Background: Digital ulcers (DUs) are common in systemic sclerosis (SSc) patients and cause significant morbidity. They are often complicated by local infection which can lead to contiguous osteomyelitis (OM). The clinical and imaging diagnosis of OM is challenging. The interpretation of MRI images, the gold standard for OM diagnosis, is problematic due to digital flexion contractures and acro-osteolysis. In our center (tertiary referral center for SSc), we use 99m-Technetium-Tc-labeled white blood cells (WBC) scintigraphy, for diagnosing OM in complicated DU. Despite the high sensitivity and specificity, it may be inconclusive in certain cases and it is a costly modality.Musculoskeletal ultrasound (US) imaging was found to be an accurate tool for OM diagnosis. Objectives: We aimed to assess the accuracy of US imaging in diagnosing contiguous OM in SSc patients with DU, compared to WBC scintigraphy. Methods: SSc patients with complicated DU, clinically suspected for OM, who were referred to WBC scan, were concurrently referred to US of the suspected DU. The US was performed by a highly skilled musculoskeletal imaging specialist, blinded to WBC scan results. Examinations were performed using the GE ML6-15-D Matrix Linear Probe LOGIQE9:R4.3.0 Ultrasound Machine. The sonographic findings indicating OM were periosteal thickening, cortical erosions, increased flow within or around periosteum on power Doppler sonography and deep soft tissue swelling. All patients had baseline hands x-ray to rule out calcinosis or acro-osteolysis. Clinical reassessment of DU healing was performed within 1-3 months. Results: Seven patients (6 females, 8 US examinations) were included in the pilot study. The mean(SD) age was 64.6(12.8), disease duration 14.6(7.4) years, 5 patients had diffuse SSc. One patient had 2 US examinations for separate events of suspected OM, in different sites.The results of both imaging tests concurred ruling in 2 cases and ruling out OM in 3 others. In the remaining 3 cases, the WBC scan was inconclusive, but the US ruled out OM. Patients that tested negative for OM on WBC scans and/or US were treated accordingly, with significantly shorter courses of antibiotics. Healing of the complicated DUs was achieved in all of them. Conclusion: In our pilot study, US imaging was found to be reliable in confirming and ruling out OM in SSc patients with complicated infected DUs, even in patients with inconclusive WBC scans. Musculoskeletal US may serve as a feasible and less expensive imaging technique for diagnosing contiguous OM in SSc-related DUs. Larger studies are required to confirm these preliminary results. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1

Abstract Background Inflammation is thought to play a role in the development of atrial fibrillation (AF). Previous studies suggested that inflammatory bowel disease (IBD) is associated with increased risk of AF. These studies also found IBD patients receiving biologic agents were at higher risk of AF than patients not receiving them. We sought to determine the association between anti-TNF treatment and the risk of AF in IBD patients Methods In this observational cohort, we included all adult IBD patients who were registered in Rambam Medical Center, diagnosed with IBD from November 1983 to October 2021. We excluded patients who were diagnosed with AF and/or stroke prior to IBD diagnosis. Disease severity was based upon IBD treatment. Mild disease was defined as no treatment, 5-ASA, or topical steroids, while moderate-to-severe disease was defined as any immunomodulator, biologic or systemic steroid therapy. Primary outcome was AF diagnosis. We used Cox proportional hazard model to compare AF in patients receiving anti-TNF treatment to those with mild disease. We further adjusted the hazard ratio of AF development based on known AF risk factors, including age, male gender, cardiovascular disease, chronic kidney disease, pervious venous thromboembolism, hyperlipidemia, diabetes, and thyroid disease. Results Our initial cohort included 5,326 patients. After exclusion, 4,886 patients were included. Median follow-up time was 8.49 years 2,720 patients were considered as having mild IBD, while 787 patients received anti-TNF medications. During follow-up period, cumulative incidence of AF was 1.50% (n=41) and 0.89% (n=7), respectively (p=0.21). Unadjusted hazard ratio of AF occurrence in anti-TNF patients was 0.6 (95% CI; 0.27-1.3, p=0.211). After adjustment, hazard ratio of AF occurence was 1.33 (95% CI; 0.53-3.3, p=0.545). Conclusion Anti-TNF treatment was not associated with increased risk of AF among IBD patients. This provides reassurance regarding the cardiovascular safety of anti-TNFs in a real-world IBD cohort.

