High Disease Activity Research Articles

Preoperative visualization of parathyroid pathology in patients with primary hyperparathyroidism using PAT/KT: a retrospective study

INTRODUCTION: Topical diagnosis of pathologically altered parathyroid glands in patients with primary hyperparathyroidism is a challenge both for specialists of radial diagnostics and for planning the scope of surgical intervention. The choice of diagnostic modality for localization of parathyroid glands depends on the availability of the method for a particular medical center. PET/CT is a promising method to determine the localization of parathyroid adenomaOBJECTIVE: To analyze the experience of using PET/CT with 11C-methionine and PET/CT with 11C-choline for preoperative diagnosis of parathyroid pathology in patients with primary hyperparathyroidism.MATERIALS AND METHODS: 72 patients diagnosed with PHPT and underwent surgical treatment were included in the study. Before surgical intervention all patients underwent laboratory and instrumental investigations in the scope of: blood tests for PTH, TTH, ionized calcium, calcitonin, 25(OH)D, creatinine, phosphorus, ultrasound of the neck, computer tomography of the neck with intravenous bolus contrasting.RESULTS: PET/CT showed the highest rates of DA in the patient group before primary surgery — 90.9%, compared with ultrasound (89.6%) and CT with IV contrast (84.9%). In the group of solitary adenomas of ectopic MTCS, PET/CT also had a higher DA — 92.8% than the other modalities. In patients with relapsed or persistent disease, the informativity rates of CT with intravenous contrast and PET/CT were similar (Se — 100%, Sp — 94.1%, DT — 96.2%).DISCUSSION: The algorithm for preoperative evaluation of patients to identify the location of pathologic parathyroid glands now includes imaging with two modalities: Neck ultrasound and radionuclide imaging: planar scintigraphy (washout/subtraction), SPECT, SPECT-CT. If the results are questionable, a CT scan of the neck with contrast or PET/CT is performed as a second step. None of the modalities has 100% diagnostic accuracy. Our study demonstrated the superiority of PET/CT over ultrasound and CT w/in contrast in a group of patients scheduled for primary surgical treatment. In a small group of patients, high informative rates of PET/CT and CT with contrast were demonstrated before reoperation, confirming the great potential of these techniques in these patients.CONCLUSION: PET/CT with 11C-methionine and PET/CT with 11C-choline have high diagnostic accuracy in patients with primary hyperparathyroidism before reoperation. PET/CT and CT with contrast showed similarly high diagnostic accuracy for the diagnosis of parathyroid adenoma with persistence or recurrence of the disease in patients with primary hyperparathyroidism.

The diagnostic value and clinical relevance of high frequency ultrasound and shear wave elastography in systemic sclerosis: an observational monocentric study.

To unravel the features of skin involvement in patients with systemic sclerosis (SSc) by high frequency ultrasound (HFU) and shear wave elastography (SWE). To assess the ultrasound capabilities to distinguish SSc patients from healthy controls (HCs). We recruited a cohort of SSc patients in this cross-sectional study. HFU and SWE were used to quantify skin thickness and skin stiffness. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic capabilities of ultrasound in SSc. The correlation analysis was used to evaluate the clinical relevance of ultrasound measurements in SSc. 20 consecutive SSc patients and 20 age-, gender- and body mass index-matched HCs were included. The skin thickness and stiffness were significantly greater in SSc patients compared with HCs. Patients with high disease activity had higher skin thickness and stiffness compared with patients with low disease activity. The area under the ROC curve (AUC) of the dorsum of middle fingers assessed by HFU was 0.847 (95% CI, 0.761-0.933). The AUC of the forearms and dorsum of hands assessed by SWE were 0.909 (95% CI, 0.829-0.989) and 0.879 (95% CI, 0.807-0.951). Further, the combined HFU and SWE tests displayed the best diagnostic performance with an AUC of 0.980 (95% CI, 0.939-1.000). A significant positive correlation between the ultrasound measurements and the modified Rodnan skin score (mRSS) was observed. The application of ultrasound can assist with disease diagnosis, it is necessary to develop a standard operating protocol to help with future implementation of ultrasound in SSc.

B-103 Correlation of Novel Markers, Anti-Sa (Citrullinated Vimentin) and Anti-CarP (Carbamylated Protein), with High Vectra® DA Disease Activity Scores in Rheumatoid Arthritis (RA)

