Inactive Patients Research Articles

Levels of VCAM-1 and ICAM-1 in serum of active and inactive Systemic Lupus Erythematosus patients as biochemical markers for risk of cardiovascular disease

Background: Cardiovascular complications represent one of the consequences of chronic autoimmune diseases such as Systemic Lupus Erythematosus (SLE), which has significant rates of morbidity and mortality. Dyslipidemia can be brought on by steroid medications, which are frequently given to SLE patients and are considered to be one of the major risk factors for cardiovascular diseases. Objectives: This study attempted to investigate a potential association between circulating vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) as risk factors for atherosclerosis and their relationship to cardiovascular risk. Patients and methods: A total of 100 patients and 50 apparently healthy controls were included in the study. All patients were from the Department of Rheumatology, Baghdad Hospital / Medical City during the period from 1 December 2021 to 1 March 2022 who were all treated with antimalarial drugs as immunosuppressants such as chloroquine (CQ) or hydroxychloroquine HCQ). They were divided according to the SLE disease activity index 2000 (SLEDAI-2K) into the active group (SLEDAI ≥ 10) and the inactive group (SLEDAI). Results: Serum VCAM and ICAM were significantly high in all study groups of SLE patients. The VCAM mean ± SD were (271.9±63.90), (247.9±82.92) and (97.7±24.69) in the active, inactive controls respectively. The ICAM mean ± SD were (3.1±0.91), (2.7±0.79) and (1.8±0.22) in the active, inactive and controls respectively. The values have increased gradually with increasing disease activity. The area under curve (AUC) of ICAM and VCAM were (0.802), (0.776) in active SLE patients and (0.858), (0.674) in inactive SLE patients. However, the AUC of VCAM and ICAM in active group were the highest. Conclusion: In SLE patients, VCAM-1 and ICAM-1 serum levels may operate as disease detection and severity differentiation indicators, and they may be linked to the number of coronary lesions in people at risk of developing CVD. Received: Aug.,2022 Accepted: Sept., 2022 Published: April 2023

Determining Disease Activity and Glucocorticoid Response in Thyroid-Associated Ophthalmopathy: Preliminary Study Using Dynamic Contrast-Enhanced MRI.

To assess the role of dynamic contrast-enhanced (DCE)-MRI of the extraocular muscles (EOMs) for determining the activity of thyroid-associated ophthalmopathy (TAO) and treatment response to glucocorticoids (GCs). We prospectively enrolled 65 patients with TAO (41 active, 82 eyes; 24 inactive, 48 eyes). Twenty-two active patients completed the GC treatment and follow-up assessment, including 15 patients (30 eyes) and 7 patients (14 eyes), defined as responsive and unresponsive, respectively. Model-free (time to peak [TTP], area under the curve [AUC], and Slopemax) and model-based (Ktrans, Kep, and Ve) parameters of EOMs in embedded simplified histogram analyses were calculated and compared between groups. Multivariable logistic regression analysis was used to identify the independent predictors. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance. Active patients exhibited significantly higher TTP at the 10th percentile (-10th), TTP-mean, and TTP at the 90th percentile (-90th); AUC-10th, AUC-mean, AUC-90th, and AUC-max; Ktrans-10th and Ktrans-mean; and Ve-10th, Ve-mean, Ve-90th, and Ve-max than inactive patients (P < 0.05). Responsive patients exhibited significantly lower TTP-min; higher Ktrans-mean and Ktrans-max; and higher Kep-10th, Kep-mean, and Kep-max than unresponsive patients (P < 0.05). TTP-mean and Ve-mean were independent variables for determining disease activity (P = 0.017 and 0.022, respectively). A combination of the two parameters could determine active TAO with moderate performance (AUROC = 0.687). TTP-min and Ktrans-mean were independent predictors of the response to GCs (P = 0.023 and 0.004, respectively), uniting which could determine the response to GCs with decent performance (AUROC = 0.821). DCE-MRI-derived model-free and model-based parameters of EOMs can assist in the evaluation of TAO. In particular, TTP-mean and Ve-mean could be useful for determining the activity of TAO, whereas TTP-min and Ktrans-mean could be promising biomarkers for determining the response to GCs.

Sarcopenia: Pathophysiology and Treatment Strategies.

