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Introduction The immune reconstitution (IR) after the allogenic hematopoietic stem cell transplantation (allo-HSCT) is a progressive process intrinsically correlated to the therapeutic success. It is essential to understand the interfering factors in IR to prevent the HSCT-related mortality. Methods We retrospectively evaluated the clinical outcomes, absolute lymphocyte counts (ALCs) and lymphocyte subtypes at different time-points of 111 pediatric patients with allogeneic HSCT for malignant and non-malignant diseases from 2013 to 2018. Results The ALCs gradually increased on D+30, D+100, and D+180 (medians 634/μL, 1022/μL and 1541/μL, respectively). On D+100, the CD3+CD8+ achieved the highest recovery rate (68%), followed by the CD16+CD56+ (47%), CD3+CD4+ (39%) and CD19+ (8%). The adequate ALC recovery was associated with age < 8 years, bone marrow grafts, myeloablative conditioning, non-use of serotherapy and non-haploidentical donors. The ALC and CD3+CD8+ on D+100 counts were higher in patients with the cytomegalovirus infection. The CD3+CD4+ recovery was associated with an age < 8 years, a non-malignant disease and a lower incidence of acute graft-versus-host disease ≥ grade 2. Furthermore, the ALC recovery on D+100 resulted in a higher overall survival, regardless of the disease type (HR 3.65, 1.05 - 12.71, p= 0.04). Conclusion Several factors influenced the IR after the allo-HSCT. The ALC ≥ 500/μL on D+100 was a simple IR predictor of survival, easily available to resource-limited centers.

Elevated neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has been shown to correlate with worse outcomes in patients undergoing vascular surgery. Limited data exists on the association of NLR and outcomes in patients undergoing lower extremity vascular surgery. We sought to investigate whether preoperative NLR correlates with outcomes in patients undergoing open lower extremity revascularization procedures.We conducted a retrospective analysis of a prospectively maintained database of patients who underwent open lower extremity revascularization procedures from January 2011 to January 2017 (N = 535). Preoperative NLR was calculated within 6 months of surgery. Primary outcomes were major adverse limb event (MALE) or death. The maximally-ranked statistic method was used to determine the NLR cut-off point. Kaplan-Meier analyses of death and MALE and NLR were used to compare the groups by NLR cut-off point. We conducted a multivariate analysis of the association between NLR and mortality using Cox proportional hazard models, including confounding variables such as age, smoking status, and diabetes. P-values0.05 were considered statistically significant.Two hundred and fifty four patients undergoing surgery from January 2011 to January 2013 were analyzed. The median NLR was 3.6 interquartile range [IQR 2.5-6.7]. The analysis showed a negative correlation between elevated NLR and mortality (P 0.001), but not MALE (P = 0.8). Controlling for multiple comorbidities including gender, age, smoking, body mass index (BMI), diabetes, hyperlipidemia, hypertension, and infection, the NLR cut-off point was a significant independent predictor of mortality (P 0.0001), but not MALE (P = 0.551). Elevated NLR was also correlated with statistically and clinically significant longer hospital stays (6.5 [IQR 3.0-12.8] days vs. 4.0 [IQR 2.0-8.0] days, P = 0.027).This study suggests that NLR is an independent predictor of mortality and hospital length of stay in patients undergoing open lower extremity revascularizations. Going forward, we plan to expand this study to include more patients and to compare NLR to other risk assessment tools.

The association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and monocyte to lymphocyte ratio (MLR) with depression has been investigated extensively while the results were conflicting. We aim to investigate whether NLR, PLR, and MLR are associated with depression, as well as to explore the potential non-linear relationship between them.This cross-sectional study was conducted based on representative samples of US adults from the National Health and Nutrition Examination Survey 2005-06 to 2017-18. Major depression was defined as a 9-item Patient Health Questionnaire of 10 or more. Multivariable logistic regression models were used to calculate the odds ratio of depression in relation to NLR, PLR, and MLR with the first quartile of their values as the reference. Restricted cubic splines (RCS) were added to the regression model to estimate the non-linear relationship between NLR, PLR, or MLR and depression.A total of 34,324 participants were included in the study and 3009 of them were diagnosed with major depression. Only PLR was significantly associated with depression after adjustment of all covariates in the multivariable logistic regression analysis. RCS showed that NLR was significantly associated with depression after adjustment of all covariates and NLR, PLR, and MLR were associated with depression in a non-linear manner.The cross-sectional design did not imply any causal inferences.NLR and PLR were associated with depression after adjustment of potential confounders in a non-linear manner. Prospective studies might be needed to further reveal the non-linear relationships.

