scholarly journals Does Sodium Intake Induce Systemic Inflammatory Response? A Systemic Review and Meta-Analysis of Randomized Studies in Humans

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2632
Author(s):  
Eirini D. Basdeki ◽  
Anastasios Kollias ◽  
Panagiota Mitrou ◽  
Christiana Tsirimiagkou ◽  
Marios K. Georgakis ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Sodium Intake ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Systemic Inflammatory Response ◽  
Population Characteristics ◽  
Systemic Review ◽  
Methodological Issues ◽  
Wide Range ◽  
Daily Sodium Intake

Experimental studies suggest that sodium induced inflammation might be another missing link leading to atherosclerosis. To test the hypothesis that high daily sodium intake induces systemic inflammatory response in humans, we performed a systematic review according to PRISMA guidelines of randomized controlled trials (RCTs) that examined the effect of high versus low sodium dose (HSD vs. LSD), as defined per study, on plasma circulating inflammatory biomarkers. Eight RCTs that examined CRP, TNF-a and IL-6 were found. Meta-analysis testing the change of each biomarker in HSD versus LSD was possible for CRP (n = 5 studies), TNF-a (n = 4 studies) and IL-6 (n = 4 studies). The pooled difference (95% confidence intervals) per biomarker was for: CRP values of 0.1(−0.3, 0.4) mg/L; TNF-a −0.7(−5.0, 3.6) pg/mL; IL-6 −1.1(−3.3 to 1.1) pg/mL. Importantly, there was inconsistency between RCTs regarding major population characteristics and the applied methodology, including a very wide range of LSD (460 to 6740 mg/day) and HSD (2800 to 7452 mg/day). Although our results suggest that the different levels of daily sodium intake are not associated with significant changes in the level of systemic inflammation in humans, this outcome may result from methodological issues. Based on these identified methodological issues we propose that future RCTs should focus on young healthy participants to avoid confounding effects of comorbidities, should have three instead of two arms (very low, “normal” and high) of daily sodium intake with more than 100 participants per arm, whereas an intervention duration of 14 days is adequate.

Phase 1b Study Of Otlertuzumab (TRU-016), An Anti-CD37 ADAPTIR™ Protein, In Combination With Rituximab In Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4165-4165
Author(s):  
Kami Maddocks ◽  
John M. Pagel ◽  
Susan O'Brien ◽  
John C. Byrd ◽  
Scott Stromatt ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adverse Events ◽  
Inflammatory Response ◽  
Research Funding ◽  
Response Rate ◽  
Systemic Inflammatory Response ◽  
Hematologic Toxicity ◽  
Color Flow ◽  
Wide Range ◽  
Phase 1B

Abstract Background CD37 is a tetraspanin protein expressed on the surface of normal and transformed B-cells across a wide range of maturational stages and demonstrates death signaling via SHP1. Otlertuzumab is a CD37-specific therapeutic protein built on the ADAPTIR™(modular protein technology) platform that has shown significantly greater direct killing of CLL cells than rituximab and higher levels of Fc-mediated cellular cytotoxicity of CLL cells than either alemtuzumab or rituximab in pre-clinical models. This phase 1b trial was conducted to evaluate the safety and efficacy of otlertuzumab in combination with rituximab in patients with previously untreated CLL. Methods Patients with untreated CLL that required treatment, had adequate organ function, ECOG ≤2, and absolute neutrophil count ≥800/μL were eligible. Patients were ineligible for chemotherapy as first-line therapy due to patient age, comorbidity, or patient refusal of chemotherapy Patients received otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then once a month for 4 months. Rituximab (375 mg/m2 the first dose then 500 mg/m2) was administered after otlertuzumab by IV infusion on the same schedule. Safety was evaluated using CTCAE and IWCLL 2008 Grading scale for Hematologic Toxicity in CLL Studies. Response was determined using the 1996 NCI and the 2008 IWCLL Criteria. Results 24 patients have been treated. Patient characteristics and adverse events are shown in the table. The majority of the patients have not completed 6 cycles of therapy. The preliminary response by investigator assessment using NCI criteria at the last assessment is an ORR 88% (21/24); 2 patients have had PD. Six patients have had CT scans and bone marrow assessments 3 months after their last dose of study drug; by IWCLL criteria 1 has a CR, 4 have a PR and 1 has SD. The patient with a CR was MRD negative by five color flow cytometry of bone marrow aspirate. One patient discontinued therapy for a systemic inflammatory response. Severe (Grade 3 or 4) neutropenia was reported in 13% of patients; the incidence of severe infections was low (8%). Serious adverse events were reported for 4 patients: pneumonia, systemic inflammatory response, and deep vein thrombosis in 1 patient; and lymph node pain, worsening sinusitis, and fever in 1 patient each. Conclusions The preliminary response rate with otlertuzumab in combination with rituximab is promising. Follow-up is ongoing and the IWCLL response rate will be presented. Disclosures: O'Brien: Emergent Product Development: Research Funding. Stromatt:Emergent Biosolutions: Employment. Awan:Lymphoma Research Foundation - Research Funding: Research Funding, Speakers Bureau; Spectrum Pharmaceuticals, Inc. - Speakers bureau: Research Funding, Speakers Bureau.

