Influence of Antisynthetase Antibodies Specificities on Antisynthetase Syndrome Clinical Spectrum TimeCourse

Introduction: Increased cardiovascular (CV) morbidity and mortality is observed in inflammatory joint diseases (IJDs) such as rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis. However, the management of CV disease in these conditions is far from being well established.Areas covered: This review summarizes the main epidemiologic, pathophysiological, and clinical risk factors of CV disease associated with IJDs. Less common aspects on early diagnosis and risk stratification of the CV disease in these conditions are also discussed. In Europe, the most commonly used risk algorithm in patients with IJDs is the modified SCORE index based on the revised recommendations proposed by the EULAR task force in 2017.Expert opinion: Early identification of IJD patients at high risk of CV disease is essential. It should include the use of complementary noninvasive imaging techniques. A multidisciplinary approach aimed to improve heart-healthy habits, including strict control of classic CV risk factors is crucial. Adequate management of the underlying IJD is also of main importance since the reduction of disease activity decreases the risk of CV events. Non-steroidal anti-inflammatory drugs may have a lesser harmful effect in IJD than in the general population, due to their anti-inflammatory effects along with other potential beneficial effects.This research was partially funded by FOREUM—Foundation for Research in Rheumatolog

Examination of vascular stiffness by pulse wave velocity in patients with rheumatic diseases of the Rhineland-Palatinate rheumatology center

