Prognostic Marker In Patients Research Articles

The ST2/IL-33 Pathway in Adult and Paediatric Heart Disease and Transplantation.

ST2 is a member of interleukin 1 receptor family with soluble sST2 and transmembrane ST2L isoforms. The ligand of ST2 is IL-33, which determines the activation of numerous intracytoplasmic mediators following the binding with ST2L and IL-1RAcP, leading to nuclear signal and cardiovascular effect. Differently, sST2 is released in the blood and works as a decoy receptor, binding IL-33 and blocking IL-33/ST2L interaction. sST2 is mainly involved in maintaining homeostasis and/or alterations of different tissues, as counterbalance/activation of IL-33/ST2L axis is typically involved in the development of fibrosis, tissue damage, inflammation and remodeling. sST2 has been described in different clinical reports as a fundamental prognostic marker in patients with cardiovascular disease, as well as marker for the treatment monitoring of patients with heart failure; however, further studies are needed to better elucidate its role. In this review we reported the current knowledge about its role in coronary artery disease, heart failure, heart transplantation, heart valve disease, pulmonary arterial hypertension, and cardiovascular interventions.

Preoperative BChE serves as a prognostic marker in patients with resectable AEG after neoadjuvant chemotherapy

BackgroundDiminished systemic serum butyrylcholinesterase (BChE), a biomarker for chronic inflammation, cachexia, and advanced tumor stage, has shown to play a prognostic role in various malignancies. The aim of this study was to investigate the prognostic value of pretherapeutic BChE levels in patients with resectable adenocarcinoma of the gastroesophageal junction (AEG), treated with or without neoadjuvant therapy.MethodsData of a consecutive series of patients with resectable AEG at the Department for General Surgery, Medical University of Vienna, were analyzed. Preoperative serum BChE levels were correlated to clinic-pathological parameters as well as treatment response. The prognostic impact of serum BChE levels on disease-free (DFS) and overall survival (OS) was evaluated by univariate and multivariate cox regression analysis, and Kaplan–Meier curves used for illustration.ResultsA total of 319 patients were included in this study, with an overall mean (standard deviation, SD) pretreatment serum BChE level of 6.22 (± 1.91) IU/L. In univariate models, diminished preoperative serum BChE levels were significantly associated with shorter overall (OS, p < 0.003) and disease-free survival (DFS, p < 0.001) in patients who received neoadjuvant treatment and/or primary resection. In multivariated analysis, decreased BChE was significantly associated with shorter DFS (HR: 0.92, 95% CI: 0.84–1.00, p 0.049) and OS (HR: 0.92, 95% CI: 0.85–1.00, p < 0.49) in patients receiving neoadjuvant therapy. Backward regression identified the interaction between preoperative BChE and neoadjuvant chemotherapy as a predictive factor for DFS and OS.ConclusionDiminished serum BChE serves as a strong, independent, and cost-effective prognostic biomarker for worse outcome in patients with resectable AEG who had received neoadjuvant chemotherapy.

The use of high-sensitivity cardiac troponin T and creatinine kinase-MB as a prognostic markers in patients with acute myocardial infarction and chronic kidney disease