Objectives: Recurrent Aphthous Stomatitis (RAS) a chronic idiopathic oral mucosal disease. But yet the etiology and pathogenesis of RAS are not exactly known, it is thought that inflammation play an important role in the pathogenesis. The aim of this study is to demonstrate the role of systemic inflammation among the possible etiological factors of RAS and to find the possible diagnostic correlation between Systemic Immune Inflammation Index (SII). Methods: Patients who were consulted the otolaryngology outpatient clinic and diagnosed with RAS between 2019–2021 were retrospectively analyzed. Neutrophil/Lymphocyte Ratio (NLR), Platelet/Lymphocyte Ratio (PLR) and SII values were calculated based on the results of complete blood count. Demographic and hematological parameters between control and RAS groups were compared. The statistical significance level was considered as

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of

Graves' disease (GD) is one of the most common autoimmune conditions, but the mechanisms underlying the associated induction of autoimmunity are not known. We explored the role of peripheral lymphocyte subpopulations in disease pathogenesis.In total, 32 patients and 40 age- and sex-matched healthy controls were recruited in this study. Peripheral levels of T, B, NK, CD4The absolute numbers of circulating Th17 cells (0.45 ± 1.16, p 0.05) between GD patients and healthy controls were not significantly different. However, the percentage of Th17 cells was significantly increased (0.25 ± 0.11, p 0.05). The absolute numbers and percentages of circulating Tregs in GD patients were significantly decreased compared with those in healthy participants (11.61 ± 2.75, p 0.05). There was a significant difference in Treg absolute numbers between the untreated and drug-treated groups. Furthermore, we found that the Treg percentage in untreated patients (mean=4.78) was not significantly different from that in the drug-treated group (mean=4.81). In addition, circulating Treg absolute numbers in GD patients with exophthalmos were significantly lower than those in GD patients without exophthalmos (9.96 ± 4.16, p 0.05). A similar trend was observed in GD patients with weight loss (11.97 ± 3.28, p 0.05).GD pathogenesis was associated with a lower Treg population and an increased Th17/Treg ratio (T helper cell 17/ regulatory T cells). Th17 cells in this study were not related to the disease. Furthermore, anti-thyroid drug therapy improved immune-mediated system disorders. Finally, we found lower absolute numbers of circulating Tregs in GD patients with certain positive signs, such as exophthalmos and/or weight loss. Thus, immune changes are correlated with partial clinical manifestations.

Immune checkpoint blockade has dramatically improved cancer therapy but remains ineffective for most colorectal tumors. In this issue of Immunity, Peuker et al. describe a microbiota-myeloid-tumor cell crosstalk that inhibits CD8