Systemic-inflammatory rheumatic diseases correlate with increased cardiovascular (CV) risk and higher morbidity and mortality rates (1). During the last years, a close associationbetween the occurence of CV events and an increase of aortic stiffness has been shown in multiple studies. Aortic stiffness has been hence described as an independent predictor of CV risk (2). An increase of aortic stiffness has also been observed in various systemic-inflammatory rheumatic diseases (3-5). Pathophysiological reasons for this seem to be inflammation associated effects, such as endothelial dysfunction, acceleration of atherosclerosis, pathologic functions of lipoporoteins, presence of various autoantibodies, abnormal vasospasm and a disruption of the normal process of elastin production/degradation within the artery wall. Peripheral and central arterial stiffness can nowadays be measured by several methods. Among these methods, carotid-femoral pulse wave velocity (cfPWV) has the most epidemiological evidence regarding a high predictive value of CV events and this modality is described in the scientific literature as the ‘‘gold standard‘‘ assessment method of aortic stiffness (6). Moreover, cfPWV is a simple, complication-free and inexpensive method for theearly detection of patients under high CV risk (7). In the present work, aortic stiffness of patients with three different systemic-inflammatory rheumatic diseases [systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA)] has been examined by cfPWV. Moreover, correlations of cfPWV with various patient- and disease associated-parameters, such as inflammation markers, disease specific autoantibodies, secondary organ involvement and traditional CV risk factors, such as diabetes, nicotine use, arterial hypertension and lipid profile have been evaluated. Hereby, it could be shown that patients with SSc and RA had significantly higher cfPWV values in comparison to healthy controls (p0.05). A possible reason for that could be the clinical heterogeneity characterising the entity of SLE.In a second step, correlations of aortic stiffness with traditional CV risk factors and disease-associated characteristics were examined. In accordance with the scientific literature, a statistically significant association between cfPWV and age could be shown in both the SSc- and RA-subgroup (p=0.004 and p=0.033, respectively). Moreover, in patients with SSc, cfPWV correlated significantly with arterial hypertension and presence of type II diabetes mellitus. In the same subgroup, patients with arthritis and/or acroosteolyses showed additionally statistically significant lower cfPWV values in comparison to their counterparts without a joint involvement. Nevertheless, statistical control via multivariable linear regression analyses showed that solely diabetes (padj0.05). A possible reason could be the known positive association between RF and age (older subjects have often higher titers of RF). Interestingly enough, a marginal correlation between cfPWV and the count of tender, rather the count of swollen, joints was found (p=0.055) (8). This could be an indication of a separate, inflammation - independent effect of pain on aortic stiffness/stiffening. Given the fact that at the time of the doctoral thesis no adequate data on this relationship existed, it was suggested that this result should be further examined (8). This examination was indeed performed subsequently by our group in another study which included patients with the known rheumatic chronic pain syndrome fibromyalgia (FM) (9). Here, we showed that included patients with FM had higher cfPWV compared with controls (9).In the SLE-subgroup, no statistically significant correlations between cfPWV and markers of activity or chronicity of the disease were established. The value of this examination in the follow-up assessments of patients with either increased cfPWV-values or past CV-eventsremains however high. In summary, the present work constituted a further step in the validation of an increased aortic stiffness in patients with some of the rheumatic diseases included. Given the fact that cfPWV is a well validated marker of CV risk, these results are of significance. Furthermore, it couldbe shown that traditional CV risk factors, rather than the examined disease associated parameters, were associated with an increased aortic stiffness and thus should be taken into account when treating patients with systemic-inflammatory rheumatic diseases. The measurement of cfPWV seems to be a valuable tool to assist identificantion of rheumatic patients under increased CV risk and thus allow early treatment initiation and ultimately prognosis improvement. Further prospective studies examining the influence of pain and / or immunosuppressive therapy on the vasculature of patients with inflammatory-rheumatic systemic diseases are needed.