Background The 3rd booster of mRNA vaccines against SARS COV2 was highly efficient against delta variant but data regarding the efficacy of the 3rd and 4th boosters against the omicron variants, among AIRD pts are scarce. Objectives We aimed to assess the effect of the 3rd and 4th booster mRNA vaccines against SARS CoV2, in preventing severe COVID-19, in AIRD patients (pts) treated with immunomodulating drugs. Methods 212 pts (mean age(SD) 57(13), disease duration 11.2(7.4), who received the 3rd booster (Pfizer) were included in the study. We performed serology tests 24 weeks after the second dose of vaccine and 4-8 weeks after the 3rd booster. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay. The test was considered positive above 50 AU/ml. Data regarding COVID-19 infection during the 5th outbreak (omicron) were collected from the medical files. The length of observation period was defined as the time from the 3rd booster to the last hospital visit or COVID 19 diagnosis, whichever occurred first. Results The 3rd booster administration (Pfizer) significantly augmented the humoral response (from mean(SD) 1121(4723) AU/ml to 12153(13687)). 58 patients received the 4th booster and 18 the 5th booster. COVID-19 was diagnosed in 103 pts (49%) within mean(SD) 224.8(106.5) days after the 3rd booster vaccination. 109 pts remained free of disease during mean(SD) follow-up 230.6(133.9). Following the 4th booster, 26 (45%) out of 58pts contracted COVID-19 within mean(SD) 97.6(78.7) days after the vaccination. One 70 year old patient (vaccinated 3 times) died and 2 other pts (rituximab treated) had severe COVID-19. The IgG Ab titer after the 3rd booster was lower in pts who contracted COVID 19 compared to those uninfected (mean(SD), median 8777.9(11716.4),3475 AU/ml vs 15348.1(14649.1),10801, p=0.004). There were no statistically significant differences between the pts with COVID-19 and those without, regarding age, type of disease, treatment and humoral response 24 weeks after the 2nd vaccination. Conclusion Despite an enhanced humoral response obtained after the 3rd booster, 49% of AIRD pts vaccinated with 3 doses and 45% of pts vaccinated with 4 doses had COVID-19 during the omicron outbreaks. Higher humoral response to the 3rd booster was associated with a lower rate of COVID19. The booster vaccines conferred 99% protection against severe COVID-19. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background A growing body of evidence suggests that the gut microbiota plays a significant role in the development of autoimmune diseases. An altered microbiota composition has been associated with gastrointestinal and extraintestinal features in systemic sclerosis (SSc) patients. Objectives To characterize differences in the gut microbiota between SSc patients and rheumatoid arthritis (RA) patients and to look for associations between microbial profiles and SSc subtypes, disease manifestations and treatment. Methods SSc and RA patients seen at our center were recruited in a prospective study. The exclusion criteria included antibiotic or probiotic treatment during the month prior to recruitment, recent hospitalizations, BMI>30, diabetes mellitus or concomitant inflammatory bowel disease. Fecal samples were collected and processed and 16S rRNA gene sequences were analyzed using the QIIME2 package. Microbiome composition was determined, beta diversity and alpha diversity were calculated and ANCOM analyses was performed. Results During 7/2018-4/2022, 49 SSc patients (mean age [SD] 53.5[13.8] and disease duration 9.4 [8.0] years) and 21 RA patients (mean age [SD] 57.1[10.4] and disease duration 15.1[10.0] years) fulfilled the criteria and were willing to participate in the study. Significant differences in beta diversity (Unweighted q=0.019, and Weighted UniFrac q=0.005) were found between RA and SSc patients’ stool microbiota, but not in alpha diversity. Composition analysis revealed higher abundance of Actinomyces and relative paucity of Coprococcus Eutactus among SSc patients compared to RA. Significant variations in beta diversity (unweighted and weighted) were associated with the subtype of SSc (diffuse - 27 vs limited - 22 patients, p [weighted] = 0.01), occurrence of interstitial lung disease (22 patients, p=0.011), renal crisis (3 patients, p=0.016), immunomodulatory treatment (33 patients, p=0.018) and biological treatment (11 patients, p=0.017). Composition analysis revealed higher relative abundance of Firmicutes in patients with GAVE [12]. Patients on biologicals (11) had higher abundance of Synergistaceae and lower of Firmicutes. The changes were consistent in recurrent fecal samples. Conclusion Significant differences on beta diversity were found between RA and SSc patients’ gut microbiota, but not on alpha diversity. Diffuse SSc, interstitial lung disease, renal crisis and immunomodulatory treatment were associated with shifts in the microbiome of SSc patients. The impact of these changes on SSc disease progression needs further elucidation. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

