C-reactive Protein Trajectories Research Articles

Characterizing CRP dynamics during acute infections.

C-reactive protein (CRP) is a common proxy of inflammation, but accurate characterizations of its dynamics during acute infections are scant. The goal of this study was to examine C-reactive protein (CRP) trajectories in hospitalized patients with viral infections, confirmed bacteremia (stratified by Gram-negative or Gram-positive bacteria), and non-bacteremic infections/inflammations, considering antibiotic treatment. Electronic medical records from Tel Aviv Sourasky Medical Center (July 2007-May 2023) were analyzed. Patients with blood cultures or positive viral tests were included. CRP levels were modeled using generalized additive mixed-effects models (GAMMs) and observed up to 150h after initial infection diagnosis. Patients with initial CRP levels > 31.9 were excluded, to remove individuals already in a highly active inflammatory process. The shapes of the CRP curves were characterized and peak CRP as well as area under the CRP curve were the primary variables of interest. Viral infections had the lowest and flattest CRP curves. Non-bacteremic infections showed intermediate levels, while bacteremia (especially Gram-negative under antibiotic treatment) had the highest CRP peaks. For instance, peak CRP ranged from 15.4mg/L in viral infections without antibiotics to 140.9mg/L in Gram-negative bacteremia with antibiotics. CRP trajectories significantly differ based on infection type and antibiotic treatment. Frequent CRP measurement could be a valuable diagnostic and risk stratification tool in hospitalized patients.

Effects of C-reactive protein trajectories of critically ill patients with sepsis on in-hospital mortality rate

Sepsis, a life-threatening condition caused by an inflammatory response to systemic infection, results in a significant social burden and healthcare costs. This study aimed to investigate the relationship between the C-reactive protein (CRP) trajectories of patients with sepsis in the intensive care unit (ICU) and the in-hospital mortality rate. We reviewed 1464 patients with sepsis treated in the ICU of Dongyang People’s Hospital from 2010 to 2020 and used latent growth mixture modeling to divide the patients into four classes according to CRP trajectory (intermediate, gradually increasing, persistently high, and persistently low CRP levels). We found that patients with intermediate and persistently high CRP levels had the lowest (18.1%) and highest (32.6%) in-hospital mortality rates, respectively. Multiple logistic regression analysis showed that patients with persistently high (odds ratio [OR] = 2.19, 95% confidence interval [CI] = 1.55–3.11) and persistently low (OR = 1.41, 95% CI = 1.03–1.94) CRP levels had a higher risk of in-hospital mortality than patients with intermediate CRP levels. In conclusion, in-hospital mortality rates among patients with sepsis differ according to the CRP trajectory, with patients with intermediate CRP levels having the lowest mortality rate. Further research on the underlying mechanisms is warranted.

Pre- and postoperative C-reactive protein as a risk factor of organ/space surgical site infection after hepatectomy.

Organ/space surgical site infection (SSI) is one of the most common complications of liver resection, with significant impact on morbidity and mortality, so patients at high risk should be identified early. This study aimed to determine whether pre- and postoperative C-reactive protein (CRP) levels could predict organ/space SSIs. The hospital records of consecutive patients who underwent hepatectomy without biliary reconstruction at our institutions between 2008 and 2015 were reviewed retrospectively. Preoperative, intraoperative, and postoperative variables were compared between patients with or without organ/space SSIs. Its risk factors were also determined. Among 443 identified patients, 55 cases (12.5%) developed organ/space SSIs; they more frequently experienced other complications and bile leakage (47.3% vs. 16.6%, p = 0.001; 40.0% vs. 8.5%, p < 0.001, respectively). Postoperative CRP elevation from postoperative day (POD) 3 to 5 was significantly more frequent in the SSI group (21.8% vs. 4.9%, p < 0.001). Multivariate analysis identified preoperative CRP ≥ 0.2mg/dL (odds ratio (OR), 2.01, p = 0.044], preoperative cholangitis (OR, 15.7; p = 0.020), red cell concentrate (RCC) transfusion (OR, 2.61, p = 0.018), bile leakage (OR, 9.51; p < 0.001), and CRP level elevation from POD 3 to 5 (OR, 3.81, p = 0.008) as independent risk factors for organ/space SSIs. Preoperative CRP elevation and postoperative CRP trajectory are risk factors for organ/space SSIs after liver resection. A prolonged CRP level elevation at POD 5 indicates its occurrence. If there were no risk factors and no CRP elevation at POD 5, its presence could be excluded.

