Pretreatment C-reactive Protein Research Articles

632P Prognostic relevance of pre-treatment c-reactive protein to albumin ratio in patients with diffuse large b cell lymphoma

Previous studies have shown that a high level of pre-treatment C-reactive protein to albumin ratio (CAR) is associated with poor outcomes in patients with diffuse large B cell lymphoma (DLBCL). However, these were single-centre studies with a relatively small number of patients. The aim of our study was to further investigate the prognostic value of CAR in a larger cohort and whether the addition of CAR to the International Prognostic Index (IPI) would result in a better discriminatory ability.

Prognostic Significance of C-reactive Protein in Patients With Non-metastatic Papillary Renal Cell Carcinoma: Results from the INternational Marker Consortium for Renal Cancer (INMARC) Cohort.

C-reactive protein is a useful biomarker for screening renal cell carcinoma (RCC); however, its significance in papillary RCC is unclear. We assessed the prognostic effect of serum C-reactive protein levels in patients with surgically treated non-metastatic papillary RCC. We established an international multi-institutional database (the INternational Marker Consortium for Renal Cancer) of 3799 patients with surgically treated RCC. Among these, data of 400 patients with non-metastatic papillary RCC were analyzed. An elevated pretreatment serum C-reactive protein level was defined as > 10 mg/L. Associations of clinical covariates with recurrence-free survival were investigated. Among the patients, 174 were African Americans, 155 were European-Americans, 50 were Asians, and 21 were of other races. Pathological T stages were 1, 2, 3, and 4 in 313, 46, 32, and 3 patients, respectively. The median pretreatment C-reactive protein level was 1.0 mg/L; 48 patients exhibited an elevated C-reactive protein level. During follow-up (median 18 months), 30 patients presented recurrence. The 1-, 3-, and 5-year recurrence-free rates were 95%, 91%, and 87%, respectively. Multivariate analysis revealed a significant association of the elevated pretreatment C-reactive protein level with poor recurrence-free survival (hazard ratio 2.47, 95% confidence interval 1.03-5.48; P=.043). The 5-year recurrence-free survival was significantly worse for patients with elevated C-reactive protein levels (67% vs. 90%; P=.001). C-reactive protein is a significant prognostic factor for patients with non-metastatic papillary RCC and can serve as a useful adjunct biomarker for screening patients with a high risk of recurrence.

Can We Predict a Higher Risk of Urothelial Bladder Cancer With a Simple Blood Test?

The COVID-19 pandemic highlighted the need to develop tools prioritizing high risk patients for urgent evaluation. Our objective was to determine whether Glasgow Prognostic Score (GPS), an inflammation-based score, can predict higher grade and stage urothelial bladder cancer in patients with gross hematuria who need urgent evaluation. We analyzed a database of 129 consecutive patients presenting with gross hematuria. GPS was calculated using pretreatment C-reactive protein (CRP) and albumin levels. Patients with bacteriuria or other known malignancies were excluded. The relationship between GPS and final diagnosis was analyzed with multivariate logistic regression. A total of 101 patients were included in the study and 24 patients were identified without any pathology and 77 with a bladder tumor. Pathology demonstrated 21 with muscle invasive, 18 with high grade non-muscle invasive, and 38 with low grade superficial bladder cancer. Twenty-six of 39 (67%) patients with high grade tumors had a GPS of 1 or 2 compared to only 8 out of 62 (13%) patients with either low grade or negative findings (p<0.0001). Ten of 21 (48%) patients with muscle invasive disease had a GPS of 2 compared to 1 out of 18 (6%) with high grade non muscle invasive tumors (p=0.04). On multivariate analysis, GPS was a strong independent predictor of high grade and stage bladder cancer. GPS may serve as a highly accessible predictor of high grade, high stage, and large urothelial bladder tumors at the time of initial evaluation and can help identify patients who need urgent evaluation.

Different Outcomes of Pelvic Inflammatory Disease after Transvaginal Oocyte Retrieval in Patients with and without Endometriosis and the Factors Influencing Its Treatment: A Retrospective Study of 66 Cases

Background: Even though endometriosis is an important risk factor for pelvic inflammatory disease (PID), it is still not clear whether endometriosis influences PID after ultrasound-guided transvaginal oocyte retrieval (TVOR). Therefore, this work was designed to explore whether endometriosis will influence PID after TVOR and study the influencing factors of receiving drainage treatment to improve the outcomes of patients with PID. Methods: A retrospective study was conducted between 2004 and 2017. Data were collected from Women’s Hospital, Zhejiang University School of Medicine, China. This study included 66 patients with acute PID symptoms after TVOR with or without endometriosis. The independent factors predicting drainage treatment were determined using univariate and multivariate logistic regression analyses, and their optimal cut-off points were ascertained using a receiver operating characteristic curve. Results: Among 66 cases, there were 53 women without endometriosis and 13 women with stage III or IV endometriosis. The significantly higher maximum body temperature (p = 0.047), longer days of fever (p = 0.043) and duration of intravenous (IV) antibiotic use (p = 0.001), and more receiving drainage treatment (p = 0.002) were found in the patients with endometriosis. In vitro fertilization (IVF) cycles (odds ratio [OR] = 6.055, 95% confidence interval [CI] = 1.360–26.961, p = 0.018), puncture cyst during TVOR (OR = 60.167, 95% CI = 2.477–1461.619, p = 0.012), and pre-treatment C-reactive protein (CRP; OR = 1.022, 95% CI = 1.003–1.041, p = 0.022) were significant independent risk factors for drainage treatment. The optimal cut-off for IVF cycles and pre-treatment CRP for patients receiving drainage treatment were 2 and 40.3 mg/L, respectively. Conclusions: Patients with endometriosis had more severe PID outcomes after TVOR, requiring more attention during treatment. Early drainage treatment is recommended for patients with pre-treatment CRP levels higher than 40.3 mg/L, puncture cyst during TVOR, and those receiving more than 2 IVF cycles.

