Search Results (285)

Background/Objectives: Erythrocyte sedimentation rate (ESR) is one of the most widely used tests for assessing inflammatory conditions. Current guidelines require that Erythrocyte Sedimentation Rate (ESR) testing be performed within four hours of collection for samples stored at RT or within 24 h if refrigerated; this is challenging with dispersed collection sites. Thus, we investigated whether testing technology affects sample stability by comparing results obtained using iSED^®, based on photometric rheology, with the classical Westergren method. Methods: Samples were evaluated at multiple time intervals. ESR values from each timepoint were plotted against their Time 0 values, and correlation statistics were analyzed using Passing-Bablok regression analysis and a Stability Drift analysis. Samples were considered stable if the correlation statistics of the Passing-Bablok analysis were statistically indistinct from the identity line. Results: Samples in the iSED/RT cohort were stable for up to 28 h after collection, while those in the iSED/4–8 °C cohort were stable for up to 48 h. Samples in the Westergren/RT cohort were stable for up to 10 h after collection, but significantly deteriorated at 12 h and beyond. Conclusions: The iSED methodology provides accurate ESR results for samples stored up to 28 h at RT and 48 h at 4–8 °C, which was significantly superior to the Westergren method for which samples were stable at RT for only 10 h. Full article

Background: Focal involvement in brucellosis complicates clinical management and increases treatment failure risk. This study evaluated the predictive value of routine inflammatory markers and, for the first time, the C-reactive protein-albumin-lymphocyte (CALLY) index for predicting focal complications. Methods: A retrospective cohort study conducted between February 2016 and January 2026 included 203 brucellosis patients, categorized into “no focal involvement” (n = 114) and “focal involvement” (n = 89) groups. Admission blood count parameters, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and CALLY index were compared using Receiver Operating Characteristic (ROC) curves, DeLong tests, and multivariate logistic regression models incorporating CRP, albumin, CALLY index, ESR, hemoglobin, MPV, age, and gender. Results: Patients with focal involvement were older (p = 0.029) and exhibited higher ESR, CRP, neutrophil-to-lymphocyte, and platelet-to-lymphocyte ratios but lower hemoglobin, mean platelet volume, albumin, and CALLY index (p < 0.001). ROC analysis showed ESR had the highest predictive value (AUC: 0.839), followed by albumin (AUC: 0.751) and the CALLY index (AUC: 0.728). DeLong tests confirmed ESR’s statistical superiority over the CALLY index (p = 0.002) and albumin (p = 0.016). In multivariate regression, ESR remained a robust independent prognostic factor (OR: 1.042, p < 0.001), whereas the CALLY index lacked independent significance. Conclusions: Despite its theoretical appeal as a novel immuno-nutritional biomarker, the CALLY index does not outperform traditional markers in predicting focal complications of brucellosis at initial presentation. ESR remains a robust, inexpensive, and statistically superior independent predictor. These findings emphasize that clinicians should continue to rely on widely accessible traditional markers like ESR for early diagnostic risk stratification, while the potential utility of composite scores like the CALLY index may be better reserved for monitoring dynamic therapeutic responses and managing chronic cases. Full article

