Baseline C-reactive Protein Research Articles

Overall Survival Prediction of Advanced Cancer Patients by Selection of the Most Significant Baseline Serum Biomarker Combination.

Introduction: Consistent association between elevated baseline serum values and C-reactive protein (CRP), cross-linked fibrin degradation products (D-dimer), lactate dehydrogenase (LDH), decreased baseline serum albumin, absolute lymphocyte count to absolute monocyte count ratio (LMR), elevated absolute neutrophil count to absolute lymphocyte count ratio (NLR), elevated platelet count to absolute lymphocyte count ratio (PLR), and between some combinations of these biomarkers and the short overall survival of patients with malignant diseases has already been reported. These biomarkers are independent prognostic factors for cancer. Here, the most significant biomarker combination of these values was searched and studied in real-life advanced cancer patients of a single center. Methods: The authors retrospectively analyzed the association of the aforementioned biomarkers and their combination and OS of 75 consecutive cancer patients with locally advanced, recurrent, or metastatic diseases. Validated cut-off determination was used. Results: CRP, albumin, and PLR showed marked association with OS. Cut-off values for significant shorter OS were 30.65 mg/L (p < 0.001), 44.35 g/L (p < 0.001), and 168.20 (p < 0.001), respectively. Based on assessed biomarker cut-offs, four patient groups were created to determine whether biomarker values were out of range (ORV) compared to cut-off: 1) No ORV biomarkers (n = 24; OS = 26.07 months); 2) one ORV biomarker (n = 21; OS = 13.50 months); 3) two ORV biomarkers (n = 20; OS = 7.97 months), and 4) three ORV biomarkers (n = 10; OS = 3.91 months). Significant differences in OS were detected between the groups: For 1. vs. 2. hazard ratio (HR) = 3.0 (95% CI: 1.5–6.2), p = 0.003; for 1. vs. 3. HR = 4.1 (95% CI: 2.0–8.3), p < 0.001; and for 1. vs. 4. HR = 10.2 (95% CI: 4.2–24.6), p < 0.001. Conclusion: Based on our analysis, we can confirm that the complex monitoring of CRP, albumin, and PLR would provide a good estimation of OS. Large scale prospective studies are warranted to explore this and other useful combinations of prognostic biomarkers and their relationship to the well-established prognostic systems in real-life.

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.

Assessment of Potential Risk Factors, Characteristics, and Outcome of Pneumothorax and Pneumomediastinum in Patients with COVID-19: A Retrospective Case-control Study

Introduction: Pneumothorax (PTX) and/or pneumomediastinum (PMD) are rare complications of Coronavirus Disease-2019 (COVID-19) and are linked to high mortality. Incidence rates vary between 0.56-2.01% in the reported literature. With clinical examination being hampered in the current pandemic setting, there is a delay in the diagnosis. There is a need to identify and establish potential predictive factors, that may aid in identifying patients with a high-risk of developing PTX and/or PMD. Aim: To identify potential risk factors and thus, explore their association with PTX and/or PMD among patients with COVID-19. Materials and Methods: A retrospective case-control study was conducted at MS Ramaiah Medical College and Hospital, Bangalore, South India over a six-month period. A total of 130 patients diagnosed with COVID-19 were recruited in a 1:3 ratio as cases and controls respectively. Cases were patients, diagnosed radiologically with PTX and/or PMD, and controls were, matched individuals without PTX and/or PMD. Patient’s clinical and laboratory parameters (complete blood count, renal and liver function tests, serum levels of inflammatory markers such as C-reactive protein (CRP), lactate dehydrogenase (LDH), and D-Dimer were tested for potential association with PTX and/or PMD. Student’s t-test, Chi-square test, multivariate and univariate logistic regression analysis were performed. Results: During the study period, there was a total of 3,251 COVID-19 admissions at the centre with 976 patients requiring Intensive Care Unit (ICU) admission. The overall incidence of PTX and/or PMD during the study period was (31/3251) 0.95%. The previous history of COVID-19, non vaccination with COVID-19 vaccine, cough as a predominant symptom, high values of baseline CRP, total bilirubin, Aspartate Transaminase (AST), and total leukocyte counts had a positive association. In-hospital mortality (54.8% vs 33.30%) and mortality 28 days (35.7% vs 7.6%) following discharge, were higher among those with PTX and/or PMD. Conclusion: Patients with a history of previous infection with COVID-19, non vaccination /incomplete-vaccination with COVID-19 vaccines, and patients with increasing total leukocyte counts and AST levels, high baseline total serum bilirubin were at increased risk of a detrimental clinical course and may indicate, the possibility of development of PTX and/or PMD in COVID-19 disease.

