Effect of Ziltivekimab on Determinants of Hemoglobin in Patients with CKD Stage 3-5: An Analysis of a Randomized Trial (RESCUE).

SIGNIFICANCE STATEMENT: Systemic inflammation in CKD can lead to anemia. Ziltivekimab, a fully human monoclonal antibody targeting the IL-6 ligand, has been shown to reduce systemic inflammation in patients with CKD. It has also been shown to increase serum albumin in patients on hemodialysis with inflammation and hyporesponsiveness to treatment with erythropoiesis-stimulating agents. This exploratory analysis of the RESCUE clinical trial found that among patients with CKD stage 3-5 and systemic inflammation, ziltivekimab treatment significantly increased hemoglobin (Hb) levels after 12 weeks compared with placebo. Ziltivekimab was also associated with significant increases in serum iron levels, total iron-binding capacity, and transferrin saturation. No major safety concerns were reported. Further clinical trials are warranted to study ziltivekimab's potential for anemia management in patients with CKD. BACKGROUND: In the phase 2 RESCUE clinical trial, ziltivekimab, a fully human monoclonal antibody against the IL-6 ligand, significantly reduced the biomarkers of inflammation compared with placebo, in patients with CKD and systemic inflammation (high-sensitivity C-reactive protein ≥2 mg/L). The aim of this subanalysis of RESCUE trial data was to assess the effect of ziltivekimab on Hb and iron homeostasis in this patient population. METHODS: This was an analysis of exploratory end points from the RESCUE trial ( NCT03926117 ), which included 264 adults with CKD stage 3-5 and high-sensitivity C-reactive protein ≥2 mg/L. Participants received placebo or subcutaneous ziltivekimab (7.5, 15, or 30 mg) (1:1:1:1) once every 4 weeks, up to 24 weeks. End points for this analysis were changes in Hb and biomarkers of iron homeostasis from baseline to week 12. RESULTS: The trial was terminated early due to the coronavirus disease 2019 pandemic, and thus, data up to week 12 are presented. Hb levels significantly increased from baseline to week 12 with ziltivekimab 7.5, 15, and 30 mg (treatment differences versus placebo: +0.57 g/dl [95% confidence interval, 0.27 to 0.86], +1.05 g/dl [0.76 to 1.33], and +0.99 g/dl [0.70 to 1.28], respectively, all P < 0.001). Ziltivekimab was associated with significant increases in serum iron levels, total iron-binding capacity, and transferrin saturation from baseline to week 12 ( P < 0.05 versus placebo for all doses and comparisons). Cases of sustained thrombocytopenia, sustained neutropenia, anemia, and iron deficiency anemia were infrequent and similar across all groups. CONCLUSIONS: Anti-inflammatory therapy with ziltivekimab improved the markers of anemia and iron homeostasis in people with stage 3-5 CKD and systemic inflammation, suggesting a possible role in anemia management.

Response to interleukin-1 blockade with anakinra in women and men with ST-segment elevation myocardial infarction.

BACKGROUND: Interleukin-1 blockade with anakinra reduces high-sensitivity C-reactive protein (hsCRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). Sex-based differences in STEMI patients have been reported, but no data are available regarding response to anakinra. METHODS: We analyzed the systemic inflammation and composite end-point of new-onset HF or death in women and men with STEMI treated with anakinra from three different Virginia Commonwealth University Anakinra Response Trial (VCUART) randomized clinical trials. RESULTS: We analyzed 139 patients, 29 (21%) were women while 110 (79%) were men. Baseline hsCRP was higher in women compared to men (8.9 [5.2-13.5] vs. 4.2 [2.1-7.7] mg/L, P<0.001). Eighty-four patients were treated with anakinra (22 [75%] women and 62 [56%] men). The area under the curve of hsCRP (hsCRP-AUC) after 14 days was numerically lower in patients receiving anakinra versus placebo both in men (86 [37-130] vs. 223 [119-374] mg day/L) and in women (73 [46-313] vs. 242 [102-988] mg day/L) (P<0.001 for multiple groups, P for interaction 0.22). The incidence of the composite endpoint was also numerically lower in the anakinra group compared to placebo, both in men (4 [6.4%] vs. 14 [29.1%]) and in women (3 [13.6%] vs. 2 [28.5%]) (P=0.019 for multiple groups, P for interaction 0.44). There were no statistically significant differences between women and men in hsCRP-AUC and death or HF events when comparing separately the anakinra and placebo groups (all P>0.05). CONCLUSIONS: Women were underrepresented in the VCUART trials, they appeared to have higher hsCRP levels at time of presentation, yet to benefit similar to men by treatment with anakinra in STEMI.

