Pretreatment C-reactive Protein Research Articles

Associations between C-reactive protein and individual symptoms of depression in a lower-middle income country.

Data on associations between inflammation and depressive symptoms largely originate from high income population settings, despite the greatest disease burden in major depressive disorder being attributed to populations in lower-middle income countries (LMICs). We assessed the prevalence of low-grade inflammation in adults with treatment-resistant depression (TRD) in Pakistan, an LMIC, and investigated associations between peripheral C-reactive protein (CRP) levels and depressive symptoms. This is a secondary analysis of two randomised controlled trials investigating adjunctive immunomodulatory agents (minocycline and simvastatin) for Pakistani adults with TRD (n = 191). Logistic regression models were built to assess the relationship between pre-treatment CRP (≥ or <3 mg/L) and individual depressive symptoms measured using the Hamilton Depression Rating Scale. Descriptive statistics and regression were used to assess treatment response for inflammation-associated symptoms. High plasma CRP (≥3 mg/L) was detected in 87% (n = 146) of participants. Early night insomnia (odds ratio 2.33, 95% CI 1.16-5.25), early morning waking (odds ratio 2.65, 95% CI 1.29-6.38) and psychic anxiety (odds ratio 3.79, 95% CI 1.39-21.7) were positively associated, while gastrointestinal (odds ratio 0.38, 95% CI 0.14-0.86) and general somatic symptoms (odds ratio 0.34, 95% CI 0.14-0.74) were negatively associated with inflammation. Minocycline, but not simvastatin, improved symptoms positively associated with inflammation. The prevalence of inflammation in this LMIC sample with TRD was higher than that reported in high income countries. Insomnia and anxiety symptoms may represent possible targets for personalised treatment with immunomodulatory agents in people with elevated CRP. These findings require replication in independent clinical samples.

C-Reactive Protein Pretreatment-Level Evaluation with Histopathological Correlation for Chondrosarcoma Prognosis Assessment-A 15-Year Retrospective Single-Center Study.

An aberrant cellular microenvironment characterized by pathological cells or inflammation represents an added risk factor across various cancer types. While the significance of chronic inflammation in the development of most diffuse tumors has been extensively studied, an exception to this analysis exists in the context of chondrosarcomas. Chondrosarcomas account for 20-30% of all bone sarcomas, with an estimated global incidence of 1 in 100,000. The average age at diagnosis is 50, and over 70% of patients are over 40. This retrospective study aimed to examine the role of C-reactive protein (CRP) as a prognostic factor in relation to the histopathological findings in chondrosarcoma. In this retrospective study, 70 patients diagnosed with chondrosarcoma and treated between 2004 and 2019 were included. Preoperative CRP levels were measured in mg/dL, with non-pathological values defined as below 0.5 mg/dL. Disease-free survival time was calculated from the initial diagnosis to events such as local recurrence or metastasis. Follow-up status was categorized as death from disease, no evidence of disease, or alive with disease. Patients were excluded if they had insufficient laboratory values, missing follow-up information, or incomplete histopathological reports. The calculated risk estimation of a reduced follow-up time was 2.25 timed higher in the patients with a CRP level >0.5 mg/dL (HR 2.25 and 95% CI 1.13-4.45) and 3 times higher in patients with a tumor size > pT2 (HR 3 and 95% CI 1.59-5.92). We can easily confirm that risk factors for reduced prognosis lie in chondrosarcoma high grading, preoperative pathological CRP- level, and a size > 8 cm. A pretreatment CRP value greater than 0.5 mg/dL can be considered a sensitive prognostic and risk factor for distant metastasis for chondrosarcoma patients.

Impact of timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis associated with upper urinary tract stones: a propensity score-matched analysis.

We aimed to assess the impact of the timing of urinary drainage on clinical outcomes in patients with obstructive pyelonephritis (OPN) associated with upper urinary tract (UUT) stones. We retrospectively evaluated the multicenter dataset of 240 patients with OPN associated with UUT stones who underwent urinary drainage. We divided the patients into two groups depending on the timing of urinary drainage; emergency drainage, defined as within 12h from admission, and delayed drainage, defined as between 12 and 48h from admission. The outcomes were the length of hospital stay, time to leukocyte normalization, and time to body temperature normalization. One-to-two propensity score matching (PSM) was applied to minimize the effect of confounders between the two groups. Subsequently, predictive patient factors for emergency drainage were analyzed using the logistic regression model. Only the time from admission to normal body temperature was significantly shorter in the emergency drainage group when compared with the delayed drainage group (median: 2 vs. 3days; p = 0.02), while there was no difference in time from drainage to body temperature normalization between the two groups. On multivariable analysis, high pretreatment C-reactive protein (CRP) was associated with implementing emergency drainage within 12h. The timing of urinary drainage was only associated with the duration of high fever, but it did not affect the postdrainage course. Emergency urinary drainage is more likely to be performed in severe patients, such as high pretreatment CRP.