Sarcopenia is becoming prevalent in older or inactive patients, which is placing a heavy burden on the social health system. Studies on the pathogenesis of sarcopenia mainly focus on adipose tissue, myoglobin autophagy, and mitochondrial dysfunction. Up to now, non-drug treatment has been the main way to treat sarcopenia, and there are no drugs specially approved for the treatment of sarcopenia. Here, the pathophysiology and treatment methods of sarcopenia have been summarized, and new drugs for sarcopenia to be researched and developed in the future have been prospected.

Increased Inflammatory Responses in Patients With Active Disseminated Non-Tuberculous Mycobacterial Infection and High Anti-Interferon-Gamma Autoantibodies.

Adult-onset immunodeficiency (AOID) is associated with the presence of anti-IFN-γ autoantibodies (auAbs). In disseminated nontuberculous mycobacterial (dNTM) infection with AOID, neutralization of IFN-γ by auAb may play a role in disease susceptibility, but other molecular mechanisms are likely to contribute. In this study, dNTM patients, including inactive, active but non-progressive and active, progressive cases were enrolled to measure plasma anti-IFN-γ auAb by ELISA and underwent whole-blood RNA sequencing. Healthy control individuals were also enrolled. Plasma IL-8 was then quantified to confirm transcriptomic analysis. Results revealed that anti-IFN-γ auAb titers were significantly increased in patients with active stage of disease. Gene expression could separate patients with active infection from individuals with no signs of infection (inactive patients and healthy controls). In active cases, there was over-expression of inflammatory pathways and under-expression of type-2 immunity pathways. Interestingly, increased levels of plasma IL-8 (p=0.0167) not only confirmed gene expression results but also correlated with the presence of neutrophilic dermatitis (p=0.0244). In conclusion, our findings highlight the value of anti-IFN-γ auAb titers for predicting disease reactivity and first propose IL-8 as a promising mediator to be further explored, given its correlation with skin reactive disease, a hallmark of active dNTM infection.

The role of urinary biomarker monocyte chemoattractant protein (MCP-1) in correlation with different histopathological classes of lupus nephritis in Egyptian patients

Lupus nephritis (LN) affects almost two-thirds of systemic lupus erythematosus (SLE) patients. Renal biopsy is the gold standard for the diagnosis of LN. However, repeated biopsies are not always performed in clinical practice, and they carry some risk. Therefore, minimally invasive techniques, as urinary biomarkers, are promising tools for the diagnosis and monitoring of SLE. Previous studies evaluated urinary monocyte chemoattractant protein-1 (MCP-1) in patients with SLE, reported higher levels of urinary MCP-1 in patients with active LN than non-active LN. Other studies reported higher levels of urinary MCP-1 in LN patients with proliferative forms (III and IV). This study aimed to evaluate urinary MCP-1 as a noninvasive diagnostic biomarker tool for LN, and to determine its association with different LN histopathological stages and chronicity indices. The study included 40 SLE patients with biopsy-proven LN class II, III, IV or V, and 20 patients with inactive LN as a control group. In LN active patients, the mean creatinine was 1.71 ± 0.55 mg/dl, and 0.84 ± 0.10 mg/dl in the control group. The mean MCP-1 level was 618.4 ± 294.2 ng/l in active LN patients and 120.05 ± 87.53 ng/l in inactive LN patients. The receiver operating characteristic (ROC) curve analysis indicated a better diagnostic performance of MCP-1 than conventional biomarkers. At area under the curve of 0.990, the best cut-off level was &gt;245 ng/L (sensitivity 97.5 %, Specificity 95 %). In conclusion, urinary MCP-1 distinguished active LN from inactive renal disease. It can be proposed as a good noninvasive diagnostic biomarker with a high sensitivity and specificity for detection of LN activity.

