Immune-inflammatory Markers Research Articles

Left Ventricular Segmental Strain Based On Speckle Tracking Echocardiography Versus Indications Of Immune Inflammation In Patients After COVID-19 Pneumonia

Background — The significance of cytokine activation and immune inflammation in subclinical damage to cardiomyocytes and resulting development of the congestive heart failure (CHF) is frequently discussed in published studies, as well as whether there are cardiac lesions in COVID-19 survivors identified by the speckle tracking echocardiography (STE). Objective — To examine the association of echocardiographic parameters with indications of immune inflammation in patients recovered from COVID-19 pneumonia depending on segmental longitudinal strain (LS) of the left ventricle (LV) identified by STE. Methods — Our study encompassed 216 patients (51.1% men, mean age of 50.1±11.1 years) distributed among two groups: Group I (n=108) included study subjects with segmental LS (≥3 LV segments) revealed by the STE; Group II (n=108) comprised patients without visually detectable LV lesions. All patients were examined three months after COVID-19 pneumonia. Results — Groups did not differ statistically significantly in terms of LV ejection fraction (68.7±4.3% in Group I vs. 68.6±4.3% in Group II; p=0.916). Global LS was significantly lower in the Group I than in the Group II at the time of the control follow-up visit three months later (-18.2 [-16.7; -19.4] % vs. -20.6 [-19.5; -22.1] %, respectively; p<0.001). When analyzing laboratory indications of immune inflammation in groups, we revealed statistically significantly higher values in Group I vs. Group II in the concentrations of interleukin 6 (3.1 [2.4;3.9] pg/mL vs. 2.5 [3.8;4.7] pg/mL; p=0.009), C-reactive protein (4.7 [2.9;8.3] mg/L vs. 3.0 [1.5; 5.3] mg/L; p<0.001), and tumor necrosis factor α (6.0 [4.8;4.1] pg/ml vs. 5.0 [4.0;6.4] pg/ml; p=0.001). In Group I, we detected diffuse lesion of LS (≥4 segments of the same LV level; 38.0% of patients) and regional lesion of LS (≥3 segments corresponding to the blood supply pools of the anterior, circumflex, or right coronary arteries; 62.0% of patients). According to logistic regression, the LS of the basal LV level (OR 3.028; 95% CI 1.909-4.802; р<0.001) in combination with LS of the apical LV level (OR 1.287; 95% CI 1.099-1.507; р=0.002) and LV lateral wall annular velocity assessed by tissue Doppler imaging, peak e’ (OR 0.774; 95% CI 0.657-0.911; р=0.002) had an independent relationship with each of diffuse and regional LS lesions. Conclusion — Based on STE data, we have identified a relationship of diffuse and regional LV lesions with features of systolic and diastolic LV dysfunction and markers of immune inflammation in patients three months after COVID-19 pneumonia.

Antibodies to cyclic citrullinated peptide and angiopoietin-like protein type 4 as markers of immune inflammation and osteoporotic processes in rheumatoid arthritis patients

Low-energy fractures in rheumatoid arthritis (RA) are more common in patients with high activity and long duration of disease, and with high titers of anti-citrullinated antibodies (ACPA). Increased expression of angiopoietin-like protein type 4 (ANGPTL4) in bone tissue has also been noted in inflammatory arthritis. The purpose of the present study was to analyze the effect of ACPA and ANGPTL4 on systemic bone mineral density in RA patients. Antibodies to ACPA and ANGPTL4 content were detected in blood serum of 96 RA patients (women, 91.7%) by enzyme immunoassay. Mineral density of the lumbar vertebrae (BMDL1-L4), hip neck, and entire femur (BMDtotal) was measured by dual-energy X-ray absorptiometry (DXA). In study group, the ACPA and ANGPTL4 tests were positive in 61.5% and 41.7% of patients, respectively. Negative correlations were shown between ACPA and BMDtotal, and of ANGPTL4 with BMDL1-L4 (p < 0.05). Separation of the patients into groups with low (n = 34) and high (n = 62) DAS28 activity demonstrated a significant increase in ACPA with increasing RA activity (p = 0.042). ACPA and ANGPTL4 scores were also significantly higher in the group of 45 RA patients with osteoporosis (OP) compared to the RA group without OP (n = 51) showing significant difference at p = 0.002 and p = 0.028, respectively. Patients’ age, body mass index (BMI), duration and activity of the disease had no significant effect on ACPA in the general group of RA patients. However, the correlation between ACPA and DAS28 proved to be significant in the group of RA patients with OP (b = 0.31, p = 0.039). Among all presented variables, the disease duration was the only significant factor for ANGPTL4 in the total group of RA patients (b = 0.31, p = 0.039). In the regression model, BMDtotal showed similar correlations with patients’ age (b = -0.28), BMI (b = 0.25), and ACPA level (b = -0.26). A search for association between BMDL1-L4 and various RA characteristics demonstrated a strong correlation with ANGPTL4 only (b = -0.74; R2 = 0.57). The revealed correlation between ANGPTL4 and decreased BMD specifically in the spongy layer of bone allows us to identify the RA patients with high ANGPTL4 levels as a risk group specifically for spinal fractures thus considering ANGPTL4 as a potential target for treatment of osteoporotic disorders.

Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis.

The Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors. The Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). A total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1-2, and 49 (16%) Grade 3-4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4-21.6 months]) than those without (10.1 months [95% CI, 8.3-12.0 months]) (p<0.001), either if Grade 1-2 (p=0.003) or Grade 3-4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0-11.2 months]) than those without (6.1 months [95% CI, 5.2-7.1 months]) (p<0.001), either if Grade 1-2 (p=0.011) or Grade 3-4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1-2 irAEs correlated with NLR <4 (p=0.013 and p=0.018), SII <1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p<0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008). These results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1-2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.

Systemic inflammation response index as an emerging biomarker in osteoarthritis patients: a bibliometric and large sample retrospective investigation.

To determine the value of the whole-blood inflammatory response index as an emerging biomarker for the assessment of disease activity in osteoarthritis (OA). Extensive analysis of the literature on OA and whole-blood inflammatory indicators were provided through a bibliometric approach. Clinical characteristics and indicators of OA patients and healthy controls (HC) were retrospectively analysed. Four whole-blood inflammatory response indices - neutrophil/lymphocyte count (NLR), platelet/lymphocyte count (PLR), monocyte/lymphocyte count (MLR), and systemic inflammation response index (SIRI), as well as clinical traits like the OA patient's self-perception and immune-inflammatory indicators were analysed for correlations. Cut-off values were determined using receiver operating characteristic (ROC) curves, and they were subsequently employed in logistic regression models to work out whole-blood inflammatory indices and disease activity. The pathophysiology of osteoarthritis has received most of the spotlight in literature studies of OA and whole-blood inflammation indicators. The "inflammation", "osteoarthritis" and "disease activity" were the top 3 key word clusters. Retrospective analysis showed that MLR, NLR, PLR, and SIRI were markedly higher in OA subjects compared to HC subjects. ROC curve consequences manifested that SIRI and NLR could separate OA from healthy controls. NLR, PLR, MLR, and SIRI proved to be related to immune-inflammatory markers, visual analogue scale (VAS) scores, and short-form (SF)-36 scores with regard to correlation analysis and association criteria. Logistic regression manifested that SIRI, NLR, and C-reactive protein (CRP) forecasted disease activity, however, the model that combined SIRI and CRP was superior to CRP alone. SIRI may serve as a non-invasive, appropriate biomarker to correlate with disease activity.

LINC00707 inhibits myocardial fibrosis and immune disorder in rheumatic heart disease by regulating miR-145-5p/S1PR1