[Features of the course of COVID-19 in patients with type 2 diabetes mellitus].

AIM: To identify the features of the course of COVID-19 in patients with type 2 diabetes mellitus (T2DM), depending on the intake of hypoglycemic therapy at the prehospital stage, in conjunction with the functional state of the kidneys. MATERIALS AND METHODS: A retrospective analysis of 291 case histories of patients with COVID-19 and T2DM hospitalized in the infection department of Semashko Regional Clinical Hospital from January to December 2021, including the main clinical and laboratory parameters. Results. Among hospitalized patients with COVID-19, patients with T2DM had a higher mortality rate. An analysis of the case histories of deceased patients with COVID-19 and T2DM showed that at admission, body mass index (BMI), C-reactive protein, and creatinine were higher than those of survivors and amounted to BMI - 33 [30; 39] and 33 [28; 36] kg/m3; p=0.039, C-reactive protein - 77 [47.5; 106.0] and 57 [27.0; 89.0] mg/l; p=0.015, in terms of creatinine level - 89 [70.0; 144.0] and 82 [66.0; 101.0] µmol/l; p=0.039, respectively. It was found that in the second week of hospitalization in the group of deceased patients with COVID-19 and T2DM, the creatinine level was statistically significantly higher than in surviving patients and amounted to 94.5 [71.5; 141.0] and 72.5 [57.0; 88.0] µmol/L; p<0.001, respectively. The probability of death in hospitalized patients with type 2 COVID-19 and T2DM depended on BMI and creatinine levels at the second week of hospitalization. Patients with prehospital correction of hyperglycemia dipeptidyl peptidase-4 inhibitors (iDPP-4)/ glucagon-like peptide-1 receptor agonists (agGLP-1)/ sodium-glucose co-transporter 2 inhibitors (iSGLT-2) had significantly lower creatinine levels at week 2 of hospitalization. CONCLUSION: In patients with moderate to severe COVID-19 with concomitant T2DM, special attention should be paid to the combination of high BMI and creatinine in the second week of hospitalization, which is a prognostically unfavorable predictor of death in such patients.

Changes of Serum C-Reactive Protein Level in Patients With Depressive Disorders After Treatment With Agomelatine Combined With Aerobic Exercise and Its Significance.

OBJECTIVE: Depressive disorders constitute a series of debilitating diseases. This study investigated the therapeutic effect of agomelatine (AG) combined with aerobic exercise (AE) on patients with moderate-severe depression (MSD) and the changes of the serum C-reactive protein (CRP) level in patients after treatment as well as its significance. METHODS: A total of 178 MSD patients were randomly assigned to the AG group (N = 90) and AG + AE group (N = 88). The severity of depressive disorders and anhedonia was assessed using the Hamilton Rating Scale for Depression (HAM-D), Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores. The serum CRP level in MSD patients was detected by turbidity assay. Patients were defined as remitters, responders, and nonresponders according to the HAM-D 17 score, and the treatment efficacy was analyzed, followed by evaluation of the serum CRP level in patients with different treatment responses. Finally, the adverse reactions of patients during treatment were statistically analyzed. RESULTS: After treatment, the HAM-D, Beck Depression Inventory, and Snaith-Hamilton Pleasure Scale scores and the serum CRP level of the 2 groups were reduced, and changes in the AG + AE group was more significant than that in the AG group. The clinical efficacy of the AG + AE group was better than that of the AG group. After treatment, the serum levels of CRP in remitters and responders were reduced, but not significantly in nonresponders. The incidence of adverse events in the AG + AE group was lower than that in the AG group. CONCLUSION: AG + AE reduced the serum level of CRP in MSD patients and had good therapeutic effects on MSD patients.

Ultrasound-guided Shoulder Intraarticular Ozone Injection Versus Pulsed Radiofrequency Application for Shoulder Adhesive Capsulitis: A Randomized Controlled Trial.