The Influence of the Pretreatment Immune State on Response to Radiation Therapy in High-Risk Prostate Cancer: A Validation Study From NRG/RTOG 0521

The immunoinflammatory state has been shown to be associated with poor outcomes after radiation therapy (RT). We conducted an a priori designed validation study using serum specimens from Radiation Therapy Oncology Group (RTOG) 0521. It was hypothesized the pretreatment inflammatory state would correlate with clinical outcomes. Patients on RTOG 0521 had serum banked for biomarker validation. This study was designed to validate previous findings showing an association between elevations in C-reactive protein (CRP) and shorter biochemical disease free survival (bDFS). CRP levels were measured in pretreatment samples. An exploratory panel of related cytokines was also measured including: monocyte chemotactic protein-1, granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17A, IL-23, and tumor necrosis factor. The primary endpoint examined was bDFS. Additional exploratory endpoints included overall survival, distant metastases, and toxicity events attributed to RT. Two hundred and two patients in RTOG/NRG 0521 had serum samples available. Median age was 66 years (48-83), and 90% of patients were White. There was not an association between CRP and bDFS (adjusted hazard ratio [HR], 1.07 per 1 log increase in CRP; 95% confidence interval, 0.83-1.38; P = .60). In the exploratory, unplanned analysis, pretreatment IL-10 was significantly associated with worse bDFS (adjusted HR, 1.61 per log increase; P = .0027) and distant metastases (HR, 1.55 per log increase; P = .028). The association of IL-10 with bDFS was maintained on a multiplicity adjustment. The exploratory analyses of pretreatment levels of interferon-γ, IL-1b, IL-2, IL-13, IL-23 were negatively associated with grade 2 or higher pollakiuria (adjusted odds ratio, 0.64, 0.65, 0.71, 0.72, and 0.74, respectively, all P < .05), and IL-6 was negatively associated with grade 2 or higher erectile dysfunction (odds ratio, 0.62; P = .027). Pretreatment CRP was not associated with a poorer bDFS after RT. In a hypothesis- generating analysis, higher baseline levels of IL-10 were associated with lower rates of bDFS. These findings require additional prospective evaluation.

Development and validation of longitudinal c-reactive protein as dynamic response predictor for PD-L1 blockade in advanced NSCLC: Findings from four atezolizumab clinical trials.

e21113 Background: Numerous studies suggested that pre-treatment C-reactive protein (CRP) is a survival predictive biomarker for cancer patients treated with anti-PD-(L)1 blockade. However, the application of longitudinal CRP levels as dynamic biomarker for advanced non-small cell lung cancer (NSCLC) patients treated with anti-PD-(L)1 remains unexplored. Methods: This study analyzed four international, multi-center clinical trials (OAK, BIRCH, POPLAR and FIR trials) to conduct post-hoc analyses of NSCLC patients undergoing atezolizumab (anti-PD-L1) single-agent treatment. CRP test was performed ≤ 96 hours before Day 1 of each cycle. 1438 patients with more than 2 times CRP results (a total of 11,253 records) in all 3 collection timepoints. The primary endpoint was overall survival (OS). First, multivariate survival analysis was conducted to include clinical factors such as gender, ECOG-PS, race and metastases as contributing risk factors. Then, multivariate joint modelling of longitudinal and time-to-event data was used to establish the relationship between longitudinal CRP and OS in the OAK study, whereas external validation was performed by time-dependent AUC analysis on the BIRCH, POPLAR and FIR studies. Results: Log-transformed longitudinal CRP levels (log(CRP)) in combination with clinical factors in absence of PD-L1 expression emerged as independent predictors of worse OS in the OAK study (HR of jointed model = 2.08, 95% CI: 1.84-2.35, p &lt; 0.001) with a high accuracy (AUC = 0.74) for predicting OS. The predictive value of longitudinal CRP was validated in the external validation cohorts with good performance in OS (BIRCH: HR = 2.77 (95% CI: 2.31-3.44), AUC = 0.76; POPLAR: HR = 1.95 (95% CI: 1.50-2.64), AUC = 0.76; and FIR: HR = 1.83 (95% CI: 1.46 -2.39), AUC = 0.72). Conclusions: The Bayesian multivariate joint model demonstrated that longitudinal CRP is a strong survival dynamic predictor for atezolizumab-treated NSCLC patients.