Οι συστηματικές φλεγμονώδεις ρευματικές παθήσεις συσχετίζονται με αυξημένο καρδιαγγειακό κίνδυνο και υψηλότερα ποσοστά νοσηρότητας και θνησιμότητας (1). Τα τελευταία χρόνια, έχει δειχθεί σε πολλές μελέτες μια στενή συσχέτιση ανάμεσα στην εμφάνιση καρδιαγγειακών συμβαμάτων και την αύξηση της αορτικής σκληρότητας. Έτσι, η αορτική σκληρότητα έχει περιγραφεί ως ανεξάρτητος προγνωστικός δείκτης καρδιαγγειακού κινδύνου (2). Αύξηση αορτικής σκληρότητας έχει επίσης παρατηρηθεί σε ασθενείς με διάφορες συστηματικές φλεγμονώδεις ρευματικές παθήσεις (3-5). Παθοφυσιολογικά, αυτό μπορεί να εξηγηθεί μέσω των επιπτώσεων της συστηματικής φλεγμονής στο καρδιαγγειακό σύστημα, όπως η δυσλειτουργία των ενδοθηλιακών κυττάρων, η επιτάχυνση της αθηροσκλήρωσης, παθολογικές λιποπρωτεινικές λειτουργίες, η παρουσία διάφορων αυτοαντισωμάτων, παθολογικός αγγειόσπασμος και η διαταραχή της φυσιολογικής διαδικασίας παραγωγής / καταστροφής της ελαστίνης εντός των αρτηριακών τοιχωμάτων. Η σκληρότητα των περιφερικών και κεντρικών αρτηριών μπορεί να μετρηθεί με διάφορες μεθόδους. Ανάμεσά τους, η μέτρηση της ταχύτητας παλμικού κύματος μεταξύ καρωτιδικής και μηριαίας αρτηρίας (carotid-femoral pulse wave velocity; cfPWV) έχει τα περισσότερα επιδημιολογικά όσον αφορά την υψηλή προγνωστική αξία αναφορικά με την εμφάνιση καρδιαγγειακών συμβαμάτων και αυτή η μέθοδος περιγράφεται στην επιστημονική βιβλιογραφία ως «gold standard» για την αξιολόγηση της αορτικής σκληρότητας (6). Επιπλέον, η cfPWV είναι μια απλή, χωρίς επιπλοκές και οικονομικά προσιτή μέθοδος για την πρώιμη ανίχνευση ασθενών υπό υψηλό καρδιαγγειακό κίνδυνο (7).Στην παρούσα εργασία, η αορτική σκληρότητα ασθενών με τρεις διαφορετικές συστηματικές φλεγμονώδεις ρευματικές παθήσεις [συστηματική σκληροδερμία (ΣΣκ), συστηματικός ερυθηματώδης λύκος (ΣΕΛ) και ρευματοειδής αρθρίτιδα (ΡA)], εξετάστηκε μέσω cfPWV. Επιπλέον, αξιολογήθηκαν οι συσχετίσεις της cfPWV με παράμετρους σχετιζόμενες τόσο με τους ασθενείς όσο και τη νόσο καθαυτή, όπως δείκτες φλεγμονής, νόσο-ειδικά αυτοαντισώματα, δευτερεύουσα συστηματική προσβολή και παραδοσιακοί παράγοντες καρδιαγγειακού κινδύνου, όπως ο σακχαρώδης διαβήτης τύπου 2, η χρήση νικοτίνης, η αρτηριακή υπέρταση και το λιπιδικό προφίλ των συμμετεχόντων.Στην παρούσα εργασία βρέθηκε ότι ασθενείς με ΣΣκ και ΡΑ είχαν σημαντικά υψηλότερες τιμές cfPWV σε σύγκριση με την υγιή ομάδα ελέγχου (p0.05). Ένας πιθανός λόγος για αυτό το εύρημα μπορεί να είναι η υψηλή κλινική ετερογένεια που χαρακτηρίζει την οντότητα του ΣΕΛ. Σε ένα δεύτερο βήμα, εξετάστηκαν οι συσχετίσεις της αορτικής σκληρότητας με παραδοσιακούς παράγοντες καρδιαγγειακού κινδύνου και επιλεγμένα χαρακτηριστικά των τριών ρευματολογικών νόσων. Βρέθηκε, ότι η cfPWV συσχετιζόταν σημαντικά με την ηλικία των ασθενών στις δύο υποομάδες ΣΣκ και ΡΑ (p=0.004 και p=0.033, αντίστοιχα). Επιπλέον, στους ασθενείς με ΣΣκ, βρέθηκαν στατιστικά σημαντικές συσχετίσεις με την παρουσία αρτηριακής υπέρτασης και σακχαρώδους διαβήτη τύπου 2. Επιπλέον, στην ίδια υποομάδα, οι ασθενείς με αρθρίτιδα και / ή ακροοστεολύσεις παρουσίασαν σημαντικά χαμηλότερες τιμές cfPWV σε σύγκριση με τους αντίστοιχους χωρίς αρθρική/οστική συμμετοχή/παθολογία. Ωστόσο, ένας επιπλέον στατιστικός έλεγχος μέσω πολυμεταβλητών γραμμικών αναλύσεων έδειξε ότι μόνο ο σακχαρώδης διαβήτης (padj0.05). Ένας πιθανός λόγος γι’αυτό μπορεί να είναι η γνωστή θετική συσχέτιση μεταξύ του RF και της ηλικίας (συχνά οι ηλικιωμένοι έχουν υψηλότερες τιμές του RF). Ενδιαφέρον παρουσίασε επίσης η τάση συσχέτισης μεταξύ της cfPWV και του αριθμού των ευαίσθητων (παρά του αριθμού των διογκωμένων) αρθρώσεων (p=0.055) (8). Αυτό το αποτέλεσμα μπορεί να είναι ένδειξη μιας ξεχωριστής, ανεξάρτητης από τη φλεγμονή, επίδρασης του πόνου στην αορτική σκληρότητα. Δεδομένου ότι κατά την περίοδο της διεξαγωγής της διδακτορικής διατριβής δεν υπήρχαν επαρκή δεδομένα για μια πιθανή συσχέτιση μεταξύ πόνου και αρτηριακής σκληρότητας, προτάθηκε ότι το αποτέλεσμα αυτό θα πρέπει να εξεταστεί περαιτέρω (8). Αυτή η εξέταση πραγματοποιήθηκε όντως στην πορεία από την ομάδα μας σε μια άλλη μελέτη «ασθενών-μαρτύρων» που εστίασε σε ασθενείς με το γνωστό σύνδρομο χρόνιου πόνου, ινομυαλγία (9). Εκεί δείξαμε ότι οι εξεταζόμενοι ασθενείς με ινομυαλγία είχαν υψηλότερη cfPWV σε σύγκριση με τους υγιείς μάρτυρες (9). Στην υποομάδα του ΣΕΛ, δε διαπιστώθηκαν στατιστικά σημαντικές συσχετίσεις ανάμεσα στην cfPWV και τους δείκτες φλεγμονώδους δραστηριότητας ή χρονιότητας της νόσου. Ωστόσο, η αξία αυτής της εξέτασης στις επαναληπτικές (διαχρονικές) αξιολογήσεις των ασθενών με αυξημένες τιμές cfPWV ή παρελθόντα καρδιαγγειακά συμβάματα παραμένει σημαντική. Συνολικά, η παρούσα εργασία αποτελεί ένα ακόμα βήμα στην επικύρωση της παρουσίας αυξημένης αορτικής σκληρότητας σε ασθενείς με ορισμένες από τις συστηματικές φλεγμονώδεις ρευματικές παθήσεις που εξετάστηκαν. Δεδομένου ότι η cfPWV είναι ένας καλά επικυρωμένος δείκτης καρδιαγγειακού κινδύνου, αυτά τα αποτελέσματα μπορούν να χαρακτηριστούν ως σημαντικά. Επιπλέον, δείχτηκε ότι η αυξημένη αορτική σκληρότητα συσχετιζόταν κυρίως με παραδοσιακούς παράγοντες καρδιαγγειακού κινδύνου και όχι με νόσο-συσχετιζόμενες ανοσολογικές παραμέτρους. Ως εκ τούτου, οι παραδοσιακοί καρδιαγγειακοί παράγοντες πρέπει να λαμβάνονται υπόψη κατά την αντιμετώπιση ασθενών με συστηματικές φλεγμονώδεις ρευματικές νόσους. Η μέτρηση της cfPWV φαίνεται να είναι ένα χρήσιμο εργαλείο για την αναγνώριση ρευματολογικών ασθενών οι οποίοι βρίσκονται υπό αυξημένο καρδιαγγειακό κίνδυνο και, συνεπώς, μπορεί να επιτρέπει την έγκαιρη έναρξη της θεραπευτικής αγωγής και,τελικά, τη βελτίωση της συνολικής πρόγνωσης. Ωστόσο, απαιτούνται περαιτέρω προοπτικές μελέτες που να εξετάζουν την επίδραση του πόνου και / ή της ανοσοκατασταλτικής θεραπείας στο αγγειακό σύστημα των ασθενών με φλεγμονώδεις ρευματικές συστηματικές παθήσεις

