Systemic Immune Inflammation Index and T-Staging Predict Prognosis in Patients with Muscle-Invasive Bladder Cancer

Objective: To explore the effect of combining the preoperative systemic immune inflammation index (SII) and T-staging to predict the prognosis of patients with muscle-invasive bladder cancer (MIBC). Methods: The clinical data of 94 MIBC patients who met the inclusion criteria of our hospital from September 01, 2012, to August 31, 2022, were collected. Data included sex, age, smoking history, tumour size, tumour number, pathology, P-grading, T-staging, SII, and overall survival (OS). The optimal cut-off of SII (863.62) was selected by obtaining the receiver operating characteristic (ROC) curve. Then, the samples were divided into the low-SII group (SII <863.62, 51 cases) and the high-SII group (SII ≥863.62, 43 cases). T-staging could be divided into T2 (61 cases) and T3 and higher stages (33 cases) according to the findings on depth of tumour invasion. Furthermore, the role of combined SII and T-staging for prognosis prediction was evaluated by performing Kaplan–Meier survival analysis and Cox proportional hazards modelling in the OS analysis. Results: MIBC patients with higher SII (≥863.62) were associated with shorter OS (p = 0.00005). Patients with more advanced T-stages had shorter OS than those with early T-stages (p = 0.00006). Furthermore, patients who had both higher SII and more advanced T-stages had markedly shorter OS (p = 0.00001). Conclusions: In patients with MIBC, a higher SII and increasing T-stage indicate a worse prognosis and shorter OS. Therefore, the combined SII and T staging approach is a reliable prognostic predictor for patients with MIBC (AU)

Patterns of adolescent perceived social support and inflammation in adulthood within major racial groups: Findings from a longitudinal, nationally representative sample.

Inflammation, the body's protective response to injury and infection, plays a critical role in physical and mental health outcomes. Elevated chronic inflammation is implicated as a predictor of disease and all-cause mortality and is linked with several psychological disorders. Given that social support is associated with lower rates of mortality and psychopathology, the links between inflammation and social support are well-studied. However, there are many significant gaps related to both the specificity and generalizability of extant findings. There is a paucity of research on the association between social support and inflammation within different racial groups. Additionally, more research is warranted to understand whether social support from different sources uniquely contributes to inflammation, above and beyond other sources of support. Thus, the current study examined whether perceived emotional social support during adolescence predicted inflammation during adulthood within several racial groups. Participants (n = 3,390) were drawn from the National Longitudinal Study of Adolescent to Adult Health (Add Health), identified as either Asian, Black, Latinx, White, or Multiracial, and had complete data on study variables. Consistent with our hypotheses and previous research, greater perceived support during adolescence was associated with lower inflammation during adulthood, but only for White participants. Contrastingly, greater perceived support during adolescence was associated with higher inflammation during adulthood for individuals who identified as Asian, Latinx, Black, or Multiracial. Furthermore, patterns of social support and inflammation within each racial group varied by relationship type. These results highlight the importance of studying relationship processes and health outcomes within racial groups to understand their unique, lived experiences.

Prognostic significance of the skeletal muscle index and systemic inflammatory index in patients with lymph node-positive breast cancer after radical mastectomy.