Salivary CRP predicts treatment response to virtual reality exposure therapy for social anxiety disorder

BackgroundSocial anxiety disorder (SAD) places a profound burden on public health and individual wellbeing. Systemic inflammation may be important to the onset and maintenance of SAD, and anti-inflammatory treatments have shown promise in relieving symptoms of SAD. In the present study, we conducted secondary analyses on data from a randomized clinical trial to determine whether C-reactive protein (CRP) concentrations and social anxiety symptoms decreased over the course of virtual reality exposure therapy, and whether changes in social anxiety symptoms as a function of treatment varied as a function of CRP. MethodAdult participants (N = 78) with a diagnosis of SAD (59 % female) were randomized to receive exposure therapy alone, or exposure therapy supplemented with scopolamine. Social anxiety symptoms, salivary CRP, and subjective units of distress were measured across three exposure therapy sessions, at a post-treatment extinction retest, and at a 1-month follow-up. ResultsCRP decreased over the course of treatment, b = −0.03 (SE = 0.01), p =.02 95 %CI [−0.06, −0.004], as did all social anxiety symptom domains and subjective distress. Higher CRP was associated with greater decreases from pre-treatment to 1-month follow-up in fear, b = −0.45 (SE = 0.15), p =.004 95 %CI [−0.74, −0.15], and avoidance, b = −0.62 (SE = 0.19), p =.002 95 %CI [−1.01, −0.23], and in-session subjective distress from pre-treatment to post-treatment, b = −0.42 (SE = 0.21), p =.05 95 %CI [−0.83, −0.001]. However, declines in CRP were not correlated with declines in fear, r = −0.07, p =.61, or avoidance, r = −0.10, p =.49, within-persons. ConclusionsVirtual reality exposure therapy may be associated with an improvement in systemic inflammation in patients with severe SAD. Pre-treatment CRP may also be of value in predicting which patients stand to benefit the most from this treatment.

Prognostic factors for overall survival in clinical node-positive patients with upper tract urothelial carcinoma.

There is sparse evidence regarding optimal management and prognosticators for oncologic outcomes in patients with clinical node-positive (cN+) upper tract urothelial carcinoma (UTUC). We retrospectively analyzed the data from 105 UTUC patients with cN1-2M0 between June 2010 and June 2022 at multiple institutions affiliated with our university. At the time of diagnosis, all patients received standard-of-care treatment including radical nephroureterectomy (RNU), chemotherapy, and/or palliative care. We employed a Cox regression model to analyze the prognostic importance of various factors on overall survival (OS). Of 105 patients, 54 (51%) underwent RNU, while 51 (49%) did not. RNU was likely to be selected in patients with younger and higher G8 score, resulting in better median OS in patients who underwent RNU than in those who did not (42 months vs. 15 months, p < 0.001). Multivariable analysis among the entire cohort revealed that low G8 score (≤14) (hazard ratio [HR]: 2.07, 95% confidence interval [CI]: 1.08-3.99), elevated pretreatment C-reactive protein (CRP) (HR: 3.35, 95%CI: 1.63-6.90), and failure to perform RNU (HR: 2.16, 95%CI: 1.06-4.42) were independent prognostic factors for worse OS. In the subgroup analyses of cohorts who did not undergo RNU, elevated pretreatment CRP was the only independent prognostic factor for worse OS in cN+ UTUC patients. RNU seems to be a reasonable treatment option in cN+ UTUC patients where applicable. Elevated pretreatment CRP appears to be a reliable prognosticator of worse OS and may be helpful in optimizing candidate selection for intensified treatment in this setting.

C-reactive Protein Is a Prognostic Factor for Survival in Metastatic Upper Tract Urothelial Carcinoma Patients Receiving Pembrolizumab.