OBJECTIVES:We aimed to assess the efficacy and patient satisfaction of subcutaneous tocilizumab (SC TCZ) in patients previously treated with intravenous tocilizumab (IV TCZ) during the COVID-19 pandemic.METHODS:We conducted a single-centre retrospective study at the Rheumatology Day Care at the Rheumatology Institute, Rambam Health Care Campus, Israel. Clinical and laboratory data of IV TCZ treated patients who switched to SC TCZ were retracted and analysed. Data were collected from the last two visits before switching to SC treatment and two visits afterwards. A telephone call conversation was conducted for all patients who continued SC treatment and did not come to follow-up visits.RESULTS:Forty patients (age 53.03 (± 15.7)) treated with IV TCZ were switched to SC TCZ in April-May 2020. Three patients were excluded from the study. Most of the patients were treated with TCZ for 6.35 (±2.89) years and had low disease activity. 26/37 (70%) patients discontinued SC TCZ therapy and switched back to IV TCZ. The majority of discontinuations were due to flare up of the underlying disease reflected by increased number of tender and/or swollen joints, prolongation of morning stiffness or increased pain VAS score. Two patients were hospitalised for IV glucocorticoids and 1 patient underwent knee arthrocentesis. 11/37 (30%) patients continued SC TCZ treatment. 3/11 (27%) expressed less satisfaction with SC TCZ therapy.CONCLUSIONS:More than half of the patients who switched from IV TCZ to SC TCZ showed signs of flare of their underlying disease or were less satisfied with SC treatment.

Background Previous studies proved that mRNA vaccinations against SARS CoV2 induced significant humoral responses in AIRD patients (pts). However, the humoral response was blunted in pts treated with CD20 depleting antibodies. There are limited data regarding the long-term outcome of the humoral response and the contribution of the booster vaccine, in immunosuppressed AIRD pts. Objectives To assess the long-term outcome of the humoral response to mRNA vaccine against SARS CoV2, in AIRD pts treated with immunomodulating drugs, and the contribution of the booster vaccination. Methods Consecutive pts treated at the Rheumatology Institute at Rambam Hospital who received their first SARS-CoV-2 (Pfizer) vaccine were recruited to the study, at their routine visit. The visit included AIRD activity assessment and questioning regarding vaccine side effects. We performed serology test 4-6 weeks and 24 weeks after receiving the second dose of vaccine. Pts who received the booster (3rd vaccine) were invited for serology tests 4-8 weeks afterwards. The immunomodulating treatment was not modified, either before or after the vaccination. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay based on a chemiluminescent microparticle immunoassay (CMIA) on the ARCHITECT ci8200system from Abbott. This assay is measuring IgG antibodies against the spike receptor-binding domain (S-RBD) of the virus. The test was considered positive above 50 AU/ml. Results 262 pts (mean age(SD) 57(13), disease duration 11.2(7.4), were recruited. The cohort included 152 pts with inflammatory joint disease, 26 pts with systemic lupus erythematosus, 62 pts with other connective tissue disease and 22 pts with vasculitis; 27 % received csDMARDs only, 35% - b/tsDMARDs only, 30% - combined therapy (csDMARDs+b/tsDMARDs) and 26% received steroids. 225 pts (86%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU/ml, IQR 58-29499). 37 (14%) pts had negative tests, 23 (62.2%) of them were rituximab treated. The IgG levels correlated with the medication used to treat the AIRD, the patients’ age but not with the type of the AIRD (Figure 1). 24 weeks afterwards, the median IgG level dropped to 282 AU/ml and 15% of the pts with previous seropositive tests became negative. The booster administration (Pfizer) significantly augmented the humoral response (median 8328 AU/ml, IQR 375-40000). De novo serologic response was observed in 10 out of 37 pts (4/23 rituximab treated pts). Figure 1. The reported side effects of the vaccine were minor (muscle sore, headache, low grade fever). The AIRD remained stable in all pts following all three vaccinations. Conclusion Although the vast majority of AIRD pts developed a substantial humoral response following the administration of the second dose of the Pfizer mRNA vaccine against SARS CoV2 virus, the humoral response significantly declined 24 weeks afterwards. An enhanced response was obtained after the third booster vaccination. Only minor side effects were reported and no apparent impact on AIRD activity was noted. Notably, 62% of the non-responders were treated with B cell depleting agents. Acknowledgements We would like to thank Mrs Tsofnat Margi and Mrs Sarit Elkouby for organisational support. Disclosure of Interests None declared

