Blood Levels Of Inflammatory Markers Research Articles

Predicting the association of different levels of physical activity on postoperative pulmonary complications using the international physical activity questionnaire in patients undergoing thoracoscopic lung surgery under general anaesthesia: protocol for a prospective cohort study

IntroductionPostoperative pulmonary complications (PPCs) occur frequently in patients undergoing lung surgery under general anaesthesia and are strongly associated with longer postoperative hospital stays and increased mortality. The existing literature has...

β-Amyloid peptide modulates peripheral immune responses and neuroinflammation in rats.

Alzheimer's disease (AD) is characterized by immune system dysregulation, impacting both central and peripheral immune responses. The study aimed to investigate the mechanism behind the neurotoxic effects of β-amyloid (Aβ) peptide in the rat brain including the study of neuroinflammation, neurodegeneration, and alterations in peripheral immune responses (PIR). The neuroinflammation brought on by Aβ1-42 and is unknown to influence PIR. Animal models were prepared, after 28 days, control, sham, and treated rats were anaesthetized and inflammatory markers of hippocampus and serum levels (reactive oxygen species, nitrite, tumor necrosis factor-α, and interleukin-1β), and some markers of PIR (splenic mononuclear cells or MNC, cytotoxicity and phagocytic index of the white blood cells leukocyte adhesion inhibition index or LAI), as well as polymorphonuclear cells of the spleen, were assessed. In addition to changes in peripheral immune responses, the present study found that AD rats had higher blood levels of inflammatory markers. Based on the study, the immune system irregularities observed in AD rats in the peripheral regions might be connected to neuroinflammation, which is facilitated by a compromised blood-brain barrier. Hence, it is viable to propose that the neuroinflammatory condition in rats with Aβ-induced AD could modify immune responses in the peripheral areas with significantly higher levels of inflammatory cytokines markers in the hippocampal tissue in Aβ-injected AD rats.

Abstract 14108: Eicosapentaenoic Acid and Docosahexaenoic Acid and Their Association With Oral Inflammatory Markers in Subjects With Clinical Coronary Artery Disease

Background: Our group previously reported that subjects with coronary artery disease (CAD) randomized to the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), had lower levels of blood inflammatory markers and prevention of progression of non-calcified coronary plaque. Macrophage inhibitory protein (MIP)-1β is an inflammatory chemokine expressed by T cells in human plaques; circulating levels are increased in patients with atherosclerosis. The relation between EPA+DHA supplementation and oral inflammatory markers is unclear. Aim: To determine if EPA+DHA supplementation lowers levels of oral inflammatory markers. Methods: Subjects with clinical CAD were randomized to EPA+DHA, 3.36 g daily, or none for 30 months; 199 underwent a dental exam. Gingival crevicular fluid was collected at baseline and 30 months and analyzed for inflammatory markers. Results: MIP-1-β level was significantly lower in the EPA+DHA group compared to control at 30 months in the left upper quadrant of the mouth but not in the right upper quadrant (Table). This difference could potentially be explained by handedness. For example, Right-handed people tend to brush the left side of the mouth better whereas left-handed individuals and ambidextrous individuals have better brushing skills on the right side of the mouth. Other inflammatory markers (MCP, TNF-a, IL-1 and IL-6) were not different between groups on either side. Conclusions: Subjects with CAD randomized to EPA+DHA had reduced levels of the oral inflammatory marker, MIP-1β, at 30 months, suggesting that EPA+DHA can confer oral health benefits in addition to lowering systemic inflammation. For greatest benefit, brushing equally on both sides of the mouth should be encouraged, for which a powered toothbrush can help as it doesn’t rely on manual dexterity and handedness. Future research should examine whether the benefit of omega-3 fatty acids on oral health increases the benefit on coronary plaque.

SERPINA3: A novel inflammatory biomarker associated with cerebral small vessel disease burden in ischemic stroke.

