Reduction In C-reactive Protein Research Articles

Alpha-lipoic acid administration affects psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes and coronary heart disease.

This investigation was performed to assess the effects of alpha-lipoic acid (ALA) supplementation on psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). This randomized, double-blind, placebo-controlled trial was performed in 60 patients with T2DM and CHD, aged 45-85 years. Patients were randomized into two groups to receive either 600mg/day ALA (n = 30) or placebo (n = 30) for 12 weeks. ALA supplementation significantly decreased Beck Depression Inventory index (BDI) (-5.1 ± 3.5 vs. -1.1 ± 4.8, P = 0.001) when compared with the placebo. ALA supplementation resulted also in a significant reduction of serum high sensitivity C-reactive protein (hs-CRP) (-0.8 ± 1.4 vs. +0.5 ± 0.6mg/L, P < 0.001) and malondialdehyde (MDA) (-0.3 ± 0.2 vs. -0.1 ± 0.3 µmol/L, P = 0.003), and a significant increase in plasma total antioxidant capacity (TAC) levels (+ 26.8 ± 36.0 vs. -4.6 ± 43.4 mmol/L, P = 0.007) when compared with the placebo. ALA intake upregulated transforming growth factor beta (TGF-β) (P = 0.03) and downregulated gene expression of interleukin-1 (IL-1) (P = 0.001) in peripheral blood mononuclear cells of patients with T2DM and CHD as well. ALA supplementation for 12 weeks in patients with T2DM and CHD had beneficial effects on BDI, hs-CRP, TAC, MDA values, and gene expression of IL-1 and TGF-β. The online version contains supplementary material available at 10.1007/s40200-022-01031-1.

Post hoc analysis of a long-term safety extension study: Responses to siltuximab in idiopathic multicentric Castleman disease patients receiving on-label dosing.

e19586 Background: Siltuximab is the only FDA- and EMA-approved therapy for idiopathic multicentric Castleman disease. Its long-term efficacy and safety were established in a 6-year extension study featuring patients who responded to treatment or had stable disease in a phase 1 or phase 2 trial. However, dosage could be adjusted at physician discretion; of 60 patients, 33 remained on the on-label dosing of 11 mg/kg administered every 3 weeks. To assess the safety and efficacy of on-label dosing, we performed a post hoc analysis in patients who maintained this dosing. Methods: A mixed-effects model was used to analyze longitudinal measurements for tumor response, C-reactive protein (CRP), hemoglobin (Hb), erythrocyte sedimentation rate (ESR), fibrinogen, albumin, and platelet counts at multiple time points. Adverse events (AEs) were also assessed. Greenhouse–Geisser correction was used to ensure that the assumption of sphericity was met for the mixed-effects model. Tukey post hoc correction was applied to determine significant differences between specific time points. Results: Of the 33 patients on 3-week dosing, one transitioned to receiving siltuximab every 6 weeks for 25 cycles but restarted 3-weekly dosing due to suspected progressive disease (PD). Disease control was observed in 31 of the 33 patients (93.9%) at their last on-study assessment (complete response [CR] in 9 [27.3%]). Quantitative analyses were performed on the 32 patients who maintained 3-weekly dosing until their last on-study assessment. Siltuximab led to sustained mean levels of CRP, Hb, ESR, fibrinogen, albumin, and platelet counts for the duration of the study. In the 19 patients with residual IL-6 activity at screening (CRP levels &gt; 4 mg/L) there was an overall reduction in CRP from baseline at multiple time points. This group showed a trend towards improved total Hb levels, which increased by 9.43% (adjusted p = 0.048) at cycle 31, and some demonstrated an improvement in ESR, fibrinogen, and albumin levels. All patients reported AEs, mostly grade 1 or 2, with no deaths. At point of enrolment into the extension study, the three most common AEs were hypertension (36.4%), fatigue (42.4%), and pain (51.5%). Conclusions: Our findings show that long-term on-label dosage of siltuximab sustains an improved inflammatory profile and disease control.[Table: see text]

Modified regimen intrapleural alteplase with pulmozyme in pleural infection management: a tertiary teaching hospital experience