Background: Psoriatic arthritis (PsA) is a chronic inflammatory disease frequently associated with obesity and metabolic comorbidities. Increasing evidence suggests that obesity is associated with systemic inflammation, insulin resistance, and adverse clinical outcomes; however, the immunometabolic profile associated with obesity in PsA has not been fully characterized. Objective: To investigate the relationship between obesity, inflammatory biomarkers, cytokine profiles, metabolic parameters, insulin resistance, and disease-related characteristics in patients with PsA. Methods: In this monocentric cross-sectional study, 224 consecutive patients fulfilling the Classification Criteria for Psoriatic Arthritis (CASPAR) for PsA were evaluated. Clinical, inflammatory, metabolic, and cytokine-related variables were analyzed within an integrated immunometabolic framework. Patients were stratified according to obesity status based on body mass index (BMI ≥ 30 kg/m²). Correlation analyses, multivariable regression analyses, and exploratory machine-learning approaches were applied to identify multidimensional patterns associated with obesity. Adjusted multivariable regression analyses were performed to account for available demographic, clinical, comorbidity-related, and therapeutic covariates. Results: Ninety-four patients (42.0%) were classified as obese and 130 (58.0%) as non-obese. Compared with non-obese patients, obese individuals exhibited significantly higher levels of C-reactive protein (CRP; 0.31 vs. 0.13 mg/dL, p < 0.001), erythrocyte sedimentation rate (ESR; 15.0 vs. 10.0 mm/h, p = 0.006), serum amyloid A (SAA; 7.7 vs. 6.4 mg/L, p = 0.008), insulin (8.0 vs. 6.1 μU/mL, p < 0.001), glycated hemoglobin (HbA1c; 38.0 vs. 37.0 mmol/mol, p = 0.003), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR; 1.29 vs. 1.21, p = 0.007), triglycerides (106.0 vs. 85.0 mg/dL, p = 0.019), and Health Assessment Questionnaire (HAQ) scores (p < 0.001). Obese patients also showed a higher prevalence of hypertension (18.1% vs. 6.9%, p = 0.018). BMI was positively correlated with several inflammatory, metabolic, and disease-related variables, including CRP (ρ = 0.383), interleukin-6 (IL-6; ρ = 0.295), insulin (ρ = 0.289), ESR (ρ = 0.245), SAA (ρ = 0.228), HbA1c (ρ = 0.199), HAQ score (ρ = 0.351), and Disease Activity Index for Psoriatic Arthritis (DAPSA) score (ρ = 0.183), while showing an inverse correlation with high-density lipoprotein cholesterol (HDL-C) (ρ = −0.189). After adjustment for age, sex, disease duration, DAPSA, hypertension, type 2 diabetes mellitus, and current therapy class, obesity remained associated with higher CRP and fasting insulin levels and with greater odds of belonging to a higher HAQ category. Machine-learning analyses identified inflammatory biomarkers, insulin resistance indices, and lipid-related parameters as the most informative features associated with obesity-related phenotypes. Conclusions: Obesity in PsA was associated with a broader immunometabolic phenotype characterized by increased inflammatory burden, metabolic dysfunction, and worse functional outcomes. These findings support the integration of metabolic and cardiovascular assessment into routine rheumatology practice and highlight obesity as an important marker of increased immunometabolic and clinical burden in PsA. Although the cross-sectional design precludes causal inference, the observed associations may help identify patients requiring closer metabolic and cardiovascular assessment. Full article

Inflammation can either encourage or suppress tumor growth, thus having a two-sided effect on cancer development. This depends on the balance between pro-tumor and anti-tumor immune responses within the tumor microenvironment (TME). Pro-tumor inflammation, driven by specific immune cells, enhances blood flow and nutrient supply to tumors, promoting the activation of dormant cancer cells (DCCs). Conversely, antitumor inflammation hinders blood flow and can force active cancer cells into a state of dormancy. Tumors actively shift this balance towards pro-tumor inflammation to create a favorable environment for growth. Therefore, anti-inflammatory therapy may be an integral part of comprehensive cancer immunotherapy. This review explores how different anti-inflammatory medications, such as glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), antihistamines, anti-leukotrienes, statins, drugs that block pro-inflammatory cytokines, agents that inhibit oxidative phosphorylation, antioxidant vitamins, anti-angiogenic drugs, and low-dose chemotherapy, can be used to combat cancer. Granulocyte counts and erythrocyte sedimentation rate (ESR) can be used to assess inflammation levels and the effectiveness of anti-inflammatory treatments. We advocate for a paradigm shift in cancer treatment, moving away from aggressive tumor destruction, which triggers uncontrolled tumor regeneration, toward long-term immunological control of tumor growth while preserving the patient’s overall health. Full article