Risk factors for the recurrence of relapsing polychondritis

BackgroundAlthough the survival rates of patients with relapsing polychondritis (RP) have increased remarkably, the high recurrence rate remains a significant concern for physicians and patients. This retrospective study aimed to investigate the risk factors for RP recurrence.MethodsPatients with RP who presented to Kyoto University Hospital from January 2000 to March 2020 and fulfilled Damiani’s classification criteria were included. Patients were classified into recurrence and non-recurrence groups. Risk factors for RP recurrence were analysed using a Cox proportional hazards model, and Kaplan–Meier survival curves were drawn.ResultsThirty-four patients were included. Twenty-five patients (74%) experienced 64 recurrences (mean: 2.56 recurrences per patient). The median duration before the first recurrence was 202 [55−382] days. The median prednisolone dose at the initial recurrence was 10 [5−12.75] mg/day. Tracheal involvement was significantly more frequent in the recurrence group at the initial presentation (44.0% vs. 0.0%, p=0.0172) than in the non-recurrence group, and pre-treatment C-reactive protein levels were significantly higher in the recurrence group than in the non-recurrence group (4.7 vs 1.15 mg/dL, p=0.0024). The Cox proportional hazards model analysis revealed that tracheal involvement (hazard ratio [HR] 4.266 [1.535−13.838], p=0.0048), pre-treatment C-reactive protein level (HR 1.166 [1.040−1.308], p=0.0085), and initial prednisolone monotherapy (HR 4.443 [1.515−16.267], p=0.0056) may be associated with recurrence. The median time before the initial recurrence was significantly longer in patients who received combination therapy with prednisolone and immunosuppressants or biologics (400 vs. 70 days, p=0.0015).ConclusionsTracheal involvement, pre-treatment C-reactive protein level, and initial prednisolone monotherapy were risk factors for recurrence in patients with RP. Initial combination therapy with prednisolone and immunosuppressants may delay recurrence.

Serum parameters as prognostic biomarkers in a real world cancer patient population treated with anti PD-1/PD-L1 therapy

Background Immune checkpoint inhibitors (ICI) are regarded as a standard of care in multiple malignancies. We hypothesized that serum parameters are of prognostic value in ICI treated patients suffering from solid tumours. Methods Data from 114 patients treated with ICIs for solid malignancies from 2015 to 2019 at the Medical University of Vienna were collected retrospectively. Data included baseline characteristics, cancer type, serum parameters such as lactate dehydrogenase (LDH), C-reactive protein (CRP), albumin (Alb) and lymphocyte counts as well as overall survival (OS) and progression free survival. Additionally, the Gustave Roussy Immune Score (GRIm score) and the Glasgow prognostic score (GPS) were calculated. Cox regression models including time-dependent effects and strata for tumour type were used. Prognostic factors were pre-selected using a relaxed LASSO approach. Results The majority of patients were male (64.9%). The most common cancer types were non-small cell lung cancer (30.7%) and renal cell carcinoma (21.9%). Increased LDH and CRP were associated with poor 6-month OS (Hazard ratios (HR)=1.16 and 1.06 per 20% LDH/CRP increase; 95% CI 1.07–1.26 and 95% CI 1.03–1.09, respectively; p < .001). Both GRIm Score and GPS had a significant influence on OS (GRIm: HR = 2.84, 95% CI 1.72–4.69; p < .001 for high vs. low; GPS HR 3.57, 95% CI 1.76–7.25; p < .001 for poor vs. good). The proportion of explained variation (PEV) of our full multivariable model was significantly higher compared to the GRIm and GPS (PEV = 29.5% vs. 14.8% and 14.65%). When grouped into quartiles according to the individual 8-weeks change, both increased LDH and CRP correlated with poor OS (LDH (p=.001) and CRP (p < .001)). Conclusion The results of this analysis suggest that serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type. Key messages In this retrospective analysis, 114 patients with solid tumours were included. The results of this analysis point out that pre-treatment LDH, CRP and albumin levels are strongly prognostic for a poor 6-month OS. In addition to that, a high GRIm-score and poor GPS were associated with a worse OS (GRIm: HR = 2.84, 95% CI 1.72–4.69; p < .001 for high vs. low; GPS HR = 3.57, 95% CI 1.76–7.25; p < .001 for poor vs. good). Pre-treatment serum parameters might have prognostic value for the outcome of cancer patients treated with ICI, regardless of the tumour type.