BackgroundCurrent management of poorly draining complex effusions favours less invasive image-guided placement of smaller tubes and adjunctive intrapleural fibrinolysis therapy (IPFT). In MIST-2 trial, intrapleural 10 mg alteplase (t-PA) with 5 mg of pulmozyme (DNase) twice daily for 72 h were used. We aimed to assess the effectiveness and safety of a modified regimen 16 mg t-PA with 5 mg of DNase administered over 24 h in the management of complex pleural infection.MethodsThis was a single centre, prospective study involving patients with poorly drained pleural infection. Primary outcome was the change of pleural opacity on chest radiograph at day 7 compared to baseline. Secondary outcomes include volume of fluid drained, inflammatory markers improvement, surgical referral, length of hospitalisation, and adverse events.ResultsThirty patients were recruited. Majority, 27 (90%) patients were successfully treated. Improvement of pleural opacity on chest radiograph was observed from 36.9% [Interquartile range (IQR 21.8–54.9%)] to 18.1% (IQR 8.8–32.7%) of hemithorax (P < 0.05). T-PA/DNase increased fluid drainage from median of 45 mls (IQR 0–100) 24 h prior to intrapleural treatment to 1442 mls (IQR 905–2360) after 72 h; (P < 0.05) and reduction of C-reactive protein (P < 0.05). Pain requiring escalation of analgesia affected 20% patients and 9.9% experienced major adverse events. None required surgical intervention.ConclusionThis study suggests that a modified regimen 16 mg t-PA with 5 mg DNase can be safe and effective for patients with poorly drained complex pleural infection.Trial registration The study was registered retrospectively on 07/06/2021 with ClinicalTrials number NCT04915586 (https://clinicaltrials.gov/ct2/show/NCT04915586).

MO563: Effect of Probiotics on Uremic Toxins Production and Inflammation in Patients Suffering from CKD Stage 3 and 4

Abstract BACKGROUND AND AIMS Probiotics are being coprescribed in the management of chronic kidney disease (CKD). Few studies have reported that probiotics could slow down the progression of CKD by regulating the intestinal flora and by reducing the uremic toxins. [1,2] Objective of our study is to assess the effect of probiotics on uremic toxins production and inflammation in patient suffering from CKD stage 3 and 4. METHOD Patients of either sex, aged 18–75 years, suffering from CKD stage 3 and 4 were enrolled. Study was conducted at Department of Nephrology, Guwahati Medical College and Hospital (GMCH), Guwahati, Assam. Patients received 1 capsule containing 45 billion of colony forming units of probiotics twice a day for 180 days. Patients were evaluated at day 0, 90 and 180. Parameters such as serum creatinine, blood urea, uric acid, C-reactive protein (CRP), hemoglobin and albumin were recorded at each visit. RESULTS During period of May 2019 to May 2020, 102 patients were enrolled and followed for 180 days. Significantly higher number of males 67 (66%) than 35 (34%) females is reported (P = 0.024). CKD stage 3 and 4 is reported in 41 (40% ) and 61 (60%), respectively. Insignificant drop of serum creatinine of -0.17 (on day 90, P = 0.146) and -0.23 (on day 180, P = 0.135) compared with baseline Sr. creatinine 2.53 ± 0.56 (mean ± SD) is reported. Significant drop in blood urea is reported on day 90 (-2.97, P = 0.014) and on day 180 (-3.60, P &amp;lt; 0.001) compared with baseline 52.11 ± 26.90 (mean ± SD). The reduction in CRP on day 90 and day 180 from baseline was found to be statistically significant (P = 0.037, 0.011). However, reduction in uric acid and increase in hemoglobin and albumin did not reach significance on day 90 and day 180. CONCLUSION Probiotics supplementation lead to decrease in blood urea and CRP. However, its effect on serum creatinine, hemoglobin, uric acid and albumin did not reach statistical significance. More randomized controlled trials are required to prove the efficacy of probiotics to retard CKD progression.

Effect of aerobic exercise on inflammatory markers in polycystic ovary syndrome: a randomized controlled trial.

Chronic low-grade inflammation has emerged as a key contributor to the pathogenesis of Polycystic Ovary Syndrome (PCOS). In this regard, the present study examined the potential effects of aerobic exercise on interleukin-6 (IL6), tumor necrosis factor (TNF), and C-reactive protein (CRP) in PCOS women. This was a randomized clinical trial that included 40 females aged 25-35 years diagnosed with PCOS. The participants were divided into two groups equal in number: the aerobic exercise group (AEM), and the metformin group (M). The AEM group performed aerobic exercise three times a week for 12 weeks in addition to metformin treatment. The M group received metformin only. Participants were assessed for IL-6, TNF-α, and CRP at baseline and after 12 weeks of intervention. The findings showed a significant reduction in IL-6, TNF-α, and CRP values in both AEM and M groups (p=0.001, p=0.01, respectively) after the end of the 12 weeks of the intervention. However, the participants who received aerobic exercise plus metformin, group AEM, showed a greater reduction in IL-6, TNF-α, and CRP (p=0.01, p = 0.01 and p=0.001, respectively). Aerobic exercise is effective in lowering IL-6, TNF-α, and CRP in polycystic ovarian women. Further clinical trials are recommended to assess the potential effects of aerobic exercise on PCOS-associated risk factors.