BACKGROUND: The role of skeletal muscle index (SMI) and systemic inflammation index (SII) for patients with lymph node-positive breast cancer remain controversial. This retrospective study aims to evaluate the individual and synergistic value of SMI and SII in outcomes prediction in this population. METHODS: Lymph node-positive breast cancer patients who received mastectomy between January 2011 and February 2013 were included in this retrospective study. We used abdominal computed tomography (CT) to measure skeletal muscle mass at the third lumbar (L3) level. The optimal cut-off values of SMI and SII were determined through maximizing the Youden index on the receiver operating characteristic (ROC) curves. Kaplan-Meier method was used to assess the correlation between SMI, SII, and overall survival (OS). The prognostic value of SMI and SII were analyzed with the multivariable Cox proportional hazards model. RESULTS: Of 97 patients included in our study (mean age: 46 [range: 27-73] years; median follow-up: 62.5 months), 71 had low SMI (sarcopenia), 59 had low SII, and 56 had low SMI + SII. Kaplan-Meier survival curves showed that both high SMI (P = 0.021, 5-year OS: 84.0% vs. 94.1%) and high SII (P = 0.043, 5-year OS: 81.0% vs. 97.3%) were associated with worse OS. Additionally, patients with either low SMI or low SII had significantly better OS (P = 0.0059, 5-year OS: 100.0% vs. 84.6%) than those with high SMI + SII. Multivariable analysis confirmed the predictive values of high SMI (P = 0.024, hazard ratio [HR]: 9.87) and high SII (P = 0.048, HR: 6.87) for poor OS. Moreover, high SMI + SII was significantly associated with poor survival (P = 0.016, HR: 16.36). CONCLUSIONS: In this retrospective analysis, both SMI and SII independently predicted the prognosis of patients with lymph node-positive breast cancer. SMI + SII might be a stronger prognostic factor than either alone based on our findings, but should be further verified in a larger study.

Preoperative prognostic nutritional index and systemic immune-inflammation index predict survival outcomes in osteosarcoma: A comparison between young and elderly patients.

OBJECTIVE: This retrospective study of patients with osteosarcoma investigated the following biomarkers of inflammation and nutritional status: neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, prognostic nutritional index (PNI), and systemic immune-inflammation index (SII). The efficacies of these indicators to predict overall survival (OS) of young and elderly patients were compared. METHODS: The data of 125 patients with osteosarcoma, comprising the young (≤20 years) and elderly (60-80 years), were reviewed. Receiver operating characteristic (ROC) curves were calculated to determine the optimal cut-off value and area under the ROC curve of each potential biomarker. Kaplan-Meier curves and a Cox proportional hazards model were used to perform survival analyses. RESULTS: The cut-off values for low and high PNI ( ≤48.5, >48.5) and low and high SII (≤607.3, >607.3) were determined. Osteosarcoma patients in low PNI group or high SII group exhibited poorer OS relative to those in high PNI or low SII groups. The univariate and multivariate analyses indicated that preoperative PNI and SII were independent prognostic factors for OS in both the young and elderly subjects. CONCLUSION: Preoperative PNI and SII can be viable biomarkers of prognosis for both young and elderly patients with osteosarcoma. Awareness of these valuable indexes will enable clinicians to evaluate the inflammatory and nutritional status of these patients and establish a framework for individualized therapy.

Hemophagocytosis, hyper-inflammatory responses, and multiple organ damages in COVID-19-associated hyperferritinemia.

Hyperferritinemia comes to light frequently in general practice. However, the characteristics of COVID-19-associated hyperferritinemia and the relationship with the prognosis were not well described. The retrospective study included 268 documented COVID-19 patients. They were divided into the hyperferritinemia group (≥ 500 µg/L) and the non-hyperferritinemia group (< 500 µg/L). The prevalence of fever and thrombocytopenia and the proportion of patients with mechanical ventilator support and in-hospital death were much higher in the hyperferritinemia group (P < 0.001). The hyperferritinemia patients showed higher median IL-6, D-dimer, and hsCRP (P < 0.001) and lowered FIB level (P = 0.036). The hyperferritinemia group had a higher proportion of patients with AKI, ARDS, and CSAC (P < 0.001). According to the multivariate analysis, age, chronic pulmonary disease, and hyperferritinemia were found to be significant independent predictors for in-hospital mortality [HR 1.041 (95% CI 1.015-1.068), P = 0.002; HR 0.427 (95% CI 0.206-0.882), P = 0.022; HR 6.176 (95% CI 2.447-15.587), P < 0.001, respectively]. The AUROC curve was 0.88, with a cut-off value of ≥ 971 µg/L. COVID-19 patients with hyperferritinemia had a high proportion of organ dysfunction, were more likely to show hyper-inflammation, progressed to hemophagocytic lymphohistiocytosis, and indicated a higher proportion of death.