Immune-endocrine biomarkers associated with mental health: A 9-year longitudinal investigation from the Hertfordshire Ageing Study

BackgroundThe study of neural-endocrine-immune system interactions has led to substantial advances in our understanding of neuropsychiatric disorders. Growing evidence reveals the pivotal roles of inflammatory cytokines signalling the brain to produce neurochemical, neuroendocrine, and neuroimmune changes which affect mood and behaviour. Ageing is accompanied by the development of low-grade systemic inflammation which may promote changes in the neural systems predisposing to geriatric depression via the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to investigate the longitudinal associations between baseline values and conditional changes (independent of baseline) in immune-endocrine biomarkers and mental health status in a population-based cohort of older adults. MethodsData from 347 subjects (200 men, 147 women) who participated in the Hertfordshire Ageing Study at baseline (1994/5, mean age 67.3 years) and at 9-year follow-up were analysed. Serum samples for analysis of inflammatory and endocrinological measures were collected at baseline and follow-up. At follow-up, depression (Hospital Anxiety and Depression Scale) and mental health (Short Form-36 questionnaire) were assessed. Baseline values and changes in biomarkers in relation to risk of high depression scores (top sex-specific third) and low mental health scores (bottom sex-specific third) were examined using logistic regression. ResultsLower baseline cortisol was related to greater risk of high depression scores; higher baseline cortisol: dehydroepiandrosterone sulphate ratio (men only) and higher baseline C-reactive protein (CRP) (women only) were related to greater risk of poor mental health scores. In addition, greater decline in cortisol was related to increased risk of high depression scores among men. These relationships were robust (p < 0.05) after controlling for sex, age, BMI, smoking, alcohol consumption and number of systems medicated. ConclusionThis study provides further evidence of the role of the HPA axis and inflammation in older adults with poor mental health. In addition, the findings highlight sex differences where increased inflammation in women and declines in cortisol in men were linked to poorer mental health. Further research is warranted to confirm these findings. This could lead to the search for potential biomarkers to stratify medications as well as developing novel intervention targets to improve mental health at older age.

Association Between Occupational Sitting With High Sensitivity C-Reactive Protein: The Jackson Heart Study

Modifiable, behavioral risk factors like occupational sitting may contribute to inflammation, an important cardiovascular risk factor. This study evaluated the association of self-reported occupational sitting with changes in c-reactive protein (CRP) and the role of sex. We examined occupational sitting and baseline CRP levels for 2889 African American participants in the Jackson Heart Study. Four multivariable linear regression models were estimated to determine the association of occupational sitting and CRP. Analyses were conducted in 2020. The mean age was 50.8 years and 61% were female. Participants who reported occupational sitting as “often/always” had CRP levels of 4.9±6.8 mg/L, “sometimes” had levels of 4.8±8.1 mg/L, and “never/seldom” had levels of 4.3±6.8 mg/L. In the unadjusted model, “often/always” engaging in occupational sitting was significantly associated with higher levels of CRP when compared to “never/seldom” ( P &lt; .05). This differed by sex with female participants who reported “often/always” occupational sitting had CRP levels of 6.0±7.6 mg/L compared to only 5.1±6.9 mg/L for “never/seldom.” Neither the overall association nor the female-specific association remained statistically significant in the adjusted models. We found an association between occupational sitting and inflammation, measured by CRP. This association varied by sex but did not remain significant after fully adjusting for covariates.