Introduction: Squamous cell carcinoma of the external auditory canal is a rare entity. Previous studies have suggested predictors for tumor recurrence. However, most of the prognostic factors were from the clinicopathological aspect. Objective: This study aims to analyze the correlation between pre-operative peripheral inflammation markers and survival outcomes, in order to identify prognostic biomarkers for patients with squamous cell carcinoma of the external auditory canal. Methods: We retrospectively analyzed patients diagnosed with squamous cell carcinoma of the external auditory canal who underwent surgery at our institute. The pre-operative circulating inflammatory markers, such as the neutrophil, lymphocyte, platelet, and monocyte counts were measured and their ratios including neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and lymphocyte-to-monocyte ratio were calculated. The prognostic value of the measured hematologic parameters in relation to the survival outcomes was also evaluated. Results: A total of 83 patients were included, of which 26 patients showed tumor recurrence and 57 without recurrence. Neutrophil counts and neutrophil-to-lymphocyte ratio were closely connected with tumor stage. In the patients with recurrence, neutrophil counts, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio were elevated (p< 0.0001, p< 0.0001 and p = 0.001), while lymphocyte counts and lymphocyte-to-monocyte ratio were decreased (p = 0.013 and p = 0.016, respectively). The receiver operating curve analysis indicated that pre-operative neutrophil-to-lymphocyte ratio is a potential prognostic marker for recurrence of squamous cell carcinoma of the external auditory canal (area under curve = 0.816), and the cut-off points was 2.325. Conclusions: Pre-operative neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte are significantly correlated with tumor recurrence in patients with external auditory canal squamous cell carcinoma. Furthermore, neutrophil-to-lymphocyte ratio may be unfavorable prognostic factors of this disease. Resumo Introdução: O carcinoma espinocelular do meato acústico externo é uma doença rara. Estudos anteriores sugeriram preditores de recorrência do tumor. Entretanto, a maioria dos fatores prognósticos se originou do aspecto clínico-patológico. Objetivo: Analisar a correlação entre marcadores inflamatórios periféricos pré-operatórios e os desfechos de sobrevida e identificar biomarcadores prognósticos para pacientes com carcinoma espinocelular do meato acústico externo. Método: Analisamos retrospectivamente pacientes com diagnóstico de carcinoma espinocelular do meato acústico externo submetidos à cirurgia em nosso instituto. Os marcadores inflamatórios circulantes pré-operatórios, como as contagens de neutrófilos, linfócitos, plaquetas e monócitos, foram medidos e as suas relações calculadas, inclusive as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos. O valor prognóstico dos parâmetros hematológicos medidos em relação aos desfechos de sobrevida também foi avaliado. Resultados: Foram incluídos 83 pacientes, entre os quais 26 apresentaram recorrência tumoral e 57 não apresentaram. A contagem de neutrófilos e a relação neutrófilo/linfócito estavam intimamente associadas ao estágio do tumor. Nos pacientes com recorrência, a contagem de neutrófilos, a relação neutrófilos/linfócitos e a relação plaquetas/linfócitos eram elevadas (p < 0,0001, p > 0,0001 e p = 0,001), enquanto a contagem de linfócitos e a relação linfócitos/monócitos estavam diminuídas (p = 0,012 ep = 0,016, respectivamente). A análise da curva, Receiver Operating Characteristic, indicou que a relação neutrófilos/linfócitos pré-operatória era um potencial marcador prognóstico para a recorrência de carcinoma espinocelular do meato acústico externo (Área sob a curva = 0,816) e o ponto de corte foi de 2,325. Conclusão: A contagem pré-operatória de neutrófilos e linfócitos, as relações neutrófilos/linfócitos, plaquetas/linfócitos e linfócitos/monócitos estão significativamente correlacionadas com a recorrência do tumor em pacientes com carcinoma espinocelular do meato acústico externo. Além disso, a relação neutrófilos/linfócitos pode ser um fator prognóstico desfavorável dessa doença.

Immunosuppressive therapy is the backbone of kidney transplantation in preventing acute rejection. T-cell depletion after doses of thymoglobulin is dose-dependent, as are their side effects. At the same time, basiliximab and other maintenance immunosuppressive drugs act at different signals on T lymphocytes. Therefore, studying the pattern of lymphocyte subset depletion depending on the induction regime given at transplantation could be an added tool in managing post-transplant recipients.This prospective observational study recruited kidney transplant recipients from August 2019 through April 2021 at the University of Malaya Medical Centre. Blood tests for lymphocyte subsets were taken at pre-transplant, 1 week, 1 month, 3 months, and 6 months post-transplantation. At transplantation, recipients received either basiliximab, low-dose thymoglobulin (cumulative dose: 1.5 mg/kg), or standard-dose thymoglobulin (cumulative dose: 5 mg/kg).A total of 39 patients were recruited: 38.5% received basiliximab (15 of 39), 15.4% received low-dose thymoglobulin (6 of 39), and 46.2% received standard-dose thymoglobulin (18 of 39). Absolute lymphocyte counts 1 week post-transplantation were 1.5 ± 0.84 × 10The effects on lymphocyte counts, CD4+ and CD8+, vary depending on the type and dose of induction immunosuppression. This could be a guiding tool in managing immunosuppression post-transplantation depending on the patient's immunologic risk.

