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Objective To investigate the clinical value of C-reactive protein/albumin ratio (CAR) in determining spontaneous bacterial peritonitis (SBP) in patients with alcoholic cirrhosis (ALC). Methods A retrospective analysis was performed for 329 ALC patients with SBP who were hospitalized in Beijing Ditan Hospital, Capital Medical University, from August 2020 to February 2022, and according to the presence or absence of SBP on admission, they were divided into non-SBP group with 246 patients and SBP group with 83 patients. The two groups were compared in terms of sex, age, comorbidities, complications, blood routine, liver and renal function, blood lipids, and coagulation markers. The independent-samples t test was used for comparison of normally distributed quantitative data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed quantitative data between two groups; the chi-square test was used for comparison of qualitative data between two groups. A multivariate binary logistic regression analysis was used to identify the risk factors for SBP. The receiver operating characteristic (ROC) curve was plotted for CAR to calculate the area under the ROC curve (AUC), the optimal cut-off value, and 95% confidence interval (CI). Results Compared with the non-SBP patients, the SBP patients had significantly higher inflammatory indicators (WBC, neutrophils, NLR, monocytes, C-reactive protein, and CAR), significantly higher aspartate aminotransferase, total bilirubin, international normalized ratio, and MELD score, and significantly lower levels of albumin and high-density lipoprotein (all P＜0.05). The multivariate logistic regression analysis showed that CAR (odds ratio [OR]=20.628, 95%CI: 6.720-74.052, P＜0.01) and red blood cell count (OR=0.600, 95%CI: 0.381-0.932, P=0.025) were independent risk factors for determining SBP in ALC patients. CAR had a significantly larger AUC than NLR and WBC (0.825 vs 0.725/0.651) and an optimal cut-off value of 0.324. The patients were divided into high-risk group and low-risk group, and the analysis showed that the high-risk group had a significantly higher proportion of patients with SBP than the low-risk group [63.2% (55/87) vs 11.6% (28/242), χ²=90.495, P＜0.01]. Conclusion CAR is a good marker for determining SBP in patients with ALC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the clinical value of high mobility group box-1 (HMGB-1), C-reactive protein (CRP), procalcitonin (PCT), and CRP to albumin (Alb) ratio in the diagnosis and evaluation of the severity of sepsis in children. PATIENTS AND METHODS: A total of 90 children, 50 with sepsis and 40 with general infection, whose symptoms did not meet the criteria for diagnosis of sepsis, were admitted to the Pediatrics Department of Jingzhou Central Hospital in Hubei Province between November 2021 and December 2022, were enrolled and selected as experimental and control group, respectively. The serum of two groups was collected within 24 hours after admission, the levels of HMGB-1 were detected by enzyme-linked immunosorbent assay (ELISA), and CRP, PCT, Alb, and hospitalization days were recorded. The differences in indicators between the two groups were compared, and correlation analysis was performed between hospitalization days and various indicators. The receiver operating characteristic (ROC) curve was drawn to evaluate the independent or combined value of CRP, PCT, HMGB-1, and CRP/Alb ratio in the early diagnosis of sepsis in children. RESULTS: These four indicators of children with sepsis were significantly higher than those in the general infection group (all p=0.000). The levels of CRP, PCT and CRP/Alb ratio were significantly positively correlated with the hospitalization days (r=0.329, 0.333, 0.329; p=0.02, 0.01, 0.002). The area under curve (AUC) of CRP, PCT, HMGB-1, and CRP/Alb ratio for the diagnosis of sepsis in children was 0.798, 0.817, 0.838, 0.809, respectively, and that of the combination of four indicators was 0.952. CONCLUSIONS: CRP, PCT, HMGB-1, and CRP/Alb ratio resulted as effective indicators for early diagnosis and evaluation of childhood sepsis, having a higher value in combined diagnosis. [ABSTRACT FROM AUTHOR]