Early control of C-reactive protein levels with non-biologics is associated with slow radiographic progression in radiographic axial spondyloarthritis.

Predicting radiographic progression is vital for assessing the prognosis of patients with radiographic axial spondyloarthritis, and C-reactive protein (CRP) may be a valuable biomarker for this purpose. This study aimed to investigate the relationship between changes in the CRP level and spinal radiographic progression in patients with radiographic axial spondyloarthritis who were initially treated with non-biologics. Patients with radiographic axial spondyloarthritis who were followed up for 18years at a single center and initially treated with nonsteroidal anti-inflammatory drugs and/or conventional disease-modifying antirheumatic drugs for 3months were included. Patients with a CRP level of <0.8mg/dL or 50% of the baseline CRP at 3months were assigned to the controlled CRP group (n=351), and the remaining patients were assigned to the uncontrolled CRP group (n=452). A generalized estimating equation was used to analyze the differences in the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) between the 2 groups. The increase in the mSASSS was slower in the controlled CRP group than in the uncontrolled CRP group (interaction term β=-.499, 95% confidence interval -0.699 to -0.300). Controlled CRP achieved in response to initial treatment with non-biologic agents for 3months was significantly associated with a slower rate of spinal radiographic change in patients with radiographic axial spondyloarthritis. The CRP level at 3months after initial non-biologic treatment is a good predictor of radiographic progression.

Dried Blood Spot Biomarkers of Oxidative Stress and Inflammation Associated with Blood Pressure in Rural Senegalese Women with Incident Hypertension.

Blood biomarkers of oxidative stress and inflammation have been associated with increased risk of hypertension development; yet their application in sub-Saharan Africa has been limited due to the lack of blood collection facilities. In this study, we evaluated the usefulness of dried blood spots (DBS), a more feasible alternative to venous blood, in rural sub-Saharan residents. We recruited 342 women with incident hypertension from rural Senegal, and measured C-reactive protein (CRP) and malondialdehyde (MDA) in DBS and concurrent blood pressure (BP) at baseline and 1-year follow-up. Associations of DBS biomarkers with current levels of and 1-year changes in BP were examined after adjusting for demographic, medical, and socioeconomic covariates. DBS concentrations of MDA were significantly associated with concurrent systolic BP (SBP) (p < 0.05), while DBS baseline concentrations of CRP were associated with longitudinal changes in SBP between baseline and follow-up. Compared to participants with baseline CRP < 1 mg/L, those with CRP of 1–3 mg/L and 3–10 mg/L had 2.11 mmHg (95%CI: −2.79 to 7.02 mmHg) and 4.68 mmHg (95%CI: 0.01 to 9.36 mmHg) increases in SBP at follow-up, respectively. The results support the use of DBS biomarkers for hypertension prevention and control, especially in settings with limited clinical resources.

Increased 1-year mortality in haemodialysis patients with COVID-19: a prospective, observational study.

