Reduction In C-reactive Protein Research Articles

Crohn's strictures open with anti-mycobacterial antibiotic therapy: A retrospective review.

BACKGROUNDMedical therapy for strictures is limited and first-line treatment consists of endoscopic balloon dilatation, strictureplasty or surgical resection. Mycobacterium tuberculosis, Helicobacter pylori and Streptococcus can all cause stenosis, for which antibiotic treatment achieves stricture resolution. Mycobacterium avium ssp. paratuberculosis is a suspected causative agent in Crohn’s disease (CD). Thus, specialized antimicrobial treatment, in particular, anti-mycobacterial antibiotic therapy (AMAT) has been proposed as a potential treatment option. To our knowledge, the opening of CD strictures has not been recorded using any form of antibiotic therapy. We hypothesized that AMAT would resolve strictures in patients with CD.AIMTo investigate the effect and outcomes of AMAT in a cohort of CD patients with an ileal stricture.METHODSA single center, retrospective, medical record case review was conducted on an observational cohort of patients with CD who had an ileal stricture on colonoscopy and were treated with AMAT. Forty patients meeting the inclusion criteria were identified from the internal medical database. Thirty (75%) patients had follow-up colonoscopy and clinical data available. The AMAT regimen was prescribed after the initial colonoscopy for a duration of at least six months until follow-up colonoscopy with the attending gastroenterologist. Patient demographics, symptoms, colonoscopy reports, inflammatory serum markers and concurrent medications were recorded at pre-treatment and follow-up between January 1995 and June 2018.RESULTSOf the patients that returned for follow-up after > 24 mo of AMAT, twenty (67%) had complete resolution (CR) of their ileal strictures, three (10%) had partial resolution and seven (23%) had no resolution. Irrespective of stricture outcome, 21 patients (70%) demonstrated clinical response to AMAT and there was a statistically significant reduction in inflammatory serum markers C-reactive protein (P < 0.0001) and erythrocyte sedimentation rate (P = 0.04) from pre-treatment to follow-up. It was observed that 11 (37%) patients experienced side effects, but no serious adverse effects were attributable to AMAT. At follow-up there were 26 (87%) patients on concomitant medication for CD and a statistically significant association between CR and AMAT with a concomitant immunomodulator (P = 0.02).CONCLUSIONThis study demonstrated a high rate of stricture resolution (67%) similar to that seen in tuberculosis strictures (70%), suggesting a shared mycobacterial origin of strictures, and perhaps disease.

Anti-inflammatory effects of oral supplementation with curcumin: a systematic review and meta-analysis of randomized controlled trials.

Chronic inflammation is a major contributor to the development of noncommunicable diseases. Curcumin, a bioactive polyphenol from turmeric, is a well-known anti-inflammatory agent in preclinical research. Clinical evidence remains inconclusive because of discrepancies regarding optimal dosage, duration, and formulation of curcumin. The aim of this systematic review, conducted and reported in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and checklist, was to evaluate the efficacy of curcumin supplementation on systemic inflammatory mediators, comparing dose, duration, and bioavailability status of interventions. The Medline, CINAHL, EMBASE, Scopus, and Cochrane literature databases were searched from 1980 to May-end 2019. Randomized controlled trials investigating effects of dietary curcumin on inflammatory mediators in humans not receiving anti-inflammatory treatment were eligible for inclusion. Two authors independently assessed titles and abstracts of identified articles for potential eligibility and respective, retrieved, full-text articles; disagreements were resolved by a third author. Evidence quality was critically appraised using the Quality Criteria Checklist for Primary Research. Thirty-two trials (N = 2,038 participants) were included and 28 were meta-analyzed using a random-effects model; effect sizes were expressed as Hedges' g (95%CI). Pooled data (reported here as weighted mean difference [WMD]; 95%CI) showed a reduction in C-reactive protein (-1.55 mg/L; -1.81 to -1.30), interleukin-6 (-1.69 pg/mL, -2.56 to -0.82), tumor necrosis factor α (-3.13 pg/mL; -4.62 to -1.64), IL-8 (-0.54 pg/mL; -0.82 to -0.28), monocyte chemoattractant protein-1 (-2.48 pg/mL; -3.96 to -1.00), and an increase in IL-10 (0.49 pg/mL; 0.10 to 0.88), with no effect on intracellular adhesion molecule-1. These findings provide evidence for the anti-inflammatory effects of curcumin and support further investigation to confirm dose, duration, and formulation to optimize anti-inflammatory effects in humans with chronic inflammation. PROSPERO registration no. CRD42019148682.