PcMSC Modulates Immune Dysregulation in Patients With COVID-19-Induced Refractory Acute Lung Injury.

Background and ObjectivesThe novel coronavirus disease 2019 (COVID-19) has been a pandemic health issue in 30 January 2020. The mortality rate is as high as 50% in critically ill patients. Stem cell therapy is effective for those who are refractory to standard treatments. However, the immune responses that underlie stem cell therapy have not been well reported, particularly, in patients associated with moderate to severe acute respiratory distress syndrome (ARDS).MethodsOn Days 0 and 4, an intravenous infusion of 2 × 107 placenta-derived mesenchymal stem cells (pcMSCs) (MatriPlax) were administered to five severe COVID-19 patients refractory to current standard therapies. Peripheral blood inflammatory markers and immune profiles were determined by multi-parameter flow cytometry and studied at Days 0, 4, and 8. Clinical outcomes were also observed.ResultsNone of the pc-MSC treated patients experienced 28-day mortality compared with the control group and showed a significant improvement in the PaO2/FiO2 ratio, Murray’s lung injury scores, reduction in serum ferritin, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. The cytokine profiles also showed a reduction in IL-1β, IFN-γ, IL-2, and IL-6, and an increase in IL-13 and IL-5 type 2 cytokines within 7 days of therapy. Lymphopenia was also significantly improved after 7 days of treatment. Immune cell profiles showed an increase in the proportions of CD4+ T cells (namely, CD4+ naïve T cells and CD4+ memory T cell subtypes), Treg cells, CD19+ B cells (namely, CD19+ naïve B cells, CD27+ switched B cell subtypes) and dendritic cells, and a significant decrease in the proportion of CD14+ monocytes (namely, CD16- classical and CD16+ non-classical subtypes), and plasma/plasmablast cells. No adverse effects were seen at the serial follow-up visits for 2 months after initial therapy.Conclusionpc-MSCs therapy suppressed hyper-inflammatory states of the innate immune response to COVID-19 infection by increasing Treg cells, decreasing monocytes and plasma/plasmablast cells, and promoting CD4+ T cells and CD19+ B cells toward adaptive immune responses in severely critically ill COVID-19 patients with moderate to severe ARDS, especially those who were refractory to current standard care and immunosuppressive therapies.

Time-Dependent Changes of Laboratory Parameters as Independent Predictors of All-Cause Mortality in COVID-19 Patients.

Simple SummarySeveral independent predictors of mortality for COVID-19 patients have been identified. However, those markers are usually parameters evaluated upon hospital admission, and clinical and biochemical parameters during the clinical course of the patients are usually neglected. To know the whole picture of COVID-19 patients it is important to evaluate the clinical course, as this will dictate how the patient progresses. We identify herein clinical and laboratory parameters from admission to discharge, or death, that distinguish between survivors and non-survivors of COVID-19, including those with independent ability to predict mortality.Independent predictors of mortality for COVID-19 patients have been identified upon hospital admission; however, how they behave after hospitalization remains unknown. The aim of this study is to identify clinical and laboratory parameters from admission to discharge or death that distinguish survivors and non-survivors of COVID-19, including those with independent ability to predict mortality. In a cohort of 266 adult patients, clinical and laboratory data were analyzed from admission and throughout hospital stay until discharge or death. Upon admission, non-survivors had significantly increased C reactive protein (CRP), neutrophil count, neutrophil to lymphocyte ratio (NLR) (p < 0.0001, each), ferritin (p < 0.001), and AST (aspartate transaminase) (p = 0.009) compared to survivors. During the hospital stay, deceased patients maintained elevated CRP (21.7 mg/dL [admission] vs. 19.3 [hospitalization], p = 0.060), ferritin, neutrophil count and NLR. Conversely, survivors showed significant reductions in CRP (15.8 mg/dL [admission] vs. 9.3 [hospitalization], p < 0.0001], ferritin, neutrophil count and NLR during hospital stay. Upon admission, elevated CRP, ferritin, and diabetes were independent predictors of mortality, as were persistently high CRP, neutrophilia, and the requirement of invasive mechanical ventilation during hospital stay. Inflammatory and clinical parameters distinguishing survivors from non-survivors upon admission changed significantly during hospital stay. These markers warrant close evaluation to monitor and predict patients’ outcome once hospitalized.

