C-reactive Protein Response Research Articles

C-reactive protein for early detection of postoperative systemic infections in intertrochanteric femoral fractures

BackgroundThis retrospective cohort study investigated perioperative C-reactive protein (CRP) value for early detection of postoperative systemic infective complications in elderly patients with intertrochanteric femoral fracture. MethodsA total of 250 patients aged ≥65 years, with intertrochanteric femoral fractures that were surgically treated between January 2011 and December 2015 were included. CRP value was measured preoperatively and on postoperative day (POD) 3, 5, and 10, and analyzed with regard to postoperative systemic infections, delirium, and death within 1 year. The patients were divided into two groups according to postoperative systemic infection, and perioperative CRP responses between the two groups were comparedusing t-test (or Man-Whitney test where appropriate). The receiver operator characteristic (ROC) curves of CRP value were used to determine the best-supported cut-off values for identifying postoperative systemic infections. Systemic infections were reclassified as pulmonary and extra-pulmonary infections. ResultsThe mean CRP values preoperatively and on POD 3, 5, and 10 were 2.82, 10.10, 3.74, and 1.89 mg/dL, respectively. Postoperative systemic infections, delirium, and death within 1 year were noted in 35 (14.0%), 30 (12.0%), and 45 (18.0%) patients, respectively. The CRP value in patients with postoperative systemic infections significantly elevated on POD 5 and 10 (p < 0.001, p < 0.001), and cut-off values were 4.71 and 1.59 mg/dL on POD 5 and 10, respectively. Postoperative delirium and death within 1 year were observed more often in the group with postoperative systemic infections (p = 0.003, p = 0.014). Although preoperatively elevated CRP values did not influence the postoperative CRP responses, they were significantly associated with delirium (p = 0.015). ConclusionsThe CRP value on POD 5 is the earliest predictor of postoperative systemic infections in elderly patients with intertrochanteric femoral fractures that are managed surgically. Moreover, when the CRP value on POD 5 is >4.71 mg/dL, the possibility of postoperative systemic infections should be considered. Level of evidenceIII, Retrospective cohort study.

Outcome and prognostic factors in metastatic urothelial carcinoma patients receiving second-line chemotherapy: an analysis of real-world clinical practice data in Japan.

The objective of the present study was to investigate the survival outcome and prognostic factors of metastatic urothelial carcinoma patients treated with second-line systemic chemotherapy in real-world clinical practice. Overall, 114 patients with metastatic urothelial carcinoma undergoing second-line systemic chemotherapy were included in this retrospective analysis. The dominant second-line chemotherapy was a paclitaxel-based combination regimen (60%, 68/114). We assessed the progression-free survival and overall survival times using the Kaplan-Meier method. The Cox proportional hazards model was applied to identify the factors affecting overall survival. The median progression-free survival and overall survival times were 4 and 9 months, respectively. In the multivariate analysis, an Eastern Cooperative Oncology Group performance status score greater than 0 at presentation, C-reactive protein level ≧1 mg/dl and poor response to prior chemotherapy were adverse prognostic indicators. Patients with 0, 1, 2 and 3 of those risk factors had a median overall survival of 17, 12, 7 and 3 months, respectively. The Eastern Cooperative Oncology Group performance status at presentation, C-reactive protein level and response to prior chemotherapy were prognostic factors for metastatic urothelial carcinoma patients undergoing second-line chemotherapy. In the future, this information might help guide the choice of salvage treatment, such as second-line chemotherapy or immune checkpoint inhibitors, after the failure of first-line chemotherapy.

Serum C-reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice.

Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high-sensitivity assays for serum C-reactive protein have shown a consistent association between cardiovascular disease risk and serum C-reactive protein concentrations. C-reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C-reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C-reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C-reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C-reactive protein genetic polymorphisms on baseline plasma C-reactive protein levels.

Exploring the Use of C-Reactive Protein to Estimate the Pharmacodynamics of Vancomycin.