Inflammation has emerged as a prominent risk factor for cerebral small vessel disease (CSVD). However, the specific association between various inflammatory biomarkers and the development of CSVD remains unclear. Serine proteinase inhibitor A3 (SERPINA3), Matrix metalloproteinase-9 (MMP-9), Tissue inhibitor metalloproteinase-1 (TIMP-1), Monocyte Chemoattractant Protein-1 (MCP-1) are several inflammatory biomarkers that are potentially involved in the development of CSVD. In this present study, we aimed to investigate the relationship between candidate molecules and CSVD features. The concentration of each biomarker was measured in 79 acute ischemic stroke patients admitted within 72 h after symptom onset. The associations between blood levels of inflammatory markers and CSVD score were investigated, as well as each CSVD feature, including white matter hyperintensities (WMH), lacunes, and enlarged perivascular spaces (EPVS). The mean age was 69.0 ± 11.8 years, and 65.8% of participants were male. Higher SERPINA3 level (>78.90 ng/mL) was significantly associated with larger WMH volume and higher scores on Fazekas's scale in all three models. Multiple regression analyses revealed the linear association between absolute WMH burden and SERPINA3 level, especially in model 3 (β = 0.14; 95% confidence interval [CI], 0.04-0.24 p ). Restricted cubic spline regression demonstrated a dose-response relationship between SERPINA3 level and larger WMH volume (p nonlineariy = 0.0366 and 0.0378 in model 2 and mode 3, respectively). Using a receiving operating characteristic (ROC) curve, plasma SERPINA3 level of 64.15 ng/mL distinguished WMH >7.8 mL with the highest sensitivity and specificity (75.92% and 60%, respectively, area under curve [AUC] = 0.668, p = 0.0102). No statistically significant relationship has been found between other candidate biomarkers and CSVD features. In summary, among four inflammatory biomarkers that we investigated, SERPINA3 level at baseline was associated with WMH severity, which revealed a novel biomarker for CSVD and validated its relationship with inflammation and endothelial dysfunction.

The effects of functional foods mixture on inflammatory cytokines and biochemical findings in hospitalized patients with COVID-19: a randomized double-blind controlled trial

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has been shown to affect nutritional recommendations. Some functional foods have been demonstrated to be useful in the treatment of people with COVID-19. However, little is known about the impact of combining functional foods on disease control. This study aimed to investigate the effects of functional foods mixture on serum levels of inflammatory cytokines and biochemical findings in patients with COVID-19.MethodsA randomized double-blind controlled trial was conducted in Baqiyatallah Al-Azam hospital in Tehran, Iran. Sixty patients were randomly assigned to receive either a soup containing functional foods (n = 30) or a usual soup (control group) (n = 30). Participants’ sociodemographic information was gathered using a general questionnaire. Blood levels of inflammatory markers and biochemical findings were assessed using standard protocols.ResultsThe results showed that soup containing functional foods was more effective in controlling serum levels of D-dimer, blood urea nitrogen, and creatinine than the control group (P < 0.05). Also, more significant improvement was found in the intervention group vs control group in terms of interleukin (IL)-1β, IL-6, IL-17, IL-10, and tumor necrose factor-α (P < 0.05). In contrast, the control intervention more efficiently controlled potassium levels and reduced quantitative C-reactive protein than the intervention group (P < 0.05).ConclusionsThis study indicates a soup containing functional foods could alleviate biomarkers of inflammation in patients with COVID-19. However, its effectiveness on biochemical findings remained inconclusive which warranted further research.Trial registrationIRCT, IRCT20180201038585N11. Registered 23 August 2021, https://www.irct.ir/trial/57338

Associations between blood inflammatory markers and bone mineral density and strength in the femoral neck: findings from the MIDUS II study