Background/Objectives: Antimicrobial resistance (AMR) represents one of the greatest challenges to modern medicine, particularly in chronic infections sustained by multidrug-resistant (MDR) pathogens and biofilm formation. SIOOT^® Oxygen–ozone major autohemotherapy (SIOOT^®-O₂-O₃-MAHT) has been proposed as an adjunctive treatment capable of exerting direct antimicrobial, antibiofilm, and immunomodulatory effects. This pilot study evaluated the clinical, microbiological, inflammatory, and mechanistic effects of standardized SIOOT^®-O₂-O₃-MAHT administered alongside conventional antibiotic therapy in patients with chronic MDR bacterial infections. Methods: A prospective longitudinal pilot study was conducted in 257 patients with chronic infectious and inflammatory disorders refractory to prolonged antibiotic treatment. Patients received standardized SIOOT^®-O₂-O₃-MAHT according to protocols from the Italian Scientific Society of Oxygen-Ozone Therapy (SIOOT) in addition to guideline-directed antibiotics. Longitudinal bacterial burden (CFU/mL), culture positivity, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were all assessed over a 12-month follow-up. In parallel, macrophage phagocytosis, intracellular bacterial killing, phago-lysosomal maturation, and methicillin-resistant Staphylococcus aureus (MRSA) biofilm disruption were investigated using confocal laser scanning microscopy, gentamicin protection assays, and scanning electron microscopy. Results: SIOOT^®-O₂-O₃-MAHT was associated with a progressive reduction in bacterial burden from a geometric mean of 6.43 × 10⁶ CFU/mL before treatment to complete microbiological clearance after one year. Mean bacterial reduction reached 98.53% after one week and 99.95% after one month, while culture positivity decreased from 100% to 0% by one year (all p < 0.0001). ESR normalization increased from 28.2% at one week to 98.1% at one year, and CRP normalization increased from 32.4% to 98.7%. Mechanistic analyses demonstrated significantly enhanced macrophage phagocytosis, phago-lysosomal maturation, intracellular MRSA killing, and marked disruption of mature MRSA biofilms following ozone treatment. Conclusions: Adjunctive SIOOT^®-O₂-O₃-MAHT was associated with reductions in bacterial burden, progressive improvement of systemic inflammatory markers, enhanced macrophage antimicrobial activity, and disruption of bacterial biofilms in patients with chronic multidrug-resistant infections. Given the prospective, non-randomized pilot design, these findings should be considered exploratory and hypothesis-generating, providing biological and clinical rationale for further investigation. Adequately powered randomized controlled trials are required to determine the efficacy, safety, and long-term clinical benefits of adjunctive oxygen–ozone therapy. Full article

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare vasculitis. A key bio-logical hallmark is peripheral blood eosinophilia while antineutrophil cytoplasmic an-tibody (ANCA) positivity is not always present. Therefore, an early phase suspicion of EGPA leading to a correct diagnosis can be challenging. We performed an observa-tional cross-sectional study limited to baseline data on 38 patients between December 2019 and December 2025 at the Allergy and Clinical Immunology Unit, Messina, Italy. Data collection included eosinophil, neutrophil, and lymphocyte counts; ANCAs and antinuclear antibodies (ANAs); erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) determination; and the Birmingham vasculitis activity score (BVAS) questionnaire: Median eosinophil counts were 685 cells/µL, the neutro-phil-to-lymphocyte ratio (NLR) was 2.29, ESR median values were 24 mm/h, and CRPs were 1.99 mg/L. ANCAs were positive in five patients, and ANAs in 20. The trend in ANA+ patients was of lower median eosinophil counts and higher ESR and CRP me-dian values and median BVASs. General, nervous system, and ENT BVAS domains had higher scores.: Disease activity in EGPA at diagnosis can be difficult to recognize. We defined it as chameleon-like and could not be captured by specific immunological sig-natures. Therefore, an early diagnosis needs multidimensional assessment, integrating laboratory parameters with clinical scores. In our EGPA cohort, ANAs were detected in just over half the patients, suggesting that rather than acting as bystanders, these could help clinicians, together with eosinophil counts, NLRs, and BVASs, to suspect EGPA at an early stage for referral to specialized medical centers. Full article

