The identification of novel, robust biomarkers for the diagnosis of rheumatic diseases (RDs) and the presence of active disease might facilitate early treatment and the achievement of favourable long-term outcomes. We conducted a systematic review and meta-analysis of studies investigating the acute phase reactant, serum amyloid A (SAA), in RD patients and healthy controls to appraise its potential as diagnostic biomarker. We searched PubMed, Scopus, and Web of Science from inception to 10 April 2024 for relevant studies. We evaluated the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024537418). In 32 studies selected for analysis, SAA concentrations were significantly higher in RD patients compared to controls (SMD = 1.61, 95% CI 1.24-1.98, p < 0.001) and in RD patients with active disease compared to those in remission (SMD = 2.17, 95% CI 1.21-3.13, p < 0.001). Summary receiving characteristics curve analysis showed a good diagnostic accuracy of SAA for the presence of RDs (area under the curve = 0.81, 95% CI 0.78-0.84). The effect size of the differences in SAA concentrations between RD patients and controls was significantly associated with sex, body mass index, type of RD, and study country. Pending the conduct of prospective studies in different types of RDs, the results of this systematic review and meta-analysis suggest that SAA is a promising biomarker for the diagnosis of RDs and active disease.

BACKGROUND: Inflammatory bowel diseases (IBD) are frequently diagnosed between the ages of 20 and 40, i.e. the most fertile period for women. The potential impact of IBD on pregnancy is therefore a frequent issue.
OBJECTIVE: To determine the impact of disease activity during pregnancy on the obstetric prognosis of women with IBD.
METHODS: Gastroenterological and obstetric data were collected for patients for all consecutive patients with IBD and pregnancy followed up at Amiens University Hospital (Amiens, France) between 2007 and 2021. Obstetrics outcome of patients with and without active disease were compared.
RESULTS: One hundred patients were included (81 with Crohn\'s Disease for 198 pregnancies, 19 with Ulcerative Colitis for 37 pregnancies). Patients with active IBD (21 patients, 24 pregnancies) were more likely to be admitted to hospital during pregnancy (66.6, vs. 5.2% in the inactive IBD group; p < 0.001), to give birth prematurely (mean term: 36.77 weeks of amenorrhoea (WA) vs. 38.7 WA, respectively; p = 0.02) and to experience very premature delivery (before 32 WA: 12.5 vs. 1.4%, respectively; p = 0.02). Patients with active disease had a shorter term at birth (38.4 WA, vs. 39.8 WA in the inactive disease group; p < 0.0001), a lower birth weight (2707 g vs. 3129 g, respectively; p = 0.01) and higher caesarean section rate (54.2 vs. 16.9%, respectively; p = 0.03).
CONCLUSIONS: Women with IBD patients are at risk of pregnancy related complications, especially when IBD is active. Controlling disease activity at conception and close monitoring of the pregnancy is essential to improve both gastroenterological and obstetric outcome.

The identification of novel, easily measurable biomarkers of inflammation might enhance the diagnosis and management of immunological diseases (IDs). We conducted a systematic review and meta-analysis to investigate an emerging biomarker derived from the full blood count, the systemic inflammation index (SII), in patients with IDs and healthy controls. We searched Scopus, PubMed, and Web of Science from inception to 12 December 2023 for relevant articles and evaluated the risk of bias and the certainty of evidence using the Joanna Briggs Checklist and the Grades of Recommendation, Assessment, Development, and Evaluation Working Group system, respectively. In 16 eligible studies, patients with IDs had a significantly higher SII when compared to controls (standard mean difference, SMD = 1.08, 95% CI 0.75 to 1.41, p < 0.001; I2 = 96.2%, p < 0.001; moderate certainty of evidence). The pooled area under the curve (AUC) for diagnostic accuracy was 0.85 (95% CI 0.82-0.88). In subgroup analysis, the effect size was significant across different types of ID, barring systemic lupus erythematosus (p = 0.20). In further analyses, the SII was significantly higher in ID patients with active disease vs. those in remission (SMD = 0.81, 95% CI 0.34-1.27, p < 0.001; I2 = 93.6%, p < 0.001; moderate certainty of evidence). The pooled AUC was 0.74 (95% CI 0.70-0.78). Our study suggests that the SII can effectively discriminate between subjects with and without IDs and between ID patients with and without active disease. Prospective studies are warranted to determine whether the SII can enhance the diagnosis of IDs in routine practice. (PROSPERO registration number: CRD42023493142).