Chronic and systematic inflammation have been related to increased risks of osteopenia and related fracture. However, studies concerning the association between low-grade inflammation and the bone mineral density (BMD) and strength of the femoral neck are still few and inconsistent. This study aimed to examine the relationships between blood inflammatory biomarkers and BMD and femoral neck strength in an adult-based cohort. We retrospectively analyzed a total of 767 participants included in the Midlife in the United States (MIDUS) study. The blood levels of inflammatory markers, including interleukin-6 (IL6), soluble IL-6 receptor, IL-8, IL-10, TNF-α and C-reactive protein (CRP), in these participants were measured, and their associations with the BMD and strength of the femoral neck were determined. We analyzed these 767 subjects with data concerning the BMD, bending strength index (BSI), compressive strength index (CSI), and impact strength index (ISI) in the femoral neck and inflammatory biomarkers. Importantly, our results suggest that strongly negative associations exist between the blood soluble IL6 receptor levels and the BMD (per SD change, Sβ = −0.15; P < 0.001), CSI (per SD change, Sβ = −0.07; P = 0.039), BSI (per SD change, Sβ = −0.07; P = 0.026), and ISI (per SD change, Sβ = −0.12; P < 0.001) in the femoral neck after adjusting for age, gender, smoked cigarettes regularly, number of years drinking, BMI and regular exercise. However, the inflammatory biomarkers, including blood IL-6 (per SD change, Sβ = 0.00; P = 0.893), IL-8 (per SD change, Sβ = −0.00; P = 0.950), IL-10 (per SD change, Sβ = −0.01; P = 0.854), TNF-α (per SD change, Sβ = 0.04; P = 0.260) and CRP (per SD change, Sβ = 0.05; P = 0.137), were not strongly associated with the BMD in the femoral neck under the same conditions. Similarly, there was no significant difference in the relationships between the inflammatory biomarkers (IL-6, IL-8, IL-10, TNF-α and CRP) and the CSI, BSI, and ISI in the femoral neck. Interestingly, in concomitant inflammation-related chronic diseases, only arthritis affected the soluble IL-6 receptor and the CIS (interaction P = 0.030) and SIS (interaction P = 0.050) in the femoral neck. In this cross-sectional analysis, we only observed that high blood levels of soluble IL-6 receptor were strongly associated with reduced BMD and bone strength in the femoral neck. The independent associations between the other inflammatory indicators, including IL-6, IL-8, IL-10, TNF-α and CRP, and the BMD and femoral neck strength in an adult-based cohort were not significant.

Correlation between Acute Kidney Injury and Inflammatory markers in Coronavirus Disease 2019

Background and Objectives: Coronavirus Disease 2019 (COVID-19) particularly when severe may commonly present with Acute Kidney Injury and may show elevated blood levels of inflammatory markers. Current study aims at determining the correlation between AKI and raised inflammatory markers in COVID-19.&#x0D; Materials and Methods: Medical records of 250 patients admitted in COVID-19 isolation intensive care unit of Farooq Hospital, Westwood Branch, Lahore between 1st July, 2021 and 30th September, 2021 were retrospectively reviewed and data comprising of demographic, clinical and laboratory parameters was collected. Patients with confirmed diagnosis of COVID-19 from Real Time Polymerase Chain Reaction (RT-PCR) were included in the study while those with incomplete medical records or known history of Chronic Kidney Disease (CKD) were excluded. Statistical analysis of collected data was then made and p value &lt; 0.05 was considered statistically significant.&#x0D; Results: Among 176 patients who fulfilled the inclusion criteria, most (138(78.4%)) were males with mean age of 51.26±15.20 years. Diabetes Mellitus was most common comorbidity observed in 70(39.8%) patients and mean length of hospital stay was 8.46±4.12 days. AKI was found in 91(51.7%) patients while remaining 85(48.3%) patients didn’t have AKI. All four inflammatory markers: C-Reactive Protein (CRP), D-dimers, ferritin and procalcitonin (PCT) were found significantly raised in COVID-19 patients having AKI compared with non-AKI group (p &lt; 0.05).&#x0D; Conclusions: Raised inflammatory markers in patients having severe COVID-19 are associated with increased risk of AKI.