Background High-sensitivity cardiac troponin T (hs-cTnT) and creatine kinase (CK)-MB are the most commonly used biomarkers for the diagnosis and prognosis of acute myocardial infarction (AMI). Chronic kidney disease (CKD) often leads to elevated hs-cTnT levels in non-AMI patients. However, studies comparing the prognostic value of both hs-cTnT and CK-MB in patients with AMI and CKD are lacking. Methods We conducted a retrospective study on AMI patients diagnosed between January 2015 and October 2020. Patients were categorized based on renal function as normal or CKD. Peak hs-cTnT and CK-MB levels during hospitalization were collected, and their diagnostic value was evaluated using receiver operating characteristic (ROC) curves. The impact on in-hospital mortality was analyzed using multivariate logistic regression. The relationship between the hs-cTnT/CK-MB ratio and in-hospital death was examined using a restricted cubic spline (RCS) curve. Results The study included 5022 AMI patients, of whom 797 (15.9%) had CKD. The AUCs of Hs-cTnT and CK-MB were higher in the CKD group [0.842 (95% CI: 0.789–0.894) and 0.821 (95% CI: 0.760–0.882)] than in the normal renal function group [0.695 (95% CI: 0.604-0.790) and 0.708 (95% CI: 0.624-0.793)]. After full adjustment for all risk factors, hs-cTnT (OR, 2.82; 95% CI, 1.03–9.86; p = 0.038) and CK-MB (OR, 4.91; 95% CI, 1.54–14.68; p = 0.007) above the cutoff values were independent predictors of in-hospital mortality in patients with CKD. However, in patients with normal renal function, only CK-MB above the cutoff (OR, 2.45; 95% CI, 1.02–8.24; p = 0.046) was a predictor of in-hospital mortality, whereas hs-cTnT was not. There was an inverted V-shaped relationship between the hs-cTnT/CK-MB ratio and in-hospital mortality, with an inflection point of 19.61. The ratio within the second quartile (9.63-19.6) was an independent predictor of in-hospital mortality in patients with CKD (OR 5.3, 95% CI 1.66–16.86, p = 0.005). Conclusions Hs-cTnT independently predicted in-hospital mortality in AMI patients with CKD, whereas its predictive value was not observed in patients with normal renal function. CK-MB was an independent predictor of in-hospital mortality regardless of renal function. Moreover, the hs-cTnT/CK-MB ratio may aid in risk stratification of AMI patients with CKD.

P-341 Tumor regression and nodal status to neoadjuvant chemotherapy as a prognostic marker in patients with locally advanced gastric and gastroesophageal cancer

P-341 Tumor regression and nodal status to neoadjuvant chemotherapy as a prognostic marker in patients with locally advanced gastric and gastroesophageal cancer

Peripheral myeloid cells as prognostic markers in patients (pts) with non-small cell lung cancer (NSCLC) treated with cemiplimab: Pooled analysis of EMPOWER-Lung 1 and EMPOWER-Lung 3 phase 3 trials.

9028 Background: Circulating innate and adaptive immune cells can modulate clinical responses to immune checkpoint inhibition in pts with cancer; however, there are no clear validated baseline clinical tests to guide clinicians, outside of programmed cell death-ligand 1 (PD-L1) IHC tests on limited biopsy specimens. High neutrophil/lymphocyte ratio (NLR) is associated with poor prognosis in NSCLC, but data are limited on the potential contribution of other immune cells such as monocytes and eosinophils in modulating systemic immune response. Further, previous correlative studies have not established clinically actionable immune cell cut-off values. Methods: We used multiple quantitative analytic methods including multivariable Cox regression and conditional decision trees to assess the prognostic importance of NLR and peripheral myeloid cells, including monocytes and eosinophils, in pts with NSCLC treated with cemiplimab in Phase 3 trials EMPOWER-Lung 1 (NCT03088540) and EMPOWER-Lung 3 (NCT03409614). In EMPOWER-Lung 1, pts with PD-L1 ≥50% were randomized 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-based chemotherapy (chemo). EMPOWER-Lung 3 was a 2-part study. In Part 1, pts with PD-L1 &lt; 50% were randomized 1:1:1 to chemo, cemiplimab 350 mg Q3W + chemo, or cemiplimab 350 mg Q3W + ipilimumab 50 mg Q6W + chemo. In Part 2, pts were randomized 2:1 to receive cemiplimab 350 mg or placebo Q3W + chemo. Results: Overall, 691 pts in EMPOWER-Lung 1 and 769 pts in EMPOWER-Lung 3 were included in this analysis. The results showed significant association between multiple factors including NLR and overall survival (OS) and progression-free survival (PFS). For pts with NLR &gt; 3.98 vs ≤3.98, median OS (95% CI) was 10 (9–13) vs 20 (17–24) months (HR: 2.04; 95% CI: 1.60–2.61; P&lt; 0.001) and median PFS (95% CI) was 4 (4–6) vs 6 (6–7) months (HR: 1.80; 95% CI: 1.50–2.18; P&lt; 0.001), respectively, accounting for known prognostic factors. In multivariable analyses, monocytes (OS HR: 1.72; 95% CI: 1.29–2.30; P&lt; 0.001; PFS HR: 1.37; 95% CI: 1.08–1.75; P= 0.010) and log eosinophils (OS HR: 0.90; 95% CI: 0.85–0.97; P= 0.003; PFS HR: 0.93; 95% CI: 0.88–0.98; P= 0.004) were significantly associated with OS and PFS in both studies. (Neutrophil + monocyte)/lymphocyte ratio was the top predictor of both OS and PFS in decision tree analysis. Peripheral blood cell count correlations were not affected by tumor PD-L1 levels (ρ &lt; 0.15 for all markers). Conclusions: This is a large and comprehensive prognostic analysis of data from two prospective Phase 3 clinical trials in advanced NSCLC. Clinically actionable peripheral blood cell count parameters, incorporating putative immunosuppressive myeloid cells (neutrophils and monocytes) and protective lymphocytes and eosinophils, may help predict response to anti–PD-1 therapy in advanced NSCLC. Clinical trial information: NCT03088540 , NCT03409614 .

