Two cases with discrepancy in the quantitative cytological assessment of cerebrospinal fluid in neonatal samples using light microscopy in comparison with Sysmex XN-1000.

We present two cases from the neonatal department with cerebrospinal fluid examination. We revealed a striking discrepancy in polymorphonuclear (PMN) and mononuclear (MN) cell counts using conventional light microscopy in comparison with automated analyzer Sysmex XN-1000 (PMNs - 13 vs. 173x106/L, MNs - 200 vs. 67x106/L in case 1 and PMNs - 13 vs. 372x106/L, MNs - 411 vs. 179x106/L in case 2). We revealed the dominant presence of hemosiderophages in both cases in cytospin slide. Even though Sysmex XN-1000 offers fast examination with a low sample volume, there is possibility of misdiagnosis, with negative impact on the patient.

Peripheral inflammatory biomarkers as predictive tools for HyperCKemia risk assessment post-seizures.

BACKGROUND: This study evaluates the potential of inflammatory biomarkers, especially the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), for early detection of hyperCKemia after seizures. Addressing the challenge of delayed hyperCKemia diagnosis, which can escalate to rhabdomyolysis, this research emphasizes the use of these accessible biomarkers. METHODS: Conducted retrospectively, data from October 1, 2022, and October 1, 2023, were extracted from electronic medical records. Following univariate analysis (P-value < 0.05 for selection), Spearman's rank correlation and binary logistics regression were employed to examine the relationship between hyperCKemia and various clinical variables. Receiver operating characteristic curves (ROCs) defined the cut-off values for seizure-related hyperCKemia. RESULTS: Among 98 seizure patients, 31 (31.63 %) developed hyperCKemia. Notable differences in leukocytes, neutrophils, CRP, and NLR levels were observed between hyperCKemia and normal CK groups (P < 0.05). Leukocytes, NLR, and CRP correlated with hyperCKemia, exhibiting odds ratios of 1.24 (95 % CI: 1.11-1.39, P < 0.001), 1.03 (95 % CI: 1.01-1.05, P = 0.001), and 1.22 (95 % CI: 1.09-1.35, P = 0.017). The optimal cut-off values were established as 9.78 × 10^9/L for leukocytes, 32.40 mg/L for CRP, and 7.35 for NLR. CONCLUSION: Elevated levels of leukocytes, CRP, and NLR post-seizure are strong indicators of hyperCKemia risk, with significant implications for enhancing clinical decision-making and patient care strategies.

Immunohistochemistry assessment of tissue neutrophil-to-lymphocyte ratio predicts outcomes in melanoma patients treated with anti-programmed cell death 1 therapy.

Elevated neutrophil-to-lymphocyte ratio (NLR) is associated with diminished immunotherapy response in metastatic melanoma. Although NLR assessment in peripheral blood is established, tissue dynamics remain insufficiently explored. This study aimed to evaluate tissue NLR (tNLR)'s predictive potential through immunohistochemistry in immunotherapy-treated melanoma. Fifty melanoma patients who underwent anti-programmed cell death 1 (PD-1) therapy were assessed. Hematological, clinical and tumor features were collected from medical records. Responses were categorized using the Response Evaluation Criteria in Solid Tumors for immunotherapy (iRECIST) guidelines. Immunohistochemistry for tumor-infiltrating T cells (cluster differentiation 3) and neutrophils (myeloperoxidase) was performed on formalin-fixed paraffin-embedded tumor samples. NLR, derived NLR (dNLR) and tNLR were calculated. Overall survival (OS) and survival following immunotherapy (SFI) were calculated from diagnosis or immunotherapy start to loss of follow-up or death. Patients with high tNLR presented improved OS ( P =  0.038) and SFI with anti-PD-1 therapy ( P =  0.006). Both NLR and dNLR were associated with OS ( P =  0.038 and P =  0.046, respectively) and SFI ( P =  0.001 and P =  0.019, respectively). NLR was also associated with immunotherapy response ( P =  0.007). In conclusion, tNLR emerged as a novel potential biomarker of enhanced survival post anti-PD-1 therapy, in contrast to classical NLR and dNLR markers.

Platelet distribution width as an useful indicator of influenza severity in children.

