The relationship between a series of inflammatory markers on the risk of heart failure in different gender groups: Analysis from NHANES 2015-2018.

BACKGROUND: A better understanding of the level-grade inflammation for the development and worsening of heart failure (HF) in different gender groups is an unmet need. We performed an updated analysis on the impact of a series of systemic inflammation markers on HF. METHODS: This compensatory cross-sectional study enrolled participants from the National Health and Nutrition Examination Survey (NHANES) 2015-2018. HF was based on the self-reported questions. Univariate and multivariate logistic regression were used to investigate the association between systemic immune-inflammation index (SII), high sensitivity C-reactive protein (hs-CRP), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and HF. For patients of different genders, P for trend was used to analyze potential linear trend relationships and the restricted cubic splines (RCS) were used to describe non-linear relationships. The additive interaction was evaluated by the relative excess risk due to interaction (RERI), attributable proportion (AP), and the synergy index (SI). The multiplicative interaction was evaluated by odds ratio (OR) and 95% confidence interval (CI) of product-term. RESULTS: A total of 5,830 participants from the NHANES database were divided into two groups: the HF group (n = 210) and the non-HF group (n = 5620). After gender stratification, hs-CRP (OR: 1.01, 95% CI: 1.00-1.03), SII (OR: 1.00, 95% CI: 1.00-1.01), NLR (OR: 1.22, 95% CI: 1.11-1.35) and LMR (OR: 0.79, 95% CI: 0.65-0.93) were independent meaningful factors for HF in males, there was no non-linear relationship between the three factors (SII, NLR, hs-CRP, all P for non-linear > 0.05) and the prevalence of HF, but we detected a non-linear relationship between LMR and the prevalence of HF in males (P for non-linear < 0.05). An additive interaction of hs-CRP and NLR on the risk of HF in males (RERI (OR): 0.67, 95% CI: 0.12-1.34; AP (OR): 0.14, 95% CI: 0.02-0.24; SI (OR): 1.22, 95% CI: 1.03-1.44). CONCLUSIONS: In summary, hs-CRP, NLR, and LMR are superior meaningful markers for HF in males. SII may be a meaningful systemic inflammation warning marker for HF, which needs to be discriminated against with caution. Only detected a non-linear relationship between LMR and the prevalence of HF in males. NLR and hs-CRP may have an additive interaction in the prevalence of male HF patients. The outcome compensated for previous studies that still needed more studies for validation.

Exploring the relations of NLR, hsCRP and MCP-1 with type 2 diabetic kidney disease: a cross-sectional study.

Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060-20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026-1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577-0.863, P < 0.001) and 0.862 (95% CI 0.7787-0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.

Neutrophil-Lymphocyte Ratio and Lymphocyte-Monocyte Ratio correlate with Chronic Prosthetic Joint Infection but are not useful markers for diagnosis.

PURPOSE: To investigate reported correlations between Neutrophil-to-Lymphocyte (NLR) and Lymphocyte-to-Monocyte (LMR) ratios and their value in diagnosis of chronic prosthetic joint infection (PJI) in a large cohort of patients from a single specialist hospital. METHODS: Diagnostic aspirations of 362 patients under investigation for PJI were identified. Of the included patients 185 patients received a final diagnosis of PJI and 177 were classed as aseptic. Established criteria (ICM 2018) were employed to define PJI. Included in the analysis are differential white cell counts, C-Reactive Protein (CRP), Synovial Leukocyte Count, Synovial Alpha-defensin ELISA and Synovial Leukocyte esterase activity. Receiver-operator characteristic (ROC) curves were calculated for each of the available diagnostic tests together with the corresponding area under the curve values (AUC). Youden's index was utilized to identify the optimal diagnostic threshold point for the NLR and LMR. Other diagnostic tests were evaluated as per the threshold values previously defined in the literature and specified in the ICM criteria. RESULTS: Using Youden's Index to identify the optimal NLR cut-off within our cohort we established a value of 2.93. This yielded a sensitivity of 0.60 and specificity of 0.64. The area under the curve (AUC) of a receiving operator characteristics (ROC) curve was 0.625. Regarding the LMR the results demonstrate similar findings; a positive correlation with a diagnosis of infection but poor sensitivity and specificity. The AUC for LMR was 0.633 and was not superior to NLR (P = 0.753). CONCLUSIONS: There is a significant correlation between higher Neutrophil-Lymphocyte and Lymphocyte-Monocyte ratios, and a diagnosis of PJI. The sensitivity and specificity of this calculation is poor and the does not add value to the diagnostic algorithm for PJI. LEVEL OF EVIDENCE: Level III Retrospective Cohort analysis.