NMDA Receptors in Health and Diseases: New Roles and Signaling Pathways—Anti-N-Methyl-D-Aspartate Receptor (NMDAR) Autoantibodies as Potential Biomarkers of Fatigue in Patients with Rheumatic Diseases

Fatigue is a widespread and complex symptom with motor and cognitive components; it is diagnosed predominantly by questionnaire. We recently published a correlation between anti-N-methyl-D-aspartate receptor (NMDAR) antibodies and fatigue in patients with SLE (systemic lupus erythematosus). In the present study, we examined whether this association also applies to patients with other rheumatic diseases. Serum samples of 88 patients with different rheumatic diseases were analyzed for the presence of anti-NR2 antibodies and Neurofilament light chain (NfL) protein. The severity of fatigue was determined according to the FSMC questionnaire (Fatigue Scale for Motor and Cognitive Functions) and correlated with the circulating antibody titer and NfL level accordingly. Positive titers of anti-NR2 antibodies were detected in patients with both autoimmune and non-autoimmune rheumatic diseases. These patients suffer predominantly from severe fatigue. The circulating NfL level did not correlate with the anti-NR2 titer and the fatigue severity in all patient groups. The association of severe fatigue with circulating anti-NR2 antibodies in patients with rheumatic diseases, independently from the main disease, suggests an individual role of these autoantibodies in fatigue pathophysiology. Thus, the detection of these autoantibodies might be a helpful diagnostic tool in rheumatic patients with fatigue

High cardiovascular risk in mixed connective tissue disease: evaluation of macrovascular involvement and its predictors by aortic pulse wave velocity

Macrovascular involvement and cardiovascular (CV) risk has not been sufficiently studied in mixed connective tissue disease (MCTD). In particular, the gold standard assessment method of aortic stiffness carotid-femoral pulse wave velocity (cfPWV) has never been evaluated in patients with this disease. The aims of the present study were therefore to examine cfPWV in MCTD and to evaluate its associations with MCTD-associated markers and traditional CV risk factors

