Reduction In C-reactive Protein Research Articles

Comparison of clinical outcome, cartilage turnover, and inflammatory activity following either intra-articular or a combination of intra-articular with intra-osseous platelet-rich plasma injections in osteoarthritis knee: A randomized, clinical trial

BackgroundThe objective of the study was to determine the changes in clinical outcome (pain and knee activity) and assess bone/ cartilage biomarkers and inflammatory activity in persons with osteoarthritis (OA) knee following a single injection of intra-articular platelet-rich plasma (IA-PRP) and combination of intra-articular, intraosseous PRP (IA+IO-PRP). MethodsThis prospective, randomized, single-blind clinical trial was conducted at a tertiary care teaching hospital in India. Ninety-six persons with OA knee with a Kellgren-Lawrence score of 3 were randomized into three groups- Group-I (IA-PRP), Group-II (IA+IO-PRP)], Group-III, [intra-articular normal saline (IA-NS)]. The primary outcome was a visual analog scale (VAS) for pain. The secondary outcomes were the Knee Injury and Osteoarthritis Outcome Score (KOOS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), bone/ cartilage turnover biomarkers [C-telopeptide (CTX-II), N-telopeptide (NTX-I), cartilage oligomeric matrix protein (COMP), N-terminal propeptide of collagen type-IIA (PIIANP), and hyaluronic acid (HA)], ultrasonography (USG) findings of the knee joint. The outcome measures were assessed at baseline, 6, and 12 weeks of follow-up. ResultsCompared to IA-NS injection, IA-PRP and IA+IO-PRP injections significantly improved VAS-pain and KOOS scores at 6 and 12 weeks. Furthermore, both PRP groups showed a significant reduction in ESR, CRP, and CTX-II at 12 weeks following PRP injections. In addition, at 12 weeks, the IA+IO-PRP group showed a significant reduction (p=0.009) in NTX-I level. Persons in the IA+IO-PRP group reported significant reductions in the synovial-effusion and infra-patellar bursitis. ConclusionsSignificant clinical improvements were noticed following IA-PRP and IA-IO-PRP injections compared to IA-NS injections. Both PRP groups reported a significant reduction in ESR, CRP, and CTX-II levels at 12 weeks. Persons in the IA+IO-PRP group reported significant changes in u-NTX-I level and knee-USG findings.

Effect of a Plant-based Intervention Among Black Individuals in the Deep South: A Pilot Study

ObjectiveTo explore the feasibility, acceptability, and clinical/behavioral outcomes of a remotely-delivered, culturally-tailored plant-based nutrition and lifestyle intervention designed to improve cardiovascular risk among Black adults in a rural, Black Belt community. MethodsWe implemented a 12-week intervention with weekly educational sessions, cooking lessons, social support, exercise, and food items. Outcome(s)Body mass index, waist circumference, total cholesterol, low-density lipoprotein, high-density lipoprotein, high-sensitivity C-reactive protein, trimethylamine N-oxide, diet/physical activity. Paired t tests analyzed preintervention and postintervention differences (n = 24). ResultsBody mass index and waist circumference were reduced (P < 0.001), and total and low-density lipoprotein cholesterol decreased by 10.8% and 13.9%, respectively (P < 0.05). There was a 25.8% reduction in high-sensitivity C-reactive protein (P = 0.02). Diet and physical activity were also improved. Conclusions and ImplicationsThis pilot study demonstrated the feasibility and acceptability of a remotely-delivered intervention focused on improving cardiovascular risk through plant-based nutrition, physical activity/wellness, social support, and cultural adaptability. Larger scale and longer-term studies are needed.

The Effect of Dietary Patterns on Inflammatory Biomarkers in Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Some evidence supports the fact that chronic low-grade inflammation contributes to the physiopathology of type 2 diabetes mellitus (T2DM), and circulating markers of inflammation (e.g., C-reactive protein (CRP), pro- and anti-inflammatory biomarkers (e.g., adiponectin), and endothelial function markers could indicate an ongoing pathology. Following certain dietary patterns (DPs) may result in favorable changes in inflammatory biomarkers. The overarching aim of this systematic review and meta-analysis is to explore the inflammatory effect of healthy DPs on inflammatory biomarkers in adults with T2DM. A systematic search of the literature was conducted using the electronic databases MEDLINE, SCOPUS, and Cochrane Central Register of Controlled Trials. A total of 10 randomized controlled clinical trials (RCTs) were analyzed. In our linear meta-analysis, the random-effects model was applied to estimate standardized mean differences (SMD) to associate the effect of the interventions. Dietary Approaches to Stop Hypertension (DASH), Diabetes UK healthy eating, Mediterranean Diet (MD), Diabetes Prevention Program (DPP), and the American Heart Association's Therapeutic Lifestyle Changes diet were associated with a significant reduction in CRP (SMD: -0.83, 99% CI -1.49, -0.17, p &lt; 0.001; I2 94%), while plasma levels of adiponectin were significantly higher with the intake of MD, DPP, and Diabetes UK healthy eating (SMD: 0.81, 99% CI 0.06,1.56, p &lt; 0.005; I2 96%), both of which indicate less inflammation. Sensitivity analyses were carried out, and potential publication bias was examined. In conclusion, low- moderate-quality evidence from RCTs suggests that, for the DPs evaluated, there are favorable changes in CRP and adiponectin.