Exploring the diagnostic and prognostic value of the C-reactive protein/lymphocyte ratio for dilated cardiomyopathy based on a real-world study.

To determine the risk factors for dilated cardiomyopathy (DCM) and construct a risk model for predicting HF in patients with DCM, We enrolled a total of 2122 patients, excluding those who did not meet the requirements. A total of 913 patients were included in the analysis (611 males and 302 females) from October 2012 to May 2020, and data on demographic characteristics, blood biochemical markers, and cardiac ultrasound results were collected. Patients were strictly screened for DCM based on the diagnostic criteria. First, these patients were evaluated using propensity score matching (PSM). Next, unconditional logistic regression was used to assess HF risk. Furthermore, receiver operating characteristic (ROC) curve analysis was conducted to determine diagnostic efficiency, and a nomogram was developed to predict HF. Finally, the Kaplan‒Meier survival curve was plotted. Of the initial 2122 patients, the ejection fraction (EF) in males was worse. We included 913 patients after the final DCM diagnosis. The results showed that the levels of NT-proBNP, WBC, PLT, neutrophils, lymphocytes, eosinophils, and IL-6, C-reactive protein (CRP) and the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and CRP/lymphocyte ratio (CLR) were higher in males than in females (P < 0.001-0.009). The nomogram showed that factors such as sex, WBC, neutrophils, PLR, and CLR could predict the risk of worsening cardiac function in patients with DCM before and after PSM (P < 0.05). The ROC curve showed that CLR with an 85.6% area demonstrated higher diagnostic efficacy than the NLR (77.0%) and PLR (76.6%, P < 0.05). Survival analysis showed a higher mortality risk in females with higher CLR levels (P < 0.001-0.009). However, high CLR levels indicated a higher mortality risk (P < 0.001) compared to sex. Male EF is lower in DCM patients. CLR could predict the risk of declined cardiac function in patients with DCM. The mortality in females with higher CLR levels was highest; however, the exact mechanism should be investigated.

Clinical value of neutrophil-to-lymphocyte ratio and prognostic nutritional index on prediction of occurrence and development of diabetic foot-induced sepsis.

Background: Diabetic foot-induced sepsis is a serious complication associated with increased disability and mortality in hospitalized patients. Early prediction of admission and detection effectively improve treatment options and prevent further deterioration. This study aims to evaluate the clinical value of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) to predict the risk of sepsis in patients with diabetic foot ulcers (DFU). Methods: Retrospective analysis was performed on 216 patients who were admitted to the Fujian Medical University Union Hospital between January 2015 and December 2022. Patients with DFU were divided into the non-sepsis (n = 166) and the DFU-induced sepsis (n = 50) groups. The independent factors of DFU-induced sepsis were determined by univariate and multivariate logistic regression analyses. A receiver operating characteristic (ROC) curve was performed to compare the area under the curves (AUC) of PNI and NLR. Results: Multivariate logistic regression analysis revealed that the PNI, NLR, international normalized ratio (INR), thrombin time (PT), and C-reactive protein (CRP) were independent prognostic factors for DFU-induced sepsis. After adjusting for potential confounders, the adjusted odds ratios of NLR for DFU-induced sepsis were 1.121 (1.072-1.172), 1.132 (1.077-1.189), and 1.080 (1.022-1.142), while those of PNI were 0.912 (0.873-0.953), 0.902 (0.856-0.950), and 1.004 (1.001-1.006). Moreover, the AUC of NLR was significantly greater than that of CRP (0.790, 95% CI: 0.689-0.891, p < 0.001 vs. 0.780, 95% CI: 0.686-0.873, p < 0.001). Conclusion: NLR and PNI have been regarded as readily and independently predictive markers in patients with DFU-induced sepsis. NLR is critical for the early detection and effective treatment of DFU-induced sepsis and is superior to CRP.

Correlation between C-reactive protein and the inflammatory ratios in acute schizophrenia inpatients: are they associated?

C-reactive protein (CRP) and inflammatory ratios have been proposed to study immune dysregulation in schizophrenia. Nevertheless, links between CRP and inflammatory ratios in acute SCZ inpatients have been understudied. This study investigated the relationship between CRP and inflammatory ratios (Neutrophil-Lymphocyte Ratio [NRL], Platelet-Lymphocyte Ratio [PLR], Monocyte-Lymphocyte ratio [MLR] and Basophil-Lymphocyte Ratio [BLR]) in a total of 698 acute SCZ inpatients; and analysed how this relationship is affected by sex and type of episode. CRP correlated with NLR (rs = 0.338, p < 0.001), PLR (rs = 0.271, p < 0.001) and MLR (rs = 0.148, p < 0.001) but not with BLR (rs = 0.059, p = 0.121). Multiple lineal regression analysis showed that high levels of NLR, MLR and PLR but not BLR were independently associated with high CRP levels. No sex-related variations were found. Significant associations were maintained for NLR and MLR in first-episode and multiepisode SCZ, although the strength of the association was stronger in multiepisode SCZ. Again, no sex-related differences were found in these associations. In conclusion, inflammatory ratios were low to moderately associated with CRP in acute SCZ inpatients. NLR and multiepisode SCZ showed the highest associations with CRP. Future studies should consider inflammatory ratios not as a substitute for CRP but as a complementary biomarker.