Effect of Selected After-School Physical Activity Protocol on Levels of CRP, miR-125a-5p, and Lipid Profile of Children with Overweight/Obesity

Background: One of the causes of arterial endothelial dysfunction in adulthood is obesity or overweight in childhood or adolescence. Objectives: This study aimed to investigate the effect of a selected after-school physical activity protocol on peak oxygen consumption (VO2peak), C-reactive protein (CRP), miR-125a-5p level, and lipid profile of male children with overweight/obesity. Methods: Twenty-four boy children with overweight/obesity (aged 13 - 15 years) were assigned to after-school physical activity (APA, BMI = 27.5±1.4 kg/m2, n = 12) and control (CON, BMI = 26.28 ± 2.3 kg/m2, n = 12) groups. The APA participants took part in exercise intervention for 12 weeks, three sessions per week. Changes in VO2peak, CRP, miR-125a-5p, and lipid profile of participants were assessed before and after exercise interventions. Results: There were significant reductions in CRP (-27.7% vs. 9.7%), miR-125a-5p (36.7% vs. 7.6%), fat percentage (-8.24% vs. 0.7%), LDL (-17.66% vs. 1.9%), and triglycerides (-15.7% vs. 5.9%) in APA and CON groups after 12-week exercise intervention (P &lt; 0.05). In contrast, a significant increase was found in HDL (7.7% vs. -0.6%) and VO2peak (4.83% vs. -1.6%) (P &lt; 0.05). There were significant between-group differences in all measured variables, except for BMI. Conclusions: After-school physical activity effectively improved the endothelial dysfunction and lipid profile of adolescents with overweight/obesity. Therefore, based on the positive effects of these physical activities performed out of school, further use of after-school physical activity programs is suggested.

Elderly Patients with Moderate-To-Severe Ulcerative Colitis Are More Likely to Have Treatment Failure and Adverse Outcome

Background and Aim: The aim of this study was to compare therapeutic responses and prognosis between elderly and nonelderly ulcerative colitis (UC) patients with moderate-to-severe activity. Methods: 148 UC patients with moderate-to-severe activity hospitalized between 2000 and 2019 were enrolled consecutively, including 74 patients with the age of diagnosis over 60 years and 74 patients diagnosed less than 60 years. Patients were matched by gender, duration (±15%), disease activity, and admission time (±1 year). They were followed up until the latest medical record or December 2019. The primary outcome was UC-related colectomy or death. Results: 148 patients were followed over median 37.5 months. For steroid use, 76.8% of elderly UC patients were responsive, lower than that in adult group (85.7%). A decreased level of clinical activity index (2.0 [−1.5 to 4.00] vs. 6.0 [3.0–8.0], p < 0.001), reduction of C-reactive protein (23.9 [3.5–65.5] vs. 27.8 [9.7–58.1] mg/L), and erythrocyte sedimentation rate (9.0 [−1.3 to 30.5] vs. 15.5 [3.8–36.5] mm/h) at 4 weeks after steroid induction was less obvious in the elderly. More elderly patients manifested steroid dependence and resistance. 28.4% of elderly UC patients took colectomy, remarkably more than adult patients (12.2%), which also occurred earlier (8.0 [0.5–44.75] vs. 39.5 [12–57.38] months, p = 0.001). Aging (hazard ratio [HR] 2.868, 95% confidence interval [CI]: 1.290–6.375, p = 0.01), male, steroid resistance, and occurrence of complications were independently related to colectomy. The rate of serious infections was significantly higher in the elderly (55.4% vs. 35.1%, p = 0.013), mainly including cytomegalovirus infection, bacterial infection, and extraintestinal infection. Aging (odds ratio [OR] 2.774, 95% CI: 1.355–5.675, p = 0.015), extensive colonic involvement, steroid resistance, and biologics usage were independently associated with a high risk of concomitant infections. Conclusion: Elderly patients with moderate-to-severe UC experienced more treatment failure and increased risk of UC-related colectomy, mortality, and severe infections, predicting demand for more strict and individualized management.

Effects of folate supplementation on recurrence and metabolic status of cervical intraepithelial neoplasia grade 2/3 in overweight and obese women: a randomized double-blind placebo-controlled trial.