PURPOSE: The present study aims to investigate the potential of platelet distribution width as an useful parameter to assess the severity of influenza in children. METHODS: Baseline characteristics and laboratory results were collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to joint detection of inflammatory markers for influenza positive children, and the scatter-dot plots were used to compare the differences between severe and non-severe group. RESULTS: Influenza B positive children had more bronchitis and pneumonia (P < 0.05), influenza A infected children had more other serious symptoms (P = 0.007). Neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and platelet parameters performed differently among < 4 years and ≥ 4 years children with influenza. Combined detection of platelet parameters and other indicators could better separate healthy children from influenza infected children than single indicator detection. The levels of platelet distribution width of children with severe influenza (A and B) infection was significantly dropped, compared with non-severe group (P < 0.05). CONCLUSIONS: Platelet distribution width could be a very useful and economic indicator in distinction and severity assessment for children with influenza.

Neutrophil to lymphocyte ratio as an assessment tool to differentiate between uterine sarcoma and myoma: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine the potential value of neutrophil to lymphocyte ratio (NLR) as an assessment tool in the clinical distinction between uterine sarcoma and uterine leiomyoma. METHODS: We comprehensively searched Web of Science, Scopus, and PubMed for relevant papers published before March 19, 2023. The standardized mean difference (SMD) was provided, along with a 95% confidence interval (CI). The random-effects model was employed to derive pooled effects due to the high levels of heterogeneity. The Newcastle-Ottawa scale was used for the quality assessment. Our study was registered in PROSPERO (CRD42023478331). RESULTS: Overall, seven articles were included in the analysis. A random-effect model revealed that patients with uterine sarcoma had higher NLR levels compared to those with uterine myoma (SMD = 0.60, 95% CI = 0.22-0.98; p = 0.002). In the subgroup analysis according to sample size, we found that patients with uterine sarcoma had elevated levels of NLR compared to those with uterine myoma in either large studies (SMD = 0.58, 95% CI = 0.04-1.13; P < 0.001) or small studies (SMD = 0.64, 95% CI = 0.33-0.96; P = 0.32). In the sensitivity analysis, we found that the final result was not significantly changed when single studies were removed, suggesting that the finding of this meta-analysis was stable. The pooled sensitivity of NLR was 0.68 (95% CI = 0.61-0.73), and the pooled specificity was 0.64 (95% CI = 0.59-0.69). CONCLUSION: NLR might be utilized as an assessment tool in clinics to help clinicians differentiate between patients with uterine sarcoma and those with myoma.

Neutrophil to Lymphocyte Ratio as an Indicator of Periprosthetic Joint Infection: A Retrospective Cohort Study.

INTRODUCTION: Periprosthetic joint infection (PJI) after total joint arthroplasty (TJA) is a serious complication posing notable clinical implications for patients and substantial economic burdens. Neutrophil to lymphocyte ratio (NLR) is an emerging biomarker of inflammation, which may better predict PJI. The objective of this review was to evaluate NLR changes in patients with confirmed PJI, to compare NLR between an aseptic revision and a revision for PJI, and to establish whether an NLR of 2.45 is an appropriate cutoff for predicting infection. METHODS: A retrospective review of patients who underwent revision TJA for PJI at a single center between January 1, 2005, and December 31, 2018, was performed and compared with an aseptic cohort who underwent aseptic revision TJA. NLR was calculated from complete blood counts performed at index surgery and at the time of revision surgery. Receiver operating characteristic curves were analyzed, along with sensitivity, specificity, and positive and negative likelihood ratios. RESULTS: There were 89 patients included in each cohort. Mean NLR in patients who underwent revision for PJI was 2.85 (± 1.27) at the time of index surgery and 6.89 (± 6.64) at the time of revision surgery ( P = 0.017). Mean NLR in patients undergoing revision for PJI (6.89) was significantly higher than aseptic revisions (3.17; P < 0.001). DISCUSSION: In patients who underwent revision surgery for PJI, NLR was markedly elevated at time of revision compared with the time of index surgery. Because it is a cost-effective and readily available test, these findings suggest that NLR may be a useful triage test in the diagnosis of PJI. LEVEL OF EVIDENCE: Level III Diagnostic Study.

Neutrophil-to-lymphocyte ratio at admission for early diagnosis, severity assessment, and prognosis of acute traumatic spinal cord injury.