Background/Objectives: Chronic recurrent multifocal osteomyelitis/chronic nonbacterial osteomyelitis (CRMO/CNO) is an auto-inflammatory bone disease for which optimal treatment and imaging-based monitoring remain incompletely defined. Methods: We conducted a single-center retrospective review of nine pediatric patients with CRMO/CNO treated with tumor necrosis factor inhibitors (TNFis). Clinical improvement was assessed using Visual Analog Scale (VAS) pain scores, erythrocyte sedimentation rate (ESR), and physical examination findings. Radiographic assessment used longitudinal, site-specific magnetic resonance imaging (MRI) scored with a simplified approach adapted from the Chronic Nonbacterial Osteomyelitis Magnetic Resonance Imaging Scoring (CROMRIS) system. Results: Our cohort was composed of six females and three males with a median age of seven years. TNFi monotherapy was initiated as a first-line therapy (n = 4) or step-up (n = 5). During a median follow-up time of 26 months, treatment was tolerated well, except for the emergence of psoriasis in three patients (n = 3), among whom one necessitated treatment change. Eight patients on TNFis achieved clinical remission, including five with complete resolution of MRI lesions. Conclusions: In this small, single-center case series, TNFi monotherapy was associated with sustained disease control, as reflected by clinical improvement and MRI-documented lesion resolution. These findings emphasize the need for validation of our observations in larger multi-center cohorts. Full article

Background/Objectives: Metabolic dysregulation has emerged as a potential modifier of disease activity and disability in multiple sclerosis (MS). However, the relationship between glycemic status and clinical outcomes in patients with MS remains incompletely understood. This study aimed to investigate the associations of glycemic regulation with disease severity, relapse activity, inflammatory markers, and metabolic characteristics in patients with MS. Methods: In this retrospective single-center observational study, 455 patients with MS aged 18–65 years were included. Patients were categorized into normoglycemia (n = 241), prediabetes (n = 98), and diabetes (n = 116) according to American Diabetes Association criteria and documented diabetes diagnosis. Demographic characteristics, Expanded Disability Status Scale (EDSS) scores, annualized relapse rate (ARR), disease-modifying therapy (DMT), hematological indices, inflammatory markers, and metabolic parameters were retrieved from electronic medical records. Associations between glycemic status and clinical outcomes were evaluated using group comparisons, Spearman correlation analyses, and multivariable linear regression models. Results: Significant differences were observed among glycemic groups for age, disease duration, EDSS score, ARR, MS phenotype, platelet count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipid parameters, estimated glomerular filtration rate, alanine aminotransferase, gamma-glutamyl transferase, triglyceride–glucose (TyG) index, and atherogenic index of plasma (all p < 0.05). HbA1c, FPG, TyG index, lipid parameters, CRP, and ESR were positively correlated with EDSS scores (all p < 0.05). In contrast, these markers showed inverse correlations with ARR. However, after adjustment for demographic and clinical variables, including age, sex, disease duration, MS phenotype, and disease-modifying therapy (DMT), neither prediabetes nor diabetes remained independently associated with disability, as measured by the EDSS score, or with ARR. Progressive MS phenotype, older age, and longer disease duration were independently associated with higher disability, whereas age, disease duration, and progressive phenotype were independently associated with lower ARR. Conclusions: Impaired glycemic status is associated with greater disability, unfavorable metabolic profiles, and increased systemic inflammation in patients with MS. Nevertheless, glycemic status was not independently associated with disability or relapse activity after adjustment for major clinical confounders. These findings suggest that metabolic dysregulation accompanies more severe clinical characteristics but may not independently drive disease progression in MS. Full article

