scholarly journals Clinical Response to the CD95-Ligand Inhibitor Asunercept Is Defined by a Pro-Inflammatory Serum Cytokine Profile

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3683
Author(s):  
Aleksandar Radujkovic ◽  
Tobias Boch ◽  
Florian Nolte ◽  
Daniel Nowak ◽  
Claudia Kunz ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Characteristic Curve ◽  
Treatment Phase ◽  
Serum Levels ◽  
Cytokine Profile ◽  
Serum Cytokine ◽  
Baseline Serum ◽  
Post Hoc Analysis ◽  
Cd95 Ligand ◽  
Post Hoc

Asunercept (APG101) is a well-tolerated CD95-ligand inhibitor that showed promising efficacy in a prospective, single-arm phase I study in anemic, transfusion-dependent patients with low and intermediate risk myelodysplastic syndrome (MDS). In this retrospective post hoc analysis, serum levels of biomarkers were measured in study patients focusing on cytokines associated with erythropoiesis, inflammation, apoptosis, bone marrow fibrosis, and inflammasome activity. Baseline serum biomarkers were correlated with treatment response, in order to propose a hypothetical responder serum profile. After an updated median follow-up of 54 months (range 7–65), response to asunercept was associated with improved overall survival (at 3-years: 67% [95%CI 36–97] versus 13% [95%CI 0–36] in responders versus non-responders, respectively). Higher baseline values of interleukin-18 (IL-18), S100 calcium-binding protein A9 (S100A9) and soluble p53 were predictive of non-response to asunercept (area under the receiver operating characteristic curve 0.79–0.82). Furthermore, non-responding patients showed a distinct, pro-inflammatory serum cytokine profile which was persistent throughout the first half of the treatment phase and appeared unaffected by asunercept. Although prospective validation is required, our post hoc analysis suggests that serum cytokine profiling based on IL-18, S100A9 and soluble p53 may represent an approach to identify and select low-risk MDS patients most likely to benefit from asunercept treatment.

scholarly journals Iron serum levels and iron homeostasis parameters in patients with nosocomial pneumonia treated with cefiderocol: post hoc analysis of the APEKS-NP study

2022 ◽  
Author(s):  
Eric P. Skaar ◽  
Roger Echols ◽  
Yuko Matsunaga ◽  
Anju Menon ◽  
Simon Portsmouth
Keyword(s):  
Nosocomial Pneumonia ◽  
Serum Iron ◽  
Iron Homeostasis ◽  
Binding Capacity ◽  
Transferrin Saturation ◽  
Efficacy And Safety ◽  
Baseline Serum ◽  
Post Hoc Analysis ◽  
Iron Binding Capacity ◽  
Post Hoc

AbstractCritically ill patients often present with low serum iron levels or anemia. We evaluated the impact of iron levels and iron homeostasis on the efficacy and safety of cefiderocol, an iron-chelator siderophore cephalosporin, in patients with nosocomial pneumonia in a post hoc analysis of the randomized, double-blind, Phase 3 APEKS-NP study (NCT03032380). Patients with Gram-negative nosocomial pneumonia received cefiderocol 2 g, 3-h infusion, q8h, or high-dose, extended-infusion meropenem 2 g, 3-h infusion, q8h, for 7–14 days. Efficacy and safety parameters, including specific iron homeostasis parameters (i.e., hepcidin, iron, total iron binding capacity, transferrin saturation), were analyzed according to baseline iron levels. In the cefiderocol and meropenem arms, 79.1% (117/148) and 83.3% (125/150) randomized patients, respectively, had low baseline serum iron levels. Rates of 14-day (12.3% [14/114] vs 11.6% [14/121]) and 28-day all-cause mortality (20.5% [23/112] vs 19.0% [23/121]), clinical cure (63.2% [72/114] vs 67.2% [82/122]), and microbiological eradication (43.6% [41/94] vs 48.1% [51/106]) at test of cure were similar in cefiderocol vs meropenem arms, respectively. In the overall safety population, rates of anemia-related adverse events were similar (cefiderocol arm 18.2% [27/148], meropenem arm 18.7% [28/150]). Changes from baseline to test of cure in hepcidin, iron, total iron binding capacity, and transferrin saturation were similar between treatment arms. Cefiderocol treatment did not affect iron homeostasis, and its efficacy and safety were not influenced by baseline serum iron levels. Clinicaltrials.gov registration: NCT03032380. Date of registration: 26 January 2017.

Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

2016 ◽  
Vol 82 ◽  
pp. 578-582 ◽  
Author(s):  
Yunes Panahi ◽  
Mahboobeh Sadat Hosseini ◽  
Nahid Khalili ◽  
Effat Naimi ◽  
Luis E. Simental-Mendía ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Randomized Controlled Trial ◽  
Controlled Trial ◽  
Serum Cytokine ◽  
Post Hoc Analysis ◽  
Randomized Controlled ◽  
Post Hoc

scholarly journals Effects of propofol and dexmedetomidine with and without remifentanil on serum cytokine concentrations in healthy volunteers: a post hoc analysis

2020 ◽  
Vol 125 (3) ◽  
pp. 267-274
Author(s):  
Dirk J. Bosch ◽  
Matijs V. Meurs ◽  
Rianne M. Jongman ◽  
Peter Heeringa ◽  
Wayel H. Abdulahad ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Serum Cytokine ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Erenumab prevents the occurrence of migraine attacks and not just migraine days: Post-hoc analyses of a phase III study

Cephalalgia ◽  
2021 ◽  
pp. 033310242110103
Author(s):  
Hans-Christoph Diener ◽  
Messoud Ashina ◽  
Shannon Ritter ◽  
Gabriel Paiva Da Silva Lima ◽  
Soeren Rasmussen ◽  
...  
Keyword(s):  
Migraine Attack ◽  
Treatment Phase ◽  
Episodic Migraine ◽  
Trial Registration ◽  
Phase Iii ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Phase Iii Study ◽  
A Minor ◽  
Post Hoc

Background This post-hoc analysis was conducted to evaluate the effect of erenumab on monthly migraine days, monthly migraine attacks, and attack duration in patients with episodic migraine to investigate whether erenumab actually prevents the occurrence of migraine attacks and/or shortens them. Methods We conducted a post-hoc analysis of the data from the STRIVE study, in 955 patients with episodic migraine. Relative changes from baseline to mean over months 4, 5 and 6 of the double-blind treatment phase in monthly migraine days, monthly migraine attacks and mean migraine attack duration were assessed. Results Erenumab reduced monthly migraine days and monthly migraine attacks compared with placebo in a similar way. Erenumab had only a minor impact on shortening the duration of migraine attacks. Conclusion These post-hoc analyses demonstrate that the decrease in monthly migraine days by erenumab is mainly driven by a reduction in the frequency of monthly migraine attacks and to a much lesser extent by shortening the duration of migraine attacks. Trial registration: This study is registered at ClinicalTrials.gov (NCT02456740)

Myeloid-related Protein 8/14 Levels in Rheumatoid Arthritis: Marker of Disease Activity and Response to Methotrexate

2016 ◽  
Vol 43 (4) ◽  
pp. 731-737 ◽  
Author(s):  
Pradeepta Sekhar Patro ◽  
Ankita Singh ◽  
Ramnath Misra ◽  
Amita Aggarwal
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Calcium Binding ◽  
Rescue Therapy ◽  
Disease Onset ◽  
Serum Levels ◽  
Characteristic Analysis ◽  
Baseline Serum ◽  
Reactive Protein ◽  
First Line Therapy