scholarly journals Re-Evaluating Biologic Pharmacotherapies that Target the Host Response during Sepsis

2019 ◽  
Vol 20 (23) ◽  
pp. 6049 ◽  
Author(s):  
Tuttle ◽  
McDonald ◽  
Anderson
Keyword(s):  
Clinical Trials ◽  
Inflammatory Response ◽  
Host Response ◽  
Multiple Organ ◽  
Systemic Inflammatory Response ◽  
Exclusion Criteria ◽  
Additional Risk ◽  
Wide Range ◽  
Post Hoc ◽  
Patient Subgroups

Multiple organ dysfunction syndrome (MODS) caused by the systemic inflammatory response during sepsis is responsible for millions of deaths worldwide each year, and despite broad consensus concerning its pathophysiology, no specific or effective therapies exist. Recent efforts to treat and/or prevent MODS have included a variety of biologics, recombinant proteins targeting various components of the host response to the infection (e.g., inflammation, coagulation, etc.) Improvements in molecular biology and pharmaceutical engineering have enabled a wide range of utility for biologics to target various aspects of the systemic inflammatory response. The majority of clinical trials to date have failed to show clinical benefit, but some have demonstrated promising results in certain patient populations. In this review we summarize the underlying rationale and outcome of major clinical trials where biologics have been tested as a pharmacotherapy for MODS in sepsis. A brief description of the study design and overall outcome for each of the major trials are presented. Emphasis is placed on discussing targets and/or trials where promising results were observed. Post hoc analyses of trials where therapy demonstrated harm or additional risk to certain patient subgroups are highlighted, and details are provided about specific trials where more stringent inclusion/exclusion criteria are warranted.

scholarly journals The Impact of Peer Assessment on Academic Performance: A Meta-analysis of Control Group Studies

2018 ◽  
Author(s):  
Kit S Double
Keyword(s):  
Academic Performance ◽  
Peer Assessment ◽  
Meta Analysis ◽  
Experimental Studies ◽  
Teacher Assessment ◽  
Medium Effect ◽  
Practice Research ◽  
Control Group ◽  
Wide Range ◽  
The Impact

Peer assessment has been the subject of considerable research interest over the last three decades, with numerous educational researchers advocating for the integration of peer assessment into schools and instructional practice. Research synthesis in this area has, however, largely relied on narrative reviews to evaluate the efficacy of peer assessment. Here we present a meta-analysis (54 studies, k = 141) of experimental and quasi-experimental studies that evaluated the effect of peer assessment on academic performance in primary, secondary, or tertiary students across subjects and domains. An overall small to medium effect of peer assessment on academic performance was found (g = 0.31, p < .001). The results suggest that peer assessment improves academic performance compared with no assessment (g = 0.31, p < .001) and teacher assessment (g = 0.28, p = .007), but was not significantly different in its effect from self-assessment (g = 0.23, p = .209). Additionally, meta-regressions examined the moderating effects of several feedback and educational characteristics (e.g. online vs offline, frequency, education level etc.). Results suggested that the effectiveness of peer assessment was remarkably robust across a wide range of contexts. These findings provide support for peer assessment as a formative practice and suggest several implications for the implementation of peer assessment into the classroom.

Sign in / Sign up

Export Citation Format

Share Document