ABSTRACT LINC00707 is a lncRNA that can regulate a variety of diseases. This study mainly investigated that the expression of LINC00707 in rheumatic heart disease (RHD) and LINC00707 regulates S1PR1 by targeting miR-145-5p to inhibit myocardial fibrosis and immune disorder in RHD. A rat model of RHD induced by inactivated group A β-hemolytic streptococcus (GSA) was established. Sixty female Lewis rats (8 weeks of age) were randomly divided into six groups, including control (Con), RHD, RHD+NC, RHD+LINC00707, RHD+miR-145-5p and RHD+LINC00707+miR-145-5p. The mRNA expression was detected by Quantitative Real-time polymerase chain reaction (qRT-PCR). Protein expression of S1PR1 was detected by western blot. The levels of myocardial damage markers (CK-MB, cTnl) and inflammatory immune markers (IL-6, IL-17 and IL-21) were measured by enzyme linked immunosorbent assay (ELISA). The Collagen III/I(COLIII/I) ratio, mRNA expression of COLIIIα1 and FSP1 of rat heart valve tissue in the RHD group was observably higher by comparison with the CON group. The expression of LINC00707 was observably lower in the RHD group. LINC00707 inhibited myocardial fibrosis and immune disorder in RHD. MiR-145-5p was the target gene of LINC00707 via Targetscan prediction. Luciferase reporter experiment confirmed that miR-145-5p was directly regulated by LINC00707. The expression of miR-145-5p in the RHD group was observably higher by comparison with the CON group and LINC00707 observably decreased the expression of miR-145-5p. miR-145-5p mimic reversed the inhibiting effect of LINC00707 on myocardial fibrosis and immune disorder. Furthermore, S1PR1 was confirmed to be downstream gene of miR-145-5p and low expressed in the RHD model. LINC00707 could inhibit myocardial fibrosis and immune disorder in RHD by regulating miR-145-5p/S1PR1.

Prognostic value of systemic immune inflammation index and geriatric nutrition risk index in early-onset colorectal cancer.

Systemic nutritional and inflammatory markers, which are easy to measure are associated with the progression and prognosis of many cancers. Nevertheless, among the various available indicators, optimal prognostic indicators for patients with early-onset colorectal cancer have not been identified. Therefore, the aim of this study was to identify optimal nutritional and inflammatory markers for early-onset colorectal cancer and examine the relationship between systemic nutritional and inflammatory markers before treatment and survival in patients with early-onset colorectal cancer. We retrospectively collected data from 236 eligible patients with early-onset colorectal cancer. Area under the prognostic curve (AUC) and concordance index (C-index) were used to compare seven systemic nutritional and inflammatory markers to identify the optimal inflammatory immune markers. Univariate and multivariate COX regression analyses were used to evaluate the prognostic value of indicators in the total study population and different subgroups. The AUC and C-index showed that the systemic immune inflammation index (SII) and geriatric nutrition risk index (GNRI) had higher prognostic values than other systemic nutritional and inflammatory indicators. Compared with patients in the low SII group, those in the high SII group had lower overall survival (HR, 4.42, 95% CI, 2.36-8.27, p = 0.000). Compared with patients in the high GNRI group, those in the low GNRI group had lower overall survival (HR, 0.33, 95% CI, 0.19-0.56, p = 0.000). SII was negatively associated with GNRI (R = -0.3, p < 0.001), and both were correlated with the tumor stage. SII and GNRI are suitable nutritional and inflammatory factors for predicting OS in patients with early-onset colorectal cancer; high SII and low GNRI were correlated with worse prognoses. Identifying the high inflammatory state and low nutritional state of patients before surgery and conducting active and timely therapeutic interventions could improve patient prognosis.

The deficit subtype of schizophrenia is associated with a pro-inflammatory phenotype but not with altered levels of zonulin: Findings from a case-control study

There is evidence that subclinical inflammation and increased gut permeability might be involved in the pathophysiology of schizophrenia. Less is known about these phenomena in patients with the deficit subtype of schizophrenia (D-SCZ) characterized by primary and enduring negative symptoms. Therefore, in the present study we aimed to compare the levels of zonulin (the marker of gut permeability) and immune-inflammatory markers in patients with D-SCZ, those with non-deficit schizophrenia (ND-SCZ) and healthy controls (HCs). A total of 119 outpatients with schizophrenia and 120 HCs were enrolled. The levels of 26 immune-inflammatory markers and zonulin were determined in serum samples. The following between-group differences were significant after adjustment for multiple testing and the effects of potential confounding factors: 1) higher levels of interleukin(IL)− 1β and C-reactive protein (CRP) in patients with D-SCZ compared to those with ND-SCZ and HCs; 2) higher levels of tumor necrosis factor-α and RANTES in both groups of patients with schizophrenia compared to HCs and 3) higher levels of IL-17 in patients with D-SCZ compared to HCs. No significant between-group differences in zonulin levels were found. Higher levels of IL-1β and CRP were associated with worse performance of attention after adjustment for age, education and chlorpromazine equivalents. Also, higher levels of IL-1β were correlated with greater severity of negative symptoms after adjustment for potential confounding factors. In conclusion, individuals with D-SCZ are more likely to show subclinical inflammation. However, findings from the present study do not support the hypothesis that this phenomenon is secondary to increased gut permeability.