GLYCEMIC VARIABILITY IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: CLINICAL IMPLICATIONS AND PHARMACOLOGICAL CONSIDERATIONS

Objective: Glycemic variability (GV), independently of glycemic control, has emerged as a prognostic marker in patients with type 2 diabetes mellitus (DM). In this study, we assessed the prognostic value of GV for predicting major adverse cardiovascular events (MACE) in our local population. We also assessed its prognostic value for diabetic microvascular complications (DMC) and its relationships with antidiabetic medications. Design and method: This was a retrospective cohort study that recruited 680 patients with type 2 DM across 2015-2017. MACE were defined as: the composite of; total death, myocardial infarction (MI), stroke, hospitalization due to heart failure, revascularization. GV was calculated for two glycemic control markers: glycated hemoglobin (G-Hb) and fasting blood sugar (FBS); via 3 metrics- standard deviation (SD), coefficient of variation (CV), and variability independent from the mean (VIM). Cox proportional hazard models and Kruskal-Wallis tests were used in the statistical analysis. Results: 105 events classified as MACE were identified in 86 patients and 104 DMC in 98 patients in an average follow-up period of 78.43 months. GV was found to be an independent predictor of MACE, particularly for FBS-CV but not a predictor of DMC. FBS-CV &gt; 17.51% as compared with &lt; 17.51% was a significant and independent predictor of MACE, with HR 1.589 (95% CI; 1.022, 2.472) (P = 0.040) (Table 1 &amp; Figure 1). DMC were predicted mainly by the duration of type DM, and by the glycemic control; similarly represented by G-Hb and FBS. Patients on metformin, and dipeptidyl peptidase (DPP) 4 inhibitors, had the lowest GV, as compared with patients whose treatments included insulin/sulphonylureas (P&lt;0.001). Conclusions: In our population, GV predicted MACE: with FBS-CV superior to the “gold standard” glycemic control marker G-Hb. Further, GV may be explained, partially at least, by the choice of antidiabetic medications: this finding might contribute to the cardiovascular protection attributed to one class rather than another.

The utility of the [-2]pro-prostate-specific antigen level as a prognostic marker in patients with castration-resistant prostate cancer treated with enzalutamide.

The prostate health index (phi) derived using [-2]pro-prostate-specific antigen (p2PSA), a precursor of PSA, has been shown to predict cancer in the gray zone. However, the utility of p2PSA in predicting outcomes for castration-resistant prostate cancer (CRPC) patients remains unknown. Therefore, in this study, we aimed to evaluate the usefulness of p2PSA in predicting the efficacy and prognosis of enzalutamide treatment in CRPC patients. We conducted a prospective study of CRPC patients treated with enzalutamide at our institution, measuring p2PSA levels in 98 pre-treatment serum samples. All patients were divided into two groups based on the median values of each parameter. The PSA progression-free survival (PSA-PFS) and overall survival (OS) were compared using the Kaplan-Meier method. This study was approved by the Institutional Review Board of Gunma University Hospital (IRB No. 2021-092, 1983). The median PSA level before enzalutamide treatment was 25.59 ng/mL, the median p2PSA level was 208.75 pg/mL, and the median phi was 187.95. PSA, p2PSA, and phi were not all predictors of PSA-PFS. However, the OS was significantly better in the low-value groups (log-rank p-values of PSA, p2PSA, and phi were 0.024, 0.034, and 0.018, respectively). In the docetaxel (DOC)-naive group (n = 58), PSA was not a predictor of OS, but p2PSA and phi were significantly associated with better OS in the low group. This relationship was not observed in the DOC-treated group. Our study elucidates the usefulness of p2PSA in predicting outcomes for CRPC patients treated with enzalutamide. It suggests that p2PSA and phi may be prognostic markers after enzalutamide administration in CRPC patients.