MP12-04 PREDICTIVE IMPACT OF EARLY CHANGES IN SERUM C-REACTIVE PROTEIN LEVELS IN NIVOLUMAB PLUS IPILIMUMAB THERAPY FOR METASTATIC RENAL CELL CARCINOMA

You have accessJournal of UrologyCME1 May 2022MP12-04 PREDICTIVE IMPACT OF EARLY CHANGES IN SERUM C-REACTIVE PROTEIN LEVELS IN NIVOLUMAB PLUS IPILIMUMAB THERAPY FOR METASTATIC RENAL CELL CARCINOMA Hidekazu Tachibana, Yuki Nemoto, Hiroki Ishihara, Hironori Fukuda, Kazuhiko Yoshida, Junpei Iizuka, Yasunobu Hashimoto, Tsunenori Kondo, Kazunari Tanabe, and Toshio Takagi Hidekazu TachibanaHidekazu Tachibana More articles by this author , Yuki NemotoYuki Nemoto More articles by this author , Hiroki IshiharaHiroki Ishihara More articles by this author , Hironori FukudaHironori Fukuda More articles by this author , Kazuhiko YoshidaKazuhiko Yoshida More articles by this author , Junpei IizukaJunpei Iizuka More articles by this author , Yasunobu HashimotoYasunobu Hashimoto More articles by this author , Tsunenori KondoTsunenori Kondo More articles by this author , Kazunari TanabeKazunari Tanabe More articles by this author , and Toshio TakagiToshio Takagi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002534.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Serum C-reactive protein (CRP) is reportedly associated with metastatic renal cell carcinoma (mRCC) activity. However, in the era of immune checkpoint inhibitors, the predictive value of CRP is unclear. In this study, we investigated the predictive impact of pretreatment CRP levels and early changes in CRP levels for the treatment of mRCC with nivolumab plus ipilimumab (NIVO-IPI) therapy. METHODS: Forty-eight patients with mRCC treated with NIVO-IPI as a first-line therapy were retrospectively analyzed. First, patients were divided into 2 groups: initial CRP ≥1.0 mg/dL and <1.0 mg/dL. Progression-free survival (PFS) was compared between the 2 groups. Second, based on the CRP change within the first three months of NIVO-IPI, patients were placed in the normal group (CRP remains <1.0 mg/dL), normalized group (CRP decreased <1.0 mg/dL), and non-normalized group (CRP remained or increased to ≥1.0 mg/dL). The predictive association between CRP change and PFS was evaluated. RESULTS: PFS was significantly lower in the high initial CRP group (n=24, 50%) compared to the normal CRP group (n=24, 50%) (median: 4.3 vs. 28.1 months, P=0.03). As for the early CRP change, the normal (2.7 vs. 28.1, P=0.0002) and normalized (2.7 vs. 11.0, P=0.0094) groups showed significantly higher PFS, compared to the non-normalized group. Meanwhile, there was no significant difference between normal and normalized groups (P=0.51). The objective response rate was higher in the normal (57.1% vs. 18.7%, P=0.015) and normalized (81.8 vs. 18.7%, P=0.0008) groups, compared to the non-normalized group. Multivariate Cox regression analysis showed that normal [Hazard ratio (HR)=0.15, 95% Confidence interval (CI)=0.02-0.70, P=0.026] and normalized (HR 0.21, 95% CI=0.05-0.73, P=0.015) CRP showed significant association with PFS. CONCLUSIONS: In the NIVO-IPI therapy for mRCC, early changes in CRP could predict PFS. This data may be useful for the early detection of ineffective NIVO-IPI therapy and conversion to subsequent therapies. Source of Funding: none © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e166 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hidekazu Tachibana More articles by this author Yuki Nemoto More articles by this author Hiroki Ishihara More articles by this author Hironori Fukuda More articles by this author Kazuhiko Yoshida More articles by this author Junpei Iizuka More articles by this author Yasunobu Hashimoto More articles by this author Tsunenori Kondo More articles by this author Kazunari Tanabe More articles by this author Toshio Takagi More articles by this author Expand All Advertisement PDF DownloadLoading ...

Differences in CRP and De Ritis ratio predictive abilities of cancer specific survival between ethnic groups.