Inconsistent evidence showed that folate supplementation may be associated with reduced risk of cancer due to improved metabolic profiles and reduced markers of oxidative stress and inflammation. The aim of this investigation was to quantify the effects of folate supplementation on the recurrence and other metabolic factors of women with cervical intraepithelial neoplasia grade 2/3 (CIN2/3). This randomized, double-blind, placebo-controlled clinical trial was performed among 60 overweight/obese women with CIN2/3. Definitive CIN2/3 confirmation was done via biopsy, pathological diagnosis, as well as colposcopy. Participants were randomly assigned to the intervention group to take 5 mg/day folate supplements or placebo group (n = 30 in each group) for 12 weeks. The results of the current study showed a non-significant decrease in recurrence of CIN2/3 in the folate group in comparison with the placebo group (3.3% vs. 16.7%, P = 0.08). Compared with the placebo, folate supplementation significantly decreased plasma homocysteine (Hcy) levels (P < 0.001), serum insulin values (in the crude model) (P = 0.01), and homeostasis model assessment of insulin resistance (P = 0.01). Also, folate supplementation resulted in a significant improvement in the quantitative insulin sensitivity check index (P = 0.002) and total antioxidant capacity (P = 0.04) and a significant reduction in high-sensitivity C-reactive protein (P = 0.015) in comparison with the placebo group. In conclusion, folate supplementation for 12 weeks among overweight/obese women with CIN2/3 showed a non-significant decrease in its recurrence and had beneficial effects on insulin sensitivity, inflammation, and oxidative stress markers.

The Effects of Probiotic Supplementation on Opioid-Related Disorder in Patients under Methadone Maintenance Treatment Programs.

Introduction Patients under methadone maintenance treatment programs (MMTPs) are susceptible to numerous complications (e.g., mental and metabolic disorders). This study evaluated the effects of probiotics on clinical symptoms, biomarkers of oxidative stress, inflammation, insulin resistance, and serum lipid content in patients receiving MMTPs. Materials and Methods A randomized, double-blind, placebo-controlled trial was conducted among 70 patients receiving MMTPs to receive either 1.8 × 109 CFU/day probiotics (n = 35) or placebo (n = 35) for 12 weeks. Clinical symptoms and metabolic profiles were measured before and after the intervention in patients receiving MMTPs. Results Compared with the placebo group, probiotic supplementation resulted in a significant improvement in the severity of depression (P < 0.05). In addition, probiotic administration significantly decreased fasting plasma glucose (FPG), total cholesterol, and low-density lipoprotein cholesterol (LDL cholesterol) (P < 0.05). Furthermore, probiotics resulted in a significant reduction in high-sensitivity C-reactive protein (hs-CRP) and a significant elevation in total antioxidant capacity (TAC) and total glutathione (GSH) levels (P < 0.05). Conclusion Treatment with probiotics for 12 weeks to patients receiving MMTPs had beneficial effects on symptoms of depression, as well as several metabolic profiles. Clinical Trial Registration: this study was registered in the Iranian website (https://www.irct.ir) for clinical trials registration (https://fa.irct.ir/trial/46363/IRCT20170420033551N9). The registration date is March 22, 2020.

A study on influence of pranayama on high sensitivity C-reactive protein and creatinine kinase levels in chronic obstructive pulmonary disease patients

Purpose: The present study is aimed to observe the differential response of pranayama in reducing high sensitivity C-reactive protein and creatinine kinase levels among chronic obstructive pulmonary disease patients in comparison to control patients. Material and Methods: An intervention study was done by enrolling 100 chronic obstructive pulmonary disease patients who were managed by therapeutics. The participants were divided into intervention and non-intervention group with 50 each sample. The intervention was in the form of sequenced yogic practices for 6 weeks. The pre-intervention and post-intervention inflammatory maker levels were estimated along with lung function estimation. Results: The result was analyzed by descriptive statistics. The mean C-reactive protein, serum creatinine kinase value decreased from 9.53 to 7.85mg/L and from 145.01 to 140.57 U/L respectively following 6 weeks of yogic practices intervention. The observed values were found to be statistically significant (p=&lt;0.05). Conclusion: The statistically significant reduction in inflammatory makers, C-reactive protein and creatinine kinase level following 6-week yogic practices in chronic obstructive pulmonary disease patient suggests including such yogic interventions in the regular management protocols of chronic obstructive pulmonary disease patients.

Cardiac Glycosides Lower C-Reactive Protein Plasma Levels in Patients with Decompensated Heart Failure: Results from the Single-Center C-Reactive Protein-Digoxin Observational Study (C-DOS).