C-reactive protein (CRP) pharmacodynamic (PD) models have the potential to provide adjunctive methods for predicting the individual exposure response to antimicrobial therapy. We investigated CRP PD linked to a vancomycin pharmacokinetic (PK) model using routinely collected data from noncritical care adults in secondary care. Patients receiving intermittent intravenous vancomycin therapy in secondary care were identified. A 2-compartment vancomycin PK model was linked to a previously described PD model describing CRP response. PK and PD parameters were estimated using a Non-Parametric Adaptive Grid technique. Exposure-response relationships were explored with vancomycin area-under-the-concentration-time-curve (AUC) and EC50 (concentration of drug that causes a half maximal effect) using the index, AUC:EC50, fitted to CRP data using a sigmoidal Emax model. Twenty-nine individuals were included. Median age was 62 (21-97) years. Fifteen (52%) patients were microbiology confirmed. PK and PD models were adequately fitted (r 0.83 and 0.82, respectively). There was a wide variation observed in individual Bayesian posterior EC50 estimates (6.95-48.55 mg/L), with mean (SD) AUC:EC50 of 31.46 (29.22). AUC:EC50 was fitted to terminal CRP with AUC:EC50 >19 associated with lower CRP value at 96-120 hours of therapy (100 mg/L versus 44 mg/L; P < 0.01). The use of AUC:EC50 has the potential to provide in vivo organism and host response data as an adjunct for in vitro minimum inhibitory concentration data, which is currently used as the gold standard PD index for vancomycin therapy. This index can be estimated using routinely collected clinical data. Future work must investigate the role of AUC:EC50 in a prospective cohort and explore linkage with direct patient outcomes.

Efectos de un año de entrenamiento con bandas elásticas sobre el dolor en mujeres menopáusicas

Background and aimsIn the literature, the relationship between elastic band resistance training, C-reactive protein responses, and skeletal pain in post-menopausal women it is not yet clear. The aim of this study was to investigate the effects of 1-year of progressive resistance training using elastic bands on CRP parameters, pain assessment, and body composition in post-menopausal women. Population: Sedentary post-menopausal (>12 months amenorrhoea) women. MethodA total of 40 women took part in a progressive resistance training program using elastic bands for 12 months (6 exercise for whole body training; 3 sets of 10 repeats). The intensity of exercise was established using the perceived effort scale OMNI-Resistance Exercise (OMNI-RES). A record was made of the body weight, blood analysis, and pain visual assessment scale, determined at baseline and one year after intervention. ResultsWhen compared with the initial levels, the results showed a reduction of 45% in the C-reactive protein and 30% in the level of pain, as well as a reduction in body weight, all of them with a level of significance of P<.05. ConclusionOne year of progressive resistance training with elastic bands has beneficial effects on inflammation and body composition, and reducing musculoskeletal pain in post-menopausal women.

Effect of pre-operative methylprednisolone on orthostatic hypotension during early mobilization after total hip arthroplasty.

Orthostatic hypotension (OH) and intolerance (OI) are common after total hip arthroplasty (THA) and may delay early mobilization. The pathology of OH and OI includes a dysregulated post-operative vasopressor response, by a hitherto unknown mechanism. We hypothesized that OI could be related to the inflammatory stress response which is inhibited by steroid administration. Consequently, this study evaluated the effect of a pre-operative high-dose methylprednisolone on OH and OI early after THA. Randomized, double-blind, placebo-controlled study in 59 patients undergoing elective unilateral THA with spinal anesthesia and a standardized multimodal analgesic regime. Patients were allocated (1 : 1) to pre-operative intravenous (IV) methylprednisolone (MP) 125 mg or isotonic saline (C). OH, OI and cardiovascular responses to sitting and standing were evaluated using a standardized mobilization protocol pre-operatively, 6, and 24 h after surgery. Systolic and diastolic arterial pressure and heart rate were measured non-invasively (Nexfin® ). The systemic inflammation was monitored by the C-reactive protein (CRP) response. At 6 h post-operatively, 11 (38%) versus 11 (37%) patients had OH in group MP and group C, respectively (RR 1.02 (0.60 to 1.75; P = 1.00)), whereas OI was present in 9 (31%) versus 13 (43%) patients (RR 0.76 (0.42 to 1.36; P = 0.42)), respectively. At 24 h post-operatively, the prevalence of OH and OI did not differ between groups, though CRP levels were significantly reduced in group MP (P < 0.001). Pre-operative administration of 125 mg methylprednisolone IV did not reduce OH or OI compared with placebo despite a reduced inflammatory response.