Low-density granulocytes (LDGs) have been implicated in the pathogenesis of several autoimmune diseases, yet their role in Sjögren’s disease (SjD) remains poorly understood. We enrolled 90 SjD patients and 30 healthy controls (HCs) and identified LDGs as CD14^−/lowCD15⁺ cells by flow cytometry, with intracellular interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) staining, and further analyzed CD16 as a maturation marker in LDGs and T helper 17 (Th17) cell frequency. LDG percentages were significantly elevated in active SjD compared with inactive patients (p < 0.001) and HCs (p < 0.0001), and correlated positively with EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) (r = 0.355, p = 0.0006), erythrocyte sedimentation rate (ESR) (r = 0.325, p = 0.0061), γ-globulin (r = 0.334, p = 0.0177), and Th17 frequency (r = 0.537, p = 0.0068). LDG expansion was accompanied by enrichment of immature CD16^−/low cells (r = −0.798, p = 0.0100). Patients with renal or pulmonary involvement showed higher LDG levels (p = 0.0004), and in SjD -associated interstitial lung disease (SjD-ILD) patients, LDG percentage showed a positive but non-significant trend with serum Krebs von den Lungen-6 (KL-6) levels (r = 0.497, p = 0.102). LDG levels decreased following treatment in longitudinally followed patients, and LDGs from active patients exhibited higher IL-6 and TNF-α production ratios relative to monocytes than those from inactive patients. Stratification by LDG levels revealed significant associations with disease activity, laboratory parameters, and organ involvement. These findings suggest that LDGs are associated with disease activity and organ involvement, may serve as potential biomarkers, and may contribute to the pathogenesis of SjD. Full article

Background: Knee osteoarthritis (KOA) in people with overweight or obesity is clinically heterogeneous, reflecting mechanical loading, synovial and systemic inflammation, metabolic dysfunction, structural severity, and pain-related factors. We evaluated multidomain outcomes after semaglutide initiation and characterized clinically relevant response patterns. Methods: This retrospective, self-controlled cohort included 93 adults treated in routine rheumatology care; 88 completed a six-month follow-up. There was no untreated concurrent comparator; within-patient changes and exposure–outcome associations were therefore interpreted as non-causal. Changes in pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, anthropometry, inflammatory markers, glycated hemoglobin (HbA1c), lipids, dose exposure, and safety were evaluated. Joint multivariable models included percentage weight loss and maximum achieved dose. Exploratory K-means phenotyping integrated dose, weight loss, body mass index (BMI) decrease, visual analog scale (VAS) and WOMAC improvement, and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and HbA1c reductions, with candidate solutions and resampling stability examined. Results: At six months, mean weight decreased by 10.88 kg, VAS pain score by 2.47 points, WOMAC total by 22.50 points, CRP by 2.67 mg/L, ESR by 7.62 mm/h, and HbA1c by 0.51 percentage points (all p < 0.001). Weight loss remained independently associated with WOMAC improvement, while achieved dose retained positive adjusted associations with pain, function, inflammatory, and metabolic changes. Exploratory clustering identified five clinically interpretable patterns along a broader response-intensity gradient, including high-burden multidomain response, high-dose concordant response, dose-modified intermediate response, inflammation-preserved response despite moderate weight loss, and dose-limited graded response. These observational coefficients and clusters cannot distinguish treatment-related effects from residual confounding or co-interventions. Conclusions: Substantial within-patient improvements were observed, but the uncontrolled design precludes causal attribution. The exploratory patterns may be compatible with contributions from baseline disease burden, dose exposure, mechanical unloading, and residual inflammatory variation; they do not establish weight-independent pharmacologic effects or validated patient subtypes. Prospective controlled, multicenter validation is required. Full article

