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.

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.

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.

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.

OBJECTIVE: We assessed levels of anxiety and depression in patients with Crohn disease (CD) to identify predictors of health-related quality of life (HRQOL).
METHODS: In this case-control study, we enrolled 50 adult patients with CD and 50 matched, healthy controls. All participants completed self-administered questionnaires including the Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Short Form-36 Health Survey (SF-36), and Short Inflammatory Bowel Disease Questionnaire (IBDQ, patients only). We analyzed the relationship between HRQOL and influencing factors.
RESULTS: Mean total scores on the SAS, SDS, and SF-36 were significantly different between patients and controls. IBDQ scores among patients in the active phase of CD were significantly lower than those in remission phase. SF-36 scores were significantly lower in patients with CD compared with healthy controls. SF-36 scores among patients with active CD were significantly lower than scores among those in remission, and SF-36 scores in patients without complications were significantly higher than in those with complications. SF-36 scores in patients with good nutritional status were also significantly higher than scores in malnourished patients with CD.
CONCLUSIONS: Depression, anxiety, disease activity, complications, and nutritional status were predictive factors of decreased HRQOL in patients with CD.

Dysregulations in the differentiation of CD4+-regulatory-T-cells (Tregs) and CD4+-responder-T-cells (Tresps) are involved in the development of active systemic lupus erythematosus (SLE). Three differentiation pathways of highly proliferative inducible costimulatory molecule (ICOS)+- and less proliferative ICOS--CD45RA+CD31+-recent-thymic-emigrant (RTE)-Tregs/Tresps via CD45RA-CD31+-memory-Tregs/Tresps (CD31+-memory-Tregs/Tresps), their direct proliferation via CD45RA+CD31--mature naïve (MN)-Tregs/Tresps, and the production and differentiation of resting MN-Tregs/Tresp into CD45RA-CD31--memory-Tregs/Tresps (CD31--memory-Tregs/Tresps) were examined in 115 healthy controls, 96 SLE remission patients, and 20 active disease patients using six color flow cytometric analysis. In healthy controls an appropriate sequence of these pathways ensured regular age-dependent differentiation. In SLE patients, an age-independently exaggerated differentiation was observed for all Treg/Tresp subsets, where the increased conversion of resting MN-Tregs/Tresps particularly guaranteed the significantly increased ratios of ICOS+-Tregs/ICOS+-Tresps and ICOS--Tregs/ICOS--Tresps during remission. Changes in the differentiation of resting ICOS+-MN-Tresps and ICOS--MN-Tregs from conversion to proliferation caused a significant shift in the ratio of ICOS+-Tregs/ICOS+-Tresps in favor of ICOS+-Tresps and a further increase in the ratio of ICOS--Tregs/ICOS--Tresps with active disease. The differentiation of ICOS+-RTE-Tregs/Tresps seems to be crucial for keeping patients in remission, where their limited production of proliferating resting MN-Tregs may be responsible for the occurrence of active disease flares.

Osteoarticular tuberculosis of the hip joint can be a debilitating disease that can result in severe cartilage degeneration, destruction, and eventual painful arthritis of the hip. Usually, a secondary affliction to a primary lung disease, Tuberculosis (TB) of the hip can be difficult to diagnose due to its indolent natural history and deep-seated nature of the hip joint itself. Untreated, ultimately TB hip leads to disabling arthritis of the hip with limitation of activities of daily living, livelihood, and socio-economic consequences. Historic surgical options such as arthrodesis and excision arthroplasty of TB hip have limitations and several disadvantages. Total hip arthroplasty (THA) is a viable option to restore mobility and relieve pain in patients with severe post-tuberculous arthritis but has been controversial in the past due to the concerns of disease reactivation. We evaluate the current role of THA in TB of the hip, its various applications in different presenting scenarios with a guide to surgical tips and tricks for managing this challenging condition.

Several facets of the host immune response to Salmonella infection have been studied independently at great depths to understand the progress and pathogenesis of Salmonella infection. The circumstances under which a Salmonella-infected individual succumbs to an active disease, evolves as a persister or clears the infection are not understood in detail. We have adopted a system-level approach to develop a continuous-time mechanistic model. We considered key interactions of the immune system state variables with Salmonella in the mesenteric lymph node to determine the final disease outcome deterministically and exclusively temporally. The model accurately predicts the disease outcomes and immune response trajectories operational during typhoid. The results of the simulation confirm the role of anti-inflammatory (M2) macrophages as a site for persistence and relapsing infection. Global sensitivity analysis highlights the importance of both bacterial and host attributes in influencing the disease outcome. It also illustrates the importance of robust phagocytic and anti-microbial potential of M1 macrophages and dendritic cells (DCs) in controlling the disease. Finally, we propose therapeutic strategies for both antibiotic-sensitive and antibiotic-resistant strains (such as IFN-γ therapy, DC transfer and phagocytic potential stimulation). We also suggest prevention strategies such as improving the humoral response and macrophage carrying capacity, which could complement current vaccination schemes for enhanced efficiency.

OBJECTIVE: Tofacitinib is an oral, small molecule Janus kinase inhibitor for the treatment of ulcerative colitis (UC). The efficacy and safety of tofacitinib in patients with moderate to severe UC, up to 1 year, have been reported. We investigated maintenance of efficacy in patients in remission after 52 weeks of maintenance treatment in the pivotal phase 3 study (OCTAVE Sustain); these patients received open-label, long-term treatment with tofacitinib 5 mg twice daily.
METHODS: Patients with moderate to severe UC who completed a 52-week, phase 3 maintenance study (OCTAVE Sustain) were eligible to enroll into the ongoing, phase 3, multicenter, open-label, long-term extension (OCTAVE Open). We analyzed data from 142 patients who were in remission following tofacitinib treatment in OCTAVE Sustain who received tofacitinib 5 mg twice daily during OCTAVE Open. We assessed efficacy (including remission [based on total Mayo score], endoscopic improvement, clinical response, and partial Mayo score up to month 36 of OCTAVE Open) and safety data.
RESULTS: After 12 months of tofacitinib 5 mg twice daily in OCTAVE Open, 68.3% of patients were in remission, 73.9% had endoscopic improvement, and 77.5% had a clinical response. At month 36, 50.4%, of the patients were in remission, 55.3% had endoscopic improvement, and 56.0% had a clinical response. The safety profile of tofacitinib 5 mg twice daily revealed no new safety risks associated with long-term exposure up to 36 months.
CONCLUSIONS: Efficacy endpoints were maintained for up to 36 months, regardless of prior tofacitinib dose, including patients who reduced from tofacitinib 10 mg to 5 mg twice daily upon OCTAVE Open entry. No new safety risks were identified. ClinicalTrials.gov: OCTAVE Sustain (NCT01458574); OCTAVE Open (NCT01470612).