C-reactive protein response patterns after antibiotic treatment among children with scalds

BackgroundScalds are the most common cause of burns in children, yet there is little information available about the inflammatory response. The aim of the study was to investigate the response to treatment with antibiotics among scalded children by following the C-reactive protein (CRP) concentration, procalcitonin (PCT) concentration, and white blood cell count (WCC) during the first two weeks after injury. MethodsAll children with scalds who presented to the Burn Centre during 2010–2016 were included in this retrospective study. All measurements of CRP, PCT, and WCC from the first 14days after injury were recorded, and each patient’s maximum values during days 0–2, 3–7, and 8–14 were used for calculations. Multivariable regression for panel data was used to study the inflammatory response after antibiotic treatment. ResultsA total of 216 children were included. C-reactive protein was 45mg/L (p<0.001) higher in the group treated with antibiotics, and decreased with 8.8mg/L per day over the studied time in this group, which was more than twice as fast as among the children who were not given antibiotics. ConclusionThe CRP response, among children with minor scalds treated with antibiotics, shows an appreciable rise during the first week of injury that subsided rapidly during the second week.

Identification of sarilumab pharmacodynamic and predictive markers in patients with inadequate response to TNF inhibition: a biomarker substudy of the phase 3 TARGET study

IntroductionInterleukin-6 (IL-6) orchestrates formation of an inflammatory pannus, leading to joint damage in rheumatoid arthritis (RA). Sarilumab is a human monoclonal antibody blocking the IL-6Rα. In TARGET (NCT01709578), a phase...

Association of Single-Nucleotide Polymorphisms of C-Reactive Protein Gene with Susceptibility to Infantile Sepsis in Southern China.

BackgroundC-reactive protein (CRP) is an important biomarker of sepsis. Several single-nucleotide polymorphisms (SNPs) in the CRP gene can determine plasma CRP levels and are risk factors in many diseases, such as cancer, arteritis, and diabetes. However, it is unknown whether polymorphisms in CRP are associated with susceptibility to and outcome of infantile sepsis. We explored the effect of these SNPs on CRP response in infantile sepsis, and compared genetic data on patients with sepsis.Material/MethodsA total of 49 infants with sepsis and 20 healthy infants were enrolled during hospitalization, and 3 SNPs in the CRP gene region (rs1205, rs2808530, and rs3091244) were genotyped and then analyzed for associations with CRP levels and sepsis.ResultsThe CRP means concentration results showed that mean CRP concentration was different in the 4 groups (healthy, sepsis, severe sepsis, and septic shock) and was positively correlated with the severity of infantile sepsis. There was also a difference in CRP SNP rs1205 between infants with septic shock and healthy infants, and between infants with septic shock and infants with sepsis. No differences were observed in SNP rs2808630 and SNP rs3091244.ConclusionsOur study suggests that rs1205 genetic variability in the CRP gene determines the CRP levels in sepsis of different severities, while SNP rs3091244 and SNP rs2808630 are not associated with sepsis. However, the results of the present study on SNP rs1205, rs3091244, and rs2808630 in the CRP gene should be interpreted with caution due to limited sample size and sample heterogeneity. Large-scale, well-designed studies are needed to validate our findings.

C-Reactive Protein Response to a Single Canakinumab Dose Predicts Long-Term Benefit

Inflammation has long been hypothesized to play a causal role in the pathogenesis of atherosclerosis, and results from the industry-funded, randomized,

C-reactive protein gene polymorphisms (rs1205) in Asian Indian patients with Takayasu arteritis: Associations and phenotype correlations.

