side effects observed during the treatment were recorded. All patients received anakinra initially and switched to canakinumab, in case of inadequate response/intolerance. RESULTS: The median (IQR) duration of treatment with anti-IL-1 agents was 35 (24-47.5) months. 101 patients were treated with anakinra and 27 patients with canakinumab. The autoinflammatory diseases activity and attacks decreased with both anakinra and canakinumab. Anakinra was effective in decreasing proteinuria and canakinumab was not effective in decreasing proteinuria in anakinra unresponsive patients. The modified FMF score was achieved in 76.2% of anakinra and 88.9% of canakinumab group. Injection site reactions (ISRs, n:15) was the most common reason of discontinuation of anakinra and most of ISRs developed in first 3 months of treatment. One severe skin rash, two anaphylactic reactions and one severe neutropenia were observed with anakinra; in the first, eighth, twelfth and fiftieth months, respectively. No severe side effects or side effect-related discontinuation of canakinumab were observed. CONCLUSIONS: Anakinra and canakinumab seem to be effective in long-term management of FMF patients. Canakinumab had a favourable safety/tolerability profile. Anakinra is also generally safe, but the serious side effects that may be observed in the short and long-term use should be taken into account.

Decreased exercise capacity, strength, physical activity level and quality of life in adult patients with familial Mediterranean fever

Background: Familial Mediterranean fever (FMF) is a systemic autoinflammatory disease that causes recurrent attacks of fever, polyserositis, arthritis or skin eruptions, resulting in pain in the abdomen, muscles, joints and chest. All of these might lead to a reduction in exercise capacity, muscle strength, physical activity level (PAL) and quality of life (QoL). Therefore, assesment of these parameters are important. The aim of this study was to assess exercise capacity, muscle strength, PAL, and QoL in patients with FMF as compared to controls. Materials and methods: A total of 40 subjects with FMF and 36 healthy control subjects participated in the study. The 6-minute walk test (6MWT) was used to assess exercise capacity. Muscle strength measurements for shoulder flexors, extensors and abductors, hip flexors, extensors and abductors, knee flexors and extensors, and ankle dorsiflexors were evaluated by hand-held dynamometer. PAL was assessed using the International Physical Activity Questionnaire-Short Form (IPAQ-SF). QoL was investigated by Nottingham Health Profile (NHP). Results: Significant differences were found between patients and healthy subjects for 6MWT (p = 0.003), muscle strength of ankle dorsiflexors (p = 0.001), hip flexors (p = 0.047), extensors (p = 0.003) and abductors (p = 0.004), total scores of IPAQ-SF (p = 0.004), and pain (p < 0.001), physical mobility (p < 0.001) and energy level (p = 0.026) subscales of NHP. However, there were no significant differences between groups for the shoulder flexion (p = 0.089), extension (p = 0.440) and abduction (p = 0.232), hand grip strength (p = 0.160) , and knee flexion (p = 0.744) and extension (p = 0.155) muscle strength and emotional reaction (p = 0.088), sleep (p = 0.070) and social isolation (p = 0.086) subsets of NHP. Conclusion: Subjects with FMF demonstrated lower exercise capacity, muscle strength, PAL and QoL than healthy peers. Therefore, it is important to evaluate and improve these parameters in patients with FMF.

Phenotypic characterization of Familial Mediterranean Fever patients harboring variants of uncertain significance

Background/aim: Familial Mediterranean Fever (FMF) is the prototype of hereditary autoinflammatory disorders and caused by mutations on the MEFV gene located on the short arm of chromosome 16. Although some MEFV variants are clearly associated with disease phenotype, there are numerous variants with unknown clinical association which are termed as variants of uncertain significance (VUS). Here, we present clinical correlations of VUS in a large cohort of adult FMF patients from three tertiary centers located in Central Anatolia. Materials and methods: All patients were recruited from FMF in Central Anatolia (FiCA) cohort. Demographic (sex, age at disease onset) and clinical features (disease characteristics, attack frequency, mean colchicine dose, colchicine nonresponsiveness, amyloidosis, and persistent inflammation) of patients with VUS were compared with those harboring pathogenic variants. Disease severity and damage were also evaluated using international severity score for FMF (ISSF) and autoinflammatory disease damage index (ADDI), respectively. Results: Among 971 participants included, MEFV gene analysis results were available for 814 patients. Twenty-six (3.2%) patients had single heterozygous VUS and 54 (6.6%) had pathogenic/VUS complex heterozygous variants. Patients with single heterozygous VUS had similar demographic/clinical features, ISSF and ADDI scores compared to those with single heterozygous pathogenic variant (p > 0.05 for all). No difference was observed in the demographic and clinical features of patients with single heterozygous pathogenic mutation and pathogenic/VUS complex heterozygous variant (p > 0.05 for all). ISSF and ADDI scores were lower in pathogenic/VUS complex heterozygous patients than those harboring single pathogenic mutation (p = 0.006 and 0.004, respectively). Conclusion: Our findings suggest that patients with single heterozygous VUS has mild FMF phenotype similar to those with single pathogenic mutation. Pathogenic/VUS complex heterozygosity does not lead to a more severe clinical phenotype than having a single pathogenic variant.