Predictors of macrovascular complications in Al-Madinah Al-Munawara type 2 diabetes mellitus patients, Saudi Arabia: A cross-sectional study

Background/aim Diabetes mellitus is a metabolic disease characterized by chronic hyperglycemia, which causes macrovascular complications that account for most of the morbidity, hospitalizations, and deaths. The goal of this study is to evaluate the relationship between macrovascular complications and associated risk factors in Al-Madinah Al-Munawara patients suffering from type 2 diabetes mellitus. Patients and methods This descriptive cross-sectional study involved 275 type 2 diabetes mellitus patients who resided in Al-Madinah Al-Munawara and visited the diabetic clinic at King Fahd Hospital on a regular basis. Participants in the study ranged in age from 20 to 65. Hemoglobin, glycated hemoglobin, serum calcium, fasting blood glucose, and lipid profile were analyzed. Results Out of 275 patients with type 2 diabetes mellitus, 113 have had macrovascular complications. A significant association (P&lt;0.05) has been observed between the age of the patients and different forms of macrovascular complications, which impact 62.7% of the elderly (41–65 years old). The prevalence of macrovascular complications was higher among females. Glycated hemoglobin levels positively correlated with the number of hospitalizations, high blood pressure, hemoglobin, and serum cholesterol levels. Macrovascular complications are positively correlated with age, sex, hypertension, and therapy type (P&lt;0.05), while physical activity has a negative significant effect on the appearance of macrovascular complications by multiple regression analysis. Conclusion In this study, diabetic macrovascular complications were prevalent. The age, sex of participants, and type of treatment were independent predictors of macrovascular complications. Hypertension has a significant positive effect on the appearance of macrovascular complications. Physically inactive patients have a higher risk of macrovascular complications.

Identifying Who Benefits the Most from a Community Health Worker-Led Multicomponent Intervention for Hypertension.

Uncontrolled hypertension is a major public health challenge in low- and middle-income countries. The Hypertension Control Program in Argentina (HCPIA) showed that a community health worker-led multicomponent intervention was effective for blood pressure (BP) reduction in resource-limited settings, but whether the intervention was equally effective across participant subgroups is unknown. To identify participants who benefit the most from the HCPIA BP control intervention. This secondary analysis used data from HCPIA, a successful 18-month cluster-randomized trial in 18 health centers with 1,432 low-income hypertensive patients in Argentina. Fifteen baseline characteristics were used to define subgroups. The proportion of controlled BP (<140/90 mmHg) was estimated using generalized linear mixed models with arm-by-subgroup interaction terms. The distribution of trial BP response among intervention patient subgroups was assessed. Participants were 53.0% female, a mean age of 56 years, and 17.4% controlled BP at baseline. After the intervention, 72.9% of intervention and 52.2% of control participants had controlled BP. The intervention was more effective in physically inactive patients (OR = 2.76, 95% CI: 1.82 and 4.21; p for interaction = 0.04), moderately active patients (OR = 3.08, 95% CI: 1.90 and 4.99; p for interaction = 0.03), and those with uncontrolled BP at baseline (OR = 2.77, 95% CI: 2.15 and 3.57; p for interaction = 0.05). Among intervention participants, 20.2% had no BP response (BP change < -4 mmHg), 41.3% had a moderate BP response (BP change: -4 mmHg to -24 mmHg), and 38.5% had a high BP response (BP change > -24 mmHg). Women (p=0.01), those who were physically inactive (p=0.03), and those not taking antihypertensive medications at baseline (p=0.001) had the greatest BP response. The effect of the intervention was consistent across many subgroups with some key groups showing a particularly strong intervention effect. These findings could be useful for planning future hypertension control programs in low- and middle-income countries.

Increased papillary microcirculation in inactive uveitis patients by optical coherence tomography angiography

Aim: To quantitatively analyze the vascular and structure abnormalities in the papillary areas in eyes with noninfectious uveitis during different periods using optical coherence tomography angiography (OCTA). Methods: Forty eyes of 40 uveitis patients in the acute phase, 12 eyes of 12 patients with inactive uveitis and 21 eyes of 21 healthy controls were included in this study. RPCvd% and pRNFL thickness in different regions were automatically measured and calculated by OCTA. Correlation between RPCvd% and pRNFL was assessed. Results: RPCvd% was significantly higher in uveitis-inactive eyes than in active eyes in the inferior quadrant (p = 0.036), whole image (p = 0.041) and inferior nasal (p = 0.001) sector. The RPCvd% in active uveitis eyes was lower compared to healthy eyes in the inside disc sector (p = 0.026). pRNFL was notably greater in the active group compared to the healthy group. Positive correlations were identified between pRNFL and RPCvd% both in active and inactive uveitis eyes. Conclusions: Compared with active uveitis, papillary microcirculation showed a significant improvement in inactive uveitis eyes (anterior or pan-uveitis). RPCvd% may serve as a sensitive indicator to supervising uveitis progression and treatment response using OCTA.