Engineered Artificial Human Neutrophils Exhibit Mature Functional Performance.

Neutrophils, a key innate immune component, are powerful effector leukocytes for mediating opposing effects on tumor progression and ameliorating pathogen infections. However, their short lifespan and complex purification process have limited neutrophil clinical applications. Here we combined genetic engineering technology with a nanodrug system to construct artificial neutrophils that display functions similar to those of native neutrophils. K562 and HL60 human leukemia cells were engineered to express the human G protein-coupled receptor hM4Di. Compared to the parental cells, engineered hM4Di-K562 and hM4Di-HL60 cells exhibited excellent chemotaxis ability towards clozapine-N-oxide (CNO) and superior bacteria phagocytic behavior, resembling native neutrophils. The antibacterial ability of the hM4Di-K562 cells was further enhanced by loading them with the glycopeptide vancomycin via mesoporous silica nanoparticles (Nano@Van). Our proposed artificial cell engineering platform provides a new avenue to investigate the physiological properties of neutrophils.

Combined use of CRP with neutrophil-to-lymphocyte ratio in differentiating between infectious and noninfectious inflammation in hemodialysis patients.

We tested whether CRP combined with the neutrophil-to-lymphocyte ratio (NLR) optimizes the prediction of infectious inflammation in hemodialysis patients. We conducted a retrospective study of 774 (mean age 71.1 ± 12.8 years, 35% women) hemodialysis patients from our institution, hospitalized between 2007 and 2021 for various reasons, with CRP levels available at admission. Infection was defined according to the International Sepsis Definition Conference criteria. An algorithm for the optimal CRP and NLR cutoff points for predicting infection was developed based on a decision tree analysis in the training cohort (n = 620) and then tested in the validation cohort (n = 154). A CRP level above 40 mg/L (obtained as the cutoff point in predicting infections in the training group, using ROC curve analysis) predicted an infection diagnosis with a sensitivity of 75% and a specificity of 76% with an odds ratio (OR) of 9.37 (95% CI: 5.36-16.39), according to a multivariate logistic regression analysis. Whereas, CRP levels above 23 mg/L together with an NLR above 9.7 predicted an infection diagnosis with a sensitivity of 69% and a specificity of 84% with an OR of 25.59 (95% CI: 9.73-67.31). All these results were reproduced in the validation set. Combined use of CRP with NLR may lower the CRP cutoff point in distinguishing between infectious and noninfectious inflammation in hemodialysis patients.

Microcirculation and neutrophil-related cytokine concentrations are not altered around narrow diameter implants in T2DM patients during wound healing.

OBJECTIVES: The aim of this study was to assess the microcirculation and the expression patterns of wound-healing-related cytokines around narrow-diameter implants in type 2 diabetes mellitus (T2DM) and normo-glycemic patients. MATERIALS AND METHODS: A total of 31 patients, 16 of which diagnosed with T2DM (HbA1c > 6.5) and 15 normo-glycemic patients, received narrow diameter implants in the posterior mandible or maxilla. During the 3-month healing period, soft-tissue perfusion was monitored via laser Doppler flowmetry. Peri-implant fluid (PICF) was harvested and analyzed for concentrations of interleukin-1ß (IL-1ß), interleukin-23 (IL-23), interleukin-17 (IL-17), and granulocyte colony-stimulating factor (G-CSF) by a multiplex, bead-based immunoassay. RESULTS: Microcirculatory perfusion patterns during wound healing exhibited no significant differences throughout the observation period. IL-1ß concentrations were expectedly elevated during the early phases of wound healing. At the first visit after surgery, IL-23 concentrations were significantly higher in implants of diabetic patients. This difference was diminished over the course of the observation period. For the other tested analytes, no differences were observable between both groups. CONCLUSION: Wound healing after implant surgery was similar in T2DM and healthy patients. Hydrophilic-surface titanium-zirconium implants with reduced diameter may be considered for implant therapy of diabetes mellitus type II patients. REGISTRATION NUMBER: NCT04630691 (clinicaltrials.gov).

