A systematic review and meta-analysis of ischemia-modified albumin in diabetes mellitus.

Aim: There is an ongoing search for novel biomarkers of diabetes. We conducted a systematic review and meta-analysis of the serum concentrations of ischemia-modified albumin (IMA), a candidate biomarker of oxidative stress, acidosis, and ischemia, in patients with pre-diabetes, different types of diabetes mellitus (type 1, T1DM, type 2, T2DM, and gestational, GDM), and healthy controls. Methods: We searched for case-control studies published in PubMed, Web of Science, and Scopus from inception to December 31, 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. Results: In 29 studies, T2DM patients had significantly higher IMA concentrations when compared to controls (standard mean difference, SMD = 1.83, 95 % CI 1.46 to 2.21, p˂0.001; I2 = 95.7 %, p < 0.001; low certainty of evidence). Significant associations were observed between the SMD and glycated hemoglobin (p = 0.007), creatinine (p = 0.003), triglycerides (p = 0.029), and the presence of diabetes complications (p = 0.003). Similar trends, albeit in a smaller number of studies, were observed in T1DM (two studies; SMD = 1.59, 95 % CI -0.09 to 3.26, p˂0.063; I2 = 95.8 %, p < 0.001), GDM (three studies; SMD = 3.41, 95 % CI 1.14 to 5.67, p = 0.003; I2 = 97.0 %, p < 0.001) and pre-diabetes (three studies; SMD = 15.25, 95 % CI 9.86 to 20.65, p˂0.001; I2 = 99.3 %, p < 0.001). Conclusion: Our study suggests that IMA is a promising biomarker for determining the presence of oxidative stress, acidosis, and ischemia in pre-diabetes and T1DM, T2DM, and GDM. However, the utility of measuring circulating IMA warrants confirmation in prospective studies investigating clinical endpoints in pre-diabetes and in different types of diabetes (PROSPERO registration number: CRD42024504690).

Diagnostic accuracy of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio in rheumatoid arthritis: a systematic review and meta-analysis.

Existing challenges with the early diagnosis of rheumatoid arthritis (RA) and active disease, mainly by non-rheumatologists, have prompted the search for novel biomarkers. Elevations in indices derived from blood cell counts, e.g., the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), have been reported in RA patients. However, their diagnostic accuracy has not been comprehensively assessed. Therefore, we conducted a systematic review and meta-analysis of studies reporting the sensitivity and specificity of the NLR and PLR, obtained by receiver operating characteristic (ROC) curve analysis, for the presence of RA and active disease. We searched electronic databases from inception to 15 March 2024 and assessed the risk of bias using the JBI Critical Appraisal Checklist (PROSPERO registration number: CRD42024533546). In 15 studies, the NLR exhibited acceptable accuracy for the presence of RA (area under the curve, AUC = 0.76, 95% CI 0.72 to 0.80) and active disease (AUC = 0.70, 95% CI 0.66 to 0.74). The PLR exhibited good accuracy for the presence of RA (AUC = 0.80, 95% CI 0.76 to 0.83). There were insufficient studies to assess the accuracy of the PLR for the presence of active disease. Our systematic review and meta-analysis suggests that the NLR and the PLR are promising biomarkers of RA (NLR and PLR) and active disease (NLR). Further research is required to investigate whether the NLR and PLR can significantly enhance the capacity to diagnose RA and active disease in clinical practice.

Circulating cell adhesion molecules in systemic sclerosis: a systematic review and meta-analysis.