HEART RATE VARIABILITY DURING PHYSICAL EFFORT IN PATIENTS WITH METASTATIC OVARIAN CANCER AND CONCOMITANT OBESITY

Introduction. One of the main factors affecting postoperative outcomes in patients with advanced ovarian cancer is the cardiopulmonary status. Several studies have reported that preoperative multifactorial rehabilitation and physical fitness can lead to reduced postoperative morbidity, mortality, shorter length of stay, and improved quality of life in cancer patients. The issue of adaptability to physical activity of overweight and obese patients who undergoing debulking surgery is insufficiently studied. The study of compensatory changes that occur in physically inactive obese patients remains relevant, especially against the background of neoadjuvant chemotherapy, in the conditions of preoperative preparation with ERAS-recommended physical activity.&#x0D; The aim of the study is to determine the differences between women with advanced ovarian cancer and obesity compared to women with normal weight in terms of heart rate variability during exercise. To assess the adaptive capabilities to physical activity of patients with advanced ovarian cancer and obesity at the stage of preoperative preparation, who undergoing debulking surgery.&#x0D; Result. Achieved METs, peak HR, CI, and HR recovery were higher in nonobese women, whereas training had no significant effect in obese women. Women who had already received neoadjuvant CT achieved a lower level of MET (6.8 ± 3.2 vs. 8.9 ± 4.1; P &lt; 0.001). Also, peak HR and CI were lower in women after neoadjuvant CT (126±27 vs. 138±20; P = 0.001 and 0.65±0.22 vs. 0.71±0.22; P = 0.001, respectively). BMI was a significant predictor of exercise capacity only in the obese subgroup, whereas age, peak HR, and prior adjuvant HT were always significantly associated with METs achieved.&#x0D; Conclusions. No significant difference was found between trained and untrained women with comorbid obesity in HR behavior or physical capacity. Different heart rate behavior in patients of this group is thus explained by obesity as such, regardless of the degree of physical training.

Immune-related visual dysfunction in thyroid eye disease: a combined orbital and brain neuroimaging study.

To investigate the pathological interplay between immunity and the visual processing system (VPS) in thyroid eye disease (TED). A total of 24 active patients (AP), 26 inactive patients (IP) of TED, and 27 healthy controls (HCs) were enrolled. Orbital magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were conducted for each participant. Multiple MRI parameters of the intraorbital optic nerve (ON) were assessed. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated. Correlation analyses were carried out on the above parameters and clinical characteristics. Visual functioning scores differentiated between the AP and IP groups. The ON subarachnoid space and ON sheath diameter were significantly higher in AP than in IP. Six vision-related brain regions were identified in TED patients compared with HCs, including right calcarine (CAL.R), right cuneus (CUN.R), left postcentral gyrus (PoCG.L), right middle temporal gyrus (MTG.R), left superior frontal gyrus (SFG.L), and left caudate (CAU.L). The brain activity of MTG.R, SFG.L, and CAU.L differentiated between the AP and IP groups. The correlation analysis revealed a close association among the vision-related brain regions, MRI parameters of ON, and clinical characteristics in AP and IP, respectively. Combined orbital and brain neuroimaging revealed abnormalities of the VPS in TED, which had a close correlation with immune statuses. Vision-related brain regions in TED might be possibly altered by peripheral immunity via a direct or indirect approach. The discovery of this study explained the disparity of visual dysfunction in TED patients with different immune statuses. With the uncovered neuroimaging markers, early detection and intervention of visual dysfunction could be achieved and potentially benefit TED patients. • Patients with different immune statuses of thyroid eye disease varied in the presentation of visual dysfunction. • The combined orbital and brain neuroimaging study identified six altered vision-related brain regions, which had a significant correlation with the MRI parameters of the intraorbital optic nerve and immunological characteristics. • Peripheral immunity might possibly give rise to alterations in the central nervous system part of the visual processing system via a direct or indirect approach.