Free Light Chains κ and λ as New Biomarkers of Selected Diseases.

Diagnostic and prognostic markers are necessary to help in patient diagnosis and the prediction of future clinical events or disease progression. As promising biomarkers of selected diseases, the free light chains (FLCs) κ and λ were considered. Measurements of FLCs are currently used in routine diagnostics of, for example, multiple myeloma, and the usefulness of FLCs as biomarkers of monoclonal gammopathies is well understood. Therefore, this review focuses on the studies concerning FLCs as new potential biomarkers of other disorders in which an inflammatory background has been observed. We performed a bibliometric review of studies indexed in MEDLINE to assess the clinical significance of FLCs. Altered levels of FLCs were observed both in diseases strongly connected with inflammation such as viral infections, tick-borne diseases or rheumatic disorders, and disorders that are moderately associated with immune system reactions, e.g., multiple sclerosis, diabetes, cardiovascular disorders and cancers. Increased concentrations of FLCs appear to be a useful prognostic marker in patients with multiple sclerosis or tick-borne encephalitis. Intensive synthesis of FLCs may also reflect the production of specific antibodies against pathogens such as SARS-CoV-2. Moreover, abnormal FLC concentrations might predict the development of diabetic kidney disease in patients with type 2 diabetes. Markedly elevated levels are also associated with increased risk of hospitalization and death in patients with cardiovascular disorders. Additionally, FLCs have been found to be increased in rheumatic diseases and have been related to disease activity. Furthermore, it has been suggested that inhibition of FLCs would reduce the progression of tumorigenesis in breast cancer or colitis-associated colon carcinogenesis. In conclusion, abnormal levels of κ and λ FLCs, as well as the ratio of κ:λ, are usually the result of disturbances in the synthesis of immunoglobulins as an effect of overactive inflammatory reactions. Therefore, it seems that κ and λ FLCs may be significant diagnostic and prognostic biomarkers of selected diseases. Moreover, the inhibition of FLCs appears to be a promising therapeutical target for the treatment of various disorders where inflammation plays an important role in the development or progression of the disease.

De Ritis oranının akut kolesistitteki rolü: retrospektif gözlemsel çalışma

Aim&#x0D; Our study aimed to evaluate the relationship between the De-Ritis ratio and prognosis and mortality in patients diagnosed with cholecystitis. &#x0D; Materials and Methods&#x0D; This retrospective observational study was conducted on patients diagnosed with acute cholecystitis who presented to the emergency medical clinic of XXX Hospital between June 1, 2020, and January 1, 2022. The Statistical Package for Social Sciences (SPSS) software (v.20; Chicago, IL, USA) was used for all statistical analyses. All results with p &lt; 0.05 were considered statistically significant.&#x0D; Results&#x0D; In our study, 174 patients were included, and 50.6% of our patients were women. The mean age was 59.0 (43.2 to 71.8). A total of 2.29% of our patients died. No statistically significant relationship was found between AST, ALT, CRP, albumin, and the De-Ritis ratio and mortality (p=0.584, p=0.533, p=0.517, p=0.07, p=0.399, respectively). When mortality rates in operated patients were examined, no statistically significant correlation was found between AST, ALT, CRP, albumin, and De-Ritis rates and mortality (p=0.248, p=0.315, p=0.451, p=0.183, p=0.688, respectively)&#x0D; Conclusion&#x0D; To the best of our knowledge, no study has examined the relationship between cholecystitis and the De-Ritis ratio. De-Ritis ratio is not used as a prognostic marker in patients with cholecystitis.