No associations between C-reactive protein and spinal pain trajectories in children and adolescents (CHAMPS study-DK)

Preliminary evidence points to a link between C-reactive protein (CRP) and spinal pain in adults. However, there is a paucity of research in younger populations. Therefore, we aimed to determine associations between CRP and spinal pain in childhood and adolescence. We identified trajectories of spinal pain from childhood to adolescence and investigated the associations between CRP and trajectory subgroups. Six- to 11-year-old children from 13 primary schools, were followed from October 2008 and until 2014. High-sensitivity CRP collected at baseline (2008) was measured using serum samples. The outcome was the number of weeks with non-traumatic spinal pain between November 2008 and June 2014. We constructed a trajectory model to identify different spinal pain trajectory subgroups. The associations between CRP and spinal pain trajectory subgroups were modelled using mixed-effects multinominal logistic regression. Data from 1556 participants (52% female), with a mean age of 8.4 years at baseline, identified five spinal pain trajectory subgroups: “no pain” (55.3%), “rare” (23.7%), “rare, increasing” (13.6%), “moderate, increasing” (6.1%), and “early onset, decreasing” (1.3%). There were no differences in baseline high-sensitivity CRP levels between spinal pain trajectory subgroups. Thus, the heterogeneous courses of spinal pain experienced were not defined by differences in CRP at baseline.

C-reactive protein: A predictor for early discharge following colorectal surgery

Objectives: Anastomotic leak following colorectal surgery is a common complication. Late diagnosis following oncological resections can lead to poorer long-term outcomes due to delays in accessing further treatment. A useful biomarker which has been identified in early detection of anastomotic leak is serum C-reactive protein (CRP). A recent meta-analysis confirmed the value of using CRP trajectory to accurately rule out an anastomotic leak after colorectal resection. The aim of this study was to establish a post-operative CRP cut-off value above which the development of anastomotic leak is more likely and to thereby facilitate earlier discharge.

The association of wound factors and symptoms of fatigue and pain with wound healing in chronic venous leg ulcers.

The purpose of this study was: (1) to characterise the association of wound area, wound exudate C-reactive protein (CRP), broad-spectrum matrix metalloprotease protein (MMPs), and symptoms of fatigue and pain in individuals with chronic venous leg ulcers (CVLUs) over time and (2) to identify factors associated with the wound healing trajectory in CVLUs. Seventy four participants with CVLU who received weekly sharp debridement were recruited from a wound care clinic during the 8-week study period. To examine associations among wound CRP, MMPs, pain, fatigue, and wound healing trajectory over time, we calculated Bayes factors (BF) based on a linear mixed model. The mean age of participants was 71.8 (SD=9.8) and the mean wound area was 2278 mm2 (SD=7085 mm2 ) at baseline. Higher fatigue was strongly associated with higher MMPs (BF=9, 95% HDI: [-.05, .43]), lower CRP (BF=11, 95% HDI: [-.02, .002]), and large areas of wound (BF=20, 95% HDI: [-.001, .01]). Higher CRP and MMPs activity in wound exudate and higher fatigue were associated with a larger wound area. To facilitate wound healing, clinicians need to utilise the multifactorial approach, which includes wound treatment and management of symptoms such as pain and fatigue, because of the molecular and psycho-behavioural factors involved in wound healing.

Change in C-reactive protein after Roux-en-Y gastric bypass through 7 years of follow-up.