INTRODUCTION: The clerkship of internal medicine is pursued in the 2nd semester of the 4th year at the Technion Medical School. Following the COVID-19 outbreak, frontal and bedside teaching was interrupted. Therefore, we decided to provide distant teaching until having the opportunity to resume clinical bedside teaching. A team of tutors composed a course of weekly units, each week assigned to a different subject in internal medicine. A total of 120 students were divided into 15 groups of 8 students, each group guided by a personal tutor. The format of each unit included online pretest, clinical virtual cases and two separate 2 hour ZOOM sessions with the tutor. The pretest was based on 1-3 chapters from Harrison's Internal Medicine textbook, 20th edition, and consisted of both clinical reasoning and knowledge questions. During ZOOM sessions with the tutor, the students practiced clinical problem solving. In addition, all the students were granted free access to the commercial Aquifer case-based virtual course for more practice. The students' feedback at the end of the learning period revealed that, although frustrated in being away from the clinics, the overall level of satisfaction from the course was good (rated 5 or 4/5 by 65% of responders) and the time was used efficiently. In conclusion, the students received a positive proactive learning experience of both theoretical aspects and clinical reasoning skills in internal medicine. There is no doubt that bedside teaching in medicine is invaluable and can't be replaced by any other means, however, given the circumstances, our format provided a reasonable temporary alternative.

BackgroundThe registration trials of messenger RNA (mRNA) vaccines against SARS-CoV-2 did not address patients with inflammatory rheumatic diseases (IRD).ObjectiveTo assess the humoral response after two doses of mRNA vaccine against SARS-CoV-2, in patients with IRD treated with immunomodulating drugs and the impact on IRD activity.MethodsConsecutive patients treated at the rheumatology institute, who received their first SARS-CoV-2 (Pfizer) vaccine, were recruited to the study, at their routine visit. They were reassessed 4–6 weeks after receiving the second dose of vaccine, and blood samples were obtained for serology. IRD activity assessment and the vaccine side effects were documented during both visits. IgG antibodies (Abs) against SARS-CoV-2 were detected using the SARS-CoV-2 IgG II Quant (Abbott) assay.ResultsTwo hundred and sixty-four patients with stable disease, (mean(SD) age 57.6 (13.18) years, disease duration 11.06 (7.42) years), were recruited. The immunomodulatory therapy was not modified before or after the vaccination. After the second vaccination, 227 patients (86%) mounted IgG Ab against SARS-CoV-2 (mean (SD) 5830.8 (8937) AU/mL) and 37 patients (14%) did not, 22/37 were treated with B cell-depleting agents. The reported side effects of the vaccine were minor. The rheumatic disease remained stable in all patients.ConclusionsThe vast majority of patients with IRD developed a significant humoral response following the administration of the second dose of the Pfizer mRNA vaccine against SARS-CoV-2 virus. Only minor side effects were reported and no apparent impact on IRD activity was noted.

Abstract Background: The registration trials of mRNA vaccines against SARS CoV2 did not address patients with autoimmune inflammatory rheumatoid diseases (AIRD). Aims: To assess the humoral response to mRNA vaccine against SARS CoV2, in AIRD patients treated with immunomodulating drugs and the impact on AIRD activity. Methods: Consecutive patients treated at the rheumatology institute who received their first SARS-CoV-2 (Pfizer) vaccine were recruited to the study, at their routine visit. The patients were invited for serology test 4-6 weeks after receiving the second dose of vaccine. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay Results: One hundred fifty-six consecutive patients (76% females) treated at a single rheumatology center (mean age (range) 59.1 (21-83) years), mean (range) disease duration 10.8 (1-55) years), were recruited to the study. Thirty-five percents of patients received conventional synthetic (cs)DMARDs only, 64% biological/targeted synthetic (b/ts) DMARDs, 34% received combined treatment with csDMARDs and b/tsDMARDs and 32% corticosteroids (mean dose(range) 5.8mg(2.5-20mg) prednisone). One hundred thirty-seven patients (88%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU/ml, range 58-29499). Nineteen (12%) patients had negative tests, 11/19 were treated with B cell depleting agents. The reported side effects of the vaccine were minor (muscle sore, headache, low grade fever). The rheumatic disease remained stable in all patients. Conclusions: The vast majority of AIRD patients developed a significant humoral response following the administration of the second dose of the Pfeizer mRNA vaccine against SARS CoV2 virus. Only minor side effects were reported and no apparent impact on AIRD activity was noted.