Temporal course of peripheral inflammation markers and indexes following acute ischemic stroke: prediction of mortality, functional outcome, and stroke-associated pneumonia.

BACKGROUND: Complete blood count derived indexes such as lymphocyte-to-neutrophil ratio (NLR) may help in predicting pneumonia and prognosis in acute stroke. However, the optimal time point for using these biomarkers is not known. METHODS: In 205 consecutive severe (NIHSS>10) acute ischemic stroke patients, daily leukocyte, lymphocyte, neutrophil, monocyte, platelet, albumin, fibrinogen, hematocrit, NLR, PLR (Platelet-to-lymphocyte-ratio), LMR (Lymphocyte-to-monocyte-ratio), and SII (systemic-immune-inflammation-index) were determined. General linear models for repeated measures (GLMR) and receiver operating characteristics [ROC] analyses were conducted to define their daily discriminative ability. RESULTS: GLMR-prognosis modeling documented that the main determinants of significant daily variations of 12 parameters studied were age and 24th-hour-NIHSS. In addition, daily changes of NLR, neutrophil, leukocyte (all increased on day-2 and remained higher) and platelet count (decreased after day-6 and stayed lower) were related significantly to survival status (mortality in 19.5%). Albumin levels (lower after day-2) were marginally associated by functional prognosis (modified-Rankin-Score≤3 in 28%). There was a borderline relationship (p = 0.05) between NLR (between day-1 and day-8) and pneumonia development (in 36%). Useful discrimination capability (95% confidence interval lower limit of area-under-curve of ROC≥0.7) was noted for NLR measured on day-6 for mortality, NLR (for 6 days, from day-3-to-day-7, and day-11) and albumin (for every day except day-11 after day-4) for reasonable prognosis and none for pneumonia development. CONCLUSIONS: Inflammatory parameters from peripheral routine blood tests showed significant variations during the first two weeks following stroke, but discriminative capacity of these changes is limited due to confounders such as age and post-treatment clinical stroke severity.

Clinically latent and autopsy-verified inflammatory disorders and malignant tumours in transplant patients.

AIMS: The number of clinical autopsies decreases while the rate of missed relevant diagnoses is known to be 2%-20%. In this study, we focused on postmortem examinations of patients after transplantation of solid organs. METHODS: A total of 122 cases were assessed for this study. Transplant organs included liver (LiTx; n=42/122, 34%), heart (n=8/122, 7%), lungs (n=32/122, 26%), kidney (KTx; n=38/122, 31%) and KTx+LiTx (n=2/122, 2%). RESULTS: The most frequent autopsy-verified causes of death were cardiac or respiratory failure (together n=85/122, 70%). The frequency of malignant tumours that were identified at autopsy was 5% (n=6/122). In 3% (n=4/122) of cases, Goldman class I discrepancies between clinical diagnosis and autopsy findings were identified. CONCLUSIONS: The rate of missed relevant diagnoses might be relatively low, but these cases nevertheless refute the contention that modern diagnostic techniques negate the need for autopsies in patients who died after transplantation.

Changes in proportionate cardiovascular mortality in patients with chronic infectious and inflammatory conditions in the United States, 1999-2018.

Treatment options for several chronic infectious and inflammatory conditions have expanded in recent years. This may have implications for evolving competing risks for chronic inflammation-associated comorbidities, including cardiovascular diseases (CVDs). Yet sparse data exist on patterns over time in cardiovascular mortality for chronic infectious and inflammatory conditions. We used data from the Centers for Disease Control and Prevention 1999-2018 Multiple Causes of Death database to investigate patterns in CVD mortality from January 1, 1999 to December 31, 2018 in several infectious and inflammatory conditions. Specifically, we determined age-adjusted proportionate CVD mortality separately for patients with the following conditions (as well as the general population): hepatitis C virus (HCV), human immunodeficiency virus (HIV), inflammatory bowel diseases (IBD), psoriasis (PSO), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Proportionate CVD mortality differed significantly in 1999 and 2018 for each condition compared with the general population (p < 0.0001). Proportionate CVD mortality decreased steadily in the general population (40.9 to 30.6%) but increased for patients with HCV (7.0 to 10.2%) and HIV (1.9 to 6.7%). For IBD, PSO, RA, and SLE, proportionate CVD mortality initially decreased followed by plateauing or increasing rates. Underlying disease-specific pathophysiologies, changes in natural history, and competing risks of chronic end-organ diseases contributing to these differences merit further study.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation.