BACKGROUND: A diseased shoulder due to pain, stiffness, or weakness negatively affects patients' quality of life and their ability to carry out activities of daily living. Adhesive capsulitis is a disease characterized by shoulder pain and global limitation of movement in the shoulder joint. Many interventions have been proposed for the treatment of primary adhesive capsulitis. The current study compares the effect of ultrasound-guided intraarticular injection of ozone versus steroid versus intraarticular application of pulsed radiofrequency. OBJECTIVES: The primary outcome of the current study was to compare the improvement in the Visual Analog Scale (VAS) after the 3 treatment modalities. The secondary outcomes included functional improvement measured by the Shoulder Pain and Disability Index (SPADI) and level of inflammatory biomarkers measured by serum intercellular adhesion molecule (ICAM-1) and high-sensitivity C-reactive protein(hs-CRP). STUDY DESIGN: The current study is a prospective, double blinded, randomized controlled trial. We employed a double blinding technique for both the patients and the outcome assessors. SETTING: Our study was carried out at the Medical Research Institute, Alexandria University, Egypt, after approval of the local ethical committee (IORG0008812). The study was registered in the "clinical trials library for protocol registration and results system" with number NCT04724317.The study included 45 patients with a diagnosis of primary adhesive capsulitis. METHODS: Patients were randomly assigned to 3 equal groups: steroid group, ozone group, and pulsed radiofrequency group. Pain and global shoulder functions were assessed using the VAS at rest and with movement, range of motion (ROM), and the SPADI. Moreover, ICAM-1 and hs-CRP were measured as inflammatory markers. RESULTS: The results of the current study reveal that all patients in all groups have had a statistically significant improvement after their intervention regarding pain, disability, ROM, and inflammatory markers. Pairwise comparisons revealed that improvement of the VAS during movement had a statistically significant improvement starting from the second week and continuing to the fourth and eighth week. VAS during rest had a significant improvement starting from follow-up week one in the steroid group. Moreover, improvement in the ROM and SPADI scores started from the second week follow-up. Percent improvement was calculated for each group and there was a statistically significant difference between groups in VAS at rest and ROM in the pulsed radiofrequency group compared to the steroid group.Regarding inflammatory markers, both ICAM-1 and hs-CRP had a significant improvement after all 3 interventions with no statistically significant difference among the groups. LIMITATIONS: This study is a single-center study. A shortage of previously published data, and heterogeneity in the published methodology of the 3 interventions limited our discussion data for comparison with the previous literature. CONCLUSION: Ultrasound-guided shoulder joint intraarticular injection of steroid, ozone, or pulsed radiofrequency application all result in a significant improvement in pain, disability, and ROM in primary adhesive capsulitis. They can be used as an effective treatment modality for this condition. Comparing groups statistically, the pulsed radiofrequency group had a more delayed, but statistically better long-term improvement compared to the other 2 groups.

Biomarkers in the era of targeted therapy in giant cell arteritis and polymyalgia rheumatica: is it possible to replace acute-phase reactants?

Research into giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) has become more important in the last few decades. Physicians are facing several challenges in managing the diagnosis, treatment, and relapses of GCA and PMR patients. The search for biomarkers could provide elements to guide a physician's decision. In this review, we aim to summarize the scientific publications about biomarkers in GCA and PMR in the past decade. The first point raised by this review is the number of clinical situations in which biomarkers could be useful: differential diagnosis of either GCA or PMR, diagnosis of underlying vasculitis in PMR, prediction of relapse or complications, disease activity monitoring, choice, and modification of treatments. The second point raised by this review is the large number of biomarkers studied, from common markers like C-reactive protein, erythrocyte sedimentation rate, or elements of blood count to inflammatory cytokines, growth factors, or immune cell subpopulations. Finally, this review underlines the heterogeneity between the studies and proposes points to consider in studies evaluating biomarkers in general and particularly in the case of GCA and PMR.

C reactive protein/Albumin ratio as predictor of prognosis in castration resistant metastatic prostate cancer.