Background: Many studies have investigated the prognostic role of the C-reactive protein/albumin ratio (CRP/Alb ratio) in patients with gynecological cancers; however, there is lack of consensus owing to conflicting results across studies. We performed a meta-analysis to determine the prognostic role of the CRP/Alb ratio in gynecological cancers. Methods: We searched the PubMed, Embase, the Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases since inception to April 2021. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the prognostic effect of the CRP/Alb ratio in gynecological cancers. Pooled odds ratios (ORs) and 95% CIs were used to investigate the association between the CRP/Alb ratio and clinicopathological features. Results: The meta-analysis included seven studies with 1,847 patients. The pooled results showed that a high pretreatment CRP/Alb ratio was associated with poor overall survival (HR, 1.84; 95% CI, 1.41–2.40; p < 0.001) and progression-/disease-free survival (HR, 2.58; 95% CI, 1.42–4.68; p = 0.002). Additionally, a high CRP/Alb ratio was significantly associated with stages III–IV disease (the International Federation of Gynecology and Obstetrics classification) (OR, 2.98; 95% CI, 1.45–6.14; p = 0.003). However, we observed a non-significant correlation between the CRP/Alb ratio and lymph node metastasis, tumor size, and histopathological grade. Conclusions: The CRP/Alb ratio is a convenient and accurate predictor of survival outcomes in gynecological cancers. A high CRP/Alb ratio also predicts tumor progression. [ABSTRACT FROM AUTHOR]

BackgroundMany studies have investigated the prognostic role of the C-reactive protein/albumin ratio (CRP/Alb ratio) in patients with gynecological cancers; however, there is lack of consensus owing to conflicting results across studies. We performed a meta-analysis to determine the prognostic role of the CRP/Alb ratio in gynecological cancers.MethodsWe searched the PubMed, Embase, the Web of Science, Cochrane Library, China National Knowledge Infrastructure, and Wanfang electronic databases since inception to April 2021. Combined hazard ratios (HRs) and 95% confidence intervals (CIs) were used to estimate the prognostic effect of the CRP/Alb ratio in gynecological cancers. Pooled odds ratios (ORs) and 95% CIs were used to investigate the association between the CRP/Alb ratio and clinicopathological features.ResultsThe meta-analysis included seven studies with 1,847 patients. The pooled results showed that a high pretreatment CRP/Alb ratio was associated with poor overall survival (HR, 1.84; 95% CI, 1.41–2.40; p < 0.001) and progression-/disease-free survival (HR, 2.58; 95% CI, 1.42–4.68; p = 0.002). Additionally, a high CRP/Alb ratio was significantly associated with stages III–IV disease (the International Federation of Gynecology and Obstetrics classification) (OR, 2.98; 95% CI, 1.45–6.14; p = 0.003). However, we observed a non-significant correlation between the CRP/Alb ratio and lymph node metastasis, tumor size, and histopathological grade.ConclusionsThe CRP/Alb ratio is a convenient and accurate predictor of survival outcomes in gynecological cancers. A high CRP/Alb ratio also predicts tumor progression.

Zhiyao Fan,1–4,* Kun Fan,1–4,* Yitao Gong,1–4,* Qiuyi Huang,1–4 Chao Yang,1–4 He Cheng,1–4 Kaizhou Jin,1–4 Quanxing Ni,1–4 Xianjun Yu,1–4 Guopei Luo,1–4 Chen Liu1–4 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Pancreatic Cancer Institute, Shanghai, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Guopei Luo; Chen LiuDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, People’s Republic of ChinaTel +86-21-6403-1446Fax +86-21-6403-1446Email luoguopei@fudanpci.org; liuchen@fudanpci.orgPurpose: The CRP/albumin (Alb) ratio, a recently reported predictor, has shown value for prognosis in various human cancers. This study aimed to determine the prognostic value of baseline CRP/Alb and to explore the relevance between postchemotherapy CRP/Alb and the efficacy of chemotherapy in advanced pancreatic cancer patients.Patients and methods: Five hundred and ninety-five patients diagnosed with locally advanced or metastatic adenocarcinoma of the pancreas were enrolled. Cut-off Finder was used to calculate the best cut‑off value for baseline CRP/Alb. The primary endpoint was overall survival, which was analyzed by Kaplan-Meier survival curves with 95% confidence intervals. The log rank test and Cox proportional hazard model were used to evaluate the univariate and multivariate analyses.Results: The optimal cut-off value for baseline CRP/Alb was determined to be 0.18. Both the baseline CRP/Alb (CRP/Alb≥0.18 vs. CRP/Alb