ABSTRACTBackgroundDialysis confers the highest risk of coronavirus disease 2019 (COVID-19) death among comorbidities predisposing to severe COVID-19. However, reports of COVID-19-associated mortality frequently refer to mortality during the initial hospitalization or first month after diagnosis.MethodsIn a prospective, observational study, we analysed the long-term (1-year follow-up) serological and clinical outcomes of 56 haemodialysis (HD) patients who were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first pandemic wave. COVID-19 was diagnosed by a positive polymerase chain reaction (PCR) test (n = 37) or by the development of anti-SARS-CoV-2 antibodies (n = 19).ResultsAfter >1 year of follow-up, 35.7% of HD patients infected by SARS-CoV-2 during the first pandemic wave had died, 6 (11%) during the initial admission and 14 (25%) in the following months, mainly within the first 3 months after diagnosis. Overall, 30% of patients died from vascular causes and 40% from respiratory causes. In adjusted analysis, a positive SARS-CoV-2 PCR test for diagnosis {hazard ratio [HR] 5.18 [interquartile range (IQR) 1.30–20.65], P = 0.020}, higher baseline C-reactive protein levels [HR 1.10 (IQR 1.03–1.16), P = 0.002] and lower haemoglobin levels [HR 0.62 (IQR 0.45–0.86), P = 0.005] were associated with higher 1-year mortality. Mortality in the 144 patients who did not have COVID-19 was 21 (14.6%) over 12 months [HR of death for COVID-19 patients 3.00 (IQR 1.62–5.53), log-rank P = 0.00023]. Over the first year, the percentage of patients having anti-SARS-CoV-2 immunoglobulin G (IgG) decreased from 36/49 (73.4%) initially to 27/44 (61.3%) at 6 months and 14/36 (38.8%) at 12 months.ConclusionsThe high mortality of HD patients with COVID-19 is not limited to the initial hospitalization. Defining COVID-19 deaths as those occurring within 3 months of a COVID-19 diagnosis may better represent the burden of COVID-19. In HD patients, the anti-SARS-CoV-2 IgG response was suboptimal and short-lived.

Learning Longitudinal Patterns and Subtypes of Pediatric Crohn Disease Treated With Infliximab via Trajectory Cluster Analysis.

The objective of this study is to identify subgroups of pediatric Crohn disease (CD) who had differential responses to the infliximab treatment through trajectory cluster analysis of disease activity using data from electronic health records. We conducted a retrospective study of 295 pediatric patients with CD who had been treated with infliximab for a minimum of one year at the Center for Inflammatory Bowel Disease at The Children's Hospital of Philadelphia between January 2010 and December 2017. The evolution of disease was described, and subgroups of patients were identified using trajectory analysis of longitudinal data of C-reactive protein (CRP). We compared patient characteristics, biomarker for disease activity, and long-term surgical outcomes across subgroups. Cox regression models were used to evaluate the added value of the subgroup classification to baseline phenotype and location in prediction of long-term surgical outcomes. We identified three subgroups of patients with differential relapse-and-remission profiles (n = 33, 65 and 197 from subgroup 1 to 3), which represented patients with a higher risk of infliximab non-response, with infliximab response but with occasional disease flares, and patients with long-term response. Patients with the best treatment response had a significantly lower frequency of complicated disease phenotypes (P = 0.01), including perianal involvement (P = 0.05), lower baseline CRP (P < 0.01) and calprotectin (P = 0.01), and lowest risk of IBD-related gastrointestinal surgery within 10 years of starting treatment (P < 0.01). Readily available longitudinal data from electronic health records can be leveraged to provide deeper characterization of treatment response in pediatric CD.

Elevated baseline C-reactive protein levels predict poor progression-free survival in sporadic vestibular schwannoma

BackgroundRecent investigations showed emerging evidence of the role of inflammation in the growth of sporadic vestibular schwannoma (VS). The present retrospective study investigated the impact of systemic inflammation on tumor progression using serum C-reactive protein (CRP) levels in a series of 87 surgically treated sporadic VS patients.MethodsThe optimal cut-off value for CRP was defined as 3.14 mg/dl according to the receiver operating characteristic curve (AUC: 0.70, 95% CI 0.47–0.92). Patient cohort was dichotomized into normal (n = 66; < 3.14 mg/dl) and high baseline (n = 21; ≥ 3.14 mg/dl) CRP groups.ResultsNo significant differences in age, sex, comorbidities influencing the systemic inflammatory state, Karnofsky performance status (KPS), tumor size, extent of resection, or MIB-1 index were identified between the two groups defined by the baseline CRP levels. Univariable analysis demonstrated that a high CRP level (≥ 3.14 mg/dl) is significantly associated with a shortened progression-free survival (PFS) (hazard ratio (HR): 6.05, 95% CI 1.15–31.95, p = 0.03). Multivariable Cox regression analysis considering age, extent of resection, KPS, tumor size, and baseline CRP confirmed that an elevated CRP level (≥ 3.14 mg/dl) is an independent predictor of shortened PFS (HR: 7.20, 95% CI 1.08–48.14, p = 0.04).ConclusionsThe baseline CRP level thus serves as an independent predictor of PFS. Further investigations of the role of inflammation and tumor inflammatory microenvironment in the prediction of prognosis in sporadic VS are needed.Graphical abstract