OBJECTIVE: To assess the association of C reactive protein/Albumin ratio (CAR) with progression free survival (PFS) and overall survival (OS) in castration resistant metastatic prostate cancer (mCRPC) patients. MATERIALS AND METHODS: A transversal study was conducted, including all patients diagnosed with mCRPC within a Central Hospital Urological Oncology consultation between December 2019 and December 2021 (n = 178) and that were submitted to systemic therapy. CRP and albumin results were collected at the beginning of the systemic treatment for mCRPC in 103 patients and, in 75 patients already under treatment at the start of the study, on that occasion (December 2019). All patients were then followed. CAR was correlated with PFS and OS. OS and PFS were measured from the day the CRP and Alb were collected until the event of interest or the final date of follow-up. The sample was divided in two groups according to an optimal cutoff point found in a ROC curve. RESULTS: The sample showed a median age of 75.76 ± 9.17 years old. Using a cut-off point of 0.22, patients with a CAR ≤ 0.22 (63.2%) showed, compared to CAR > 0.22, longer PFS (15.92 vs. 9.46 months, r = -0.13, p < 0.05) and OS (p = < 0.05, 25,72 vs. 15.79 months, r = -0,24, p < 0.05). Better OS in patients with CAR ≤ 0.22 vs > 0.22 was detected on both the group evaluated at the beginning of systemic treatment (26.96 vs 17.63 months, p < 0.05) and the group of patients already under treatment (23.90 vs 11.54 months, p < 0.05). Dividing the sample according to the first line treatment chosen, we found OS of 26.25 vs 5.9 months (p < 0.05), 27.71 vs 22.57 months (p < 0.05) and 27.36 vs 23.75 months (p = 0.12), for docetaxel, abiraterone and enzalutamide, respectively. CONCLUSIONS: According to this study, higher values of CAR are associated with lower PFS and OS in mCRPC patients. We found a cut-off value of 0.22 providing the best discrimination for prognosis. CAR is a good prognosis biomarker, irrespective of the moment of evaluation and chosen treatment option.

Effectiveness of biosimilar infliximab CT-P13 compared to originator infliximab in biological-naïve patients with rheumatoid arthritis and axial spondyloarthritis: data from the Portuguese Register.

OBJECTIVES: To compare the effectiveness of the infliximab biosimilar CT-P13 with originator infliximab over 24 months of follow-up in biological-naïve patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA). METHODS: Biological-naïve patients from the Rheumatic Diseases Portuguese Register (Reuma.pt), with a clinical diagnosis of RA or axSpA, who were starting either the infliximab biosimilar CT-P13 or the originator infliximab after 2014 (date of market entry of CT-P13 in Portugal), were included. Patients on biosimilar and originator were compared regarding different response outcomes at 3 and 6 months, adjusting for age, sex and baseline C-reactive protein (CRP). The main outcome was the change in DAS28-erytrocyte sedimentation rate (ESR) for RA and the ASDAS-CRP for axSpA. Additionally, the effect of infliximab biosimilar vs originator on different response outcomes over 24 months of follow-up was tested with longitudinal generalized estimating equations (GEE) models. RESULTS: In total, 140 patients were included, 66 (47%) of which with RA. The distribution of patients starting the infliximab biosimilar and the originator was the same between the two diseases (approximately 60% and 40%, respectively). From the 66 patients with RA, 82% were females, mean age was 56 years (SD 11) and mean DAS28-ESR 4.9 (1.3) at baseline. As for the patients with axSpA, 53% were males, mean age was 46 years (13) and mean ASDAS-CRP 3.7 (0.9) at baseline. There were no differences in efficacy between RA patients treated with the infliximab biosimilar and the originator, either at 3 months (∆DAS28-ESR: -0.6 (95% CI -1.3; 0.1) vs -1.2 (-2.0; -0.4)), or at 6 months (∆DAS28-ESR: -0.7 (-1.5; 0.0) vs -1.5 (-2.4; -0.7)). This was also true for patients with axSpA (∆ASDAS-CRP at 3 months: -1.6 (-2.0; -1.1) vs -1.4 (-1.8; -0.9) and at 6 months: -1.5 (-2.0; -1.1) vs -1.1 (-1.5; -0.7)). Results were similar with the longitudinal models over 24 months. CONCLUSION: There are no differences in effectiveness between the infliximab biosimilar CT-P13 and the infliximab originator in the treatment of biological-naïve patients with active RA and axSpA in clinical practice.

Importance of Blood Glucose Management Before 18F-FDG PET/CT in 322 Patients with Bacteremia of Unknown Origin.