Ziltivekimab for Treatment of Anemia of Inflammation in Patients on Hemodialysis: Results from a Phase 1/2 Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

Patients with CKD who are on hemodialysis are hyporesponsive to erythropoiesis-stimulating agents (ESAs) because of anemia of inflammation. Interleukin-6 (IL-6) induced hepcidin expression is a key mediator of such inflammation. This phase 1/2, placebo-controlled trial assessed effects of ziltivekimab, a novel anti-IL-6 ligand antibody, in patients on hemodialysis with rs855791, a single nucleotide polymorphism of the TMPRSS6 gene that is hypothesized to heighten susceptibility to IL-6-mediated inflammatory effects. After a screening period documenting stable ESA and iron dosing, we randomized 61 patients with elevated IL-6 (≥4 pg/ml) to receive placebo or ziltivekimab (doses of 2, 6, or 20 mg), administered intravenously every 2 weeks for 12 weeks during hemodialysis. ESA dose adjustments were allowed after 4 weeks. We analyzed safety and effects on inflammation, iron metabolism, serum albumin, and anti-drug antibodies. No patient experienced dose-limiting toxicity. Four patients (two each in the 6- and 20-mg cohorts) died of a treatment-emergent adverse event. Compared with patients receiving placebo, those receiving ziltivekimab experienced significantly greater reductions of high-sensitivity C-reactive protein, serum amyloid A, and fibrinogen from baseline to end of treatment. Median ESA usage decreased by 15,000, 15,000, or 33,000 IU/wk per patient in the 2-, 6-, and 20-mg ziltivekimab cohorts, respectively, compared with no change in the placebo group. We also noted significant dose responses for decreased ESA resistance index and increased serum iron, total iron binding capacity, transferrin saturation, and serum albumin. Ziltivekimab significantly improved markers of inflammation, reduced ESA requirements, and increased serum albumin in patients on hemodialysis with inflammation and hyporesponsiveness to ESA therapy. Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Doses of COR-001, NCT02868229.

Inflammatory cytokine and plasma C-reactive protein response to ketoacidosis in adults with type 1 diabetes: Egyptian multicenter study

BackgroundIn adults with diabetic ketoacidosis (DKA), high plasma levels of C-reactive protein (CRP) and inflammatory cytokines such as interleukin-6 (IL-6) were reported to be sensitive markers of infection. However, elevation of both CRP and the pro-inflammatory cytokines which regulate CRP are probable without infection and may act as indicator of systemic inflammatory response (SIR). So, we wanted to determine if increased plasma CRP levels occur in young patients with severe DKA who do not have clinical evidence of infection and to relate observed changes in CRP level to the pro-inflammatory cytokine levels.ResultsUpon admission of 30 DKA patients with age ranging from 17 to 40 years, we found significant elevation of CRP (P = 0.001) and IL-6 (P = 0.001) in DKA patients than control group. After resolution of DKA, there was significant reduction in CRP and IL-6 compared to before DKA correction (P value = 0.054 and 0.001), respectively. There was a significant negative correlation between CRP after correction of DKA and RBCs (P = 0.042), and serum K (P = 0.021) and between CRP prior to DKA correction and PH (P = 0.025).ConclusionsPatients with DKA without infection had increased levels of CRP and inflammatory cytokines. Intensive insulin therapy has a powerful anti-inflammatory effect that, at the time of DKA improvement, can normalize levels of CRP and inflammatory cytokines, and this beneficial effect is greater for IL-6 than CRP.