Introduction: Patients with systemic sclerosis (SSc) have an increased risk of endothelial dysfunction, atherosclerosis, and cardiovascular events compared to the general population. Therefore, the availability of robust circulating biomarkers of endothelial dysfunction and atherogenesis may facilitate early recognition and management of cardiovascular risk in SSc. We sought to address this issue by conducting a systematic review and meta-analysis of studies investigating various types of circulating cell adhesion molecules involved in endothelial dysfunction and atherogenesis (i.e., immunoglobulin-like vascular cell, VCAM-1, intercellular, ICAM-1, platelet endothelial cell, PECAM-1, neural cell, NCAM, Down syndrome cell, DSCAM, and endothelial cell-selective, ESAM, adhesion molecules, E-, L-, and P-selectin, integrins, and cadherins) in SSc patients and healthy controls. Methods: We searched PubMed, Scopus, and Web of Science from inception to 1 May 2024. Risk of bias and certainty of evidence were assessed using validated tools. Results: In 43 eligible studies, compared to controls, patients with SSc had significantly higher plasma or serum concentrations of ICAM-1 (standard mean difference, SMD=1.16, 95% CI 0.88 to 1.44, p<0.001; moderate certainty), VCAM-1 (SMD=1.09, 95% CI 0.72 to 1.46, p<0.001; moderate certainty), PECAM-1 (SMD=1.65, 95% CI 0.33 to 2.98, p=0.014; very low certainty), E-selectin (SMD=1.17, 95% CI 0.72 to 1.62, p<0.001; moderate certainty), and P-selectin (SMD=1.10, 95% CI 0.31 to 1.90, p=0.007; low certainty). There were no significant between-group differences in L-selectin concentrations (SMD=-0.35, 95% CI -1.03 to 0.32, p=0.31; very low certainty), whereas minimal/no evidence was available for cadherins, NCAM, DSCAM, ESAM, or integrins. Overall, no significant associations were observed between the effect size and various patient and study characteristics in meta-regression and subgroup analyses. Discussion: The results of this systematic review and meta-analysis suggest that specific circulating cell adhesion molecules, i.e., ICAM-1, VCAM-1, PECAM-1, E-selectin, and P-selectin, can be helpful as biomarkers of endothelial dysfunction and atherogenesis in the assessment of cardiovascular risk in SSc patients. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024549710.

Higher scores of the Kessler Psychological Distress Scale (K10) are associated with lower serum ergothioneine and higher serum asymmetric dimethyl-l-arginine concentrations in a cohort of middle-aged and older adults.

BACKGROUND: Ergothioneine (ERT) and asymmetric dimethyl-l-arginine (ADMA) have been associated with cognitive decline and dementia in older adults, but their interplay with psychological distress remains unexplored. This study aimed to measure the serum concentrations of ERT and ADMA in a representative sample of older community-dwelling adults and to determine their association with psychological distress. METHODS: Data on clinical, lifestyle, demographic characteristics, and serum concentrations of ERT and ADMA were collected from a population-based sample of older Australian adults (mean age 65.5 ± 7.5 years) from the Hunter Community Study. Psychological distress was assessed using the self-reported Kessler Psychological Distress Scale (K10). RESULTS: In individuals with psychological distress, serum ERT concentrations decreased by 24 %, while ADMA concentrations increased by 6 %. In adjusted analysis, accounting for age and sex, only ERT remained independently associated with psychological distress. For each unit increase in ERT, the odds of experiencing psychological distress decreased by approximately 68 %. CONCLUSION: The trend of decreasing serum ERT concentrations observed in older adults with increasing psychological distress suggests a potential link between this compound and mental health. Given the dietary origin of ERT, its integration offers therapeutic opportunities that warrant investigation in intervention studies.

Complete Blood Count-Based Biomarkers as Predictors of Clinical Outcomes in Advanced Non-Small Cell Lung Cancer Patients with PD-L1 < 50% Treated with First-Line Chemoimmunotherapy.

Background: The aim of the study was to investigate a series of complete blood cell count-based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC and PD-L1 < 50% who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78-10.82 vs. 3.31; IQR: 2.15-4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82-21.20 vs. 9.20; IQR: 7.45-11.20, p = 0.013), and systemic inflammation index (SII, median: 1395; IQR: 929-3334 vs. 945; IQR: 552-1373, p = 0.025), but only NLR and NMR remained independently associated with clinical response in multivariate logistic regression. In the univariate analysis, white blood cells (OR:1.2202; 95% CI: 1.0339-1.4400, p = 0.019), neutrophils (OR:1.2916; 95% CI: 1.0692-1.5604, p = 0.008), NLR (OR:1.3601: 95% CI: 1.0949-1.6896, p = 0.005) and NMR (OR:1.2159; 95% CI: 1.00396-1.4221, p = 0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR, and MLR were independently associated with survival; NLR, at a cut-off value of 4.0, showed the better AUC (0.749) in predicting OS. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

The vascular endothelial growth factor as a candidate biomarker of systemic lupus erythematosus: a GRADE-assessed systematic review and meta-analysis.