Recent randomized controlled multi-center trials JUPITER, CANTOS and COLCOT impressively demonstrated the effect of anti-inflammatory therapy on secondary prevention of cardiovascular events. These studies also rapidly re-vitalized the question of whether the C-reactive protein (CRP), the prototype human acute phase protein, is actively involved in atherosclerosis and its sequelae. Direct CRP inhibition may indeed improve the specificity and effectiveness of anti-inflammatory intervention. In the present paper, we report on the final results of our single-center C-reactive protein-Digoxin Observational Study (C-DOS). Methods and Results: Based on the experimental finding that cardiac glycosides potently inhibit hepatic CRP synthesis on the transcriptional level in vitro, 60 patients with decompensated heart failure, NYHA III–IV, severely reduced Left Ventricular Ejection Fraction (LVEF < 40%), and elevated CRP plasma levels were treated by either digoxin + conventional heart failure therapy (30 patients) or by conventional heart failure therapy alone (30 patients). Plasma CRP levels in both groups were assessed for 21 d. Plasma CRP levels on d1, d3 and d21 were compared by regression analysis. CRP levels d21–d1 significantly declined in both groups. Notably, comparative CRP reduction d21–d3 in digoxin versus the control group also revealed borderline significance (p = 0.051). Conclusions: This small observational trial provides the first piece of evidence that cardiac glycosides may inhibit CRP synthesis in humans. In case of further pharmacological developments, cardiac glycosides may emerge as lead compounds for chemical modification in order to improve the potency, selectivity and pharmacokinetics of CRP synthesis inhibition in cardiovascular disease.

Effects of Resistance Training on C-Reactive Protein and Inflammatory Cytokines in Elderly Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Chronic low-grade inflammation that accompanies aging is associated with adverse health outcomes and may exacerbate the severity of infectious disease such as COVID-19. Resistance training (RT) has the potential to improve chronic low-grade inflammation, but the evidence remains inconclusive. This study evaluated the effects of RT on chronic low-grade inflammation in elderly adults. MEDLINE, EMBASE, Cochrane Library, CINAHL, RISS, NDSL, and KoreaMed were searched. We included studies that assessed the effect of RT on C-reactive protein (CRP), interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α in those aged ≥60 years. The effect size was estimated using fixed or random-effects models. Subgroup analysis was performed regarding age, health status, training method, number of exercises, intensity, weekly frequency, and duration. In the 18 randomized controlled trials (539 patients) included, RT was effective in alleviating CRP (effect size = −0.72, 95% confidence interval = −1.06 to −0.38, p < 0.001), IL-10 (−3.34, −6.16 to −0.53, p = 0.02), and TNF-α (−0.56, −1.08 to −0.03, p = 0.04) in elderly adults and tended to reduce IL-6 (−0.59, −1.18 to 0.00, p = 0.05). Subgroup analyses showed CRP reduction regardless of age, training method, number of exercises, intensity, weekly frequency, and duration. RT can be used to ameliorate chronic low-grade inflammation in elderly adults.

Safety and efficacy study of allogeneic human menstrual blood stromal cells secretome to treat severe COVID-19 patients: clinical trial phase I & II

BackgroundCell-free Mesenchymal stromal cells (MSCs) have been considered due to their capacity to modulate the immune system and suppress cytokine storms caused by SARS-CoV-2. This prospective randomized double-blind placebo-controlled clinical trial aimed to assess the safety and efficacy of secretome derived from allogeneic menstrual blood stromal cells (MenSCs) as a treatment in patients with severe COVID-19.MethodsPatients with severe COVID-19 were randomized (1:1) to either MenSC-derived secretome treatment or the control group. Subjects received five intravenous infusions of 5 mL secretome or the same volume of placebo for five days and were monitored for safety and efficacy for 28 days after treatment. Adverse events, laboratory parameters, duration of hospitalization, clinical symptom improvement, dynamic of O2 saturation, lymphocyte number, and serial chest imaging were analyzed.ResultsAll safety endpoints were observed without adverse events after 72 h of secretome injection. Within 28 days after enrollment, 7 patients (50%) were intubated in the treated group versus 12 patients (80%) in the control group. Overall, 64% of patients had improved oxygen levels within 5 days of starting treatment (P < 0.0001) and there was a survival rate of 57% in the treatment group compared to 28% in the control group was (P < 0.0001). Laboratory values revealed that significant acute phase reactants declined, with mean C-reactive protein, ferritin, and D-dimer reduction of 77% (P < 0.001), 43% (P < 0.001), and 42% (P < 0.05), respectively. Significant improvement in lymphopenia was associated with an increase in mean CD4+ and CD8+ lymphocyte counts of 20% (P = 0.06) and 15% (P < 0.05), respectively. Following treatment, percentage of pulmonary involvement showed a significant improvement in the secretome group (P < 0.0001). This improvement differed significantly between survivors and those who were dying (P < 0.005).ConclusionsFor the first time, this study demonstrated that in hospitalized patients with severe COVID-19, therapy with MenSCs-derived secretome leads to reversal of hypoxia, immune reconstitution, and downregulation of cytokine storm, with no adverse effects attributable to the treatment. Given these outcomes, it may be possible to use this type of treatment for serious inflammatory lung disease with a mechanism similar to COVID-19 in the future. However, it is necessary to evaluate the safety and efficacy of MenSCs-derived secretome therapy in clinical trials on a larger population of patients.Trial registration: ClinicalTrials.gov Identifier: NCT05019287. Registered 24AGUEST 2021, retrospectively registered, https://clinicaltrials.gov/ct2/show/record/NCT05019287. IRCT, IRCT20180619040147N6. Registered 04/01/2021.

