Biomarkers of Inflammation and Progression During Immunotherapy in Patients With Metastatic Renal Cell Carcinoma.

BACKGROUND/AIM: Biomarkers that would identify patients unlikely to respond to immunotherapy with immune checkpoint inhibitors (ICIs) remain an unmet medical need. PATIENTS AND METHODS: In the present study, we have retrospectively evaluated the association between biomarkers of immune activation and outcome in metastatic renal cell carcinoma (mRCC) patients treated with ICIs. The laboratory and clinical data of 79 consecutive patients with histologically confirmed mRCC treated with ICI-based immunotherapy have been analyzed. RESULTS: Patients who progressed or died at 4 months had higher prognostic score, higher serum C-reactive protein (CRP) and neopterin, and urinary neopterin, and lower serum albumin and hemoglobin concentration. CONCLUSION: Biomarkers of activation of immune response, in particular serum neopterin/creatinine ratio, are associated with outcome in mRCC patients treated with ICI immunotherapy.

Serum IL-6 in combination with synovial IL-6/CRP shows excellent diagnostic power to detect hip and knee prosthetic joint infection.

BACKGROUND: The diagnosis of prosthetic joint infection (PJI) is still a challenge in some patients after total joint replacement. Interleukin-6 (IL-6) strongly participates in the arrangement of the host-bacteria response. Therefore, increased levels of IL-6 should accompany every PJI. PURPOSE: The aim of the study was to show diagnostic characteristics of serum IL-6 for the diagnosis of prosthetic joint infection (PJI). We also compared the diagnostic values of serum IL-6 with synovial IL-6 (sIL-6) and synovial C-reactive protein (sCRP). STUDY DESIGN: We performed a prospective study of 240 patients in whom serum IL-6 was determined before total hip (n = 124) or knee (n = 116) reoperations. The PJI diagnosis was based on the MSIS (Musculoskeletal Infection Society) criteria (2011). Receiver operating characteristic plots were constructed for IL-6, sIL-6, and sCRP. RESULTS: PJI was diagnosed in 93 patients, and aseptic revision was diagnosed in 147 patients. The AUC (area under curve) for IL-6 was 0.938 (95% CI; 0.904-0.971). The optimal IL-6 cut-off value for PJI was 12.55 ng/L. Positive and negative likelihood ratios for IL-6 were 8.24 (95% CI; 4.79-14.17) and 0.15 (95% CI; 0.09-0.26), respectively. The optimal sIL-6 and sCRP cut-off values were 20,988 ng/L and 8.80 mg/L, respectively. Positive and negative likelihood ratios for sIL-6 were 40.000 (95% CI; 5.7-280.5) and 0.170 (95% CI; 0.07-0.417), respectively. Negative likelihood ratio for sCRP was 0.083 (95% CI; 0.022-0.314). CONCLUSIONS: The present study identified the cut-off values for serum/synovial IL-6 and synovial CRP for diagnostics of PJI at the site of THA and TKA and separately for each site. The diagnostic odds ratio for serum/synovial IL-6 and synovial CRP is very good. Simultaneous positivity of serum IL-6 either with synovial IL-6 or synovial CRP almost excludes false negative detection of PJI at the site of interest.

The role of nCD64 in the diagnosis of neonatal sepsis in preterm newborns.

BACKGROUND: Diagnosing neonatal sepsis is difficult, particularly in preterm newborns. A promising method appears to be evaluation of cell surface markers by flow cytometry. METHODS: This prospective study investigated 217 newborns suspected of having early- or late-onset neonatal sepsis. In all, flow cytometry was used to determine the proportion of CD64-positive neutrophils (nCD64). Based on the clinical course and laboratory test results, newborns were categorized as having proven, possible, clinical or no neonatal sepsis. Subsequently, associations between the categories and nCD64 values were analyzed. RESULTS: There were significant associations between nCD64 values and the development of sepsis in newborns with both early- or late-onset sepsis. CONCLUSION: nCD64expression is significantly elevated in preterm newborn with early and late onset sepsis. The results show that nCD64 is a reliable marker for diagnosing neonatal sepsis.