There is an ongoing search for novel biomarkers of endothelial damage, active disease, and organ dysfunction in systemic lupus erythematosus (SLE). We investigated the role of the vascular endothelial growth factor (VEGF) as a candidate biomarker by conducting a systematic review and meta-analysis of studies examining VEGF concentrations in SLE patients and healthy controls. We searched electronic databases (PubMed, Scopus, and Web of Science) from inception to 31 May 2024 (inclusion criteria: VEGF measurement in SLE patients and healthy controls and SLE patients with and without active disease or specific organ dysfunction in case-control studies, recruitment of adult participants, and availability of the full text in the English language; exclusion criteria: non-case-control studies, participants under 18 years, articles reporting duplicate or irrelevant data, and animal studies). We assessed the risk of bias and the certainty of evidence using the JBI Critical Appraisal Checklist and GRADE, respectively (PROSPERO registration number: CRD42024561636). Circulating VEGF concentrations were significantly higher in SLE patients than in controls (22 studies; standardised mean difference, SMD = 0.71, 95% CI 0.44 to 0.98, p < 0.001; low certainty of evidence). In SLE patients, VEGF concentrations were significantly higher in those with active disease (six studies; SMD = 1.10, 95% CI 0.27 to 1.92, p = 0.009; very low certainty of evidence) and lupus nephritis (four studies; SMD = 0.80, 95% CI 0.03 to 1.57, p = 0.042; very low certainty of evidence). Only one study reported VEGF concentrations in SLE patients with and without pulmonary arterial hypertension. The effect size of the differences in VEGF concentrations between SLE patients and controls was not associated with disease duration, use of glucocorticoids and immunosuppressors, biological matrix assessed, or analytical method used. However, it was significantly associated with the study's geographical location. The evidence was limited by the high but partially explainable heterogeneity and the presence of publication bias which was addressed with the "trim-and-fill" method (SLE presence), the high but partially explainable heterogeneity and lack of assessment of publication bias because of the limited study number (active disease), and the limited study number preventing the identification of sources of heterogeneity, sensitivity analysis, and assessment of publication bias (lupus nephritis). Our results highlight VEGF's potential role as a SLE biomarker and the need for further research, also given the aforementioned limitations, investigating VEGF concentrations in a wide range of SLE patient subgroups.

Effect of a Phytochemical-Rich Olive-Derived Extract on Anthropometric, Hematological, and Metabolic Parameters.

BACKGROUND: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, and anti-ageing effects to protect normal tissues, and it can exert anti-angiogenic and pro-apoptotic effects on cancer cells. Metabolites found in different parts of the olive tree, including leaves, also possess properties that might help in cancer prevention and promote wellness in aging. Olive mill wastewater (OMWW), a liquid residue produced during olive oil extraction, represents an environmental issue. However, it is rich in phytochemicals with potential beneficial properties. Dietary supplements based on OMWW can be produced for nutritional supplementation with advantages to the ecology. PURPOSE: This work aims to measure hematochemical, anthropometric, and metabolomic parameters in volunteers taking an OMWW dietary supplement, Oliphenolia® (OMWW-OL). METHODS: The supplementation of OMWW-OL 25 mL twice daily for 30 days was tested on a pilot cohort of volunteers with characteristics close to metabolic syndrome. Hematochemical, anthropometric, serum biomarkers and serum metabolomic parameters were analyzed before the intervention, at 30 days, and 30 days after stopping consumption. RESULTS: A total of 29 volunteers were enrolled, and 23 completed the study. The participants' parameters at baseline were measured, and then twice daily at 30 days of treatment and 30 days after assumption discontinuation. Although treatment was with an olive derivative, their weight did not increase. Their body mass index, instead of augmenting, slightly decreased, particularly in the women. Also, hydration increased, especially in the women, while blood pressure, glycemia, and insulin decreased. Cholesterol, high-density lipoproteins, and triglycerides were stable, and LDL levels decreased, while vitamin D levels, alongside calcium, perceptibly increased. Albumin also increased. All the values were in support of an equilibrium, with no damaging effects. By mass spectrometry analysis, we also found favorable changes in the vitamin D/histamine and homocysteine/methionine ratios, an increase in a new metabolite of unknown formula, and the vitamin D/unknown metabolite ratio. CONCLUSIONS: Supplementation of OMWW-OL has no detrimental effects and might imply the beneficial modulation of several biological parameters. Although this is a small pilot study, with limited potency, it preliminarily suggests that the OMWW extract use could be potentially valuable for people at risk of metabolic syndrome. Some of these parameters could also be relevant in supporting healthy ageing and in cancer prevention.