The pathophysiological mechanism underlying Graves' disease (GD) remains incompletely understood. Inhibitory receptors on B cells are critical for humoral immunity, which plays a key role in GD pathogenesis. This study aimed to investigate B cell subsets distribution and inhibitory receptor expression on these subsets in GD patients. Peripheral blood was drawn from 41 healthy controls and 46 GD patients (21 patients with moderate GD, 25 patients with severe GD). B cell subset distribution and CD22, CD32b and CD72 expression on B cells were analyzed by flow cytometry. Serum cytokines were examined by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, the naïve B cell percentage was increased, while the preswitched memory and conventional memory B cell percentages were decreased. The inhibitory receptors expression, especially CD32b, on B cell subsets was significantly decreased in patients with GD. In addition, the inhibitory receptors expression on B cell subsets from severe GD patients exhibited a decreasing trend compared with those from moderate GD patients. These results suggest that abnormal B cell subset distribution occurs in GD. Impaired inhibitory receptors, in particular CD32b, play a crucial role in GD pathogenesis and might be a therapeutic target to rebuild self-immune tolerance in GD.

Purpose B cells play a key role in outcomes of cancer patients and responses to checkpoint blockade immunotherapies. However, the effect of radiation therapy on B cell populations is poorly understood. Here we characterize the effects of radiation on the development, survival, and phenotype of physiological B-cell subsets. Methods and Materials Naive and immunized tumor bearing and nontumor bearing mice were treated with large-field or focal stereotactic radiation and distinct B-cell subsets of varying developmental stages were analyzed by flow cytometry and real-time reverse transcription polymerase chain reaction. Results We first report that focal stereotactic radiation is highly superior to large-field radiation at inducing tumor infiltration of B cells, CD8+ T cells, and macrophages. We observed that radiation affects B cell development in the bone marrow, increasing frequencies of early pro-B cells and late pro-B cells while inducing upregulation of programmed cell death protein 1. We then demonstrate that class switched B cells and plasma cells are highly resistant to radiation therapy compared with naive B cells and upregulate activation markers programmed cell death 1 ligand 2 and major histocompatibility complex class II) after radiation. Mechanistically, radiation upregulates Xbp1 and Bcl6 in plasma cells, conferring radioresistance. Furthermore, using an immunization approach, we demonstrate that radiation enhances activation-induced cytidine deaminase mediated class switching and somatic hypermutation in primed B cells. Conclusions These data demonstrate that stereotactic radiation is superior to large-field radiation at inducing infiltration of immune cells into tumors and that plasma cells and class switched B cells are highly resistant to radiation therapy. These results represent the most comprehensive analysis of the effects of radiation on B cells to date and identify novel mechanisms by which radiation modulates immune cells within the tumor microenvironment.

Recent data imply that strengthening host immunity by checkpoint inhibition improves outcome in invasive fungal infections (IFI), particularly in candidiasis.To assess T-cell exhaustion in this context, we compared peripheral blood mononuclear cells (PBMCs) and serum samples of patients with invasive Candida albicans infection (IC, n = 21) to PBMCs or tumor-infiltrating lymphocytes (TILs) from cancer patients (n = 14) and PBMCs of healthy controls (n = 20). Type and differentiation of lymphocytes and expression of 29 immune-regulatory molecules were analyzed by flow cytometry. C. albicans specific responses were assessed by FluoroSpot (n = 8) and antibody measurement (n = 14).Fractions and phenotypes of lymphocyte subsets in PBMCs of IC patients were similar compared to PBMCs of controls, while they were different in TILs. PBMCs of patients with IC showed increased expression of immune-checkpoint molecules. The pattern of upregulated molecules was similar to TILs, but not present in PBMCs of control cancer patients. Fractions of T-cells expressing PD-1 and TIGIT were higher in IC patients that died. FluoroSpot analysis showed a Candida-specific IFN-y or IL-2 response in 5/8 patients, enhanced by addition of nivolumab in vitro.Together with preclinical data and preliminary evidence of clinical efficacy in mucormycosis, our results support clinical evaluation of immune-checkpoint inhibition in IFI treatment.NCT04533087; retrospectively registered on August 31, 2020.

Chronic obstructive pulmonary disease (COPD) is characterized by a progressive, persistent immune response to cigarette smoke, and it has been suggested that immune dysregulation is involved in its pathogenesis. A subset of regulatory B cells (Bregs) with high levels of the surface markers CD24 and CD38 (CD24hiCD38hi) has previously been shown to exert an immunosuppressive function. This study investigated the levels and activity of CD24hiCD38hi Bregs in stable COPD (sCOPD). Testing the peripheral blood from 65 patients with sCOPD and 39 control subjects for CD24hiCD38hi Breg subsets by flow cytometry showed that the patients with sCOPD had significantly lower levels of CD24hiCD38hi Bregs and IL-10+ B cells. The patients with sCOPD had lower serum interleukin-10 levels than the controls. The patients with most severe sCOPD had the lowest levels of CD24hiCD38hi Bregs. Spearman correlation analysis showed that the levels of CD24hiCD38hi Bregs in the patients with sCOPD positively correlated with serum interleukin-10 concentrations but not with levels of C-reactive protein. Compared to healthy controls, functional studies showed that Breg cells from patients with sCOPD exhibit a decreased suppressive function. We conclude that sCOPD is characterized by the exhaustion of CD24hiCD38hi regulatory B cells compartment. Therefore, CD24hiCD38hi Bregs may contribute to the pathogenesis of sCOPD.