394 Background: Studies have discussed the prognostic use of C-reactive protein (CRP) and De Ritis ratio (AST/ALT or AAR) in the evaluation of renal malignant masses. Elevated pre-treatment CRP has been shown to be associated with non-cancer mortality. Additionally increased preoperative AAR has been found to be a prognostic factor for overall survival. With studies showing the ethnic disparities in mortality rate in certain underserved ethnic groups, there is a need for investigation into possible ethnic differences. Our aim is to evaluate the association between these elevated preoperative markers and all-cause mortality (ACM) and cancer specific mortality (CSM) among ethnic groups. Methods: Retrospective review of the International Marker Consortium for Renal Cancer (INMARC) was performed. Patients with renal malignancies who underwent partial or radical nephrectomy (PN, RN) were included. Patients were grouped according to ethnicity and African American (AA), White, Asian, and Hispanic ethnic groups were selected for descriptive, survival and multivariable analysis of outcomes. A Cox-regression multivariable analysis (MVA) was performed for each group. The primary outcome was overall survival and cancer specific survival from time of surgery to last follow-up, which was evaluated using Kaplan-Meyer Analysis (KMA). Results: A total of 4,810 patients were analyzed (627 AA, 2,344 White, 462 Hispanic, 1,094 Asian). Preoperative CRP and AAR were considered elevated if above 5 mg/L and 1.26, respectively. Descriptive analysis showed significant differences in age, diabetes mellitus status, hypertension status, tumor size, surgery type (PN vs. RN), preoperative CRP, preoperative AAR, ACM and CSM between ethnicities (p-value &lt;0.001). MVA revealed elevated CRP to be predictive of ACM in AA (p&lt;0.001, HR 2.830, 95% CI [1.728, 4.635]) and White (p&lt;0.001, HR 2.933, 95% CI [2.272, 3.785]) patients. Elevated AAR was only predictive for all ACM in Asian (p=0.004, HR 2.546, 95% CI [1.358, 4.775]) patients. MVA showed similar results for CSM with elevated CRP found to be a significant independent risk factor for CSM in AA (p&lt;0.001, HR 7.006, 95% CI [2.649, 18.531]) and White (p&lt;0.001, HR 3.391, 95% CI [2.403, 4.784]) patients while elevated AAR is a significant independent risk factor for all CSM in Asian (p=0.041, HR 2.374, 95% CI [1.034, 5.448]) patients. KMA revealed statistically significant impact of elevated CRP on ACM and CSM in AA, White, and Asian patients (p&lt;0.001). It also showed a statistically significant effect of elevated AAR in Asian patients (p&lt;0.001). Conclusions: CRP has broad utilities in prognostic abilities for non-Asian ethnic sub-cohorts. However, AAR has predictive abilities in Asian patients. These results show the importance of using different lab markers for preoperative assessment in renal masses and the need for further research in ethnic differences in clinical presentation.

Predictive Impact of Early Changes in Serum C-Reactive Protein Levels in Nivolumab Plus Ipilimumab Therapy for Metastatic Renal Cell Carcinoma.

Serum C-reactive protein (CRP) is reportedly associated with metastatic renal cell carcinoma (mRCC) activity. However, in the era of immune checkpoint inhibitors, the predictive value of CRP is unclear. In this study, we investigated the predictive impact of pretreatment CRP levels and early changes in CRP levels for the treatment of mRCC with nivolumab plus ipilimumab (NIVO-IPI) therapy. Forty-eight patients with mRCC treated with NIVO-IPI as a first-line therapy were retrospectively analyzed. First, patients were divided into 2 groups: initial CRP ≥ 1.0 mg/dL and < 1.0 mg/dL. Progression-free survival (PFS) was compared between the 2 groups. Second, based on the CRP change within the first 3 months of NIVO-IPI, patients were placed in the normal group (CRP remains < 1.0 mg/dL), normalized group (CRP decreased < 1.0 mg/dL), and non-normalized group (CRP remained or increased to ≥ 1.0 mg/dL). The predictive association between CRP change and PFS was evaluated. PFS was significantly lower in the high initial CRP group (n=24, 50%) compared to the normal CRP group (n=24, 50%) (median: 4.3 vs. 28.1 months, P=.03). As for the early CRP change, the normal (2.7 vs. 28.1, P=.0002) and normalized (2.7 vs. 11.0, P=.0094) groups showed significantly higher PFS, compared to the non-normalized group. Meanwhile, there was no significant difference between normal, and normalized groups (P=.51). The objective response rate was higher in the normal (57.1% vs. 18.7%, P=.015) and normalized (81.8 vs. 18.7%, P=.0008) groups, compared to the non-normalized group. Multivariate Cox regression analysis showed that normal [Hazard ratio (HR)=0.15, 95% Confidence interval (CI)=0.02-0.70, P=.026] and normalized (HR 0.21, 95% CI=0.05-0.73, P=.015) CRP showed significant association with PFS. In the NIVO-IPI therapy for mRCC, early changes in CRP could predict PFS. This data may be useful for the early detection of ineffective NIVO-IPI therapy and conversion to subsequent therapies.

Clinical efficacy of linagliptin combined with irbesartan in patients with diabetic nephropathy.

ABSTRACTObjective:To determine the clinical efficacy of linagliptin combined with irbesartan in patients with diabetic nephropathy (DN).Methods:Seventy-two patients who were admitted to our department of endocrinology in our hospital during January 2018 and June 2019 were randomly divided into a control group (administered with irbesartan only, n=36) and a treatment group (treated with irbesartan and linagliptin, n=36). The course of treatment lasted for three months. FBG (fasting blood glucose), 2hPBG (2h postprandial blood sugar), HbA1C (hemoglobin A1c), Cys-C (cystatin C), SCr (serum creatinine), BUN (blood urea nitrogen), UACR (urine albumin-to-creatinine ratio), CRP (C-reactive protein), IL-6 (interleukin-6), and SOD (superoxide dismutase) were tested pre- and post-treatment to evaluate the clinical efficacy and adverse effects of the two treatment plans after three months of treatment.Results:Compared with the pre-treatment levels, FBG, 2hPBG, HbA1c, Cys-C, SCr, BUN, UACR, CRP, IL-6, and SOD in both groups were significantly improved following the three-month treatment (P<0.05, respectively). Post-treatment levels of FBG, 2hPBG, HbA1c, Cys-C, SCr, BUN, UACR, CRP, and IL-6 in the treatment group were significantly lower than in the control group (P<0.05, respectively), while the treatment group exhibited a higher level of SOD compared with the control group (P<0.05). No serious adverse reaction occurred in either group (P>0.05).Conclusion:Combined-modality treatment with linagliptin and irbesartan shows favorable clinical efficacy in treating diabetic nephropathy as it effectively protects the kidneys and improves kidney function by inhibiting inflammatory and oxidative stress responses.