Dietary Supplementation with D-Ribose-L-Cysteine Prevents Hepatic Stress and Pro-Inflammatory Responses in Male Wistar Rats Fed a High-Fructose High-Fat Diet.

Diets rich in fats and fructose are associated with the pathogenesis of oxidative stress-induced non-alcoholic fatty liver disease. Therefore, we investigated the effect of D-ribose-L-cysteine (DRLC) in high-fructose high-fat (HFHF) diet-fed rats. Twenty rats (n = 5), divided into four groups, were simultaneously exposed to HFHF and/or DRLC (250 mg/kg) orally during the 8 weeks of the study. Results showed that HFHF precipitated pro-inflammation and selective disruption of the oxidative stress markers. There were significant decreases in the level of antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC), hepatic SOD and GPX. Significant increases in serum levels of uric acid (UA), tumour necrosis factor-alpha (TNF-α), C-reactive protein (CRP) and hepatic Xanthine oxidase (XO) were observed in the HFHF compared to the control. In the HFHF + DRLC group, oxidative stress was mitigated due to differences in serum levels of SOD, GPX, TAC, TNF-α, liver SOD, and XO relative to control. The administration of DRLC alone caused significant reductions in malondialdehyde, UA and CRP and a significant increase in SOD compared to the control. DRLC prevents hepatic and systemic oxidative stress and pro-inflammatory events in HFHF diet-fed rats.

Transcutaneous Auricular Vagus Nerve Stimulation Improves Inflammation but Does Not Interfere with Cardiac Modulation and Clinical Symptoms of Individuals with COVID-19: A Randomized Clinical Trial.

Transcranial auricular vagus nerve stimulation (taVNS) has shown effectiveness in reducing inflammation and depression. Thus, this study evaluated its effect on inflammation, cardiac autonomic modulation, and clinical symptoms in individuals affected by COVID-19. Methods: There were 52 randomized participants hospitalized with COVID-19 diagnosis who were to receive active (a-taVNS) or sham taVNS (s-taVNS) for 90 min twice a day for seven consecutive days. Interleukin 6 (IL-6), 10 (IL-10), cortisol, C-reactive protein (CRP), heart rate variability (HRV), and clinical symptoms were assessed before and after seven days of treatment. There were also seven- and fourteen-day follow-ups for clinical symptoms, including anxiety and depression levels, as well as a six-month follow-up for memory and attention levels. Results: There was significant reduction in CRP −23.9%, (95% CI −46.3 to −1.4) and IL-6 −37.7%, (95% CI −57.6 to −17.7) for the a-taVNS group. There were no changes in IL-10, cortisol levels, or in HRV results (p > 0.05) in both groups. There were no changes regarding clinical symptoms, except for a significant decrease in depression level (−2.85, 95% CI −5.44 to −0.27) in the a-taVNS group. Conclusion: taVNS showed effects on CRP, IL-6, and depression levels; however, it did not affect other clinical symptoms.

Early CRP Trends in Childhood Osteomyelitis Predict Complicated Disease.

Acute hematogenous osteomyelitis (AHO) remains a cause of severe illness among children. Contemporary research aims to identify predictors of acute and chronic complications. Trends in C-reactive protein (CRP) after treatment initiation may predict disease course. We have sought to identify factors associated with acute and chronic complications in the New Zealand population. A retrospective review of all patients younger than16 years with presumed AHO presenting to a tertiary referral centre between 2008 and 2018 was performed. Multivariate was analysis used to identify factors associated with an acute or chronic complication. An "acute" complication was defined as the need for 2 or more surgical procedures, a hospital stays longer than 14 days, or recurrence despite intravenous antibiotics. A "chronic" complication was defined as growth or limb length discrepancy, avascular necrosis, chronic osteomyelitis, pathologic fracture, frozen joint, or dislocation. One hundred fifty-one cases met the inclusion criteria. The median age was 8 years (69.5% male). Within this cohort, 53 (34%) experienced an acute complication and 18 (12%) a chronic complication. Regression analysis showed that contiguous disease, delayed presentation, and failure to reduce CRP by 50% at day 4/5 predicted an acutely complicated disease course. Chronic complication was predicted by the need for surgical management and failed CRP reduction by 50% at day 4/5. CRP trends over 96 hours after the commencement of treatment differentiate patients with AHO likely to experience severe disease. Level II, retrospective study.

C-Reactive Protein as a Predictor of Survival and Length of Hospital Stay in Community-Acquired Pneumonia.