Abstract Background Citrullination and carbamylation are post-translational modifications where autoantibodies against citrullinated and carbamylated proteins in RA have been associated with more aggressive disease. At the same time, Vectra® DA is blood test that yields a RA disease activity score from 1 to 100. Here, 120 patient samples were analyzed to assess the relationship of disease activity as measured by Vectra® score and the presence of Anti-Sa (Citrullinated Vimentin) and Anti-CarP (Carbamylated Protein). Methods Serum samples were analyzed for Vectra® DA (which is validated for adults with RA) where 12 biomarker measurements (VCAM-1, EGF, VEGF-A, IL-6, TNF-RI, MMP-1, YKL-40, Leptin, Resistin, SAA, CRP) together with patient age, gender and adiposity are used to generate a score where established categories are low for 1 to 29, moderate for 30 to 44, and high for 45 to 100. Anti-Sa and Anti-CarP were by ELISA lab-developed tests (LDT) with a cut-off for positive of >20 Units (U). Results Anti-Sa and Anti-CarP for 40 samples from each Vectra® DA category are reported. Patients with the highest Vectra® scores (mean 58.2, range 46.8 - 87.5) had highest rates of positivity for Anti-Sa (52.5%) and Anti-CarP (35%). In contrast, the group with the lowest Vectra® scores (mean 11.8, range 3.8 - 18.1) were infrequently positive for Anti-Sa (17.5%) and Anti-CarP (0%). Frequencies with moderate Vectra® scores (mean 37.1, range 32.4 - 41.8) were mid-range: Anti-Sa (25%) and 7.5% for Anti-CarP (7.5%). Of note, positivity of Anti-Sa was analytically stronger, i.e. higher titer, in patients with moderate or high Vectra® (mean 90.0U or 81.7U), compared to values seen in those with low Vectra® (mean 60.4 U). Conclusions Our analysis of 120 patient samples demonstrates that high disease activity as determined by Vectra® DA corresponds to higher positivity of novel autoantibody markers, Anti-Sa and Anti-CarP. High Vectra® DA scores (>44) are associated with a 20% 1-year risk of radiographic progression while low scores (<30) carry only a 1% risk. Here, we found that patients with high Vectra® scores were 3 times more likely to test positive for Anti-Sa than those with low disease activity scores. At the same time, Anti-CarP occurred in high frequency (35%) with high Vectra® in contrast to zero positivity observed with low Vectra® scores. Thus, our findings support Anti-CarP’s reported association with more active disease with higher risk of developing joint erosions. Also of note, patients with high Vectra® scores had particularly high Anti-Sa positivity - both a 52.5% positivity rate as well as higher Anti-Sa levels (titers) than the group with lower Vectra® scores. These data corroborate other studies where Anti-Sa not only predicted more aggressive, rapid disease progression, but its titers correlated with clinical measures of disease activity. Taken together, our data support the consistency and clinical usefulness of the Vectra® score along with novel autoantibody markers, Anti- Anti-Sa and Anti-CarP, in order to assess RA severity, prognosis, and patient-specific treatment strategies.

Practical Recommendations from the Gulf Region on the Therapeutic Use of Cladribine Tablets for the Management of Relapsing Multiple Sclerosis: Impact of the Latest Real-World Evidence on Clinical Practice.

Cladribine tablets (CladT), like alemtuzumab, acts as an immune reconstitution therapy. However, CladT is administered orally (alemtuzumab is given by infusion) and without the potential for serious side effects that limit the therapeutic use of alemtuzumab in multiple sclerosis (MS). Treatment with CladT, given initially as short courses of treatment 1year apart, provides years of freedom from MS disease activity in responders to treatment. The appearance of mild or moderate MS disease activity after the initial 2years of treatment may prompt careful follow-up or a further course of CladT, depending on the nature of the activity and individual circumstances. The appearance of severe MS disease activity requires a switch to an alternative high-efficacy disease-modifying treatment (DMT). The accumulating data from CladT-treated people with MS in real-world studies, including those with follow-up durations extending for years beyond the initial treatment, have demonstrated long-term freedom from MS disease activity in a good proportion of patients. This clinical experience has also confirmed that treatment with CladT is generally safe and well tolerated. The best time to prescribe a high-efficacy DMT is the subject of debate, with evidence that earlier versus later use of such agents may provide more effective long-term protection from disability progression. High-efficacy DMTs have traditionally been reserved for use in people with MS and high disease activity on presentation or breakthrough disease on one or more DMTs, as per the current product labels. The latest evidence from real-world studies suggests that CladT is effective and safe in DMT-naïve patients, including those with shorter disease duration.

Clinical enthesitis in patient with psoriatic arthritis, a systematic literature review with meta-analysis

Objectives: Enthesitis is considered a hallmark of psoriatic arthritis (PsA). The objective was to assess clinical enthesitis in PsA including its prevalence in different contexts, scores used and consequences of enthesitis.Methods: A systematic literature review with meta-analysis was conducted in PubMed 2010-2023, focusing on manuscripts involving adult PsA patients and reporting information related to enthesitis. Data collected included the prevalence of clinical enthesitis (i.e., number of patients with at least one enthesitis); scores used: Leeds Enthesitis Index (LEI), MASES, SPARCC; and impact of enthesitis on disease activity, patient-reported outcomes and use of analgesics. Univariate random-effects meta-analysis was applied for pooling percentages and means.Results: Overall, 212 studies, i.e., 84,262 PsA patients were analyzed. The pooled prevalence of enthesitis in the overall population was 41.6% [95% confidence interval, 37.4-45.8]; with 67.2% [62.0-72.6] in trials and 27.8% [24.5-31.2] in observational studies. The number of enthesitis varied according to the score used, with the lowest observed for the LEI which was the most widely-used score (63.7%). Patients with enthesitis had higher disease activity and disease burden in comparison with those without enthesitis.Conclusion: Enthesitis is a frequent manifestation in PsA, concerning close to half the patients, and is more prevalent in trials than in observational studies, reflecting recruitment patterns. The clinical assessment of enthesitis remains challenging, with heterogeneity in the scores used influencing the results: the most used score was the LEI which also led to the lowest prevalence of enthesitis. Links with patients’ quality of life should be further explored.

