Inflammation Score Research Articles

Head-to-head comparison of composite and individual biomarkers to predict clinical benefit to PD-1 blockade in non-small cell lung cancer.

The efficacy of PD-1 blocking agents in advanced NSCLC has shown prolonged effectiveness, but only in a minority of patients. Multiple biomarkers have been explored to predict treatment benefit, yet their combined performance remains inadequately examined. In this study, we assessed the combined predictive performance of multiple biomarkers in NSCLC patients treated with nivolumab. Pretreatment samples from 135 patients receiving nivolumab were used to evaluate the predictive performance of CD8 tumor-infiltrating lymphocytes (TILs), intratumoral (IT) localization of CD8 TILs, PD-1 high expressing TILs (PD1T TILs), CD3 TILs, CD20 B-cells, tertiary lymphoid structures (TLS), PD-L1 tumor proportion score (TPS) and the Tumor Inflammation score (TIS). Patients were randomly assigned to a training (n = 55) and validation cohort (n = 80). The primary outcome measure was Disease Control at 6 months (DC 6m) and the secondary outcome measure was DC at 12 months (DC 12m). In the validation cohort, the two best performing composite biomarkers (i.e. CD8+IT-CD8 and CD3+IT-CD8) demonstrated similar or lower sensitivity (64% and 83%) and NPV (76% and 85%) compared to individual biomarkers PD-1T TILs and TIS (sensitivity: 72% and 83%, NPV: 86% and 84%) for DC 6m, respectively. Additionally, at 12 months, both selected composite biomarkers (CD8+IT-CD8 and CD8+TIS) demonstrated inferior predictive performance compared to PD-1T TILs and TIS alone. PD-1T TILs and TIS showed high sensitivity (86% and 100%) and NPV (95% and 100%) for DC 12m. PD-1T TILs could more accurately discriminate patients with no long-term benefit, as specificity was substantially higher compared to TIS (74% versus 39%). Composite biomarkers did not show improved predictive performance compared to PD-1T TILs and TIS alone for both the 6- and 12-month endpoints. PD-1T TILs and TIS identified patients with DC 12m with high sensitivity. Patients with no long-term benefit to PD-1 blockade were most accurately identified by PD-1T TILs.

Comparison of Protein Energy Wasting Assessment on Quality of Life Regular Hemodialysis Patients

Background. Protein energy wasting (PEW) is one of several markers of the quality of hemodialysis (HD) services in Indonesia, however not many studies conducted PEW assessement with quality of life (QoL) domain of regular HD patients. Aim: To determine comparison of PEW assessment with QoL domains in regular HD patients. Method: A Cross-sectional study with total sampling of 105 regular HD patients at Sanjiwani Gianyar General Hospital, on June to July 2022, The PEW assessments: body mass index (BMI), serum albumin, subjective global assessment (SGA), malnutrition inflammation score (MIS), and the International Society of Renal Nutrition and Malnutrition (ISRNM) with QoL domains by KDQOL-SF (Kidney Disease Quality of Life Short Form). Results. Most of the subjects were men (54.2%), the mean age was51.66 years and mean duration of HD was 50.28 months. The mean of BMI, serum creatinine, and serum albumin were 23.46 kg/m2, 9.70 mg/dL, and 3.86 mg/dL respectively, and median MIS 5. This study obtained significant correlation of BMI and QoL domains: work status, physical functioning, role of physics, energy/fatigue, and SF 12 physical composite. The MIS also significantly correlated with emotional well-being, sleep, and burden of disease. And ISRNM significantly correlated with energy/fatigue, and sexual function, On logistic regression analysis, this study obtained that albumin was significantly related to general health, emotional well-being, and energy/fatigue, Conclusion: Assessment of PEW (BMI, serum albumin, MIS, SGA, and ISRNM ) were related to several domains of QoL.