Markers of neutrophil mediated inflammation associate with disturbed continuous electroencephalogram after out of hospital cardiac arrest.

BACKGROUND: Achieving an acceptable neurological outcome in cardiac arrest survivors remains challenging. Ischemia-reperfusion injury induces inflammation, which may cause secondary neurological damage. We studied the association of ICU admission levels of inflammatory biomarkers with disturbed 48-hour continuous electroencephalogram (cEEG), and the association of the daily levels of these markers up to 72 h with poor 6-month neurological outcome. METHODS: This is an observational, post hoc sub-study of the COMACARE trial. We measured serum concentrations of procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), osteopontin (OPN), myeloperoxidase (MPO), resistin, and proprotein convertase subtilisin/kexin type 9 (PCSK9) in 112 unconscious, mechanically ventilated ICU-treated adult OHCA survivors with initial shockable rhythm. We used grading of 48-hour cEEG monitoring as a measure for the severity of the early neurological disturbance. We defined 6-month cerebral performance category (CPC) 1-2 as good and CPC 3-5 as poor long-term neurological outcome. We compared the prognostic value of biomarkers for 6-month neurological outcome to neurofilament light (NFL) measured at 48 h. RESULTS: Higher OPN (p = .03), MPO (p < .01), and resistin (p = .01) concentrations at ICU admission were associated with poor grade 48-hour cEEG. Higher levels of ICU admission OPN (OR 3.18; 95% CI 1.25-8.11 per ln[ng/ml]) and MPO (OR 2.34; 95% CI 1.30-4.21) were independently associated with poor 48-hour cEEG in a multivariable logistic regression model. Poor 6-month neurological outcome was more common in the poor cEEG group (63% vs. 19% p < .001, respectively). We found a significant fixed effect of poor 6-month neurological outcome on concentrations of PCT (F = 7.7, p < .01), hsCRP (F = 4.0, p < .05), and OPN (F = 5.6, p < .05) measured daily from ICU admission to 72 h. However, the biomarkers did not have independent predictive value for poor 6-month outcome in a multivariable logistic regression model with 48-hour NFL. CONCLUSION: Elevated ICU admission levels of OPN and MPO predicted disturbances in cEEG during the subsequent 48 h after cardiac arrest. Thus, they may provide early information about the risk of secondary neurological damage. However, the studied inflammatory markers had little value for long-term prognostication compared to 48-hour NFL.

Effect of ozone therapy on neutrophil/lymphocyte, platelet/lymphocyte ratios, and disease activity in ankylosing spondylitis: a self-controlled randomized study.

This retrospective self-controlled randomized study was carried out with the participation of 53 patients diagnosed with ankylosing spondylitis according to the modified New York criteria. The patients who did not receive medical treatment or did not change their medical treatment within the last 6 months were included in the study. There was a statistically significant decrease in the patients' neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, monocyte/lymphocyte ratio, C-reactive protein, Visual Analog Scale, Bath Ankylosing Spondylitis Functional Index, and Bath Ankylosing Spondylitis Disease Activity Index scores measured after ozone therapy. There was a positive correlation between neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, mean platelet volume/lymphocyte ratio, monocyte/lymphocyte ratio and C-reactive protein, Visual Analog Scale, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index before and after ozone therapy. Our study revealed that the changes in the decreasing tendency of the markers measured in complete blood count after ozone therapy were correlated with the disease activity, which can contribute to understand the effect of ozone therapy on biomarkers.

Hematological characteristics of COVID-19 patients with fever infected by the Omicron variant in Shanghai: A retrospective cohort study in China.

BACKGROUND: A wave of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread in Shanghai, China. Hematological abnormalities have been reported in coronavirus disease 2019 (COVID-19) patients; however, the difference in hematological parameters between COVID-19 patients with fever and patients who are febrile from other causes remains unexplored. METHODS: This retrospective cohort study enrolled 663 SARS-CoV-2 positive patients identified by RT-PCR. Clinical parameters, including age, sex, and threshold cycle values of all COVID-19 patients, and hematological parameters of COVID-19 patients in the fever clinic were abstracted for analysis. RESULTS: Overall, 60.8% of COVID-19 patients were male, and the median age was 45 years. Most of COVID-19 patients were asymptomatic, while 25.8% of patients showed fever and 10.9% of patients had other emergencies. COVID-19 patients with fever had significantly lower white blood cells (WBCs), neutrophils, lymphocytes, platelets and C-reactive protein (CRP), and significantly higher monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and mean platelet volume-to-platelet ratio (MPR) levels, compared with those in SARS-CoV-2 negative patients with fever from other causes (p < 0.05). Neutrophil-to-lymphocyte ratio (NLR), PLR, and systemic inflammatory index (SII) levels were significantly higher in COVID-19 patients with emergencies (p < 0.05). WBCs showed the best performance with an area under the curve (0.756), followed by neutrophils (0.730) and lymphocytes (0.694) in the diagnosis of COVID-19 in the fever clinic. CONCLUSION: WBCs, neutrophils, lymphocytes, platelets, CRP and MLR, PLR, and MPR may be useful in early diagnosis of COVID-19 in the fever clinic.