342. Secondary Infections following Tocilizumab for Treatment of COVID-19 Pneumonia

BackgroundGuidelines recommend use of tocilizumab (TCZ), an inhibitor of pro-inflammatory IL-6 signaling, for hospitalized patients with progressive severe or critical Coronavirus disease 2019 (COVID-19). The incidence of infectious complications following the use of TCZ for COVID-19 has not been well-described.MethodsWe conducted a retrospective, observational matched cohort study of severely ill, hospitalized adult patients with confirmed COVID-19 who were treated with TCZ between 2/24/2021 and 6/1/2021. The intervention group, comprised of patients who received a single dose of TCZ, was matched based on c-reactive protein (CRP) and fraction of inspired oxygen (FiO2) with a control group who did not receive TCZ, and were hospitalized between 10/12/2020 and 3/6/2021. The primary outcome of the study was diagnosis of a bacterial or fungal infection after day 3 of the index hospitalization. Secondary outcomes included all-cause mortality during the study period and length of stay. Results75 patients who received TCZ were identified during the study period, and matched 1:1 with 75 control patients. Baseline CRP and FiO2 were similar between groups, while the median age in the TCZ group was younger (61 versus 71 years), reflecting the epidemiology of the outbreak during the TCZ and control study periods. 15 bacterial and fungal infections were identified in the TCZ group (20.0%) and 4 (5.3%) infections in the control group (p = 0.012). The majority of infections in both groups were bacterial, with a disproportionate number of bloodstream infections in the TCZ group [7 (9.3%) vs 2(2.6%); p = 0.166]. 28 patients (37.3%) died in the TCZ group compared to 39 (52.0%) in the matched control (p = 0.068). Median time to discharge was similar between TCZ and control patients (11 versus 12 days; 95% CI -2,2).ConclusionSecondary infections in adult patients with severe and critical COVID-19 were more common in patients who had received TCZ. Prospective studies are needed to confirm and further describe this association.Disclosures All Authors: No reported disclosures

Risk factors for progression of juvenile-onset non-radiographic axial spondyloarthritis to juvenile-onset ankylosing spondylitis: a nested case–control study

ObjectiveTo evaluate the clinical characteristics of juvenile-onset non-radiographic axial spondyloarthritis (nr-axSpA) and to investigate risk factors associated with progression to juvenile-onset ankylosing spondylitis (JoAS).MethodsA nested case–control study was conducted using...

The effect of plasmalogen precursor supplementation on blood plasmalogen and C‐reactive protein levels and cognition in cognitively impaired persons