To determine the impact of thyroid eye disease (TED) on patients in various stages of the disease.
TED is a debilitating and potentially sight-threatening inflammatory autoimmune disease that is frequently misdiagnosed. Challenging quality-of-life (QoL) issues can persist long after the active phase of disease has subsided.
A 62-question survey was designed as a hypothesis-generating instrument to identify key issues confronting patients ≥18 years old with physician-diagnosed TED. Questions focused primarily on physical and emotional status, and QoL experiences in the 2 months prior to the survey. Data for individual questions are presented as summary statistics. Correlations between questions were determined using χ2 analyses.
The 443 respondents were 18 to >80 years old; >90% female, and >80% from the United States. Time since TED diagnosis ranged from <1 year to >10 years. Participants provided >500 free-form responses describing experiences of living with TED. Physical signs/symptoms were experienced by 307/443 (69%) patients. Of those responding to the QoL questions (N = 394), 53 (13%) reported symptoms improving, 73 (19%) reported symptoms worsening, and 255 (65%) reported no change in the 2 months prior to the survey. The most bothersome signs/symptoms were dry/gritty eyes, light sensitivity, bulging eyes, and pressure or pain behind the eyes. Respondents <60 years were significantly (p < 0.0001) more likely to report symptomatic TED than older patients. Of 394 respondents, 179 (45%) reported feeling depressed and/or anxious, 174 (44%) reported concern about their appearance, and 73 (19%) avoided public situations; 192 (49%) reported declines in confidence or feelings of general well-being, and 78 (20%) reported an inability to achieve goals. Activities limited by TED included reading, driving, and socializing. The proportion of respondents experiencing these negative QoL measures was higher when patients reported experiencing >5 symptoms, had been diagnosed within the last 5 years, or were <60 years of age.
Physical manifestations of TED impact QoL for patients through all phases of the disease. It is essential that physicians and healthcare professionals become more familiar with patient experiences such as those described here to better help patients manage their disease.

Whole T cell interferon gamma release assays such as QuantiFERON-TB Gold Plus (QTF-TB) are used to evaluate Mycobacterium tuberculosis complex (MTC) exposure but fail to discriminate latent tuberculosis infection (LTBI) from active disease. In this study conducted in a low-burden area, 1215 patients presenting MTC risk and tested both for QTF-TB and mycobacterial infection (microscopy, culture, and/or PCR) were selected, as well as 1298 controls screened with QTF-TB before medical recruitment. The humoral response (LIODetect®TB-ST) was further evaluated in 199 selected patients. In patients with active disease, MTC positivity (culture and/or PCR with species identification) was associated with QTF-TB positivity (45/56, 80.4 %). Although QTF-TB1/TB2 peptides were not suitable for discriminating against active MTC disease from LTBI, the cut-off value of 4.4 IFN-γ IU/mL produced the best diagnostic performance for MTC detection. Lower levels of QTF-TB were reported among patients with isolated active pulmonary MTC as compared to a lymph-nodal location and a disseminated form. Next, antibodies were detected in 4/55 (7.3 %) active MTC disease cases, while negative in cases of LTBI and indeterminate/negative QTF-TB. In conclusion, the added value to combine cellular (QTF-TB) and humoral (LIODetect®TB-ST) assays to predict an active MTC disease is limited.