AI-based fully automated left atrioventricular coupling index as a prognostic marker in patients undergoing stress-CMR

The left atrioventricular coupling index (LACI) is a strong and independent predictor of heart failure (HF) in individuals without clinical cardiovascular disease. To determine in patients undergoing stress CMR whether fully automated artificial intelligence-based LACI can provide incremental prognostic value to predict HF. Between 2016 and 2018, we conducted a study including all consecutive patients with abnormal vasodilator stress CMR [inducible ischemia or late gadolinium enhancement (LGE)]. Control subjects with normal CMR were selected using propensity score-matching. LACI was defined as the ratio of LA to LV end-diastolic volumes. The primary outcome included hospitalization for acute HF or cardiovascular death using Cox regression. In 2662 patients [65 ± 12 years, 68% men, 1:1 matched patients (1331 with normal and 1331 with abnormal CMR)], LACI was positively associated with the primary outcome [median follow-up 5.2 (4.8–5.5) years] before and after adjustment for risk factors in the overall propensity-matched population [adjusted hazard ratio (HR), 5.94 (95%CI, 3.74–9.45) per 0.1% increment], patients with abnormal [adjusted HR, 6.38 (95%CI, 3.77–10.8) per 0.1% increment], and normal CMR [adjusted HR, 6.15 (95%CI, 2.97–12.7) per 0.1% increment; all P < 0.001]. After adjustment, a higher LACI of ≥ 25% showed the greatest improvement in model discrimination and reclassification over and above traditional risk factors and stress CMR findings (C-statistic improvement: 0.15; NRI = 0.705; IDI = 0.398, all P < 0.001; LR-test P < 0.001). LACI is independently associated with hospitalization for HF and cardiovascular death in patients undergoing stress CMR, with an incremental prognostic value over traditional risk factors including inducible ischemia and LGE (Fig. 1).

The inflammatory prognostic index as a potential predictor of prognosis in metastatic gastric cancer

Clinical studies aimed at identifying effective and simple prognostic markers for gastric cancer are still being carried out. Inflammatory prognostic index (IPI) is being recognized as a promising prognostic marker in patients with Non-Small Cell Lung Cancer. To evaluate the prognostic utility of IPI in stage 4 gastric cancer. A total of 152 patients with stage 4 gastric cancer, whose laboratory parameters, progression-free survival (PFS) and overall survival (OS) data could be accessed, were evaluated. Kaplan Meier analysis was used for survival analyses. Hazard ratios were expressed with 95% CI values. All methods were performed in accordance with the relevant guidelines and regulations. Study was approved by the Manisa Celal Bayar University’s Non-Invasive Clinical Research Ethics Committee (approval No. E-85252386-050.04.04-49119, date: 22.03.2021). We confirm that all methods were performed in accordance with relevant named guidelines and regulations. Median age at diagnosis was 63 years (range: 32–88). The number of patients who received first-line chemotherapy was 129 (84.9%). Median PFS with first-line treatment was 5.3 months, while it was 3.3 months with second-line treatment. Median OS was 9.4 months. Median IPI score was 22.2. We evaluated IPI score for its value in detecting survival status with ROC analysis and identified an IPI cut-off score of 14.6. Low IPI score was significantly associated with longer PFS and OS compared to high IPI (PFS in high vs. low IPI, 3.6 vs. 7 months; p < 0.001) (OS in high vs. low IPI, 6.6 vs. 14.2 months; p < 0.001). IPI score can be an independent prognostic index that is inexpensive, easy to access and evaluate for patients with metastatic gastric cancer, and may be useful in predicting survival in daily practice.

Prognostic values of systemic inflammation and nutrition-based prognostic indices in oropharyngeal carcinoma.