Background: The C-reactive protein (CRP)-toserum albumin ratio is associated with a poor prognosis in patients with several cancers. The purpose of this study was to clarify the relationship between the preoperative CRP/Alb ratio and overall survival of pancreatic ductal adenocarcinoma (PDAC) in patients who received radical surgery and S-1 adjuvant chemotherapy. Patients and Methods: We included 117 patients who underwent radical surgery with S-1 adjuvant chemotherapy. We constructed receiver operating characteristic curve (ROC curve) of the CRP/Alb ratio to determine the cut-off value. We analyzed the relationship among the CRP/Alb ratio, clinicopathological status, and survival. Results: The optimal cut-off value of the CRP/Alb ratio was 0.036. All patients were divided into a high-ratio group (CRP/Alb ratio ≥0.036) and low-ratio group (CRP/Alb ratio <0.036). The 5-year overall survival (OS) rates in the high- and low-ratio groups were 22.5% and 36.4%, respectively (p=0.0089). The 5-year disease-free survival (DFS) rates in the high- and low-ratio groups were 12.5% and 22.1%, respectively (p=0.0097). The univariate and multivariate analyses of the OS showed that the pathological N factor and CRP/Alb ratio were independent factors of the survival. The univariate and multivariate analyses of the RFS showed that the pathological N factor, resection margin, and CRP/Alb ratio were independent factors of the survival. Conclusion: The preoperative CRP/Alb ratio is a strong prognostic factor for PDAC patients with undergo curative resection with S-1 adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Yong-Jiang Li, Xi Yang, Wen-Biao Zhang, Cheng Yi, Feng Wang, Ping Li Department of Oncology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte–monocyte ratio (LMR), and neutrophil–platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. Keywords: Ewing sarcoma, inflammatory biomarkers, prognosis, survival, CRP/Alb ratio

Objective and Background: Survival predictions by subjective evaluations are important for end-stage patients. However, subjective evaluations based on experience are difficult. Therefore, we investigated whether the Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and C-reactive protein (CRP)/albumin ratio (CRP/Alb ratio) calculated from the laboratory values of objective evaluations are useful for predicting survival times in end-stage patients. Methods: We retrospectively investigated the age, sex, death cause, CRP levels, Alb levels, and lymphocyte counts in 363 cancer and noncancer patients who died in the 12-month period between April 2015 and March 2016. A multivariate analysis was performed to calculate GPS, PNI, and the CRP/Alb ratio from laboratory values and adjusted for confounding factors. Results: PNI and CRP/Alb ratio exhibited negative and positive correlations with survival days, respectively. All GPS, PNI, and CRP/Alb ratio were useful to predict two to four remaining weeks. Interestingly, CRP/Alb ratio, but not GPS or PNI, was higher in patients with predicted short-term survival of zero to two weeks than in that of two to four weeks (odds ratio 2.32; 95% confidence interval 1.61–3.34). Discussion: These results suggest that the CRP/Alb ratio is an independent factor that is beneficial to predict short-term survival of within two weeks. [ABSTRACT FROM AUTHOR]

Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), Glasgow Prognostic Score (GPS), C-reactive protein to albumin ratio (CRP/Alb ratio), lymphocyte-monocyte ratio (LMR), and neutrophil-platelet score (NPS), were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC) analysis was generated to determine optimal cutoff values; areas under the curves (AUCs) were assessed to show the discriminatory ability of the biomarkers; Kaplan-Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005), GPS (HR 2.27, P=0.006), NLR (HR 2.07, P=0.013), and PLR (HR 1.85, P=0.032) were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and NPS may not be suitable as prognostic indicators in Ewing sarcoma. [ABSTRACT FROM AUTHOR]