We investigated the effects of blood glucose levels on the performance of 18F-FDG PET/CT for detecting an infection focus in patients with bacteremia. Methods: A total of 322 consecutive patients with bacteremia who underwent 18F-FDG PET/CT between 2010 and 2021 were included. Logistic regression analysis was performed to evaluate the association between finding a true-positive infection focus on 18F-FDG PET/CT and blood glucose level, type of diabetes, and use of hypoglycemic medication. C-reactive protein, leukocyte count, duration of antibiotic treatment, and type of isolated bacteria were considered as well. Results: Blood glucose level (odds ratio, 0.76 per unit increase; P = <0.001) was significantly and independently associated with 18F-FDG PET/CT outcome. In patients with a blood glucose level between 3.0 and 7.9 mmol/L (54-142 mg/dL), the true-positive detection rate of 18F-FDG PET/CT varied between 61% and 65%, whereas in patients with a blood glucose level between 8.0 and 10.9 mmol/L (144-196 mg/dL), the true-positive detection rate decreased to 30%-38%. In patients with a blood glucose level greater than 11.0 mmol/L (200 mg/dL), the true-positive detection rate was 17%. In addition to C-reactive protein (odds ratio, 1.004 per point increase; P = 0.009), no other variables were independently associated with 18F-FDG PET/CT outcome. Conclusion: In patients with moderate to severe hyperglycemia, 18F-FDG PET/CT was much less likely to identify the focus of infection than in normoglycemic patients. Although current guidelines recommend postponing 18F-FDG PET/CT only in cases of severe hyperglycemia with glucose levels greater than 11 mmol/L (200 mg/dL), a lower blood glucose threshold seems to be more appropriate in patients with bacteremia of unknown origin and other infectious diseases.

Increased vascular risk factors, atherosclerosis, and psychological distress among Indian adults with refractory epilepsy in comparison to well-controlled epilepsy.

OBJECTIVE: Comparison of cardiovascular risk factors, atherosclerosis, and psychological distress among adults with refractory versus well-controlled epilepsy. METHODS: The cross-sectional study consisted of two groups of 40 people each: Group I - People with well-controlled epilepsy, Group II - People with refractory epilepsy. Age- and gender-matched people of 20-50 years were recruited. People who were diabetic, smokers, hypertensive, alcoholic, pregnant, with infections, and lactating women were excluded from the study. Biochemical parameters, fasting glucose, lipid profile, fasting insulin, leptin, adiponectin, Lp[a], hsCRP, TyG INDEX, HOMA1-%S, HOMA1-IR, HOMA1-%B, QUICKI, FIRI, AIP, AC, CLTI, MLTI, CRI-I, CRI-II, and CIMT were estimated. Stress levels [PSS-10, GAD-7 & PHQ-9] were assessed based on the scoring system from the questionnaires. RESULTS: The existence of metabolic syndrome, levels of triglycerides, TyG index, MDA, OSI, CIMT, AIP, and stress scores [PSS-10, GAD-7 & PHQ-9] were significantly higher in the refractory-epilepsy group in comparison to the well-controlled group. There were associations between LDL -C and CIMT as well as between GAD-7 and CIMT among all the study subjects. There were no significant differences in the levels of glucose homeostasis parameters, hsCRP, leptin, adiponectin, and Lp[a] between the two groups. Based on the ROC analysis, MDA [AUC = 0.853] and GAD-7 [AUC = 0.900] are useful in the differential diagnosis of the study groups. CONCLUSION: People with refractory epilepsy had increased levels of vascular risk factors, atherosclerosis, and stress levels compared to people with well-controlled epilepsy. Suitable disease management and therapeutic approaches to address cardiovascular and psychological distress could be planned out among people with refractory epilepsy to improve their quality of life.

Investigation of the Relationship between Inflammation and Oxidative Stress Markers and Treatment Response in First-Attack Major Depression Patients: A Follow-Up Study. / Ilk Atak Major Depresyon Hastalarinda Inflamasyon ve Oksidatif Stres Belirteçleri ile Tedavi Yaniti Iliskisinin Incelenmesi: Bir Izlem Çalismasi.

