Lower C-reactive Protein Levels Research Articles

The Predictive Potential of the Baseline C-Reactive Protein Levels for the Efficiency of Immune Checkpoint Inhibitors in Cancer Patients: A Systematic Review and Meta-Analysis

BackgroundThe relationship between baseline C-reactive protein (CRP) level and the prognosis of cancer patients receiving immune checkpoint inhibitor (ICI) treatment remains controversial. The aim of this meta-analysis was to clarify whether baseline CRP level can serve as a biomarker to predict the efficiency of ICI therapy.MethodsAll associated articles published in the Cochrane Library, EMBASE, and PubMed databases from the inception of the database to December 30, 2021, were retrieved. Progression-free survival (PFS) and overall survival (OS) outcomes were meta-analyzed using the random-effects model and adjusted using the trim-and-fill method because of publication bias.ResultsThirty-three studies (6,124 patients) conducted between 2013 and 2021 were identified. The pooled outcomes implied that high baseline CRP level patients had significantly worse OS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.48, 95% CI = 1.41–1.56; HR = 1.46, 95% CI = 1.34–1.59) and PFS (adjusted pooled value for univariate and multivariate analysis outcomes: HR = 1.29, 95% CI = 1.15–1.45; HR = 1.20, 95% CI = 1.02–1.40) than low baseline CRP level patients, irrespective of cancer or ICI type. Further analysis indicated that 1 mg/dl was appropriate as a cutoff value for determining the low or high level of baseline CRP to predict the OS or PFS of cancer patients receiving ICI treatment (univariate analysis: HR = 1.56, 95% CI = 1.24–1.97, P = 0.909; multivariate analysis: HR = 1.58, 95% CI = 1.23–2.03, P = 0.521).ConclusionsHigh baseline CRP level (>1 mg/dl) may be an indicator for worse OS and PFS of cancer patients treated with ICIs. More high-quality prospective studies are warranted to assess the predictive value of CRP for ICI treatment.

Association between C-reactive protein levels and antipsychotic treatment during 12 months follow-up period after acute psychosis

BackgroundA potential role of inflammatory pathways in the pathology of schizophrenia has been suggested for at least a subgroup of patients. Elevated levels of the inflammatory marker C-reactive protein (CRP) have been observed, with associations to pathogenesis and symptoms. The current evidence regarding effects of antipsychotics on CRP levels is ambiguous. ObjectivesTo examine and compare the influence on CRP levels of three pharmacologically diverse new generation antipsychotics during a one-year follow-up in schizophrenia spectrum disorder. MethodsIn a multicenter, pragmatic and rater-blinded randomized trial, the effects of amisulpride, aripiprazole and olanzapine were compared in 128 patients with schizophrenia spectrum disorder. All had positive symptoms of psychosis at study entry. Clinical and laboratory assessments including the measurement of CRP levels were conducted at baseline, and 1, 3, 6, 12, 26, 39, and 52 weeks thereafter. ResultsFor all antipsychotic drugs analysed together, there was an increase in CRP levels during the one-year follow-up. Aripiprazole, as opposed to amisulpride and olanzapine, was associated with a reduced CRP level after one week, after which the CRP level caught up with the other drugs. Compared to those previously exposed to antipsychotic drugs, antipsychotic-naïve patients had lower CRP levels at all follow-up time points, but with the same temporal patterns of change. ConclusionTreatment with amisulpride, aripiprazole and olanzapine showed different effects on CRP levels in patients with schizophrenia spectrum disorders, modified by previous antipsychotics exposure status. This finding suggests that antipsychotic drugs may vary with respect to their influence on pro-inflammatory pathways. Trial registrationClinicalTrials.gov ID: NCT01446328; URL: http://www.clinicaltrials.gov/.

C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population.

Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear. A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined. For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29-2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25kg/m2 (P=4×10-6 ). Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.

Comparison of C-reactive protein and Vitamin D3 level among Patients of Allergic Rhinitis while on treatment with either Nasal Fluticasone or Combination Therapy of Montelukast and Levocetirizine: A Randomized Control Study