The number of available treatment options for urothelial carcinoma has increased recently. Upper tract urothelial carcinoma (UTUC) is relatively rare compared with bladder cancer. There are few reports on the efficacy of immune checkpoint inhibitors (ICIs) for metastatic UTUC, and ICIs may occasionally show less efficacy and cause severe side effects. Therefore, it is important to predict the treatment response and change the treatment strategy as appropriate. We investigated the prognostic factors for treatment response in patients with metastatic UTUC treated with pembrolizumab at our hospital. Patients who received pembrolizumab for UTUC between January 2018 and June 2023 were analyzed. Patients who presented with bladder cancer complications at initial diagnosis were excluded. The primary endpoints assessed were overall survival (OS) and progression-free survival (PFS). Statistical analyses were conducted using laboratory values obtained before and after pembrolizumab administration. The relationship between cancer and inflammation is important. Therefore, we analyzed this relationship using prognostic factors for urothelial carcinoma as previously reported. Specifically, pretreatment C-reactive protein (CRP) level, neutrophil-to-lymphocyte ratio (NLR), and NLR/albumin values were examined. Forty-seven patients were analyzed. The median PFS was 66 days (24-107 days), and the median OS was 164 days (13-314 days). A CRP level <1 before the first cycle was a useful factor in the multivariate analysis for both OS and PFS [OS: p=0.004, hazard ratio (HR)=3.244, 95% confidence interval (CI)=1.464-7.104; PFS: p=0.003, HR=2.998, 95%CI=1.444-6.225]. CRP level is a prognostic factor for pembrolizumab treatment response in patients with UTUC.

Which treatment should we choose for tubo-ovarian abscesses? Results of an 8-year clinical training in a tertiary center.

Tubo-ovarian abscess (TOA) is inflammation of the pelvic organs, mainly originating from the lower genital tract and intestinal tract. Treatment options include antibiotic therapy, surgical drainage, and radiologically guided (interventional) drainage. In our study, we aimed to evaluate the treatment method to be chosen and thus to manage patients with tuba ovarian abscesses (TOAs) most accurately. This is a retrospective cohort study, and patients who applied to a tertiary center diagnosed with tuba ovarian abscess (TOA) were included. TOA size (cm), pre-treatment C-reactive protein (CRP) value, pre-treatment white blood cell (WBC) value, previous operation type, postoperative complication, and antibiotics used were screened. 305 patients were included in the study, and medical treatment was applied to 140 patients, organ-sparing surgical drainage to 50 patients, and surgical treatment to 115 patients. TOA dimensions measured at the time of diagnosis were significantly lower in patients for whom only medical treatment was sufficient. Pre-treatment CRP levels, WBC levels, and length of stay were significantly lower in patients for whom only medical treatment was sufficient. There was no significant difference between the pre-and post-procedure CRP difference, antibiotics, and hospitalization time. Preferring minimally invasive treatment in cases requiring invasive treatment reduces the frequency of complications. Treatment of tuba ovarian abscesses (TOA) with minimally invasive methods will be more beneficial in terms of patient morbidity.

Association between pretreatment C-reactive protein level and survival in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A meta-analysis

BackgroundCurrent evidence suggests that C-reactive protein (CRP) levels may affect cancer prognosis. However, the effect of CRP has not been validated in immunotherapy recipients with non-small cell lung cancer (NSCLC). Therefore, we performed a meta-analysis to explore the prognostic value of CRP level in patients with NSCLC treated with immune checkpoint inhibitors. MethodsPubMed, Web of Science, Embase, and Scopus databases were systematically retrieved for eligible publications, and hazard ratios (HRs) with corresponding 95% confidence intervals (95%CIs) were extracted and merged to evaluate the correlation between pretreatment CRP levels and overall survival (OS) and progression-free survival (PFS). Subgroup and sensitivity analyses were conducted to confirm these findings. ResultsThirty-five cohorts consisting of 4698 patients were included in the primary analysis. Pooled results demonstrated that a higher pretreatment CRP level is associated with worse OS and PFS (OS: HR = 1.13, 95 %CI:1.09–1.18; PFS: HR = 1.16, 95 %CI:1.10–1.22). These findings remained robust after further statistical analyses. ConclusionPretreatment CRP level could be a promising biomarker for NSCLC immunotherapy. However, prospective studies are required to validate these findings.

Survival and biomarkers for cachexia in non-small cell lung cancer receiving immune checkpoint inhibitors.