The effects of acupuncture and related techniques on patients with rheumatoid arthritis: A systematic review and meta-analysis.

One new type of acupuncture and related techniques (ACNRT) is increasingly used by rheumatoid arthritis (RA) patients to control their disease and improve their quality of life. However, the efficacy of using ACNRT in combination with western medicine (WM) for this purpose remains unknown. Randomized controlled trials of ACNRT and WM treatments for RA from January 1, 2000, to January 31, 2021, were searched for in the databases PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials, as well as in three Chinese databases: China National Knowledge Infrastructure, Wanfang Data, and Airiti Library. The primary outcomes consisted of inflammatory markers including C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor. The secondary outcomes were clinical characteristics including pain visual analog scale (VAS) score, Disease Activity Score (DAS-28), swollen joints count (SJC), tender joints count (TJC), morning stiffness, and the results of a health assessment questionnaire. The three types of ACNRT used in the focal trials were acupuncture, moxibustion, and electro-acupuncture. Two qualified researchers extracted data from these trials' results and independently assessed their risk of bias. Statistical analyses were performed using Comprehensive Meta-Analysis V3 software. A total of 12 RCTs with 874 patients met the inclusion criteria. As compared with the patients who received WM treatment alone, those who were given integrated ACNRT/WM treatment showed greater reductions in CRP (weighted mean difference [WMD]: -6.299; 95% CI: -9.082 to -3.517), ESR (WMD: -6.563; 95% CI: -8.604 to -4.522), VAS (WMD: -1.089; 95% CI: -1.575 to -0.602), DAS-28 (WMD: -0.633; 95% CI: -1.006 to -0.259), SJC (WMD: -1.921; 95% CI: -3.635 to -0.207), and TJC (WMD: -1.491; 95% CI: -2.941 to -0.042). This meta-analysis of RA provides reliable evidence in favor of ACNRT plus WM. However, longer term, high-quality, repeatable, multicenter randomized controlled trials with larger sample sizes are needed.

Infliximab: a single-centre, prospective, observational evaluation of TDM data in patients with IBD

ObjectivesTherapeutic drug monitoring of infliximab (IFX) is important to optimise treatment of inflammatory bowel disease (IBD). A recent IBD consensus statement recommends targeting trough serum concentrations of >3 μg/mL, higher...

Spillover Effects of a Family-Based Childhood Weight-Management Intervention on Parental Nutrient Biomarkers and Cardiometabolic Risk Factors

ABSTRACTBackgroundParental involvement has been shown to favorably affect childhood weight-management interventions, but whether these interventions influence parental diet and cardiometabolic health outcomes is unclear.ObjectivesThe aim was to evaluate whether a 1-y family-based childhood weight-management intervention altered parental nutrient biomarker concentrations and cardiometabolic risk factors (CMRFs).MethodsSecondary analysis from a randomized-controlled, parallel-arm clinical trial (NCT00851201). Families were recruited from a largely Hispanic population and assigned to either standard care (SC; American Academy of Pediatrics overweight/obesity recommendations) or SC + enhanced program (SC+EP; targeted diet/physical activity strategies, skill building, and monthly support sessions). Nutrient biomarkers (plasma carotenoids and fat-soluble vitamins, RBC fatty acid profiles) and CMRFs (BMI, blood pressure, glucose, insulin, lipid profile, inflammatory and endothelial dysfunction markers, adipokines) were measured in archived samples collected from parents of participating children at baseline and end of the 1-y intervention.ResultsParents in both groups (SC = 106 and SC+EP = 99) had significant reductions in trans fatty acid (–14%) and increases in MUFA (2%), PUFA n–6 (ɷ-6) (2%), PUFA n–3 (7%), and β-carotene (20%) concentrations, indicative of lower partially hydrogenated fat and higher vegetable oil, fish, and fruit/vegetable intake, respectively. Significant reductions in high-sensitivity C-reactive protein (hsCRP; –21%) TNF-α (–19%), IL-6 (–19%), and triglycerides (–6%) were also observed in both groups. An additional significant improvement in serum insulin concentrations (–6%) was observed in the SC+EP parents. However, no major reductions in BMI or blood pressure and significant unfavorable trajectories in LDL-cholesterol and endothelial dysfunction markers [P-selectin, soluble intercellular adhesion molecule (sICAM), thrombomodulin] were observed. Higher carotenoid, MUFA, and PUFA (n–6 and n–3) and lower SFA and trans fatty acid concentrations were associated with improvements in circulating glucose and lipid measures, inflammatory markers, and adipokines.ConclusionsThe benefits of a family-based childhood weight-management intervention can spill over to parents, resulting in apparent healthier dietary shifts that are associated with modest improvements in some CMRFs.