AbstractBackgroundDecreased blood and brain plasmalogens levels are associated with decreased cognition in humans. 1‐O‐alkyl‐2,3‐diacylglycerol (ADG) plasmalogen precursors containing docosahexaenoic acid (DHA) at the sn‐2 position have been shown to increase blood plasmalogens and to be neuroprotective in animal models of neurodegeneration. The goal of this study was to evaluate the effect of dietary DHA‐ADG supplementation on blood plasmalogen and C‐Reactive Protein (CRP) levels and cognition in cognitively impaired persons.MethodTwenty persons (9M/11F), aged 37‐81 (average = 68) with mild to moderate cognitive impairment [CDR: 13(0.5); 3(1); 4(2)] were administered an escalating dose of DHA‐ADG [1.0ml/day for 30 days; 2.0ml/day for 60 days; 4.0ml for 30 days]. Blood plasmalogen and CRP levels and cognitive status were measured at baseline and the end of each month. Cognitive status was determined using the Quick Dementia Rating System (QDRS), which was used to derive the participant’s Clinical Dementia Rating (CDR).ResultOverall, maximum average DHA ethanolamine plasmalogen levels were achieved by the end of the 2nd month [224% of baseline, 95%CI = 173‐273%] and this level of elevation was sustained for the duration of the study. Of the 20 participants, 14 (70%) exhibited robust and sustained plasmalogen elevations (&gt;150%, &gt;2 months, ADG Responder). Of the 14 ADG responders, 10 exhibited improvements on QDRS and 6 of these 10 exhibited improvements of at least one CDR level. Of the 14 ADG responders, 4 had baseline CRP levels &gt;1.0. In each of these 4 subjects, CRP levels decreased by &gt;0.5 by the end of the 4th month. DHA‐ADG was well tolerated at all dosages and no adverse reactions were observed. No cognitive improvement was observed in any of the ADG non‐responders.ConclusionDHA‐ADG was effective at elevating blood plasmalogen levels at the dosages studied. 10/14 (71%) of cognitively impaired persons experienced improved levels of cognition when blood DHA‐plasmalogens were elevated by &gt;150%. In all persons with elevated baseline CRP levels, DHA‐plasmalogen elevation was associated with a decrease in blood CRP. This analysis suggests that DHA‐ADG supplementation may be beneficial for patients with mild to moderate cognitive impairment.

Analysis of pleiotropic genetic effects on cognitive decline and systemic inflammation in the Women’s Health Initiative Memory Study

SNPs associated with C-reactive protein (CRP) and plasma lipids have been investigated for polygenic overlap with Alzheimer's disease (AD) risk SNPs. Previously, we reported pleiotropic effects between SNPs associated with cognitive impairment (CI) and SNPs associated with systemic inflammation as measured by CRP and plasma lipids in the Health and Retirement Study (HRS). We sought to replicate our results in the Women's Health Initiative Memory Study (WHIMS). Analysis of SNP pleiotropic effects was completed using data from 6,078 non-Hispanic White women (aged 71.4 [SD 7.4] at baseline) for whom genetic, cognitive, and/or biomarker data were available. We identified CI using WHIMS adjudicated case status (normal vs. mild cognitive impairment or probable dementia). Secondary phenotypes included baseline CRP and plasma lipid levels (HDL, LDL, and total cholesterol [TC]). Genome-wide association analyses were conducted for all phenotypes. A conditional false discovery rate framework defined genetic pleiotropy. Genetic pleiotropy was identified if SNPs were associated with CI conditional on association with secondary phenotypes (CRP, HDL, LDL, TC) at an FDR < 0.05. Functional genomic bioinformatics analysis and comparison with prior findings were conducted. Genetic pleiotropy was observed for CI conditional on association with the secondary phenotypes of plasma CRP, HDL, LDL, and TC. These results replicate associations for SNPs in the APOE, APOC1, PVRL2/NECTIN2 loci reported in the prior HRS study for CRP, LDL, TC. The odds ratios for the association of these SNPs with CI ranged from 0.5 to 4.0, consistent with moderate effect sizes for the APOE ε2 or ε4 alleles. For WHIMS, FDR significant results were observed in both directions for several of the traits (CRP, lipids), further supporting evidence of genetic pleiotropy. Moreover, we observed associations for SNPs in the APOE, APOC1, PVRL2/NECTIN2 loci for CI conditional on HDL. We identified polygenic overlap between CI and CRP, LDL, HDL, and TC phenotypes in WHIMS, largely replicating prior results in the HRS. The variants and associated genes identified are involved in pathological processes including metabolic, cardiovascular, and immune response and are potentially important for AD risk prediction and development of therapeutic approaches based on anti-inflammatory mechanisms.

High Baseline C-Reactive Protein Level Can Predict the Occurrence of the Jarisch-Herxheimer Reaction in Patients with Active Syphilis.