• CRP/Alb ratio and CRP/Fib ratio are significantly higher in PJI. • CRP/Alb ratio and the CRP/Fib ratio had the highest sensitivity in PJI. • CRP/Alb ratio and the CRP/Fib ratio may be important predictors in PJI. Testing for systemic inflammation markers is considered a simpler method for diagnosing periprosthetic joint infection (PJI). Changes in the C-reactive protein/albumin ratio (CRP/Alb ratio) and C-reactive protein/fibrinogen ratio (CRP/Fib ratio) are associated with PJI. This study aimed to evaluate the application of CRP/Alb and CRP/Fib ratios as novel inflammation-based markers for the diagnosis of PJI. We retrospectively evaluated 445 patients who underwent total hip and knee revision arthroplasties between January 2010 and February 2021. Of these, 129 patients were also independently evaluated for PJI with coagulation-related comorbidities. The patients were divided into two groups: the aseptic revision (268 patients) and PJI revision groups (187 patients). Subsequently, we evaluated the diagnostic value of the CRP/Alb and CRP/Fib ratios compared to other inflammation-based diagnoses using the area under the curve (AUC) values. The AUC values of the CRP/Alb and CRP/Fib ratios were 0.880 and 0.872, respectively, suggesting similar diagnostic potentials for PJI. The CRP/Alb and CRP/Fib ratios were better than the erythrocyte sedimentation rate (ESR), Alb, and Fib, whose AUC values were 0.765, 0.352, and 0.730, respectively, for the diagnosis of PJI. The optimal cut-off for the CRP/Alb ratio was 0.13, with good sensitivity (85.0%) and specificity (78.4%). The optimal cut-off CRP/Fib ratio was 2.04, with good sensitivity (81.3%) and specificity (80.6%). Notably, the CRP/Alb and CRP/Fib ratios had the highest sensitivity, followed by four conventional inflammatory markers, namely, CRP, ESR, Alb, and Fib, which had sensitivities of 80.2%, 67.4%, 50.8%, and 54.0%, respectively. Similar findings were observed in patients with coagulation-related comorbidities. Both the CRP/Alb and CRP/Fib ratios were significantly higher in patients with PJI than in those with aseptic failure and showed better sensitivity and specificity for diagnosing PJI than classical inflammatory markers. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in cancer. However, the role of the CRP/Alb ratio in advanced pancreatic cancer (PC) has not been examined. A retrospective study of 233 patients with advanced PC was conducted. We investigated the relationship between the CRP/Alb ratio, clinicopathological variables, and overall survival (OS). The optimal cutoff point of the CRP/Alb ratio was 0.54. A higher CRP/Alb ratio was significantly associated with an elevated neutrophil-lymphocyte ratio (NLR) ( P < 0.001) and higher modified Glasgow prognostic score (mGPS) ( P < 0.001). Using univariate analyses, we found that the age ( P = 0.009), disease stage ( P < 0.001), NLR ( P < 0.001), mGPS ( P < 0.001), and CRP/Alb ratio ( P < 0.001) were significant predictors of OS. Patients with a higher CRP/Alb ratio had a worse OS than patients with a lower CRP/Alb ratio (hazard ratio (HR) 3.619; 95 % CI 2.681-4.886; P < 0.001). However, the CRP/Alb ratio was identified as the only inflammation-based parameter with an independent prognostic ability in the multivariate analyses ( P < 0.001). The pretreatment CRP/Alb ratio is a superior prognostic and therapeutic predictor of OS in advanced PC. [ABSTRACT FROM AUTHOR]

Objective: The present study aimed to investigate the impact of preoperative C-reactive protein to albumin (CRP/Alb) ratio on the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC)., Methods: 82 patients who underwent hepatic resection for mass-forming type of ICC were evaluated. The relationship between preoperative CRP/Alb ratio and survival outcomes was investigated., Results: The optimal cutoff value of CRP/Alb ratio for assessing overall survival (OS) was determined as 0.089. Univariate analysis for recurrence-free survival (RFS) showed that CRP/Alb ratio >0.089, carbohydrate antigen 19-9 (CA 19-9) >37 U/mL, lymph node metastasis, vascular invasion, and multiple tumors were significantly associated with postoperative recurrence. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.006), and multiple tumors (p < 0.001). Univariate analysis for OS showed that CRP/Alb ratio >0.089, CA 19-9 >37 U/mL, lymph node metastasis, vascular invasion, multiple tumors, and positive surgical margin were significantly associated with overall death. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.01), and multiple tumors (p = 0.005)., Conclusion: Preoperative CRP/Alb ratio may predict poor long-term outcomes after hepatic resection in patients with ICC., .