OBJECTIVE: There is a need to biomarkers for major depression (MD). The goals of this study are to compare serum levels of oxidative stress markers malondialdehyde (MDA) and F2-isoprostane and inflammation markers tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) between patients with first-episode MD and healthy controls, to investigate the change of these markers after treatment and to investigate the relationship between levels of these markers and treatment response. METHOD: Our study was performed in 30 first-episode MD patients and 30 healthy volunteers. During the clinical evaluation Hamilton Depression Rating Scale and Clinical Global Impression Scale were applied to the participants. Serum levels of markers were measured at the baseline and after 8 weeks of treatment. RESULTS: Compared to the control group, first-episode MD patients had significantly higher IL-6, CRP and MDA levels and lower F2- isoprostane levels. There was no difference between the groups in terms of TNF-α levels. TNF-α, IL-6, MDA and F2-isoprostane levels decreased significantly after treatment, whereas there was no significant change in CRP levels with treatment. Baseline F2-isoprostane levels were found to be significantly higher in treatment responders than nonresponders (p<0.05). CONCLUSION: In our study, it was shown that there are irregularities related to inflammatory processes and oxidative stress in MD, even in patients who had their first-episode and did not take medication, and these irregularities can be resolved after treatment. While there was a relationship between treatment response and baseline F2-isoprostane levels, there was no relationship with other biomarkers.

Effect of curcumin on rheumatoid arthritis: a systematic review and meta-analysis.

Objective: The aim of this study is to evaluate the effectiveness and safety of curcumin in rheumatoid arthritis patients. Methods: A computerized search from PubMed, Embase, Cochrane Library, and Web of Science databases was performed until 3 March 2023. Literature screening, basic data extraction and risk of bias evaluation were independently performed by two researchers each. The quality evaluation of the literature was performed according to the Cochrane Handbook for Risk of Bias Assessment tool for treatment evaluation. Results: The current study includes six publications covering 539 rheumatoid arthritis patients. The activity of rheumatoid arthritis was assessed using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), protein, disease activity score (DAS), rheumatoid factor (RF), Visual Analogue Scale (VAS) pain, tender joint count (TJC) and swollen joint count (SJC). ESR (MD = -29.47, 95% CI [-54.05, -4.88], Z=2.35, P = 0.02), DAS28 (MD = -1.20, 95% CI [-1.85, -0.55], Z=3.62, P = 0.0003), SJC (MD = -5.33, 95% CI [-9.90, -0.76], Z = 2.29, P = 0.02) and TJC (MD = -6.33, 95% CI [-10.86, -1.81], Z = 2.74, P = 0.006) showed significantly change in experimental patients compared with controls. Conclusion: Curcumin is beneficial for rheumatoid arthritis treatment. Inflammation levels and clinical symptoms in patients with rheumatoid arthritis can be improved by curcumin supplementation. Large sample randomized controlled trials on the effects of curcumin on patients with rheumatoid arthritis are needed in the future. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier (CRD42022361992).

Associations between peripheral inflammation and clinical phenotypes of bipolar depression in a lower-middle income country.

OBJECTIVE: There has been increased interest in repurposing anti-inflammatories for the treatment of bipolar depression. Evidence from high-income countries suggests that these agents may work best for specific depressive symptoms in a subset of patients with biochemical evidence of inflammation but data from lower-middle income countries (LMICs) is scarce. This secondary analysis explored the relationship between pretreatment inflammatory markers and specific depressive symptoms, clinical measures, and demographic variables in participants with bipolar depression in Pakistan. METHODS: The current study is a cross-sectional secondary analysis of a randomized controlled trial of two anti-inflammatory medications (minocycline and celecoxib) for bipolar depression (n = 266). A series of logistic and linear regression models were completed to assess the relationship between C-reactive protein (CRP) (CRP > or < 3 mg/L and log10CRP) and clinical and demographic features of interest and symptoms of depression. Baseline clinical trial data was used to extract clinical and demographic features and symptoms of depression were assessed using the 24-item Hamilton Depression Rating Scale. RESULTS: The prevalence of low-grade inflammation (CRP > 3 mg/L) in the sample was 70.9%. After adjusting for baseline body mass index, socioeconomic status, age, gender, symptoms related to anhedonia, fatigue, and motor retardation were most associated with low-grade inflammation. CONCLUSIONS: Bipolar disorder (BD) patients from LMICs may experience higher rates of peripheral inflammation than have been reported in Western populations with BD. Future trials of repurposed anti-inflammatory agents that enrich for participants with these symptom profiles may inform the development of personalized treatment for bipolar depression in LMICs.

The association of systemic inflammation and cognitive functions of pre-school aged children residing in a Schistosoma haematobium endemic area in Zimbabwe.