Short-term impacts of air pollution on the platelet-lymphocyte ratio and neutrophil-lymphocyte ratio among urban adults in China.

The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure. In this study, we included 3487 urban adults from the Wuhan-Zhuhai cohort. Individual inhalation exposure to air pollutants was estimated by combining participants' daily breath volume and ambient concentrations of six air pollutants (including fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3)). The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date. Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model. We found that PLR was negatively related to PM2.5 (lag02-lag06), PM10 (lag02-lag07), NO2 (lag02-lag07), and SO2 (lag03-lag05) and NLR was negatively related to PM10 (lag05 and lag07). In the BKMR model, a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed, whereas PM10 and NO2 appeared to be more important than the other pollutants in the mixture. The negative impact of air pollutants was stronger in males, participants with lower body mass index (< 24 kg/m2), those cooking meals at home, drinkers, and non-exercisers. In conclusion, short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood. PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants.

Neutrophil-to-lymphocyte ratio is not associated with risk of sarcopenia in elderly COVID-19 patients.

BACKGROUND: To assess the existence of association between neutrophil to lymphocyte ratio (NLR) and the risk of sarcopenia in COVID-19 patients. METHODS: A retrospective cross-sectional study was conducted in a university hospital with patients with an active COVID-19 infection admitted to the nursing ward or intensive care unit (ICU) between September to December 2020. Sarcopenia risk was assessed using the Strength, Assistance for walking, Rise from a chair, Climb stairs and Falls (SARC-F). Biochemical analyses were assessed by circulating of C-reactive protein, D-dimer, neutrophils, lymphocytes count and NLR. Sixty-eight patients were evaluated and divided into tertiles of NLR values and the association between NLR and sarcopenia risk were tested using the linear regression analyses and p<0.05 were considered as significant. RESULTS: Sixty-eight patients were evaluated and divided in NLR tertiles being the 1st (men=52.2%; 71.1±9.0 y; NLR: 1.1-3.85), 2nd (women=78.3%; 73.2±9.1 y; NLR: 3.9-6.0) and 3rd (men=72.7%; 71.7±10.4 y; NLR: 6.5-20.0). There was a difference between the tertiles in relation to the first to the biochemical parameters of total neutrophils count (p=0.001), C-reactive protein (p=0.012), and D-dimer (p=0.012). However, no difference was found in linear regression analysis between tertiles of NLR and SARC-F, if in total sample (p=0.054) or divided by sex, if men (p=0.369) or women (p=0.064). CONCLUSION: In elderly patients hospitalized with COVID-19, we do not find an association between the risk of sarcopenia and NLR.

[The Clinical Value of Neutrophil CD64 Index in Hematological Malignancies with Pulmonary Infection].

OBJECTIVE: To investigate the clinical value of neutrophil CD64 index in hematological malignancies with pulmonary infection. METHODS: The cohort study method was used to retrospectively analyze the clinical data of 125 patients with hematological malignancies and pulmonary infections who were treated in The Third Affiliated Hospital of Soochow University. All the patients were divided into four stages according to the diagnosis and treatment process: non-infected stage (T1), the symptoms of infection had appeared before using antibiotics (T2), one week after anti-infective treatment (T3), and after stopping antibiotics (T4). CD64 index, C-reactive protein (CRP), blood cell count, and immune cell level were compared before and after infection (T1 vs T2), the correlation between CD64 index and other indicators were explored, the change trends of the significantly different indicators in the course of the disease were observed, and the diagnostic efficacy of CD64 index and CRP were compared. The surviving patients were followed up for whether reinfection occurred within 30 days after discharge, and the re-examination results of indices before discharge (in stage of T4) between reinfected and non-reinfected patients were compared to find the risk factors of reinfection. RESULTS: Before and after infection, the CD64 index, CRP, CD14+HLA-DR+, CD4+, and lymphocyte counts were significantly different (all P<0.05). There was a negative correlation of CD64 index with CD14+HLA-DR+ (r=-0.395, P<0.001), a negative correlation with CD3+ (r=-0.1.87, P=0.047), and a negative correlation with lymphocyte count (r=-0.230, P=0.006), while a positive correlation with CRP(r=0.313, P<0.001). The area under the curve of CD64 index, CRP, and CD64 index combined with CRP was 0.790 (95%CI: 0.711-0.868), 0.754(95%CI: 0.667-0.841), and 0.835(95%CI: 0.762-0.907), respectively; the sensitivity was 59.6%, 72.7%, and 74.7%, the specificity was 89.2%, 73.0%, and 78.4%, and the cut-off value was 0.488, 0.457, and 0.531, respectively. There were only two re-examination indexes showed significantly different before discharge between reinfected patients and non-reinfected patients: CD14+HLA-DR+ (F=8.524, P=0.004) and CD64 index (F=9.993, P=0.002). The increase of CD64 index was an independent risk factor for reinfection within 30 days after discharge from the hospital (HR=1.790, 95%CI: 1.343-2.386, P<0.001). CONCLUSION: CD64 index has diagnostic value in patients with hematological malignancies and pulmonary infection, and its specificity is higher than that of CRP. The combination of the two indicators can improve the diagnostic sensitivity. CD64 index has a predictive value for reinfection within 30 days after infection treatment.