A 39-year-old man was admitted with acute heart failure due to severe aortic regurgitation induced by annuloaortic ectasia associated with Takayasu\'s arteritis. Because of the active inflammatory phase associated with Takayasu\'s arteritis, surgery is typically performed following immune suppression by steroid therapy. Herein, we report a favorable recovery in the active inflammatory phase. Steroid therapy was initiated shortly following surgery. The decision to perform aortic root replacement without prior steroid therapy was made because the patient\'s risk of subsequent heart failures was deemed high and was complicated by other comorbidities.

Total hip arthroplasty (THA) provides a good treatment option for the patients in late arthritis stage. We present our experience of THA in various spectrums of disease.
Retrospective study including 23 advanced tubercular hip arthritis patients over a period of 13 years. The patients with active discharging sinus were excluded from the study. The patients were divided into three groups: group 1 (healed TB), group 2 (active TB), and group 3 (intraoperative surprise). The preoperative and postoperative antitubercular treatment (ATT) was administered to all the patients as per the protocol for various duration. All patients underwent THA (cementless or hybrid) after investigations including MRI. The patients were followed up with clinic-radiological and laboratory investigations.
The mean age of the patients was 58.2 years with 16 males and seven females. There were 14 healed TB hips, eight active TB hips, and one intraoperative TB hip patient. Preoperative ATT duration in group 1 varied from one to two weeks and in group 2 patient\'s average was 9.6 weeks (range: 6-12weeks). Postoperatively, ATT was given for a minimum of ten months extending to 16 months. Cementless THA was performed in 17 patients and hybrid THA (cemented stem) in six patients. Only one patient had aseptic loosening of the stem and revision arthroplasty was done.
THA is a viable option and provides mobile, stable hip in tubercular hip arthritis even in active TB hip patients. ATT is important in the management and prevent the reactivation of the disease.

Coping with a chronic disease such as rheumatoid arthritis (RA) involves significant changes in life and promotes stressful situations. The inability to cope with stress can contribute to the lack of effectiveness of therapy. The aim of this study was to evaluate the relationship between perceived stress, coping strategies, and the clinical status of RA patients determined by C-reactive protein (CRP) and Disease Activity Score (DAS28). 165 subjects were studied, 84 of them had RA and the rest were controls. Standardised questionnaires were used: the Inventory for the Measurement of Coping Strategies (Mini-COPE) and the Perceived Stress Scale (PSS-10). A self-administered questionnaire was used to collect sociodemographic data. The blood levels of protein CRP and cortisol were determined. DAS28 was obtained from medical records. The study was cross-sectional. The mean severity of perceived stress PSS-10 was not significantly different between the control and study groups. RA patients most often used coping strategies such as active coping, planning, and acceptance. Compared to the control group, they used the strategy of turning to religion significantly more often (1.8 vs 1.4; p = 0.012). Women with RA who had higher cortisol levels were more likely to use positive reevaluation, seeking emotional support and instrumental support, as well as the denial strategy. In men with RA, high stress was associated with twice as high CRP levels compared to patients with low stress (p = 0.038). As the levels of CRP protein levels (p = 0.009) and the DAS28 index (p = 0.005) increased, patients were more likely to use a denial strategy.