Background\ud The use of accurate prediction tools and early intervention are important for addressing severe coronavirus disease 2019 (COVID-19). However, the prediction models for severe COVID-19 available to date are subject to various biases. This study aimed to construct a nomogram to provide accurate, personalized predictions of the risk of severe COVID-19.\ud \ud Methods\ud This study was based on a large, multicenter retrospective derivation cohort and a validation cohort. The derivation cohort consisted of 496 patients from Jiangsu Province, China, between January 10, 2020, and March 15, 2020, and the validation cohort contained 105 patients from Huangshi, Hunan Province, China, between January 21, 2020, and February 29, 2020. A nomogram was developed with the selected predictors of severe COVID-19, which were identified by univariate and multivariate logistic regression analyses. We evaluated the discrimination of the nomogram with the area under the receiver operating characteristic curve (AUC) and the calibration of the nomogram with calibration plots and Hosmer-Lemeshow tests.\ud \ud Results\ud Three predictors, namely, age, lymphocyte count, and pulmonary opacity score, were selected to develop the nomogram. The nomogram exhibited good discrimination (AUC 0.93, 95% confidence interval [CI] 0.90–0.96 in the derivation cohort; AUC 0.85, 95% CI 0.76–0.93 in the validation cohort) and satisfactory agreement.\ud \ud Conclusions\ud The nomogram was a reliable tool for assessing the probability of severe COVID-19 and may facilitate clinicians stratifying patients and providing early and optimal therapies.

Donor Unrestricted T Cells (DURTs) are characterized by their use of antigen presentation molecules that are often invariant. As these cells recognize diverse mycobacterial antigens, often found in BCG, these cells have the potential to either serve as targets for vaccination, or as a means to enable the induction of traditional T and B cell immunity. Here, we will review specific DURT family members, and their relationship to BCG.

Granzyme B (GrB)-producing B cells are proposed to be a kind of regulatory B cells (Bregs) and have been revealed to be implicated in the pathogenesis of autoimmune diseases. Nevertheless, their role in SLE remains elusive. In this study, the frequencies of GrB-producing Bregs in peripheral blood of heathy control (HC) and systemic lupus erythematosus (SLE) were evaluated by flow cytometry, and their correlation with SLE patient clinical and immunological features were analyzed. The expression of GrB in HC and SLE B cells were also further detected by RT-qPCR analysis and ELISpot. The function of GrB-producing Bregs in HC and SLE patients was further investigated by in vitro CD4+ effector T cells-B cells co-culture assays with GrB blockade. We found that GrB-producing Bregs were significantly decreased in SLE patients and correlated with the clinical and immunological features. Moreover, these cells were functionally impaired under SLE circumstance. The negative correlation between GrB-producing Bregs and CD4+ T cells observed in healthy individuals disappeared in SLE patients. In vitro cell co-culture assay further showed that GrB-producing Bregs from SLE patients failed to suppress the Th1, Th2 and Th17 cell inflammatory responses, partially due to the dampened capacity of down-regulating TCR zeta and inducing T cell apoptosis. Taken together, these results revealed the disturbance of GrB-producing Bregs in SLE that might contribute to the disease initiation and progression.