202 A CTS Team Approach to Immune Signatures of PTSD Susceptibility

OBJECTIVES/GOALS: Post-traumatic stress disorder (PTSD) develops in a subset of individuals (15-25%) exposed to trauma. We report our preliminary findings investigating underlying peripheral immune responses related to risk and resilience to PTSD. METHODS/STUDY POPULATION: Sprague-Dawley rats (half male) were exposed to predator scent stress in the form of the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) once for 10 minutes. Seven days later, rats were assessed for persistent anxiety-like behavior using the acoustic startle response task (ASR) and elevated plus maze (EPM). Tail blood was collected for later inflammation analysis at three time points: 1) prior to experiment start, 2) after TMT exposure, and 3) after ASR and EPM. Using a with-in subjects design, our experiment elucidates the connection between PTSD-like symptoms and baseline immune function, inflammatory stress responses, and chronic inflammatory state after stress exposure. RESULTS/ANTICIPATED RESULTS: In comparison to healthy controls, humans with PTSD show elevated blood levels of inflammatory markers. Human studies also show a relationship between baseline immune dysfunction and later PTSD development. In agreement with this literature, we anticipate PTSD-like rats will have increased blood levels of inflammation markers at all three time points compared to resilient and control rats. These findings will back-translate human findings in support of the predator scent stress preclinical model of PTSD. DISCUSSION/SIGNIFICANCE: Our findings will elucidate the temporal aspects of proinflammatory markers and PTSD development. This study will indicate if baseline peripheral immune dysfunction, inflammatory response immediately after stress exposure, and/or chronic inflammatory state predicts ptsd-like behavior in rats.

Adopting Natural Host Immune Response Against Zoonosis

Zoonosis originated from the transmission of pathogens between species. Rapid mutation causes the pathogens to develop resistance to treatments. Thus, there is an urgent need for medications that could maintain efficacy when encountering new strains. This study aims to discern the possibility of overcoming threats from EIDs by recreating immune responses of natural hosts and reinforcing them in the human system. The methodology used is literature study, as the resarcher utilized data presented by similar studies. References will be taken from clinical trials and studies on related topics from PubMed, ResearchGate, and NCBI. Within multiple research papers, it was found that several experts support the idea of mimicking hosts' immunity through the use of interferon. Treatments with IFN-2b significantly reduce viral infection of SARS-CoV-2 in the upper respiratory tract and increase blood levels of inflammatory markers, according to research conducted in Wuhan. Similar results apply in other trials, proving that interferon managed to contain the invasion of pathogens. This is shown through a reduction in the severity of infections, the duration of viral clearance, and levels of mortality. The results conclude that the use of interferon benefits the patient’s recovery progress by mimicking the natural host’s immune response and heightening the viral clearance rate. More research needs to be done to explore the effect of excessive IFN-$\alpha$/$\beta$ usage on immunity.

The Managing Cancer and Living Meaningfully (CALM) Intervention Alleviates Chemotherapy-Related Cognitive Impairment in Patients with Breast Cancer by Modulating Pan-Immune-Inflammation Values.

The number of patients with breast cancer is increasing worldwide, resulting in a growing number of patients with chemotherapy-related cognitive impairment (CRCI), which seriously affects their quality of life. CRCI is associated with inflammatory factors and systemic inflammatory markers such as pan-immune-inflammation value (PIV) and monocyte-to-lymphocyte ratio (MLR), which can reflect the level of inflammation in the body. While the Managing Cancer and Living Meaningfully (CALM) intervention has been demonstrated to alleviate CRCI in patients with breast cancer, the specific mechanism remains unclear. This study evaluated the impact of the CALM intervention on systemic inflammation. Ninety patients with breast cancer with CRCI were enrolled and randomized into care as usual (CAU) and CALM intervention groups. All patients were assessed using the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Mini-Mental State Exam (MMSE), and Functional Assessment of Cancer Therapy-Breast (FACT-B) before and after the CAU/CALM intervention. The blood levels of inflammatory markers were also analyzed before and after the intervention. Compared to the CAU group, the CALM group showed significantly improved cognitive function and significantly decreased PIV (P < .05). PIV was significantly negatively correlated with FACT-Cog (P < .05). The levels of other inflammatory markers, including MLR, neutrophil-to-lymphocyte ratio (NLR), granulocyte-to-lymphocyte ratio (GLR), and systemic immune-inflammation index (SII), were also reduced in the CALM group. PIV is an important marker of inflammation. The CALM intervention may improve the cognitive function of patients by regulating the systemic inflammation marker PIV through the neuroimmune axis.

The innate immune system in human kidney inflammaging.