An optimized method of extracting and quantifying active Neutrophil serine proteases from human whole blood cells.

PURPOSE: Neutrophil serine proteases (NSPs) are implicated in numerous inflammatory diseases. Thus, a robust methodology to monitor and quantify NSPs is important to study disease progression and evaluate the effect of pharmacological interventions. A comparison of the various methods used to extract NSPs from neutrophil granulocytes has not been published, providing the impetus to conduct this method optimization and comparison study. METHODS: Two NSP recovery methodologies were evaluated on samples from five human donors: zymosan stimulation and cell pellet extraction. For the zymosan stimulation method, 1 mL donor blood was added to zymosan and samples were incubated at 37°C for 30 min while shaking. Samples were then centrifuged, and the plasma was collected for quantitation of NSP activity. For the cell pellet extraction procedure, 2 mL whole blood samples were centrifuged into white blood cell pellets following red blood cell lysis. To each pellet, three sequential lysis steps were performed using either 0.05% Nonidet P-40 Substitute (NP40) or 0.02% Triton X-100 lysis buffers under agitation followed by centrifugation. NSP activities were quantified using an exogenous peptide substrate specific to each of the three NSPs being analyzed: neutrophil elastase, cathepsin G, and proteinase 3. RESULTS AND DISCUSSION: The zymosan stimulation method resulted in lower recovery of active NSPs and was unable to stimulate significant release of active cathepsin G. In contrast, the NP40 pellet extraction method showed consistent inter-donor NSP release with greater recoveries of active NSPs than the Triton method or the zymosan stimulation method. Overall, the pellet extraction procedure provided 13.3-fold greater recovery of active neutrophil elastase, 283-fold greater recovery of active cathepsin G, and 2.9-fold greater recovery of active proteinase 3 than the zymosan method. CONCLUSION: The NP40 cell pellet extraction method resulted in greater extraction of active NSPs compared to the other methods investigated here, which may allow for a more accurate and complete biomarker profile when evaluating human clinical samples.

Examining the role of systemic chronic inflammation in diet and sleep relationship.

BACKGROUND: It is well known that systemic chronic inflammation (SCI), which can be modulated by diet, is associated with poor sleep outcomes. However, the role of SCI in diet health and sleep quality relationship has not been well established. METHODS: Here, by using the UK Biobank data set, we assessed the association between markers of SCI (leukocyte, platelet, lymphocyte, neutrophil, and basophil counts; C-reactive protein levels and neutrophil to lymphocyte ratio (NLR)), habitual intake of food groups, diet health and sleep quality in 449,084 participants. We also formally tested the possibility that SCI might mediate the relationship between diet health and sleep quality. RESULTS: Our results revealed (i) negative associations between SCI and food groups that are abundant in healthy diets (fruit, vegetable and oily and non-oily fish) and (ii) positive associations between SCI and food groups that are abundant in unhealthy diets (processed meat). Sleep quality was also negatively associated with platelet counts, CRP levels and NLR. Crucially, however, while platelet and neutrophil counts, CRP levels and NLR fully mediated the association between diet health and sleep quality, leukocyte, lymphocyte and basophil counts partially mediated the associations between diet health and sleep quality. CONCLUSION: Reducing SCI via dietary interventions could be an effective primary and/or complementary strategy to increase sleep quality. Further interventional trials are warranted to (i) establish the strength of associations, preferably by using validated diet and sleep measures and (ii) examine longer term effects of anti-inflammatory diets on sleep-, diet- and inflammation-related health outcomes.

Albumin to Globulin ratio, Neutrophil to Lymphocyte ratio, and Globulin levels do not outperform ESR or CRP when diagnosing periprosthetic joint infection.