Poor prognostic factors independently impact remission and treatment escalation in rheumatoid arthritis regardless of disease activity: A nationwide prospective cohort study

Objective: To elucidate the impact of poor prognostic factors (PPFs) in daily practice on achieving remission and the requirement for biologic or targeted synthetic DMARDs (b/tsDMARDs) in a large Korean cohort of patients with rheumatoid arthritis (RA).Methods: Using the KORean Observational study Network for Arthritis (KORONA) database, patients with RA were categorized into three groups based on the number of PPFs (0–1, 2, or ≥3): the presence of functional limitation, extra-articular disease, seropositivity, and bone erosions. Factors related to achieving remission and to initiating b/tsDMARDs were evaluated using Cox proportional hazard regression analyses after adjusting confounders.Results: Among 5,076 patients with RA, Group L (PPF ≤1), Group M (PPFs 2), and Group H (PPFs ≥3) were 1,788 (35.2%), 2,027 (39.9%), and 1,261 (24.9%), respectively. Group H had higher disease activity and worse patient-reported outcomes than Groups L and M. Among moderately-to-highly active patients at baseline, Group H was significantly less likely to attain point (hazard ratio [HR]=0.55, 95% confidence interval [CI] 0.38–0.79) and sustained (HR=0.45, 95% CI 0.21-0.99) Boolean-based remission in 5-year. Groups M (HR=1.47, 95% CI 1.10–1.96) and H (HR=1.69, 95% CI 1.22–2.32) had an increased risk of escalation to b/tsDMARDs, compared to Group L among b/tsDMARDs-naïve patients at baseline.Conclusion: Achieving remission was particularly challenging for Group H, and more patients in Groups M and H initiated b/tsDMARDS during the 5-year observation period. Therefore, the presence of PPFs ≥3 significantly influences both patients' outcomes and clinician's treatment decisions regardless of disease activity.

Association of RIPK1 and RIPK2 Gene Polymorphisms with Rheumatoid Arthritis in a Chinese Han Population.

Rheumatoid arthritis (RA) is a systemic autoimmune disease with an obscure pathogenesis. This study aims to identify the susceptibility conferred by specific single nucleotide polymorphisms (SNPs), namely rs17548629 within the RIPK1 gene and rs10094579 within the RIPK2 gene, in RA. Additionally, it investigates the associations between inflammatory markers and biochemical parameters at various stages of the disease. We analyzed 394 patients with RA and 258 normal controls (NCs), examining SNPs within the RIPK1 (rs17548629) and RIPK2 (rs10094579) genes using polymerase chain reaction (PCR) and sequencing techniques. Profiles of RA patients were evaluated for inflammatory markers, including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), as well as biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea, glucose, uric acid, and creatinine. Additionally, disease-specific indicators included cyclic citrullinated peptide (CCP), rheumatoid factor (RF), antinuclear antibodies (ANA), and anti-keratin antibodies. The Disease Activity Score 28 (DAS28), based on ESR, was used to categorize RA patients into groups of high, moderate, or low disease activity. We found a significant association between the RIPK1 rs17548629 genotype and RA in the additive model (p < 0.001; OR = 3.23), over-dominant model (p < 0.001; OR = 0.27), and dominant model (p < 0.001; OR = 3.94). The frequency of the C allele at rs17548629 was significantly higher in NCs than in RA patients (p < 0.001; OR = 0.322). When compared with normal controls, the RIPK1 rs17548629 genotype demonstrated significant associations with both anti-CCP-positive RA patients (p < 0.001) and anti-CCP-negative RA patients (p < 0.001). Similarly, this genotype was associated with RF-positive RA patients (p < 0.001). Furthermore, the RIPK2 rs10094579 genotype was significantly associated with CRP levels in RA patients with low disease activity in the over-dominant model (p = 0.029; OR = 0.065, adjusted for age and sex). The presence of the RIPK1 rs17548629 genotype is associated with RA under additive, co-dominant, and dominant models. The T allele mutation at rs17548629 increases the risk of RA in the Chinese population. The RIPK1 rs17548629 genotype was identified as being associated with RF-positive RA patients, whereas no significant association was observed in RF-negative individuals. These findings suggest that this SNP may modulate the risk of RA in an RF-dependent manner. Furthermore, the RIPK2 rs10094579 genotype correlates with CRP levels in RA patients exhibiting low disease activity. This association underscores the necessity for caution when reducing the dosage of therapy in RA patients with low disease activity who carry the CA genotype at RIPK2 rs10094579. Additional research is warranted to explore other genotypes that may influence RA susceptibility and to refine potential treatment strategies.