Exploring the Analgesic Efficacy and mechanisms of low-dose esketamine in pregnant women undergoing cesarean section: A randomized controlled trial

BackgroundPostoperative pain is a prevalent concern following a cesarean section. This study aimed to investigate the effect and mechanism of low-dose (0.1 mg/kg) esketamine on postoperative pain management in pregnant women undergoing cesarean sections, specifically in cases where both patient-controlled intravenous analgesia (PCIA) and patient-controlled epidural analgesia (PCEA) were employed. MethodsPregnant women intending to undergo elective cesarean section were divided into four subgroups based on the intravenous administration of esketamine and the specific analgesia methods employed: E1 (0.1 mg/kg esketamine + PCEA), E2 (0.1 mg/kg esketamine + PCIA), C1 (saline + PCEA), and C2 (saline + PCIA). The primary outcome was the maximum pain score within 24 h postoperatively. Secondary outcomes included the pressure pain threshold and tolerance at 30 min and 24 h postoperatively, along with the inflammation and adverse event index scores. ResultsA total of 118 pregnant women were assigned to the four groups: E1 (n = 29), E2 (n = 29), C1 (n = 30), and C2 (n = 30). Compared with those in the control groups (C1 + C2), the maximum postoperative pain scores within 24 h in the esketamine groups (E1 + E2) were significantly lower (4 [2–5] vs. 4 [4–6], P = 0.002), and the E1 group exhibited superior analgesic effects compared with other groups. No significant differences were observed in postoperative hyperalgesia or inflammation across the four groups. Notably, esketamine combined with PCIA increased the incidence of postoperative nausea and vomiting (7 [25 %] vs. 0 [0 %]; P = 0.005). ConclusionThe administration of low-dose (0.1 mg/kg) esketamine effectively alleviates pain following cesarean section, and the analgesic effect is notably enhanced in combination with PCEA. Importantly, these effects do not appear to be mediated through anti-inflammatory mechanisms or the inhibition of hyperalgesia. Clinical trial registration numberNCT05414006.

Serum SIRT3 levels in epilepsy patients and its association with clinical outcomes and severity: A prospective observational study.

In this prospective observational study, we aimed to investigate the serum levels of sirtuin (SIRT)3 in epilepsy patients and its association with the severity of the disease. This prospective observational study included 203 patients with symptomatic epilepsy and 100 healthy controls who visited our hospital from November 2019 to November 2022. The severity of the disease in epilepsy patients was assessed using the National Hospital Seizure Severity Scale (NHS3). We used enzyme-linked immunosorbent assay to measure the serum levels of SIRT3, interleukin (IL)-6, IL-1β, tumor necrosis factor-alpha, and C-reactive protein in all patients. In addition, the cognitive function of all study participants was evaluated using the Mini-Mental State Examination and the Montreal Cognitive Assessment (MOCA). All data were analyzed using SPSS 25.0 software. The MOCA scores of the epilepsy patients were significantly lower compared to the healthy volunteers (P < 0.05). The serum SIRT3 levels were decreased significantly in patients with refractory epilepsy (183.16 ± 17.22 pg/mL) compared to non-refractory epilepsy patients (199.00 ± 18.68 pg/mL). In addition, serum SIRT3 levels were negatively correlated with the inflammatory factors IL-6 (Pearson's correlation -0.221, P = 0.002) and NHS score (Pearson's correlation -0.272, P < 0.001) of epilepsy patients, while positively correlated with MOCA scores (Pearson's correlation 0.166, P = 0.018). Furthermore, the receiver operating characteristic curve demonstrated that serum SIRT3 could be used to diagnose epilepsy, as well as refractory epilepsy. Finally, logistic regression analysis showed that SIRT3 (OR = 1.028, 95%CI: 1.003-1.054, P = 0.028), IL-6 (OR = 0.666, 95%CI: 0.554-0.800, P < 0.001), IL-1β (OR = 0.750, 95%CI: 0.630-0.894, P = 0.001), and NHS3 (OR = 0.555, 95%CI: 0.435-0.706, P < 0.001) were risk factors for refractory epilepsy. In conclusion, our findings demonstrated that serum SIRT3 levels were significantly decreased in epilepsy patients and further decreased in patients with refractory epilepsy. This study might provide new therapeutic targets and comprehensive treatment strategies for epilepsy patients.