STUDY DESIGN: A retrospective study. OBJECTIVE: This study examined the value of neutrophil-to-lymphocyte ratio at admission for early diagnosis, severity assessment, and prognosis of acute traumatic SCI. SETTING: The First People's Hospital of Neijiang, China. METHODS: This was a single-center, retrospective, cohort study of patients treated within 12 h of acute SCI between January 2018 and October 2022. Ninety-four SCI patients were selected as the Observation group, including 26 with complete injury (AIS grade A) and 68 with incomplete injury (AIS grade B-D), while 94 patients with simple spinal fracture were randomly selected as the Control group. Eighty-one observation group patients underwent surgical treatment, of which 33 had a higher AIS grade (Good prognosis subgroup) and 48 a lower or equal grade post-surgery (Poor prognosis subgroup). Univariate and multivariate analyses were performed to assess predictors of early diagnosis, severity, and 6-month outcome. RESULTS: Initial white blood cell count, neutrophil count, monocyte count, and NLR were higher in the Observation group than the Control group, while lymphocyte count was lower in the Observation group. Multivariate logistic regression analysis identified NLR as an independent predictor of early diagnosis. Spinal canal encroachment ≥50%, neutrophil count, and NLR were higher in the complete injury subgroup, and spinal canal encroachment ≥50% was an independent predictor of complete injury, while NLR was not. The NLR was higher in the poor prognosis subgroup and was an independent risk factor. CONCLUSIONS: Peripheral blood NLR is useful for early diagnosis of acute SCI and is predictive of clinical outcome.

Neutrophil-to-lymphocyte ratio as a promising non-invasive biomarker for symptom assessment and diagnosis of interstitial cystitis/bladder pain syndrome.

BACKGROUND: Our study aims to investigate the association between the serum neutrophil-to-lymphocyte ratio (NLR) and interstitial cystitis (IC), as well as to explore whether NLR can serve as a diagnostic marker to distinguish IC from overactive bladder (OAB). We postulate that elevated NLR levels are intricately linked to the onset and clinical presentation of IC, and that the NLR profiles in OAB patients exhibit discernible disparities from those of IC patients. METHODS: In a retrospective analysis, we scrutinized the medical records of 70 women diagnosed with IC/BPS, 20 women diagnosed with OAB, and a randomly selected cohort of 150 healthy women who underwent physical examinations during the same temporal frame. A comprehensive panel of blood tests was administered to all participants, and NLR was determined through the calculation of the neutrophil-to-lymphocyte proportion. Additionally, symptom assessment questionnaires and urination diaries were collected from IC/BPS patients. RESULTS: NLR levels exhibited significant distinctions among the IC/BPS, Normal, and OAB groups (P < 0.001). Within the IC/BPS group, Hunner type interstitial cystitis (HIC) demonstrated notably divergent NLR levels in comparison to non-Hunner type interstitial cystitis (NHIC) (p = 0.001). Additionally, we observed positive correlations between NLR and Nighttime voids (r = 0.268, p = 0.029), ICPI (r = 0.327, p = 0.007), ICSI (r = 0.369, p = 0.002), PUF Symptom Scale (r = 0.263, p = 0.032), and PUF (r = 0.297, p = 0.015). The receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.765 for NLR in distinguishing IC/BPS from the Normal group, and an AUC of 0.707 in discerning IC from OAB. Furthermore, the AUC of NLR was 0.723 for identifying HIC and NHIC patients. CONCLUSIONS: Our study unveils the prospective utility of serum NLR as a promising biomarker for both diagnostic and symptom evaluation purposes in IC/BPS patients. It effectively demarcates this condition from OAB, which presents with similar clinical features. Consequently, NLR demonstrates potential as a non-invasive diagnostic instrument to distinguish between the subtypes of IC, particularly HIC and NHIC, which manifest similar symptoms within the IC/BPS spectrum.

Assessment of prognostic biomarkers in sudden sensorineural hearing loss: A systematic review and meta-analysis.