Work productivity impairment in patients with familial Mediterranean fever and effects of interleukin-1 antagonists.

INTRODUCTION: Familial Mediterranean fever (FMF) is characterized by recurrent attacks of fever, serositis, and arthritis. Some patients suffer from associated inflammatory conditions and damage related to FMF that may potentially impair work productivity which have not been studied to date. METHODS: Consecutive FMF patients who were attending a tertiary referral center and age-and sex-matched healthy subjects enrolled into the study. Disease activity was assessed with autoinflammatory disease activity index (AIDAI) and patient global assessment. Damage was evaluated using Autoinflammatory Disease Damage Index (ADDI). Quality of life (QoL) and work productivity were determined with 36-Item Short Form Health Survey (SF-36) and Work Productivity and Activity Impairment Specific Health Problem v2.0 (WPAI:SHP), respectively. RESULTS: There were 111 FMF patients, 60 female (54%), mean age 32.7±8.7 years. There were significant impairments in all domains of the SF-36 QoL in FMF patients. Of the 111 patients enrolled, 65 (58.6%) were employed in a paid work. Mean% ±SD impairment in work productivity both assessed as absenteeism (9.3±23.2% vs. 0.7±2.6, p=0.013) and presenteeism (35.2±32.6% vs. 9.6±14.7, p<0.001) were significantly higher in FMF patients compared to healthy subjects. Impairment in work productivity was correlated with the number of attacks, disease activity, colchicine resistance, and disease-associated damage. Impairment was most significant in colchicine-resistant FMF patients but lower in those on interleukin (IL)-1 antagonist treatments. CONCLUSIONS: FMF causes significant work impairment and reduced QoL which is associated with disease activity and damage. The use of IL-1 antagonists may help to improve work productivity and QoL in FMF patients with frequent attacks. Key points • Work productivity is impaired in patients with FMF. • Disease activity was an independent predictor for impaired work productivity. • IL-1 antagonists may improve work productivity and quality of life in FMF patients with frequent attacks.

Appendectomy history is associated with severe disease and colchicine resistance in adult familial Mediterranean fever patients

Background/aim: Peritonitis attacks of Familial Mediterranean Fever (FMF) usually requires emergency medical admissions and it's hard to distinguish a typical abdominal attack from surgical causes of acute abdomen. Therefore, history of abdominal surgery, particularly appendectomy, is very common in patients with FMF. However, history of appendectomy might also give some clues about the course of FMF in the adulthood. This study was to determine whether the history of appendectomy help to anticipate disease course of FMF in the adulthood. Materials and methods: All patients recruited from FMF in Central Anatolia (FiCA) cohort, comprising 971 adult subjects. All patients fulfilled the Tel Hashomer criteria. Demographic data, FMF disease characteristics, co-morbid conditions, past medical history, surgical history and disease complications were meticulously questioned and laboratory features and genotype data (if available) were recruited from patient files. Results: Appendectomy history was evident in 240 (24.7%) subjects. Disease onset was earlier and peritonitis is strikingly more prevalent (97.1% vs. 89.6%, p < 0.001) in appendectomized patients. These patients had reported almost two fold more frequent attacks in the last year compared to appendix intact patients (median 3.5 vs. 2 attacks, p = 0.001) without a difference in frequency of musculoskeletal and skin attacks. Severe disease was more common (10% vs. 5.9%, p = 0.038) due to involvement of more attack sites throughout the life and more frequent attacks. Appendectomy patients had used higher daily doses of colchicine to control disease (1.43 ± 0.6 mg vs. 1.27 ± 0.52 mg, p = 0.002) but colchicine resistance was also more common in these patients, 15% vs. 6.7% respectively, p < 0.001. Conclusion: Appendectomy history is common in FMF patients and associated with frequent serositis attacks in adulthood. These patients require higher colchicine doses with a lower rate of response and more need for Interleukin-1 antagonist therapies.

Prognostic value of interleukin-18 and its association with other inflammatory markers and disease severity in COVID-19.