The presence of cachexia negatively impacts the prognosis of patients with cancer. However, the mechanisms behind the development of cachexia and its prognostic impact on immunotherapy efficacy are not fully understood. We retrospectively screened patients with advanced or recurrent non-small cell lung cancer (NSCLC) who received PD-1/PD-L1 inhibitor monotherapy. Among 183 patients, pre-treatment plasma samples were available from 100 patients. We defined cancer cachexia as weight loss of at least 5% during the past 6 months or weight loss of at least 2% and BMI <20. We analyzed 75 soluble immune mediators in pre-treatment plasma samples to explore the possible mechanisms behind the development of cancer cachexia. We also investigated whether cancer cachexia affects prognosis. Among 100 patients, 35 had cancer cachexia. Logistic regression analysis identified ghrelin, c-reactive protein (CRP), pentraxin-3 (PTX-3), and osteopontin (OPN) as factors associated with cachexia. Patients with cachexia had worse progression-free survival (PFS) and overall survival (OS), although we did not detect statistically significant differences. Analyzing the soluble immune mediators associated with cachexia, the combination of cachexia and PTX-3 or OPN expression levels was predictive for PFS and the combination of cachexia and CRP or OPN expression levels was predictive for OS. Pre-treatment ghrelin, CRP, PTX-3, and OPN may be associated with cachexia. Among patients with NSCLC who received PD-1/L1 inhibitor monotherapy, those with cachexia had worse survival than those without cachexia. Larger studies will be required to confirm our data and better understand the mechanisms behind the development of cachexia.

High level of C-reactive protein as a predictive factor for immune-related adverse events of immune checkpoint inhibitors in non-small cell lung cancer: a retrospective study.

Several risk factors for the immune-related adverse events (irAEs) during treatment with immune checkpoint inhibitors (ICIs) have been reported, of which include high levels of C-reactive protein (CRP). In this study, we aim to evaluate CRP levels before ICIs treatments as potential predictive biomarkers of irAEs incidence rate and overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). Between December 1, 2015 to December 31, 2019, we retrospectively collected all adult patients with NSCLC who received at least one dose of an ICI targeting the PD-1/PD-L1 axis at the Iwate Medical University Hospital in Japan. In this study the patients were categorized into low and high groups with a cut-off value of 10 mg/L as the baseline level of CRP before the ICI treatment. The primary endpoint was relationship between CRP levels at baseline and incidence of irAEs. The secondary endpoints were the relationship of progression-free survival (PFS) and OS. A total of 101 irAEs, and 25 severe irAEs were observed. The incidence of the most irAEs was higher in the high CRP group compared to the low CRP group (54.4% vs. 34.5%, respectively, P=0.003). The most frequent irAEs were skin rush (28.8%), followed by pneumonitis (19.2%), hypothyroidism (15.4%), and hepatotoxicity (9.6%). The most common grade 3 or 4 irAEs was pneumonitis (7.9%), which tended to be more frequent in the high CRP group. In multivariate analysis, patients with high CRP levels had an adjusted OR of 2.41 and were associated with an increased risk of developing irAEs (95% CI: 1.16-4.43, P=0.020). The high CRP group was related with shorter PFS compared to the low CRP group (2.2 vs. 3.3 months, respectively, P=0.006). The high CRP group were also related with shorter OS compared to the low CRP group (8.9 vs. 39.1 months, respectively, P<0.001). The results suggest that higher level of pretreatment CRP is involved in the development of irAE and poor prognosis. Identification of patients at high risk of irAEs would be of great help. Future multicenter prospective studies are needed to expand on this study.

C-reactive protein as a response biomarker to immune checkpoint blockade: A meta-analysis.