Sudden sensorineural hearing loss (SSNHL) is defined as hearing loss of more than 30 dB in less than 72 h. SSNHL is a frequent complaint and an emergency in otolaryngology. Various biomarkers have been used to determine the prognosis of SSNHL. This systematic review and meta-analysis aims to evaluate the relationship between the different biomarkers and the prognosis of SSNHL. We searched English-language literature up to October 2022 in four databases, including PubMed, Google Scholar, Cochrane, and Science Direct. This search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. This study was reported in the International Prospective Register of Systematic Reviews (PROSPERO) database (ID = CRD42022369538). All studies examining the role of neutrophil to lymphocyte ratio (NLR) concluded that higher NLR is associated with a worse prognosis. The results of studies regarding the relationship between platelet to lymphocyte ratio (PLR) and tumor necrosis factor (TNF) are controversial. Other factors shown to be associated with SSNHL include Glycated hemoglobin (HbA1C), blood glucose, iron levels, serum endocan, salusin-beta, and bone turnover biomarkers. This meta-analysis showed that PLR, NLR, and neutrophils were significantly different between recovered and non-recovered patients. PLR, NLR, and neutrophil count are reliable tools to assess the prognosis of patients with SSNHL.

Assessment and predictive ability of the absolute neutrophil count in peripheral blood for in vivo CAR T cells expansion and CRS.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is an advanced and effective immunotherapy for relapsed or refractory B-cell malignancies. High expansion of CAR T cells in vivo and durable antitumor activity indicate a persistent therapeutic response. However, this treatment is linked to a high frequency of adverse events, such as cytokine release syndrome (CRS), which affects its efficacy and can even be life-threatening. At present, a variety of markers associated with clinical response and treatment toxicity after CAR T cells infusion have been reported. Although these biomarkers can act as effective indicators reflecting CAR T cells expansion as well as CRS, they fail to predict the expansion rate of CAR T cells. Hence, further investigation is urgent to find a new biomarker to fill this void. METHODS: We analyzed the association between the absolute neutrophil count (ANC) and CAR expansion and CRS in 45 patients with B-cell malignancies from two clinical trials. We proposed that ANC could be a practical biomarker for CAR T cells expansion and CRS, and conducted a feasibility analysis on its predictive ability. RESULTS: In this study, 17 B-cell hematological malignancy patients with anti-B-cell maturation antigen CAR-treated and 28 with CAR19/22 T-cell-treated were enrolled and divided into an ANC-absence group and an ANC-presence group. The results showed that ANC absence correlated positively with CAR expansion and the expansion rate. The ANC can be used as a predictive marker for CAR T cells expansion. Moreover, the patients with ANC absence experienced a more severe CRS, and ANC performed a predictive ability for CRS. In addition, the peak serum concentration of several cytokines involved in CRS was higher in patients with ANC absence. CONCLUSION: Thus, we suggest ANC as an evaluative and predictive biomarker for CAR expansion and CRS during CAR T cell therapy, which can help to maximize clinical efficacy, reduce treatment-related toxicity and prolong survival.

A Comparative Assessment of the Inflammatory Markers in Patients with Fibromyalgia under Duloxetine Treatment.

BACKGROUND: This study was carried out to compare the levels of inflammatory markers in the complete blood count before and after they began receiving duloxetine in patients with fibromyalgia syndrome (FMS). METHODS: The patient and control groups were composed of 40 patients diagnosed with FMS in accordance with the 2016 American College of Rheumatology (ACR) criteria and 40 healthy volunteers, respectively. The data collection tools comprised the sociodemographic information form, the fibromyalgia impact questionnaire (FIQ), and the sleep hygiene index (SHI), which were used to assess patients' sociodemographic characteristics, FMS disease activity, and sleep quality, respectively. The inflammatory markers of the patient group were assessed by complete blood count before and after the duloxetine treatment and compared with those of the control group. RESULTS: The white blood cell (WBC), neutrophil, and lymphocyte counts were significantly higher in the patient group than in the control group (p < 0.001, p = 0.036 and p = 0.004, respectively). Moreover, platelet distribution width (PDW) was significantly lower, whereas mean platelet volume (MPV) was significantly higher in the patient group than in the control group (p < 0.001 for both cases). In addition to patients' platelet-to-lymphocyte ratio (PLR) values, C-reactive protein (CRP) levels, and white blood cell (WBC) counts decreasing but not significantly (p = 0.083, p = 0.068, and p = 0.065, respectively), their neutrophil-to-lymphocyte ratio (NLR), hemoglobin (Hgb), and hematocrit (Hct) values declined substantially after commencing duloxetine treatment (p = 0.001, p = 0.008, and p = 0.001, respectively). CONCLUSIONS: The significant reduction in NLR, Hgb, and Hct levels following duloxetine treatment may indicate that these parameters can be utilized as biomarkers in determining the efficacy of treatment and in the follow-up of the treatment in FMS patients.