Investigating bilirubin concentrations in schizophrenia: A systematic review and meta-analysis.

Schizophrenia, a severe mental disorder characterized by chronic disability and poor quality of life, has been shown to be associated with alterations in redox balance. Recent research has suggested a potential link between the antioxidant bilirubin and schizophrenia, although findings have been inconsistent. To address this gap, we conducted a systematic review and meta-analysis to evaluate possible alterations in bilirubin concentrations in schizophrenia. A comprehensive search of major databases was conducted to identify articles reporting total and unconjugated bilirubin in schizophrenic patients and healthy controls in case-control studies. Our meta-analysis included 18 studies investigating 16,245 participants. The pooled results did not reveal any significant association between schizophrenia and total bilirubin concentrations. Additionally, such effect was strongly influenced by the results of a single study in sensitivity analysis. Subgroup and meta-regression analyses based on various factors such as study design, sample size, and geographical region showed no significant associations with the effect size, nor they identified sources of heterogeneity. Furthermore, publication bias assessments were conducted to ensure the robustness of the findings. Overall, our findings summarize the available evidence regarding the possible role of bilirubin as a biomarker of schizophrenia and highlight the importance of conducting further research in this area.

Resistin and omentin in breast cancer: A systematic review and meta-analysis.

Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women globally. Resistin, omentin and ghrelin, adipokines involved in inflammation and metabolic regulation, have been implicated in cancer development, yet their associations with BC remain unclear. This systematic review and meta-analysis aimed to elucidate the relationships between resistin, omentin, and ghrelin concentrations and BC, while exploring potential moderators such as body mass index (BMI) and menopausal status. A comprehensive search of electronic databases up to 13 May 2024 identified studies comparing resistin and omentin, but not ghrelin, concentrations in BC patients and healthy controls. Standardized mean differences (SMDs) were calculated using random-effects models, and meta-regression and subgroup analyses were performed to investigate sources of heterogeneity. Analysis of 11 studies showed that BC patients exhibited significantly higher resistin concentrations compared to controls, with a pooled SMD of 2.05 (95 % CI 1.24 to 2.86, p < 0.001). Meta-regression indicated that BMI significantly moderated the resistin-BC association (p = 0.003). In contrast, omentin concentrations presented a complex picture, with a pooled SMD of -0.27 (95 % CI -1.39 to 0.84, I^2 = 96.2 %, p < 0.001), indicating substantial heterogeneity and inconclusive results, whereas only one study investigated ghrelin. Our findings support a significant association between elevated resistin concentrations and BC, suggesting a potential role of resistin in BC pathophysiology. The data on omentin and ghrelin remain inconclusive, warranting further investigation. Future research should focus on large, longitudinal studies with standardized methodologies to validate these findings and clarify the role of adipokines in BC.

A systematic review and meta-analysis of the diagnostic accuracy of the neutrophil-to-lymphocyte ratio and the platelet-to-lymphocyte ratio in systemic lupus erythematosus.