Phagocytic cell death leads to enhanced release of pro-inflammatory S100A12 in familial Mediterranean fever

BackgroundFamilial Mediterranean fever (FMF) is a prototypical autoinflammatory syndrome associated with phagocytic cell activation. Pyrin mutations are the genetic basis of this disease, and its expression has been shown in monocytes, granulocytes, dendritic cells, and synovial fibroblasts. Pyrin functions as a cytosolic pattern recognition receptor and forms a distinct pyrin inflammasome. The phagocyte-specific protein S100A12 is predominantly expressed in granulocytes and belongs to the group of damage associated molecular patterns (DAMP). S100A12 can be detected at massively elevated levels in the serum of FMF patients, even in clinically inactive disease. Whether this is crucial for FMF pathogenesis is as yet unknown, and we therefore investigated the mechanisms of S100A12 release from granulocytes of FMF patients presenting clinically inactive.ResultsWe demonstrate that FMF neutrophils from patients in clinical inactive disease possess an intrinsic activity leading to cell death even in exogenously unstimulated neutrophils. Cell death resembles NETosis and is dependent on ROS and pore forming protein gasdermin D (GSDMD), as inhibitors for both are capable of completely block cell death and S100A12 release. When pyrin-activator TcdA (Clostridium difficile toxin A) is used to stimulate, neutrophilic cell death and S100A12 release are significantly enhanced in neutrophils from FMF patients compared to neutrophils from HC.ConclusionsWe are able to demonstrate that activation threshold of neutrophils from inactive FMF patients is decreased, most likely by pre-activated pyrin. FMF neutrophils present with intrinsically higher ROS production, when cultured ex vivo. This higher baseline ROS activity leads to increased GSDMD cleavage and subsequent release of, e.g., S100A12, and to increased cell death with features of NETosis and pyroptosis. We show for the first time that cell death pathways in neutrophils of inactive FMF patients are easily triggered and lead to ROS- and GSDMD-dependent activation mechanisms and possibly pathology. This could be therapeutically addressed by blocking ROS or GSDMD cleavage to decrease inflammatory outbreaks when becoming highly active.

Association of soluble triggering receptor expressed on myeloid cells-1 with rheumatoid arthritis in Iraqi patients: A case-control study.

Rheumatoid arthritis (RA) is a common chronic immune-mediated inflammatory arthritis, impacting 0.5-1% of the global population, and leading to progressive deterioration of the musculoskeletal and joint systems. This study aims to analyze the serum levels of soluble triggering receptors expressed on myeloid cells-1 (sTREM-1) in Iraqi patients with RA and healthy individuals. It also intends to assess the diagnostic significance of these receptors, investigate their association with disease activity and examine their correlation with the sociodemographic and clinical characteristics of the patients. From December 2020 to June 2021, 117 RA patients with a mean age of 50 years participated in the study. The patients were categorized into inactive and active disease groups based on their DAS28 score and CDAI, as determined by a Rheumatologist. The serum levels of a specific triggering receptor expressed on myeloid cells-1 (TREM-1) (Pg/mL) were measured. The results showed that the active RA patients had significantly higher levels of the receptor (270.17±187) compared to both the inactive RA patients (112.81±37.48) and the healthy controls (43.89±29.53) (P < 0.001). The sTREM-1 demonstrated a high discriminatory ability (AUC ≥ 0.936) between RA and control groups. Moreover, a direct association was observed between the DAS-28ESR and sTREM-1 levels.

Clinical utility of serum Galactin-9 in evaluation of systemic lupus erythematosus patients