The effect of green Mediterranean diet on cardiometabolic risk; a randomised controlled trial

BackgroundA Mediterranean diet is favourable for cardiometabolic risk.ObjectiveTo examine the residual effect of a green Mediterranean diet, further enriched with green plant-based foods and lower meat intake, on cardiometabolic risk.MethodsFor...

Abstract 15565: Long-term Dietary and Weight Changes Following a Short-term Dietary Intervention Study: 4-year Follow-up of the Evade Cad Trial

Introduction: The randomized EVADE CAD trial demonstrated greater reduction in high sensitivity C-reactive protein and LDL-cholesterol with a vegan vs. AHA-recommended diet in patients with coronary artery disease on guideline-directed medical therapy. The 8-week intervention included provision of groceries, cooking tools, and regular contact with a registered dietitian. Methods: Trial participants underwent telephone follow-up to obtain self-reported dietary adherence, 24-hour dietary recall, self-reported weight, and major adverse cardiovascular events (MACE). Supporting medical documents for MACE were reviewed by investigators. Results: Two participants in the vegan arm withdrew during the trial leaving 98 participants available for follow-up. The vegan group reported significantly lower dietary adherence at all follow-ups when compared to the AHA group; however, adherence rates were numerically higher in both groups when assessed by 24-hour dietary recall vs. self-report (F1A-B). The two groups did not differ in self-reported rating of the healthiness of their current diet (F1C). Both groups continued to have significantly lower weight when compared to baseline up to 3 years follow-up, but only the vegan group remained lower at year 4. Percent weight lost from baseline did not differ between groups. Cumulative MACE incidence also did not differ between groups (F2). Conclusions: Although the vegan diet was not sustainable long-term when compared to the AHA-recommended diet, both groups did not differ in self-reported rating of the healthiness of their current diet or incidence of MACE and had sustained weight loss after the active intervention was complete.

Efficacy of therapeutic plasma exchange in the treatment of penn class 3 and 4 cytokine release syndrome complicating COVID-19

ObjectivesCytokine release syndrome (CRS) is a potentially severe complication of COVID-19 most commonly resulting in respiratory failure. This ten-patient study was designed to determine the efficacy of therapeutic plasma exchange (TPE) in improving oxygenation and in reducing the cytokine load in a critically ill subset of patients. MethodsFive single volume plasma exchanges over eight days within a 14-day study period. In mechanically ventilated patients, oxygenation was measured via the PaO2/FiO2 (P/F) ratio and the oxygenation index (OI) daily for 14 days. Supplemental oxygen requirements were tracked daily for non-ventilated patients. ResultsNon-ventilated patients were liberated from supplemental oxygen after TPE. The response was rapid with an 87% average reduction in oxygenation requirements following and average time to return to room air of 5.25 days. All mechanically ventilated patients demonstrated improvement in oxygenation with a 78% average improvement in the P/F ratio and a 43% improvement in OI. C-reactive protein (CRP) and serum levels of IL-6, IL-8, IL-10, TNFα, IFNγ and GM-CSF, were measured daily with immediate post TPE levels drawn on days 1, 2, 4, 6 and 8. All patients demonstrated significant reductions in CRP, IL-6, IL-10 and TNFα. ConclusionsIn the majority of patients with Penn class 3 and 4 CRS complicating COVID-19, TPE demonstrated a prompt improvement in oxygenation and reduction in cytokine load without compromising patient safety. As this pilot study was envisioned to be hypothesis generating, expanded trials using TPE alone and in conjunction with novel pharmacologic agents are warranted. RegistrationClinicalTrials.gov NCT04374149.

Wand Stretching Exercise Decreases Abdominal Obesity Among Adults With High Body Mass Index Without Altering Fat Oxidation.