Pre-treatment inflammatory parameters predict survival from endometrial cancer: A prospective database analysis

PurposeInflammation predisposes to tumorigenesis by damaging DNA, stimulating angiogenesis and potentiating pro-proliferative and anti-apoptotic processes. The aim of this study was to investigate whether pre-treatment biomarkers of systemic inflammation are associated with survival outcomes in endometrial cancer. Patients and methodsWomen with endometrial cancer were recruited to a prospective database study. Pre-treatment systemic markers of inflammation, including C-reactive protein (CRP), Glasgow Prognostic Score and lymphocyte-based ratios [neutrophil-lymphocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII)], were analysed in relation to overall, endometrial cancer-specific and recurrence-free survival using Kaplan-Meier estimation and multivariable Cox regression. ResultsIn total, 522 women of mostly White British ethnicity, with a median age of 66 years (interquartile range (IQR), 56, 73) and BMI of 32 kg/m2 (IQR 26, 39) were included in the analysis. Most had low-grade (67.2%), early-stage (85.4% stage I/II), endometrioid (74.5%) tumors. Women with pre-treatment CRP ≥5.5 mg/L had a 68% increase in overall (adjusted HR = 1.68, 95% CI 1.00–2.81, p = 0.049) and a two-fold higher cancer-specific mortality risk than those with CRP <5.5 mg/L (adjusted HR = 2.04, 95%CI 1.03–4.02, p = 0.04). Absolute lymphocyte count, NLR, MLR and SII were associated with adverse clinico-pathologic factors, but not overall, cancer-specific or recurrence-free survival in the multivariable analysis. ConclusionIf confirmed in an independent cohort, CRP may offer a simple, low-cost test to refine pre-treatment risk assessment and guide personalised care in endometrial cancer. Our participants were mostly of White British ethnicity and further studies are needed to confirm the utility of CRP as a prognostic biomarker in other populations.

C-Reactive Protein and C-Reactive Protein-Based Scores to Predict Survival in Esophageal and Junctional Adenocarcinoma: Systematic Review and Meta-Analysis.

Esophageal adenocarcinoma (EAC) has a poor prognosis; predictive markers of prognosis would facilitate advances in personalized therapy. C-reactive protein (CRP) and CRP-based scores are increasingly recommended across oncology; however, their role and value in EAC is unclear. This systematic review and meta-analysis examined CRP cut-point and scores and how they may best be applied in predicting survival in EAC. A systematic literature search was conducted in EMBASE, Medline, Web of Science, Cochrane, Scopus and CINAHL databases, from inception to 1st October 2020. Studies reporting data from adults with EAC including adenocarcinoma of the gastro-esophageal junction (AEG), pre-treatment CRP or CRP-based score and Hazard Ratio (HR) for survival were included. QUIPS tool assessed risk of bias. Meta-analysis was undertaken. A total of 819 records were screened. Eight papers were included, with data for 1475 people. CRP cut-points ranged from 2.8 to 10 mg/L. The Glasgow Prognostic Score (GPS) and modified GPS were the most commonly reported scores. On meta-analysis, elevated preoperative GPS/mGPS was significantly associated with worse overall survival (hazards ratio [HR] 1.81, 95% confidence interval [CI] 1.25-2.62, p = 0.002); results were similar in subgroup analyses of multimodal treatment, M0 disease, and R0 resection. This is the first review to evaluate comprehensively the evidence for CRP and CRP-based scores in EAC. Meta-analysis demonstrated that elevated preoperative GPS or mGPS was significantly associated with reduced overall survival in EAC, including AEG. There is insufficient evidence to support use of CRP alone. Future studies should examine GPS/mGPS in EAC prospectively, alone and combined with other prognostic markers.

Pre-Treatment C-Reactive Protein Predicts Survival in Small Cell Lung Cancer Patients

Improved prognostication of small cell lung cancer (SCLC) patients could strengthen the treatment strategy and, thereby, potentially improve the overall survival (OS) of these patients. C-reactive protein (CRP) has been proposed as a prognostic indicator of inferior survival, although so far, only based on data from smaller studies. Data on SCLC patients diagnosed from January 2009 to June 2018 were extracted from the Danish Lung Cancer Registry and the clinical laboratory information system. CRP measurements were divided at the clinical cut-off value of 8 mg/L or 75 nmol/L) and stratified into quartiles. Cox proportional hazards model assessed the prognostic value of the CRP level. C-statistics further evaluated the biomarker’s prognostic value. In total, 923 patients were included. A pre-treatment CRP level above the clinical cut-off significantly correlated to inferior OS (adjusted hazard ratio (HR) = 1.25 (95% confidence interval (CI): 1.08–1.46). When divided into quartiles, a level-dependent correlation was observed with only the highest quartiles significantly associated with OS (3rd quartile: adjusted HR = 1.26 (95% CI: 1.03–1.55) 4th quartile: adjusted HR = 1.44 (95% CI: 1.17–1.77)). Adding CRP level to already well-established prognostic factors improved the prognostication of SCLC patients. In conclusion, high pre-treatment CRP level is an independent prognostic factor in SCLC patients.