Aim of the workTo evaluate the levels of serum Galactin-9 (Gal-9) in systemic lupus erythematosus (SLE) patients and to assess its association with disease activity, severity, and renal affection. Patients and methodsThe study included 50 SLE patients and 50 matched controls. SLE disease activity index (SLEDAI) was assessed and patients subdivided into active (SLEDAI > 4) and inactive (SLEDAI ≤ 4). Renal affection in SLE patients was assessed by rSLEDAI. Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR-DI) was assessed.Serum Gal-9 levels were measuredby Enzyme-Linked Immunosorbent Assay (ELISA). ResultsThe mean age of SLE patients was 31.1 ± 8.7 years and the majority of studied groups were females. Gal-9 was significantly higher in SLE patients in comparison to healthy control (890.1 ± 1740.4 vs. 266.8 ± 37.9 ng/L); p < 0.0001) and in active compared to inactive LN patients (1377.9 ± 2273.8 vs. 317.6 ± 40.4, P < 0.001) was detected. Serum Gal-9 correlated with anti-dsDNA positivity (r = 0.29, p = 0.04), SLEDAI (r = 0.61, p ≤ 0.0001), and rSLEDAI (r = 0.61, p ≤ 0.0001). At a cut-off value of 299 ng/l Gal-9 can significantly differentiate SLE patients from controls (AUC 0.97; p < 0.0001) at a sensitivity of 88 %, specificity of 75 %, and accuracy of 83.3 %. Gal-9 at a cut-off value 335 ng/l can significantly differentiate active from inactive SLE patients (AUC 0.94; p < 0.0001) at a sensitivity of 90 %, specificity of 84.2 %, and accuracy of 88 %. Gal-9 was significant predictor for SLE activity. ConclusionThe serum Gal-9 levels were significantly high in SLE patients compared to healthy controls and these high levels were associated with disease activityand renal affection in SLE patients.

Effects of Physical Activity, Vascular Burden and Clinical Diagnosis on White Matter Integrity

AbstractBackgroundAlzheimer’s disease (AD) is the most common type of dementia. Both degenerative and vascular pathology tend to contribute to dementia as AD coexists with single or multiple cardiovascular risk factors (vascular burden). Modifiable lifestyle factor such as physical activity has been associated with lower vascular burden (VB) and a lower risk of dementia. To test whether physical activity characterised as being inactive or active helped preserve white matter microstructure in a sample consisting of healthy controls and patients from the clinical AD continuum (mild cognitive impairment to dementia) with either low or high VB.Method213 participants were recruited from three memory clinics and were classified as being either physically active (n = 113) or inactive (n = 100) based on the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) questionnaire. Voxel‐wise tract‐based spatial statistics (TBSS) was carried out using a set of 5000 permutations and threshold‐free cluster enhancement (TFCE) to find significant clusters for fractional anisotropy (FA), axial diffusivity (AxD), mean diffusivity (MD) and radial diffusivity (RD).ResultParticipants who were physically active had higher FA and lower AxD, MD and RD values relative to the inactive participants. Changes in indices of WM integrity were widespread across the brain covering mainly association and projection tracts but a few commissural tracts. A three‐way interaction effect between Group × Physical Activity × VB was found for FA that was present in mainly projection tracts with a rightward asymmetry along with some association and commissural tracts. Post hocs revealed greater FA in physically active patients with high VB compared with inactive patients with high VB in projection and association/limbic tracts with a rightward asymmetry. Furthermore, the patients with high VB showed higher FA in bilateral projection fibers and cerebellar regions compared with inactive controls with high VB.ConclusionTBSS analysis revealed that high risk patients such as those with high VB achieved the maximum benefit by being physically active as it led to a much greater preservation of white microstructure relative to controls with high VB. This preservation of white matter microstructure was only observed in patients but not in controls.

Fecal miR-223 is a noninvasive biomarker for estimating Crohn's disease activity.

MicroRNA-223 (miR-223) has emerged as a promising noninvasive biomarker for Crohn's disease (CD). However, it is unclear which tissue derived miRNA-223 can more accurately estimate CD disease activity. To collect serum, terminal ileal mucosa biopsy and fecal samples from CD patients and healthy controls. The CD Activity Index (CDAI) score, Montreal classification, maintenance medicines, peripheral blood inflammatory markers, fecal calprotectin (FC) and the Simple Endoscopic Score for CD (SES-CD) were recorded. To compare the expression of miR-223 in the serum, intestinal tissue, and feces. MiR-223 expression levels in the serum, intestinal tissue and feces of CD patients were significantly higher than those of controls. The level of miR-223 in the serum, intestinal tissue and feces increased significantly in active CD patients compared with that in inactive CD patients. The levels of serum, intestinal tissue and fecal miR-223 were correlated with the CDAI. Serum miR-223 was also correlated with C-reactive protein (CRP) and IL-6, tissue miR-223 correlated with IL-6 and FC, and fecal miR-223 correlated with FC. In terms of the association with FC, fecal miR-223 had a higher Spearman r value than tissue miR-223. The area under the curve (AUC) values of serum, tissue and fecal miR-223 to diagnose CD were similar to those of CRP and FC (AUC > 0.8). The AUC values of tissue and fecal miR-223 to evaluate CD disease activity were 0.832 and 0.818, respectively, and were higher than serum miR-223, CRP and FC. Fecal miR-223 had a higher specificity of 92.3%. Fecal miR-223 might be a novel, noninvasive biomarker for estimating the disease activity of CD patients.