Relationship Between Early and Established Rheumatoid Arthritis Vascular Change of the Dorsalis Pedis Artery Observed with Ultrasound Imaging

BackgroundDespite early treatment of rheumatoid arthritis (RA) being well established to prevent erosive joint damage, studies report persistent moderate to high disease activity. Other pathologies, for example, rheumatoid vasculitis (RV) may contribute symptoms that may not be captured by existing clinical assessment. ObjectivesTo investigate ultrasound-observed changes in the proximal dorsalis pedis artery (DPA) between early (≤ 5 y) and established (>5 y) RA and the RA Disease Activity Index-5 (RADAI-5). MethodsParticipants with early (n = 20) and established RA (n = 20) were recruited. Five parameters of the DPA were examined with a previously established ultrasound method. Independent t-tests and Cohen d statistics assessed differences and effect size between ultrasound parameters and RADAI-5, and the two groups. Pearson correlation assessed associations between ultrasound parameters and RADAI-5. ResultsMajority of participants (98%) demonstrated arterial wall thickening regardless of disease duration. However, lumen diameter (Cohen's d = 0.972, p = 0.004) and artery diameter (Cohen's d = 0.694, p = 0.034) were decreased in established RA compared to early RA. No strong associations were found between RADAI-5 and ultrasound parameters, except for lumen diameter in early RA demonstrating a fair association to RADAI-5 (r = 0.445). The mean RADAI-5 score indicated moderate to high disease activity with no difference between early and established RA (p = 0.283). ConclusionArterial wall thickening of the DPA indicating the precursory changes of RV was observed in most RA participants, with reductions in artery and lumen diameter occurring in established disease. However, the long-standing instrument RADAI-5 may not reflect symptoms and clinical impacts related to vascular changes among people with RA.

High disease activity influences the presence of vertebral fractures in rheumatoid arthritis.

It is important to assess the risk of vertebral fractures (VFs) in patients with rheumatoid arthritis (RA), as RA is associated with a high risk of VFs. However, the epidemiology and risk of VFs in patients with RA remain inconclusive. The present study therefore clarified the prevalence and associated factors of VFs in patients with RA. We included 107 patients (19 men and 88 women) and retrospectively investigated the number and location of VFs, bone mineral density (BMD), RA disease activity score for 28 joints based on C-reactive protein (DAS28-CRP), and history of medication for RA and osteoporosis. Based on the investigated items, we assessed the prevalence of VFs in patients with RA and the association between the clinical parameters of RA patients and VFs. The average age, disease duration, and DAS28-CRP were 67.9 years old, 14.9 years, and 2.2, respectively. We found that the prevalence of VFs in patients with RA was 30.8%, and 84.8% of patients with VFs and 62.2% of those without VFs had been treated for osteoporosis. We further found that the prevalence of VFs in patients with RA with a history of anti-osteoporotic agent use was 37.8%. In univariate analyses, patients with RA with VFs had significantly higher DAS28-CRP values, a higher rate of corticosteroid use, and lower BMD (p = 0.018, p = 0.004, and p < 0.001, respectively) than those without VFs. A multivariable logistic regression analysis and ordinal logistic analysis revealed that the DAS28-CRP and BMD were independent factors associated with the presence (p = 0.042 and p = 0.011, respectively) and number (p = 0.036 and p = 0.048, respectively) of VFs. The prevalence of VFs was relatively high in patients with RA, regardless of the use of anti-osteoporotic agents. A high disease activity score and low BMD are associated with the presence and number of VFs in patients with RA. Based on these findings, to reduce VFs in RA patients, it is important to tightly control the disease activity of RA in addition to osteoporosis treatment.

Ultrasound 7 score and serum chemerin in rheumatoid arthritis: Relation to disease activity