Background: The C-reactive protein (CRP)-to-serum albumin ratio is associated with a poor prognosis in patients with several cancers. The purpose of this study was to clarify the relationship between the preoperative CRP/Alb ratio and overall survival of pancreatic ductal adenocarcinoma (PDAC) in patients who received radical surgery and S-1 adjuvant chemotherapy., Patients and Methods: We included 117 patients who underwent radical surgery with S-1 adjuvant chemotherapy. We constructed receiver operating characteristic curve (ROC curve) of the CRP/Alb ratio to determine the cut-off value. We analyzed the relationship among the CRP/Alb ratio, clinicopathological status, and survival., Results: The optimal cut-off value of the CRP/Alb ratio was 0.036. All patients were divided into a high-ratio group (CRP/Alb ratio ≥0.036) and low-ratio group (CRP/Alb ratio <0.036). The 5-year overall survival (OS) rates in the high- and low-ratio groups were 22.5% and 36.4%, respectively (p=0.0089). The 5-year disease-free survival (DFS) rates in the high- and low-ratio groups were 12.5% and 22.1%, respectively (p=0.0097). The univariate and multivariate analyses of the OS showed that the pathological N factor and CRP/Alb ratio were independent factors of the survival. The univariate and multivariate analyses of the RFS showed that the pathological N factor, resection margin, and CRP/Alb ratio were independent factors of the survival., Conclusion: The preoperative CRP/Alb ratio is a strong prognostic factor for PDAC patients with undergo curative resection with S-1 adjuvant chemotherapy., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Introduction: The C-reactive protein to albumin ratio (CAR) has been shown to provide prognostic information in several cancers. The objective in the study is to examine the prognostic value of CAR in patients with RCC who underwent nephrectomy.Material and Methods: The record data from multi-institutional study of 1,028 patients was analyzed in the study. The cut-off value of the CAR was defined by receive operating characteristic (ROC) analysis. Overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) were evaluated, and univariate and multivariate analyses were conducted to assess the predictive value of the variables including CAR.Result: The optimal cut-off value of 0.073 in CAR was defined according to the ROC analysis. The AUC in CAR for CSS was greater than that of NLR and PLR, and that for RFS was also greater than GPS and mGPS. Multivariate analysis demonstrated that the CAR was an independent prognostic factor for OS (P < 0.001), CSS (P < 0.001) in total cohort and RFS (P = 0.029) in nonmetastatic cohort.Conclusion: The findings of the present study suggested that the preoperative CAR is an independent prognostic indicator of OS, CSS and RFS for patients with RCC. Since CAR can be assessed prior to surgery, clinicians should this take into account for the treatment decision making. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in cancer. However, the role of the CRP/Alb ratio in advanced pancreatic cancer (PC) has not been examined. A retrospective study of 233 patients with advanced PC was conducted. We investigated the relationship between the CRP/Alb ratio, clinicopathological variables, and overall survival (OS). The optimal cutoff point of the CRP/Alb ratio was 0.54. A higher CRP/Alb ratio was significantly associated with an elevated neutrophil-lymphocyte ratio (NLR) (P < 0.001) and higher modified Glasgow prognostic score (mGPS) (P < 0.001). Using univariate analyses, we found that the age (P = 0.009), disease stage (P < 0.001), NLR (P < 0.001), mGPS (P < 0.001), and CRP/Alb ratio (P < 0.001) were significant predictors of OS. Patients with a higher CRP/Alb ratio had a worse OS than patients with a lower CRP/Alb ratio (hazard ratio (HR) 3.619; 95 % CI 2.681-4.886; P < 0.001). However, the CRP/Alb ratio was identified as the only inflammation-based parameter with an independent prognostic ability in the multivariate analyses (P < 0.001). The pretreatment CRP/Alb ratio is a superior prognostic and therapeutic predictor of OS in advanced PC., Competing Interests: Compliance with ethical standards Ethics The study protocol was approved by the ethics committee of Southern Medical University, and written informed consent for the utilization of clinical data was obtained from all enrolled patients. Conflicts of interest None