Background SARS-CoV-2 vaccination is recommended in patients with inborn errors of immunity (IEIs); however, little is known about immunogenicity and safety in these patients. Objective We sought to evaluate the impact of genetic diagnosis, age, and treatment on antibody response to COVID-19 vaccine and related adverse events in a cohort of patients with IEIs. Methods Plasma was collected from 22 health care worker controls, 81 patients with IEIs, and 2 patients with thymoma; the plasma was collected before immunization, 1 to 6 days before the second dose of mRNA vaccine, and at a median of 30 days after completion of the immunization schedule with either mRNA vaccine or a single dose of Johnson & Johnson’s Janssen vaccine. Anti-spike (anti-S) and anti-nucleocapsid antibody titers were measured by using a luciferase immunoprecipitation systems method. Information on T- and B-cell counts and use of immunosuppressive drugs was extracted from medical records, and information on vaccine-associated adverse events was collected after each dose. Results Anti-S antibodies were detected in 27 of 46 patients (58.7%) after 1 dose of mRNA vaccine and in 63 of 74 fully immunized patients (85.1%). A lower rate of seroconversion (7 of 11 [63.6%]) was observed in patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy. Previous use of rituximab and baseline counts of less than 1000 CD3+ T cells/mL and less than 100 CD19+ B cells/mL were associated with lower anti-S IgG levels. No significant adverse events were reported. Conclusion Vaccinating patients with IEIs is safe, but immunogenicity is affected by certain therapies and gene defects. These data may guide the counseling of patients with IEIs regarding prevention of SARS-CoV-2 infection and the need for subsequent boosts.

Although both sarcopenia and systemic inflammation affect the outcomes of head and neck cancer (HNC) patients, the association between sarcopenia and systemic inflammation and the combined prognostic effect of these factors in HNC patients remain unknown. This study aimed to evaluate the effect of sarcopenia with systemic inflammation on survival and disease control in HNC patients.We retrospectively reviewed medical records of HNC patients treated between 2009 and 2016. The skeletal muscle area was measured using a single computed tomography image slice at the level of the third cervical vertebra. A prognostic score (SPLR) was developed based on sarcopenia and the platelet-lymphocyte ratio (PLR), and its prognostic value was evaluated.Overall, 164 patients were enrolled. In the multivariate analysis, sarcopenia was significantly associated with poor overall survival (OS) (p0.01). However, neither sarcopenia nor a high PLR was an independent prognostic factor for disease-free survival (DFS) or locoregional recurrence-free survival (LRFS). A high PLR was an independent predictor for sarcopenia (p0.01). A high SPLR was associated with older age, lower serum hemoglobin, and lower body mass index (all p0.05). Multivariate analysis revealed that SPLR was a significant independent predictor of OS, DFS, and LRFS (all p0.05).Systemic inflammation is significantly associated with sarcopenia. The survival and oncological effects of sarcopenia were enhanced when PLR was high. Thus, the combination of these two parameters may be useful for identifying HNC patients at a risk of poor survival outcomes.

The production of high-affinity antibodies is a key feature of the vertebrate immune system. Antibodies neutralize and clear pathogens, thereby protecting against infectious diseases. However, dysregulated production of antibodies can cause immune pathologies, such as autoimmunity and immune deficiency. Long-lived humoral immunity depends on B-cell help provided by T follicular helper (Tfh) cells, which support the differentiation of antigen (Ag)-specific B cells into memory and plasma cells. Tfh cells are generated from naive CD4+ T cells following the receipt of inputs from various cell surface receptors, and can undergo further differentiation into subsets with specialised effector functions to induce and maintain serological memory. While genetically modified mice have provided great understanding of the requirements for generating Tfh cells, it is critical that requirements for human Tfh cell generation and function are also established. Key insights into the molecular requirements for human Tfh cells have been elucidated from the systematic analysis of humans with monogenic germline variants that cause inborn errors of immunity characterised by impaired humoral immunity following infection or vaccination or immune dysregulation and autoimmunity. In this review we will discuss how studying rare 'experiments of nature' has enabled discovery of non-redundant molecules and pathways necessary for Tfh cell generation, differentiation, regulation and function in humans, and how these findings inform us about basic and clinical immunology.

Background Effective dose to immune cell (EDIC), an estimated radiation dose to the circulating lymphocytes, is of significance for overall survival (OS) in non-small cell lung cancer. This study aimed to validate the EDIC’s OS effect on limited-stage small cell lung cancer (LS-SCLC). Method and materials This study included LS-SCLC patients received definitive chemo-radiation in one single center from 2012 to 2017. All patients had multiple complete-blood-count tests including lymphocyte count at pre-, during- and end- radiotherapy. EDIC, computed according to doses of the lung, heart, and the total body, was assessed for its correlation with lymphocyte nadir, OS and progression free survival (PFS). Results Of 503 eligible patients, the mean EDIC was 7.34 Gy. The mean lymphocyte nadir was 0.48 × 109 cells/L, significantly lower than 1.65 × 109 cells/L at pre-radiotherapy (p Conclusions This study demonstrated that EDIC is an independent predictor for lymphocyte nadir, PFS and OS. EDIC may serve as a predictor for lymphocyte nadir and a surrogate marker for OS in LS-SCLC. More attention should be paid to EDIC to decease the lymphocyte toxicity and improve survival.