The wide range of clinical and serological manifestations in systemic lupus erythematosus (SLE) and the lack of accepted diagnostic criteria warrant the identification of novel, more accurate biomarkers. Hematological indices derived from full blood cell counts, particularly the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), have shown promise in SLE; however, a critical appraisal of their diagnostic accuracy is lacking. We sought to address this issue by conducting a systematic review and meta-analysis of the diagnostic accuracy of the NLR and PLR in SLE. The electronic databases PubMed, Scopus, and Web of Science were systematically searched from inception to 15 March 2024 for studies reporting the sensitivity and specificity of the NLR and PLR, obtained by receiver operating characteristic (ROC) curve analysis, for the presence of SLE, disease severity, organ involvement (lupus nephritis, pericarditis, and pleural disease), and complications (infections). The risk of bias was assessed using the JBI Critical Appraisal Checklist (PROSPERO registration number: CRD42024531446). The NLR exhibited good accuracy for the diagnosis of SLE (eight studies; area under the curve, AUC = 0.81, 95% CI 0.78-0.85) and lupus nephritis (nine studies; AUC = 0.81, 95% CI 0.77-0.84), but not for severe disease (nine studies; AUC = 0.69, 95% CI 0.65-0.73) or infections (six studies; AUC = 0.73, 95% CI 0.69-0.77). The PLR exhibited good accuracy for the diagnosis of severe disease (six studies; AUC = 0.85, 95% CI 0.81-0.87). There were an insufficient number of studies to assess the accuracy of the PLR for the diagnosis of SLE, lupus nephritis, or infections. No study investigated the NLR and PLR in SLE patients with pericarditis or pleural disease. Therefore, the NLR and the PLR have a relatively high diagnostic accuracy for the presence of SLE and lupus nephritis (NLR) and severe disease (PLR). Further studies are warranted to determine whether the NLR and PLR, in combination with clinical evaluation and other serological biomarkers, can enhance the diagnosis and management of SLE.

A systematic review and meta-analysis of the association between the D-dimer and rheumatic diseases.

INTRODUCTION: There is good evidence that specific autoimmune rheumatic diseases (RDs), for example, rheumatoid arthritis and systemic lupus erythematosus (SLE), are associated with a state of hypercoagulability and an increased risk of venous thromboembolism (VTE). However, limited information regarding this association is available for other autoimmune or autoinflammatory RDs. We sought to address this issue by conducting a systematic review and meta-analysis of the association between the d-dimer, an established marker of hypercoagulability and VTE, and RDs and the possible clinical and demographic factors mediating this association. METHODS: We searched the electronic databases PubMed, Web of Science, and Scopus from inception to January 31, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. RESULTS: In 31 studies selected for analysis (2724 RD patients and 3437 healthy controls), RD patients had overall significantly higher d-dimer concentrations when compared to controls (standard mean difference = 0.93, 95% CI 0.76-1.10, p < .001; I2 = 86.1%, p < .001; moderate certainty of evidence). The results were stable in a sensitivity analysis. Significant associations were observed between the effect size of the between-group differences in d-dimer concentration and age, specific RD and RD category, RD duration, fibrinogen, plasminogen activator inhibitor, C-reactive protein, and erythrocyte sedimentation rate. CONCLUSIONS: Overall, patients with RDs have significantly higher d-dimer concentrations when compared with healthy controls, indicating a state of hypercoagulability. The alterations in d-dimer concentrations are mediated by age, specific RD and RD category, RD duration, and markers of anticoagulation and inflammation. Further research is warranted to investigate d-dimer concentrations across the spectrum of RDs and their utility in predicting and managing VTE in these patients (PROSPERO registration number: CRD42024517712).

The role of bilirubin as a biomarker of rheumatic diseases: a systematic review and meta-analysis.