Background and objectives. Chemerin is an adipokine associated with inflammation. Musculoskeletal ultrasonography is now widely used for detecting and monitoring RA due to its availability, practicality, and cost-effectiveness. The aim of the study is to determine how accurate serum chemerin levels are as a biomarker of active rheumatoid arthritis (RA) disease and to find a link between these levels and ultrasonographic findings. Materials and methods. This case-control study included 44 RA cases and 44 matched-age and sex-healthy controls. Seven joints in the hand and foot were assessed by the German-ultrasound 7 (GUS 7) score through greyscale (GSUS) and power Doppler US (PDUS) in all cases. Disease activity score 28 (DAS28) evaluated RA activity, and serum chemerin levels were measured in cases and controls. Both DAS28-CRP and DAS28-ESR were used in the assessment of the disease. Outcomes. The mean age of patients was 43.48 years versus 39.18 years of controls. 86.4% of patients were females; versus 75% of the control group. 47.7% of the studied patients had moderate disease activity, 31.8% had high disease activity, and 20.5% had low disease activity. There was a statistically significant higher median chemerin serum level among RA cases compared to the control group (898.94 versus 247.81 ng/ml, p &lt;0.001). There was a significant difference in median chemerin between inactive and active patients (352.1 versus 1032.6 ng/ml (p &lt;0.001). The serum chemerin can differentiate between RA patients and controls with a higher sensitivity of 81.8%, a specificity of 88.6%, and an accuracy of 85.2%. There was a statistically significant positive association between chemerin and RA activity (p &lt;0.001). The combination of serum chemerin level and tenosynovitis GSUS score and DAS2-ESR to differentiate between active and inactive RA patients was highly significant with the highest sensitivity of 100%. Conclusions. Chemerin can serve as an advantageous marker for assessing RA activity. The US-7 score is a complementary method used in standard assessment to determine synovial inflammation in RA. The combined use of serum chemerin and the US 7 score could be of high value for detecting disease activity in RA.

Racial Disparities and Achievement of the Low Lupus Disease Activity State (LLDAS): A CARRA Registry Study.

Differential disease control may contribute to racial disparities in outcomes of childhood-onset systemic lupus erythematosus (cSLE). We evaluated associations of race and individual- or neighborhood-level social determinants of health (SDoH) with achievement of low lupus disease activity state (LLDAS), a clinically relevant treatment target. In this cSLE cohort study using the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, the primary exposure was self-reported race and/or ethnicity and collected SDoH included insurance status and area deprivation index (ADI). Outcomes included LLDAS, disease activity, and time-averaged prednisone exposure. Associations between race and/or ethnicity, SDoH, and disease activity were estimated with multivariable regression models, adjusting for disease-related and demographic factors. Among 540 children with cSLE, 27% identified as Black, 25% White, 23% Latino/a, 11% Asian, 9% more than one race, and 5% Other. More Black children (41%) lived in neighborhoods of highest ADI compared to White children (16%). Black race was associated with lower LLDAS achievement (adjusted OR 0.56, 95% CI: 0.38-0.82) and higher disease activity (adjusted β: 0.94, 95% CI: 0.11, 1.78). Highest ADI was not associated with lower LLDAS achievement upon adjustment for renal disease and insurance. However, renal disease was found to be a significant mediator (p=0.04) of the association between ADI and prednisone exposure. Children with cSLE identifying as Black are less likely to achieve LLDAS and have higher disease activity. Living in areas of higher ADI may relate to renal disease and subsequent prednisone exposure. Strategies to address root causes will be important to design interventions mitigating cSLE racial disparities.

Clinical factors as predictors of the development of severe recurrence of chronic spontaneous urticaria after completion of omalizumab therapy

Chronic spontaneous urticaria (CSU) affects about 1% of population, and its prevalence is increasing. The disease occurs in both children and adults, with predominance among women. At least two possible causes of CSU have been identified, two autoimmune endotypes, with different types of autoantibodies associated with activation of skin mast cells. In clinical practice, patients with CSU receive therapy accordance the clinical recommendations of the Ministry of Health of Russia for treatment of urticaria, according to the doctor’s algorithm of actions. In patients with CSU, symptoms are difficult to relieve due to special mechanisms of development this variant of disease. In recent years, specific markers, including clinical and laboratory parameters, have been described that can predict response to treatment patients with CSU. In clinical practice, we encounter difficulties in managing these patients. One of these is recurrence of urticaria symptoms after cessation of omalizumab treatment, which negatively affects compliance of patients and its psycho-emotional background. A retrospective analysis of 14 patients with CSU with resumption symptoms after completion of omalizumab treatment was carried out. Patients were divided into two groups: 1 group – 10 patients that symptoms began controlled with antihistamines (go to 1st therapy stage); and 2 group – 4 patients who need re-prescription of omalizumab (stay on 3rd treatment stage). The duration of CSU, activity according to UAS7, combination with development of angioedema, presence of concomitant allergic and autoimmune pathologies, level of CRP, total IgE, and presence of TPO antibodies were analyzed. There was no tendency relapses severity CSU after omalizumab discontinuation with age, gender, duration of the disease, presence of concomitant allergic diseases and drug hypersensitivity. In patients with high disease activity was tendency toward more severe relapses of CSU. The search and study of predictors response to treatment of CSC remains actual task. Further research to identify predictors of response to treatment and relapses severity help identify groups of patients for early transition to more effective treatment methods, which optimize and personalize management of patients with CSU.