Elderly individuals with chronic disorders tend to develop inflammaging, a condition associated with elevated levels of blood inflammatory markers, and increased susceptibility to chronic disease progression. Native and adaptive immunity are both involved in immune system senescence, kidney fibrosis and aging. The innate immune system is characterized by a limited number of receptors, constantly challenged by self and non-self stimuli. Circulating and kidney resident myeloid and lymphoid cells are all equipped with pattern recognition receptors (PRRs). Recent reports on PRRs show kidney overexpression of toll-like receptors (TLRs) in inflammaging autoimmune renal diseases, vasculitis, acute kidney injury and kidney transplant rejection. TLR upregulation leads to proinflammatory cytokine induction, fibrosis, and chronic kidney disease progression. TLR2 blockade in a murine model of renal ischemia reperfusion injury prevented the escape of natural killer cells and neutrophils by inflammaging kidney injury. Tumor necrosis factor-α blockade in endothelial cells with senescence-associated secretory phenotype significantly reduced interleukin-6 release. These findings should encourage experimental and translational clinical trials aimed at modulating renal inflammaging by native immunity blockade.

Does Hypertension Alone Increase Mortality In Young Hypertensive Patients With COVİD-19? Single Center Retrospective Study Of 100 Patients

Purpose: Whether hypertension is an independent risk factor for the severity of COVID-19 symptoms and COVID-19 mortality is still unclear. In this study, it was aimed to investigate the effect of hypertension independently in the course of COVID-19 by comparing clinical characteristics and laboratory measurements in COVID-19 patients with and without preexisting hypertension. Materials and Methods: Fifty COVID-19 patients under the age of 45 with preexisting hypertension without accompanying chronic diseases were compared with 50 normotensive COVID-19 patients. All patients received the same treatment protocol. The frequency of symptoms, blood levels of inflammatory markers, length of hospital stay, intensive care unit (ICU) requirement, and mortality rates were compared between the groups. Results: Peak leukocyte count (8.1±2.7 x 103/mm3 vs. 6.9±1.9x103/mm3, p=0.012), peak C-reactive protein (52.7±9.7mg/L vs. 18.9±3.7 mg/L, p=0.024), and peak erythrocyte sedimentation rate (ESR) (55.5±5.7 mm/h, vs. 33.4±5.1 mm/h, p<0.01) were significantly higher in hypertensive patients compared to normotensive ones (all values respectively). Hospital stay duration was significantly longer in hypertensive patients than the normortensive ones. (hypertensive group 11±2.4 days; normotensive group 9.1±2.2 days, p=0.001). Conclusions: COVID-19 patients having hypertension have higher levels of inflammatory markers, higher levels of troponin, and longer hospital stay compared to COVID-19 subjects without hypertension. It appears that hypertensive patients tend to have a more severe COVID-19 infection than normotensive patients.

Vitamin D deficiency as a predictor of severity in patients with COVID-19 infection.

As an immune modulator, vitamin D has been implicated in the coronavirus disease 2019 (COVID-19) severity. This study aimed to investigate the association between vitamin D levels and the severity of COVID-19 infection. A cross-sectional study, which included 124 patients diagnosed with COVID-19 and were selected from Ain Shams University Hospitals and assigned to two groups; mild and severe COVID-19. All patients underwent detailed history taking, clinical data, and different laboratory investigations as complete blood count, blood urea nitrogen, serum creatinine, liver enzymes, C-reactive protein, D-dimer, ferritin and serum vitamin D concentration. In addition to findings of initial chest computed tomography (CT) were recorded. COVID-19 Reporting and Data System (CO-RADS) and CT chest severity scores (CT SS) were reported. In this study of 124 COVID-19-positive individuals, a high prevalence of hypovitaminosis D was found (97.6%). Lower vitamin D levels were significantly associated with more severe COVID-19 cases (p-value < 0.001), higher blood levels of inflammatory markers including (D-dimer, CRP, and ferritin), a higher CT SS and longer disease duration. Serum vitamin D can be used as a predictor for the severity of COVID-19 infection with a specificity of 96.6%, and sensitivity of 45.5%. The high frequency of hypovitaminosis D in severe COVID-19 patients provides further evidence of a potential link to poor prognosis and severity of the disease, so vitamin D deficiency may be a marker of poor prognosis in these patients.