Long-term change in CRP is not well characterized in the context of RYGB. To report C-reactive protein (CRP) after Roux-en-Y gastric bypass surgery (RYGB). Between 2006 and 2009 1770 adults enrolled in a prospective cohort study underwent Roux-en-Y gastric bypass (RYGB) at 1 of 10 U.S. hospitals. Research assessments were conducted before surgery and annually postoperatively for up to 7 years. This study included those with high-sensitivity CRP assessed before surgery and 1 or more follow-up assessments (n = 1180). Before surgery, participants' median age was 46 years, and the median body mass index (BMI) was 46 kg/m2; 80% were female. Before surgery, mean (95% confidence interval [CI]) CRP was the highest of all time points (1.01 [.95-1.08] mg/L); it then decreased to a nadir of .18 (.15-.22) mg/L at 2 years postoperatively (P < .001). CRP was higher at 7 years (.26 [.22, .29] mg/L) than at 2 years postoperatively (P < .001) but remained lower at 7 years than preoperatively (P < .001). Additionally, only 3.2% (95% CI: 1.6%-4.8%) of participants had elevated CRP (>1 mg/dL) 7 years postoperatively versus 32.9% (95% CI: 30.2%-35.3%) preoperatively (P < .001). Several preoperative factors were associated with following a less favorable CRP trajectory over time, including higher preoperative CRP level, higher BMI, current smoking, and diabetes. The vast majority of adults who underwent RYGB experienced a sustained improvement in CRP throughout 7 years of follow-up with nonelevated values. However, those with higher preoperative CRP and BMI levels and diabetes and who smoke may benefit from additional testing and monitoring to ensure nonelevated inflammation after surgery.

C-reactive protein trajectories and the risk of all cancer types: A prospective cohort study.

A single CRP measurement is insufficient to examine the association of long‐term patterns of CRP concentration with cancer risk. We prospectively examined the relationship between CRP trajectory patterns and new‐onset cancers among 52 276 participants. Latent mixture modeling was used to identify CRP trajectories. Cox proportional hazards regression models were used to evaluate the association between CRP trajectory patterns and the risk of overall and specific‐site cancer. Four CRP trajectories patterns were identified: low‐stable pattern (n = 43 258), moderate‐increasing pattern (n = 2591), increasing‐decreasing pattern (n = 2068) and elevated‐decreasing pattern (n = 4359). Relative to the low‐stable pattern, the moderate‐increasing trajectory pattern was associated with an elevated risk of overall, lung, breast, leukemia, bladder, stomach, colorectal, liver, gallbladder or extrahepatic bile duct cancer and leukemia. Participants in the increasing‐decreasing trajectory pattern were associated with an elevated risk of overall, lung, breast, bladder, pancreatic and liver cancer. The increasing‐decreasing trajectory pattern was also associated with decreased risk of colorectal cancer in the multivariate analyses. Elevated‐decreasing trajectory pattern was associated with increased risk of leukemia and decreased risk of esophageal and colorectal cancer. CRP trajectories play an important role in the occurrence of cancers, especially in the lung, breast, bladder, stomach, colorectal, liver, gallbladder and extrahepatic bile duct cancer and leukemia.

Role of the triad of procalcitonin, C-reactive protein, and white blood cell count in the prediction of anastomotic leak following colorectal resections

PurposeThe enhanced recovery after surgery (ERAS) program expedites patient recovery after major surgery. This study aimed to investigate the role of the triad of procalcitonin (PCT), C-reactive protein (CRP), and white blood cells (WBC) trajectories as a predictive biomarker for the anastomotic leak (AL) after colorectal surgery.MethodPatients who had colorectal anastomosis were prospectively included. Postoperative clinical and laboratory parameters and outcomes were collected and analyzed. The 5-day trajectories of PCT, CRP, and WBC were evaluated. Based on the trajectory of the three biomarkers, we compared patients with and without AL as detected during the first 30 days after surgery using the area under receiver operator characteristic curves (AUC) for logistic estimation.ResultsThis study included 205 patients, of whom 56% were men and 43.9% were women with a mean age of 56.4 ± 13.1 years. Twenty-two patients (10.7%) had AL; 77.3% underwent surgery, and 22.7% were treated with drainage and antibiotics. Procalcitonin was the best predictor for AL compared to CRP and WBC at three days postoperatively (AUC: 0.84, 0.76, 0.66, respectively). On day 5, a cutoff value of 4.93 ng/mL for PCT had the highest sensitivity, specificity, and negative predictive value. The predictive power of PCT was substantially improved when combined with either CRP or WBC, or both (AUC: 0.92, 0.92, 0.93, respectively).ConclusionThe 5-day trajectories of combined CRP, PCT, and WBC had a better predictive power for AL than the isolated daily measurements. Combining the three parameters may be a reliable predictor of early patient discharge, which would be highly beneficial to ERAS programs.

Early biochemical predictors of clinically relevant pancreatic fistula after distal pancreatectomy: a role for serum amylase and C-reactive protein.