2559 Background: Tumor-promoting inflammation is a hallmark of cancer pathogenesis and is associated with poor outcomes and treatment resistance. C-reactive protein (CRP) is a routinely measured acute phase reactant whose synthesis is stimulated by cytokines and may thereby represent a surrogate for tumor promoting inflammation. Pre-treatment CRP has been associated with resistance to immune checkpoint blockade (ICB) in several studies. However, whether post-treatment changes in CRP correlate with ICB outcomes has not been systematically examined. Methods: We performed a systematic review to identify cohort studies or clinical trials in solid tumor patients receiving ICB therapy with CRP response comparator pairs (high/low) available. We included studies that had hazard ratio (HR) of overall survival (OS), progression-free survival (PFS), or odds ratio (OR) of objective response rate (ORR) available. We performed a meta-analysis using a random-effect model to evaluate if post-treatment changes in CRP are associated with ORR, PFS, or OS. Subgroup analysis for primary cancer type was performed. Heterogeneity was assessed using the I-squared statistic. Results: We screened 691 eligible studies; 19 met inclusion criteria and 2,101 patients were included. Patients experiencing post-ICB declines in CRP had improved ORR HR=4.67 [95% CI] [2.81-7.78] (p&lt;0.0001, I2=42%), PFS HR=2.47 [1.98-3.09] (p&lt;0.0001, I2=18%), and OS HR=2.28 [1.68-3.08] (p&lt;0.0001, I2=56%). Heterogeneity among subgroups was low in ORR (I2=14.6%) and PFS analysis ( I2=0%), and moderate in OS analysis (I2=64.2%). Conclusions: In patients receiving ICB therapy, post-treatment declines in CRP were associated with improved ORR, PFS, and OS across multiple histologies. These findings support the integration of on-treatment CRP decline as a clinically relevant response biomarker for novel therapies directed at modulating tumor-promoting inflammation. A meta-regression analysis will help determine optimal post-treatment CRP cutpoints. Pooled OR of ORR [95%CI] and HR [95%CI] of PFS and OS with subgroup analysis results and heterogeneity assessment. [Table: see text]

C-reactive protein (CRP) as a prognostic biomarker in patients with bladder cancer: A meta-analysis.

e16502 Background: CRP is an acute phase reactant synthesized by hepatocytes in response to inflammatory cytokines including interleukin-6. Peripheral blood CRP, a routinely measured analyte, may reflect tumor microenvironments skewed towards tumor-promoting inflammation. CRP may therefore represent an attractive biomarker to select patients with bladder cancer (BCa) more likely to benefit from therapies directed at modulating tumor-promoting inflammation. Methods: A systematic review was performed to identify studies reporting outcomes based on pre-treatment CRP values in patients with localized and advanced BCa and urothelial carcinoma (UC). The hazard ratio (HR) of overall survival (OS), cancer-specific survival (CSS), relapse-free survival (RFS), and progression-free survival (PFS) between groups with high and low CRP values as defined in each study was extracted. Meta-analysis using the random-effect model was performed to pool HR. Meta-regression analysis was conducted to assess the relationship between CRP cutoff and HR for OS. Subgroup analyses were performed according to clinical disease state and therapies administered. Heterogeneity was assessed using I2 statistics. Results: Overall, 938 articles were identified at initial screening; 22 studies comprising 2,899 patients were included in the meta-analysis. For OS, 17 datasets from 16 studies were used. High CRP levels were associated with decreased OS (HR=2.03, 95%CI:1.67-2.47, p&lt;0.01) although high heterogeneity was observed (I2=91%). Subgroup analyses according to anticancer interventions showed that high CRP values were related to shorter OS, particularly in patients treated with immune checkpoint blockade (ICB; HR=1.78, 95%CI: 1.47-2.15, p&lt;0.01). In meta-regression analysis, the correlation between CRP cutoff value and OS HR was not observed when all 16 studies were considered (Regression coefficient=0.03, 95%CI: -0.13-0.18, p=0.73). However, CRP cutoff value was significantly associated with the HR for OS (Regression coefficient=-0.21, 95%CI: -0.36 to -0.06, p=0.01) when the analysis was limited to eight studies assessing ICB in advanced BCa/UC. Pooled HR of CSS, RFS, and PFS is shown in Table. Conclusions: High CRP values were associated with poorer clinical outcomes in patients with BCa/UC, particularly among patients with advanced disease treated with ICB. CRP may represent an attractive biomarker to enrich populations more likely to benefit from therapies that modulate tumor-promoting inflammation. [Table: see text]

Systemic Immune-Inflammation Index Predicts Restenosis after Interventions for Lower Extremity Arteriosclerosis Obliterans.