Low-volume high-intensity interval training for children with obesity: a commentary

Obesity is the most common chronic disease in childhood, and is a risk factor for cardiovascular diseases (CVD) later in life. Being obese is inversely associated with physical activity and cardiorespiratory fitness (CRF) in children. Increased CRF may negate the detrimental effects of obesity-associated risk factors for CVD, while poor CRF has been associated with increased arterial stiffness and higher levels of blood inflammatory markers. The use of time efficient high-intensity interval training (HIIT) to reduce CVD risk factors and body mass, improve CRF and other health parameters has become popular during the last years in adults with obesity. However, a relatively few studies have investigated the effect of HIIT on body composition, CRF and cardiometabolic biomarkers in children with obesity. It is expected that low-volume HIIT programs are feasable for community-based body mass reduction and health promotion in children with obesity.

Longitudinal study of inflammatory markers and psychopathology in schizophrenia

ObjectiveSchizophrenia is associated with abnormal levels of blood inflammatory markers, which may be correlated with levels of psychopathology. Few previous studies have explored whether baseline inflammatory marker levels predict longitudinal changes in psychopathology. In the present study, we explored this association in a cohort of patients with schizophrenia. MethodWe investigated inflammatory markers and psychopathology after 3, 6, and 12 months of antipsychotic treatment for subjects with baseline and follow-up data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial. Linear regression models, controlling for multiple potential confounding factors, were used to investigate these associations. ResultsThere was a significant decrease in monocyte, ICAM, and adiponectin levels between baseline and 12 months. Higher baseline blood interleukin-6 (IL-6) predicted greater reduction in PANSS total and general subscale scores at 3 and 6 months, and PANSS negative subscale scores at 3 months (β = −0.10 to −0.16, p < 0.05 for each). Higher baseline blood leptin levels predicted greater reduction in PANSS total, negative and general subscale scores at 6 months (β = −0.09 to −0.11, p < 0.05 for each). In post-hoc analyses, associations between baseline IL-6 levels and symptom reduction were strongest in patients treated with either ziprasidone or quetiapine. Changes in blood inflammatory markers were generally not associated with changes in psychopathology. ConclusionsOur findings provide additional support that measuring blood inflammatory markers may be relevant to the clinical care of patients with schizophrenia. Specifically, these markers may help guide selection of antipsychotic treatment towards more personalized medicine approaches for patients with schizophrenia.

Competing interplay between systemic and periodontal inflammation: obesity overrides the impact of oral periphery

ObjectivesWe aimed at investigating whether the interaction between the local inflammation, periodontitis, and obesity is independently associated with systemic inflammation.MethodsFrom the population-based Study of Health in Pomerania, 3366 participants, without (2366) and with (1000) obesity, were studied for the association of periodontitis, measured as probing depth (PD) and plaque together with body mass index (BMI) on C-reactive protein (CRP). Quantile regression was used to evaluate the association between periodontal, anthropometric, and inflammatory variables (outcomes).ResultsThe overall prevalence of obesity in this adult population was 31.4% in men and 28.1% in women. Both PD and plaque were positively associated with CRP, revealing an increasing impact across the CRP concentration distribution. Adjusting the regression of CRP or fibrinogen on PD for waist circumference attenuated but did not abolish the PD coefficients. Dental plaque was similarly associated with these interrelations. Association between PD and a dental plaque was different among participants with low-, medium-, or high-risk CRP concentrations.ConclusionLocal and systemic sources of inflammation contribute to blood levels of inflammatory markers. The respective contributions depend on the relative rate in each of the inflammation-inducing risks and are dominated by adiposity.Clinical relevanceKeeping systemic inflammation low in order to prevent age-related disease sequelae.

Highly Bioavailable Curcumin Derivative Ameliorates Crohn's Disease Symptoms: A Randomized, Double-Blind, Multicenter Study.