Effect of Siegesbeckiae Herba on immune-inflammation of rheumatoid arthritis: Data mining and network pharmacology

Rheumatoid arthritis (RA) is an autoimmune disease, resulting in an overall poor prognosis. Siegesbeckiae Herba is a natural botanical herb that possesses a variety of biological activities, particularly its anti-rheumatism property. This study collected the clinical data of 7657 RA patients who received treatment with traditional Chinese medicine prescriptions before December 2021 in the Department of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine. The levels of immune-inflammatory indicators including Hs-CRP, ESR, RF, C3, C4, IgA, IgG, and IgM were observed before and after the treatment. Association rules between Siegesbeckiae Herba and immune-inflammatory indicators were analyzed by Apriori algorithm. Protein-protein interaction network diagram, core gene and drug-active ingredient-target diagram were drawn by Cytoscape3.7.2 software. GO and KEGG analysis was performed by DAVID database. Autodock software was used to conduct molecular docking and in vitro experiments were performed to verify the action mechanism of Siegesbeckiae Herba on RA. Data mining results showed that the use of Siegesbeckiae Herba was strongly associated with the improvement of immune-inflammatory markers of RA. The results of network pharmacology and molecular docking showed that the main target proteins including Bax, CASP3, CASP8, CASP9, COX2, TNF, and IL-17 of Siegesbeckiae Herba were closely related to apoptosis and inflammatory signaling pathways in the treatment of RA. In vitro cell experiments results showed that Kirenol, the main active ingredient of Siegesbeckiae Herba, up-regulated the expressions of pro-apoptotic proteins Bax, caspase3, caspase8, and caspase9 in RA-fibroblast-like synoviocytes (RA-FLSs) and down-regulated the expressions of COX2, TNF, and IL-17. Siegesbeckiae Herba promoted the apoptosis of RA-FLSs and alleviated immune-inflammatory responses in RA.

Correlation study between apparent diffusion coefficients and the prognostic factors in breast cancer

To analyse the correlation between apparent diffusion coefficients (ADC) derived from intratumoural and peritumoural regions with prognostic factors and immune-inflammatory markers in breast cancer (BC). In this retrospective study, 89 patients (age range, 28-66 years; median, 45 years) with a diagnosis of invasive BC who underwent routine blood tests and multiparametric magnetic resonance imaging (MRI) were enrolled. The study cohort was stratified according to tumour maximum cross-section ≥20 mm, lymph node metastasis (LNM), time-signal intensity curve (TIC) type, and receptor status. Minimum, maximum, mean, and heterogeneity values of tumour ADC (ADCtmin, ADCtmax, ADCtmean, and ADCheter), maximum values of peritumoural ADC (ADCpmax), and the ratio of peritumoural-tumour ADC (ADCratio) were obtained on the ADC maps. Linear regression analyses were performed to investigate the correlation between immune-inflammatory markers, prognostic factors and ADC values. HER-2 was positively associated with ADCtmax, ADCtmean, and ADCpmax values (β=0.306, p=0.004; β=0.283, p=0.007; β=0.262, p=0.007, respectively), while platelet-to-lymphocyte ratio (PLR) was positively associated with ADCpmax and ADCratio values (β=0.227, p=0.020; β=0.231, p=0.020, respectively). Among ADC parameters, ADCpmax showed the highest predictive values for evaluating the presence of LNM (AUC, 0.751; sensitivity, 70.4%; specificity, 77.1%). The ADCpmax value could provide additional assistance in predicting prognostic factors of BC.

Significance of immune-inflammatory markers in predicting clinical outcome of COVID-19 patients.