Despite the impact of childhood diarrhea on morbidity and mortality, our understanding of its sequelae has been significantly hampered by the lack of studies that examine samples across the entire intestinal tract. Infant rhesus macaques are naturally susceptible to human enteric pathogens and recapitulate the hallmarks of diarrheal disease such as intestinal inflammation and growth faltering. Here, we examined intestinal biopsies, lamina propria leukocytes, luminal contents, and fecal samples from healthy infants and those experiencing growth faltering with distant acute or chronic active diarrhea. We show that growth faltering in the presence or absence of active diarrhea is associated with a heightened systemic and mucosal pro-inflammatory state centered in the colon. Moreover, polyclonal stimulation of colonic lamina propria leukocytes resulted in a dampened cytokine response, indicative of immune exhaustion. We also detected a functional and taxonomic shift in the luminal microbiome across multiple gut sites including the migration of Streptococcus and Prevotella species between the small and large intestine, suggesting a decompartmentalization of gut microbial communities. Our studies provide valuable insight into the outcomes of diarrheal diseases and growth faltering not attainable in humans and lays the groundwork to test interventions in a controlled and reproducible setting.

The neutrophil-lymphocyte ratio (NLR) and the absolute lymphocyte count (ALC) have been proposed as prognostic markers in non-small cell lung cancer (NSCLC). The objective of this study was to examine the association of NLR/ALC before and after curative-intent radiotherapy for NSCLC on disease recurrence and overall survival.A retrospective study of consecutive patients who underwent curative-intent radiotherapy for NSCLC across nine sites in the UK from 1 October 2014 to 1 October 2016. A multivariate analysis was carried out to assess the ability of pre-treatment NLR/ALC, post-treatment NLR/ALC and change in NLR/ALC, adjusted for confounding factors using the Cox proportional hazards model, to predict disease recurrence and overall survival within 2 years of treatment.In total, 425 patients were identified with complete blood parameter values. None of the NLR/ALC parameters were independent predictors of disease recurrence. Higher pre-NLR, post-NLR and change in NLR plus lower post-ALC were all independent predictors of worse survival. Receiver operator curve analysis found a pre-NLR2.5 (odds ratio 1.71, 95% confidence interval 1.06-2.79, P0.05), a post-NLR5.5 (odds ratio 2.36, 95% confidence interval 1.49-3.76, P0.001), a change in NLR3.6 (odds ratio 2.41, 95% confidence interval 1.5-3.91, P0.001) and a post-ALC0.8 (odds ratio 2.86, 95% confidence interval 1.76-4.69, P0.001) optimally predicted poor overall survival on both univariate and multivariate analysis when adjusted for confounding factors. Median overall survival for the high-versus low-risk groups were: pre-NLR 770 versus 1009 days (P = 0.34), post-NLR 596 versus 1287 days (P ≤ 0.001), change in NLR 553 versus 1214 days (P ≤ 0.001) and post-ALC 594 versus 1287 days (P ≤ 0.001).NLR and ALC, surrogate markers for systemic inflammation, have prognostic value in NSCLC patients treated with curative-intent radiotherapy. These simple and readily available parameters may have a future role in risk stratification post-treatment to inform the intensity of surveillance protocols.

Introduction Symptoms of COVID-19 vary in severity and presentation. When admitting patients to the hospital, it is desirable to isolate patients with COVID-19 from those without the disease. However, reliably identifying patients with COVID-19 in the emergency department before hospital admission is often limited by the speed and availability of testing. Previous studies determined a low lymphocyte count is commonly found in patients with COVID-19. We sought to explore the sensitivity of absolute lymphocyte count in patients presenting to the emergency department requiring subsequent hospitalization who were found to have COVID-19. Methods A retrospective chart review was performed on 312 patients with laboratory-confirmed COVID-19 who were admitted to the hospital from the emergency department. The absolute lymphocyte count for these patients was used to calculate sensitivities at various cut-off values. The relationships between absolute lymphocyte count and variables, including age, sex, need for intubation, and mortality, were also explored. Results Cut-off values for absolute lymphocyte count ranged from 1.1 K/uL to 2.0 K/uL, with sensitivities of 72% and 94%, respectively. Additionally, lower mean absolute lymphocyte counts were identified in males, patients who required intubation, and patients who died. Conclusion Knowing the sensitivity of absolute lymphocyte count in patients with COVID-19 may help identify patients who are unlikely to have the disease. Additionally, absolute lymphocyte count can be used as a marker of disease severity in patients with COVID-19.