BACKGROUND: Older age and longer disease duration (DD) may impact the effectiveness of disease-modifying therapies in patients with multiple sclerosis (MS). Siponimod is a sphingosine 1-phosphate receptor modulator approved for the treatment of active secondary progressive MS (SPMS) in many countries. The pivotal phase 3 EXPAND study examined siponimod versus placebo in a broad SPMS population with both active and non-active disease. In this population, siponimod demonstrated significant efficacy, including a reduction in the risk of 3-month confirmed disability progression (3mCDP) and 6-month confirmed disability progression (6mCDP). Benefits of siponimod were also observed across age and DD subgroups in the overall EXPAND population. Herein we sought to assess the clinical impact of siponimod across age and disease duration subgroups, specifically in participants with active SPMS.
METHODS: This study is a post hoc analysis of a subgroup of EXPAND participants with active SPMS (≥ 1 relapse in the 2 years before the study and/or ≥ 1 T1 gadolinium-enhancing magnetic resonance imaging lesion at baseline) receiving oral siponimod (2 mg/day) or placebo during EXPAND. Data were analyzed for participant subgroups stratified by age at baseline (primary cut-off: < 45 year ≥ 45 years; and secondary cut-off: < 50 years or ≥ 50 years) and by DD at baseline (< 16 years or ≥ 16 years). Efficacy endpoints were 3mCDP and 6mCDP. Safety assessments included adverse events (AEs), serious AEs, and AEs leading to treatment discontinuation.
RESULTS: Data from 779 participants with active SPMS were analyzed. All age and DD subgroups had 31-38% (3mCDP) and 27-43% (6mCDP) risk reductions with siponimod versus placebo. Compared with placebo, siponimod significantly reduced the risk of 3mCDP in participants aged ≥ 45 years (hazard ratio [HR]: 0.68; 95% confidence interval [CI]: 0.48-0.97), < 50 years (HR: 0.69; 95% CI: 0.49-0.98), ≥ 50 years (HR: 0.62; 95% CI: 0.40-0.96), and in participants with < 16 years DD (HR: 0.68; 95% CI: 0.47-0.98). The risk of 6mCDP was significantly reduced with siponimod versus placebo for participants aged < 45 years (HR: 0.60; 95% CI: 0.38-0.96), ≥ 45 years (HR: 0.67; 95% CI: 0.45-0.99), < 50 years (HR: 0.62; 95% CI: 0.43-0.90), and in participants with < 16 years DD (HR: 0.57; 95% CI: 0.38-0.87). Increasing age or longer MS duration did not appear to increase the risk of AEs, with an observed safety profile that remained consistent with the overall active SPMS and overall SPMS populations in EXPAND.
CONCLUSIONS: In participants with active SPMS, treatment with siponimod demonstrated a statistically significant reduction in the risk of 3mCDP and 6mCDP compared with placebo. Although not every outcome reached statistical significance in the subgroup analyses (possibly a consequence of small sample sizes), benefits of siponimod were seen across a spectrum of ages and DD. Siponimod was generally well tolerated by participants with active SPMS, regardless of baseline age and DD, and AE profiles were broadly similar to those observed in the overall EXPAND population.

OBJECTIVE: The aim of this study was to investigate the burden of disease among a real-world cohort of patients with prevalent Crohn\'s disease (CD) in Germany.
METHODS: We conducted a retrospective cohort analysis using administrative claims data from the German AOK PLUS health insurance fund. Continuously insured patients with a CD diagnosis between 01 October 2014 and 31 December 2018 were selected and followed for at least 12 months or longer until death or end of data availability on 31 December 2019. Medication use (biologics, immunosuppressants (IMS), steroids, 5-aminosalicylic acid) was assessed sequentially in the follow-up period. Among patients with no IMS or biologics (advanced therapy), we investigated indicators of active disease and corticosteroid use.
RESULTS: Overall, 9284 prevalent CD patients were identified. Within the study period, 14.7% of CD patients were treated with biologics and 11.6% received IMS. Approximately 47% of all prevalent CD patients had mild disease, defined as no advanced therapy and signs of disease activity. Of 6836 (73.6%) patients who did not receive advanced therapy in the follow-up period, 36.3% showed signs of active disease; 40.1% used corticosteroids (including oral budesonide), with 9.9% exhibiting steroid dependency (≥ 1 prescription every 3 months for at least 12 months) in the available follow-up.
CONCLUSIONS: This study suggests that there remains a large burden of disease among patients who do not receive IMS or biologics in the real world in Germany. A revision of treatment algorithms of patients in this setting according to the latest guidelines may improve patient outcomes.