The epidemic of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale affecting many countries and territories. There is rapid onset of generalized inflammation resulting in acute respiratory distress syndrome. We, thus, aimed to explore the potential of immune-inflammatory parameters in predicting the severity of COVID-19. Age, neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Lactate Dehydrogenase (LDH), C-reaction protein (CRP), and procalcitonin (PCT) of 611 patients with laboratory-confirmed COVID-19 were investigated and compared. Patients were divided on the basis of severity and survival into two groups. Data were expressed as mean or median values and percentages. The receiver operating characteristic curve was applied to determine the optimal cut-off values of these biomarkers. The median age was 50 years and the male to female ratio was 3.7:1. The mean NLR, LMR, PLR, LDH, CRP, and Procalcitonin for the non-severe group were 4.16, 10.8, 133.7, 666.1, 49.9, and 0.15, respectively. In the severe group mean values of the above-mentioned immune-inflammatory markers were 17.8, 4.69, 268.2, 1277, 158.6, and 3.05, respectively. Elevated levels were significantly associated with disease severity. In ROC curve analysis, NLR had the largest area under the curve at 0.923 with the highest specificity (0.83) and sensitivity (0.88). This study shows that NLR, PLR, LDH, CRP, and Procalcitonin may be a rapid, widely available, useful predictive factor for determining the severity of COVID-19 patients.

Adjunctive minocycline for major depressive disorder: A sub-study exploring peripheral immune-inflammatory markers and associated treatment response

BackgroundAdjunctive minocycline shows promise in treating affective and psychotic disorders; however, the therapeutic mechanism remains unclear. Identifying relevant biomarkers may enhance the efficacy of novel adjunctive treatment candidates. We thus investigated the peripheral immune-inflammatory profile in a randomized controlled trial (RCT) of minocycline in major depressive disorder (MDD). MethodsThis sub-study investigated serum samples from a RCT evaluating minocycline (200 mg/day, 12 weeks) in addition to treatment as usual for MDD (ACTRN12612000283875). Of the original sample (N = 71), serum assays were conducted in 47 participants (placebo n = 24; minocycline n = 23) targeting an array of 46 immune-inflammatory analytes including cytokines, chemokines, and acute-phase reactants. General estimating equations (GEE) were used to assess whether analyte concentration at baseline (effect modification) and change in analytes (change association) influenced change in Montgomery-Åsberg Depression Rating Scale (MADRS) score over time. The Benjamini–Hochberg approach was applied when adjusting for false discovery rates (FDR). ResultsGEE models revealed several interaction effects. After adjusting for FDR several change association-models survived correction. However, no such models remained significant for effect modification. Three-way group × time × marker interactions were significant for complement C3 (B = −10.46, 95%CI [-16.832, −4.095], q = 0.019) and IL-1Ra (B = −9.008, 95%CI [-15.26, −2.751], q = 0.036). Two-way group × biomarker interactions were significant for ICAM-1/CD54 (B = −0.387, 95%CI [-0.513, −0.26], q < 0.001) and IL-8/CXCL8 (B = −4.586, 95%CI [-7.698, −1.475], q = 0.036) indicating that increases in the serum concentration of these analytes were associated with an improvement in MADRS scores in the minocycline group (compared with placebo). ConclusionsChange in complement C3, IL-1Ra, IL-8/CXCL8, and ICAM-1 may be associated with greater change in depressive scores following adjunctive minocycline treatment in MDD. Further investigations are needed to assess the utility of these biomarkers.

The Effects of a Single Bout of High- or Moderate-Intensity Yoga Exercise on Circulating Inflammatory Mediators: A Pilot Feasibility Study.