Introduction: Community-acquired pneumonia (CAP) presents high mortality rates and high healthcare costs worldwide. C-reactive protein (CRP) has been widely used as a biomarker for the management of CAP. We evaluated the performance of CRP threshold values and ΔCRP as predictors of CAP survival and length of hospital stay. Methods: A total of 173 adult patients with CAP were followed for up to 30 days. We measured serum CRP levels on days 1, 4, and 7 (D1, D4, and D7) of hospitalization, and their variations between different days were calculated (ΔCRP). A multivariate logistic regression model was created with CAP 30-day survival and length of hospital stay as dependent variables, and absolute CRP values and ΔCRP, age, sex, smoking habit (pack-years), pO2/FiO2 ratio on D1, WBC on D1, and CURB-65 score as independent variables. Results: A total of six patients with CAP died (30-day mortality 3.47%). No difference was found in CRP levels and ΔCRP between survivors and non-survivors. Using a cut-off level of 9 mg/dL, the AUC (95% CI) for the prediction of survival of CRP on D4 and D7 were 0.765 (0.538–0.992) and 0.784 (0.580–0.989), respectively. A correlation between CRP values on any day and length of hospital stay was found, with it being stronger for CRPD4 and CRPD7 (p < 0.0001 and p = 0.0024, respectively). A reduction of CRP > 50% from D1 to D4 was associated with 4.11 fewer days of hospitalization (p = 0.0308). Conclusions: CRP levels on D4 and D7, but not ΔCRP, could fairly predict CAP survival. A reduction of CRP > 50% by the fourth day of hospitalization could predict a shorter hospital stay.

Efficacy of drug regimen with and without oseltamivir in hospitalized patients with COVID-19: A retrospective study

IntroductionCoronavirus disease 2019 (COVID-19) is the most critical issue in nowadays medicine. We aimed to evaluate the use and therapeutic outcomes of oseltamivir, an antiviral drug for patients with COVID-19. Materials and methodIn an observational study conducted at Imam Khomeini Hospital in Amol, Iran, data for 544 patients with laboratory and CT scan result confirmed COVID-19 were retrospectively collected between February 24th and April 13th 2020. To compare the characteristics of patients based on gender, the chi-square test was used. Logistic regression was used to evaluate the effect of oseltamivir on the outcome of treatment. Logrank test were used to compare the length of hospital stay in people treated with oseltamivir and drugs other than oseltamivir. ResultsKaplan–Meier and logrank test showed no significant reduction in hospitalization time and survival rate following treatment with oseltamivir. However, a significant increase in lymphocytes count and reduction of C-reactive protein (CRP) level detected. ConclusionAdministration of oseltamivir for patients with COVID-19 didn't show any improvement in hospitalization duration and survival rate.

S890 A Diet High in Fruits and Vegetables During Biologic Induction May Improve Response to Biologics in Patients With Inflammatory Bowel Disease

Introduction: Several biologics now exist as treatment for inflammatory bowel disease (IBD) but effective induction of remission still ranges between 20-40% for most. Studies suggest that diet may modify intestinal inflammation. In this study, we sought to examine the effect of diet on biochemical response to biologic induction therapies. Methods: We conducted a single-center retrospective analysis of patients with IBD seen at a tertiary referral center from 2019 to 2021. A validated 26-item diet questionnaire, the Dietary Screener Questionnaire (DSQ), was completed as part of a pre-check-in process before each clinic visit. IBD patients who completed a DSQ within three months of induction of a biologic (anti-TNFs, vedolizumab, ustekinumab) and who had markers of inflammation available pre and post-induction (C-Reactive Protein (CRP)) were included. Follow up period was 3 months post-induction. Using linear and average mixed-effects models, we examined the contribution of food items in the DSQ (i.e., processed meats, red meats, fruits, vegeTables) to a reduction in CRP following induction. We used pre-induction biochemical markers as a baseline reference. Current steroid use, prior biologic exposure, age, gender, body mass index (BMI), smoking status, IBD type (ulcerative colitis (UC) or Crohn’s disease (CD)), and class of biologic were added as covariates in the models. Results: A total of 105 patients were included in this study (62.9% had CD and 32.4% had UC). The most common biologic was anti-TNFs (52.4%). The mean CRP value pre-induction was 13.4 (SD 20.2) and post-induction was 6.63 (SD 12.4). On multivariable analyses adjusting for covariates mentioned, we found an independent effect of high daily intake of fruits and vegeTables on reduction in CRP. For every 1 unit increase in daily fruits and vegeTables, there was a reduction in CRP value by 1.82 post-induction of biologics (p=0.04), Table. Red meat intake, processed meats, fiber from whole grains, and dairy were not associated with CRP reduction (Table). Conclusion: In this preliminary analysis, we find that a diet high in fruits and vegeTables during induction of biologics may independently improve biochemical response. Future clinical drug trials should consider dietary assessment and the influence of diet on response to medication treatment. Table 1. - Average Marginal Effects (AME) Assessing the Contribution of Each Variable on the Reduction of CRP Level During Induction Factor Average Mixed Effects (AME) Standard Error (SE) p-value Age 0.1253 0.07186 0.862 Gender (Male) 0.30313 0.23377 0.1977 BMI 0.08005 0.07203 0.2701 IBD- Ulcerative Colitis -0.33136 0.14984 0.0304 Previous biologic use -0.03417 0.14799 0.818 anti-TNF biologic induced (ref) 1.29018 0.94172 0.1734 Ustekinumab induced 0.10442 0.15699 0.5082 Vedolizumab induced 0.1059 0.17734 0.5525 Steroids on induction 0.23593 0.14915 0.1181 Diet Factors Red Meat -0.01567 0.17881 0.9303 Processed Meat -0.32794 0.34438 0.343 Fiber 0.5546 0.05404 0.3071 Calcium 0.15903 0.19979 0.4277 Whole grain (cups) -0.40034 0.26105 0.1279 Added sugar (teaspoons) -0.01585 0.0235 0.5014 Dairy (cups) 0.0488 0.32823 0.8821 Fruit (cups) 0.62825 0.76457 0.413 Fruits and Vegetables daily (cups) -1.8186 0.87858 0.0406