To investigate the association between the pretreatment systemic immune-inflammation index (SII) and restenosis after interventions for lower extremity arteriosclerosis obliterans (ASO). We retrospectively evaluated 309 patients with ASO who underwent endovascular interventions between January 2018 and December 2021. Pretreatment inflammatory markers, including the SII, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), and C-reactive protein (CRP) were collected. The logistic regression model was used to determine the associations between these inflammatory markers and restenosis. Clinical manifestations, ankle-brachial index (ABI), and quality of life after intervention also were compared. The pretreatment SII (p < 0.001), NLR (p < 0.001), PLR (p < 0.001), SIRI (p = 0.002), AISI (p < 0.001), and CRP (p = 0.036) were significantly higher in patients with restenosis than in those without restenosis. Among the four markers, SII had the highest area under the curve (AUC) in predicting restenosis (SII vs. NLR vs. PLR vs. SIRI vs. AISI vs. CRP: 0.715 vs. 0.689 vs. 0.695 vs. 0.643 vs. 0.691 vs. 0.596). Multivariate analysis revealed that the pretreatment SII was the only independent factor for restenosis (hazard ratio [HR]: 4.102; 95% confidence interval [CI]: 1.155-14.567; p = 0.029). Moreover, a lower SII was associated with significantly better improvements in clinical manifestations (Rutherford classification 1-2: 67.5% vs. 52.9%, p = 0.038) and ABI (median: 0.29 vs. 0.22; p = 0.029), together with better quality of life (p < 0.05 for physical functioning, social functioning, pain, and mental health). The pretreatment SII is an independent predictor of restenosis after interventions in patients with lower extremity ASO, providing more accurate prognosis prediction than other inflammatory markers.

Sequencing impact and prognostic factors in metastatic castration-resistant prostate cancer patients treated with cabazitaxel: A systematic review and meta-analysis.

Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel. PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel. Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56-0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33-2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62-2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25-1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27-2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28-1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00-2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52-12.72), low albumin (pooled HR:1.09, 95% CI: 1.05-1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20-1.99). Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit.

Serum YKL-40 Levels in Patients with Asthma or COPD: A Pilot Study.

Background and Objectives: Bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) are not only common obstructive respiratory conditions but also major causes of morbidity and mortality worldwide. There is, however, a surprising lack of blood-based biomarkers for separating between these pulmonary disorders. The aim of this study was to assess the practical relevance of using serum YKL-40, single or combined, for this purpose. Materials and Methods: Subjects included Romanian patients with BA (n = 24) or COPD (n = 27). YKL-40, fibrinogen, pre-treatment C-reactive protein (CRP), post-treatment CRP, erythrocyte sedimentation rate, interleukin 6 (IL-6), procalcitonin (PCT), absolute neutrophil count, neutrophil percentage, absolute lymphocyte count, lymphocyte percentage, absolute eosinophil count, and eosinophil percentage were measured and compared between these patients. Results: This is the first study investigating the clinical significance of serum YKL-40 in delineating between COPD and BA in Caucasian populations. Only fibrinogen and YKL-40 levels were different between COPD and BA, with the measured values being significantly elevated. These patients exhibited distinct inflammatory profiles. Using the upper quartiles of these variables for the pooled study population (YKL-40: 5100 pg/mL; fibrinogen: 552 mg/dL) as cut-off values, subjects were classified into high or low groups. High YKL-40 adults revealed significantly increased PCT levels. High fibrinogen subjects, by contrast, showed significantly elevated IL-6 concentrations and pre-treatment CRP levels. Low YKL-40 and fibrinogen patients showed the absence of COPD. Conclusions: Combined use of serum YKL-40 and fibrinogen may be useful for identifying the absence of COPD.

Elevation of C-reactive protein during concurrent chemoradiotherapy is a poor predictive factor for head and neck cancer

ObjectiveThe prognostic role of pretreatment C-reactive protein (CRP) has been reported for head and neck cancer. However, little is known about the relationship between the changes in CRP levels during treatment and prognosis. This study aimed to investigate the correlation between CRP elevation during concurrent chemoradiotherapy (CCRT) and survival outcomes. MethodsThe medical records of patients with oropharyngeal, hypopharyngeal, and laryngeal cancer treated with CCRT at the University of Tsukuba Hospital and National Hospital Organization Mito Medical Center from April 2014 to December 2019 were retrospectively reviewed. Patients were divided into normal (<0.3 mg/dl) and elevated (≥0.3 mg/dl) CRP groups according to the CRP level after the first cycle of cisplatin. The primary endpoint was progression-free survival (PFS). ResultsA total of 74 patients were enrolled, of whom 36 (49%) showed elevated CRP levels after the first cycle of cisplatin. The 3-year PFS was 83.3% and 61.0% in the normal and elevated CRP groups, respectively, showing significant differences between the two groups. ConclusionElevated CRP levels after the first cycle of cisplatin is an objective predictive marker for survival in patient with head and neck squamous cell carcinoma treated with CCRT.