Background: Cognitive function is negatively impacted by schistosomiasis and might be caused by systemic inflammation which has been hypothesized to be one of the mechanisms driving cognitive decline, This study explored the association of systemic inflammatory biomarkers; interleukin (IL)-10, IL-6, IL-17, transforming growth factor (TGF-ß), tumor necrosis factor (TNF-α), C-reactive protein (CRP) and hematological parameters with cognitive performance of preschool-aged children (PSAC) from an Schistosoma haematobium endemic area. Methods: The Griffith III tool was used to measure the cognitive performance of 136 PSAC. Whole blood and sera were collected and used to quantify levels of IL-10, TNF-α, IL-6, TGF-ß, IL-17 A and CRP using the enzyme-linked immunosorbent assay and hematological parameters using the hematology analyzer. Spearman correlation analysis was used to determine the relationship between each inflammatory biomarker and cognitive performance. Multivariate logistic regression analysis was used to determine whether systemic inflammation due to S. haematobium infection affected cognitive performance in PSAC. Results: Higher levels of TNF-α and IL-6, were correlated with lower performance in the Foundations of Learning domain (r = -0.30; p < 0.001 and r = -0.26; p < 0.001), respectively. Low cognitive performance in the Eye-Hand-Coordination Domain was observed in PSAC with high levels of the following inflammatory biomarkers that showed negative correlations to performance; TNF-α (r = -0.26; p < 0.001), IL-6 (r = -0.29; p < 0.001), IL-10 (r = -0.18; p < 0.04), WBC (r = -0.29; p < 0.001), neutrophils (r = -0.21; p = 0.01) and lymphocytes (r = -0.25; p = 0.003) The General Development Domain correlated with TNF-α (r = -0.28; p < 0.001) and IL-6 (r = -0.30; p < 0.001). TGF-ß, L-17A and MXD had no significant correlations to performance in any of the cognitive domains. The overall general development of PSAC was negatively impacted by S. haematobium infections (OR = 7.6; p = 0.008) and (OR = 5.6; p = 0.03) where the PSAC had higher levels of TNF-α and IL-6 respectively. Conclusion: Systemic inflammation and S. haematobium infections are negatively associated with cognitive function. We recommend the inclusion of PSAC into mass drug treatment programs.

Inflammation markers and the risk of hypertension in people living with HIV.

Background: The incidence of hypertension is high in people living with HIV (PLWH). High-sensitivity C-reactive protein (hsCRP), systemic inflammation response index (SIRI), and neutrophil-to-monocyte ratio (NMR) are considered economic and convenient parameters that reflect the levels of inflammation in patients. Our aim was to explore whether indirect inflammation markers are associated with hypertension in PLWH. Methods: This was a case-control study. The case group (hypertension) comprised PLWH with hypertension, and the control group (non-hypertension) comprised sex- and age-(± 3 years)-matched PLWH without hypertension. Demographic parameters, hsCRP, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune- inflammation index (SII), SIRI, lymphocyte-to-monocyte ratio (LMR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), NMR, time to HIV diagnosis, antiretroviral therapy (ART) duration, recent CD4+ and CD8+ cell counts, recent CD4+/CD8+ ratio, recent HIV viral load (HIV-RNA),and recent ART regimen were obtained from the patients' electronic medical records. A t-test or Wilcoxon rank-sum test was performed to compare differences between the two groups, and conditional logistic regression was used to analyze the risk factors of hypertension. Correlations between inflammation markers and CD4+ cell counts, CD8+ cell counts, and CD4+/CD8+ ratio were analyzed using Spearman's correlation. Results: In the hypertension group, body mass index (BMI), hsCRP, NLR, SII, SIRI, NMR, time to HIV diagnosis, ART duration, CD4+ and CD8+ cell counts, and CD4+/CD8+ ratio, the ratio of HIV-RNA < 100 copies/mL were all higher than those in the non-hypertension group, while the PNR was lower than that in the non-hypertension group. ART duration, CD4+ cell counts, HIV-RNA < 100 copies/mL, hsCRP, SIRI, and NMR were positively associated with hypertensive risk in PLWH. CD8+ cell counts and CD4+/CD8+ ratio was negatively associated with hypertensive risk in PLWH. SIRI was negatively correlated with CD4+ cell counts and CD8+ cell counts, but positively correlated with CD4+/CD8+ ratio. Conclusions: We identified positive associations between inflammation markers hsCRP, SIRI, NMR and hypertensive risk in PLWH. Alleviating inflammation may help control or delay the occurrence of hypertension in PLWH.