Normal C-reactive protein (CRP) in active Takayasu arteritis (TA) is a dilemma. We attempted to validate our pilot study finding of rs1205 in CRP gene being protective against TA. Genomic DNA of 104 patients and 185 sex-matched healthy controls were genotyped for rs1205 by Taqman assay. Clinical details, demography, angiographic and activity scores (Indian Takayasu arteritis score 2010) were recorded prospectively at baseline and during follow-up visits for 12 months. Minor allele frequency (MAF) and genotype distribution between patients and controls as well as patient subgroups were compared using χ2 test with Bonferroni correction (pc ) and logistic regression was performed to determine independent associations. The majority of patients (n = 84) and controls (n = 166) were females. MAF of T allele of rs1205 was less frequent in patients (27%) as compared to controls (37.6%), P = 0.013, pc = 0.026 with an odds ratio of 0.632 irrespective of gender. Frequency of CC genotype was higher in cases (53.8%) than controls (37.3%), P = 0.006, pc = 0.018. A dominant model of genotype-phenotype association revealed CC to be associated with more frequent coronary arterial and ascending aorta involvement than the other genotypes clubbed together (P = 0.01 and P = 0.014, respectively). Blunted CRP response seems to be less frequent in patients with CC genotype (P = 0.064). T allele of rs1205 in CRP gene was less frequent in TA. CC genotype was associated with involvement of coronary arteries and ascending aorta. CC genotype was less commonly associated with blunted CRP response (CT + TT > CC).

Quantitative Metabolic Volumetric Product on 18Fluorine-2fluoro-2-deoxy-D-glucose-positron Emission Tomography/Computed Tomography in Assessing Treatment Response to Disease-modifying Antirheumatic Drugs in Rheumatoid Arthritis: Multiparametric Analysis Integrating American College of Rheumatology/European League Against Rheumatism Criteria.

The purpose of this study was to assess the role of fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the evaluation of treatment response evaluation to disease-modifying antirheumatic drug (DMARD) therapy in patients of rheumatoid arthritis (RA). A total of ten patients with proven diagnosis of RA as per the 2010 American College of Rheumatology/European League against Rheumatism (EULAR) criteria were prospectively evaluated. All patients underwent clinical and biochemical evaluation and a baseline FDG-PET/CT with assessment of maximum standardized uptake value and metabolic volumetric product (MVP) values. DMARD therapy was started with a combination of hydroxychloroquine and sulfasalazine. On follow-up at 3 and 6 months, the response to treatment was assessed by clinical, biochemical, and FDG-PET/CT parameters. These parameters were analyzed in a combined manner, and the patients were grouped into 4 categories as per response to DMARD therapy - complete response, good response, mixed response, and no response. Evaluation of treatment response in ten patients at 3rd month and in nine patients at 6 months showed (a) agreement for MVP, biochemical parameters with clinical symptomatic assessment in all patients, (b) while agreement for EULAR score was noted in only three patients and disagreement in seven patients with clinical symptoms Response EULAR (rEULAR) (0.37) and at 6 months in only three patients and disagreement in six patients, rEULAR (0.52). The correlation factors at 3rd month and 6th months were, respectively, as follows: rMVP (0.67 and 0.75), response RA factor (0.54 and 0.74), response erythrocyte sedimentation rate (0.81 and 0.73), response C-reactive protein (0.78 and 0.51), and response anti-cyclic citrullinated peptide antibodies (0.33 and 0.54). The overall response to DMARD therapy at 3 months was assessed with results showing good response by four cases (40%), mixed response by 1 (10%), no response by 5 (50%), and complete response by none (0%). Step-up therapy at 3 months was initiated in four patients showing nonresponse/progression on clinical symptomatic assessment; of these, two patients showed a good response, one mixed response, and the remaining one continued to show nonresponse at 6 months follow-up. One patient who had a minimal response at 3 months on PET-CT (only 5.96% reduction of MVP) was continued on the same DMARD in view of clinical symptomatic good response (at 3 months) but ultimately had disease progression in all scales and worsening of symptom (at 6 months). FDG-PET/CT-based assessment of inflammatory activity noted in the joints of RA with quantitative parameters can be a promising approach for the whole body assessment of RA disease activity and treatment response assessment, especially in inconclusive cases and correlates well with other parameters. MVP can be used as a useful objective and adjunct parameter for assessing response to treatment.