Systemic chronic inflammation (SCI) is persistent, health-damaging, low-grade inflammation that plays a major role in immunosenescence and in development and progression of many diseases. But currently, there are no recognized standard biomarkers to assess SCI levels alone, and SCI is typically measured by combining biomarkers of acute inflammation and infection, e.g., CRP, IL-6, and TNFα. In this review, we highlight 10 properties and characteristics that are shared by the blood protein soluble urokinase plasminogen activator receptor (suPAR) and SCI, supporting the argument that suPAR is a biomarker of SCI: (1) Expression and release of suPAR is upregulated by immune activation; (2) uPAR and suPAR exert pro-inflammatory functions; (3) suPAR is associated with the amount of circulating immune cells; (4) Blood suPAR levels correlate with the levels of established inflammatory biomarkers; (5) suPAR is minimally affected by acute changes and short-term influences, in contrast to many currently used markers of systemic inflammation; (6) Like SCI, suPAR is non-specifically associated with multiple diseases; (7) suPAR and SCI both predict morbidity and mortality; (8) suPAR and SCI share the same risk factors; (9) suPAR is associated with risk factors and outcomes of inflammation above and beyond other inflammatory biomarkers; (10) The suPAR level can be reduced by anti-inflammatory interventions and treatment of disease. Assessing SCI has the potential to inform risk for morbidity and mortality. Blood suPAR is a newer biomarker which may, in fact, be a biomarker of SCI since it is stably associated with inflammation and immune activation; shares the same risk factors as many age-related diseases; is both elevated by and predicts age-related diseases. There is strong evidence that suPAR is a prognostic marker of adverse events, morbidity, and mortality. It is associated with immune activity and prognosis across diverse conditions, including kidney disease, cardiovascular disease, cancer, diabetes, and inflammatory disorders. Thus, we think it likely represents a common underlying disease-process shared by many diseases; that is, SCI. We review the supporting literature and propose a research agenda that can help test the hypothesis that suPAR indexes SCI, with the potential of becoming the new gold standard for measuring SCI.

Independent and joint effects of high-sensitivity c-reactive protein and hypoalbuminemia on long-term all-cause mortality among coronary artery disease: a prospective and multicenter cohort study.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) plays an important role in hypoalbuminemia as a representative of inflammation, which is closely associated with poor prognosis among patients with coronary artery disease (CAD). The present study aimed to evaluate the independent and joint effects of high hs-CRP levels and hypoalbuminemia on long-term mortality among CAD patients. METHODS: A total of 1449 CAD patients were included from a prospective, multicenter, observational cohort study (REICIN, NCT01402232) of patients referred for coronary angiography (CAG). The primary endpoint was long-term all-cause death. RESULTS: During a median follow-up of 2.9 (2.0-3.0) years, a total of 107 (7.4%) patients died. The long-term mortality was higher among CAD patients with high hs-CRP levels (> 3 mg/L) than those with the low hs-CRP levels (≤ 3 mg/L; 10.7% versus 4.1%; hazard ratio [HR] 2.49; 95% confidence interval [CI] 1.48-4.17). Similarly, CAD patients with hypoalbuminemia had higher mortality than those without hypoalbuminemia (12.2% versus 4.9%; HR 1.93; 95% CI 1.20-3.08). When hs-CRP and albumin were combined, CAD patients with high hs-CRP levels (> 3 mg/L) and with hypoalbuminemia were at the highest risk of death compared with their reference group (hs-CRP ≤ 3 mg/L and albumin > 35 g/L; HR 3.79; 95% CI 1.91-7.52). CONCLUSIONS: High hs-CRP levels and hypoalbuminemia were independently and jointly associated with long-term mortality among CAD patients. Patients with high hs-CRP levels and hypoalbuminemia had the highest risk of long-term mortality compared with other groups.