RationaleWe designed a wand-based muscle stretching (WE) exercise program, which has become increasingly popular in physical therapy and has been used for elderly patients with adhesive capsulitis. However, studies regarding the effects of WE training on abdominal obesity and measures of cardiovascular risk factors among overweight/obese adults aged ≥55 years are rare.PurposeThe objective of this study is to evaluate the effects of a 15-week wand stretching exercise program on waist circumference and cardiovascular risk factors in sedentary adults aged 55–70 years.MethodsA total of 124 participants were randomly assigned to either participate in wand stretching exercise (WE) over a 15-week period or a control group (n = 62 each). Sixty participants in the WE group (26 overweight and 34 obese) and 51 in the control group (29 overweight and 22 obese) completed the study. The WE program included wand-assisted muscle stretching exercise on both the upper body and lower body for 40 min per day, 5 days per week, whereas the control group maintained their sedentary lifestyle.ResultsNo significant improvements were observed in plasma glucose, insulin, and the homeostatic model assessment of insulin resistance (HOMA-IR) after exercise training. Compared with the control group, the WE group had more significant reductions in waist circumference among participants with a body mass index (BMI) < 25 kg/m2 (−2.6 cm, 95% CI: −4.19 to −0.97 cm, d = 0.48) and BMI > 25 kg/m2 (−2.5 cm, 95% CI: −4.1 to −0.9 cm, d = 0.59) (both P < 0.01). Furthermore, within groups, a significant increase in % fat free mass was observed after WE training. The basal metabolic rate was slightly increased, but the fat oxidation rate remained unaltered in the WE group. Improvements in low-density lipoprotein cholesterol to high-density lipoprotein cholesterol were minimal after WE. Significant reductions in high-sensitivity C-reactive protein were observed after WE only for participants with a BMI <25 kg/m2.ConclusionThe results suggest redistribution of a carbon source from the abdominal region to challenged skeletal muscle, following prolonged WE training. This abdominal fat reducing outcome of the WE is unlikely to be associated with fatty acid oxidation.

Effect of Sleep Surgery on C-Reactive Protein Levels in Adults With Obstructive Sleep Apnea: A Meta-Analysis.

To evaluate associations between sleep surgery and CRP (C-reactive protein) levels in adults with obstructive sleep apnea (OSA). Meta-analysis. Two authors independently searched PubMed, Medline, EMBASE, and Cochrane review databases until July 2019. The keywords used were sleep apnea, OSA, sleep apnea syndromes, surgery, C-reactive protein (CRP), and inflammatory markers. The effects of sleep surgery on CRP levels were examined using a random-effects model. Nine studies with 277 patients were analyzed (mean age: 46.5 years; 92% men; mean sample size: 30.8 patients). The mean change in the apnea-hypopnea index (AHI) after surgery was significantly reduced by -21.1 (95% confidence interval [CI], -28.4 to -13.7) events/hr. Overall, sleep surgery resulted in a significant reduction of CRP levels in patients with OSA (standardized mean difference [SMD] = -0.39, 95% CI, -0.67 to -0.11). Patients with postoperative AHI reduction >20 events/hr achieved a greater reduction in CRP than those with AHI reduction <20 events/hr (SMD: -0.72 vs. -0.14, P for heterogeneity = .007). According to subgroup analysis, differences in the CRP levels after surgery were nonsignificant in the different countries (i.e., United States vs. other countries), CRP types (i.e., CRP vs. high-sensitivity CRP), surgical procedures (i.e., pharyngeal surgery vs. other surgical procedures), and follow-up period (i.e., <6 vs. >6 months). Sleep surgery for OSA resulted in a significant reduction of CRP levels in adults. The beneficial effect of surgery on CRP levels is greater in patients with large improvement in OSA (i.e., AHI reduction >20 events/hr) after sleep surgery. Laryngoscope, 131:1180-1187, 2021.

Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

BackgroundResuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose at admission are at high risk of morbidity and mortality. This has been attributed to the post-cardiac arrest syndrome (PCAS) which encompasses multiple interacting components, including systemic inflammation. Elevated levels of circulating interleukin-6 (IL-6), a pro-inflammatory cytokine, is associated with worse outcomes in OHCA patients, including higher vasopressor requirements and higher mortality rates. In this study, we aim to reduce systemic inflammation after OHCA by administering a single infusion of tocilizumab, an IL-6 receptor antibody approved for use for other indications.MethodsInvestigator-initiated, double-blinded, placebo-controlled, single-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Brief inclusion criteria: OHCA of presumed cardiac cause, persistent unconsciousness, age ≥ 18 years. Intervention: 80 patients will be randomized in a 1:1 ratio to a single 1-h intravenous infusion of either tocilizumab or placebo (NaCl). During the study period, patients will receive standard of care, including sedation and targeted temperature management of 36 ° for at least 24 h, vasopressors and/or inotropes as/if needed, prophylactic antibiotics, and any additional treatment at the discretion of the treating physician. Blood samples are drawn for measurements of biomarkers included in the primary and secondary endpoints during the initial 72 h. Primary endpoint: reduction in C-reactive protein (CRP). Secondary endpoints (abbreviated): cytokine levels, markers of brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, adverse events, and follow-up assessment of cerebral function and mortality.DiscussionWe hypothesize that reducing the effect of circulating IL-6 by administering an IL-6 receptor antibody will mitigate the systemic inflammatory response and thereby modify the severity of PCAS, in turn leading to lessened vasopressor use, more normal hemodynamics, and better organ function. This will be assessed by primarily focusing on hemodynamics and biomarkers of organ damage during the initial 72 h.In addition, pro-inflammatory and anti-inflammatory cytokines will be measured to assess if cytokine patterns are modulated by IL-6 receptor blockage.Trial registrationClinicalTrials.gov Identifier: NCT03863015; submitted February 22, 2019, first posted March 5, 2019.EudraCT: 2018-002686-19; date study was authorized to proceed: November 7, 2018.

Tocilizumab Use in COVID-19 Cytokine-release Syndrome: Retrospective Study of Two Centers.

IntroductionCytokine-release syndrome (CRS) in COVID-19 patients can cause multiorgan failure and higher mortality. We used a structured protocol based on clinical, biochemical, and interleukin 6 (IL-6) criteria for the identification of the subset of patients with CRS and analyzed the use of tocilizumab for their treatment.Materials and methodsWe did a retrospective case-control analysis of all COVID-19 patients between 15 March and 15 May 2020 with severe to critical disease in ICU. They were evaluated for CRS, and 22 patients who met the criterion were given tocilizumab. The primary objective was to evaluate the effect of tocilizumab on escalation of respiratory support and ICU mortality. The secondary objectives were ICU length of stay, trends of inflammatory markers, and any adverse effects.ResultsThe need for escalation of respiratory support was significantly lower in the tocilizumab group as compared to standard treatment (p = 0.001). The mortality at day 7 and 28 was also significantly lower in the tocilizumab group (p = 0.007 and p = 0.001 respectively). There was a significant reduction in C-reactive protein (CRP) who received tocilizumab (p = 0.033).ConclusionIn our limited number of patients, timely intervention with tocilizumab in COVID-19 patients with CRS significantly improved overall ICU outcome by reducing the need for invasive ventilation and mortality.How to cite this articleNasa P, Singh A, Upadhyay S, Bagadia S, Polumuru S, Shrivastava PK, et al. Tocilizumab Use in COVID-19 Cytokine-release Syndrome: Retrospective Study of Two Centers. Indian J Crit Care Med 2020;24(9):771–776.

COVID-19 recovery: potential treatments for post-intensive care syndrome

COVID-19 recovery: potential treatments for post-intensive care syndrome

Once-Daily Low Inflammatory Foods Everyday (LIFE) Smoothie or the Full LIFE Diet Lowers C-Reactive Protein and Raises Plasma Beta-Carotene in 7 Days.