The new curcumin derivative Theracurmin® has a 27-fold higher absorption rate than natural curcumin powder. Theracurmin® is an inhibitor of nuclear factor-κB, which mediates the expression of inflammatory cytokines. The effect of Theracurmin® on inflammatory bowel disease in humans has not been explored; therefore, we investigated the efficacy and safety of Theracurmin® in patients with Crohn's disease. In this randomized, double-blinded study performed at 5 independent medical centers in Japan, Theracurmin® (360 mg/day, n = 20) or placebo (n = 10) was administered to patients with active mild-to-moderate Crohn's disease for 12 weeks. The agent's efficacy was assessed by evaluating clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. In the Theracurmin® group, a significant reduction in clinical disease activity was observed in week 12 relative to that in week 0 (p = 0.005). On intention-to-treat analysis, clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, which were significantly higher than those in the placebo group (all 0%; p = 0.033, p = 0.020, and p = 0.020, respectively). Furthermore, reduction in endoscopic Crohn's disease severity (p = 0.032) was observed at week 12 in the Theracurmin® group. The endoscopic remission rates were 15% and 0% in the Theracurmin® and placebo groups, respectively. Significant healing of anal lesions (p = 0.017) was observed at week 8 in the Theracurmin® group. No serious adverse events were observed in either group throughout the study. Theracurmin® shows significant clinical and endoscopic efficacy together with a favorable safety profile in patients with active mild-to-moderate Crohn's disease. UMIN000015770.

Serum inflammatory profiles – association with breast cancer risk including dietary patterns: a case-control study

AbstractBreast cancer is the most common cancer among women worldwide. Diet and inflammation have been associated with carcinogenesis. However, there are limited studies regarding both blood levels of inflammatory markers and diet with respect to the risk of breast cancer. We assessed the association between serum inflammatory profiles and breast cancer (BC) risk with including dietary patterns (DPs). This case-control study involved 420 women aged 40–79 years from north-eastern Poland, including 190 newly-diagnosed breast cancer cases. The serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6) and leukocytes (including neutrophil and lymphocyte count) were marked in 129 post-menopausal women (82 controls, 47 cases) using a Cobas Integra 400plus auto-analyser, an immune-analyser Cobas e411 (Roche Diagnostics®) and haematology analyser MEK-7300 (Nihon Kohden®), respectively. A posteriori inflammatory profiles were derived with a Principal Component Analysis (PCA). A logistic regression analysis was performed. The odds ratios (ORs) and 95% confidence interval (95% CI) were calculated. The ORs were adjusted for: age, BMI, socioeconomic status, overall physical activity, smoking status, abuse of alcohol, age at menarche, number of children, oral contraceptive use, hormone-replacement therapy use, family history of breast cancer, vitamin/mineral supplements use, hormone receptor status of breast cancer and PCA-driven DPs (‘Non-Healthy’, ‘Prudent’, and ‘Margarine and Sweetened Dairy’) score. Two serum inflammatoryprofiles were identified. The ‘CRP-IL-6’ profile was loaded heavily by the interleukin-6 (factor loading 0.78) and C-reactive protein (factor loading 0.75). The ‘Neutrophil-Lymphocyte’ profile was loaded heavily by the lymphocyte (factor loading 0.86) and neutrophil count (factor loading 0.70). The risk of BC was six times higher (OR = 6.05; 95%Cl: 1.93–18.91; p &lt; 0.05) in the third tertile of serum ‘CRP-IL-6’ profile compared to the first or second tertile. The risk of BC was three times higher (OR = 3.11; 95%Cl: 1.05–9.20; p &lt; 0.05) at the level of serum IL-6 &gt; 3.10 pg/mL and seven times higher (OR = 7.48; 95%Cl: 2.31–24.29; p &lt; 0.05) at the level of serum neutrophil count &gt; 3.90 103/μL. No significant association between BC risk and serum ‘Neutrophil-Lymphocyte’ profile and also CRP or lymphocyte count considered separately was revealed. Concluding, the elevated serum levels of both C-reactive protein and interleukin-6, as well as elevated levels of interleukin-6 and neutrophil count considered separately, were associated with higher risk of postmenopausal breast cancer, independently of dietary patterns. Therefore, women should be screened for blood concentrations of multiple potential pro-inflammatory markers in the breast cancer prevention.