A Novel Highly Bioavailable Curcumin Formulation Improves Symptoms and Diagnostic Indicators in Rheumatoid Arthritis Patients: A Randomized, Double-Blind, Placebo-Controlled, Two-Dose, Three-Arm, and Parallel-Group Study.

Rheumatoid arthritis (RA) is an autoimmune, chronic systemic inflammatory disorder. The long-term use of currently available drugs for the treatment of RA has many potential side effects. Natural phytonutrients may serve as alternative strategies for the safe and effective treatment of RA, and curcuminoids have been used in Ayurvedic medicine for the treatment of inflammatory conditions for centuries. In this study, a novel, highly bioavailable form of curcumin in a completely natural turmeric matrix was evaluated for its ability to improve the clinical symptoms of RA. A randomized, double-blind, placebo-controlled, three-arm, parallel-group study was conducted to evaluate the comparative efficacy of two different doses of curcumin with that of a placebo in active RA patients. Twelve patients in each group received placebo, 250 or 500 mg of the curcumin product twice daily for 90 days. The responses of the patients were assessed using the American College of Rheumatology (ACR) response, visual analog scale (VAS), C-reactive protein (CRP), Disease Activity Score 28 (DAS28), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) values. RA patients who received the curcumin product at both low and high doses reported statistically significant changes in their clinical symptoms at the end of the study. These observations were confirmed by significant changes in ESR, CPR, and RF values in patients receiving the study product compared to baseline and placebo. The results indicate that this novel curcumin in a turmeric matrix acts as an analgesic and anti-inflammatory agent for the management of RA at a dose as low as 250 mg twice daily as evidenced by significant improvement in the ESR, CRP, VAS, RF, DAS28, and ACR responses compared to placebo. Both doses of the study product were well tolerated and without side effects.

Different Adjuvants Induce Common Innate Pathways That Are Associated with Enhanced Adaptive Responses against a Model Antigen in Humans.

To elucidate the role of innate responses in vaccine immunogenicity, we compared early responses to hepatitis B virus (HBV) surface antigen (HBsAg) combined with different Adjuvant Systems (AS) in healthy HBV-naïve adults, and included these parameters in multi-parametric models of adaptive responses. A total of 291 participants aged 18–45 years were randomized 1:1:1:1:1 to receive HBsAg with AS01B, AS01E, AS03, AS04, or Alum/Al(OH)3 at days 0 and 30 (ClinicalTrials.gov: NCT00805389). Blood protein, cellular, and mRNA innate responses were assessed at early time-points and up to 7 days after vaccination, and used with reactogenicity symptoms in linear regression analyses evaluating their correlation with HBs-specific CD4+ T-cell and antibody responses at day 44. All AS induced transient innate responses, including interleukin (IL)-6 and C-reactive protein (CRP), mostly peaking at 24 h post-vaccination and subsiding to baseline within 1–3 days. After the second but not the first injection, median interferon (IFN)-γ levels were increased in the AS01B group, and IFN-γ-inducible protein-10 levels and IFN-inducible genes upregulated in the AS01 and AS03 groups. No distinct marker or signature was specific to one particular AS. Innate profiles were comparable between AS01B, AS01E, and AS03 groups, and between AS04 and Alum groups. AS group rankings within adaptive and innate response levels and reactogenicity prevalence were similar (AS01B ≥ AS01E > AS03 > AS04 > Alum), suggesting an association between magnitudes of inflammatory and vaccine responses. Modeling revealed associations between adaptive responses and specific traits of the innate response post-dose 2 (activation of the IFN-signaling pathway, CRP and IL-6 responses). In conclusion, the ability of AS01 and AS03 to enhance adaptive responses to co-administered HBsAg is likely linked to their capacity to activate innate immunity, particularly the IFN-signaling pathway.