Recent evidence suggests that pancreatic inflammation plays a pivotal role in the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy but few data are available for distal pancreatectomy (DP). The aim of this study was to evaluate the impact of early biochemical markers on the occurrence of CR-POPF after DP. Clinical and laboratory data for 432 consecutive DP patients were reviewed. Serum amylase was evaluated on postoperative day (POD) 1, and drain fluid amylase (DFA) and C-reactive protein (CRP) were evaluated on POD 2 and 3. Receiver operator characteristic (ROC) curves were performed for all biochemical markers and an area under the curve (AUC) was computed. Multivariable regression analyses to identify the factors associated with CR-POPF and severe postoperative morbidity (Clavien-Dindo grade ≥ 3) were performed. At 90 days after surgery, CR-POPF occurred in 155 (36%) patients, severe complications in 66 (15%) patients. ROC curve analyses showed that DFA on POD2 had the largest AUC (0.753, p < 0.001), followed by serum amylase on POD 1 (0.651, p < 0.001), serum CRP on POD3 (0.644, p < 0.001), and CRP change between POD 2 and POD 3 (0.644, p < 0.001). Multivariable analysis identified male gender (OR 2.29, 95% CI 1.36-3.86; p = 0.002), DFA ≥ 1500 U/Lon POD2 (OR 4.63, 95% CI 2.72-7.89; p < 0.001), serum amylase ≥ 100 U/L on POD 1 (OR 1.72, 95% CI 1.01-2.93; p = 0.046), and CRP increase by at least 25mg/L on POD 3 compared to the previous day (OR 1.89, 95% CI 1.11-3.21; p = 0.019) as independent predictors of CR-POPF, yielding a valid regression model (AUC 0.765, 95% CI 0.714-0.816, p < 0.001). Postoperative serum amylase and CRP trajectory represent useful early biochemical markers for CR-POPF in addition to DFA. Our findings suggest that these laboratory tests should be incorporated into clinical practice to aid postoperative patient and drain management.

Informing antimicrobial management in the context of COVID-19: understanding the longitudinal dynamics of C-reactive protein and procalcitonin

BackgroundTo characterise the longitudinal dynamics of C-reactive protein (CRP) and Procalcitonin (PCT) in a cohort of hospitalised patients with COVID-19 and support antimicrobial decision-making.MethodsLongitudinal CRP and PCT concentrations and trajectories of 237 hospitalised patients with COVID-19 were modelled. The dataset comprised of 2,021 data points for CRP and 284 points for PCT. Pairwise comparisons were performed between: (i) those with or without significant bacterial growth from cultures, and (ii) those who survived or died in hospital.ResultsCRP concentrations were higher over time in COVID-19 patients with positive microbiology (day 9: 236 vs 123 mg/L, p < 0.0001) and in those who died (day 8: 226 vs 152 mg/L, p < 0.0001) but only after day 7 of COVID-related symptom onset. Failure for CRP to reduce in the first week of hospital admission was associated with significantly higher odds of death. PCT concentrations were higher in patients with COVID-19 and positive microbiology or in those who died, although these differences were not statistically significant.ConclusionsBoth the absolute CRP concentration and the trajectory during the first week of hospital admission are important factors predicting microbiology culture positivity and outcome in patients hospitalised with COVID-19. Further work is needed to describe the role of PCT for co-infection. Understanding relationships of these biomarkers can support development of risk models and inform optimal antimicrobial strategies.

Temporal evolution of C-reactive protein levels and its association with the incident hospitalization risk among individuals with stage 3-4 chronic kidney disease.

Elevated C-reactive protein (CRP) levels as an inflammatory marker have been associated with poor outcomes in patients with chronic kidney disease (CKD). However, its single assessment may not reflect clinical significance before an adverse clinical endpoint. We studied the CRP level trajectories, which may be related with the intensity of the inflammatory process, and its association with time-to-first hospitalization in CKD. A cohort of 739 patients with stage 3-4 CKD were retrospectively observed for seven years. The time-to-event outcome was all-cause hospitalization. Clinical and laboratory features were measured at baseline. Longitudinal changes in naturally logged CRP levels were modeled using the Joint Longitudinal-Survival model adjusted with baseline covariates. Logged CRP changes were evaluated with a median measurement (interquartile range) of 4 (2, 7), during a median (interquartile range) follow-up of 2.3 (1.2, 3.9) years. The estimated mean increase in logged CRP was 0.35mg/L per year. 299 (40.5%) patients reached the endpoint, and increase in logged CRP with time was associated with increased risk of hospitalization (HR 1.96; 95% CI 1.05-3.66; p = 0.034), but baseline logged CRP did not have a significant effect on the time-to-first hospitalization (HR 0.98; 95% CI 0.85-1.13; p = 0.736). All-cause hospitalization was associated significantly with CRP trajectories. Temporal evolutions of these repeatedly measured biomarkers might predict clinical outcomes in patients with CKD and may be useful for individual risk profiling. Furthermore, early management may provide an opportunity to better patient survival.