OBJECTIVE: To evaluate the relative performance of clinical readouts including serum C-reactive protein (CRP) levels, the erythrocyte sedimentation rate (ESR), globulin (GLB) levels, the albumin to GLB ratio (A/G), and the neutrophil to lymphocyte ratio (NLR) when diagnosing periprosthetic joint infection (PJI). METHODS: Clinical data was collected from 115 individuals diagnosed in our department between January 2017 and December 2020 with either chronic PJI (29 female, 24 male; median age 71.00 years [range, 41-94 years]) or aseptic loosening (30 female, 32 male; median age 68.50 years [range, 34-85 years]). Patient demographic data were compared, and the relative sensitivity and specificity of preoperative GLB, ESR, CRP, NLR, and A/G values as predictors of PJI diagnosis were assessed. RESULTS: Median globulin levels in the PJI and aseptic groups were 31.700 g/L (interquartile range [IQR], 28.400-35.300) and 26.600 g/L (IQR, 24.375-30.550), respectively (p < 0.001). The median A/G values in the PJI and aseptic groups were 1.150 (IQR, 0.960-1.255) and 1.510 (IQR, 1.265-1.670), respectively (p < 0.001). The median NLR values in the PJI and aseptic groups were 2.510 (IQR, 1.900-3.335) and 1.850 (IQR, 1.425 to 2.362), respectively (p < 0.001). The median ESR values in the PJI and aseptic groups were 53.000 mm/h (IQR, 35.000-76.500) and 16.000 mm/h (IQR, 7.000-33.000), respectively (p < 0.001). Median CRP levels in the PJI and aseptic groups were 24.890 mg/L (IQR, 10.595-54.095) and 2.245 mg/L (IQR, 0.865-8.6075), respectively (p < 0.001). Area under the receiver operating characteristic (ROC) curve (AUC) values for CRP, ESR, GLB, A/G, and NLR were 0.841 (95% confidence interval, 0.761-0.903), 0.850 (0.771-0.910), 0.747 (0.658-0.824), 0.779 (0.692-0.851), and 0.708 (0.616-0.789), respectively. When GLB > 26.6 g/L, A/G < 1.32, and NLR > 2.1 were utilized as threshold values to diagnose PJI, GLB and A/G were found to exhibit superior sensitivity (90.57%, 81.13%) to that observed for CRP (71.70%) and ESR (79.25%), but the specificity of these two metrics (GLB: 51.61%, A/G: 72.58%) was significantly reduced relative to that for CRP (87.10%) or ESR (75.81%). ROC analyses further revealed that NLR did not exhibit significant advantages in sensitivity (73.58%) or specificity (70.97%) relative to CRP or ESR. CONCLUSION: Globulin levels, NLR values, and A/G values do not outperform ESR or CRP levels when used to diagnose PJI.

COVID-19 Sequelae and the Host Proinflammatory Response: An Analysis From the OnCovid Registry.

BACKGROUND: Fifteen percent of patients with cancer experience symptomatic sequelae, which impair post-COVID-19 outcomes. In this study, we investigated whether a proinflammatory status is associated with the development of COVID-19 sequelae. METHODS: OnCovid recruited 2795 consecutive patients who were diagnosed with Severe Acute Respiratory Syndrome Coronavirus 2 infection between February 27, 2020, and February 14, 2021. This analysis focused on COVID-19 survivors who underwent a clinical reassessment after the exclusion of patients with hematological malignancies. We evaluated the association of inflammatory markers collected at COVID-19 diagnosis with sequelae, considering the impact of previous systemic anticancer therapy. All statistical tests were 2-sided. RESULTS: Of 1339 eligible patients, 203 experienced at least 1 sequela (15.2%). Median baseline C-reactive protein (CRP; 77.5 mg/L vs 22.2 mg/L, P < .001), lactate dehydrogenase (310 UI/L vs 274 UI/L, P = .03), and the neutrophil to lymphocyte ratio (NLR; 6.0 vs 4.3, P = .001) were statistically significantly higher among patients who experienced sequelae, whereas no association was reported for the platelet to lymphocyte ratio and the OnCovid Inflammatory Score, which includes albumin and lymphocytes. The widest area under the ROC curve (AUC) was reported for baseline CRP (AUC = 0.66, 95% confidence interval [CI]: 0.63 to 0.69), followed by the NLR (AUC = 0.58, 95% CI: 0.55 to 0.61) and lactate dehydrogenase (AUC = 0.57, 95% CI: 0.52 to 0.61). Using a fixed categorical multivariable analysis, high CRP (odds ratio [OR] = 2.56, 95% CI: 1.67 to 3.91) and NLR (OR = 1.45, 95% CI: 1.01 to 2.10) were confirmed to be statistically significantly associated with an increased risk of sequelae. Exposure to chemotherapy was associated with a decreased risk of sequelae (OR = 0.57, 95% CI: 0.36 to 0.91), whereas no associations with immune checkpoint inhibitors, endocrine therapy, and other types of systemic anticancer therapy were found. CONCLUSIONS: Although the association between inflammatory status, recent chemotherapy and sequelae warrants further investigation, our findings suggest that a deranged proinflammatory reaction at COVID-19 diagnosis may predict for sequelae development.