Prognostic Value of C-Reactive Protein, Glasgow Prognostic Score, and C-Reactive Protein-to-Albumin Ratio in Colorectal Cancer.

Background: Emerging evidence suggests that inflammatory response biomarkers are predictive factors that can improve the accuracy of colorectal cancer (CRC) prognoses. We aimed to evaluate the prognostic significance of C-reactive protein (CRP), the Glasgow Prognostic Score (GPS), and the CRP-to-albumin ratio (CAR) in CRC.Methods: Overall, 307 stage I–III CRC patients and 72 colorectal liver metastases (CRLM) patients were enrolled between October 2013 and September 2019. We investigated the correlation between the pretreatment CRP, GPS, and CAR and the clinicopathological characteristics. The Cox proportional hazards model was used for univariate or multivariate analysis to assess potential prognostic factors. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value of each prognostic score. We established CRC survival nomograms based on the prognostic scores of inflammation.Results: The optimal cutoff levels for the CAR for overall survival (OS) in all CRC patients, stage I–III CRC patients, and CRLM patients were 0.16, 0.14, and 0.25, respectively. Kaplan–Meier analysis and log-rank tests demonstrated that patients with high CRP, CAR, and GPS had poorer OS in CRC, both in the cohorts of stage I–III patients and CRLM patients. In the different cohorts of CRC patients, the area under the ROC curve (AUC) of these three markers were all high. Multivariate analysis indicated that the location of the primary tumor, pathological differentiation, and pretreatment carcinoembryonic antigen (CEA), CRP, GPS, and CAR were independent prognostic factors for OS in stage I–III patients and that CRP, GPS, and CAR were independent prognostic factors for OS in CRLM patients. The predictors in the prediction nomograms included the pretreatment CRP, GPS, and CAR.Conclusions: CRP, GPS, and CAR have independent prognostic values in patients with CRC. Furthermore, the survival nomograms based on CRP, GPS, and CAR can provide more valuable clinical significance.

Plasma matrix metalloproteinase-9 level change with omalizumab treatment in chronic spontaneous urticaria.

Matrix metalloproteinase-9 (MMP-9) is an enzyme that contributes to inflammation and tissue remodelling. In chronic urticaria, increased plasma levels of MMP-9 and its correlation with disease severity have been shown in several studies, suggesting that MMP-9 could be used to evaluate the effects of new treatments. We aimed to compare MMP-9 levels in chronic urticaria patients with those of healthy patients. Then we planned to investigate the changes in plasma MMP-9 levels with chronic urticaria treatment, the role of this enzyme in demonstrating the efficacy of treatment, and its correlation with C-reactive protein (CRP). Forty-one patients with chronic urticaria who were scheduled for omalizumab treatment and 41 sex- and age-matched healthy volunteers were included in the study. In the patient group, before treatment and at the end of the 12th week, the urticaria activity score used for 7 consecutive days (UAS7) was calculated, and the MMP-9 and CRP levels were measured. Plasma MMP-9 levels were measured from venous blood in the control group. The plasma MMP-9 levels of the patients before treatment were significantly higher than those of the control group (P<.01). In the patient group, there was no significant relationship between the UAS7 score and the MMP-9 and CRP levels before treatment. The UAS7 values were 28±7 before omalizumab treatment and 5±6 at the end of the 12th week (P<.0001). The post-treatment MMP-9 levels (1818±297pg/mL) were higher compared with the pre-treatment values (1617±380) (P<.05). The post-treatment CRP levels of the patients (2.41±2.17mg/L) were lower than their pre-treatment CRP levels (8.20±19.70) (P<.05). MMP-9 levels were not associated with the severity of disease, and MMP-9 levels were not decreased with treatment response. Therefore, MMP-9 cannot be used as a parameter of disease activity in chronic urticaria or to evaluate the efficacy of new treatments.

