COVID-19 Vaccination Before Initiating Rituximab Treatment Induces Strong Serological Response in Autoimmune Rheumatic Disease, Reducing Post-Pandemic Concerns About the Impact of Rituximab.

OBJECTIVE: Rituximab (RTX)-treated patients exhibit suboptimal responses to COVID-19 vaccines. However, existing research primarily involves patients already receiving RTX when vaccines were introduced, failing to account for the current landscape where patients are vaccinated before initiating RTX. Our objective was to compare the serological response to COVID-19 vaccines in patients vaccinated before or after RTX initiation. METHODS: We included 254 RTX-treated patients with autoimmune inflammatory rheumatic diseases (AIIRDs) and 113 blood donors (BDs) in a retrospective, observational cohort study. Patients were categorized based on the timing of RTX treatment relative to primary COVID-19 vaccination. Serological vaccine responses were assessed using three immunoassays, and logistic regression analysis was used to identify predictors of serological response. RESULTS: Patients vaccinated before initiating RTX treatment had significantly higher seroconversion rates of SARS-CoV-2 immunoglobulin G (87%) and neutralizing antibodies (91%) compared with those receiving RTX before and after vaccination (n = 132) (61% and 65%, respectively). In the logistic regression analysis, a positive serological response was associated with the number of vaccines administered >9 months after the last RTX treatment. Patients receiving the highest number of vaccines with >9 months after RTX showed a response comparable to that of the BDs. CONCLUSION: Vaccinating before RTX initiation yields a robust serological response in patients with AIIRDs. Furthermore, we highlight the reversibility of antibody impairment after RTX treatment cessation, provided that adequate vaccinations occur within a minimum of 9 months after RTX. Our findings offer essential insights for clinical decision-making regarding COVID-19 vaccination and RTX treatment, alleviating concerns about future RTX use.

Validity and reliability of measurement of peripheral oxygen saturation during the 6-Minute Walk Test in patients with systemic sclerosis.

Peripheral oxygen saturation (SpO2) using the fingers may have important limitations due to Raynaud's phenomenon and sclerodactyly in patients with systemic sclerosis (SSc). Sensors located at more central body positions may be more accurate as these as less prone to Raynaud attacks. To determine the validity and reliability of the SpO2 measured at the finger, forehead, and earlobe during the 6-Minute Walk Test (6MWT). Eighty two patients with SSc had an arterial line placed while performing the 6MWT. Peripheral oxygen saturation was simultaneously measured by finger, forehead, and earlobe sensors and compared to the arterial oxygen saturation (SaO2) measured before and after the 6MWT. 40 patients repeated the 6MWT one week later to determine re-test reliability. We used Bland-Altman plots to display the agreement between SpO2 and SaO2. The intraclass correlation coefficient for repeated measurement of minimum SpO2 was calculated. The mean difference between SpO2 and SaO2 after the 6MWT was - 3% (SD: ± 5), 0% (SD: ± 2), and 1% (SD: ± 2) for the finger, forehead, and earlobe, respectively. The minimum SpO2 measured at the finger demonstrated the poorest re-test reliability: The ICC (95% CI) showed good agreement using the ear and forehead probe (ICCear = 0.89 [95% CI 0.80; 0.94]; ICCforehead = 0.77 [95% CI 0.60; 0.87]), while a modest reliability was found using the finger probe (ICCfinger = 0.65 95% CI [0.43; 0.80]). SpO2 should be measured using either the earlobe or forehead during the 6MWT in patients with SSc. Clinical Trials.Gov (NCT04650659).

High-resolution peripheral quantitative computed tomography for the assessment of acro-osteolysis and calcinosis in patients with systemic sclerosis.

OBJECTIVE: To assist the development of future treatments in systemic sclerosis (SSc), the development of reliable outcome measures is pivotal. We aimed to evaluate the use of high-resolution peripheral quantitative CT (HR-pQCT) for visualization and gradation of acro-osteolysis (AO) and calcinosis compared to conventional hand radiographs (CR) in patients with SSc. METHODS: HR-pQCT scans of the 2nd to 4th fingers, CR, nail fold capillaroscopy, and a clinical examination were conducted. Images were reviewed for the presence and degree of AO and calcinosis according to semiquantitative grading scales. RESULTS: Forty patients were included. Fourteen had AO according to CR, whereas HR-pQCT revealed AO in 18 patients. The sensitivity and specificity of classifying patients as having AO by HR-pQCT when CR was used as reference were 93% (95% CI: 66-99%) and 80% (95% CI: 59-93%), respectively. By CR and with HR-pQCT as reference, the sensitivity and specificity were 72% (95% CI: 47-90%) and 95% (95% CI: 76-99%). Patients with AO had more or larger calcifications than patients without AO according to the proposed HR-pQCT grading system, with a median grade of 2 (IQR: 1-3) versus 0 (IQR: 0-1) (P<0.01). Grade 3 changes were observed exclusively in patients with AO (n=6/14, 42.9%). Assessment of AO and calcinosis by HR-pQCT demonstrated moderate to excellent test-retest reliability. CONCLUSION: HR-pQCT allowed precise and reliable classification and grading of acro-osteolysis and acral calcinosis. The modality could prove helpful for detecting and monitoring these lesions as well as facilitating early diagnosis and guide treatment of these patients.