Background: Acute rheumatic fever (ARF) is a clinical syndrome triggered by group A streptococcal (GAS) infections and characterized by fever, carditis, and arthritis as its main manifestations. Diagnosis relies on the revised Jones criteria. We report a rare case of ARF diagnosed in Switzerland. Case Presentation: An 18-year-old woman presented to the emergency department five days after returning from a one-week stay in Egypt with intermittent fever and a transient sore throat, followed by migratory joint pain. Laboratory testing revealed leukocytosis, elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Chest X-ray, urine analysis, and (travel-associated) pathogen-testing (Epstein–Barr virus, Cytomegalovirus, human immunodeficiency virus, Malaria, Dengue, Zika, Chikungunya) were unremarkable. Blood cultures remained negative. Initially, a viral respiratory infection was suspected and symptomatic treatment established. Days later the patient was re-evaluated due to persistent symptoms. Leukocyte count (Lc) and CRP further increased and subcutaneous nodules appeared. The antistreptolysin-O (ASO)-titer was elevated more than three times higher than the normal upper limit and proofed serological evidence of a preceding streptococcal infection (GAS throat culture had not been performed). ARF was diagnosed according to the Jones criteria. Treatment with amoxicillin and a high dose of acetylsalicylic acid (ASA) led to a rapid clinical improvement. Secondary prophylaxis with depot penicillin (benzathine penicillin G; 1.2 million units; once monthly) was initiated to prevent rheumatic heart disease. Conclusions: This case highlights a rare occurrence of ARF following travel to Egypt, with probable acquisition of group A streptococcal infection during the trip. It emphasizes consideration of ARF even in Western countries with low ARF-prevalence if clinical history is suggestive. Early recognition and initiation of antimicrobial and anti-inflammatory therapy is crucial to prevent cardiac involvement. To the best of our knowledge, this represents one of the first cases diagnosed in Switzerland in the past 20 years. Full article

Background/Objectives: The erythrocyte sedimentation rate (ESR) is a widely used biomarker of systemic inflammation, with established roles in rheumatologic, infectious, and malignant disease. The Westergren method remains the reference procedure, but automated analyzers are increasingly used clinically, and methodological differences may introduce systematic bias. This study evaluated analytical agreement between the Vision C automated ESR analyzer (EDTA) and the Westergren reference (sodium citrate). Methods: This prospective, single-center study followed CLSI EP09-ED3. A total of 228 consecutive adult patients were enrolled. Agreement was assessed by Bland–Altman analysis, Passing–Bablok regression, and Pearson correlation, with subgroup analyses (<40, 40–80, >80 mm/h) and against RCPA allowable total error (TEa) specifications. Results: Bland–Altman analysis showed a significant mean bias of −3.30 mm/h (95% CI: −4.25 to −2.35), with increasing dispersion at higher ESR values indicating heteroscedasticity; regression-based limits of agreement therefore widened progressively with ESR magnitude. Passing–Bablok regression showed no proportional bias but a significant constant bias; subgroup regression was not performed due to truncated ranges. Correlation was strong overall (r = 0.961, p < 0.001) and declined across subgroups (r = 0.821, 0.740, 0.687), consistent with range restriction rather than reduced agreement. The analyzer met RCPA TEa criteria across both ranges (≤20 mm/h: bias −2.55 mm/h within ±6.0 mm/h; >20 mm/h: percentage bias −10.49% within ±30%), including the high-ESR subgroup (approximately 6–9%). Conclusions: The Vision C analyzer showed a significant, level-dependent negative bias versus Westergren, widening at higher ESRs; strong correlation and RCPA TEa compliance across the full range, including the high subgroup, support its suitability for routine use. Wide regression-based limits and the limited high subgroup sample size (n = 20) warrant caution and further study but do not support routine manual confirmation, since predefined acceptance criteria are met. Method-specific reporting and consistent instrument use in follow-up are recommended. Full article

The erythrocyte sedimentation rate (ESR) is a routine marker of inflammation in human medicine, and it is influenced by erythrocyte features and the level of some plasma proteins. The Westergren method is the reference technique in humans; however, this manual technique has been scarcely used in animals and has not been validated. An automated veterinary in-clinic device (MINI-PET) is able to measure ESR on EDTA-blood tubes. This study aimed to evaluate the comparability of ESR values measured with two tests in cats and dogs admitted to a veterinary clinic and in anemic individuals. Analytical comparability and decision limits were calculated in both species and clinical groups. Comparisons were also made between the two species. The two ESR methods had different decision limits in the investigated population of dogs and cats, and a method-specific interpretation of their results is suggested. Healthy cats had significantly higher values than healthy dogs using both the Westergren and MINI-PET methods. By both methods, anemic individuals had higher ESR values than the matched subgroups with erythrogram values within the reference range, probably due to concurrent inflammation in most anemic animals studied. In general, ESR measures should be evaluated in conjunction with erythrogram values. Full article