S766 The Effect of Mirikizumab on Fecal Calprotectin and C-Reactive Protein in Phase 3 Studies of Patients With Moderately-to-Severely Active Ulcerative Colitis

Introduction: This study explores the effect of mirikizumab (miri) on inflammatory biomarkers fecal calprotectin (FC) and C-reactive protein (CRP) in patients with moderately-to-severely active ulcerative colitis (UC). Methods: In LUCENT-1 (NCT03518086), 1162 patients were randomized 3:1 to receive intravenous miri 300 mg or placebo (PBO) every 4 weeks for 12 weeks. Patients (N=544) who achieved clinical response with miri at Week (W) 12 were re-randomized 2:1 in LUCENT-2 (NCT03524092) to receive blinded miri 200 mg or PBO subcutaneously every 4 weeks through W40 (52 weeks continuous therapy). Treatment comparison of change from baseline in FC and CRP levels were made using ANCOVA analysis. Comparison of proportion of patients achieving FC ≤250 μg/g used a Cochran–Mantel Haenszel test treating missing data as nonresponse. Results: At baseline, the median FC was 1556.0 µg/g in the miri group and 1465.0 µg/g in the PBO group (Table); the proportion of patients with FC >250 µg/g were similar between treatment groups (miri: 90.4%; PBO: 88.9%). At both W4 and W12 of LUCENT-1, miri-treated patients showed greater reduction in FC from baseline compared to PBO (p< .001). Among patients with baseline FC level >250 µg/g, a greater proportion of miri-treated patients achieved an FC level of ≤250 µg/g compared to PBO (34.3% vs 20.1%; adjusted risk difference: 14.6%; 95% confidence interval [CI]: 8.3%–20.9%; p< .001) at W12. For those who continued with maintenance therapy in LUCENT-2, at W40, miri-treated patients sustained greater FC reduction from baseline compared to PBO (p< .001). A greater proportion of miri-treated patients with induction baseline FC >250 µg/g achieved FC level of ≤250 µg/g compared to PBO (50.7% vs 19.3%; adjusted risk difference: 29.1%; 95% CI: 20.5%–37.7%; p< .001) at W40. At baseline, the median CRP was 4.0 mg/L in the miri group and 4.3 mg/L in the PBO group (Table). At W12, patients in the miri group showed greater reduction in CRP from baseline compared to PBO (p< .001). Among those who continued in LUCENT-2, at W40, miri-treated patients sustained greater reduction in CRP from baseline compared to PBO (p< .001). Conclusion: Patients treated with miri in both induction and maintenance studies were more likely to achieve an FC ≤ 250 µg/g and showed significantly greater reductions from baseline in FC and CRP when compared to PBO. Table 1. - Fecal calprotectin and c-reactive protein values at baseline, week 12, and week 40 Biomarker Study Time Point Treatment n Median (IQR) LS Mean (SE)b LS Mean Difference b (95% CI b ) Between TreatmentP-value b Fecal Calprotectin LUCENT-1 Baseline Placebo 243 1465.0 (618.0-2839.0) 2970.1 (303.5) - - Miri 300 mg IV 722 1556.0 (635.0-3210.0) 3121.4 (176.1) Week 12 Placebo 243 1040.0 (290.0-2427.0) 2386.0 (206.9) -1164.1 (-1613.1, -715.0) < .001 Miri 300 mg IV 722 398.0 (95.0-1311.0) 1221.9 (129.9) LUCENT-2 (miri induction responder) Week 40 a Placebo 156 496.0 (112.5-1956.0) 1862.6 (221.4) -839.6 (-1323.1, -356.2) < .001 Miri 200 mg SC 302 155.0 (40.0-657.0) 1022.9 (172.4) C-Reactive Protein LUCENT-1 Baseline Placebo 279 4.3 (1.2-9.3) 9.4 (0.9) - - Miri 300 mg IV 837 4.0 (1.5-9.5) 9.3 (0.5) Week 12 Placebo 279 3.1 (1.0-9.0) 8.4 (0.6) -3.7 (-5.0, -2.5) < .001 Miri 300 mg IV 837 1.7 (0.7-4.9) 4.7 (0.4) LUCENT-2 (miri induction responder) Week 40 a Placebo 178 1.6 (0.7-5.1) 7.0 (0.7) -3.3 (-4.9, -1.7) < .001 Miri 200 mg SC 359 1.4 (0.5-4.0) 3.6 (0.5) ANCOVA=analysis of covariance; CI=confidence interval; IQR=interquartile range; IV=intravenous; LS=least square; miri=mirikizumab; n=number of patients with baseline and post-baseline value at specified timepoint; SC=subcutaneous; SE=standard error.a52 weeks of continuous therapy.bANCOVA model for endpoint measures; patients with missing value at the designated timepoint had their last value carried forward, with the exception that patients who discontinued due to an adverse event had their baseline value carried forward.