The identification of novel, yet easily measurable biomarkers of inflammation and oxidative stress might assist in the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of studies investigating the circulating concentrations of bilirubin, the end product of heme metabolism and a potent endogenous antioxidant with anti-inflammatory properties, in patients with RDs and healthy controls. The electronic databases PubMed, Scopus, and Web of Science were searched from inception to 31 December 2023 for relevant articles. We 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 17 eligible studies, all with low risk of bias, compared to controls, patients with RDs had significantly lower concentrations of total bilirubin (standard mean difference, SMD=-0.68, 95% CI -0.91 to -0.44, p<0.001; I2 = 92.5%, p<0.001; low certainty of evidence), direct (conjugated) bilirubin (SMD=-0.67, 95% CI -0.92 to -0.41, p<0.001; I2 = 81.7%, p<0.001; very low certainty of evidence), and the active antioxidant and anti-inflammatory indirect (unconjugated) form of bilirubin (SMD=-0.71, 95% CI -1.18 to -0.24, p=0.003; I2 = 95.1%, p<0.001; very low certainty of evidence). The results of the meta-analysis were stable in sensitivity analysis. In meta-regression, there were no significant associations between the SMD of total bilirubin and several clinical and demographic characteristics, including age, male to female ratio, number of participants, liver enzymes and erythrocyte sedimentation rate. In subgroup analysis, the SMD of total bilirubin was significant across a range of RDs, including rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren syndrome, and myositis. Therefore, the results of our systematic review and meta-analysis suggests that the reductions in bilirubin concentrations observed in patients with RDs reflect a state of impaired antioxidant and anti-inflammatory defence due to bilirubin consumption and highlight the promising role of this endogenous product as a biomarker of RDs. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023500649.

The potential role of serum amyloid A as biomarker of rheumatic diseases: a systematic review and meta-analysis.

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 association between bilirubin concentrations and inflammatory bowel disease: Insights from a systematic review and meta-analysis.

BACKGROUND: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), poses a significant challenge to health care systems because of its chronic nature and increasing global prevalence. Effective management of IBD requires accurate diagnostic tools and biomarkers. This systematic review and meta-analysis aimed to evaluate the relationship between bilirubin concentrations and IBD activity and outcomes. METHODS: A comprehensive search of electronic databases identified 11 studies that included 2606 subjects with IBD and 3607 healthy controls. RESULTS: Bilirubin concentrations were significantly lower in subjects with IBD when compared to controls (SMD = -0.96, 95% CI -1.21 to -0.70; p < .001). Although substantial heterogeneity was observed, sensitivity analysis confirmed the robustness of the results. Publication bias was detected, but subgroup analyses did not significantly alter the results. Meta-regression showed that age was a significant factor influencing the association between bilirubin concentrations and IBD. Subgroup analyses showed a more pronounced reduction in bilirubin concentrations in subjects with CD than those with UC. CONCLUSION: This study supports the potential utility of bilirubin as a biomarker in IBD, emphasizing the need for further research to validate its clinical significance.

The relationship between haemoglobin concentrations and obstructive sleep apnea syndrome: A systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis investigates the relationship between haemoglobin (Hb) concentrations and obstructive sleep apnea syndrome (OSAS). METHODS: Following PRISMA guidelines, we searched PubMed, EMBASE, and Cochrane Library from inception to March 8, 2024. Eligible studies included cross-sectional, cohort, and case-control designs comparing Hb concentrations in OSAS patients and healthy controls. Two reviewers independently screened records and extracted data. The risk of bias was assessed using the Joanna Briggs Institute checklist. RESULTS: A total of 27 studies involving 6499 OSAS subjects and 5199 controls were included. Hb concentrations were significantly higher in OSAS patients compared to controls (SMD: 0.28; 95 % CI: 0.18 to 0.39; I2 = 84.4 %). Subgroup analysis by OSAS severity showed that severe OSAS patients had higher Hb concentrations than those with mild/moderate OSAS. Sensitivity analyses confirmed the robustness of the findings. However, 7 studies reported opposite results, indicating possible regional or methodological differences. CONCLUSION: Hb concentrations are elevated in OSAS patients, with higher levels observed in severe cases. The significant heterogeneity and the predominance of studies from Turkey highlight the need for further research in diverse populations. Limitations include potential publication bias and variability in study designs.

Ischemia-modified albumin in rheumatic diseases: A systematic review and meta-analysis.