Objective.Myeloid-related proteins (MRP) 8/14 belong to a family of calcium-binding proteins produced by myeloid cells. Baseline serum levels of MRP8/14 have been shown to predict response to biologicals in rheumatoid arthritis (RA). Because methotrexate (MTX) is the first-line therapy in RA, we studied whether MRP8/14 levels can predict response to MTX.Methods.Patients with active RA disease who were naive to disease-modifying antirheumatic drugs were enrolled. All patients were treated with MTX only, to a maximum of 25 mg/week or the maximal tolerated dose. At 4 months, the European League Against Rheumatism response was assessed. All patients who needed rescue therapy after 2 months or who did not respond at 4 months were classified as nonresponders.Results.Ninety patients were enrolled, of whom 3 discontinued MTX within 4–6 weeks, so 87 patients were analyzed [74 women, median (interquartile range; IQR) for the Disease Activity Score at 28 joints (DAS28) was 4.43 (4.1–5.1)]. The median (IQR) serum MRP8/14 level at baseline was 19.95 µg/ml (11.49–39.06). The serum MRP8/14 had good correlation with DAS28-C-reactive protein (CRP; r = 0.35, p = 0.001). The MRP8/14 levels fell significantly after 4 months of treatment (10.28 µg/ml, 5.95–16.05, p < 0.001). Among 87 patients, 69 were responders. The median (IQR) baseline level of MRP8/14 was higher among responders compared with nonresponders: 23.99 µg/ml (15.39–42.75) versus 9.58 µg/ml (6.11–24.93, p = 0.00250). The levels declined in the responders, from 23.99 µg/ml (15.39–42.75) to 10.41 µg/ml (5.83–15.61, p < 0.001), but not in the nonresponders, from 9.58 µg/ml (6.11–24.93) to 9.19 µg/ml (7.74–21.96, p = 0.687). Receiver-operation characteristic analysis showed that MRP8/14 was a better predictor of response than CRP and erythrocyte sedimentation rate, especially with early disease onset (< 1-yr duration).Conclusion.MRP8/14 is a good marker of disease activity in RA, and higher levels predict response to MTX.

scholarly journals Serum Cytokine Profile in Patients with Septic Shock/Severe Sepsis and Thrombocytopenia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1426-1426
Author(s):  
Panagiotis Tsirigotis ◽  
Konstantinos Gkirkas ◽  
Spiros Chondropoulos ◽  
Ioannis Papassotiriou ◽  
Anastasia Bartzeliotou ◽  
...  
Keyword(s):  
Septic Shock ◽  
Logistic Regression ◽  
Severe Sepsis ◽  
Hospital Mortality ◽  
Serum Levels ◽  
Cytokine Profile ◽  
Multiple Logistic Regression ◽  
Serum Cytokine ◽  
Group A ◽  
Group B