There is a knowledge gap in the physiological effects of short-term yoga exercise interventions. To evaluate the feasibility of a randomized controlled trial (RCT) assessing the acute effects of a yoga exercise protocol practiced at 2 intensities (high or moderate) on temporal responses of a battery of systemic circulatory cytokines in healthy yoga-naïve adults. This study was a three-arm, pre-post pilot-RCT employing a single bout of yoga exercise intervention. Groups were high-intensity yoga (HY, n = 10), moderate-intensity yoga (MY, n = 10), and a sedentary, no-intervention control group (CON, n = 10). Blood samples were collected at baseline and post-intervention at 6 timepoints (0-, 30-, 60-, 120-, 180-minutes, and 24-hours post-intervention) and were processed with a pre-defined inflammatory panel of 13 cytokines. Heart rate (HR) was assessed with a Polar H10® device. The PROMIS Pain intensity Questionnaire was used to assess body soreness. We demonstrate feasibility of recruitment, randomization, and retention of participants based upon predetermined metrics, including: proportion of eligible to enrolled participants (55%); recruitment period (11-months); participant retention (97%); completion rate for questionnaires (99%); completion of physiological measures (98%); and adherence to the yoga exercise protocol (88%). Cytokine levels over time were heterogeneous within and between groups. Responses of a subset of cytokines were positively correlated with 1 another in high- and moderate-intensity yoga exercise groups but not in the control group. Median values for HR were 91 (IQR: 71-95) in the HY, 95 (IQR: 88-100) in the MY, and 73 (IQR: 72-75) in the CON. Pre-post changes in body soreness after the yoga exercise intervention were most evident in the HY group. Along with observed trends in select cytokines, findings encourage a more definitive trial aimed at understanding the short-term effects of yoga exercise on inflammatory immune markers and pain in sedentary healthy adults. Clinicaltrials.gov ID# NCT04444102.

Modified Geriatric Nutrition Risk Index as a Prognostic Predictor for Unresectable/Recurrent Esophageal Cancer.

This study aimed to evaluate the prognostic value of modified geriatric nutritional risk index (mGNRI) in patients with unresectable/recurrent esophageal cancer (EC). We included 143 patients aged >65 years with unresectable/recurrent EC. The mGNRI was calculated as (1.489/CRP in mg/dl) + (41.7 × body mass index/22). Participants were divided into two groups: low-mGNRI (mGNRI <80, n=90) and high-mGNRI (mGNRI ≥80, n=53). We retrospectively examined the relationship between mGNRI and the prognosis of EC. Median survival time in the low-mGNRI group was significantly lower than that in the high-mGNRI group (5.1 vs. 16.9 months, p<0.001). Multivariate analysis revealed that low mGNRI [hazard ratio (HR)=3.85, p<0.001] and absence of chemotherapy or chemoradiotherapy (HR=2.69, p<0.001) were independent and unfavorable prognostic factors of overall survival. Among patients who received chemotherapy or chemoradiotherapy, the mGNRI-low group had a significantly poorer prognosis than the mGNRI-high group (p<0.001). The mGNRI was the most appropriate prognostic index compared with other immune-inflammatory markers by the Akaike and Bayesian information criteria. In patients with unresectable/recurrent EC, low mGNRI was correlated with unfavorable prognosis and was a useful independent prognostic factor.

P1.15-04 Dynamic Profiling of Blood Immunophenotypes and Radiomic Features to Predict Immunotherapy Response in Advanced Non-small Cell Lung Cancer

Up to date, no predictive biomarkers can robustly identify patients with non-small cell lung cancer (NSCLC) who will benefit from immune checkpoint inhibitors (ICIs). Thus, we sought to non-invasively decode tumor-immune interactions implicated in ICI response by exploring the dynamic of blood immune-inflammatory markers and radiomic features in a cohort of advanced NSCLC treated with ICIs.

Association between inflammatory markers levels, inflammatory intake of diet and adherence to the mediterranean diet

Background and Aims : The beneficial effects of the Mediterranean Diet (Med-Diet) in Cardiovascular Disease (CVD) prevention have been attributed to its anti-inflammatory effects. Recent data aimed to verify a pro-/anti-inflammatory potential of Med-Diet, although suffering from the lack of quantitative evaluation of food groups intake (by commonly used Food Frequency Questionnaires FFQ). We aimed to address this issue by evaluating the anti-inflammatory potential of Med-Diet, analyzing quantitative dietary intakes and relating to circulating immune-inflammatory markers.