Serum C-reactive protein (CRP), a marker of systemic inflammation, is associated with increased risk for numerous inflammation-driven chronic diseases. A prior longitudinal study showed that the Low Inflammatory Foods Everyday (LIFE) diet, which is rich in dark green leafy vegetables (DGLV), lowered CRP over a mean follow-up period of 6 months. In this retrospective study, we investigate whether patients who consume the LIFE diet or their regular diet plus one component of the LIFE diet (LIFE smoothie), experience reductions in high-sensitivity CRP (hsCRP) in 7 days. Sixteen patients in a community practice met inclusion criteria. Patient compliance was assessed by patient interviews and measurements of beta-carotene, which is abundant in DGLV. Following the interventions, CRP decreased in both the LIFE diet (-0.47 mg/L, P = .02) and smoothie groups (-1.2 mg/L, P = .04). No statistically significant difference in reduction was observed between groups (P = .18). Plasma beta-carotene increased in both groups (+23.2, P = .02; +20.6, P = .006, respectively). These findings suggest that the LIFE diet or a regular American diet supplemented with the LIFE smoothie may quickly reduce systemic inflammation and the risk of many chronic diseases.

Vitamin D sufficiency, a serum 25-hydroxyvitamin D at least 30 ng/mL reduced risk for adverse clinical outcomes in patients with COVID-19 infection.

BackgroundTo investigate the association between serum 25-hydroxyvitamin D levels and its effect on adverse clinical outcomes, and parameters of immune function and mortality due to a SARS-CoV-2 infection.Study designThe hospital data of 235 patients infected with COVID-19 were analyzed.ResultsBased on CDC criteria, among our study patients, 74% had severe COVID-19 infection and 32.8% were vitamin D sufficient. After adjusting for confounding factors, there was a significant association between vitamin D sufficiency and reduction in clinical severity, inpatient mortality serum levels of C-reactive protein (CRP) and an increase in lymphocyte percentage. Only 9.7% of patients older than 40 years who were vitamin D sufficient succumbed to the infection compared to 20% who had a circulating level of 25(OH)D< 30 ng/ml. The significant reduction in serum CRP, an inflammatory marker, along with increased lymphocytes percentage suggest that vitamin D sufficiency also may help modulate the immune response possibly by reducing risk for cytokine storm in response to this viral infection.ConclusionTherefore, it is recommended that improving vitamin D status in the general population and in particular hospitalized patients has a potential benefit in reducing the severity of morbidities and mortality associated with acquiring COVID-19.

The effects of soy supplementation on inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials

BackgroundSoy products contain several compounds with anti-inflammatory properties like genistein and daidzein which reported to act through different pathways. Present study conducted considering the inconsistent results and lack of any comprehensive review regarding randomized controlled trials which assess the effect of soy products on inflammatory markers. MethodsFollowing electronic databases were searched up to March 2020: PubMed, Scopus, ISI web of science, and Cochrane Library All randomized trials which assessed the effect of soy product supplementation on c-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were included for last analysis. Treatment effects were expressed as mean difference (MD) and the standard deviation (SD) of outcomes. To estimate the overall effect the random-effects model was employed. ResultsFinally, 51 randomized trial were included for present study. Last analysis showed that soy product supplementation lead to significant reduction in CRP (MD −0.27 mg/L; 95% CI: −0.51, −0.02, p = 0.028) but it did not affect IL-6 (MD 0.0 pg/ml; 95% CI: −0.06, 0.06, p = 0.970) and TNF-α (MD = −0.04 pg/ml; 95% CI: −0.11, 0.03, p = 0.252). Subgroup analysis showed that soy supplementation had a significant impact on decreasing IL-6 and TNF-α levels when studies had a long-term intervention (≥12 weeks) and used low dose isoflavone (<100 mg/day). ConclusionIn conclusion, present systematic review and meta-analysis found a significant reduction in CRP levels after soy supplementation whiles IL-6 and TNF-α did not affect.