C-reactive protein as a marker of infection in children with severe acute malnutrition in Khartoum state, Sudan

Severe acute malnutrition and acute systemic infection are often synergistic in children and lead to considerable mortality. The main aim of this research was to determine whether children with severe acute malnutrition can mount an acute phase reactant response measured by C-reactive protein. This was a descriptive, cross-sectional, hospital-based study that was carried out in the five main children hospitals in Khartoum state, from November 1st, 2012 to March 1st, 2013. 132 children with severe acute malnutrition were included in the study. Data collection included history, examination and C-reactive protein measurement. The data were analyzed using Statistical Package for Social Sciences (SPSS) for descriptive and inferential statistics. The main results revealed that 93(70.5%) children between 12-23 months of age and most of them had marasmus. Diarrhoea was the commonest presenting symptoms in 86.4%, followed by fever and vomiting. Most of the children (82.6%) had positive C-reactive protein with variable levels. In conclusion malnourished children are able to synthesize C-reactive protein in response to an infectious process and the magnitude of this response is increased in those with severe infections.

Erratum to: Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia.

Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). Conclusion: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury.

The effect of pre-operative methylprednisolone on early endothelial damage after total knee arthroplasty: a randomised, double-blind, placebo-controlled trial.

We wished to evaluate whether inhibition of the systemic inflammatory response by a single pre-operative dose of methylprednisolone reduced markers of early endothelial damage after fast-track total knee arthroplasty. We randomly allocated 70 patients undergoing elective unilateral total knee arthroplasty (1:1) to receive either pre-operative intravenous methylprednisolone 125 mg (methylprednisolone group) or isotonic saline (control group). All procedures were performed under spinal anaesthesia without a tourniquet, using a standardised multimodal analgesic regime. The outcomes included changes in Syndecan-1 concentrations, a marker of glycocalyx degradation, markers of endothelial cell damage and activation (plasma soluble thrombomodulin and sE-Selectin), and permeability by vascular endothelial growth factor, as well as C-reactive protein concentrations. Blood samples were collected at baseline and 2 h, 6 h and 24 h after surgery, with complete sampling from 63 patients for analyses. Methylprednisolone significantly reduced markers of endothelial damage at 24 h following surgery compared with saline (methylprednisolone group vs. control group, adjusted means (SEM)) expressed by circulating Syndecan-1: 11.6 (1.0) ng.ml-1 vs. 13.4 (1.1) ng.ml-1 p = 0.046; soluble thrombomodulin: 5.1 (0.1) ng.ml-1 vs. 5.7 (0.2) ng.ml-1 , p = 0.009; sE-Selectin: 64.8 (1.8) ng.ml-1 vs. 75.7 (1.9) ng.ml-1 , p = 0.001, and vascular endothelial growth factor: 35.3 (2.7) ng.ml-1 vs. 58.5 (2.8) ng.ml-1 , p < 0.001. The effect of the intervention increased with time for soluble thrombomodulin, sE-Selectin and vascular endothelial growth factor, and was more pronounced in patients with high baseline values. Finally, methylprednisolone reduced the C-reactive protein response 24 h postoperatively; 31.1 (1.1) mg.l-1 vs. 68.4 (1.1) mg.l-1 , p < 0.001. Pre-operative administration of methylprednisolone 125 mg reduced circulating markers of endothelial activation and damage, as well as the systemic inflammatory response (C-reactive protein) early after fast-track total knee arthroplasty. These findings may have a positive effect on surgical outcome, but require studies in major surgery.

Biomarkers of hepatic injury and function in neonatal hypoxic ischemic encephalopathy and with therapeutic hypothermia.

We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.