We conducted the present study to compare the vitamin D3 status and C-reactive protein (CRP) among allergic rhinitis patients who were on treatment with either intranasal Fluticasone or oral Levocetrizine and Montelukast therapy. Material and Methods: The study was a prospective randomized, single blinded, comparative, parallel group study, with two intervention groups conducted at Civil Hospital Jogindernagar of Himachal Pradesh, India. A total of Fifty patients diagnosed with allergic rhinitis was randomly allocated to either Group A receiving oral Montelukast and Levocetrizine or Group B receiving Fluticasone propionate aqueous nasal spray and followed up for 6 weeks. Vitamin D status and C-reactive protein (CRP) after 6 weeks was taken as primary outcome variables. Results: Among Group A , Recovery at 6 weeks was occurred in 9 (36%) patients while in Group B Recovery at 6 weeks was occurred in 17(68 %) patients.(p value 0.046). There was statistically significant lower mean CRP level was found in group B as compared to Group A (p value 0.003). Although, lower mean Vit D3 level was found in group B as compared to Group A but this difference was not found to be statistically significant. (p value 0.218). Although, lower mean CRP and higher mean Vit D3 level was found in recovered patients in group A as compared to who were not recovered but this difference was not found to be statistically significant(p value 0.198 and 0.324 respectively). Similarly,higher mean CRP and Vit D3 level was found in recovered patients in group B as compared to who were not recovered but this difference was not found to be statistically significant.( p value 0.804 andp value 0.418). Similarly ,in recovered patients there was no statistical significant difference in mean CRP and Vit D3 level(P value 0.9536 and 0.2486 respectively) in both groups, although the mean CRP and Vit D3 level were higher in Group A as compared to group B. But in non recovered patients, the mean CRP level was statistically higher in Group A as compared to group B(P value0.0029) while there was no statistical significant difference in Vit D3 level in both groups.(p value-0.8919). Conclusion: Study concluded that there was no statistical significant difference in mean Vitamin D3 and CRP levels in both groups as well as there was no significant association between Vitamin D3 and CRP levels and recovery status of patients in both groups.

Negative Appendicectomy Rate: Incidence and Predictors.

IntroductionAcute appendicitis is a common emergency surgical presentation. The gold standard treatment is surgery. Like any surgical procedure, appendicectomy is associated with complications. Negative appendicectomy (NA) can occur, and its incidence is 15%-39%. This study aimed to evaluate the rate and predictors of NA in a cohort.Patients and methodsA retrospective study over a year through which data of patients who underwent emergency appendicectomies were collected and analyzed. The absence of inflammatory process and/or other significant pathology in the appendix was considered negative for appendicitis. An utter definition of NA was the absence of inflammatory cells in the appendix. The NA rate (NAR) was calculated using the standard criteria (NAR-SDC) and the strict criteria (NAR-STC). The routine laboratory parameters for diagnosing acute appendicitis on admission were collected. Increased inflammatory markers in the form of leucocytosis of total WBC > 11,000 per mm, elevated CPR > 5 mg/L, and isolated elevated total serum bilirubin > 20 µmol/L, were suggestive of acute appendicitis.ResultsThree hundred and seventy-two patients were included, 179 males and 193 females with a median age were 27 (5-94) years. The median duration of symptoms and waiting time to surgery were two days and one day, respectively. The mean admission WBC, C-reactive protein (CRP) and serum bilirubin levels were 12,600 (3,000-38,000)/mm3, 66.9 (1-323) mg/L and 12.7 (4-38) µmol/L respectively. Laparoscopic appendicectomy was performed in 93.5% of patients with a conversion rate of 4.6%. NAR-SDC was 10.2% and NAR-STC was 25.8%. NAR was significantly higher in females than males (39.4% versus 11.1%; p-value 0.0001). Patients with NA were younger (p-value 0.0001), had lower mean total WBC (p-value 0.014), CRP (p-value 0.0001) and total serum bilirubin (p-value 0.0001) levels on admission.ConclusionNA is still a major problem in the management of patients with acute right lower abdominal pain. Our NAR compared favourably with reported rates. Female gender, duration of symptoms more than three days, and lower total WBC were independent predictors of NA.

OP06 The influence of different prednisolone tapering algorithms on the effectiveness of infliximab in patients with Ulcerative Colitis – A real-world cohort study