Differences and similarities in clinical and functional responses among patients receiving tofacitinib monotherapy, tofacitinib plus methotrexate, and adalimumab plus methotrexate: a post hoc analysis of data from ORAL Strategy

BackgroundThis post hoc analysis assessed clinical and functional responses to tofacitinib monotherapy, tofacitinib + methotrexate (MTX), and adalimumab + MTX, in patients with rheumatoid arthritis enrolled in the ORAL Strategy study, including evaluation of patient-level data using cumulative probability plots.MethodsIn the 12-month, phase IIIb/IV ORAL Strategy study, patients with rheumatoid arthritis and an inadequate response to MTX were randomized to receive tofacitinib 5 mg twice daily (BID), tofacitinib 5 mg BID + MTX, or adalimumab 40 mg every other week + MTX. In this post hoc analysis, cumulative probability plots were generated for mean percent change from baseline (%∆) in the Clinical Disease Activity Index (CDAI; clinical response) and mean change from baseline (∆) in the Health Assessment Questionnaire-Disability Index (HAQ-DI; functional response) at month 12. Median C-reactive protein (CRP) levels by time period were summarized by CDAI remission (≤ 2.8) status at months 6 and 12.ResultsData for 1146 patients were analyzed. At month 12, cumulative probability plots for %∆CDAI and ∆HAQ-DI were similar across treatments in patients with greater response. At lower levels of response, patients receiving tofacitinib monotherapy did not respond as well as those receiving combination therapies. With tofacitinib + MTX, numerically higher baseline CRP levels and numerically larger post-baseline CRP reductions were seen in patients achieving CDAI remission at months 6 and 12 vs those who did not.ConclusionsThese results suggest that patients with a greater response did well, irrespective of which therapy they received. Patients with lesser response had better outcomes with combination therapies vs tofacitinib monotherapy, suggesting they benefitted from MTX. High pre-treatment CRP levels may be associated with better response to tofacitinib + MTX.Trial registrationClinicalTrials.gov, NCT02187055. Registered on 08 July 2014.

Can Pre-Treatment Inflammatory Parameters Predict the Probability of Sphincter-Preserving Surgery in Patients with Locally Advanced Low-Lying Rectal Cancer?

There is evidence suggesting that pre-treatment clinical parameters can predict the probability of sphincter-preserving surgery in rectal cancer; however, to date, data on the predictive role of inflammatory parameters on the sphincter-preservation rate are not available. The aim of the present cohort study was to investigate the association between inflammation-based parameters and the sphincter-preserving surgery rate in patients with low-lying locally advanced rectal cancer (LARC). A total of 848 patients with LARC undergoing radiotherapy from 2004 to 2019 were retrospectively reviewed in order to identify patients with rectal cancer localized ≤6 cm from the anal verge, treated with neo-adjuvant radiochemotherapy (nRCT) and subsequent surgery. Univariable and multivariable analyses were used to investigate the role of pre-treatment inflammatory parameters, including the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for the prediction of sphincter preservation. A total of 363 patients met the inclusion criteria; among them, 210 patients (57.9%) underwent sphincter-preserving surgery, and in 153 patients (42.1%), an abdominoperineal rectum resection was performed. Univariable analysis showed a significant association of the pre-treatment CRP value (OR = 2.548, 95% CI: 1.584–4.097, p < 0.001) with sphincter preservation, whereas the pre-treatment NLR (OR = 1.098, 95% CI: 0.976–1.235, p = 0.120) and PLR (OR = 1.002, 95% CI: 1.000–1.005, p = 0.062) were not significantly associated with the type of surgery. In multivariable analysis, the pre-treatment CRP value (OR = 2.544; 95% CI: 1.314–4.926; p = 0.006) was identified as an independent predictive factor for sphincter-preserving surgery. The findings of the present study suggest that the pre-treatment CRP value represents an independent parameter predicting the probability of sphincter-preserving surgery in patients with low-lying LARC.

Preoperative Elevation of C-Reactive Protein Is a Predictor for Adverse Oncologic Survival Outcomes for Renal Cell Carcinoma: Analysis from the International Marker Consortium Renal Cancer (INMARC).

We sought to analyze the usefulness of pretreatment C-reactive protein (CRP) as a predictor of survival and oncological outcomes in patients with renal cell carcinoma (RCC). Retrospective international analysis of patients with RCC with pretreatment CRP values from 2006 to 2017. A CRP of more than >5 mg/L was deemed elevated. The cohort was subdivided into 2 groups for analysis (normal CRP ≤5 mg/L; elevated CRP >5). Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Kaplan-Meier analyses (KMA) and multivariable analyses (MVA) were used to delineate survival outcomes and their predictors. We analyzed 2445 patients (1641 male/804 female; normal CRP 1056/elevated CRP 1389; mean follow-up 36 months). Patients with elevated CRP had a higher incidence of hypertension (P=.001), higher body mass index (P < .001), and larger tumor size (6.0 cm vs 3.9 cm; P < .001). MVA for RFS demonstrated elevated CRP (hazard ratio [HR], 1.85; P=.005), tumor size (HR, 1.1; P < .001), and high tumor grade (HR, 3.1; P < .001) to be independent risk factors. For normal vs elevated CRP, KMA for RFS of stages 1-4 RCC revealed a 5-year RFS of 93% vs 88% (P=.001), 95% vs 83% (P=.163), 84% vs 62% (P=.001), and 58% vs 60% (P=.513), respectively. KMA MA KMA for OS of stages 1-4 RCC revealed a 5-year OS of 98% vs 81% (P=.001), 94% vs 80% (P=.103), 94% vs 65% (P=.001), and 99% vs 38% (P < .001), respectively. Pretreatment CRP was an independent predictor of RFS and OS in an international multicenter cohort of patients with RCC.