Pretreatment systemic inflammation and nutrition-based prognostic indices (SINBPI) have demonstrated significance. This study investigated the prognostic value of pretreatment SINBPI for patients with oropharyngeal cancer and identified unfavorable prognostic markers. We retrospectively reviewed the data of 124 patients with oropharyngeal squamous cell carcinoma (OPSCC) who received definitive treatment between January 2010 and December 2018. The prognostic utility of the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index, and high-sensitivity modified Glasgow prognostic score (HS-mGPS) was assessed for disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) using univariate and multivariate analyses. Multivariate analyses revealed that human papillomavirus (HPV) status and HS-mGPS were significantly associated with DFS, DSS, and OS. Patients with a HS-mGPS of 2 had a significantly higher rate of treatment-related deaths than those with a HS-mGPS of 0 or 1. The combination of the HS-mGPS and PLR had more accurate predictive ability in DFS and OS compared with the HS-mGPS alone, and the combination of the HS-mGPS and LMR had more accurate predictive ability in DSS and OS. Our results indicated that the HS-mGPS was a useful prognostic marker for patients with OPSCC, and combined markers consisting of the HS-mGPS and PLR or LMR may provide more accurate prognostic predictions.Level of Evidence: 3.

Effect of elevated serum ferritin on the risk of death in patients with decompensated cirrhosis: a meta-analysis.

It is still debatable whether serum ferritin is a potential prognostic marker in patients with decompensated cirrhosis. In this meta-analysis, we hope to investigate the relationship between elevated serum ferritin and the risk of death in patients with decompensated cirrhosis. We systematically searched PubMed, Embase, Web of Science, Cochrane Library, CNKI, SinoMed, WAN FANG, and ClinicalTrials.gov without language restrictions from inception to 3 October 2022, and finally identified a total of eight eligible studies with 1829 patients. The pooled prevalence of elevated serum ferritin in decompensated cirrhosis was 40.6% [95% confidence interval (CI) 32.1-49.2%], and it was higher in males, patients with alcohol-associated liver disease, those with Child-Pugh grade C, those with hepatic encephalopathy, and nonsurvivors. Nonsurvivors had significantly higher serum ferritin levels than survivors [mean difference 247.90; 95% CI, 130.97-364.84]. With a pooled unadjusted hazard ratio of 2.38 (95% CI, 1.78-3.18), high serum ferritin was associated with an increased risk of death in patients with decompensated cirrhosis, with low heterogeneity among the included studies. In conclusion, high serum ferritin levels were associated with mortality in patients with decompensated cirrhosis. More prospective and homogeneous clinical studies are required to validate our findings.

Gustave Roussy immune score is a prognostic marker in patients with small cell lung cancer undergoing immunotherapy: a real-world retrospective study.

The utilization of the Gustave Roussy Immune Score (GRIm-Score) in patient selection for immunotherapy was initially reported. The objective of this retrospective study is to assess the potential of the GRIm-Score, a novel prognostic score based on nutritional and inflammatory markers, as a prognostic predictor in patients with small cell lung cancer (SCLC) undergoing immunotherapy. This retrospective study conducted at a single center included 159 patients with SCLC who received immunotherapy. The objective of the study was to investigate potential differences in overall survival (OS) and progression-free survival (PFS) among patients stratified by their GRIm-Score, utilizing the Kaplan-Meier survival analysis and the log-rank test. The final independent prognostic factors were identified through both propensity score matching (PSM) analysis and multivariable Cox proportional hazards regression analysis. Our analysis of the 159 patients revealed that there was a significant decrease in both OS and PFS with each increase in the GRIm-Score group, displaying a stepwise pattern. Moreover, even after conducting PSM analysis, the significant associations between the modified three-category risk scale-based GRIm-Score and survival outcomes remained significant. Both the total cohort and PSM cohort were subjected to multivariable analysis, which demonstrated that the three-category risk assessment-based GRIm-Score was a valuable predictor of both OS and PFS. In addition, the GRIm-Score may serve as a valuable and non-invasive prognostic predictor for SCLC patients undergoing PD1/PD-L1 immunotherapy.