A Review of Platelet-Activating Factor As a Potential Contributor to Morbidity and Mortality Associated with Severe COVID-19.

The precise mechanisms of pathology in severe COVID-19 remains elusive. Current evidence suggests that inflammatory mediators are responsible for the manifestation of clinical symptoms that precedes a fatal response to infection. This review examines the nature of platelet activating factor and emphasizes the similarities between the physiological effects of platelet activating factor and the clinical complications of severe COVID-19.

Low-grade inflammation as a risk factor for cardiovascular events and all-cause mortality in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. METHODS: Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. RESULTS: 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2-11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01-1.46 and HR 1.26, 95% CI 1.10-1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. CONCLUSION: Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

Angiotensin II receptor blocker intake associates with reduced markers of inflammatory activation and decreased mortality in patients with cardiovascular comorbidities and COVID-19 disease.

AIMS: Patients with cardiovascular comorbidities have a significantly increased risk for a critical course of COVID-19. As the SARS-CoV2 virus enters cells via the angiotensin-converting enzyme receptor II (ACE2), drugs which interact with the renin angiotensin aldosterone system (RAAS) were suspected to influence disease severity. METHODS AND RESULTS: We analyzed 1946 consecutive patients with cardiovascular comorbidities or hypertension enrolled in one of the largest European COVID-19 registries, the Lean European Open Survey on SARS-CoV-2 (LEOSS) registry. Here, we show that angiotensin II receptor blocker intake is associated with decreased mortality in patients with COVID-19 [OR 0.75 (95% CI 0,59-0.96; p = 0.013)]. This effect was mainly driven by patients, who presented in an early phase of COVID-19 at baseline [OR 0,64 (95% CI 0,43-0,96; p = 0.029)]. Kaplan-Meier analysis revealed a significantly lower incidence of death in patients on an angiotensin receptor blocker (ARB) (n = 33/318;10,4%) compared to patients using an angiotensin-converting enzyme inhibitor (ACEi) (n = 60/348;17,2%) or patients who received neither an ACE-inhibitor nor an ARB at baseline in the uncomplicated phase (n = 90/466; 19,3%; p<0.034). Patients taking an ARB were significantly less frequently reaching the mortality predicting threshold for leukocytes (p<0.001), neutrophils (p = 0.002) and the inflammatory markers CRP (p = 0.021), procalcitonin (p = 0.001) and IL-6 (p = 0.049). ACE2 expression levels in human lung samples were not altered in patients taking RAAS modulators. CONCLUSION: These data suggest a beneficial effect of ARBs on disease severity in patients with cardiovascular comorbidities and COVID-19, which is linked to dampened systemic inflammatory activity.

Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study.

Objective: Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes. Approach and Results: Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34-expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3+/-2.4 pg/mL and 0.1+/-1.0 mg/L; P=0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, -0.17; P<0.001). Using linear regression, IL-6 and high-sensitivity CRP levels declined by -0.59 (95% CI, -0.90 to -0.20) pg/mL and -0.13 (-0.28 to 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables, as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95% CI, 9-13) greater risk of death/myocardial infarction. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts. Conclusions: Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes.

Postoperative Neutrophil-to-Lymphocyte Ratio Is Associated with Mortality in Adult Patients After Cardiopulmonary Bypass Surgery: A Cohort Study.