Patients with Rheumatic Diseases do not have an Increased Risk of MRSA Carrier Status

<p></p><p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>. </b><a href="https://link.springer.com/article/10.1007/s40744-018-0116-4">https://link.springer.com/article/10.1007/s40744-018-0116-4</a></p><p></p><p></p><p> </p><p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p><br></p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p><br><p></p

A comparative analysis of clinical, para-clinical, and laboratory factors in ICU and Non-ICU admitted COVID-19 patients: identifying predictive markers for ICU admission

Introduction: Health care systems all over the world face numerous challenges as a result of the rapid spread of the COVID-19 virus that has resulted in increased mortality rates. About 40% of ICU-admitted COVID-19 patients were not severely ill at the time of admission. Thus, by using appropriate ICU admission predictors, clinicians can identify potential critical patients early on. It can also result in suitable resource allocation and consideration for these patients. Therefore, the current study was done with the aim of identifying clinical characteristics and laboratory data that could predict ICU admission in cases with COVID-19.Methods: This two-center retrospective observational study was done in Imam Reza and Ghaem Hospitals, Mashhad, Iran. Overall, 334 COVID-19 patients who referred to these hospitals from February to May 2020 were enrolled in this study. The participants were separated into two groups according to ICU admission status. All demographic, clinical, and paraclinical information were extracted from the medical records of the patients. Results: The present study composed of 88 ICU and 246 non-ICU-admitted COVID-19 patients. No significant differences were found in age between the two groups of patients (P=0.154). Multivariate regression analysis revealed that higher levels of CRP (OR=1.01, 95%CI 1.001-1.010, P=0.016), WBC (OR=1.11, 95% CI 1.01-1.22, P=0.03), and HRCT scores (OR=1.08, 95%CI=1.01-1.16, P=0.037) were linked to higher odds of ICU admission.Conclusion: This study suggests that higher levels of CRP, WBC, and LDH, as well as the HRCT score at the time of admission, were potential independent predictors of ICU admission during inpatient treatment in COVID-19 patients

The clinical phenotype of systemic sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort

To evaluate clinical associations of anti-PM/Scl antibodies in patients with SSc in a multicentre international cohort, with particular focus on unresolved issues, including scleroderma renal crisis (RC), malignancies, and functional outcome of interstitial lung disease (ILD)

Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study

Abstract OBJECTIVE: Arthritis, myositis and interstitial lung disease (ILD) constitute the classic clinical triad of anti-synthetase syndrome (ASSD). These patients experience other accompanying features, such as Raynaud's phenomenon, fever or mechanic's hands. Most ASSD patients develop the complete triad during the follow-up. In the present study we aimed to determine whether the subsequent appearance of accompanying features may suggest the development of triad findings lacking at the onset in anti-Jo1 positive ASSD patients. METHODS: Anti-Jo1 positive patients presenting with incomplete ASSD (no >2 classic triad features) were assessed. Clinical characteristics and clusters of disease manifestations were retrospectively collected and analyzed in a large international multicenter cohort of ASSD patients. RESULTS: 165 patients (123 women) with incomplete ASSD were identified. Ninety-five patients (57.5%) developed new classic triad manifestations after 15months median (IQR 9-51) and 40 (24%) developed new accompanying features after 19months median (IQR 6-56) from disease onset. During the follow-up, the ex-novo occurrence of triad features was observed in 32 out of 40 patients (80%) with new accompanying findings and in 63 out of 125 patients (50.5%) without new accompanying findings (p=0.002). In patients with at least one new accompanying feature the odds ratio for the occurrence of new triad manifestations was 3.94 with respect to patients not developing ex-novo accompanying findings (95% CI 1.68-9.21, p=0.002). CONCLUSION: Anti-Jo1 ASSD patients with incomplete forms at disease onset are at high risk for the subsequent occurrence of lacking classic triad findings. Although all ASSD patients should be carefully assessed for the occurrence of new triad features, a closer follow-up should be considered in the subgroup of patients developing ex novo accompanying findings. These patients, indeed, have near four-fold increased risk for new classic triad manifestation occurrence with respect to patients not presenting ex novo accompanying findings