Interaction between reacetylated chitosan and albumin in alcalescent media

Interaction of chitosan and its derivatives with proteins of animal blood at blood pH relevant conditions is of a particular interest for construction of antimicrobial chitosan/protein-based drug delivery systems. In this work, the interaction of a series of N-reacetylated oligochitosans (RA-CHI) having Mw of 10–12 kDa and differing in the degree of acetylation (DA 19, 24, and 40 %) with bovine serum albumin (BSA) in alkalescent media is described in first. It is shown that RA-CHI forms soluble complexes with BSA in solutions with pH 7.4 and a low ionic strength. Light scattering study shows that soluble RA-CHI complexes have spherical form with the radius of about 100 nm. Circular dichroism, fluorescent spectroscopy, and micro-IR spectroscopy studies show that the secondary structure of BSA in soluble complexes remain intact. Isothermal titration calorimetry of RA-CHI with DA 24 % and BSA mixing in the buffers with different ionization heats reveals a significant contribution of electrostatic forces to the binding process and an additional ionization of chitosan due to the proton transfer from the buffer substance. An increase of ionic strength to the blood relevant value 0.15 M suppresses the binding. It is shown that application of RA-CHI with higher DA value leads to a decrease in the affinity of RA-CHI to BSA and an alteration of the interaction mechanism. The finding opens an opportunity to the application of N-reacetylated chitosan derivatives in the complex systems compatible with blood plasma proteins.

The effect of alemtuzumab on neurodegeneration in relapsing-remitting multiple sclerosis: A five-year prospective mono-center study

BackgroundRelapsing-remitting multiple sclerosis (RRMS) is an inflammatory and neurodegenerative disease. After two or more short courses of alemtuzumab (ALZ), an immune reconstitution is achieved, which long-term results in reduced disease activity. We aimed to investigate the effect of ALZ on measures of neurodegeneration (i.e., brain atrophy, and retinal layer thinning). MethodsWe designed an observational prospective mono-center study in RRMS patients initiating ALZ treatment. Patients were assessed at baseline (month 0) and thereafter annually for five years with clinical measures, synthetic magnetic resonance imaging (SyMRI) and optical coherence tomography (OCT), with a re-baseline SyMRI scan and an OCT exam 24 months after initiating ALZ. Persons with neurological symptoms but without evidence of neurological disease served as symptomatic controls (SCs, n = 27). ResultsForty-nine RRMS patients were included. Baseline median expanded disability status scale [2.0 (IQR 1.5)] was unchanged during follow-up, 71 % were progression-free, 33 % achieved no evidence of disease activity-3 (NEDA-3). Between baseline and month 60, SyMRI showed a reduction of brain parenchymal fraction (BPF) and grey matter (GM) volume in patients. The BPF reduction was greater in RRMS patients than in SCs (p < 0.05), and more pronounced in patients with high pre-baseline disease activity than in those without (p < 0.01). OCT showed significant thinning of macular ganglion cell and inner plexiform layers (mGCIPL) and in peripapillary retinal nerve fiber layer (pRNFL) in patients. In contrast, absolute values of white matter (WM) volume and myelin content (MyC) quantified by SyMRI, were stable or increased after re-baseline (month 24) and up to month 60, and this increase appeared limited to patients without high pre-baseline disease activity and to patients with NEDA-3 or disability worsening during follow-up. A strong positive correlation between WM volume and GM volume at baseline was lost after ALZ intervention for their delta values, i.e., change from re-baseline (month 24) to month 60. While the positive baseline correlation between WM volume and MyC increased for their delta values, the positive baseline correlation between GM volume and MyC changed to negative for their delta values. ConclusionWe showed that neurodegeneration continued in RRMS patients under ALZ treatment, but it appeared to be limited to BPF and GM, and more pronounced in patients with disease activity. Our data suggest that patients who respond to ALZ treatment show signs of remyelination. OCT and SyMRI have potential to quantify measures of neurodegeneration that is affected by treatment intervention in RRMS.

Mortality and prognostic factors among inpatients with systemic lupus erythematosus in China: A 20-year retrospective study.