Model-based assessment of neutrophil-mediated phagocytosis and digestion of bacteria across in vitro and in vivo studies.

Neutrophil granulocytes are key components of the host response against pathogens, and severe neutropenia, with neutrophil counts below 0.5 × 106 cells/mL, renders patients increasingly vulnerable to infections. Published in vitro (n = 7) and in vivo (n = 5) studies with time-course information on bacterial and neutrophil counts were digitized to characterize the kinetics of neutrophil-mediated bacterial killing and inform on the immune systems' contribution to the clearance of bacterial infections. A mathematical model for the in vitro dynamics of bacteria and the kinetics of neutrophil-mediated phagocytosis and digestion was developed, which was extended to in vivo studies in immune-competent and immune-compromised mice. Neutrophil-mediated bacterial killing was described by two first-order processes-phagocytosis and digestion-scaled by neutrophil concentration, where 50% of the maximum was achieved at neutrophil counts of 1.19 × 106 cells/mL (phagocytosis) and 6.55 × 106 cells/mL (digestion). The process efficiencies diminished as the phagocytosed bacteria to total neutrophils ratio increased (with 50% reduction at a ratio of 3.41). Neutrophil in vivo dynamics were captured through the characterization of myelosuppressive drug effects and postinoculation neutrophil influx into lungs and by system differences (27% bacterial growth and 9.3% maximum capacity, compared with in vitro estimates). Predictions showed how the therapeutically induced reduction of neutrophil counts enabled bacterial growth, especially when falling below 0.5 × 106 cells/mL, whereas control individuals could deal with all tested bacterial burdens (up to 109 colony forming units/g lung). The model-based characterization of neutrophil-mediated bacterial killing simultaneously predicted data across in vitro and in vivo studies and may be used to inform the capacity of host-response at the individual level.

The predictive role of laboratory parameters in cardiovascular risk assessment in obese.

The significance of cardiovascular diseases in mortality is indisputable. It is well-established that cardiovascular diseases are more prevalent among individuals with obesity. This study aimed to determine the predictive value of easily accessible hematological and biochemical parameters in assessing cardiovascular risk among obese patients. The study was designed as an observational retrospective. Department of Family Medicine, study was carried out between 25/06/2022 to 30/10/2022. The data of 439 obese patients were analyzed retrospectively. Using the online Heart Score system, the patients were classified into low, medium, high, and very high cardiovascular risk categories. The hemogram and certain biochemistry values of the patients at the time of admission were examined. Receiver operating characteristic (ROC) analyses were conducted to discriminate cardiovascular risk classes based on laboratory values. Markers with high diagnostic value, including a high area under the curve (AUC) value, sensitivity, and specificity, were presented. Significant differences were observed between the groups in terms of age, systolic blood pressure, diastolic blood pressure, total cholesterol, low-density lipoprotein, glucose, HbA1c, hemoglobin, platelet count, neutrophil (NEU) count, and platelet-lymphocyte ratio parameters (P < .05). The white blood cell count and NEU count of patients in the high-risk groups were found to have significantly higher AUC values compared to the moderate-risk group (AUC values of .737 and .779, respectively). The white blood cell and NEU parameters were found to have a positive predictive value in estimating the degree of cardiovascular risk. These parameters can potentially serve as biomarkers in identifying individuals at high risks for cardiovascular diseases.

Ambient NO2 hinders neutrophil extracellular trap formation in rats: Assessment of the role of neutrophil autophagy.

NO2 has been known to impair immunity and exacerbate susceptibility to infectious diseases. However, scant notice has been taken of the effect of NO2 on neutrophils. Neutrophil extracellular traps (NETs) formation is necessary for NETosis development by neutrophils as an immune system against pathogens. By analyzing the morphology and signature components of NETs, we focused for the first time on finding that 10 ppm of NO2 exposure for 15 consecutive days can hinder the formation of NETs. Next, we used NO2 in vivo derivatives to probe the mechanism for NETs formation in vitro. Our findings showed that NO2 suppression of respiratory burst levels and mitogen-activated protein kinase (MAPK)/Phosphoinositide 3-kinase (PI3K)-protein kinase B (AKT) signaling was related to NO2 reduction in NETs formation. Inhibition of phorbol myristate acetate (PMA)-induced NETs formation by NO2 hindered autophagy, as evidenced by increased mTOR protein expression, decreased LC3 protein expression, and reduced autophagic vesicles. By activating mTOR-mediated autophagy, rapamycin (Rapa) reduced the inhibition of PMA-induced NETs by NO2. This study will provide valuable insights into the mechanisms of immunotoxicity of NO2, new insights into the etiology of diseases linked to NETs formation, and a theoretical basis for protection against such illnesses.