Hematological indices: potential markers of disease activity in ankylosing spondylitis patients treated with biological drugs

BackgroundSome important hematological indices implement acute phase reactions. They can be used to assess disease activity and therapeutic response in many inflammatory conditions. This work aimed to determine whether different hematological indices can be used to assess disease activity and therapeutic response in patients with ankylosing spondylitis (AS) on biological drugs.Patients and methodsNinety-seven AS patients and a similar number of controls were involved in the current study. The Ankylosing Spondylitis Disease Activity Score (ASDAS) was used to assess the disease activity. Different complete blood count parameters and indices were assessed.ResultsThere was a significant difference between the patients and controls as regards mean corpuscular volume, mean corpuscular hemoglobin, red blood cells count, red cell distribution width, mean platelet volume, platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Moreover, there was a statistical correlation between ASDAS on one side and hemoglobin (Hb), hematocrit (HTC), lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), PLR, and SII on the other side. When the patient group was divided into 2 subgroups according to ASDAS, with patients with inactive and low disease activity in one subgroup and those with very high and high disease activity in another subgroup, there was a significant difference as regards Hb, HTC, mean corpuscular hemoglobin concentration, NLR, PLR, SII, and also ESR and CRP levels. Moreover, there was a significant correlation between PLR and SII levels on one side and ESR on the other side.ConclusionHematological indices such as PLR, NLR, and SII might be potential markers for follow-up of disease activity and therapeutic response in AS patients treated with biological therapy. This emphasizes the significance of a comprehensive approach for AS patient assessment and follow-up of therapeutic drugs, considering inflammatory markers, hematological indices, and disease activity scores.

Childhood Nutritional Factors and Cardiometabolic Outcomes at 9–11 y of Age: Findings from the ROLO Longitudinal Birth Cohort Study

BackgroundChildhood represents a critical period of nutritional risk in the programming of later chronic disease. Few longitudinal studies have explored repeated measures of nutrition throughout the first decade of life in relation to preteen cardiometabolic outcomes. ObjectivesThis research aimed to explore associations of early feeding practices (human milk exposure and duration and timing of introduction to solids) and childhood dietary quality and inflammatory scores (at 5 and 9–11 y and change during childhood) on preteen cardiometabolic outcomes. MethodsThis is an analysis of children from the ROLO longitudinal birth cohort study (n = 399). Information on early feeding practices were obtained at postnatal study visits. Food frequency questionnaires collected maternal-reported dietary intakes for each child at 5 and 9–11 y of age. Healthy Eating Index (HEI)-2015 and the Children’s Dietary Inflammatory Index (C-DII) scores were calculated. Anthropometry, body composition, blood pressure, heart rate, cardiorespiratory endurance, and blood biomarkers were obtained at 9–11 y. Crude and adjusted linear regression models examined nutritional exposure associations with preteen cardiometabolic outcomes. ResultsIn the adjusted model, any human milk exposure was associated with lower body fat (%) at 9–11 y (β: −2.86; 95% confidence interval [CI]: −5.46, −0.27; P = 0.03), than never receiving human milk. At 5 y, diet scores were favorably associated with lean mass at 9–11 y (P < 0.05 for both). Higher preteen HEI-2015 scores were associated with lower preteen leptin levels (tertile 3 compared with tertile 1—β: −2.92; 95% CI: −5.64, −0.21; P = 0.03). Diet quality significantly deteriorated (HEI-2015 score decreased) and became more proinflammatory (C-DII score increased) from 5 to 9–11 y of age. Diet quality/inflammation deterioration (compared with improvement) or overall change in dietary scores were not related to preteen cardiometabolic outcomes. ConclusionsExposure to human milk in early life was associated with lower preteen adiposity, irrespective of duration. Diet quality/inflammatory potential deteriorated between early childhood and the preteen years, highlighting a potential period for intervention.