INTRODUCTION: The identification of novel, easily measurable disease biomarkers might enhance the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta-analysis of ischemia-modified albumin (IMA), a marker of oxidative stress, acidosis, and ischemia, in RD patients and healthy controls. METHODS: We searched PubMed, Web of Science, and Scopus from inception to January 15, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. RESULTS: In 20 studies investigating a total of 1188 RD patients (mean age 45 years, 64% females) and 981 healthy controls (mean age 44 years, 66% females), RD patients had significantly higher IMA concentrations when compared to controls (standard mean difference, SMD = 0.50, 95% CI: 0.18-0.83, p = .003; I2 = 92.4%, p < .001; low certainty of evidence). In subgroup analysis, the pooled SMD was significantly different in studies investigating ankylosing spondylitis (p < .001), Behçet's disease (p < .001), and rheumatoid arthritis (p = .033), but not familial Mediterranean fever (p = .48). Further associations were observed between the pooled SMD and the broad classification of autoimmune and/or autoinflammatory diseases, the study country, and the method used to measure IMA. CONCLUSION: Our study suggests that IMA is a promising biomarker of oxidative stress, acidosis, and ischemia, as it can effectively discriminate between patients with different types of RDs and healthy controls. Our results warrant confirmation in longitudinal studies of patients with different types of RDs and different ethnicities (PROSPERO registration number: CRD42024509126).

Association between blood Pentraxin-3 concentrations and rheumatic diseases: A systematic review and meta-analysis.

BACKGROUND: Among the Pentraxins, the long Pentraxin-3 (PTX-3) is associated with several processes, particularly in the earliest phases of the innate humoral response. Increased blood PTX-3 concentrations have been observed in a wide range of conditions, from infectious to cardiovascular disorders. Since its increase is more rapid than C-reactive protein (CRP), PTX-3 can be useful to detect and monitor early inflammation. To dissect its pathophysiological role in rheumatic diseases (RD), we conducted a systematic review and meta-analysis comparing blood PTX-3 concentrations in RD patients and healthy individuals and investigating possible associations with clinical, demographic, and study characteristics. METHODS: We performed a search of published evidence until April 2024 in PubMed, Web of Science and Scopus, which led to the selection of 60 relevant manuscripts from a total of 1072 records. RESULTS: Our synthesis revealed a statistically significant difference in PTX-3 concentrations between RD patients and controls (standard mean difference, SMD = 1.02, 95% CI 0.77-1.26, p < .001), that correlated with CRP concentrations. The effect size was associated with geographical region of study conduction, RD type, with a reduction of the observed heterogeneity in patients with low LDL-cholesterol and triglycerides concentrations. CONCLUSIONS: Our study has shown a significant increase in blood PTX-3 concentrations in RD patients, which was associated with specific patient characteristics. Nevertheless, additional studies are needed to better define the utility of measuring PTX-3 in the early phase of RD. Our study was conducted in compliance with the PRISMA 2020 statement (study protocol available at PROSPERO CRD42024516600).

Ocular Tics and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS).

Little is known about ocular tics in Pediatric Autoimmune Neuropsychiatric Disorders associated with Streptococcal infections (PANDAS). In this retrospective study, we examined the clinical records of children with motor tics referred to the Ophthalmology Unit, Azienda Ospedaliero-Universitaria di Sassari, Italy, in 2010-2019. The presence of ocular tics was investigated. Data about antistreptolysin O (ASO) and anti-DNase B antibody titers, erythrocyte sedimentation rate (ESR), plasma C-reactive protein (CRP), and antibiotic use were recorded. Forty children (thirty-four boys and six girls; mean age: 7.65 ± 2.5 years) with motor tics were identified; thirty-three (82.5%) showed ocular tics. Children with ocular tics had significantly higher titers of anti-DNase B antibodies (p = 0.04) and CRP (p = 0.016) than those with extraocular tics. A diagnosis of PANDAS was made in 24 (60%) children. PANDAS children with oculomotor tics had significantly higher titers of anti-DNase B antibodies (p = 0.05) than those with extraocular tics. Oral antibiotics were given to 25/33 (76%) children with ocular tics and 21/24 (87.5%) with PANDAS. All treated patients showed marked improvement/complete resolution of symptoms. Results suggest that higher titers of anti-DNase B antibodies may be implicated in the pathogenesis of ocular tics in PANDAS. Oral antibiotics may be beneficial in improving ocular tics. Further research is necessary to confirm our findings.