To summarize the causes of death and clinical characteristics of systemic lupus erythematosus (SLE) hospitalized patients in the last 20 years to improve SLE survival rates by detecting critical SLE early. In this case-control study, 218 SLE death cases were retrospectively analyzed from January 2002 to December 2022, with 110 SLE inpatients chosen at random as controls. The clinical symptoms, causes of death, and risk factors in patients with SLE were investigated. There were 218 deaths among 9538 patients with SLE, including 188 women and 30 men. The death rate fell steadily from 4.14% in 2002 to 1.96% in 2013 and remained at 1.84% from 2014 to 2022. The standardized mortality ratio (SMR) was 4.98 [95% CI (4.06-5.89)] from 2002 to 2012 and 3.39 [95% CI (2.74-4.04)] from 2013 to 2022. Infection, lupus-induced multiple organ failure syndrome (MODS), and neuropsychiatric lupus (NPLE) were the leading causes of death, accounting for 31.19%, 15.14%, and 11.47% of overall deaths. Age had a significant association with the major causes of death. Logistic regression analysis showed NPLE[OR = 10.772,95% CI (3.350,34.633), p < 0.001], lupus pulmonary involvement (LP)[OR = 3.844,95%CI (1.547,9.552), p = 0.004], pneumonia[OR = 3.439,95%CI(1.552,7.621), p = 0.002], thrombocytopenia[OR = 14.941,95%CI (4.088,54.604), p < 0.001], creatinine>177μmol/L[OR = 8.644,95%CI (2.831,26.388), p < 0.001], glutamic transaminase(AST) > 60U/L[OR = 5.762,95%CI (2.200,15.088), p < 0.001], total bilirubin > 34μmol/L[OR = 16.701,95%CI (3.349,83.294), p = 0.001], higher SLE Disease Activity Index (SLEDAI)[OR = 1.089,95%CI (1.032,1.149), p = 0.002] and SLE Damage Index (SDI)[OR = 3.690,95%CI (2.487,5.474), p < 0.001] correlated positively with death. From 2002 to 2013, the mortality rate among patients with SLE fell steadily but remained unchanged from 2014 to 2022. Patients with SLE had significantly higher SMR than the general population. Childhood-onset SLE had a poorer prognosis than adult-onset SLE. Infection, MODS, and NPLE were the three leading causes of death. Major organ involvement and high disease activity were risk factors for mortality.

Gender differences in clinical features and quality of life of patients with axial spondyloarthritis and psoriatic arthritis.

The aim of the current study was to compare the clinical and treatment characteristics and dimensions of health-related quality of life between female and male patients with axial spondyloarthritis (SpA) and psoriatic arthritis (PsA). The present study is cross-sectional and comprises 119 patients with axial SpA and 198 patients with PsA. Clinical data were collected by standardized and self-reported instruments. Disease activity was evaluated by the Ankylosing Spondylitis Disease Activity Score with C-reactive protein and the Disease Activity in PSoriatic Arthritis (for SpA and PsA, respectively). Health-related quality of life was assessed with the Medical Outcomes Study 36-item Short Form Survey. Patients were stratified by gender, and the socio-demographic, clinical, and quality-of-life data were compared. Women with axial SpA and PsA had significantly lower education (p<0.001, p=0.004, respectively) and higher disease activity (p<0.001, p=0.003, respectively). Female patients with axial SpA were more frequently under second-line therapy (p=0.026) and glucocorticoid treatment (p=0.005), while women with PsA had more radiographic progression (p=0.006). Female patients with axial SpA and PsA had worse scores in the dimensions of quality of life regarding physical role, bodily pain, vitality, and mental health. Women with axial SpA had lower scores in general health, while women with PsA had lower scores in physical and social functioning. Women with axial SpA and PsA had worse scores than men in most clinical and treatment characteristics and health-related quality of life dimensions.

Assessment of hepcidin in Egyptian patients with rheumatoid arthritis and its relation to anemia: a single-center study

BackgroundRheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disorder characterized by synovial inflammation that leads to joint damage, bony erosions, and related deformities. Between 30 and 70% of RA patients will experience anemia. Early detection of anemia is of great importance. This study aimed to evaluate the serum level of hepcidin (HEP) in RA patients and to assess its relation to disease activity and anemia. The current cross-sectional study included 44 cases with RA in addition to 44 healthy controls. The disease activity in the RA patient was assessed by using the disease activity score (DAS) 28 score-CRP. The serum levels of HEP and ferritin were assessed in both groups using enzyme-linked immunosorbent assay (ELISA) technique.ResultsHepcidin level in the RA group was statistically significantly higher as compared to the control group (p = 0.001). The prevalence of Anemia of chronic disease (ACD) was 40.9%, and iron deficiency anemia (IDA) was 27.3% which accounted for 68.2% of the total anemia cases. The HEP level was statistically significantly higher in the RA patients with ACD than those without anemia (P = 0.028), RA patients with IDA (P < 0.001), and control group (P < 0.001). There was a statistically significant positive correlation between HEP level and serum ferritin level (p = 0.005). HEP level was significantly and inversely correlated with hemoglobin (Hb) in patients with ACD. Serum HEP level is higher in RA patients with high disease activity than those with moderate activity, low activity, and patients in remission (p = 0.380). However, the difference was not statistically significant. The best cutoff point of HEP level to identify RA patients from healthy controls was > 355.5 Pg/ml. This point showed moderate sensitivity (70.5%) with moderate specificity (63.6%) with a statistically significant value.ConclusionsWe found the anemia, and particularly ACD, is more common in RA patients. In RA patients with ACD, serum HEP levels were considerably higher. Although serum HEP showed no diagnostic significance when it came to evaluating disease activity, it could be a dependable non-invasive biomarker for the diagnosis of various forms of anemia in RA patients.

The Impact of Pregnancy Readiness on Lupus Activity, Maternal Mental Health, and Pregnancy Outcomes.