Dietary and lifestyle inflammation scores in relation to colorectal cancer recurrence and all-cause mortality: A longitudinal analysis

Aim.The aim of this study was to longitudinally investigate dietary and lifestyle inflammation scores and their interaction in relation to risk of colorectal cancer (CRC) recurrence and all-cause mortality. MethodsData of two prospective cohort studies among CRC survivors was used. Information about diet and/or lifestyle was available for 2739 individuals for at least one of the following time points: at diagnosis, six months after diagnosis and two years after diagnosis. The dietary and lifestyle inflammation scores (DIS and LIS) were used to evaluate the inflammatory potential of diet and lifestyle. Joint modelling, combining mixed models and Cox proportional hazards regression, were used to assess associations between DIS and LIS over time and CRC recurrence and all-cause mortality. Interactions between DIS and LIS were assessed using time-dependent Cox proportional hazard regression. ResultsThe median follow-up time was 4.8 (IQR 2.9-6.9) years for recurrence and 5.7 (IQR 3.5-8.5) years for all-cause mortality, with 363 and 453 events, respectively. A higher DIS as well as LIS was associated with a higher risk of all-cause mortality (HRDIScontinuous 1.09 95%CI 1.02; 1.15; HRLIScontinuous 1.24 95%CI 1.05; 1.46). Individuals who were in the upper tertile of both DIS and LIS had the highest all-cause mortality risk (HR 1.62 95%CI 1.16; 2.28), compared to the individuals in the lowest tertile of both DIS and LIS. No consistent associations with recurrence were observed. ConclusionA more pro-inflammatory diet and lifestyle was associated with a higher risk of all-cause mortality, but not recurrence, in CRC survivors.

Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study.

The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort ( n = 79) by the propensity score matching method. The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

The Impact of Gardening on Dietary Inflammation: Mixed-Effect Models and Propensity Score Analyses

Gardening has been found to increase vegetable intake and reduce BMI; this suggests that it may improve diets by lowering inflammatory content. The goal of this study goal was to evaluate the effect of gardening on Dietary Inflammatory Index scores. Longitudinal data were collected annually between 2015 and 2018 from adults in low-income, urban neighborhoods of Cleveland and Columbus, Ohio. The authors measured the association between gardening and Dietary Inflammatory Index in the full data set using multivariable mixed-effect models with a random intercept for participant (Model 1; n=409). To further explore potential causation, the author used propensity score analyses in a subset of the data by building a 1-to-1 matched model (Model 2; n=339). Of 409 adults, 30.3% were gardeners with Dietary Inflammatory Index scores ranging from -6.228 to +6.225. Participating in gardening was associated with lower Dietary Inflammatory Index scores in the mixed-effects model (-0.45; 95% CI= -0.85, -0.04; Model 1) and the 1-to-1 matched model (-0.77; 95% CI= -1.40, -0.14; Model 2). The analyses indicate that gardeners had lower Dietary Inflammatory Index scores than nongardeners, implying lower diet-driven inflammation. These findings highlight the potential for a causal relationship between gardening and Dietary Inflammatory Index, which should be confirmed in future studies. If this relationship is validated, strategies to increase gardening may be worth testing as primary prevention tools for diet-driven chronic disease.

Associations of dietary inflammatory index scores and serum inflammatory factors with the risk of osteoporosis: a cross-sectional study from Xinjiang, China

BackgroundPrevious studies have shown that the inflammatory potential of the diet is associated with a variety of chronic noncommunicable diseases characterized by a chronic low-grade inflammatory response. However, the relationships between dietary inflammatory potential and organismal inflammatory status and osteoporosis have been less studied. This study aimed to investigate the relationships among inflammatory diet, inflammatory state and osteoporosis in the Xinjiang multiethnic population.MethodsThe participants consisted of 4452 adults aged 35 to 74 years from Xinjiang, China. The dietary inflammatory index (DII) was calculated using dietary data collected with a semiquantitative food frequency questionnaire, and information about osteoporosis was derived from quantitative ultrasound measurements. The relationships of the DII score and inflammatory factors with the risk of osteoporosis were analysed using multivariate logistic regression, and the nonlinear associations between DII and osteoporosis were further analysed using restricted cubic splines.ResultsThe results showed that proinflammatory diets were associated with a greater risk of osteoporosis (T3 vs. T1: OR = 1.87; 95% CI = 1.44, 2.45) and that there was no nonlinear relationship between the DII and the risk of osteoporosis. Increased concentrations of the inflammatory factors IL-6, IL-10, IL-12p70, IL-17, and IL-23 were associated with a greater risk of osteoporosis.ConclusionsThe risk of osteoporosis can be reduced by increasing the consumption of an appropriate anti-inflammatory diet.