The effects of L-carnitine supplementation on indicators of inflammation and oxidative stress: a systematic review and meta-analysis of randomized controlled trials.

Several trials investigated the efficacy of L-carnitine administration on markers of inflammation and indicators of oxidative stress; however, their findings are controversial. The aim of this study was to conduct a comprehensive meta-analysis and a critical review, which would analyze all randomized controlled trials (RCTs) in order to determine the effects of L-carnitine supplementation on inflammatory markers and oxidative stress. An electronic search was performed using Scopus, Cochrane Library, PubMed, Google scholar and Web of Science databases on publications from 1990 up to May 2020. Human RCTs conducted in healthy subjects or participants with certain disorders which investigating the efficacy of L-carnitine supplementation compared to control (placebo, usual treatment or no intervention) on inflammation and oxidative markers were included. Data were pooled applying a random-effects model and as the overall effect size, weighted mean difference (WMD) was presented. Between heterogeneity among studies was computed using Cochran's Q test and I-square (I2). Quality of studies assessed using the Jadad scale. Dose-response analysis was measured using meta-regression. The funnel plot, as well as the Egger's regression test was applied to determine the publication bias. 44 trials (reported 49 effect sizes for different outcomes of interest) met the inclusion criteria for this meta-analysis. According to the findings, L-carnitine supplementation resulted in a significant reduction in C-reactive protein (CRP) (WMD: -0.10; 95% CI: -0.14, -0.06), interleukin 6 (IL-6) (WMD: -1.87; 95% CI: -2.80, -0.95), tumor necrosis factor-α (TNF-α) levels (WMD: -1.43; 95% CI: -2.03, -0.84), and malondialdehyde (MDA) (WMD: -0.47; 95% CI: -0.76, -0.18) levels, while there was a significant increase in superoxide dismutase (SOD) (WMD: 2.14; 95% CI: 1.02, 3.25). However, no significant effects of L-carnitine on glutathione peroxidase (GPx) (WMD: 0.02; 95% CI: -0.01, 0.05) and total antioxidant capacity (TAC) (WMD: 0.14; 95% CI: -0.05, 0.33) were found. L-carnitine supplementation was associated with lowering of CRP, IL-6, TNF-α, and MDA, and increasing SOD levels, but did not affect other inflammatory and oxidative stress biomarkers.

Efficacy of Hydroxychloroquine and Tocilizumab in Patients With COVID-19: Single-Center Retrospective Chart Review.

BackgroundDuring the initial phases of the COVID-19 pandemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ) and tocilizumab (TCZ); however, evidence on their efficacy and safety have been controversial.ObjectiveThe purpose of this study is to evaluate the overall clinical effectiveness of HCQ and TCZ in patients with COVID-19. We hypothesize that HCQ and TCZ use in these patients will be associated with a reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis.MethodsA retrospective cohort study was performed to determine the impact of HCQ and TCZ use on hard clinical outcomes during hospitalization. A total of 176 hospitalized patients with a confirmed COVID-19 diagnosis was included. Patients were divided into two comparison groups: (1) HCQ (n=144) vs no-HCQ (n=32) and (2) TCZ (n=32) vs no-TCZ (n=144). The mean age, baseline comorbidities, and other medications used during hospitalization were uniformly distributed among all the groups. Independent t tests and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios with 95% CIs, respectively.ResultsThe unadjusted odds ratio for patients upgraded to a higher level of care (ie, intensive care unit) (OR 2.6, 95% CI 1.19-5.69; P=.003) and reductions in C-reactive protein (CRP) level on day 7 of hospitalization (21% vs 56%, OR 0.21, 95% CI 0.08-0.55; P=.002) were significantly higher in the TCZ group compared to the control group. There was no significant difference in the odds of in-hospital mortality, upgrade to intensive medical care, need for invasive mechanical ventilation, acute kidney failure necessitating dialysis, or discharge from the hospital after recovery in both the HCQ and TCZ groups compared to their respective control groups. Adjusted odds ratios controlled for baseline comorbidities and medications closely followed the unadjusted estimates.ConclusionsIn this cohort of patients with COVID-19, neither HCQ nor TCZ offered a significant reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis. These results are similar to the recently published preliminary results of the HCQ arm of the Recovery trial, which showed no clinical benefit from the use of HCQ in hospitalized patients with COVID-19 (the TCZ arm is ongoing). Double-blinded randomized controlled trials are needed to further evaluate the impact of these drugs in larger patient samples so that data-driven guidelines can be deduced to combat this global pandemic.