Abstract Background Data regarding the influence of prednisolone tapering on clinical outcomes among patients with ulcerative colitis (UC) are limited. We aimed to investigate the influence of different prednisolone tapering algorithms on the effectiveness of infliximab (IFX) among patients with UC. Methods This Danish retrospective single-center study included all patients with UC who were treated with IFX between 2009 and 2019 at Herlev University Hospital. The patients were grouped according to the prednisolone tapering: standard (≤5 mg/week), fast (>5 mg/week), or direct discontinuation after an initial course of less than one week. Finally, we included a control group of patients treated with IFX monotherapy. The primary outcome was corticosteroid-free clinical remission at weeks 14 and 52 defined as a partial Mayo score ≤1. Variables with a p-value ≤0.20 in univariable regression analysis were included in multivariable analysis. A subgroup analysis containing patients with acute severe ulcerative colitis (ASUC) treated with at least 40 mg of prednisolone at initiation of IFX was performed. Results The study included 148 patients with UC of whom 81 (54.7%) were treated with prednisolone at the initiation of IFX. No association between prednisolone tapering and corticosteroid-free clinical remission with IFX at weeks 14 or 52 was observed (Figure 1 and Table 2). However, a higher proportion of patients in the standard tapering group achieved a C-reactive protein (CRP) level less than 5 mg/L at week 14 as compared with the fast-tapering group (23/23 (100%) vs. 14/18 (77.8%); p=0.03) and directly discontinuation group (6/10 (60%); p=0.03). This difference was not explained by prednisolone usage. In addition, none of the patients within the standard tapering regime (0/24; 0%) had severe activity at week 14 whereas this was seen in 4/19 (21.1%) in the fast tapering regime (p=0.03). In the subgroup analysis of 33 patients with ASUC, the standard tapering algorithm was associated with higher clinical remission as compared with the fast tapering regime at week 14 (9/14 (64.3%) vs. 5/19 (27.8%); p=0.02) and clinical response or remission at week 52 (12/14 (85.7%) vs. 7/19 (36.8%); p=0.01, Figure 2). Conclusion This study demonstrated no overall impact of prednisolone tapering algorithms on short and long-term effectiveness of IFX in patients with UC. However, standard tapering resulted in lower CRP levels and fewer cases of severe disease activity in the overall cohort and higher rate of short and long-term clinical response among ASUC patients, as compared with fast tapering regimes. Taken together, the data indicate that longer corticosteroid exposure in patients with high disease burden might improve IFX responses.

Association between Frequency of Toothbrushing and Metabolic Syndrome among Adolescents: A 5-Year Follow-Up Study.

This study longitudinally examines the relationship between the frequency of toothbrushing and the development of selected components of metabolic syndrome (MetS), along with the potential role of salivary biomarkers in this relationship. In 2014, 6317 12-year-old children underwent health examinations (T1), of which, 348 children participated in the second stage of data collection in 2019 (T2). The association between the change in the metabolic status during the 5-year follow-up examination (between T1 and T2) and frequency of toothbrushing was assessed using multinomial logistic regression analyses. At T2, healthy adolescents had significantly higher odds of toothbrushing twice or more daily compared with adolescents with components of MetS (OR = 1.99, 95% CI 1.15–3.45). Adolescents who were healthy at T1 but developed components of MetS at T2, had significantly higher frequencies of dining-out compared with adolescents with components of MetS at both T1 and T2 (OR = 0.09, 95% CI 0.02 to 0.49). Adolescents who were ‘healthy’ at both T1 and T2 had significantly (p < 0.05) lower levels of C-reactive protein (T2), insulin (T1 and T2), interleukin-6 (T1) and adiponectin (T1) compared with adolescents who had components of MetS. Toothbrushing and frequency of dining-out were associated with the presence of MetS components.

Mitochondrial DNA Copy Number Is Associated With Treatment Response and Cognitive Function in Euthymic Bipolar Patients Receiving Valproate.

BackgroundBipolar disorder (BD) is associated with cognitive impairment and mitochondrial dysfunction. However, the associations among mitochondrial DNA copy number (MCN), treatment response, and cognitive function remain elusive in BD patients.MethodsSixty euthymic BD patients receiving valproate (VPA) and 66 healthy controls from the community were recruited. The indices of metabolic syndrome (MetS) were measured. Quantitative polymerase chain reaction analysis of blood leukocytes was used to measure the MCN. Cognitive function was measured by calculating perseverative errors and completed categories on the Wisconsin Card Sorting Test (WCST). The VPA treatment response was measured using the Alda scale.ResultsBD patients had significantly higher MCN, triglyceride, and C-reactive protein (CRP) levels, waist circumference, and worse performance on the WCST than the controls. Regression models showed that BD itself and the VPA concentration exerted significant effects on increased MCN levels. Moreover, the receiver operating characteristic curve analysis showed that an MCN of 2.05 distinguished VPA responders from nonresponders, with an area under the curve of 0.705 and a sensitivity and specificity of 0.529 and 0.816, respectively. An MCN level ≥2.05 was associated with 5.39 higher odds of being a VPA responder (P = .006). BD patients who were stratified into the high-MCN group had a higher VPA response rate, better WCST performance, lower CRP level, and less MetS.ConclusionsThe study suggests a link between the peripheral MCN and cognitive function in BD patients. As an inflammatory status, MetS might modulate this association.