Among individuals with systemic lupus erythematosus (SLE) who became pregnant, we explored the impact of medical readiness for pregnancy and personal readiness for pregnancy on the following aspects of maternal health: (1) provider-reported disease activity, (2) patient-perceived disease activity, (3) mood symptoms, (4) pregnancy-related health behaviors, and (5) pregnancy outcomes. All study participants were enrolled in a prospective registry, met Systemic Lupus Collaborating Clinics (SLICC) criteria for SLE, and had at least one pregnancy. Patient-reported outcomes were collected at the first rheumatology visit during pregnancy. "Medically ready" for pregnancy was defined as (1) <1 g of proteinuria, (2) no rheumatic teratogens at conception, and (3) continuing pregnancy-compatible SLE medications after conception. "Personally ready" was defined as planned pregnancy based on a London Measure of Unplanned Pregnancy score ≥10. Multivariable logistic regression models estimated the association of pregnancy readiness with each outcome of interest. Among the 111 individuals enrolled, lack of medical readiness for pregnancy was associated with significantly higher rates of active disease and worse pregnancy outcomes; however, these patients did not perceive themselves as having higher disease activity. Lack of personal readiness for pregnancy was associated with significantly higher patient-perceived disease activity. Although medical readiness did not impact depressive symptoms substantially, lack of personal readiness for pregnancy was associated with much higher maternal depressive symptoms. To improve pregnancy outcomes among individuals with SLE, greater focus is needed on improving medical optimization before conception. For maternal mental health and quality of life, greater focus is needed on decreasing the incidence of unplanned pregnancy.

Effect of joint hypermobility on outcomes of children with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is common in pediatric rheumatology. Despite treatment, many patients experience persistent disease activity. Joint hypermobility (JH), defined by an excessive range of motion across multiple joints, is prevalent in children and adolescents and may influence disease outcomes in JIA. This study examines the impact of JH on symptoms in youth and young adults with JIA. Data were obtained from the PR-COIN network and included patients under 21years old with a diagnosis of JIA. Patients with JIA and JH were matched with those having JIA-only based on age, sex assigned at birth, JIA subtype, and medication exposure. Clinical data, including disease activity measures, patient well-being, and pain ratings, were collected at baseline and follow-up visits. The sample included 420 patients with JIA + JH and 2100 with JIA only. The JIA + JH group exhibited higher disease activity at baseline, more active arthritis joints, elevated physician global assessment of disease activity scores, and worse patient-reported well-being. These differences persisted over time. The JIA + JH group had a 19-20% greater likelihood of maintaining high disease activity scores and worsening over subsequent visits, indicating a significant impact of JH on disease progression. JH in youth with JIA is associated with higher and persistent disease activity, suggesting that JH significantly contributes to the disease burden in patients with JIA and should be considered in treatment strategies. Future research should further explore the mechanisms by which JH influences disease activity and investigate comprehensive management approaches to improve outcomes for this population. Key Points • Children with JIA and joint hypermobility (JH) exhibit significantly higher disease activity at baseline compared to those with JIA only, including more active arthritis joints and elevated physician global assessment scores. • The presence of JH in JIA patients is associated with poorer patient-reported well-being and higher overall disease activity scores, which persist over time despite treatment. • JIA + JH patients have a 19-20% greater likelihood of maintaining high disease activity and worsening over subsequent visits, indicating a significant impact of JH on disease progression. • The study suggests that JH should be considered an important clinical factor in the management of JIA, with targeted interventions needed to address the increased disease activity and improve overall patient outcomes.

Low Haemoglobin is Inversely Associated with Disease Activity in Rheumatoid Arthritis: A Cross-Sectional Study from a Tertiary Care Hospital.

Extra-articular manifestations especially haematological abnormalities are common in Rheumatoid arthritis (RA). The aim is to study the haematological parameters and its correlation with disease severity and gender. A cross-sectional study was conducted at a tertiary centre among 50 RA patients who attended the Rheumatology or General Medicine OPD from January 2020 to June 2021. The number of swollen joints, tender joints, the patient's global assessment, rheumatoid factor, and complete blood counts were recorded. Disease Activity Score (DAS-28) was calculated from these variables and data was analysed using SPSS version 29 with p<0.05 considered as statistically significant. Of the study subjects, forty (80%) were females; thirty (60%) belonged to the age group 41-50 years. Median age was 42.4(18, 50) years. 79 % (19 out of 24) of subjects with normal haemoglobin had moderate disease activity on DAS 28 score and 50% (13/26) of participants with low haemoglobin levels had high disease activity. Simple linear regression analysis showed low haemoglobin is inversely associated with DAS 28 score (R2 = 0.407, F= 32.888, p < 0.001). Compared to females, males had a higher haemoglobin level which was statistically significant. Female patients had statistically significant higher DAS 28 scores than males (p = 0.016). Low haemoglobin levels are associated with high disease activity in RA patients and males had less severe disease than females.