Insight into the longitudinal relationship between chronic subclinical inflammation and obesity from adolescence to early adulthood: a dual trajectory analysis.

This study aimed to understand the longitudinal relationship between C-reactive protein (CRP) and body mass index (BMI) from adolescence to early adulthood. CRP and BMI were collected from participants of the Raine Study Gen2 at 14-, 17-, 20- and 22-year follow-ups (n = 1312). A dual trajectory analysis was conducted to assess the association between CRP and BMI trajectories, providing conditional probabilities of membership of CRP trajectory membership given BMI trajectory membership. Best model fit was assessed by systematically fitting two to eight trajectory groups with linear and quadratic terms and comparing models according to the Bayesian Information Criterion statistic. The three CRP trajectories were; "stable-low" (71.0%), "low-to-high" (13.8%) and "stable-high" (15.2%). Participants in a "high-increasing" BMI trajectory had a higher probability of being in the "stable-high" CRP trajectory (60.4% of participants). In contrast, individuals in the "medium-increasing" BMI trajectory did not have a significantly increased probability of being in the "stable-high" CRP trajectory. These findings support that chronic sub-clinical inflammation is present through adolescence into early adulthood in some individuals. Targeting chronic sub-clinical inflammation though obesity prevention strategies may be important for improving future health outcomes.

Serial measurement of pancreatic stone protein for the early detection of sepsis in intensive care unit patients: a prospective multicentric study

BackgroundThe early recognition and management of sepsis improves outcomes. Biomarkers may help in identifying earlier sub-clinical signs of sepsis. We explored the potential of serial measurements of C-reactive protein (CRP), procalcitonin (PCT) and pancreatic stone protein (PSP) for the early recognition of sepsis in patients hospitalized in the intensive care unit (ICU).MethodsThis was a multicentric international prospective observational clinical study conducted in 14 ICUs in France, Switzerland, Italy, and the United Kingdom. Adult ICU patients at risk of nosocomial sepsis were included. A biomarker-blinded adjudication committee identified sepsis events and the days on which they began. The association of clinical sepsis diagnoses with the trajectories of PSP, CRP, and PCT in the 3 days preceding these diagnoses of sepsis were tested for markers of early sepsis detection. The performance of the biomarkers in sepsis diagnosis was assessed by receiver operating characteristic (ROC) analysis.ResultsOf the 243 patients included, 53 developed nosocomial sepsis after a median of 6 days (interquartile range, 3–8 days). Clinical sepsis diagnosis was associated with an increase in biomarkers value over the 3 days preceding this diagnosis [PSP (p = 0.003), PCT (p = 0.025) and CRP (p = 0.009)]. PSP started to increase 5 days before the clinical diagnosis of sepsis, PCT 3 and CRP 2 days, respectively. The area under the ROC curve at the time of clinical sepsis was similar for all markers (PSP, 0.75; CRP, 0.77; PCT, 0.75).ConclusionsWhile the diagnostic accuracy of PSP, CRP and PCT for sepsis were similar in this cohort, serial PSP measurement demonstrated an increase of this marker the days preceding the onset of signs necessary to clinical diagnose sepsis. This observation justifies further evaluation of the potential clinical benefit of serial PSP measurement in the management of critically ill patients developing nosocomial sepsis.Trial registration The study has been registered at ClinicalTrials.gov (no. NCT03474809), on March 16, 2018. https://www.clinicaltrials.gov/ct2/show/NCT03474809?term=NCT03474809&draw=2&rank=1.