BACKGROUND Cardiopulmonary bypass (CPB) contributes to the development of systemic inflammatory response after cardiothoracic surgery. As a measure of inflammation and immune reaction, the neutrophil-to-lymphocyte ratio (NLR) has been linked to poor outcomes in a variety of diseases. However, it remains to be seen whether postoperative NLR is associated with CPB patient mortality. The purpose of this research was to explore the prognostic role of the postoperative NLR in adult patients undergoing cardiothoracic surgery with cardiopulmonary bypass. MATERIAL AND METHODS This is an analysis of data stored in the databases of the MIMIC-III, which contains data of critically ill patients for over 50,000. The exposure of interest was postoperative NLR. The primary outcomeaThis study incorporates data from the MIMIC III database, which includes more than 50 000 critically ill patients. The variable of interest was postoperative NLR. The primary outcome was 30-day mortality and the secondary outcomes were 90-day mortality, length of intensive care unit stay, and length of hospital stay. was 30-day mortality, the secondary outcome was 90-day mortality, length of hospital stay and length of ICU stay. RESULTS We enrolled 575 CPB patients. The ROC curve for the postoperative NLR to estimate mortality was 0.741 (95% confidence interval [CI]: 0.636-0.847, P<0.001), and the critical value was 7.48. There was a significant difference between different postoperative NLR levels in the Kaplan-Meier curve (P=0.045). Furthermore, elevated postoperative NLR was associated with increased hospital mortality (hazard ratio [HR]: 1.1, 95% CI: 1.0-1.1, P=0.021). However, there was no important relationship in these patients between the postoperative NLR levels and 90-day mortality (HR: 1.1, 95% CI: 1.0-1.5, P=0.465). CONCLUSIONS Our findings suggest that higher postoperative NLR is associated with greater hospital mortality in adult patients undergoing cardiopulmonary bypass surgery.

Standardized measurement of coronary inflammation using cardiovascular computed tomography: integration in clinical care as a prognostic medical device.

AIMS: Coronary computed tomography angiography (CCTA) is a first-line modality in the investigation of suspected coronary artery disease (CAD). Mapping of perivascular fat attenuation index (FAI) on routine CCTA enables the non-invasive detection of coronary artery inflammation by quantifying spatial changes in perivascular fat composition. We now report the performance of a new medical device, CaRi-Heart®, which integrates standardized FAI mapping together with clinical risk factors and plaque metrics to provide individualized cardiovascular risk prediction. METHODS AND RESULTS: The study included 3912 consecutive patients undergoing CCTA as part of clinical care in the USA (n = 2040) and Europe (n = 1872). These cohorts were used to generate age-specific nomograms and percentile curves as reference maps for the standardized interpretation of FAI. The first output of CaRi-Heart® is the FAI-Score of each coronary artery, which provides a measure of coronary inflammation adjusted for technical, biological, and anatomical characteristics. FAI-Score is then incorporated into a risk prediction algorithm together with clinical risk factors and CCTA-derived coronary plaque metrics to generate the CaRi-Heart® Risk that predicts the likelihood of a fatal cardiac event at 8 years. CaRi-Heart® Risk was trained in the US population and its performance was validated externally in the European population. It improved risk discrimination over a clinical risk factor-based model [Δ(C-statistic) of 0.085, P = 0.01 in the US Cohort and 0.149, P < 0.001 in the European cohort] and had a consistent net clinical benefit on decision curve analysis above a baseline traditional risk factor-based model across the spectrum of cardiac risk. CONCLUSION: Mapping of perivascular FAI on CCTA enables the non-invasive detection of coronary artery inflammation by quantifying spatial changes in perivascular fat composition. We now report the performance of a new medical device, CaRi-Heart®, which allows standardized measurement of coronary inflammation by calculating the FAI-Score of each coronary artery. The CaRi-Heart® device provides a reliable prediction of the patient's absolute risk for a fatal cardiac event by incorporating traditional cardiovascular risk factors along with comprehensive CCTA coronary plaque and perivascular adipose tissue phenotyping. This integration advances the prognostic utility of CCTA for individual patients and paves the way for its use as a dual diagnostic and prognostic tool among patients referred for CCTA.