Prognostic Value of Inflammation Scores and Hematological Indices in IgA and Membranous Nephropathies: An Exploratory Study.

Background and Objectives: Systemic-inflammation-based prognostic scores and hematological indices have shown value in predicting outcomes in various clinical settings. However, their effectiveness in predicting outcomes specifically for IgA nephropathy (IgAN) and membranous nephropathy (MN), the most common primary glomerular diseases diagnosed by kidney biopsy, has not been thoroughly investigated. Materials and Methods: We conducted a retrospective, observational study involving 334 adult patients with biopsy-proven IgAN (196 patients) and MN (138 patients) from January 2008 to December 2017 at a tertiary center. We assessed six prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-C-reactive protein ratio (LCRP)] and two hematological indices [red blood cell distribution width (RDW), platelet distribution width (PDW)] at diagnosis and examined their relationship with kidney and patient survival. Results: End-stage kidney disease (ESKD) occurred more frequently in the IgAN group compared to the MN group (37% vs. 12%, p = 0.001). The mean kidney survival time was 10.7 years in the IgAN cohort and 13.8 years in the MN cohort. After adjusting for eGFR and proteinuria, lower NLR and higher LCRP were significant risk factors for ESKD in IgAN. In the MN cohort, no systemic-inflammation-based scores or hematological indices were associated with kidney survival. There were 38 deaths (19%) in the IgAN group and 29 deaths (21%) in the MN group, showing no significant difference in mortality rates. The mean survival time was 13.4 years for the IgAN group and 12.7 years for the MN group. In the IgAN group, a lower PLR was associated with a higher mortality after adjusting for age, the Charlson comorbidity score, eGFR, and proteinuria. In patients with MN, higher NLR, PLR, and RDW were associated with increased mortality. Conclusions: NLR and LCRP are significant predictors of ESKD in IgAN, while PLR is linked to increased mortality. In MN, NLR, PLR, and RDW are predictors of mortality but not kidney survival. These findings underscore the need for disease-specific biomarkers and indicate that systemic inflammatory responses play varying roles in the progression and outcomes of these glomerular diseases. Future studies on larger cohorts are necessary to validate these markers.

Exploring the Therapeutic Potential of Green-Synthesized Gold Nanoparticles and Ericaria selaginoides Extract for Inflammatory Bowel Disease.

Addressing disease remission and treatment adherence in inflammatory bowel diseases (IBDs), such as Crohn's disease, poses significant challenges due to underlying oxidative and inflammatory processes. Nanotechnology emerges as a promising avenue for enhancing therapeutic outcomes in IBD by optimizing drug bioactivity, reducing toxicity, and extending circulation time. Gold nanoparticles, known for their resistance to gastrointestinal pH and possessing antioxidant and anti-inflammatory properties, offer particular promise. They can be produced by green synthesis with seaweed Ericaria selaginoides (ES), itself associated with gastroprotective and anti-inflammatory activities. In a murine model of Crohn's disease induced with 8% acetic acid, pretreatment with dexamethasone (0.2 mL/30 g) or Au@ES (25 and 50 mg/kg) effectively mitigated inflammatory features. Notably, ES (50 mg/kg) and Au@ES (50 mg/kg) administration resulted in significant reductions in both macroscopic and microscopic inflammation scores compared to the disease control group. Furthermore, these treatments normalized inflammatory cytokine expression while safeguarding myenteric plexus glial cells. They also impeded neutrophil activation, leading to reduced myeloperoxidase activity and lipid peroxidation, coupled with increased glutathione levels. In conclusion, ES and Au@ES exhibit potent efficacy in counteracting inflammation and oxidation processes in an experimental Crohn's disease model, suggesting their potential as alternative therapeutic strategies for IBD.