Associations between seven-year C-reactive protein trajectory or pack-years smoked with choroidal or retinal thicknesses in young adults

Inflammation and cigarette smoking predispose to macular diseases, and choroidal and retinal thinning. We explored the choroidal and retinal thicknesses in young adults against their 7-year C-reactive protein (CRP) level trajectory and pack-years smoked. Participants from the Raine study, a longitudinal cohort study, had serum CRP levels analysed at the 14-, 17-, and 20-year follow-ups. Group-based trajectory modelling was used to classify participants according to their 7-year CRP levels. At the 20-year follow-up (at 18–22 years old), participants completed questionnaires on their smoking history, and underwent optical coherence tomography imaging to obtain their choroidal and retinal thicknesses at the macula. Three CRP trajectories were identified: consistently low CRP levels (78% of sample), increasing (11%), or consistently high (11%). 340 and 1035 participants were included in the choroidal and retinal thickness analyses, respectively. Compared to those in the “Low” trajectory group, participants in the “Increasing” and “High” groups had 14–21 μm thinner choroids at most macular regions. Every additional pack-year smoked was linked with a 0.06–0.10 μm thinner retina at the inner and outer macular rings, suggesting a dose-dependent relationship between smoking and thinner retinas. These associations may suggest that an increased risk of future visual impairment or eye disease associated with these risk factors may be present since young adulthood.

Multi-trajectory analysis of C-reactive protein and low back pain from adolescence to early adulthood.

To identify low back pain (LBP) trajectories from early adolescence through to early adulthood and to investigate whether sustained levels of elevated subclinical C-reactive protein (CRP) are linked with these LBP trajectories. We analysed longitudinal data from 1513 participants who were enrolled in the Raine Study cohort. Data on LBP with impact on daily living and CRP were collected at the ages of 14, 17, 20, and 22. We constructed group-based trajectory models to identify discrete trajectories of LBP with impact. We then evaluated how the CRP trajectories and the LBP with impact trajectories evolved jointly over time using a multi-trajectory analysis. The model identified three LBP trajectories. One subgroup included almost half the participants (46.1%) who had a consistently low probability of LBP. Another subgroup comprising 43.5% of participants had an increasing probability of LBP, while one in ten participants (10.4%) had a decreasing probability of LBP. There were no associations between elevated CRP and LBP trajectory subgroup membership. Although young people follow distinct trajectories of LBP, CRP trajectories do not appear to be a distinguishing factor of the LBP trajectories. Previously reported associations between CRP and LBP may be explained by comorbidity or other factors. Future studies undertaking trajectory analysis should consider comorbidity clusters. Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.

Postoperative Trends of Serum C-Reactive Protein Levels after Primary Shoulder Arthroplasty-Normal Trajectory and Influencing Factors.

Background—Postoperative serum C-reactive protein (CRP) is an important diagnostic parameter for systemic inflammation and reflects surgical trauma. While trends and normal trajectories after total knee (TKA) or hip arthroplasty (THA) are established, there is no reference standard for shoulder arthroplasty (SA). Therefore, the aim of this study was to research CRP trends and influencing factors following SA. Methods—This retrospective study analyzed postoperative serum CRP levels and trajectories in 280 patients following SA. Influence of prosthesis design, sex, operating time, BMI, and humeral augmentation with bone cement were analyzed using descriptive statistics and (non-) parametric testing. Results—There is a CRP trend with a peak on day two or three, with a subsequent decrease until day seven. Reverse and stemmed prostheses show a statistically higher CRP peak than stemless prostheses or hemiarthroplasties (HA). There was no influence of gender, body mass index (BMI), operating time, or bone cement. Conclusion—The presented findings may contribute to a better understanding of the postoperative CRP course after SA. The results of this retrospective study should be validated by a prospective study design in the future.

C-Reactive Protein (CRP) Levels in Immune Checkpoint Inhibitor Response and Progression in Advanced Non-Small Cell Lung Cancer: A Bi-Center Study.