BackgroundThe Jarisch–Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis.MethodsThis prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal–Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment.ResultsTwenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986–19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033–26,150 ng/mL] vs 3489 ng/mL [IQR 924–160,640] ng/mL, p = 0.0059, 95% CI 4002–17,098 ng/mL, area under the curve 0.799, 95% CI 0.632–0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL).ConclusionA high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.

Early Fall in C-Reactive Protein (CRP) Level Predicts Response to Tocilizumab in Rapidly Progressing COVID-19: Experience in a Single-Arm Pakistani Center.

IntroductionThere are conflicting studies regarding the efficacy of tocilizumab use in coronavirus disease 2019 (COVID-19) disease. There is a special need to identify the parameters that could predict its response in early COVID-19 disease.ObjectiveTo report our experience with tocilizumab and correlate the magnitude of fall in c-reactive protein (CRP) as a predictor of its response to treatment in early COVID-19 disease.MethodsAll confirmed COVID-19 cases admitted to a tertiary healthcare hospital in Peshawar Pakistan, receiving ≥1 dose of intravenous tocilizumab, between March and September 2020 were included. Relevant clinical data of the patients were recorded and further divided into two categories based on the relative fall in CRP levels, 48 hours after tocilizumab administration. Adequate response (≥50% fall from baseline CRP), primary outcomes (fall in oxygen requirement and inflammatory biomarkers), and secondary outcome (all-cause mortality at day 28) were recorded. All outcomes were compared based on falls in CRP levels.ResultsA total of 27 patients were included. Males were 24 (88.8%) while females were three (11.1%). The mean age was 60.9±11.6 years. The mean day of illness at the time of tocilizumab administration was 4.26±3 days. After 48 hours of tocilizumab administration, 17 (62.9%) patients showed clinical improvement, with the mean SaO2/FiO2 ratio prior to treatment significantly increased (p<0.01). A significant reduction in CRP and ferritin levels was seen post-treatment (p <0.01 and p<0.01, respectively). Twenty (74.1%) patients demonstrated adequate response to tocilizumab while seven (25.9%) showed an inadequate response. Patients with adequate response had higher chances of improvement in oxygenation and lower in-hospital mortality (p-value 0.009 and 0.020, respectively).ConclusionsTocilizumab shows clinical improvement in a vast majority of patients. Being an early and sensitive predictor, a fall of ≥50% in CRP at 48 hours can be used to predict the overall response to tocilizumab as a guide to treatment.

A Prospective Phase II Study of Simultaneous Modulated Accelerated Radiotherapy Concurrently With CDDP/S1 for Esophageal Squamous Cell Carcinoma in the Elderly.

BackgroundTo explore the efficacy and toxicity of simultaneous modulated accelerated radiotherapy (SMART) concurrently with cisplatin (CDDP) and S1 (tegafur/gimeracil/oteracil) in elderly patients with esophageal squamous cell carcinoma (ESCC).MethodsThis single-arm, phase II study enrolled pathologically confirmed, stage II–IVa ESCC of 70–80 years old and Eastern Cooperative Oncology Group performance status (ECOG PS) 0–2. Patients received SMART (64 Gy to gross tumor volume and 48 Gy to clinical target volume in 30 fractions) with concurrent CDDP (day 1 of each week) and S1 (days 1–14, 22–35). The primary endpoint was objective response rate (ORR). The secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicities.ResultsThirty-seven eligible patients were analyzed with median follow-up of 25.7 months for all and 46.1 months for survivors. The ORR was 88.9%. Patients with baseline weight loss <5% (p=0.050) and nutritional risk index (NRI) ≥105.2 (p=0.023) had better tumor response. Median PFS was 13.8 months with 2-year PFS of 37.5%. Median OS was 27.7 months with 2-year OS of 57.5%. OS was significantly associated with ECOG PS (p=0.005), stage (p=0.014), gross tumor volume (p=0.004), baseline NRI (p=0.036), baseline C-reactive protein (CRP) level (p=0.003) and tumor response (p=0.000). CRP level (p=0.016) and tumor response (p=0.021) were independently prognostic of OS. ≥grade 3 anemia, neutropenia and thrombocytopenia occurred in 2.7%, 10.8% and 13.5% of patients; ≥grade 3 esophagitis and pneumonitis occurred in 18.9% and 2.7% of patient, respectively.ConclusionSMART concurrently with CDDP/S1 yielded satisfactory response rate, survival outcome and tolerable treatment-related toxicities in elderly patients with ESCC. Further studies are warranted to validate the results.

