Inflammatory subphenotypes previously identified in ARDS are associated with mortality at intensive care unit discharge: a secondary analysis of a prospective observational study.

BACKGROUND: Intensive care unit (ICU)-survivors have an increased risk of mortality after discharge compared to the general population. On ICU admission subphenotypes based on the plasma biomarker levels of interleukin-8, protein C and bicarbonate have been identified in patients admitted with acute respiratory distress syndrome (ARDS) that are prognostic of outcome and predictive of treatment response. We hypothesized that if these inflammatory subphenotypes previously identified among ARDS patients are assigned at ICU discharge in a more general critically ill population, they are associated with short- and long-term outcome. METHODS: A secondary analysis of a prospective observational cohort study conducted in two Dutch ICUs between 2011 and 2014 was performed. All patients discharged alive from the ICU were at ICU discharge adjudicated to the previously identified inflammatory subphenotypes applying a validated parsimonious model using variables measured median 10.6 h [IQR, 8.0-31.4] prior to ICU discharge. Subphenotype distribution at ICU discharge, clinical characteristics and outcomes were analyzed. As a sensitivity analysis, a latent class analysis (LCA) was executed for subphenotype identification based on plasma protein biomarkers at ICU discharge reflective of coagulation activation, endothelial cell activation and inflammation. Concordance between the subphenotyping strategies was studied. RESULTS: Of the 8332 patients included in the original cohort, 1483 ICU-survivors had plasma biomarkers available and could be assigned to the inflammatory subphenotypes. At ICU discharge 6% (n = 86) was assigned to the hyperinflammatory and 94% (n = 1397) to the hypoinflammatory subphenotype. Patients assigned to the hyperinflammatory subphenotype were discharged with signs of more severe organ dysfunction (SOFA scores 7 [IQR 5-9] vs. 4 [IQR 2-6], p < 0.001). Mortality was higher in patients assigned to the hyperinflammatory subphenotype (30-day mortality 21% vs. 11%, p = 0.005; one-year mortality 48% vs. 28%, p < 0.001). LCA deemed 2 subphenotypes most suitable. ICU-survivors from class 1 had significantly higher mortality compared to class 2. Patients belonging to the hyperinflammatory subphenotype were mainly in class 1. CONCLUSIONS: Patients assigned to the hyperinflammatory subphenotype at ICU discharge showed significantly stronger anomalies in coagulation activation, endothelial cell activation and inflammation pathways implicated in the pathogenesis of critical disease and increased mortality until one-year follow up.

Association between advanced lung cancer inflammation index and all-cause and cardiovascular mortality among stroke patients: NHANES, 1999-2018.

Background: Stroke was a major global public health challenge, and its prognosis was remarkably associated with inflammation levels and nutritional status. The advanced lung cancer inflammation index (ALI) was a comprehensive indicator that combined inflammation and nutritional status. Currently, the relationship between ALI and the prognosis of stroke patients was not yet known. The purpose of the current study was to estimate their relationship. Methods: Cohort data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were collected. The association between ALI and all-cause and cardiovascular disease (CVD) mortality in stroke patients was estimated using a multivariable adjusted Cox model. Their non-linear relationship was analyzed by restricted cubic spline analysis. Sensitivity analysis was constructed through stratified analysis and interaction analysis. Results: 1,440 stroke patients were included in this study. An elevated ALI was significantly related to a reduced risk of all-cause mortality in stroke patients but not related to CVD mortality. A reverse J-shaped non-linear association between ALI and all-cause mortality in stroke patients, with an inflection point at 83.76 (the lowest of the mortality risk). On the left side of the inflection point, for each 10 U increase in ALI, there was a 16% reduction in the risk of all-cause mortality. However, on the right side, the risk increased by 6%. There was no remarkable interaction between stratified variables and ALI. Conclusion: This was the first study on the relationship between ALI and all-cause and CVD mortality in stroke patients. Elevated ALI was closely associated with a reduced risk of all-cause mortality. A reverse J-shaped non-linear relationship existed between the two, with an inflection point at 83.76. These findings implied that controlling the ALI of stroke patients within an appropriate range was crucial for their prognosis (such as weight management, albumin supplementation, anti-inflammatory treatment). The dynamic variation in ALI was also advantageous for clinicians in establishing personalized ALI criteria to maximize the long-term survival of stroke patients.

Evaluation of inflammatory biomarkers affecting mortality in acute cholecystitis in the emergency department.