Assessment of uncertainties in threshold doses for tissue reactions following acute external radiation exposure.

The study aimed to estimate threshold doses and their uncertainties for some human health effects after short-term high dose-rate radiation exposure by quantile technique and the effective dose threshold technique based on distribution functions. The relative uncertainty (U) of the threshold dose was estimated using the error propagation technique. The quantile technique provided statistically significant estimates of threshold doses for acute radiation syndrome onset (0.44 ± 0.12 Gy, U = 143%) and lethality (1.84 ± 0.44 Gy, U = 117%) but relative uncertainties were high. The effective threshold dose technique provided statistically significant and more precise threshold dose estimates for acute radiation syndrome onset (0.73 ± 0.02 Gy, U = 18%) and lethality (6.83 ± 0.08 Gy, U = 36%), as well as agranulocytosis (3.51 ± 0.03 Gy, U = 16%) and vomiting onset in the prodromal period (1.54 ± 0.02 Gy, U = 16%). Threshold doses estimated for the change in the peripheral blood neutrophil and leukocyte counts during the first days after short-term high dose-rate radiation exposure were not statistically significant.

The value of NLR versus MLR in the short-term prognostic assessment of HBV-related acute-on-chronic liver failure.

BACKGROUND: Systemic inflammation is associated with the development and progression of hepatitis B-associated acute-on-chronic liver failure (HBV-ACLF). The neutrophil-to-lymphocyte ratio (NLR) has been reported to be a prognostic biomarker in patients with HBV-ACLF. However, the role of the monocyte-to-lymphocyte ratio (MLR) as a prognostic inflammatory biomarker in multiple diseases is rarely mentioned in HBV-ACLF. METHODS: We included a total of 347 patients with HBV-ACLF who met the definition of the Chinese Guidelines for the Diagnosis and Treatment of Liver Failure (2018 edition). Among them, 275 cases were included retrospectively, and 72 cases were collected prospectively. Clinical characteristics and laboratory examination data were collected from medical records within 24 h after diagnosis to calculate MLR and NLR levels, and lymphocyte subpopulation counts were collected in prospectively included patients. RESULTS: Of the 347 patients with HBV-ACLF, 128 patients in the non-surviving group had a mean age of 48.87 ± 12.89 years; 219 patients in the survival group had a mean age of 44.80 ± 11.80 years and a combined 90-day mortality rate of 36.9%. The median MLR was higher in the non-survivors than in the survivors (0.690 vs 0.497, P < 0.001). MLR values were significantly associated with 90-day mortality in HBV-ACLF (OR 6.738; 95% CI 3.188-14.240, P < 0.001). The AUC for the predictive power of the combined MLR and NLR analysis for HBV-ACLF was 0.694, and the calculated MLR threshold was 4.495. In addition, in the analysis of peripheral blood lymphocyte subsets in HBV-ACLF, a significant decrease in the number of circulating lymphocytes was found in HBV-ACLF patients in the non-surviving group (P < 0.001), with a predominant decrease in the number of CD8 + T cells and no significant difference in the number of CD4 + T cells, B cells or NK cells. CONCLUSION: Increased MLR values are associated with 90-day mortality in patients with HBV-ACLF, and the MLR may serve as a potential prognostic indicator for patients with HBV-ACLF. Decreased CD8 + T-cell counts may be associated with poor survival in patients with HBV-ACLF.

Neutrophil-only Histological Assessment of Ulcerative Colitis Correlates with Endoscopic Activity and Predicts Long-term Outcomes in a Multicentre Study.