The Clinical Significance of the Expression of the Serum BMP 6 in the Patients with Tumor-related Anemia with Lower Levels of CRP and Hepcidin

<i>Objective:</i> To research the expression characteristic and clinical significance of the serum bone morphogenetic protein 6 (BMP6) at the lower expression condition of serum C-reactive protein (CRP) and Hepcidin (Hepc) in patients with tumor-related anemia. <i>Methods:</i> 113 hospitalized tumor patients from October 2019 to June 2020 and 20 healthy volunteers (control group) were recruited. We used enzyme-linked immunosorbent assay (ELISA) to determine the levels of BMP6, soluble-hemojuvelin (s-HJV) and Hepc, Electrochemiluminescence method to determine SF level, and particle-enhanced immune transmission turbidity method to determine CRP level, then analyzed their expression characteristics, correlations and clinical significance. <i>Results:</i> (1) The levels of BMP6, Hepc and CRP of anemia group were respectively 426.18±202.83mg/mL, 6.58±5.41ug/L and 19.10±18.24mg/L, which were all higher than 334.37±171.32mg/mL, 4.60±2.28ug/L and 3.62±3.46mg/L of non-anemia group (<i>t</i>=2.5804, 2.4750 and 3.4144, <I>P</I><0.01, <I>P</I><0.05 and <I>P</I><0.01, respectively). (2) The level of s-HJV was 0.71±0.28ng/mL, which was obviously lower than 1.07±1.01ng/mL (<i>t</i>=2.6529, <I>P</I><0.01) in non-anemia group. (3) There were negative correlations between BMP6 and both Hb and s-HJV (respectively <i>r</i>=-0.2807, <i>t</i>=3.0812 and <i>r</i>=-0.2497, <i>t</i>=2.7230, respectively, <I>P</I> both <0.01), but there were no correlations between BMP6 and CRP, Hepc and SF. (4) Hepc was positively correlated with both CRP and SF (<i>r</i>=0.2004, <i>t</i>=2.0660 and <i>r</i>=0.3089, <i>t</i>=3.1045, <I>P</I><0.05 and <I>P</I><0.01, respectively). Hepc was negatively correlated with Hb (<i>r</i>=-0.2524, <i>t</i>=2.7525, <I>P</I><0.01). Hepc had no correlation with s-HJV (<I>P</I>>0.05). (5) The BMP6 in the normal CRP group was 461.86±142.91 mg/mL, which was significantly higher than 364.51± 129.84 mg/mL in elevated CRP group (<I>F</I>=11.35, <I>P</I><0.01). (6) Hepc, s-HJV and SF in the normal CRP group were 5.17±3.49ug/L, 0.69±0.26ng/mL and 149.89±142.34ng/mL, respectively, which were all significantly lower than 9.02±7.14ug/L, 0.76±0.33ng/mL and 288.36±254.51ng/mL in the elevated CRP group (<I>F</I>=9.56, 4.67 and 2.84, <I>P</I>=0.000, 0.09, 0.046, respectively). <i>Conclusions:</i> When tumor patients with anemia is in a low-level condition of CRP and Hepc, the high expression of BMP6 is an important cause for the occurrence and development of anemia.

Factors affecting the occurrence of osseous lesions in septic shoulder arthritis and the recurrence rate after arthroscopic surgery

The purpose of this study was to determine the incidence of osseous lesions and the recurrence rate after arthroscopic surgery in shoulder septic arthritis patients and evaluate the influencing factors. We retrospectively reviewed 44 patients who underwent arthroscopic surgery for septic arthritis of the shoulder between January 2012 and September 2019. The average age of the patients was 65.57 ± 14.2 years, and 56.8% were female patients. The minimum follow-up period was 12 months (average, 32.8 ± 14.2 months; range, 12-72 months). We assessed variables including sex, age, underlying diseases, duration from symptom onset to magnetic resonance imaging (MRI), duration from symptom onset to surgery, radiologic results (radiography and MRI), history of injection therapy, and postoperative infection. The incidence of osseous lesions and the recurrence rate were calculated according to independent variables. In addition, multivariate logistic regression was performed to identify the risk factors for osseous lesions and recurrent infection after adjustment for other variables. Twenty-one patients had an osseous lesion on MRI, and 12 patients had evidence of bone erosion on radiographs. In univariate analyses, significant (P < .05) risk factors for the presence of osseous lesions were female sex, lower C-reactive protein level, and longer duration from symptom onset to MRI. The overall infection recurrence rate was 22.7% (10 of 44 patients). Culture results and the duration from symptom onset to surgery were significant risk factors for recurrent infection (P < .05). As the duration from symptom onset to MRI increased by 1 day, the probability of osseous lesions increased 1.31-fold (95% confidence interval, 1.08- to 1.59-fold; P = .007), and this probability was significantly higher after correction for other risk factors. To reduce the severity of septic shoulder infection, timely diagnosis and treatment are essential. Even if osseous lesions are present, good results can be obtained if meticulous débridement is performed through arthroscopic surgery. However, functional and radiologic long-term follow-up studies are needed in patients with osseous lesions.