Excellent AUC for joint fluid cytology in the detection/exclusion of hip and knee prosthetic joint infection.

BACKGROUND AND AIM: The aim of this study was to evaluate the characteristics of synovial fluid (SF) white cell count (SWCC) and neutrophil/lymphocyte percentage in the diagnosis of prosthetic joint infection (PJI) for particular threshold values. METHODS AND RESULTS: This was a prospective study of 391 patients in whom SF specimens were collected before total joint replacement revisions. SF was aspirated before joint capsule incision. The PJI diagnosis was based only on non-SF data. Receiver operating characteristic plots were constructed for the SWCC and differential counts of leukocytes in aspirated fluid. Logistic binomic regression was used to distinguish infected and non-infected cases in the combined data. PJI was diagnosed in 78 patients, and aseptic revision in 313 patients. The areas (AUC) under the curve for the SWCC, the neutrophil and lymphocyte percentages were 0.974, 0.962, and 0.951, respectively. The optimal cut-off for PJI was 3,450 cells/µL, 74.6% neutrophils, and 14.6% lymphocytes. Positive likelihood ratios for the SWCC, neutrophil and lymphocyte percentages were 19.0, 10.4, and 9.5, respectively. Negative likelihood ratios for the SWCC, neutrophil and lymphocyte percentages were 0.06, 0.076, and 0.092, respectively. CONCLUSIONS: Based on AUC, the present study identified cut-off values for the SWCC and differential leukocyte count for the diagnosis of PJI. The likelihood ratio for positive/negative SWCCs can significantly change the pre-test probability of PJI.

Prognostic Significance of Serum and Urinary Neopterin Concentrations in Patients with Rectal Carcinoma Treated with Chemoradiation.

AIM: To analyze the prognostic significance of serum and urinary neopterin concentrations in patients with rectal adenocarcinoma treated with (chemo)radiation. PATIENTS AND METHODS: Urinary and serum neopterin and peripheral blood cell count were determined in 49 patients with rectal carcinoma before the start of (chemo)radiation. RESULTS: Neopterin concentrations exhibited a significant inverse correlation with hemoglobin and positive correlation with leukocyte count, platelet count and platelet-to-lymphocyte ratio. Increased serum neopterin concentration was associated with significantly inferior relapse-free survival (RFS) and overall survival. However, a significant association was observed only in 28 patients treated in the neoadjuvant setting. Although increased urinary neopterin was also associated with inferior RFS and overall survival, this was not statistically significant. The neutrophil-to-lymphocyte ratio was also associated with poor prognosis. CONCLUSION: The data presented herein indicate a prognostic significance of serum neopterin concentrations in patients with rectal cancer treated with neoadjuvant chemoradiation.

Prognostic factors in patients with esophageal carcinoma treated with chemoradiation: single center experience.

BACKGROUND/AIMS: The trimodality therapy including chemotherapy, external beam radiation and surgery is widely accepted as the standard of care in patients with locoregional esophageal carcinoma. METHODOLOGY: We have performed a retrospective analysis of patients with locoregional esophageal carcinoma treated with chemoradiation. RESULTS: One-hundred and fifty-two consecutive patients with non-metastatic adenocarcinoma or squamous cell esophageal carcinoma treated with chemoradiation were included in the present analysis. The median survival of the whole group was 12 months. The estimated 3- and 5-year survival rates were 24% and 19%, respectively. On multivariate analysis, female sex, weight loss and serum albumin were independent negative predictors of survival. Among 140 patients who survived more than 3 months, weight loss, female sex and therapy with paclitaxel were negatively associated with prognosis, and among 109 patients surviving more than 6 months the dose of cisplatin and surgery were independent prognostic factors. Pathologic complete response was not predictive of prognosis. CONCLUSIONS: Long-term survival is obtained in only about 20% of patients with carcinoma of the esophagus treated with chemoradiation. Female sex, weight loss and low serum albumin are independent indicators of poor prognosis. Among treatment-related factors, higher dose of cisplatin and esophagectomy were independent predictors of better prognosis, while administration of paclitaxel was associated with poor prognosis.