Investıgatıon of the effects of treatment with enoxaparın sodıum and hyperbarıc oxygen therapy on the recovery of rats wıth achılles tendon rupture

PurposeIn this study, we aimed to investigate the effects of hyperbaric oxygen therapy and enoxaparin sodium, which are known to accelerate bone tissue healing as well as tendon and soft tissue healing, on the healing of Achilles tendon rupture.MethodsThirty-six rats were used in the present study. All rats were divided into groups of nine. The groups were the enoxaparin sodium group, enoxaparin sodium and hyperbaric oxygen group, hyperbaric oxygen group and control group. After 21 days, the process was completed, and the rats were sacrificed. Achilles tendon samples were evaluated histopathologically.ResultsThe groups were compared according to the results of statistical analysis based on the histopathological data. There was no significant difference between the groups in terms of acute inflammation (p = 0.785) or chronic inflammation (p = 0.827) scores, but there were significant differences in neovascularization (p = 0.009), proliferation (p < 0.001) and fibrosis (p = 0.006) scores.ConclusionOur study showed that the use of enoxaparin sodium and hyperbaric oxygen had a positive effect on the healing of the Achilles tendon. Based on these results, we believe that the use of enoxaparin sodium and hyperbaric oxygen therapy after Achilles tendon rupture will be beneficial for healing and preventing complications.

Chronic Low-Grade Inflammation and Brain Structure in the Middle-Aged and Elderly Adults.

Low-grade inflammation (LGI) mainly acted as the mediator of the association of obesity and inflammatory diet with numerous chronic diseases, including neuropsychiatric diseases. However, the evidence about the effect of LGI on brain structure is limited but important, especially in the context of accelerating aging. This study was then designed to close the gap, and we leveraged a total of 37,699 participants from the UK Biobank and utilized inflammation score (INFLA-score) to measure LGI. We built the longitudinal relationships of INFLA-score with brain imaging phenotypes using multiple linear regression models. We further analyzed the interactive effects of specific covariates. The results showed high level inflammation reduced the volumes of the subcortex and cortex, especially the globus pallidus (β [95% confidence interval] = -0.062 [-0.083, -0.041]), thalamus (-0.053 [-0.073, -0.033]), insula (-0.052 [-0.072, -0.032]), superior temporal gyrus (-0.049 [-0.069, -0.028]), lateral orbitofrontal cortex (-0.047 [-0.068, -0.027]), and others. Most significant effects were observed among urban residents. Furthermore, males and individuals with physical frailty were susceptive to the associations. The study provided potential insights into pathological changes during disease progression and might aid in the development of preventive and control targets in an age-friendly city to promote great health and well-being for sustainable development goals.

Joint Inflammation Correlates with Joint GPR30 Expression in Males and Hippocampal GPR30 Expression in Females in a Rat Model of Rheumatoid Arthritis.

It is not entirely clear how the interaction between joint inflammation and the central nervous system (CNS) response in rheumatoid arthritis (RA) works, and what pathophysiology underlies the sex differences in coexisting neuropsychiatric comorbidities. It is known that estrogen hormones reduce inflammation in RA and that this occurs mainly via the stimulation of G protein-coupled receptor-30 (GPR30), also known as G protein-coupled estrogen receptor (GPER) 1. However, changes in GPR30 expression and sex differences induced by local and systemic inflammation in RA are not yet known. Our aim was to reveal sex differences in the expression and association of joint GPR30 with local and systemic inflammation, clinical course and furthermore with hippocampal GPR30 expression during pristane-induced arthritis (PIA) in Dark Agouti (DA) rats, an animal model of RA. Furthermore, we demonstrated sex-specific differences in the association between joint and systemic inflammation and hippocampal microglia during PIA. Our results suggest sex-specific differences not only in the clinical course and serum levels of pro-inflammatory cytokines but also in the expression of GPR30. Female rats show greater synovial inflammation and greater damage to the articular cartilage compared to males during PIA attack. Male rats express higher levels of synovial and cartilaginous GPR30 than females during PIA, which correlates with a less severe clinical course. The correlation between synovial and cartilaginous GPR30 and joint inflammation scores (Krenn and Mankin) in male rats suggests that the more severe the joint inflammation, the higher the GPR30 expression. At the same time, there is no particular upregulation of hippocampal GPR30 in males. On the other hand, female rats express higher levels of neuroprotective GPR30 in the hippocampus than male rats at the basic level and during PIA attack. In addition, females have a higher number of Iba-1+ cells in the hippocampus during PIA attack that strongly correlates with the clinical score, serum levels of IL-17A, and Krenn and Mankin scores. These results suggest that male rats are better protected from inflammation in the joints and female rats are better protected from the inflammation in the hippocampus during a PIA attack, independently of microglia proliferation. However, in the remission phase, synovial GPR30 expression suddenly increases in female rats, as does hippocampal GPR30 expression in males. Further experiments with a longer remission period are needed to investigate the molecular background of these sex differences, as well as microglia phenotype profiling.