The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio and systemic sclerosis and its complications: a systematic review and meta-analysis.

Introduction: The identification of new, easily measurable biomarkers might assist clinicians in diagnosing and managing systemic sclerosis (SSc). Although the full blood count is routinely assessed in the evaluation of SSc, the diagnostic utility of specific cell-derived inflammatory indices, i.e., neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), has not been critically appraised in this patient group. Methods: We conducted a systematic review and meta-analysis of studies investigating the NLR, PLR, and MLR, in SSc patients and healthy controls and in SSc patients with and without relevant complications. PubMed, Scopus, and Web of Science were searched from inception to 23 February 2024. Risk of bias and certainty of evidence were assessed using validated tools. Results: In 10 eligible studies, compared to controls, patients with SSc had significantly higher NLR (standard mean difference, SMD=0.68, 95% CI 0.46 to 0.91, p<0.001; I2 = 74.5%, p<0.001), and PLR values (SMD=0.52, 95% CI 0.21 to 0.83, p=0.001; I2 = 77.0%, p=0.005), and a trend towards higher MLR values (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I2 = 94.1%, p<0.001). When compared to SSc patients without complications, the NLR was significantly higher in SSc with interstitial lung disease (ILD, SMD=0.31, 95% CI 0.15 to 0.46, p<0.001; I2 = 43.9%, p=0.11), pulmonary arterial hypertension (PAH, SMD=1.59, 95% CI 0.04 to 3.1, p=0.045; I2 = 87.6%, p<0.001), and digital ulcers (DU, SMD=0.43, 95% CI 0.13 to 0.74, p=0.006; I2 = 0.0%, p=0.49). The PLR was significantly higher in SSc patients with ILD (SMD=0.42, 95% CI 0.25 to 0.59, p<0.001; I2 = 24.8%, p=0.26). The MLR was significantly higher in SSc patients with PAH (SMD=0.63, 95% CI 0.17 to 1.08, p=0.007; I2 = 66.0%, p=0.086), and there was a trend towards a higher MLR in SSc patients with ILD (SMD=0.60, 95% CI -0.04 to 1.23, p=0.066; I2 = 94.1%, p<0.001). Discussion: Pending the results of appropriately designed prospective studies, the results of this systematic review and meta-analysis suggest that blood cell-derived indices of inflammation, particularly the NLR and PLR, may be useful in the diagnosis of SSc and specific complications. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024520040.

Platelet Dynamics in Neurodegenerative Disorders: Investigating the Role of Platelets in Neurological Pathology.

Background: Neurological disorders, particularly those associated with aging, pose significant challenges in early diagnosis and treatment. The identification of specific biomarkers, such as platelets (PLTs), has emerged as a promising strategy for early detection and intervention in neurological health. This systematic review aims to explore the intricate relationship between PLT dynamics and neurological health, focusing on their potential role in cognitive functions and the pathogenesis of cognitive disorders. Methods: Adhering to PRISMA guidelines, a comprehensive search strategy was employed in the PubMed and Scholar databases to identify studies on the role of PLTs in neurological disorders published from 2013 to 2023. The search criteria included studies focusing on PLTs as biomarkers in neurological disorders, their dynamics, and their potential in monitoring disease progression and therapy effectiveness. Results: The systematic review included 104 studies, revealing PLTs as crucial biomarkers in neurocognitive disorders, acting as inflammatory mediators. The findings suggest that PLTs share common features with altered neurons, which could be utilised for monitoring disease progression and evaluating the effectiveness of treatments. PLTs are identified as significant biomarkers for detecting neurological disorders in their early stages and understanding the pathological events leading to neuronal death. Conclusions: The systematic review underscores the critical role of PLTs in neurological disorders, highlighting their potential as biomarkers for the early detection and monitoring of disease progression. However, it also emphasises the need for further research to solidify the use of PLTs in neurological disorders, aiming to enhance early diagnosis and intervention strategies.