Efficacy of methotrexate in polymyalgia rheumatica in routine rheumatology clinical care.

Current guidelines recommend methotrexate (MTX) as a glucocorticoid-sparing agent in patients with polymyalgia rheumatica (PMR) who relapse or suffer glucocorticoid adverse effects, although there is no level 1 evidence to support this recommendation. To review the effect of MTX in PMR on inflammation and glucocorticoid dose. Patients with PMR from rheumatology outpatient clinics at two tertiary centres were identified. A structured case note review was conducted for patient characteristics at diagnosis and medications including glucocorticoid and MTX use. There were 70 patients, 61% female; mean (range) age of 70 (51-87) years. At the time of diagnosis, median (±interquartile range) erythrocyte sedimentation rate (ESR) was 38.5 (26-74) mm/h and C-reactive protein (CRP) 34.5 (6-74 mg/L) with median initiating prednisolone dose of 15 mg (range 5-60 mg). MTX was prescribed in 22 (31%) patients. Mean disease duration at MTX initiation was 2.5 years (1-7 years), with median (range) MTX dose of 10 mg (5-20 mg). At MTX initiation, median (interquartile range) (±standard deviation) ESR was 33 (13-60 mm/h) and CRP 19 (8-42 mg/L). Reasons for commencing MTX were disease relapse (34%) or inability to wean prednisolone dose (66%). Six months after MTX initiation, there was significant reduction in ESR (P = 0.012), CRP (P = 0.0003) and prednisolone dose (P < 0.0001). Eleven (50%) patients stopped MTX, five due to controlled PMR, and six due to adverse effects. In this study of PMR patients in tertiary care, 31% were co-prescribed MTX, after prolonged disease duration. MTX was associated with improved inflammatory activity and reduced prednisolone dose, with a relatively high risk of adverse events.

The Effect of Plant Derived Bioactive Compounds on Inflammation: A Systematic Review and Meta‐Analysis

A growing number of people worldwide are changing their lifestyle leading to an increasing number of overweight and obese individuals with metabolic syndrome (MetS). With obesity and MetS come an elevated inflammatory state resulting in increased risk of Type 2 diabetes, cardiovascular disease, among other lifestyle diseases. Fruits and vegetables (FV) contain phytochemicals with health beneficial effects including anti-oxidative and anti-inflammatory properties. This systematic review and meta-analysis aims to investigate the effects of diets high in FV, and plant-based products on C-reactive protein (CRP). A systematic search in PUBMED and EMBASE gave rise to 883 articles, 16 of which are included in the meta-analysis. The effects of plant-based products and diets are investigated in subgroups including overweight, obese, and diabetes; as wells as the effect of plant-oils and anthocyanin on CRP. The analysis shows an overall significant reduction in CRP for all articles (p = 0.0006). A significant decrease in diabetic (p = 0.01), overweight (p = 0.005), and obese patients (p = 0.05) is observed, including significant effects of anthocyanins (p = 0.001) and plant-oils (p <0.00001) on CRP. These findings strongly support the recommendation for diets high in FV and plant-oils to help attenuate elevated CRP.

Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. Clinical trial registrationurl: https://www.clinicaltrials.gov. Unique identifier: NCT03288584.