Background/Objectives: Axial spondyloarthritis (axSpA) was long considered a male disease, yet women often report higher disease activity; whether this reflects sex differences or comorbidity is unclear. In an under-studied Saudi cohort, we examined sex differences in disease activity and function and associations with fibromyalgia and body mass index (BMI). Methods: A retrospective cross-sectional analysis of de-identified baseline data included 160 adults who met the Assessment of SpondyloArthritis International Society (ASAS) criteria at a single center. Between-sex comparisons used Benjamini–Hochberg correction; sequential multivariable regression evaluated attenuation of the sex–disease activity association after covariate adjustment. Results: Of 160 patients, 56 (35%) were women. Women more often had non-radiographic disease, higher BMI, fibromyalgia, and elevated erythrocyte sedimentation rate (ESR) (all q < 0.05), and scored higher on the symptom-based Bath Ankylosing Spondylitis Disease Activity Index (BASDAI; median 5.65 [IQR 4.67–6.60] vs. 5.15 [4.30–5.72]; p = 0.007, q = 0.044). The Bath Ankylosing Spondylitis Functional Index (BASFI) was borderline (q = 0.052), and C-reactive protein (CRP)-anchored Ankylosing Spondylitis Disease Activity Score (ASDAS-CRP) did not differ significantly (median 3.70 [IQR 3.00–3.90] vs. 3.50 [3.00–3.80]; p = 0.099, q = 0.148). The female BASDAI difference was attenuated after adjustment for concomitant fibromyalgia. Higher ESR was partly attenuated after adjustment for BMI, whereas CRP did not differ by sex. In the analysis restricted to participants without fibromyalgia, between-sex estimates for BASDAI, BASFI, and ASDAS-CRP were smaller and imprecise. Conclusions: The attenuation of the female-sex association with BASDAI after adjustment for concomitant fibromyalgia should be interpreted as statistical attenuation only. Because fibromyalgia and BASDAI share symptom domains, particularly pain and fatigue, this attenuation may partly reflect overlapping symptom content and possible classification circularity rather than an explanatory or causal relationship. Full article

Background: Local cryotherapy is widely used to support recovery after exercise-induced muscle damage, but the optimal timing of cold application remains unclear. This study evaluated whether immediate or delayed local cooling influences recovery from exercise-induced muscle fatigue. Methods: Forty-eight healthy adults (39 women, 9 men; age 22 ± 3 years) performed a single-leg eccentric leg-extension protocol to induce delayed-onset muscle soreness (DOMS) and were randomized to immediate cooling (ICG), delayed cooling (DCG; starting 24 h post-exercise), or control (CG) in a 1:1:1 ratio. Reusable gel packs (20 min per session) were applied to the vastus lateralis. DOMS, maximal voluntary isometric contraction (MVIC), creatine kinase (CK), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and ultrasound-derived muscle thickness (MT) were assessed at baseline and at 24, 48 and 72 h post-exercise and analyzed using linear mixed-effects models. Results: No condition or condition-by-time interactions were detected for the primary outcomes (DOMS, MVIC). Significant linear time effects were observed for DOMS, CK and ESR; MVIC decreased acutely and gradually recovered. A contrast-specific time-by-condition interaction for CRP did not indicate a systematic recovery advantage, and MT showed only minor temporal fluctuations. Conclusion: Neither immediate nor delayed cooling provided a meaningful recovery advantage over the control. The protocol reproducibly elicited fatigue and recovery dynamics, supporting its utility as a framework for future cryotherapy research. Full article