Immune Dysfunction as Measured by the Systemic Immune-Inflammation Index is Associated with the Sub-Type of Minimal Residual Disease and Outcome in Stage II Colon Cancer Treated with Surgery alone.

OBJECTIVE: Within 5 years after curative surgery for stage II colon cancer 25% of patients will relapse due to minimal residual disease (MRD). MRD is the net result of the biological properties of subpopulations of primary tumour cells which enable them to disseminate, implant in distant tissues and survive and the immune system's ability to eliminate them. We hypothesize that markers of immune dysfunction such as the systemic inflammation index (SII) are associated with the sub-type of MRD defined by bone marrow micro-metastasis (mM) and circulating tumour cells (CTCs). A higher immune dysfunction being associated with a more aggressive MRD and worse prognosis. METHODS AND PATIENTS: Blood and bone marrow samples were taken to detect CTCs and mM using immunocytochemistry with anti-CEA one month after surgery. The SII, absolute neutrophil, platelet and lymphocyte counts (ANC, APC, ALC) were determined immediately pre-surgery and one month post-surgery. These were compared with the sub-types of MRD; Group I MRD (-); Group II mM positive and Group III CTC positive; cut-off values of SII of >700 and >900 were used. Follow-up was for up to 5 years or relapse and survival curves using Kaplan-Meier (KM) were calculated. RESULTS: One hundred and eighty one patients (99 women) participated, mean age 68 years, median follow up 4.04 years; I: = 105 patients, II: N= 36 patients, III: N=40 patients. The SII significantly decreased post-surgery only in Group I patients. The frequency of SII >700 and >900 was significantly higher in Group III, between Groups I and II there was no significant difference.  The SII was significantly associated with the number of CTCs detected. The 5-year KM was 98% Group I, 68% Group II and 7% Group III. CONCLUSIONS: The results of the study suggest that the severity of immune dysfunction as determined by the SII is associated with differing sub-types of MRD and a worse prognosis; increasing immune dysfunction is associated with a more aggressive CTC positive MRD sub-type; a more severe immune dysfunction is associated with a higher number of CTCs detected.
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The Impact of NOTCH Pathway Alteration on Tumor Microenvironment and Clinical Survival of Immune Checkpoint Inhibitors in NSCLC.

The treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) has been proven to induce lasting tumor remission. Screening suitable populations for immunotherapy through predictive markers is an important approach to improving the clinical benefits of patients. Evidence has shown that there may be a close connection between NOTCH signaling and the tumor microenvironment (TME). Hence, we explored the impact of the mutation status of NOTCH signaling on the prognosis of NSCLC patients treated with immunotherapy with the aim to apply NSCLC immunotherapy to the greatest extent possible. We examined two clinical cohorts of NSCLC patients receiving ICIs (MSKCC and NG cohorts). The mutation and prognostic data of the ICI-treated cohort were used to evaluate the association between the mutation status of NOTCH signaling and prognosis following immunotherapy. The expression and mutation data of The Cancer Genome Atlas (TCGA)-NSCLC cohort were used to analyze the differences in the immune microenvironment under different NOTCH signaling mutation states. In the ICI-treated cohorts, the univariate and multivariate Cox regression analyses indicated that high-mutated NOTCH signaling could serve as an independent predictor of NSCLC patients receiving ICIs. Patients with high-mutated NOTCH signaling had significantly improved progression-free survival (PFS) (P = 0.03, HR = 0.69; MSKCC cohort) and prolonged overall survival (OS) (P = 0.004, HR = 0.34; NG cohort). Additionally, high-mutated NOTCH signaling was related to the inflammatory immune microenvironment, inflammatory expression profile, and enhanced immunogenicity. According to this study, high-mutated NOTCH signaling may serve as a biomarker for the prediction of the prognosis of NSCLC patients treated with ICIs. A series of prospective clinical studies and molecular mechanism explorations are still needed in the future.