Quantitative Magnetic Resonance Imaging in Perianal Crohn's Disease at 1.5 and 3.0 T: A Feasibility Study.

Perianal Crohn’s Disease (pCD) is a common manifestation of Crohn’s Disease. Absence of reliable disease measures makes disease monitoring unreliable. Qualitative MRI has been increasingly used for diagnosing and monitoring pCD and has shown potential for assessing response to treatment. Quantitative MRI sequences, such as diffusion-weighted imaging (DWI), dynamic contrast enhancement (DCE) and magnetisation transfer (MT), along with T2 relaxometry, offer opportunities to improve diagnostic capability. Quantitative MRI sequences (DWI, DCE, MT and T2) were used in a cohort of 25 pCD patients before and 12 weeks after biological therapy at two different field strengths (1.5 and 3 T). Disease activity was measured with the Perianal Crohn’s Disease Activity index (PDAI) and serum C-reactive protein (CRP). Diseased tissue areas on MRI were defined by a radiologist. A baseline model to predict outcome at 12 weeks was developed. No differences were seen in the quantitative MR measured in the diseased tissue regions from baseline to 12 weeks; however, PDAI and CRP decreased. Baseline PDAI, CRP, T2 relaxometry and surgical history were found to have a moderate ability to predict response after 12 weeks of biological treatment. Validation in larger cohorts with MRI and clinical measures are needed in order to further develop the model.

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity

Association between Insufficient Interleukin-6 (IL-6) Inhibition and Worsening Outcomes in COVID-19 and Idiopathic Multicentric Castleman Disease (iMCD), and a Mathematical Model to Predict Optimal Dosing to Completely Block IL-6 Activity

Aspirin-Induced Delayed Urticaria in Children with Kawasaki Disease: A Retrospective Case-Control Study.

BackgroundAspirin remains a key component of the standard therapy for Kawasaki disease (KD) in children. Although it is well known that aspirin can cause hypersensitivity such as aspirin-induced urticaria (AIU), AIU in children with KD has not been described.MethodsA retrospective case-control study was conducted to investigate AIU clinical features, biochemical parameters, treatment and outcomes in children with KD. Furthermore, biomarkers for predicting AIU were explored using the receiver operating characteristic (ROC) curve analysis.ResultsWe identified 46 AIU cases with 22 boys and 24 girls during April 2015–May 2019. Eighty-nine age-matched KD patients without AIU were randomly chosen as controls. The proportions of children with allergy history and aspirin doses administered in the 2 groups were found not to be significantly different. AIU group had substantially higher baseline C-reactive protein and NT-proBNP levels, and increased neutrophil percent. AIU appeared 6.0 (4.0, 8.0) days after aspirin treatment. Aspirin withdrawal and anti-allergic treatment were applied for AIU, and AIU disappeared in 1–3 days. Baseline NT-proBNP predicted AIU with an AUC of 0.70 (95% CI [0.60 to 0.79]) for sensitivity and specificity of 72.1% and 62.5%, respectively, for a cut-off value of 612.9 mg/L. The length of hospital stay for AIU patients was significantly greater compared with controls.ConclusionAIU in KD children is not related to gender or aspirin dose, and those with AIU have more severe inflammation at admission. Aspirin should be withdrawn for AIU management. Baseline NT-proBNP may serve as a valuable biomarker to predict AIU.