Probiotic supplementation induces remission and changes in the immunoglobulins and inflammatory response in active ulcerative colitis patients: A pilot, randomized, double-blind, placebo-controlled study.

Clinical studies of using probiotics for managing ulcerative colitis (UC) in Jordan are rare. Therefore, we aimed to evaluate the effect of probiotic supplementation on the clinical disease activity and biochemical parameters in patients with mild-to-moderately active UC. thirty mild-to-moderate ulcerative colitis patients were included and randomly assigned to participate in a double-blinded randomized study to receive the treatment (3×1010 of probiotic capsules [containing nine Lactobacillus and five Bifidobacterium species], or a placebo), and included in the intention-to-treat analysis. Only 24 completed the study and were included in the per-protocol analysis. Both groups were compared in terms of clinical disease activity and biochemical parameters at the beginning and the end of the study. Registered under ClinicalTrials.gov Identifier no. NCT04223479. There was a significant induction of remission in the probiotic group presented by improvement in the partial mayo score (PMS). Probiotic group had significantly lower stool frequency (0.00±0.00 vs. 1.17±1.19), global assessment (0.42±0.51 vs. 1.00±0.74, p=0.035), and total PMS score (1.33±0.49 vs. 3.42±1.78). In terms of mean and percent of change in post-to pre-treatment values, there was a significant reduction in C-reactive protein, and an increase in hemoglobin, hematocrit, and RBC levels in the probiotic group (p<0.05). Additionally, there was a significant reduction in the IgA level and an increase in IL-10 levels among the probiotic group compared to the placebo group (p=0.039). The use of probiotic therapy had significantly induced remission in UC patients, this was evidenced by the improvement in the Partial Mayo score. Furthermore, probiotic therapy had an appropriate effect on changes in hemoglobin, hematocrit, C-reactive protein, IgA, and IL-10 levels. This study was registered at ClinicalTrials.gov with the number NCT04223479.

S1056 Change in C-Reactive Protein 72 Hours Following Admission Associates With Inpatient and One-Year Colectomy Risk in Severe Ulcerative Colitis

Introduction: Ulcerative colitis (UC) morbidity remains high despite multiple therapeutic advances. Early identification of risk for failure of medical therapies and need for colectomy becomes pivotal to avoid unnecessary and dangerous delays in care. Many presently-validated risk appraisal scores require subjective data to inform risk. Our study aimed to determine the predictive value of the change in C-reactive protein (CRP) during hospitalization for severe UC. Methods: We designed a retrospective study including patients ≥ 18 years old with an admission for UC at a single academic center between 1/1/2013 and 4/1/2018. Cases were identified using the ICD-9 code 556.X and ICD-10 code K51.X and separately, manually verified. Clinical variables of interest and laboratory values were obtained via chart review or extracted from the electronic medical record. Data was analyzed using Wilcoxon rank-sum test for continuous variables, and Fischer’s exact test for categorical variables. Statistical analysis was conducted using JMP ® 13.1.0. Results: 122 hospitalized patients met the inclusion criteria with a median age of 30.2 (IQR: 22.8-46.9) years. 72 (59%) patients were male and 89 (73.6%) were Caucasian. 27 (22.3%) patients required inpatient colectomy and 49 (41.5%) had a colectomy within one year of index admission. Percent change in CRP between admission and 72 hours was predictive of inpatient colectomy (P=0.051), whereas the value of CRP on admission or at 72 hours was not (Table). Among patients with an increase in CRP at 72 hours, 9/21 (42.9%) required inpatient colectomy as compared to 18/101 (17.8%) without an increase in CRP (P=0.019). The percent change in CRP at 72 hours was also predictive of 1-year colectomy risk (-53.3 (50.7) vs -33.7 (49.6), P=0.003). Conclusion: Percent change in CRP between admission and 72-hours predicts both inpatient and 1-year colectomy risk in patients hospitalized with UC. Percent change better prognosticates the need for surgery compared to CRP on admission alone. Herein, we show that a reduction in CRP by 50% 72 hours from admission is an objective and easily determined measurement to risk stratify patients early in the admission for UC. Table 1. - Predictors of colectomy during inpatient admission Risk Factors: Colectomy No Colectomy P-value Age (years), mean (SD) 37.98 (18.51) 35.08 (14.3) 0.644 Male Sex, n (%) 14 (51.85) 58 (61.05) 0.506 White Race, n (%) 21 (77.78) 68 (72.34) 0.631 Presentation with Severe Colitis, n (%) 27 (100) 82 (86.32) 0.07 Prior Admission requiring IV Steroids, n (%) 17 (62.96) 34 (35.79) 0.015 Hospitalization in prior 4 weeks, n (%) 23 (39.0%) 50 (24.5%) 0.047* Biologic naïve, n (%) 7 (25.93) 50 (52.63) 0.024 Single prior biologic class 12 (44.44) 33 (34.74) Multiple prior biologic classes 8 (29.63) 12 (12.63) Steroids usage prior to Presentation, n (%) 17 (62.96) 53 (55.79) 0.66 Inpatient salvage therapy 13 (48.15) 61 (64.21) < 0.001 Laboratory Data: Mean (SD) Admission CRP 45.7 (35.1) 52.89 (56.31) 0.7 72 hour CRP 37.41 (45.03) 26.52 (34.43) 0.178 72 hour change in CRP % -26.5 (58.74) -47.19 (55.81) 0.051