Inhibition of Cathepsin S in Autoimmune CD25KO Mouse Improves Sjögren Disease-Like Lacrimal Gland Pathology.

CD25KO mice are a model of Sjögren disease (SjD) driven by autoreactive T cells. Cathepsin S (CTSS) is a protease crucial for major histocompatibility complex class II presentation that primes T cells. We investigated if a diet containing CTSS inhibitor would improve autoimmune signs in CD25KO mice. Four-week female CD25KO mice were randomly chosen to receive chow containing a CTSS inhibitor (R05461111, 262.5 mg/kg chow) or standard chow for 4 weeks. Cornea sensitivity was measured. Inflammatory score was assessed in lacrimal gland (LG) histologic sections. Flow cytometry of LG and ocular draining lymph nodes (dLNs) investigated expression of Th1 and Th17 cells. Expression of inflammatory, T- and B-cell, and apoptotic markers in the LG were assessed with quantitative PCR. The life span of mice receiving CTSS inhibitor or standard chow was compared. CD4+ T cells from both groups were isolated from spleens and adoptively transferred into RAG1KO female recipients. Mice receiving CTSS inhibitor had better cornea sensitivity and improved LG inflammatory scores. There was a significant decrease in the frequency of CD4+ immune cells and a significant increase in the frequency of CD8+ immune cells in the dLNs of CTSS inhibitor mice. There was a significant decrease in Th1 and Th17 cells in CTSS inhibitor mice in both LGs and dLNs. Ifng, Ciita, and Casp8 mRNA in CTSS inhibitor mice decreased. Mice that received the CTSS inhibitor lived 30% longer. Adoptive transfer recipients with CTSS inhibitor-treated CD4+ T cells had improved cornea sensitivity and lower inflammation scores. Inhibiting CTSS could be a potential venue for the treatment of SjD in the eye and LG.

Association of dietary and lifestyle inflammation score (DLIS) with chronic migraine in women: a cross-sectional study

Due to more frequent and intense attacks, chronic migraine (CM) sufferers usually report more disability compared to patients with episodic migraine (EM). There is increasing evidence that points to inflammatory diet and lifestyle as a probable underlying cause of migraine. The present study investigated the association of dietary and lifestyle inflammation scores (DLIS) with the odds of CM in Iranian women. In the current study, 285 women with migraine enrolled. Migraine was diagnosed by a single neurologist based on the third edition of the International Classification of Headache Disorders (ICHD-III). The women were categorized into CM and EM groups based on their attack frequency per month. Adherence to the dietary inflammation score (DIS), Lifestyle Inflammatory Score (LIS), and DLIS (DIS + LIS) was assessed based on last year’s dietary intakes collected using a semi-quantitative food frequency questionnaire (FFQ). The Odds Ratio (OR) for CM across the DIS, LIS, and DLIS tertiles were assessed through logistic regression. Most of the participants were overweight or obese (74.4%). The percentage of women with CM was 40.7%. Women with CM had significantly higher DIS (P = 0.002) and DLIS (P = 0.04) than women with EM. There was a significant positive association between CM and DIS. Those in the third tertile of the DIS had almost two times higher chance of experiencing chronic migraine compared with those in the first tertile [OR = 2.02; 95% CI 1.06–3.82; P = 0.03]. the P-value for the trend also was significant (0.03). In terms of LIS and DLIS tertiles, no significant association was observed. Adherence to the more inflammatory diets was associated with higher chances of experiencing CM in women.