Procalcitonina es superior a recuento linfocitario, índice neutrófilo/linfocito y proteína C reactiva para la predicción de mortalidad a 30 días de pacientes con COVID-19 en el servicio de urgencias / Procalcitonin concentration in the emergency department predicts 30-day mortality in COVID-19 better than the lymphocyte count, the neutrophil-to- lymphocyte ratio, or the C-reactive protein level

Introducción. Existen múltiples variables demográficas y clínicas predictivas de mortalidad en pacientes con COVID-19. Sin embargo, hay menos información sobre el valor pronóstico de los biomarcadores inflamatorios. Métodos. Estudio de cohorte retrospectivo. Se incluyeron de forma consecutiva todos los pacientes con COVID-19, confirmado por laboratorio, atendidos en un servicio de urgencias hospitalario (SUH) y con valor basal de los siguientes biomarcadores: recuento linfocitario, índice neutrófilo/linfocito (INL), proteína C reactiva (PCR) y procalcitonina (PCT). La relación entre los biomarcadores y la mortalidad total a 30 días se analizó mediante una regresión de Cox y gráficos de dosis-respuesta. Resultados. Se incluyeron 896 pacientes, 151 (17%) fallecieron en los primeros 30 días. La mediana de edad fue de 63 años (51-78) y 494 (55%) eran hombres. El valor de INL, PCR y PCT fue mayor, mientras que el recuento linfocitario fue menor, en los pacientes que fallecieron respecto a los que sobrevivieron (p < 0,001). La PCT fue superior al recuento linfocitario, INL y PCR en la predicción de mortalidad a 30 días (ABC 0,79 [IC 95%: 0,75-0,83] vs 0,70 [IC 95%: 0,65-0,74], p < 0,001; 0,74 [IC 95%: 0,69-0,78], p = 0,03; y 0,72 [IC 95%: 0,68-0,76], p < 0,001). Los puntos de decisión de PCT propuestos, 0,06 ng/l para exclusión y 0,72 ng/l para inclusión de muerte a 30 días, podrían facilitar la toma de decisiones en urgencias. Hubo 357 pacientes (40%) con valores de PCT en estas categorías. El análisis multivariable mostró una mayor asociación con la mortalidad para PCT que en los otros biomarcadores estudiados. Conclusión. PCT es el biomarcador con mejor capacidad para predecir mortalidad a 30 días por cualquier causa en pacientes con COVID-19 valorados en un SUH.

Background. Although many demographic and clinical predictors of mortality have been studied in relation to COVID-19, little has been reported about the prognostic utility of inflammatory biomarkers. Methods. Retrospective cohort study. All patients with laboratory-confirmed COVID-19 treated in a hospital emergency department were included consecutively if baseline measurements of the following biomarkers were on record: lymphocyte counts, neutrophil-to-lymphocyte ratio NRL, and C-reactive protein (CRP) and procalcitonin (PCT) levels. We analyzed associations between the biomarkers and all-cause 30-day mortality using Cox regression models and dose–response curves. Results. We included 896 patients, 151 (17%) of whom died within 30 days. The median (interquartile range) age was 63 (51-78) years, and 494 (55%) were men. NLR, CRP and PCT levels at ED presentation were higher, while lymphocyte counts were lower, in patients who died compared to those who survived (P < .001). The areas under the receiver operating characteristic curves revealed the PCT concentration (0.79; 95% CI, 0.75-0.83) to be a better predictor of 30-day mortality than the lymphocyte count (0.70; 95% CI, 0.65-0.74; P < .001), the NLR (0.74; 95% CI, 0.69-0.78; P = .03), or the CRP level (0.72; 95% CI, 0.68-0.76; P < .001). The proposed PCT concentration decision points for use in emergency department case management were 0.06 ng/L (negative) and 0.72 ng/L (positive). These cutoffs helped classify risk in 357 patients (40%). Multivariable analysis demonstrated that the PCT concentration had the strongest association with mortality. Conclusion. PCT concentration in the emergency department predicts all-cause 30-day mortality in patients with COVID-19 better than other inflammatory biomarkers.