Efficacy of a standardized herbal formulation from Glycyrrhiza glabra L. as an adjuvant treatment in hospitalized patients with COVID-19: A Randomized Controlled trial

IntroductionAs no specific pharmacological intervention has been known for COVID-19, medicinal plants may be a suitable candidate for management of this disease. The aim of this study was to investigate the efficacy of a herbal syrup from licorice as an adjuvant treatment in hospitalized patients with COVID-19. Materials and methods213 hospitalized patients diagnosed with COVID-19 were assigned to receive either standardized licorice syrup as an adjuvant treatment plus standard care [Syrup Group (SYRUP), N = 91], or standard care alone [Standard Group (STANDARD), N = 104], for 7 days. The primary endpoint was duration of hospitalization in survivors. The secondary endpoints included 25% increase in oxygen saturation, C-reactive protein (CRP) difference and lymphocyte difference from baseline, number of death and number of patients transferred to ICU. ResultsMean duration of admission was 5.24 days in SYRUP and 7.14 days in STANDARD (p < 0.001). Oxygen saturation increased in 86 of 91 patients (94.5%) in the licorice group, compared to 83 of 104 patients (79.8%) in the control group (p = 0.002). There was no significant difference between the two groups in the number of patients died during hospitalization (p = 0.837). Five patients in SYRUP and 16 patients in STANDARD were transferred to ICU (p < 0.026). Mean reduction in CRP (p < 0.001) and mean increase in the number of lymphocytes (p = 0.008) in SYRUP were significantly higher than STANDARD. DiscussionLicorice syrup as an adjuvant treatment demonstrated promising results on duration of hospital admission, O2 saturation as well as inflammatory markers in COVID-19 patients; however, further clinical studies with larger sample size are suggested to achieve more conclusive results.

Effect of Aqueous Extract of Alstonia Boonei on Liver Enzymes and Its Anti-Inflammatory Activity on Formalin- Induced Arthritic Wistar Rats

The anti-inflammatory effect of the aqueous extract of Alstonia boonei on the level of liver biomarker in the plasma of normal and arthritic rats was evaluated using the formalin-induced arthritis inflammation tests. Thirty (30) adult female Wister rats were divided into six groups of five rats each. Group 1 as control, group 2(formalin induced group) while groups 3, 4 and 5 were respectively gavage with 150mg/kg, 300mg/kg and 600mg/kg body weight of the extract daily while group 6 was given reference drug( 5mg/kg body weight of indomethacin for 5 days). After formalin treatment, the paw thickness in formalin-induced group was increased compared with control group. The levels of TNF-alpha, CRP, liver enzymes were increased with severe chronic inflammation sign at histopathologically observation. The animals were sacrificed 24hours after the end of treatments, the skin sample of the right paw was taken for TNF alpha evaluation and blood samples were obtained for assay of the levels of ALT, AST, ALP and C-reactive protein(CRP). Liver enzymes were determined using colorimetric methods while TNFalpha and CRP was determined using ELISA technique. Oral administration of the extract produced significant anti-edematogenic, anti-inflammatory activity and dramatic reduction in liver enzymes, TNF alpha and CRP with a dose of 150mg/kg and 300 mg/kg throughout the period of the experiment. This effect of A.boonei at 300mg/kg was similar to indomethacin group which showed a highly significant (p&lt;0.05) inhibition compared to control group.The result of this study suggests that aqueous extract of A. boonei possesses chronic anti-inflammatory activity which may be mediated by either inhibition or by blocking the release of prostaglandins, histamine and pro-inflammatory cytokine (TNF alpha),which suggest that Alstonia boonei is an alternatve approach for treatment of chronic inflammatory disease, thus supporting its usage for anti- inflammatory treatment and potential effect to resuscitate the hepatocytes.

Meta-analysis of the effect of sodium-dependent glucose transporter 2 inhibitors on C-reactive protein in type 2 diabetes.

Background:As novel hypoglycemic drugs, the effects of sodium-dependent glucose transporter 2 inhibitors (SGLT-2I) on inflammatory factors such as C-reactive protein (CRP) remain unclear.Methods:We conducted a meta-analysis of studies on SGLT-2I in the treatment of type 2 diabetes (T2DM) to observe the changes of CRP in patients with T2DM. We searched 4 electronic databases (CNKI, PubMed, EMBASE, and Cochrane Library) for articles published up to December 31, 2021. Studies were analyzed using a random-effects model to obtain standard deviation mean differences (SMDs) and 95% confidence intervals (CIs). Sensitivity and subgroup analyses were performed. Publication bias was evaluated using funnel plots and Egger test.Results:We included data from 927 patients in 13 confirmatory trials that showed a significant decrease in CRP among patients with T2DM treated with SGLT-2I. The decrease was more significant with than without SGLT-2I. In subgroup analysis according to nationality, medication, and comorbidities, CRP reduction was associated with nationality, SGLT-2I type, and the presence of comorbidities. Sensitivity analysis showed that our results were reliable and found no evidence of substantial publication bias.Conclusions:SGLT-2I could reduce CRP levels in patients with T2DM.Registration:International Prospective Register for Systematic Reviews (PROSPERO) number CRD42021268079.