Construction and evaluation of a prognostic model for severe acute pancreatitis based on CT scores and inflammatory factors

To construct a prognostic model for severe acute pancreatitis (SAP) based on CT scores and inflammatory factors, and to evaluate its efficacy. 128 patients with SAP diagnosed admitted to the First Hospital Affiliated to Hebei North College from March 2019 to December 2021 were enrolled and given Ulinastatin combined with continuous blood purification therapy. The levels of C-reactive protein (CRP), procalcitonin (PCT), interleukins (IL-6, IL-8), tumor necrosis factor-α (TNF-α), and D-dimer were measured before and on the third day of treatment. An abdominal CT was performed on the third day of treatment to assess the modified CT severity index (MCTSI) and extra-pancreatic inflammatory CT score (EPIC). Patients were divided into the survival group (n = 94) and the death group (n = 34) according to the 28-day survival prognosis after admission. The risk factors for the SAP prognosis were analyzed using Logistic regression, which was then used to build nomogram regression models. The value of the model was evaluated using the concordance index (C-index), calibration curves and decision curve analysis (DCA). Before treatment, the levels of CRP, PCT, IL-6, IL-8 and D-dimer in the death group were higher than those in the survival group. After treatment, the levels of IL-6, IL-8 and TNF-α in the death group were higher than those in the survival group. MCTSI and EPIC scores in the survival group were lower than those in the death group. Logistic regression analysis shows that, pre-treatment CRP > 140.70 mg/L, D-dimer > 2.00 mg/L, and post-treatment IL-6 > 31.28 ng/L, IL-8 > 31.04 ng/L, TNF-α > 31.04 ng/L, and MCTSI > 8 points were all independent risk factors for SAP prognosis [odds ratios (OR) and 95% confidence intervals (95%CI) were 8.939 (1.792-44.575), 6.369 (1.368-29.640), 8.546 (1.664-43.896), 5.239 (1.108-24.769), 4.808 (1.126-20.525), 18.569 (3.931-87.725), all P < 0.05]. Model 1 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α) had a lower C-index than that model 2 (consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI; 0.988 vs. 0.995). The mean absolute error (MAE) and mean square error (MSE) of model 1 (0.034, 0.003) were higher than those of model 2 (0.017, 0.001). When the threshold probability was in the range of 0-0.66 or 0.72-1.00, the net benefit of model 1 was lower than that of model 2. When the threshold probability was in the range of 0.66-0.72, the net benefit of model 1 was higher than that of model 2. In addition, model 2 had a higher C-index than acute physiology and chronic health evaluation II (APACHE II) and bedside index of acute pancreatitis severity (BISAP, 0.995 vs. 0.833, 0.751). Model 2 had a lower MAE (0.017) and MSE (0.001) than APACHE II (0.041, 0.002). Model 2 had a lower MAE than BISAP (0.025). Model 2 had a higher net benefit than both APACHE II and BISAP. The prognostic assessment model of SAP consisting of pre-treatment CRP, D-dimer, and post-treatment IL-6, IL-8 and TNF-α, and MCTSI has high discrimination, precision and clinical application value, and is superior to APACHE II and BISAP.

Is CRP/Albumin Ratio (CAR) a New Parameter to be Added to Risk Stratification Systems in Metastatic Renal Cell Carcinoma Patients?

To evaluate the effect of pretreatment C-reactive protein (CRP)/Albumin ratio (CAR) on prognosis and its association with IMDC (International metastatic renal cell carcinoma database consortium) risk score and overall survival (OS) in metastatic renal cell carcinoma (mRCC) patients. Descriptive study. Department of Medical Oncology, Dokuz Eylul University, Izmir, Turkey, between 2007 and 2020. Clinico-pathological and treatment-related data of mRCC patients were retrospectively evaluated and included in the study. CAR was used as a prognostic inflammatory score. CAR threshold value for OS has been obtained by ROC analysis. The prognostic value of CAR was tested using Kaplan-Meier and Cox-regression models. IMDC-CAR model was created by adding CAR to IMDC risk stratification. OS was 91 months in patients with CAR below the threshold value of 0.072 (<0.072), while OS was 51 months in patients with CAR of 0.072 and above (p=0.005). According to IMDC risk stratification, intermediate and poor risk groups showed similar survival times (p>0.05). However, when CAR was added to the IMDC risk score in the intermediate group, it was divided into 3 subgroups with different prognoses (p=0.02). CAR is an independent predictor of OS in mRCC patients. In this study, it has been demonstrated that more accurate prognosis prediction could be made by adding CAR to IMDC indicators in the intermediate risk group, which constitutes a highly heterogeneous group according to IMDC risk stratification. Renal cell cancer, Albumin, C-reactive protein, IMDC, Prognosis.

Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide-platinum-atezolizumab treatment.

The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free-survival (PFS) when compared to the placebo group in treatment-naïve extensive stage (ES) small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy have become mainstay treatment modalities as first-line treatment in ES-SCLC. Nevertheless, real-world data are still lacking and the search for potential biomarkers is essential. This study aimed to evaluate potential predictive biomarkers applicable in ES-SCLC under combination therapy. Patients with ES-SCLC under etoposide-platinum-atezolizumab enrolled from seven university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. p-values below 0.05 were considered statistically significant. A total of 41 patients were evaluated. Six-month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, nine (22.0%) showed stable disease, and four (9.8%) showed progressive disease. During the induction phase, grade I-II AEs occurred in 22 (53.7%) patients, and grade III-IV AEs occurred in 26 (63.4%) patients. During the maintenance phase, nine out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase (LDH), c-reactive protein (CRP), and forced vital capacity (%) were significant factors. In multivariate analysis for PFS, sex, and LDH were significant. In ES-SCLC under etoposide-platinum-atezolizumab, pretreatment CRP, LDH and FVC (%) were independent predictive factors.

Reduction of blood C-reactive protein concentration complements the resolution of sputum bacillary load in patients on anti-tuberculosis therapy.

BackgroundTuberculosis (TB) is a difficult-to-treat disease requiring the combination of four antibiotics for a minimum of 6 months. Rapid and quantitative biomarkers to monitor treatment response are urgently needed for individual patient management and clinical trials. C-reactive protein (CRP) is often used clinically as a rapid marker of inflammation caused by infection. We assessed the relationship of TB bacillary load and CRP as biomarkers of treatment response.MethodsXpert MTB/RIF-confirmed pulmonary TB cases were enrolled for treatment response assessment in Mozambique. Treatment response was measured using the Tuberculosis Molecular Bacterial Load Assay (TB-MBLA) in comparison with standard-of-care Mycobacterium Growth Indicator Tube (MGIT) culture at baseline and at weeks 1, 2, 4, 8, 12, 17, and 26 of treatment. Blood CRP concentration was measured at baseline, week 8, and week 26. Treatment response was defined as increase in MGIT culture time to positivity (TTP), and reduction in TB-MBLA-measured bacillary load and blood CRP concentration.ResultsOut of the 81 screened presumptive TB cases, 69 were enrolled for 6-month treatment follow-up resulting in 94% treatment completion rate. Four participants did not complete TB treatment and 22 participants had missing CRP or TB-MBLA results and were excluded from TB-MBLA-CRP analysis. The remaining 43 participants—median age, 31 years old [interquartile range (IQR): 18–56]; 70% (30/43) male; and 70% (30/43) infected with HIV—were considered for analysis. Culture TTP and bacillary load were inversely correlated, Spearman’s r = −0.67, p < 0.0001. Resolution of sputum bacillary load concurred with reduction of blood CRP, r = 0.70, p < 0.0001. At baseline, bacillary load had a median (IQR) of 6.4 (5.5–7.2), which reduced to 2.4 (0.0–2.9) and 0.0 (0.0–0.0) log10 CFU/ml at months 2 and 6 of treatment, respectively. Correspondingly, blood CRP reduced from 1.9 (1.6–2.1) at baseline to 1.3 (0.9–1.7) and 0.4 (0.1–0.8) log10 mg/dl at months 2 and 6 of treatment, respectively. CRP reduction trialed bacteriological resolution at a rate of −0.06 log10 mg/dl compared to a bacillary load of 0.23 log10 CFU/ml per week. Consequently, 14 (33%) and 37 (88%) patients had reduced CRP to normal concentration and bacillary load to zero by the end of treatment, respectively. Pre-treatment CRP concentration and bacillary load, and resolution during treatment were slightly lower in HIV co-infected patients but not significantly different from HIV-uninfected TB patients.ConclusionTB-MBLA-measured bacillary load and blood CRP complement each other in response to anti-TB therapy. Slow CRP reduction probably reflects residual TB bacilli in the lung not expectorated in sputum. Combining both measures can improve the accuracy of these biomarkers for monitoring TB treatment response and shorten turnaround time since the results of both assays could be available in 24 h.