Background: Biomarkers for predicting response to immune checkpoint inhibitors (ICI) are scarce and often lack external validation. This study provides a comprehensive investigation of pretreatment C-reactive protein (CRP) levels as well as its longitudinal trajectories as a marker of treatment response and disease outcome in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy with anti PD-1 or anti PD-L1 agents. Methods: We performed a retrospective bi-center study to assess the association between baseline CRP levels and anti PD-(L)1 treatment outcomes in the discovery cohort (n = 90), confirm these findings in an external validation cohort (n = 101) and explore the longitudinal evolution of CRP during anti PD-(L)1 treatment and the potential impact of dynamic CRP changes on treatment response and disease outcome in the discovery cohort. Joint models were implemented to evaluate the association of longitudinal CRP trajectories and progression risk. Primary treatment outcomes were progression-free survival (PFS) and overall survival (OS), while the objective response rate (ORR) was a secondary outcome, respectively. Results: In the discovery cohort, elevated pretreatment CRP levels emerged as independent predictors of worse PFS (HR per doubling of baseline CRP = 1.37, 95% CI: 1.16–1.63, p < 0.0001), worse OS (HR per doubling of baseline CRP = 1.42, 95% CI: 1.18–1.71, p < 0.0001) and a lower ORR ((odds ratio (OR) of ORR per doubling of baseline CRP = 0.68, 95% CI: 0.51–0.92, p = 0.013)). In the validation cohort, pretreatment CRP could be fully confirmed as a predictor of PFS and OS, but not ORR. Elevated trajectories of CRP during anti PD-(L)1 treatment (adjusted HR per 10 mg/L increase in CRP = 1.22, 95% CI: 1.15–1.30, p < 0.0001), as well as a faster increases of CRP over time (HR per 10 mg/L/month faster increase in CRP levels = 13.26, 95% CI: 1.14–154.54, p = 0.039) were strong predictors of an elevated progression risk, whereas an early decline of CRP was significantly associated with a reduction in PFS risk (HR = 0.91, 95% CI: 0.83–0.99, p = 0.036), respectively. Conclusion: These findings support the concept that CRP should be further explored by future prospective studies as a simple non-invasive biomarker for assessing treatment benefit during anti PD-(L)1 treatment in advanced NSCLC.

C-reactive protein trajectory in the first 48 hours predicts the need for intervention in conservative management of acute diverticulitis.

C-reactive protein (CRP) is a useful marker for monitoring response to treatment in sepsis. The aim of this study was to examine the use of CRP trajectory in predicting the need for intervention in conservatively managed patients with acute diverticulitis (AD). A retrospective review of patients with AD who were managed conservatively was performed. They were divided into four groups based on CRP relative to the median at day 0 and 2: 'Low rise' (levels below median at day 0 and 2), 'High rise' (levels above median at day 0 and 2), 'Rapid rise' (levels below median at day 0 but above median at day 2) and 'Decline' (levels above median at day 0 but below median at day 2). Intervention was required in 64 of 456 (14%) with 30 (48%) of these performed after day 2 of admission. There were 150 patients (54%) in the 'Low rise', 76 (27%) in the 'Decline', 26 patients (9%) in the 'Rapid rise' and 25 patients (9%) in the 'High rise' groups. Within these groups 5%, 8%, 19% and 32% of patients required intervention (P = 0.001). On multivariate analysis, patients with a pelvic abscess were more likely to need intervention (odds ratio 19.1 (confidence interval 6.2-59.4), P < 0.0001). The CRP trajectory during the initial 48 h of admission can predict the need for intervention in AD patients being managed conservatively. Patients with a 'Rapid rise' or 'High rise' in CRP from day 0 to 2 are more likely to need intervention.

Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

BackgroundChronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-wide association study identified DNA methylation correlates of C-reactive protein (CRP)—a widely used acute-phase inflammatory biomarker. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure.MethodsWe utilise a DNA methylation-based score for CRP and investigate its trajectories with age, and associations with cognitive ability in comparison with serum CRP and a genetic CRP score in a longitudinal study of older adults (n = 889) and a large, cross-sectional cohort (n = 7028).ResultsWe identified no homogeneous trajectories of serum CRP with age across the cohorts, whereas the epigenetic CRP score was consistently found to increase with age (standardised β = 0.07 and 0.01) and to do so more rapidly in males compared to females. Additionally, the epigenetic CRP score had higher test-retest reliability compared to serum CRP, indicating its enhanced temporal stability. Higher serum CRP was not found to be associated with poorer cognitive ability (standardised β = − 0.08 and − 0.05); however, a consistent negative association was identified between cognitive ability and the epigenetic CRP score in both cohorts (standardised β = − 0.15 and − 0.08).ConclusionsAn epigenetic proxy of CRP may provide a more reliable signature of chronic inflammation, allowing for more accurate stratification of individuals, and thus clearer inference of associations with incident health outcomes.