Evidence Supporting the Diethylstilbestrol Induction of Endometriosis Via Immune-Inflammatory Pathway in Rat Model

Endometriosis is a benign reproductive disorder distinguished by chronic inflammation and anomalous progress of stromal cells and glands outside the uterus. Though the etiology of endometriosis is still a matter of debate, the immuneinflammatory mediators are thought to play a major role. Macrophage infiltration and proinflammatory intermediaries in the peritoneal environment peritoneal milieu impact ovarian, uterine function and pelvic morphology, resulting in endometriosis symptoms and signs. The endometriosis model system was developed using diethylstilbestrol (DES) which is examined to develop the disease via the immune-inflammatory pathway. The immune-inflammatory markers (NFKB, MAPK, TNF-α, IL-6 and STAT- 3) were investigated in this study. The results demonstrated that the DES induced endometriosis animal model had a higher level of CA-125, a biomarker of endometriosis. Endometriosis-induced groups had increased levels of NFKB, MAPK, TNF-α, IL-6 and STAT-3 which clearly depicts the immune-inflammatory role in the induction. Finally, the results conclude that DES induced endometriosis via the immune-inflammatory pathway.&#x0D;

165P Dynamic evolution of blood immune-inflammatory descriptors in advanced non-small cell lung cancer undergoing first-line immunotherapy-based regimens

The groundbreaking results of Immune Checkpoint Inhibitors (ICIs) in NSCLC still involve a limited subset of cases, thus imposing an optimization of patient selection. With the aim to non-invasively intercept tumor-host events implicated in cancer immune surveillance and response to immunotherapy, we explored the dynamic of blood immune-inflammatory markers in a cohort of advanced NSCLC treated with first-line ICIs. Peripheral blood was prospectively collected at baseline (T0) and at first radiological disease assessment (T1) from 47 consecutive NSCLC patients undergoing first-line ICI-based therapy. We performed a flow-cytometric analysis of circulating CD3+, CD8+, CD4+, NK, NKT and Tregs as their expression of functional molecules (PD-1, Granzyme B [GnzB], Perforin [Perf]) and proliferative index (Ki67). Soluble PD-L1 (sPD-L1) was determined by immunoassay together with Lung Immune Prognostic Index (LIPI: LDH + derived Neutrophil-to-Lymphocyte Ratio). All these parameters were correlated to objective response rate (ORR) according to RECIST v1.1 criteria. From October 2020 to August 2021, 47 advanced NSCLC patients candidate to receive first-line ICI-based therapy were enrolled. Median age was 67.8 years (range 41-82), 66% were males and 81% underwent chemo-immunotherapy. ORR resulted 51%. Among baseline parameters, number of metastatic sites, bone lesions and poor LIPI negatively correlated with ORR (p<0.05), while a trend towards favorable response was apparent in tissue PD-L1high cases (ORR=67% vs 28% in PD-L1neg). A significant proliferative burst of CD8+PD-1+ lymphocytes carrying cytotoxic molecules (GnzB+, Perf+) coupled with sPD-L1 decline characterized responders. Conversely, CD8+ GnzB+/Perf+ and NK cells dramatically dropped in non-responders (χ2 test, p<0.01). Furthermore, the kinetic and extent of Treg counteraction, likely triggered by the expanding (Ki67+) pool of effector lymphocytes, appeared to be a distinctive feature of responsive patients. Our results suggest that tracking the evolution of blood immune-inflammatory profiles may provide valuable predictors of ICI efficacy in NSCLC patients.

Do immune inflammatory markers correlate with anal dysplasia and anal cancer risk in patients living with HIV?

People living with HIV (PLWH) are at an elevated risk for developing anal cancer. As screening is invasive, markers predicting those at highest risk for anal cancer could guide individualized screening. Neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and prognostic nutritional index (PNI) are surrogate inflammatory/immune markers known to correlate with cancer outcomes. This study aims to assess whether these markers correlate with anal cancer risk in PLWH. This is a retrospective single-institution cohort study of PLWH at a single academic medical center who were diagnosed with or screened for anal dysplasia between 2001 and 2019. Aforementioned markers collected within one year of diagnosis were recorded. Regression modeling was used to estimate odds of anal cancer. Receiver operating characteristic analysis was utilized to determine optimal cutoff for screening values. Five-hundred-fourteen patients were included. NLR and PNI were significantly associated with cancer risk on univariate (p = 0.03, p = 0.001) and multivariate analyses (p = 0.03, p = 0.01). NLR increased across all grades of dysplasia. PLR was not associated with cancer risk. A NLR of ≥ 1.64 can be utilized to capture 76% of cancer patients in our cohort. NLR values in patients living with HIV correlate with risk of anal cancer and increasing grades of dysplasia. A cutoff NLR of ≥ 1.64 can be used to help capture those at risk. NLR is a promising marker of risk of anal cancer and progression of anal dysplasia in patients with HIV infection and could be used to risk-stratify screening and surveillance intervals.