Highly Bioavailable Curcumin Derivative 'Theracurmin®' for Crohn's Disease: A Randomized, Double-Blind, Placebo-Controlled Multicentre Study

Background: The new curcumin derivative, Theracurmin® has a 27-fold higher absorption rate than the natural curcumin powder. Its pharmacologic actions include inhibition of the nuclear factor NF-κB, known to mediate the expression of inflammatory cytokines. We were interested to evaluate efficacy of Theracurmin® in patients with Crohn's disease (CD). Methods: Theracurmin® (360mg/day, n=20) or placebo (n=10) was administered to patients with active mild to moderate CD for 12 weeks. Efficacy assessment included clinical and endoscopic remission, healing of anal lesions, and blood levels of inflammatory markers. Findings: In the Theracurmin® group, significant reduction of clinical disease activity was observed at 12 weeks relative to week 0 (P=0.005). The clinical remission rates were 35%, 40%, and 40% at weeks 4, 8, and 12, respectively, significantly higher than in the placebo group (P=0.033, P=0.020, and P=0.020). Further, in the Theracurmin® group, significant healing of anal lesions (P=0.017) and endoscopic CD severity (P=0.032) were observed at weeks 8 and 12, respectively, relative to week 0. However, the mucosal healing rate at week 12 in the Theracurmin® group was 15.0%. No serious adverse event was observed in either group throughout our observation time. Interpretation: In this study, Theracurmin® in patients with active mild to moderate CD produced significant clinical and endoscopic efficacy together with a favourable safety profile. Trial registration: UMI15770 Funding Statement: Theracurmin® was a gift from Theravalues Corporation, Tokyo, Japan. The authors received no external funding for this study. Declaration of Interests: All authors acknowledge having no conflict of interest in connection with the publication of this manuscript. Ethics Approval Statement: At each institution, the study protocol was reviewed and approved by the committee on the Ethics of Clinical Trials involving human subjects. Further, the trial was conducted by adherence to the principles of Good Clinical Practice (GCP) and the ethical standards laid down in the 1964 Helsinki Declaration and its subsequent amendments. Similarly, informed consent was obtained from all patients after explaining the purpose of the study and the nature of the procedures involved.

Perinatal Ureaplasma Exposure Is Associated With Increased Risk of Late Onset Sepsis and Imbalanced Inflammation in Preterm Infants and May Add to Lung Injury.

Background: Controversy remains concerning the impact of Ureaplasma on preterm neonatal morbidity.Methods: Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for Ureaplasma parvum and U. urealyticum using culture technique and polymerase chain reaction. Neonatal outcomes were followed until death or discharge. Multi-analyte immunoassay provided cord blood levels of inflammatory markers. Using multivariate regression analyses, perinatal Ureaplasma exposure was evaluated as risk factor for the development of bronchopulmonary dysplasia (BPD), other neonatal morbidities until discharge and systemic inflammation at admission.Results: 40/103 (39%) infants were positive for Ureaplasma in one or both specimens, with U. parvum being the predominant species. While exposure to Ureaplasma alone was not associated with BPD, we found an increased risk of BPD in Ureaplasma-positive infants ventilated ≥5 days (OR 1.64; 95% CI 0.12–22.98; p = 0.009). Presence of Ureaplasma was associated with a 7-fold risk of late onset sepsis (LOS) (95% CI 1.80–27.39; p = 0.014). Moreover, Ureaplasma-positive infants had higher I/T ratios (b 0.39; 95% CI 0.08–0.71; p = 0.014), increased levels of interleukin (IL)-17 (b 0.16; 95% CI 0.02–0.30; p = 0.025) and matrix metalloproteinase 8 (b 0.77; 95% CI 0.10–1.44; p = 0.020), decreased levels of IL-10 (b −0.77; 95% CI −1.58 to −0.01; p = 0.043) and increased ratios of Tumor necrosis factor-α, IL-8, and IL-17 to anti-inflammatory IL-10 (p = 0.003, p = 0.012, p < 0.001).Conclusions: Positive Ureaplasma screening was not associated with BPD. However, exposure contributed to BPD in infants ventilated ≥5 days and conferred an increased risk of LOS and imbalanced inflammatory cytokine responses.