The Relationship Between Gestational Diabetes Mellitus and Adipocytokine Levels.

The aim of this study was to compare adiponectin, resistin, visfatin, and irisin levels between pregnant women diagnosed gestational diabetes mellitus (GDM) and healthy pregnant women and to evaluate the role of these parameters in GDM pathophysiology and early diagnosis. Fifty GDM and 50 healthy pregnant women were included in the study. Anthropometric measurements of pregnant women were performed. Fasting blood glucose, hemoglobin A1c, 75 gr OGTT, low density lipoprotein, triglyceride, and complete blood count results were recorded. Adiponectin, irisin, visfatin, resistin, and C-reactive protein (CRP) levels were evaluated. Serum adiponectin levels were significantly lower (p<0.001) and serum resistin and CRP levels were significantly higher (p=0.000 and p=0.027, respectively) in pregnant women with GDM compared to healthy pregnants. There was no significant difference between groups according to serum irisin and visfatin levels (p=0.942 and p=0.332, respectively). There was a negative correlation between adiponectin level and FPG, visfatin, and resistin, while a positive correlation was found between irisin level. While there was a positive correlation between resistin and CRP levels, there was a negative correlation between adiponectin level. While there was a positive correlation between irisin and adiponectin levels, there was a negative correlation between weight and body mass index. In this study, we think that elevated serum resistin and CRP levels and decreased adiponectin levels in GDM patients may play a role in glucose metabolism changes. Further studies are needed on this subject.

Relationship between fatty acid intake and chronic neck/shoulder/upper limb pain without elevated CRP in a Japanese population: a cross-sectional analysis of the Shika study.

Abstract Although chronic pain (CP) is classified as inflammatory or non-inflammatory, the involvement of fatty acid intake in this process has not yet been examined in detail. Therefore, the present study investigated whether the relationship between CP and fatty acid intake differs between high and low C-reactive protein (CRP) levels in middle-aged and elderly individuals in the Shika study. One-thousand and seven males and 1216 females with mean ages of 68⋅78 and 69⋅65 years, respectively, participated in the present study. CRP was quantified by blood sampling from participants who responded to a CP questionnaire. The brief-type self-administered diet history questionnaire (BDHQ) was used to assess fatty acid intake. Interactions were observed between CP and CRP on monounsaturated fatty acids (MUFA) and eicosadienoic acid in a two-way analysis of covariance adjusted for sex, age, lack of exercise, lack of sleep, current smoking and drinking status, and BMI. MUFA (OR 1⋅359) and eicosadienoic acid (OR 1⋅072) were identified as significant independent variables for CP in a multiple logistic regression analysis, but only in the low CRP group. Only a high intake of MUFA and eicosadienoic acid was associated with chronic neck/shoulder/upper limb pain without elevated CRP. In psychogenic and neuropathic pain without elevated CRP, an increased intake of MUFA and eicosadienoic acid, a family member of n-6 fatty acids, appears to affect CP. Further longitudinal studies are needed to elucidate this relationship.

Efficacy and safety of unilateral biportal endoscopy compared with microscopic decompression in the treatment of lumbar spinal stenosis: A protocol for systematic review and meta-analysis.

Objective:Systematic evaluation of the efficacy and safety of unilateral biportal endoscopic decompression in the treatment of lumbar spinal stenosis.Methods:We conducted a systematic literature search and compared the randomized controlled trials (RCTs) and retrospective studies of unilateral biportal endoscopy (UBE) and microscopic decompression (MD) in the treatment of lumbar spinal stenosis from several databases.Results:Seven studies were included. The results of meta-analysis showed that the operation time of UBE was shorter than that of MD. [SMD = −0.443, 95% CI (−0.717, −0.169), P = .002]. Compared with MD, the patients’ back pain was slighter on the 1st day, 1–2 months and 6 months after UBE. During the long-term follow-up, there was no significant difference in back pain between MD and UBE [SMD = −0.519, 95% CI (−0.934, −0.104), P = .014]. There was no significant difference in lower limb visual analogue score (VAS) score between UBE decompression and MD [SMD = −0.105, 95% CI (−0.356, 0.146), P = .412]. The results of meta-analysis showed that the C-reactive protein (CRP) level of UBE was lower than that of MD [weighted mean difference = −1.437, 95% CI (−2.347, −0.527), P = .002]. There was no significant difference in other clinical effects between the 2 groups.Conclusion:The operation time of UBE was shorter than that of MD, and it was superior to micro decompression in early back VAS score, lower limb VAS score and early postoperative CRP level. There was no statistical difference between UBE and MD in other outcomes.