BACKGROUNDS AND AIMS: Absence of neutrophils is the minimum standard to consider histological remission of ulcerative colitis [UC]. The PICaSSO Histological Remission Index [PHRI] is a new simple index for UC, based only on the detection of neutrophils. We evaluate PHRI's correlation with endoscopy and its prognostic value compared with other established indices. METHODS: Consecutive patients with UC underwent colonoscopy at two referral centres [Birmingham, UK, and Milan, Italy,] and were followed up for 2 years. Correlation between histology (PHRI, Nancy [NHI], and Robarts [RHI] indexes) and endoscopy (Mayo Endoscopic Score [MES], Ulcerative Colitis Endoscopic Index of Severity [UCEIS], and PICaSSO index) was calculated as Spearman coefficients. Diagnostic performance of endoscopy was assessed with receiver operating characteristic [ROC] curves and outcome stratification with Kaplan-Meier curves. RESULTS: A total of 192 patients with UC was enrolled, representing all grades of endoscopic severity. Correlation between histology and endoscopy did not differ significantly when using PHRI instead of NHI or RHI. In particular, PHRI's correlation with MES, UCEIS, and PICaSSO was 0.745, 0.718, and 0.694, respectively. Endoscopically-assessed remission reflected the absence of neutrophils [PHRI = 0] with areas under the ROC curve of 0.905, 0.906, and 0.877 for MES, UCEIS, and PICaSSO, respectively. The hazard ratio for disease flare between patients in histological activity/remission was statistically similar [p >0.05] across indexes [2.752, 2.706, and 2.871 for RHI, NHI, and PHRI, respectively]. CONCLUSION: PHRI correlates with endoscopy and stratifies risk of relapse similarly to RHI and NHI. Neutrophil-only assessment of UC is a simple yet viable alternative to established histological scores.

Development of Duffy Null-Specific Absolute Neutrophil Count Reference Ranges.

This study establishes a Duffy null phenotype­specific absolute neutrophil count reference range to optimize care and improve health equity.

Real-time assessment of neutrophil metabolism and oxidative burst using extracellular flux analysis.

Neutrophil responses are critical during inflammatory and infective events, and neutrophil dysregulation has been associated with poor patient outcomes. Immunometabolism is a rapidly growing field that has provided insights into cellular functions in health and disease. Neutrophils are highly glycolytic when activated, with inhibition of glycolysis associated with functional deficits. There is currently very limited data available assessing metabolism in neutrophils. Extracellular flux (XF) analysis assesses real time oxygen consumption and the rate of proton efflux in cells. This technology allows for the automated addition of inhibitors and stimulants to visualise the effect on metabolism. We describe optimised protocols for an XFe96 XF Analyser to (i) probe glycolysis in neutrophils under basal and stimulated conditions, (ii) probe phorbol 12-myristate 13-acetate induced oxidative burst, and (iii) highlight challenges of using XF technology to examine mitochondrial function in neutrophils. We provide an overview of how to analyze XF data and identify pitfalls of probing neutrophil metabolism with XF analysis. In summary we describe robust methods for assessing glycolysis and oxidative burst in human neutrophils and discuss the challenges around using this technique to assess mitochondrial respiration. XF technology is a powerful platform with a user-friendly interface and data analysis templates, however we suggest caution when assessing neutrophil mitochondrial respiration.

A Tandem-Locked Fluorescent NETosis Reporter for the Prognosis Assessment of Cancer Immunotherapy.

NETosis, the peculiar type of neutrophil death, plays important roles in pro-tumorigenic functions and inhibits cancer immunotherapy. Non-invasive real-time imaging is thus imperative for prognosis of cancer immunotherapy yet remains challenging. Herein, we report a Tandem-locked NETosis Reporter 1 (TNR1 ) that activates fluorescence signals only in the presence of both neutrophil elastase (NE) and cathepsin G (CTSG) for the specific imaging of NETosis. In the aspect of molecular design, the sequence of biomarker-specific tandem peptide blocks can largely affect the detection specificity towards NETosis. In live cell imaging, the tandem-locked design allows TNR1 to differentiate NETosis from neutrophil activation, while single-locked reporters fail to do so. The near-infrared signals from activated TNR1 in tumor from living mice were consistent with the intratumoral NETosis levels from histological results. Moreover, the near-infrared signals from activated TNR1 negatively correlated with tumor inhibition effect after immunotherapy, thereby providing prognosis for cancer immunotherapy. Thus, our study not only demonstrates the first sensitive optical reporter for noninvasive monitoring of NETosis levels and evaluation of cancer immunotherapeutic efficacy in tumor-bearing living mice, but also proposes a generic approach for tandem-locked probe design.