Early C-reactive protein kinetics predicts immunotherapy response in non-small cell lung cancer in the phase III OAK trial.

Static biomarkers like programmed death-ligand 1 (PD-L1) are insufficient to accurately predict response to immune checkpoint inhibition. Therefore, on-treatment biomarkers, which measure immediate therapy-associated changes, are currently shifting into the focus of immuno-oncology. A prime example of a simple predictive on-treatment biomarker is the early C-reactive protein (CRP) kinetics with its predictive CRP flare-response phenomenon. Here, we were able to confirm the predictive value of CRP flare-response kinetics in the pivotal phase III OAK trial (NCT02008227), which compared atezolizumab with docetaxel in patients with non-small cell lung cancer. Of note, CRP flare-response predicted favorable outcomes only in the immune checkpoint inhibition-treated subgroup, which suggests that it is an immunotherapy-specific phenomenon. In conclusion, we have for the first time validated the high predictive value of early CRP kinetics in a pivotal phase III trial, justifying the broad use of this cost-effective and easy-to-implement on-treatment biomarker to optimize therapy monitoring for patients with non-small cell lung cancer.

Polymyalgia rheumatica during combination therapy with atezolizumab plus bevacizumab for advanced hepatocellular carcinoma.

The combination therapy of atezolizumab, an anti-programmed cell death ligand-1 antibody, plus bevacizumab (Atz/Bev) is widely used to treat patients with advanced hepatocellular carcinoma (HCC). The development of polymyalgia rheumatica (PMR) during immune checkpoint inhibitor therapy for patients with HCC has not been reported to date. Two patients who developed PMR during Atz/Bev therapy for advanced HCC are reported. Both patients developed fever, bilateral symmetrical shoulder pain, morning stiffness, and an elevated C-reactive protein level. Their symptoms improved rapidly with prednisolone (PSL) 15-20 mg/d, and their C-reactive protein levels decreased. In PMR, long-term low-dose PSL should be administered. In the present patients who developed PMR as immune-related adverse events, starting with a small dose of PSL resulted in rapid improvement of symptoms.

Cardiometabolic Risk Factors in Atorvastatin-Treated Women with Euthyroid Autoimmune Thyroiditis.

INTRODUCTION: Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity. METHODS: We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto's) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29). Plasma lipids, glucose homeostasis markers, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before atorvastatin treatment and 6 months later. RESULTS: At entry, both groups differed in antibody titers, insulin sensitivity, and plasma levels of uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. Atorvastatin-induced reduction in hsCRP and homocysteine, but not in total cholesterol and LDL-cholesterol, was more pronounced in group B than in group A. Only in group B, the drug decreased uric acid and fibrinogen and increased 25-hydroxyvitamin D. In group A, atorvastatin reduced insulin responsiveness. CONCLUSION: The obtained results indicate that euthyroid women with Hashimoto's thyroiditis may benefit to a lesser degree from atorvastatin treatment than other populations of women with hypercholesterolemia.

Assessing acute colitis induced by dextran sulfate sodium in rats and its impact on gastrointestinal fluids.

Dextran sulfate sodium (DSS) is commonly used to induce colitis in rats. While the DSS-induced colitis rat model can be used to test new oral drug formulations for the treatment of inflammatory bowel disease, the effect of the DSS treatment on the gastrointestinal tract has not been thoroughly characterized. Additionally, the use of different markers to assess and confirm successful induction of colitis is somewhat inconsistent. This study aimed to investigate the DSS model to improve the preclinical evaluation of new oral drug formulations. The induction of colitis was evaluated based on the disease activity index (DAI) score, colon length, histological tissue evaluation, spleen weight, plasma C-reactive protein, and plasma lipocalin-2. Furthermore, the study investigated how the DSS-induced colitis affected the luminal pH, lipase activity, and concentrations of bile salts, polar lipids, and neutral lipids. For all evaluated parameters, healthy rats were used as a reference. The DAI score, colon length, and histological evaluation of the colon were effective disease indicators in DSS-induced colitis rats, while spleen weight, plasma C-reactive protein, and plasma lipocalin-2 were not. The luminal pH of the colon and bile salt- and neutral lipid concentrations in regions of the small intestine were lower in DSS-induced rats compared to healthy rats. Overall, the colitis model was deemed relevant for investigating ulcerative colitis-specific formulations.