Abstract Introduction Sepsis is the result of an uncontrolled inflammatory response to various stimuli such as bacterial infections. Sepsis can be complicated by hemodynamic instability, multi-organ dysfunction and hematological abnormalities. Patients with severe sepsis usually develop thrombocytopenia due to various reasons, and the presence of thrombocytopenia is considered as a negative prognostic marker. The aim of the present study was to determine the cytokine profile in serum of patients with severe sepsis and thrombocytopenia. Patients and Methods Serum cytokine profile was analyzed in a cohort of 112 consecutive patients with severe sepsis and/or septic shock treated in the intensive care unit (ICU) of our institute from October/2009 to September/2012. Patients were divided in two groups (A and B). Group A consisted of 43 patients with severe sepsis and thrombocytopenia (platelet count below 70X103/ìl), while group B consisted of 69 patients without thrombocytopenia. Patients with thrombocytopenia due to disseminated intravascular coagulation (DIC), suspected drug etiology, or due to any obvious etiology such as hematologic malignancy were excluded from our analysis. A cohort of 10 healthy volunteers served as control group. Serum levels of IFNã, IL-8, ICAM, VCAM, and SUPAR (soluble urokinase plasminogen activation receptor) were estimated by using Luminex xMAP technology. Statistical analyses were performed using NCSS software. The following variables were entered in a multiple logistic regression model: 1) age and sex, 2) active malignancy vs. not, 3) septic shock vs. severe sepsis, 4) APACHEII score, 5) SOFA score, 6) serum IFNã, ICAM, VCAM, IL-8, and SUPAR levels, and 7) platelet number. All parameters were estimated on day of admission. Results Hospital Mortality: Overall 65 out of 112 patients died during their hospital stay. The overall hospital mortality was 58%. In multivariate analysis non-survivors had higher APACHE score (p=0.01) and had lower platelet counts (p<0.001) as compared with survivors. Plasma cytokine levels in patients with and without thrombocytopenia: Patients in group A had a different cytokine profile as compared with patients in group B. Serum levels of VCAM and IFNã were not different between group A and B. However, patients with sepsis and thrombocytopenia had statistically significantly higher serum levels of ICAM, IL-8 and SUPAR (p<0.0001) in comparison with patients with severe sepsis and normal PLT count. Predictive value of serum cytokine for thrombocytopenia: Serum levels of ICAM, IL-8, and SUPAR were good predictors of the presence of thrombocytopenia in patients with sepsis. The ROC curves of ICAM, IL-8, and SUPAR serum levels in predicting thrombocytopenia in patients with sepsis are shown in Figure 1. The AUCs were 0.785 (95% CI, 0.696 – 0.857, p<0.001), 0.729 (95% CI, 0.637 – 0.809, p<0.001), 0.789 (95% CI, 0.701 – 0.861, p<0.001) for ICAM, IL-8 and SUPAR levels respectively. However in multiple logistic regression analysis serum levels of ICAM was the most powerful predictor of thrombocytopenia. Conclusion Thrombocytopenia is not an uncommon finding in patients with severe sepsis. Although DIC or drug reactions are well known causes of low PLT counts, the pathogenesis of thrombocytopenia in patients with sepsis remains poorly understood. High levels of ICAM, IL-8 and SUPAR are usually associated with severe endothelial dysfunction. In our study, we showed that patients with thrombocytopenia have a specific serum cytokine profile expression consistent with the presence of endothelial damage. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Vitamin D3 Supplementation Increases Long-Chain Ceramide Levels in Overweight/Obese African Americans: A Post-Hoc Analysis of a Randomized Controlled Trial

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 981
Author(s):  
Li Chen ◽  
Yanbin Dong ◽  
Jigar Bhagatwala ◽  
Anas Raed ◽  
Ying Huang ◽  
...  
Keyword(s):  
Vitamin D ◽  
African Americans ◽  
Vitamin D3 ◽  
Dose Response ◽  
Serum Levels ◽  
Sphingolipid Metabolism ◽  
Post Hoc Analysis ◽  
Vitamin D3 Supplementation ◽  
Post Hoc ◽  
Long Chain

Sphingolipid metabolism plays a critical role in cell growth regulation, lipid regulation, neurodevelopment, type 2 diabetes, and cancer. Animal experiments suggest that vitamin D may be involved in sphingolipid metabolism regulation. In this study, we tested the hypothesis that vitamin D supplementation would alter circulating long-chain ceramides and related metabolites involved in sphingolipid metabolism in humans. We carried out a post-hoc analysis of a previously conducted randomized, placebo-controlled clinical trial in 70 overweight/obese African-Americans, who were randomly assigned into four groups of 600, 2000, 4000 IU/day of vitamin D3 supplements or placebo for 16 weeks. The metabolites were measured in 64 subjects (aged 26.0 ± 9.4 years, 17% male). Serum levels of N-stearoyl-sphingosine (d18:1/18:0) (C18Cer) and stearoyl sphingomyelin (d18:1/18:0) (C18SM) were significantly increased after vitamin D3 supplementation (ps < 0.05) in a dose–response fashion. The effects of 600, 2000, and 4000 IU/day vitamin D3 supplementation on C18Cer were 0.44 (p = 0.049), 0.52 (p = 0.016), and 0.58 (p = 0.008), respectively. The effects of three dosages on C18SM were 0.30 (p = 0.222), 0.61 (p = 0.009), and 0.68 (p = 0.004), respectively. This was accompanied by the significant correlations between serum 25-hydroxyvitamin D3 [25(OH)D] concentration and those two metabolites (ps < 0.05). Vitamin D3 supplementations increase serum levels of C18Cer and C18SM in a dose–response fashion among overweight/obese African Americans.

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