BACKGROUND: The effectual immune response is crucial to defeat viral infections. However, exuberant immune response with features of macrophage activation syndrome (MAS) lead detrimental consequences in COVID-19 patients. Interleukin (IL)-18 is one of the leading cytokines in MAS which has not been studied in COVID-19. OBJECTIVE: To investigate the association of IL-18 with the other inflammatory markers and disease severity in COVID-19 for predicting disease prognosis. METHODS: Patients with COVID-19 who had confirmed diagnosis with SARS-CoV-2 nucleic acid RT-PCR were enrolled into the study. Data on demographic and clinical characteristics, and laboratory values of CRP, ferritin, d-dimer and procalcitonin were measured on admission. Patients were followed up prospectively with a standardized approach until hospital discharge or death. Individuals were classified as asymptomatic, mild and severe pneumonia according to their clinical, laboratory and radiological characteristics. Worse outcome was defined as requirement of intensive care unit (ICU) admission or death. Blood samples were collected at enrollment and serum levels of IL-6 and IL-18 were determined by ELISA. Association between IL-18 and other inflammatory markers and prognosis were analyzed. RESULTS: There were 58 COVID-19 patients (50% male) with a median age of 43 (min 22-max 81) years. Twenty age and sex matched healthy subjects were served as control group. The study population was divided into three groups according to disease severity: asymptomatic (n = 20), mild pneumonia group (n = 27) and a severe group (n = 11). During follow up nine (15.5%) patients required ICU admission and three of them were died eventually. Serum IL-18 were correlated with other inflammatory markers and biochemical markers of organ injury; creatinine, liver enzymes and troponin. Serum IL-18 levels were remarkably higher in COVID-19 patients compared to healthy subjects with being highest in severe pneumonia group (p < 0.001). IL-18 serum concentrations were almost four-fold higher in patients with worse outcome compared to good outcome (p < 0.001). Serum IL-18 above the cut off value of 576 pg/mL on admission was associated with 11.7 fold increased risk of ICU admission. CONCLUSIONS: The serum concentrations of IL-18 correlate with other inflammatory markers and reflect disease severity. Results of the present study shed light on role of IL-18 on COVID-19 pathogenesis and might provide an evidence for the clinical trials on IL-18 antagonists for the treatment of severe COVID-19 patients.

Diagnostic Role of 18F-Fluorodeoxyglucose Positron Emission Tomography for the Evaluation of Patients With Inflammation of Unknown Origin.

BACKGROUND: Sometimes, the underlying causes of inflammation cannot be established despite meticulous investigation, including medical history, physical examination, laboratory tests, and radiologic procedures. Rheumatologists are often faced with patients whose condition is known as inflammation of unknown origin (IUO). Differential diagnosis of IUO is diverse, and investigation of these cases is challenging and time-consuming. OBJECTIVE: The study aimed to assess the diagnostic role of positron emission tomography/computed tomography (PET/CT) in the evaluation of patients with IUO. METHODS: The study sample consisted of 97 adult patients with IUO who have not been previously diagnosed with an infectious, inflammatory, or malignant disease. The necessary data were collected from January 2015 to June 2018 with a 6-month follow-up period. The patients were screened using PET/CT after a specific diagnosis could not be established with detailed laboratory and radiologic evaluations. RESULTS: A final diagnosis was established at follow-up, and 47 (54%) of the 97 patients had inflammatory diseases, 30 (34.4%) had malignancies, and 10 (11.4%) had infections. Despite meticulous investigation, 10 patients were left undiagnosed in the follow-up. PET/CT aided diagnosis in 59 patients (60.8%), but it was not helpful in 38 patients (39.2%). PET/CT was positive in 30 (63%) of the 47 patients with inflammatory diseases, whose final diagnosis was inflammatory rheumatic disease, as follows: large-vessel vasculitis in 19 patients, polymyalgia rheumatica in 7 patients, and seronegative arthritis or other rare miscellaneous diseases in 4 patients. The sensitivity of PET/CT was 67% with a specificity and diagnostic accuracy of 100% and 71%, respectively. CONCLUSIONS: Investigation of the underlying etiology of IUO is time-consuming and challenging. PET/CT may help identify the final diagnosis more quickly by locating an obscure inflammatory site; thus, it may reduce the number of unnecessary biopsies, diagnostic time, anxiety, work loss, morbidity, and mortality.

Folfirinox versus gemcitabine-cisplatin combination as first-line therapy in treatment of pancreaticobiliary cancer

Background/aim: The purpose of this study was to compare efficacy and safety of a combination chemotherapy regimen consisting of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) and gemcitabine-cisplatin as first-line therapy in patients with pancreatic cancer. Materials and methods: Pancreaticobiliary cancer patients who had Eastern Cooperative Oncology Group performance status score of 0 or 1 (on a scale of 0 to 5, with higher scores indicating greater severity of illness) were evaluated to receive folfirinox or gemcitabine plus cisplatin. The primary endpoints were progression-free and overall survival time. Safety analysis was also evaluated as secondary measures. Results: There were 32 patients in the folfirinox group and 36 patients in the gemcitabine-cisplatin group. The median overall survival was 18.1 months (7.5­28.7) in the folfirinox group as compared with 9.7 months (6.5­13) in the gemcitabine-cisplatin group (p = 0.009). Median progression-free survival was 16.2 months (9­23.4) in the folfirinox group and 6.9 months (6.1­7.6) in the gemcitabine- cisplatin group (p = 0.001). Conclusion: Folfirinox is an option for the first-line treatment of patients with pancreatic cancer and good performance status.