Raynaud's phenomenon.

Raynaud's phenomenon (RP) is a vasospastic condition of the extremities in response to cold or stress, affecting approximately 3% to 5% of the population. While most patients have primary RP, the condition can also occur secondary to a variety of underlying medical conditions. RP may be the presenting symptom of connective tissue diseases, especially systemic sclerosis, and RS may therefore provide an opportunity for early diagnosis and treatment. This review addresses the causes, clinical features, diagnostic workup, and treatment possibilities of RS.

Mortality of patients examined at a diagnostic centre: A matched cohort study.

BACKGROUND: 'Diagnostic Centres' has been established to provide a diagnostic pathway for patients with non-specific, serious symptoms that could be cancer. As little is known about the prognosis, we aimed to 1) analyse mortality of patients examined at the diagnostic centre, stratified on diagnostic outcome (cancer, serious-non-malignant disease, or other/no diagnosis), and 2) compare mortality for cancer patients examined at the diagnostic centre with cancer patients diagnosed through other routes. METHOD: Retrospective cohort study including 938 patients examined at the Diagnostic Centre, Silkeborg Regional Hospital, Denmark, during 2012-2014. Cancer patients examined at the diagnostic centre were matched (1:10) to a reference group of cancer patients diagnosed through other routes. Information on diagnosis, death, comorbidity and socioeconomic factors was obtained by linkage to national Danish registers. Mortality was assessed by Kaplan Meier mortality survival analysis and hazard ratios of death were estimated using Cox proportional regression analysis while adjusting for confounders. RESULTS: The 1-year cumulative mortality was 28% in cancer patients examined at the diagnostic centre. The hazard ratio of death was seven times increased in cancer patients compared to patients with other/no diagnosis. The hazard ratio of death was 0.91 (95% CI: 0.68; 1.22) in cancer patients examined at the diagnostic centre compared to cancer patients diagnosed through other routes. DISCUSSION: The mortality among cancer patients examined at the diagnostic centre was comparable to cancer patients diagnosed through other routes. The results indicate that cancer patients with non-specific serious symptoms do not have a worse prognosis than other cancer patients.

Routine blood tests and probability of cancer in patients referred with non-specific serious symptoms: a cohort study.

BACKGROUND: Danish cancer patients have lower survival rates than patients in many other western countries. Half of the patients present with non-alarm symptoms and thus have a long diagnostic pathway. Consequently, an urgent referral pathway for patients with non-specific serious symptoms was implemented throughout Denmark in 2011-2012. As part of the diagnostic workup, a panel of blood tests are performed for all patients referred by their general practitioner (GP) to the urgent referral pathway. In this study, we analysed the probability of being diagnosed with cancer in GP-referred patients with abnormal blood test results. METHOD: We performed a cohort study that included all patients aged 18 years or older referred by their GP to Silkeborg Regional Hospital for analysis of a panel of blood tests. All patients were followed for 3 months for a cancer diagnosis in the Danish Cancer Registry. The likelihood ratio and post-test probability of subsequently finding cancer were calculated in relation to abnormal blood test results. RESULTS: Among the 1499 patients included in the study, 12.2% were subsequently diagnosed with cancer. The probability of cancer increased with the number of abnormal blood tests. Patients with specific combinations of two abnormal blood tests had a 23-62% probability of cancer. Only a few single abnormal blood tests were linked with a high post-test probability of cancer, and most abnormalities were not specific to cancer. CONCLUSIONS: A number of specific abnormal blood tests and combinations of abnormal blood tests markedly increased the probability of cancer being diagnosed. Still, abnormal blood test results should be interpreted cautiously as most are non-specific to cancer. Thus, results from the blood test panel may strengthen the suspicion of cancer, but blood tests cannot be used as a stand-alone tool to rule out cancer.

Clinical characteristics and risk of serious disease in patients referred to a diagnostic centre: A cohort study.