Anti-Inflammatory and Analgesic Effects of Rosehip in Inflammatory Musculoskeletal Disorders and Its Active Molecules.

Osteoarthritis and rheumatoid arthritis are the most common diseases of the musculoskeletal system, which greatly reduce the quality of life of people. In addition to non-steroidal anti- inflammatory drugs used in treatment, molecules isolated from natural sources are also considered as new options in the treatment of these inflammatory diseases. In this review, in vitro, in vivo and clinical studies on standardized rosehip (Rosa canina L.) fruits without seed used for joint health due to their anti-inflammatory, analgesic and antioxidant effects and active compounds isolated from these fruits are presented. It is reported that the anti-inflammatory action mechanism of standardized rosehip powder is due to its antioxidant activity, inhibiting NF-B signaling and pro-inflammatory enzymes, decreasing inflammatory cytokine and chemokine production, and lowering C reactive protein levels. The galactolipid (2S)-1,2-di-O-[(9Z,12Z,15Z)-octadeca-9,12,15- trienoyl]-3-O-ß-D-galactopyranosyl glycerol (GOPO), isolated from rosehip seeds and fruits, has been found to exhibit potent anti-inflammatory effects in vitro, clinically reducing the complaints of patients with osteoarthritis and improving their quality of life. Additionally, triterpene acid mixture (ursolic acid, oleanolic acid, and betulinic acid), also isolated from rosehip, has been reported to reduce the production of interleukin-6 and Tumor necrosis factor-α. Studies on the anti-inflammatory mechanism of action of rosehip and its active ingredients and their effects on osteoarthritis and rheumatoid arthritis have shown that more detailed clinical studies are required on standardized rosehip powders and preparations enriched in active compounds.

Associations of circulating C-reactive proteins, APOE ε4, and brain markers for Alzheimer’s disease in healthy samples across the lifespan

The apolipoprotein E gene ε4 allele (APOE ε4) and higher circulating level of C-reactive protein (CRP) have been extensively investigated as risk factors for Alzheimer’s disease (AD). Paradoxically, APOE ε4 has been associated with lower levels of blood CRP in middle-aged and older populations. However, few studies have investigated this intriguing relation and its impact on neurological markers for AD in younger ages, nor across the whole lifespan. Here, we examine associations of blood CRP levels, APOE ε4, and biomarkers for AD in a cognitively healthy lifespan cohort (N up to 749; 20–81 years of age) and replicate the findings in UK Biobank (N = 304 322; 37–72 years of age), the developmental ABCD study (N = 10 283; 9–11 years of age), and a middle-aged sample (N = 339; 40–65 years of age). Hippocampal volume, brain amyloid-β (Aβ) plaque levels, cerebrospinal fluid (CSF) levels of Aβ and tau species, and neurofilament protein light protein (NFL) were used as AD biomarkers in subsamples. In addition, we examined the genetic contribution to the variation of CRP levels over different CRP ranges using polygenic scores for CRP (PGS-CRP). Our results show APOE ε4 consistently associates with low blood CRP levels across all age groups (p < 0.05). Strikingly, both ε4 and PGS-CRP associated mainly with blood CRP levels within the low range (<5mg/L). We then show both APOE ε4 and high CRP levels associate with smaller hippocampus volumes across the lifespan (p < 0.025). APOE ε4 was associated with high Aβ plaque levels in the brain (FDR-corrected p = 8.69x10-4), low levels of CSF Aβ42 (FDR-corrected p = 6.9x10-2), and lower ratios of Aβ42 to Aβ40 (FDR-corrected p = 5.08x10-5). Blood CRP levels were weakly correlated with higher ratio of CSF Aβ42 to Aβ40 (p = 0.03, FDR-corrected p = 0.4). APOE ε4 did not correlate with blood concentrations of another 9 inflammatory cytokines, and none of these cytokines correlated with AD biomarkers. ConclusionThe inverse correlation between APOEε 4 and blood CRP levels existed before any pathological AD biomarker was observed, and only in the low CRP level range. Thus, we suggest to investigate whether APOEε 4 can confer risk by being associated with a lower inflammatory response to daily exposures, possibly leading to greater accumulation of low-grade inflammatory stress throughout life. A lifespan perspective is needed to understand this relationship concerning risk of developing AD.

Nutritional and prognostic significance of abdominal wall thickness measured during percutaneous endoscopic gastrostomy in older individuals with dysphagia.