PO-1142 Low TMT may be a negative predictive and prognostic marker in patients with GBM treated with CCRT

PO-1142 Low TMT may be a negative predictive and prognostic marker in patients with GBM treated with CCRT

ALDH1 and CD 44 serve as prognostic markers in patients with breast cancer

ALDH1 and CD 44 serve as prognostic markers in patients with breast cancer

Potential of cell-free hemoglobin and haptoglobin as prognostic markers in patients with ARDS and treatment with veno-venous ECMO

BackgroundHemolysis is associated with increased mortality in patients with sepsis, ARDS, or therapy with extracorporeal membrane oxygenation (ECMO). To quantify a critical threshold of hemolysis in patients with ARDS and treatment with veno-venous ECMO, we aimed to identify cutoff values for cell-free hemoglobin (CFH) and haptoglobin (Hp) plasma concentrations associated with a significant increase in ICU mortality.MethodsPatients with ARDS admitted to a tertiary ARDS referral center between 01/2007 and 12/2018 and treatment with veno-venous ECMO were included. Cutoff values for mean CFH (mCFH) and mean Hp (mHp) plasma concentrations dividing the cohort into groups with significantly different ICU mortalities were calculated and patient characteristics were compared. A multiple logistic regression model with stepwise backward variable selection was included. In addition, cutoff values for vulnerable relative timespans for the respective CFH and Hp concentrations were calculated.ResultsA quantitative cutoff value of 11 mg/dl for mCFH separated the cohort (n = 442) regarding ICU mortality (mCFH ≤ 11 mg/dl: 38%, [95%-CI: 32.22–43.93] (n = 277) vs. mCFH > 11 mg/dl: 70%, [61.99–76.47] (n = 165), p < 0.001). Analogously, a mHp cutoff value ≤ 0.39 g/l was associated with a significant increase in ICU mortality (mHp ≤ 0.39 g/l: 68.7%, [60.91–75.61] (n = 163) vs. mHp > 0.39 g/l: 38.7%, [33.01–44.72] (n = 279), p < 0.001). The independent association of ICU mortality with CFH and Hp cutoff values was confirmed by logistic regression adjusting for confounders (CFH Grouping: OR 3.77, [2.51–5.72], p < 0.001; Hp Grouping: OR 0.29, [0.19–0.43], p < 0.001). A significant increase in ICU mortality was observed when CFH plasma concentration exceeded the limit of 11 mg/dl on 13.3% of therapy days (≤ 13.3% of days with CFH > 11 mg/dl: 33%; [26.81–40.54] (n = 192) vs. > 13.3% of days with CFH > 11 mg/dl: 62%; [56.05–68.36] (n = 250), p < 0.001). Analogously, a mortality increase was detected when Hp plasma concentration remained ≤ 0.39 g/l for > 18.2% of therapy days (≤ 18.2% days with Hp ≤ 0.39 g/l: 27%; [19.80–35.14] (n = 138) vs. > 18.2% days with Hp ≤ 0.39 g/l: 60%; [54.43–65.70] (n = 304), p < 0.001).ConclusionsModerate hemolysis with mCFH-levels as low as 11 mg/dl impacts mortality in patients with ARDS and therapy with veno-venous ECMO. Furthermore, a cumulative dose effect should be considered indicated by the relative therapy days with CFH-concentrations > 11 mg/dl. In addition, also Hp plasma concentrations need consideration when the injurious effect of elevated CFH is evaluated.

The Geriatric Nutritional Risk Index is a prognostic marker in patients with metastatic colorectal cancer.

The Geriatric Nutritional Risk Index (GNRI) is a nutritional index for elderly patients that is associated with prognosis in cancer patients. We investigated using the GNRI in patients with metastatic colorectal cancer to predict prognosis. This study included 419 metastatic colorectal cancer patients who received first-line chemotherapy between February 2005 and December 2020. First, we calculated pre-treatment GNRI and divided the patients into four groups according to the values (G1-G4). We evaluated patient characteristics and overall survival in the four groups. Overall, 419 patients were included. The median follow-up was 34.4months. Lower GNRI was positively associated with a lower grade Eastern Cooperative Oncology Group Performance Status (p = 0.009), synchronous metastases (p < 0.001), primary tumor resection prior to chemotherapy (p = 0.006), and did not undergo resection after chemotherapy (p < 0.001). Patients with low GNRI had significantly shorter overall survival than the group with high GNRI (median OS: G1 = 19.3months [M], G2 = 30.8M, G3 = 38M, G4 = 39.7M; log-rank test, p < 0.001). Multivariate Cox regression analysis showed that GNRI was an independent prognostic factor (G3: HR = 0.49, 95% CI = 0.35-0.69; G4: HR = 0.67, 95% CI = 0.48-0.93). In the subgroup analysis of overall survival, we found no interaction between clinicopathological factors and the prognostic value of GNRI. Interestingly, younger patients (< 70years) but not older patients showed a significant difference in overall survival according to GNRI, despite being the metric being designed for elderly patients. Pretreatment GNRI can be a prognostic marker for patients with mCRC who received systemic chemotherapy.

Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion.

Tumor-associated macrophages are one of the key components of the tumor microenvironment. The immunomodulatory activity and function of macrophages in malignant pleural effusion (MPE), a special tumor metastasis microenvironment, have not been clearly defined. MPE-based single-cell RNA sequencing data was used to characterize macrophages. Subsequently, the regulatory effect of macrophages and their secreted exosomes on T cells was verified by experiments. Next, miRNA microarray was used to analyze differentially expressed miRNAs in MPE and benign pleural effusion, and data from The Cancer Genome Atlas (TCGA) was used to evaluate the correlation between miRNAs and patient survival. Single-cell RNA sequencing data showed macrophages were mainly M2 polarized in MPE and had higher exosome secretion function compared with those in blood. We found that exosomes released from macrophages could promote the differentiation of naïve T cells into Treg cells in MPE. We detected differential expression miRNAs in macrophage-derived exosomes between MPE and benign pleural effusion by miRNA microarray and found that miR-4443 was significantly overexpressed in MPE exosomes. Gene functional enrichment analysis showed that the target genes of miR-4443 were involved in the regulation of protein kinase B signaling and lipid biosynthetic process. Taken together, these results reveal that exosomes mediate the intercellular communication between macrophages and T cells, yielding an immunosuppressive environment for MPE. miR-4443 expressed by macrophages, but not total miR-4443, might serve as a prognostic marker in patients with metastatic lung cancer.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in patients with extensive-stage small cell lung cancer treated with atezolizumab in combination with chemotherapy.

Atezolizumab is now the standard treatment for extensive-stage small cell lung cancer (ES-SCLC). Herein, we investigated the prognostic role of inflammatory markers in patients treated with atezolizumab plus chemotherapy and evaluated the efficacy and safety of adding atezolizumab to chemotherapy for patients with ES-SCLC and prognostic and predictive factors as a real-life experience. This retrospective study included 55 patients who received front-line atezolizumab with etoposide plus platin regimen for ES-SCLC. We analyzed the survival outcomes and factors that may predict response and survival. The objective response rate (ORR) was 81.8%. At a median follow-up of 23.5 months, the median progression-free survival (PFS) time was 10.8 months, and the median overall survival (OS) time was 15.2 months. In univariate analysis for PFS, limited-stage disease at the time of diagnosis, the presence of prophylactic cranial irradiation (PCI), the presence of liver metastasis, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were found to be prognostic factors (P = .041, P = .034, P = .031, P = .004, and P = <.001, respectively). In other words, while the median PFS time was 14.1 months in patients with PLR ≤ 135.7, it was 7.5 months in patients with > 135.7. Similarly, median PFS was 14.9 months in patients with NLR ≤ 3.43, while it was 9.6 months in patients with > 3.43. Univariate analysis for OS revealed that limited stage at the time of diagnosis, NLR and PLR were significant prognostic indicators (P = .01, P = .006, and P = .007, respectively). Median OS time for patients with both NLR ≤ 3.43 and PLR ≤ 135.7 was significantly better than that of patients with NLR > 3.43 and PLR > 135.7 (16.9 vs 11.3 and 16.9 vs 11.5 months, respectively). Logistic regression analysis demonstrated that PLR was an independent significant predictive factor for the response to atezolizumab plus chemotherapy (OR: 0.07, P = .028). The patients with PLR ≤ 135.7 were significantly good responders to atezolizumab plus chemotherapy treatment. Real-life data demonstrated a significant correlation between survival and NLR and, PLR in ES-SCLC patients treated with atezolizumab. In addition, PLR was a significant predictive indicator of response to atezolizumab plus chemotherapy.