IL-2 produced by HBV-specific T cells as a biomarker of viral control and predictor of response to PD-1 therapy across clinical phases of chronic hepatitis B.

There are no immunological biomarkers that predict control of chronic hepatitis B (CHB). The lack of immune biomarkers raises concerns for therapies targeting PD-1/PD-L1 because they have the potential for immune-related adverse events. Defining specific immune functions associated with control of HBV replication could identify patients likely to respond to anti-PD-1/PD-L1 therapies and achieve a durable functional cure. We enrolled immunotolerant, HBeAg+ immune-active (IA+), HBeAg- immune-active (IA-), inactive carriers, and functionally cured patients to test ex vivo PD-1 blockade on HBV-specific T cell functionality. Peripheral blood mononuclear cells were stimulated with overlapping peptides covering HBV proteins +/-α-PD-1 blockade. Functional T cells were measured using a 2-color FluoroSpot assay for interferon-γ and IL-2. Ex vivo functional restoration was compared to the interferon response capacity assay, which predicts overall survival in cancer patients receiving checkpoint inhibitors. Ex vivo interferon-γ+ responses did not differ across clinical phases. IL-2+ responses were significantly higher in patients with better viral control and preferentially restored with PD-1 blockade. Inactive carrier patients displayed the greatest increase in IL-2 production, which was dominated by CD4 T cell and response to the HBcAg. The interferon response capacity assay significantly correlated with the degree of HBV-specific T cell restoration. IL-2 production was associated with better HBV control and superior to interferon-γ as a marker of T cell restoration following ex vivo PD-1 blockade. Our study suggests that responsiveness to ex vivo PD-1 blockade, or the interferon response capacity assay, may support stratification for α-PD-1 therapies.

Evaluation of Serum Visfatin as a Biomarker of Lupus Nephritis in Egyptian Patients with Systemic Lupus Erythematosus.

One of the most significant consequences of systemic lupus erythematosus (SLE) is lupus nephritis (LN). Visfatin, an adipokine that is significantly expressed in visceral fat and is a marker of endothelial dysfunction in chronic kidney disease, has multiple proinflammatory actions. We aimed to evaluate the state of serum visfatin in SLE patients and to detect its possible correlation with the disease's activity and effects on the kidney affection. Fifty patients with active LN, 50 patients with inactive lupus, and 50 healthy people had their serum visfatin levels tested. Chemical and immunological markers of SLE and LN were measured. The SLE Disease Activity Index (SLEDAI) was used to measure the disease's activity. Renal biopsies from the LN subgroup were collected and classified using the modified classification of the World Health Organization. The serum visfatin of patients with active LN was significantly greater than that of inactive lupus patients and the healthy controls (20.56 ± 1.07 ng/mL, 16.77 ± 1.02 ng/mL, and 9.96 ± 1.46 ng/mL, P <0.001). SLEDAI and serum visfatin levels were shown to be significantly correlated (P = 0.000057). Serum visfatin levels were likewise significantly correlated with the index of histological activity in the active group (P <0.00001). Serum visfatin was raised in individuals with active LN and was related to the SLEDAI and disease severity scores. Serum visfatin could be utilized as a noninvasive biomarker for evaluating the severity of LN and risk stratification of the risk.