Pathway Phenotypes Underpinning Depression, Anxiety, and Chronic Fatigue Symptoms Due to Acute Rheumatoid Arthritis: A Precision Nomothetic Psychiatry Analysis.

Rheumatoid arthritis (RA) is a chronic inflammatory and autoimmune disorder which affects the joints in the wrists, fingers, and knees. RA is often associated with depressive and anxiety symptoms as well as chronic fatigue syndrome (CFS)-like symptoms. This paper examines the association between depressive symptoms (measured with the Beck Depression Inventory, BDI), anxiety (Hamilton Anxiety Rating Scale, HAMA), CFS-like (Fibro-fatigue Scale) symptoms and immune–inflammatory, autoimmune, and endogenous opioid system (EOS) markers, and lactosylcer-amide (CD17) in RA. The serum biomarkers were assayed in 118 RA and 50 healthy controls. Results were analyzed using the new precision nomothetic psychiatry approach. We found significant correlations between the BDI, FF, and HAMA scores and severity of RA, as assessed with the DAS28-4, clinical and disease activity indices, the number of tender and swollen joints, and patient and evaluator global assessment scores. Partial least squares analysis showed that 69.7% of the variance in this common core underpinning psychopathology and RA symptoms was explained by immune–inflammatory pathways, rheumatoid factor, anti-citrullinated protein antibodies, CD17, and mu-opioid receptor levels. We constructed a new endophenotype class comprising patients with very high immune–inflammatory markers, CD17, RA, affective and CF-like symptoms, and tobacco use disorder. We extracted a reliable and replicable latent vector (pathway phenotype) from immune data, psychopathology, and RA-severity scales. Depression, anxiety, and CFS-like symptoms due to RA are manifestations of the phenome of RA and are mediated by the effects of the same immune–inflammatory, autoimmune, and other pathways that underpin the pathophysiology of RA.

Peripheral inflammatory cytokines and motor symptoms in persons with Parkinson's disease

BackgroundMany of the motor symptoms of Parkinson's disease (PD) impact quality of life and are not fully ameliorated by current pharmacological and surgical treatments. A better understanding of the pathophysiology underlying these symptoms is needed. Previous research has suggested that inflammation may play a significant role in PD pathophysiology and progression, but there is limited research exploring how inflammation directly relates to motor symptoms in PD. Thus, the purpose of this study was to evaluate associations between peripheral immune inflammatory markers and motor symptoms of PD, specifically, tremor, bradykinesia, and postural and gait instability. We hypothesized that peripheral inflammatory cytokines would predict the severity of motor symptoms in persons with PD, and that there will be higher levels of peripheral inflammatory cytokine markers in persons with PD when compared to age-matched healthy older adults. MethodsTwenty-six participants with PD and fourteen healthy older adults completed the study. For participants with PD, the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) was recorded and scored by two Movement Disorders Neurologists masked to the study. A blood sample was collected from both participants with PD and the healthy older adults. Through the MILLIPLEX® map High Sensitivity Human Cytokine Kit, key inflammation-related markers were analyzed (TNF-α, IFN-γ, IL-1β, IL-8, IL-2, IL-7, IL-5, IL-13, IL, 4, IL-10 IL-12p70, GM-CSF, and IL-6). ResultsResults revealed significantly higher levels of IL-6 in persons with PD when compared to healthy older adults (p ​= ​0.005). Moreover, results revealed that higher levels of IL-4 (p ​= ​0.011) and lower levels of IFNγ (p ​= ​0.003) significantly predicted more severe tremor in persons with PD. No other associations between the peripheral inflammation markers and other motor symptoms were observed. ConclusionsOverall, these results are consistent with a growing body of literature that implicates inflammatory cytokines in the PD, and further suggests that inflammatory cytokines, or lack thereof, may be associated with tremor in persons with PD.