One-Year Clinical Outcomes in an IBD Cohort Who Have Previously Had Anti-TNFa Trough and Antibody Levels Assessed.

Loss of response (LOR) is a big concern for anti-TNFa therapies in inflammatory bowel disease. Immunomonitoring may be useful to optimize response rates and overcome secondary LOR. This was an observational retrospective cohort study of a group of patients with inflammatory bowel disease on infliximab (IFX) and adalimumab (ADA) who had anti-TNFa trough and antibody levels measured, during maintenance phase of treatment. Anti-TNFa trough and antibody levels were measured using standard enzyme-linked immunosorbent assay techniques. Baseline patient characteristics were determined and patients were reviewed 1 year later. Clinical assessment took place with partial Mayo scores for ulcerative colitis and Harvey-Bradshaw index for Crohn's disease. C-reactive protein (CRP) and albumin were also measured. Poor outcomes were defined as the following: need for rescue steroids, dose intensification, surgery, or treatment discontinuation. Seventy-four patients were included in the study, 37 (50%) were female, mean age 41 years, 61 (82%) had Crohn's disease, and 42 (57%) ulcerative colitis. Forty-two (57%) patients received IFX and 32 (43%) ADA. Mean IFX trough was 3.6 μg/mL and mean ADA troughs were 3.78 μg/mL. Twenty-seven percent of patients (n = 20) overall had a poor outcome, with a similar proportion in each group 24% (n = 10) IFX and 31% (n = 10) ADA (P value 0.24). Of the cohort, 14.2% (6/42) treated with IFX had subtherapeutic trough levels, 6.2% (2/32) of ADA patients had a trough level <1 μg/mL (P value = 0.273) There was no difference in mean trough according to outcome (4.9 μg/mL poor versus 5.4 μg/mL good, P value 0.14). Low IFX trough levels did correlate with high CRP, low albumin and response rates, mean CRP 6.66 μg/mL (n = 3), mean albumin 37 g/L for patients with low trough levels and poor response versus CRP 2.0 μg/mL (n = 24), mean albumin 43 g/L for patients with high trough levels and good response (P = 0.009, 95% confidence interval, -0.78 to -0.12). LOR is still a big concern with anti-TNFa therapies. Stand-alone anti-TNFa trough and antibody levels are not useful at predicting LOR/disease progression at 1 year, but low trough levels do correlate well with elevated CRP, hypoalbuminaemia, and poor response rates.

High physical fitness is associated with reduction in basal- and exercise-induced inflammation.

C-reactive protein (CRP) increases after strenuous exercise. It has been a concern that prolonged strenuous exercise may be harmful and induce a deleterious inflammatory response. The purpose of this study was to (a) assess and quantify the magnitude of CRP response following an endurance cycling competition in healthy middle-aged recreational cyclists. (b) Identify important determinants of this response. (c) Identify the relationship between CRP, myocardial damage (cardiac Troponin I (cTnI)), and myocardial strain (B-type natriuretic peptide [BNP]). (d) Identify the relationship between CRP and clinical events, defined as utilization of healthcare services or self-reported unusual discomfort.Race time was used as a measure of physical fitness. A total of 97 individuals (43±10years of age, 74 [76%] males) were assessed prior to and 0, 3, and 24hours following the 91-km mountain bike race "Nordsjørittet" (Sandnes, Norway, June 2013). There was a highly significant increase in CRP from baseline to 24hours (0.9 (0.5-1.8) mg/L vs. 11.6 (6.0-17.5) mg/L (median[IQR]), P<.001), with no correlation of CRP to cTnI and BNP at any time-point. CRP was strongly correlated to race time at baseline (r=.38, P<.001) and at 24 hours following the race (r=.43, P<.001), In multivariate models, race time was an independent predictor of CRP both at baseline and at 24 hours (P<.01). There was no relationship between CRP levels and clinical events. In conclusion, high physical fitness was associated with reduction in both basal- and exercise-induced CRP. No adverse relationship was found between high intensity physical exercise, CRP levels, and outcomes.