Changes in circulating sirtuin 1 after bariatric surgery

Background and aimsObesity is associated with chronic inflammation and oxidative stress. Weight loss after bariatric surgery improves the inflammatory state and risk of cardiovascular disease. Improvement in metabolic dysfunction might be associated with changes in the activity of sirtuin 1 (SIRT1) and we aimed to investigate the effect of bariatric surgery on its circulating levels. Methods and resultsThis is a sub-study of a prospective cohort study, including 110 subjects with morbid obesity. The surgical procedure was either laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Blood was sampled at inclusion and six and 12 months after surgery. SIRT1 was measured in EDTA plasma with an enzyme-linked immunosorbent assay. The mean age in the population was 43 years, 80% were women and mean body mass index (BMI) was 38.8 kg/m2. RYGB and SG were performed in 89 and 21 subjects, respectively. SIRT1 concentration was significantly reduced from baseline to six and 12 months after surgery, with mean values (SD) 156.8 (82.6), 119.5 (65.6) and 94.9 (45.6) ng/mL, respectively, (p ≤ 0.002, all), accompanied by significant reductions in C-reactive protein (CRP), BMI and triglycerides from inclusion (p < 0.001, all). Type of surgery did not differently modify SIRT1 levels (p = 0.09). CRP and triglycerides were both positively predictive of SIRT1 levels (p ≤ 0.001, both). ConclusionSIRT1 concentration was significantly lower six and 12 months after bariatric surgery. CRP and triglycerides independently predicted SIRT1 levels, suggesting that reduction in SIRT1 levels might not intrinsically be related to weight reduction, but to improvement in metaflammation.

Reduction of C-reactive protein, low-density lipoprotein cholesterol, and its relationship with cardiovascular events of different lipid-lowering therapies: A systematic review and meta-analysis of randomized controlled trials.

Background:To evaluate the reductions of C-reactive protein (CRP) and low-density lipoprotein cholesterol (LDL-C) in different lipid-lowering drugs, and to assess the relationships between the reductions of CRP, LDL-C, and cardiovascular (CV) events.Methods:We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to September 1, 2021. Randomized controlled trials (RCTs) comparing statins, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9-mAbs), or ezetimibe against placebo with a treatment duration of at least 4 weeks and data on the effects of cholesterol-lowering interventions on LDL-C and CRP were included in this meta-analysis. The weighted mean difference (WMD) and 95% confidence interval (CI) were calculated.Results:Compared with placebo treatment, statins and ezetimibe treatments resulted in a significant decrease in LDL-C level (statins: WMD −47.94 mg/dL, 95% CI −51.21 to −44.67 mg/dL; ezetimibe: WMD −22.84 mg/dL, 95% CI −26.76 to −18.92 mg/dL) and CRP level (statins: WMD −0.67 mg/L, 95% CI −0.90 to −0.45 mg/dL; ezetimibe: −0.64 mg/L, 95% CI −1.07 to −0.21 mg/dL). Compared with placebo treatment, treatment with PCSK9-mAbs resulted in significant decrease in LDL-C level (WMD −54.24 mg/dL, 95% CI −59.77 to −48.70 mg/dL), while the concentration of CRP did not decrease significantly. Meta-regression analysis showed no significant association between change in CRP level and change in LDL-C level. Subgroup comparisons suggested that treatment with PCSK9-mAbs showed a greater reduction in LDL-C level when compared with the statins group and ezetimibe group, while the risks of CV death, myocardial infarction (MI), and stroke showed no significant differences.Conclusion:Based on the current study, our results suggested that statins, ezetimibe, and PCSK9-mAbs are effective in reducing LDL-C levels. Treatment with statins and ezetimibe also demonstrated a significant effect on CRP. The traditional lipid-lowering strategy including statin and ezetimibe showed similar benefit on CV outcomes compared with the PCSK9-mAbs treatment.

Reduction of blood C-reactive protein concentration complements the resolution of sputum bacillary load in patients on anti-tuberculosis therapy.