The significance of abdominal wall thickness (AWT) for nutritional assessment remains unclear. This study aimed to evaluate the nutritional and prognostic significance of AWT measured during percutaneous endoscopic gastrostomy (PEG) in older patients with dysphagia. This single-center retrospective cohort study enrolled older adults with dysphagia who underwent PEG for enteral nutrition using the introducer technique between February 2010 and January 2019. We examined the association between AWT measured during PEG and nutritional status items, including body mass index (BMI), serum albumin (Alb), total lymphocyte count (TLC), total cholesterol (TC), hemoglobin (Hb), and C-reactive protein (CRP). The shaft length of the PEG tube inserted, which is an approximation value of the AWT, was used for statistical analysis. Patients were divided into three groups: low-AWT group (shaft length ≤2.5cm), medium-AWT group (shaft length 3.0-3.5cm), and high-AWT group (shaft length ≥4.0cm). We performed the Kruskal-Wallis test and multiple linear regression analysis with multiple imputation. We performed survival analysis using the Kaplan-Meier method, log-rank test, and Cox regression analysis. A total of 520 patients were identified: 115, 258, and 147 patients in the low-AWT, medium-AWT, and high-AWT groups, respectively. Higher AWT was significantly associated with higher BMI, Alb, TLC, TC, Hb, and lower CRP levels. Multiple linear regression analysis revealed that BMI and TLC were significant predictors of AWT (BMI: coefficient 1.16E-01, 95% confidence interval [CI], 9.77E-02-1.33E-01, P<0.001; TLC: coefficient 1.18E-04, 95% CI, 2.72E-05-2.09E-04, P=0.011). The median survival time was the longest in the high-AWT group (low-AWT, 359 days; medium-AWT, 851 days; high-AWT, 1662 days; P<0.001). The hazard ratio for the high-AWT group relative to the medium-AWT group was 0.59 (95% CI, 0.41-0.85, P=0.004), and that relative to the low-AWT group was 0.34 (95% CI, 0.24-0.51, P<0.001). Higher AWT was associated with better nutritional status and survival. AWT may help assess nutritional status and predict survival in older dysphagic patients with PEG.

Early life, life course and gender influences on levels of C-reactive protein among migrant Bangladeshis in the UK.

Background and objectivesHumans co-evolved with pathogens, especially helminths, that educate the immune system during development and lower inflammatory responses. The absence of such stimuli in industrialized countries is associated with higher baseline levels of C-reactive protein (CRP) among adults who appear at greater risk for inflammatory disorders. This cross-sectional study examined effects of early life development on salivary CRP levels in 452 British-Bangladeshis who spent varying periods growing up in Bangladesh or UK. We also analyzed how gender and central obesity modulate effects on CRP. We hypothesized that: (i) first-generation Bangladeshis with higher childhood exposure to pathogens would have chronically lower CRP levels than second-generation British-Bangladeshis; (ii) effects would be greater with early childhoods in Bangladesh; (iii) effects by gender would differ; and (iv) increasing obesity would mitigate early life effects.MethodologySaliva samples were assayed for CRP using ELISAs, and anthropometric data collected. Participants completed questionnaires about demographic, socioeconomic, lifestyle and health histories. Data were analyzed using multiple linear regression.ResultsFirst-generation migrants who spent early childhoods in mostly rural, unhygienic areas, and moved to UK after age 8, had lower salivary CRP compared to the second-generation. Effects differed by gender, while waist circumference predicted higher CRP levels. CRP increased with years in UK, alongside growing obesity.Conclusions and implicationsOur study supports the hypothesis that pathogen exposure in early life lowers inflammatory responses in adults. However, protective effects differed by gender and can be eroded by growing obesity across the life course which elevates risks for other inflammatory disorders. Lay Summary: Migrants to the UK who spent early childhoods in less hygienic environments in Bangladesh that help to educate their immune systems had lower levels of the inflammatory marker, C-reactive protein (CRP) compared to migrants who grew up in UK. Both gender and increasing obesity were associated with increased levels of CRP.

Ratio of serum amyloid A to C-reactive protein is constant in the same patients but differs greatly between patients with inflammatory diseases.

C-reactive protein (CRP) is commonly monitored to track the activity of inflammation and has become the gold standard in the management of all inflammatory diseases. Indeed, serum amyloid A (SAA) have seemed to correlate moderately with CRP, but the discrepancy of CRP and SAA levels has often been reported, especially in rheumatoid arthritis. Then, we examined CRP reflects a real magnitude of inflammation in patients with rheumatic and infectious inflammatory diseases. A total of 414 patients with infectious and non-infectious inflammatory diseases were enrolled. At initial visit, each patient underwent a clinical assessment and had also laboratory tests such as SAA and CRP. In each patient, we carried out a longitudinal analysis of CRP and SAA levels. We determined the inter-individual correlation between SAA and CRP and also clarified intra-individual changes of SAA/CRP ratio. SAA and CRP levels changed approximately linearly over time within individuals irrespective of rheumatic and infectious inflammatory diseases. However, SAA/CRP ratios differed dramatically between patients (from 0.117 to 50.8, median 5.71). In patients with high SAA/CRP ratio (>8.44), SAA is a better predictor of inflammation than CRP. In contrast, CRP is a better predictor in patients with low ratio (<3.52). Our results suggest that the SAA/CRP ratio differed greatly between individuals but was constant in intra-individuals. Low CRP levels could be accompanied by SAA levels predicting any degree of inflammation, implying that CRP is not reflecting a real magnitude of inflammation. To evaluate the real magnitude of inflammation, to access the SAA/CRP ratio in advance is essential.