Relationship between bilirubin and systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high prevalence worldwide. This study aimed to examine the correlation between serum bilirubin levels and SLE. The Cochrane library, Embase, PubMed, and China National Knowledge Infrastructure (CNKI) databases were examined and assessed until March 2023. RevMan 5.3 software was utilized for the analysis of clinical trails. Five case-control studies were chosen and incorporated, examining the levels of serum bilirubin in patients with SLE compared to healthy individuals, as well as in active SLE patients versus inactive ones, in different sexes and in SLE patients with or without lupus nephritis (LN). The results of this meta-analysis demonstrated that serum bilirubin in healthy individuals were obviously increased compared to SLE patients (MD = 4.76; 95% CI, 3.15-6.38, p < .00001). Additionally, inactive SLE patients had higher levels of bilirubin than active SLE patients (MD = 3.15; 95% CI, 0.46-5.84, p = .02), and SLE patients without lupus nephritis had higher levels of serum bilirubin than those with lupus nephritis (MD = 4.91;95% CI, 2.87-6.95, p < .00001). Nevertheless, there were no disparities observed among SLE patients of varying sexes (MD = 0.34; 95% CI, -0.01 to 0.69, p = .06). The concentration of serum bilirubin may potentially be used as an indicator for estimating the advancement of SLE and reflecting the presence of kidney complications in individuals with SLE. Furthermore, more high quality studies were needed to identify these findings.

Depression- and anxiety-associated disrupted brain structural networks revealed by probabilistic tractography in thyroid associated ophthalmopathy

BackgroundPatients with thyroid-associated opthalmopathy (TAO) have widespread white matter (WM) abnormalities in the emotional and cognitive functional regions. However, the topological representation of these WM abnormalities and the network-level structural aberrations underlying TAO and concomitant affective disorders are still unclear. MethodsWe used probabilistic diffusion tractography and graph theory to investigate brain network topology in 37 active, 35 inactive TAO patients and 23 healthy controls. Then, we evaluated the partial correlations between network topological metrics and clinical parameters. ResultsFor global topology, only active TAO patients exhibited significantly decreased global (Eglob) and local (Eloc) efficiency compared with controls, while no significant difference was observed between active and inactive TAO patients. For regional topology, we found a significantly decreased nodal efficiency in the left orbital superior frontal gyrus (ORBsup), medial orbital superior frontal gyrus (ORBsupmed), hippocampus and amygdala in active TAO patients compared with inactive ones. Intriguingly, Eglob, Eloc, and nodal efficiency of left ORBsup, ORBsupmed, olfactory cortex, gyrus rectus, hippocampus, right parahippocampal gyrus and amygdala had significantly positive correlations with anxiety/depression scores, bilateral exophthalmos and intraocular pressure in active TAO patients, while no significant correlation was observed in inactive TAO patients. LimitationsNo longitudinal follow-up. ConclusionsWM networks of TAO are characterized by decreased local specialization and global integration in the active phase, and decreased nodal efficiency highly related to anxiety and depression in the emotional and cognitive regions. Our findings provide new insight regarding the neurobiological mechanisms of TAO and contribute to the treatment of concomitant affective disorders.

The Association between Levels of Physical Activity and Lifestyle, Life Expectancy, and Quality of Life in Patients with Alzheimer’s Disease

Background: Engaging in physical activity could help improve the quality of life in patients with Alzheimer’s disease. The objective of this study was to determine the association between the levels of physical activity and lifestyle, life expectancy, and quality of life in patients with Alzheimer’s disease in Iran and Italy. Methods: A total of 165 participants from Iran and Italy were enrolled in this cross-sectional study. In Iran, 85 patients participated in the study. In Italy, we enrolled 80 patients at the Sapienza University teaching hospital, Policlinico Umberto 1 in Rome. The inclusion criteria in this study include patients over 60 years old, non-smokers, and non-users of antidepressants and hypnotics. Results: The results of Tukey’s post hoc test of the study conducted in Iran showed that the lifestyle of patients with moderate (p = 0.001) and low (p = 0.009) physical activity levels was significantly better than inactive patients. Life expectancy in patients with moderate physical activity levels was significantly higher than inactive patients (p = 0.011). The quality of life was significantly better in patients with moderate (p = 0.001) and low (p = 0.002) physical activity levels than inactive patients. On the other hand, the findings of Tukey’s post hoc test of the study in Italy showed that the quality of life in patients with low (p = 0.001) and moderate physical activity levels (p = 0.01) was significantly higher than inactive patients. Conclusions: A low to moderate level of physical activity could be associated with an improved lifestyle, life expectancy, and quality of life in patients with Alzheimer’s disease compared to inactivity.