BackgroundTuberculosis (TB) is a difficult-to-treat disease requiring the combination of four antibiotics for a minimum of 6 months. Rapid and quantitative biomarkers to monitor treatment response are urgently needed for individual patient management and clinical trials. C-reactive protein (CRP) is often used clinically as a rapid marker of inflammation caused by infection. We assessed the relationship of TB bacillary load and CRP as biomarkers of treatment response.MethodsXpert MTB/RIF-confirmed pulmonary TB cases were enrolled for treatment response assessment in Mozambique. Treatment response was measured using the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) in comparison with standard-of-care Mycobacterium Growth Indicator Tube (MGIT) culture at baseline and at weeks 1, 2, 4, 8, 12, 17, and 26 of treatment. Blood CRP concentration was measured at baseline, week 8, and week 26. Treatment response was defined as increase in MGIT culture time to positivity (TTP), and reduction in TB-MBLA-measured bacillary load and blood CRP concentration.ResultsOut of the 81 screened presumptive TB cases, 69 were enrolled for 6-month treatment follow-up resulting in 94% treatment completion rate. Four participants did not complete TB treatment and 22 participants had missing CRP or TB-MBLA results and were excluded from TB-MBLA-CRP analysis. The remaining 43 participants—median age, 31 years old [interquartile range (IQR): 18–56]; 70% (30/43) male; and 70% (30/43) infected with HIV—were considered for analysis. Culture TTP and bacillary load were inversely correlated, Spearman’s r = −0.67, p < 0.0001. Resolution of sputum bacillary load concurred with reduction of blood CRP, r = 0.70, p < 0.0001. At baseline, bacillary load had a median (IQR) of 6.4 (5.5–7.2), which reduced to 2.4 (0.0–2.9) and 0.0 (0.0–0.0) log10 CFU/ml at months 2 and 6 of treatment, respectively. Correspondingly, blood CRP reduced from 1.9 (1.6–2.1) at baseline to 1.3 (0.9–1.7) and 0.4 (0.1–0.8) log10 mg/dl at months 2 and 6 of treatment, respectively. CRP reduction trialed bacteriological resolution at a rate of −0.06 log10 mg/dl compared to a bacillary load of 0.23 log10 CFU/ml per week. Consequently, 14 (33%) and 37 (88%) patients had reduced CRP to normal concentration and bacillary load to zero by the end of treatment, respectively. Pre-treatment CRP concentration and bacillary load, and resolution during treatment were slightly lower in HIV co-infected patients but not significantly different from HIV-uninfected TB patients.ConclusionTB-MBLA-measured bacillary load and blood CRP complement each other in response to anti-TB therapy. Slow CRP reduction probably reflects residual TB bacilli in the lung not expectorated in sputum. Combining both measures can improve the accuracy of these biomarkers for monitoring TB treatment response and shorten turnaround time since the results of both assays could be available in 24 h.

Therapeutic plasma exchange: A potential therapeutic modality for critically ill adults with severe acute respiratory syndrome coronavirus 2 infection.

BackgroundSevere acute respiratory syndrome coronavirus 2 infection can be severe and fatal due to cytokine storm. Therapeutic plasma exchange (TPE) potentially mitigates the harmful effects of such cytokines. We investigated the use of TPE, as rescue therapy, in patients with severe Coronavirus disease 2019 (COVID‐19) infection.Study Design and MethodsA retrospective analysis on COVID‐19 patients admitted to the intensive care unit and treated with TPE from April 17, 2020 to July 2, 2020. This group was compared with COVID‐19 patients who received standard therapy without TPE. The following outcomes were analyzed: changes in laboratory parameters, length of hospital stay (LOS), days on mechanical ventilation, mortality at days 14 and overall mortality.ResultsA total of 95 patients were included, among whom 47% (n = 45) received TPE. Patients who received TPE had reductions in C‐reactive protein (P = .002), ferritin (P < .001) and interleukin‐6 (P = .013). After employing entropy‐balancing matching method, those on TPE were also more likely to discontinue inotropes (72% vs 21%; P < .001). However, they were more likely to be associated with longer LOS (23 vs 14 days; P = .002) and longer days on ventilatory support (14 vs 8 days; P < .001). Despite marginal mortality benefit at 14‐days (7.9% vs 24%; P = .071), there was no significant differences in overall mortality (21% vs 31%; P = .315) between the groups.ConclusionsTPE was effective in reducing inflammatory markers in patients with severe COVID‐19 infection, however, further research is warranted.

Unmet Need for Further LDL-C Lowering in India despite Statin Therapy: Lipid Association of India Recommendations for the Use of Bempedoic Acid.

Lipid-lowering therapy plays a crucial role in reducing adverse cardiovascular (CV) events in patients with established atherosclerotic cardiovascular disease (ASCVD) and familial hypercholesterolemia. Lifestyle interventions along with high-intensity statin therapy are the first-line management strategy followed by ezetimibe. Only about 20-30% of patients who are on maximally tolerated statins reach recommended low-density lipoprotein cholesterol (LDL-C) goals. Several factors contribute to the problem, including adherence issues, prescription of less than high-intensity statin therapy, and de-escalation of statin dosages, but in patients with very high baseline LDL-C levels, including those with familial hypercholesterolemia and those who are intolerant to statins, it is critical to expand our arsenal of LDL-C-lowering medications. Moreover, in the extreme risk group of patients with an LDL-C goal of ≤30 mg/dL according to the Lipid Association of India (LAI) risk stratification algorithm, there is a significant residual risk requiring the addition of non-statin drugs to achieve LAI recommended targets. This makes bempedoic acid a welcome addition to the existing non-statin therapies such as ezetimibe, bile acid sequestrants, and PCSK9 inhibitors. A low frequency of muscle-related side effects, minimal drug interactions, a significant reduction in high-sensitivity C-reactive protein (hsCRP), and a lower incidence of new-onset or worsening diabetes make it a useful adjunct for LDL-C lowering. However, the CV outcomes trial results are still pending. In this LAI consensus document, we discuss the pharmacology, indications, contraindications, advantages, and evidence-based recommendations for the use of bempedoic acid in clinical practice.