BACKGROUND: Little is known about the clinical characteristics of patients referred to a diagnostic centre through the Danish urgent referral pathway for non-specific serious symptoms. We aimed at estimating the distribution of serious disease and the diagnostic value of clinical characteristics for the diagnosis of cancer and serious non-malignant disease in these patients. METHOD: A cohort study of 938 patients referred by their GP to the diagnostic centre at Silkeborg Regional Hospital. All patients were followed up for three months in national registries. The likelihood ratio (LR) of cancer or serious non-malignant disease were calculated in relation to clinical characteristics. RESULTS: A total of 327 (34.9%) patients were diagnosed with new serious disease within three months: 118 patients (12.6%) with malignant disease and 209 patients (22.3%) with non-malignant disease. Most patients presented general symptoms. The highest LR of cancer was found for abdominal mass, high lactate dehydrogenase or abnormal findings in the diagnostic imaging. The highest LR of non-malignant disease was found for swollen joints or abnormal auscultation of lung or chest. CONCLUSIONS: Patients referred by their GP to the diagnostic centre have high risk of serious disease. A multidisciplinary diagnostic approach is needed to embrace the diagnostic spectrum.

Effectiveness and drug adherence of biologic monotherapy in routine care of patients with rheumatoid arthritis: a cohort study of patients registered in the Danish biologics registry.

OBJECTIVES: To estimate the prevalence of Danish RA patients currently on biologic monotherapy and compare the effectiveness and drug adherence of biologic therapies applied as monotherapy. METHODS: All RA patients registered in the Danish biologics database (DANBIO) as receiving biologic DMARD (bDMARD) treatment as monotherapy without concomitant conventional synthetic DMARDs (csDMARDs) during the study period 1 May, 2011 through 30 April 2013 were eligible for inclusion. All patient files were checked to ensure that they were in accordance with the treatment registration in DANBIO. Descriptive statistics for prevalence, effectiveness and drug adherence of bDMARD monotherapy were calculated. RESULTS: Of the 775 patients on bDMARD monotherapy, adalimumab (21.3%), etanercept (36.6%) and tocilizumab (15.3%) were the most prevalent biologic agents administered. At the 6-month follow-up, the overall crude clinical disease activity index remission rate in patients still on a biologic drug was 22%, the 28-joint DAS remission rate was 41% and the response rate of those with a 50% improvement in ACR criteria was 28%. At the 6-month follow-up, the drug adherence rates were similar for the different bDMARDs, with the exception of infliximab, which had significantly poorer drug adherence (P < 0.001). The overall drug adherence (except for infliximab) was approximately 70% after 2 years. CONCLUSION: Nearly one in five (19%) biologic treatments for RA was prescribed in Denmark as monotherapy, of which 70% were on monotherapy from bio-initiation and 30% were on monotherapy after cessation of a concomitant csDMARD. Acceptable drug adherence and remission rates were achieved with bDMARDs. With the exception of infliximab, no statistically significant differences were observed between anti-TNFs and biologics with other modes of action.

[Immunoglobulin G4-related disease is a newly recognized inflammatory disease]. / Immunglobulin G4-relateret sygdom er en ny inflammatorisk sygdom.

IgG4-related disease is a newly recognized inflammatory disease characterized by tissue infiltrates of IgG4 positive plasma cells. The disease was first recognized in pancreas but has now been described in nearly every organ. The diagnosis is based on the presence of dense lymphoplasmocytic infiltrates rich in IgG4 positive plasma cells. We describe a case of a 76-year-old man with IgG4-related disease involving the kidneys.

Gender and age effects on the continuous reaction times method in volunteers and patients with cirrhosis.

Minimal hepatic encephalopathy (MHE) is a metabolic brain disorder occurring in patients with liver cirrhosis. MHE lessens a patient's quality of life, but is treatable when identified. The continuous reaction times (CRT) method is used in screening for MHE. Gender and age effects on the CRT method are unknown and may confound the results. The aim of this study was to standardise the CRT method outcomes for age and gender effects. We studied 121 volunteers without known disease and 181 patients with cirrhosis by a CRT test. Reaction time to an auditory signal was measured 100 times, the 10th, 50th, and 90th reaction time percentiles were recorded, and the CRT index was calculated as the 50th percentile/(90th percentile-10th percentile), as a measure of intra-individual stability in reaction times. In volunteers, men reacted faster than women and their reaction times slowed with age. However, neither the gender nor the age effect was present regarding the CRT index. The patients with cirrhosis reacted slower and with a higher degree of instability than volunteers. Male patients reacted faster than female patients, and reaction times tended to slow with age. As among the volunteers, there was no gender or age effect on CRT index for the patients with cirrhosis. Age and gender influenced reaction times of both volunteers and patients with cirrhosis. The CRT index, however, was independent of age and gender in both groups. Screening of patients with cirrhosis using the CRT index, therefore, identifies brain dysfunction rather than effects of gender and age.