Hydroxychloroquine shortened hospital stay and reduced intensive care unit admissions in hospitalized COVID-19 patients.

Effectiveness of hydroxychloroquine against SARS-CoV-2 has been highly controversial. In our research, we aimed to investigate the effects of hydroxychloroquine on disease outcomes in hospitalized patients with COVID-19. A total of 393 hospitalized patients with COVID-19 were retrospectively assigned to the standard of care therapy group (n = 180) or the standard of care plus hydroxychloroquine group (n = 213). The standard of care therapy comprised favipiravir, low molecular weight heparin, acetylsalicylic acid. Status of oxygenation at baseline and on the seventh day, laboratory tests at baseline and at discharge were recorded. Length of hospital stay, administration of anti-inflammatory treatment, admission to the intensive care unit and 28th day mortality were set as primary endpoints. There were no statistically significant differences between groups in terms of oxygen delivery route and mortality after seven days of treatment (p = 0.592). C-reactive protein levels of the standard of care plus hydroxychloroquine group were significantly lower than that of the standard of care group at discharge (p = 0.034). Patients in the standard of care plus hydroxychloroquine group had shorter hospital stay (p = 0.007). The standard of care plus hydroxychloroquine group was favored over standard of care group in terms of rate of intensive care unit admissions (21.7% vs. 10.8%; relative risk with 95% CI = 0.49 [0.31-0.80], p = 0.003). Hydroxychloroquine in addition to standard of care was associated with less intensive care unit admissions, early discharge and greater C-reactive protein reduction. There was no difference in 28-day mortality.

P198 An inflammatory serum metabolomic signature predicts response to vedolizumab treatment in people with Crohn’s Disease

Abstract Background While Vedolizumab (VDZ) is an established treatment for Crohn’s disease (CD), primary non-response is well-recognised – there is an urgent clinical need for biomarkers that predict response, before initiation of treatment. Metabolomic profiling is a rapidly growing field in biomarker discovery and can distinguish between active and quiescent inflammatory bowel diseases. Here, we sought to identify a metabolic signature able to predict response to VDZ. Methods Prospective serum samples from 62 CD patients before (baseline) and post-treatment follow-up (FU) (median 30 weeks, IQR 27–35) were analyzed. Patients were stratified into n=35 responders (R) and n=27 non-responders (NR) using endoscopic (≥50% reduction in SES-CD score), clinical (≥3 point drop in HBI or HBI ≤4, no systemic steroids), and/or biochemical assessments (≥50% reduction in C-reactive protein (CRP) and fecal calprotectin (fCal) or a basal CRP ≤5 g/mL and fecal calprotectin ≤250 µg/g). Untargeted metabolomic profiling was carried out using high-resolution nuclear magnetic resonance (NMR) spectroscopy. Significant differences in metabolite signatures were identified by orthogonal partial least squares discriminant analysis (OPLS-DA). Model accuracy (acc.) was assessed by external 10-fold cross-validation (CV), permutation testing, and validated on an independent test set. Results We first demonstrate that bowel preparation required for endoscopy had a significant impact on the serum metabolite profile (CV acc. 77±4%, acc. n=10 independent test set 80%, KS test p-value &amp;lt; 0.001) and samples taken from patients at colonoscopy were excluded from further analysis. This reduced the cohort size; 19 baseline (12R/7NR) and 25 FU (16R/9NR). No significant difference in baseline fCal or CRP was observed between R and NR (t-test p-value &amp;gt;0.05). The metabolite profiles at baseline and FU were indistinguishable (KS test p-value &amp;gt; 0.05) suggesting the metabolome was stable. However, high (&amp;gt;300 µg/g) fCal values were associated with elevated N-acetyl-glycoprotein (GlycA), a known inflammatory marker, elevated serum glucose along with decreased lipoprotein and lactate levels (CV acc. 74±3%, acc. n=10 independent test set 100%, KS test p-value &amp;lt; 0.001). This same metabolite signature predicts response (CV acc. 61±5%, acc. n=6 independent test set 83%, KS test p-value &amp;lt; 0.001) with responders exhibiting increased metabolic inflammation at baseline. Conclusion Here, we identify an inflammatory metabolic signature which predicts response to VDZ. Work to confirm these findings in a larger cohort and extend this method to investigate infliximab, adalimumab and ustekinumab treated patients, as part of the EPIC Pioneer study, is ongoing.