OBJECTIVES: The aim of this study was to investigate the effectiveness of pan-immune inflammation value (PIV), systemic immune-inflammatory index (SII), and systemic inflammation response index (SIRI) in predicting mortality in acute cholecystitis (AC). BACKGROUND: Abdominal pain is one of the most frequent complaints encountered by physicians at emergency department (ED). METHODS: This clinical study is a cross-sectional study among patients admitted to the emergency department of a tertiary hospital and diagnosed with AC. Total survival curves were estimated by the Kaplan‒Meier method. Differences according to risk groups were determined by the log-rank test. RESULTS: A total of 789 patients (survival: 737, non-survival: 52) diagnosed with AC were enrolled in the study. NLR and SII had an excellent diagnostic power in predicting 30-day mortality in the receiver operating characteristic (ROC) analysis, while the diagnostic power of SIRI and PIV was acceptable. It was observed that the probability of survival period decreased in the presence of NLR (>11.07), SII (>2315.18), SIRI (>6.55), and PIV (>1581.13) above the cut-off levels. The HRs of NLR, SII, SIRI, and PIV were 10.52, 7.44, 6.34, and 5.6, respectively. CONCLUSION: NLR, SII, SIRI, and PIV may be useful markers in predicting 30-day mortality in patients with AC (Tab. 3, Fig. 5, Ref. 25).

Inflammatory potential of diet and mortality in Australian adults.

OBJECTIVE: Inflammation is implicated in chronic diseases including cancer and CVD, which are major causes of mortality. Diet can influence inflammation status. We therefore examined whether the inflammatory potential of a person's diet is associated with mortality. DESIGN: The inflammatory potential of the usual diet was assessed by calculating Dietary Inflammatory Index (DII) scores from repeated FFQ data (collected in 1992, 1994 and 1996), placing each participant's diet on a continuum from anti- to pro-inflammatory. DII scores were analysed as a continuous variable and as categories by creating quartile groups. Death registry data were used to ascertain all-cause mortality and separately mortality from CVD, cancers and other causes between 1992 and 2022. Cox proportional hazard regression analysis was used to calculate adjusted hazard ratios (HR) with 95 % CI, comparing higher and lowest quartile groups, or HR change per one DII unit increase. SETTING: Nambour, Australia. PARTICIPANTS: A community-based sample of 1440 adults aged 25-75 years. RESULTS: During follow-up, 488 participants died, including 188 from CVD, 151 from cancer and 170 from other causes. Participants in the most pro-inflammatory diet group were at increased risk of all-cause mortality (HRQ4 v. Q1 = 1·55; 95 % CI 1·19, 2·03; P < 0·001) and other-cause mortality (HRQ4 v. Q1 = 1·69; 95 % CI 1·12, 2·54; P 0·01). A one-unit increase in DII score was associated with a 36 % increased risk of CVD among those younger than 55 years of age (HR for a one-unit increase in DII score 1·36, 95 % CI 1·04, 1·78). The risk of cancer mortality was also increased for those with a more pro-inflammatory diet in age ≤ 55 years (HR for a one-unit increase in DII score 1·20, 95 % CI 1·02, 1·40) and age 56-65 years (HR for a one-unit increase in DII score 1·11, 95 % CI 1·00, 1·23). CONCLUSIONS: A pro-inflammatory diet increases the risk of all-cause mortality. Our results support the promotion of anti-inflammatory diets to help promote longevity.

Paediatric-onset immune-mediated inflammatory disease is associated with an increased mortality risk-A nationwide study.

BACKGROUND: Paediatric-onset immune-mediated inflammatory diseases (pIMID) show more aggressive phenotypes than when diagnosed in adults. However, data on mortality are often extrapolated from adult studies. AIM: To estimate the effect of pIMID on mortality. METHODS: In a population-based cohort study using the nationwide Danish healthcare registers, we included all patients diagnosed with pIMID in Denmark from 1980 to 2018. PIMID were defined as ICD codes indicative of autoimmune hepatitis, primary sclerosing cholangitis, Crohn's disease, ulcerative colitis, juvenile idiopathic arthritis, lupus erythematosus, or vasculitis registered before age 18 years. All-cause mortality was the primary outcome; cause-specific mortality was the secondary outcome. We used Cox survival analysis to estimate hazard ratios (HR), and Aalen survival analysis to estimate rate differences. RESULTS: We included 11,581 individuals diagnosed with pIMID and 99,665 reference individuals, accounting for 1,371,994 person-years of follow-up. Median and interquartile (IQR) age at diagnosis was 12.6 (7.9-15.9) years. During follow-up, 152 patients with pIMID and 316 reference individuals died; adjusted HR (aHR) was 3.8 (95% confidence interval [CI] 3.1-4.7). This corresponded to 6.9 (95% CI: 5.3-8.5) additional deaths per 10,000 person-years. The strongest associations were found for gastrointestinal diseases (aHR 22.8; 95% CI 9.6-64.1), gastrointestinal cancers (aHR 19.2; 95% CI 5.0-74.2) and lymphoproliferative disorders (aHR 6.8; 95% CI 2.8-16.8). CONCLUSION: Patients diagnosed with pIMID have a fourfold higher risk of mortality when followed into early adulthood compared with reference individuals. This underlines the severe disease course of pIMID and highlights the need for multidisciplinary care.

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.

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.

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.

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.

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.

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.

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.

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.