The clinical value of nutritional and inflammatory indicators in predicting pneumonia among patients with intracerebral hemorrhage

Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079–0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT < 6, an increase of 1 point in CONUT was associated with a 1.39 times higher risk of SAP. Similarly, our findings indicate that CONUT has the potential to predict the prognosis of patients with ICH. Among the inflammatory and nutritional markers, CONUT stands out as the most reliable predictor of SAP in patients with ICH. Additionally, it proves to be a valuable indicator for assessing the prognosis of patients with ICH.

Genomic, immunologic, and prognostic associations of TROP2 (TACSTD2) expression in solid tumors.

TROP2 (TACSTD2) expression is associated with decreased overall survival (OS) in some solid tumors, and the TROP2-targeting antibody-drug conjugate (ADC) sacituzumab govitecan has been approved in breast and urothelial carcinomas. We aimed to explore the multi-omic landscape associated with TACSTD2 gene expression in various solid tumors to identify patients most likely to benefit from this approach. Breast (N = 11 246), colorectal (N = 15 425), hepatocellular (N = 433), pancreatic (N = 5488), and urothelial (N = 4125) tumors were stratified into quartiles by TACSTD2 gene expression, analyzed by next-generation DNA sequencing, whole transcriptome sequencing, and immunohistochemistry at Caris Life Sciences (Phoenix, AZ). Survival data were obtained from insurance claims, and Kaplan-Meier estimates were calculated for molecularly defined cohorts. Several pathogenic mutations were associated with TACSTD2-high tumors, including TP53 in breast, colorectal (CRC), pancreatic, and hepatocellular cancers; KRAS in pancreatic and CRC cancers; ARID1A and FGFR3 in urothelial cancer; and CTNNB1 in hepatocellular cancer. TACSTD2-low breast tumors were enriched for copy number amplifications in CCND1 and FGF/R family member genes. TACSTD2 high was generally associated with more immune cell infiltration and greater T-cell inflammation scores. Patients with TACSTD2-high breast, CRC, and pancreatic cancers demonstrated a significantly shorter OS than TACSTD2-low tumors. This was restricted to CRC with microsatellite stable tumors and patients with pancreatic cancer with KRAS-mutant tumors. Patients with breast cancer with TACSTD2-high tumors also experienced significantly worse OS following immune checkpoint inhibitors. TACSTD2 expression is associated with key driver alterations and a more active immune microenvironment, suggesting possible combinatorial strategies with TROP2-targeting ADCs plus immunotherapy in various solid tumors.

Cardiovascular and All-Cause Mortality Is Affected by Serum Magnesium and Diet Pattern in a Cohort of Dialysis Patients.

Background: Hypomagnesaemia is associated with an increased overall mortality in patients with chronic kidney disease on dialysis (CKD-5D). Mediterranean-style diet (MD), having a high magnesium content, can serve as a form of dietary magnesium supplementation. We examined whether there is a potential link between increased Mediterranean Diet score (MDS) and elevated serum magnesium (sMg) to assess its impact on reducing mortality risk in CKD-5D patients. Methods: In this multi-center prospective observational study, 117 CKD-5D patients (66 on hemodialysis and 51 on peritoneal dialysis) with a mean age of 62 ± 15 years were studied for a median follow-up period of 68 months. After baseline assessment, including measurement of sMg and MDS, all patients were followed up for cardiovascular (CV) and all-cause mortality. Results: Forty deaths occurred, 58% of which were cardiovascular. Patients who were above the median value of sMg (2.2 mg/dL) had a 66% reduction in CV (crude HR, 0.34; 95% CI, 0.11-0.70), and 49% reduction in all-cause (crude HR, 0.51; 95% CI, 0.27-0.96) mortality, even after adjustment for age, malnutrition inflammation score, left ventricular mass index, peripheral vascular disease and diabetes. Similar results were obtained when sMg was analyzed as a continuous variable. sMg was associated directly with MDS (r = 0.230; p = 0.012). Conclusions: Higher sMg levels are strongly and independently associated with reduced CV and all-cause mortality in CKD-5D patients. A strong correlation exists between MDS and sMg. Elevated sMg levels, achieved through MD adherence, can significantly reduce CV mortality, implicating MD as a mediator of the association between sMg and CV mortality.