Low-Calorie Ketogenic Diet with Continuous Positive Airway Pressure to Alleviate Severe Obstructive Sleep Apnea Syndrome in Patients with Obesity Scheduled for Bariatric/Metabolic Surgery: a Pilot, Prospective, Randomized Multicenter Comparative Study.

Obstructive sleep apnea syndrome (OSAS) and obesity are frequently associated with hypertension (HTN), dyslipidemia (DLP), and insulin resistance (IR). In patients with obesity and OSAS scheduled for bariatric surgery (BS), guidelines recommend at least 4 weeks of preoperative continuous positive airway pressure (CPAP). Low-calorie ketogenic diets (LCKDs) promote pre-BS weight loss (WL) and improve HTN, DLP, and IR. However, it is unclear whether pre-BS LCKD with CPAP improves OSAS more than CPAP alone. We assessed the clinical advantage of pre-BS CPAP and LCKD in patients with obesity and OSAS. Seventy patients with obesity and OSAS were randomly assigned to CPAP or CPAP+LCKD groups for 4 weeks. The effect of each intervention on the apnea–hypopnea index (AHI) was the primary endpoint. WL, C-reactive protein (CRP) levels, HTN, DLP, and IR were secondary endpoints. AHI scores improved significantly in both groups (CPAP, p=0.0231; CPAP+LCKD, p=0.0272). However, combining CPAP and LCKD registered no advantage on the AHI score (p=0.863). Furthermore, body weight, CRP levels, and systolic/diastolic blood pressure were significantly reduced in the CPAP+LCKD group after 4 weeks (p=0.0052, p=0.0161, p=0.0008, and p=0.0007 vs baseline, respectively), and CPAP+LCKD had a greater impact on CRP levels than CPAP alone (p=0.0329). The CPAP+LCKD group also registered a significant reduction in serum cholesterol, LDL, and triglyceride levels (p=0.0183, p=0.0198, and p<0.001, respectively). Combined with CPAP, LCKD-induced WL seems to not have a significant incremental effect on AHI, HTN, DLP, and IR but lower CRP levels demonstrated a positive impact on chronic inflammatory status.

Differences in Inflammation, Treatment, and Outcomes Between Black and Non-Black Patients Hospitalized for COVID-19: A Prospective Cohort Study

PurposeRacial disparities in coronavirus disease 2019 (COVID-19) outcomes have been described. We sought to determine whether differences in inflammatory markers, use of COVID-19 therapies, enrollment in clinical trials, and in-hospital outcomes contribute to racial disparities between Black and non-Black patients hospitalized for COVID-19. MethodsWe leveraged a prospective cohort study that enrolled 1325 consecutive patients hospitalized for COVID-19, of whom 341 (25.7%) were Black. We measured biomarkers of inflammation and collected data on the use COVID-19-directed therapies, enrollment in COVID-19 clinical trials, mortality, need for renal replacement therapy, and need for mechanical ventilation. ResultsCompared to non-Black patients, Black patients had a higher prevalence of COVID-19 risk factors including obesity, hypertension, and diabetes mellitus and were more likely to require renal replacement therapy (15.8% vs 7.1%, P < .001) and mechanical ventilation (37.2% vs 26.6%, P < .001) during their hospitalization. Mortality was similar between both groups (15.5% for Blacks vs 14.0% for non-Blacks, P = .49). Black patients were less likely to receive corticosteroids (44.9% vs 63.8%, P< .001) or remdesivir (23.8% vs 57.8%, P < .001) and were less likely to be enrolled in COVID-19 clinical trials (15.3% vs 28.2%, P < .001). In adjusted analyses, Black race was associated with lower levels of C-reactive protein and soluble urokinase receptor and higher odds of death, mechanical ventilation, and renal replacement therapy. Differences in outcomes were not significant after adjusting for use of remdesivir and corticosteroids. ConclusionsRacial differences in outcomes of patients with COVID-19 may be related to differences in inflammatory response and differential use of therapies.