BACKGROUND: Decreased peripheral lymphocyte counts are associated with outcome after RT in several solid tumors, though appear late during or after the radiation course and often correlate with other clinical factors. Here we investigate if absolute lymphocyte counts (ALC) are independently associated with recurrence in pediatric medulloblastoma early during RT. METHODS: We assessed 202 medulloblastoma patients treated between 2000 and 2016 and analyzed ALC throughout therapy, focusing on both early markers (ALC during week 1 – ALC(wk1); grade 3+ Lymphopenia during week 2 – Lymphopenia(wk2)) and late markers (ALC nadir). Uni- and multivariable regressions were used to assess association of clinical and treatment variables with ALC and of ALC with recurrence. RESULTS: Thirty-six recurrences were observed, with a median time to recurrence of 1.6 years (Range 0.2–10.3) and 7.1 years median follow-up. ALC during RT was associated with induction chemotherapy (p

Inflammation is an early feature of acute limb ischaemia (ALI), hence the potential prognostic significance of inflammatory biomarkers. This study aimed to assess the value of pre-operative inflammatory biomarkers, specifically the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), for predicting an adverse outcome after revascularisation for ALI.All patients submitted to lower limb revascularisation for Rutherford IIa or IIb ALI at the authors' institution between 2009 and 2019 were screened retrospectively. Pre-operative NLR and PLR were analysed, along with other known prognostic factors. Primary outcome was the composite endpoint of 30 day death or amputation.A total of 345 patients were included, 84 of whom suffered the primary outcome (24.3%). The median follow up was 23.1 months (3.1 - 52.2). Higher age (OR 1.05 per year increase, 95% CI 1.01 - 1.09), diabetes (OR 2.63, 95% CI 1.14 - 6.06), Rutherford grade IIb vs. IIa (OR 5.51, 95% CI 2.11 - 14.42), higher NLR (OR 1.28 per unit increase, 95% CI 1.12 - 1.47), and fasciotomy need (OR 3.44, 95% CI 1.14 - 10.34) were independently associated with 30 day death or amputation, whereas pre-operative statin or anticoagulant medication were associated with a risk reduction (OR 0.23, 95% CI 0.53 - 0.96 and OR 0.20, 95% CI 0.05 - 0.84, respectively). PLR did not show an independent effect on this population. Pre-operative NLR presented a good discriminative ability (AUC 0.86, 95% CI 0.82 - 0.90). A cut off NLR level ≥ 5.4 demonstrated a 90.5% sensitivity and 73.6% specificity for 30 day death or amputation. Kaplan-Meier analysis showed that patients with pre-operative NLR ≥ 5.4 had significantly lower 30 day, six month and one year amputation free survival when compared with those with NLR5.4 (64.8 ± 4.0%, 44.1 ± 4.1%, and 37.5 ± 4.1% vs. 98.5 ± 0.9%, 91.9 ± 2.0%, and 85.9 ± 2.5%, log rank p.001).In this study, higher pre-operative NLR was associated with 30 day death or amputation following intervention for Rutherford grade IIa or IIb ALI. NLR potentially stands as a simple, widely available and inexpensive biomarker that can refine decision making and possibly contribute to ALI morbidity and mortality reduction.

Purpose. - To define the factors which may be related to brain metastasis (BM) in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who developed brain metastases after definitive treatment. Patients and methods. - A total of 208 patients with LA-NSCLC, without BM who received definitive radiotherapy (RT) or RT + chemotherapy (CT) between January 2005 and January 2016 were evaluated retrospectively. Platelet, neutrophil, lymphocyte counts, LDH, CRP, Hb levels, neutrophil-to-lymphocyte radio (NLR), platelet-to-lymphocyte radio (PLR), advanced lung cancer inflammation index (ALI) and FDG-PET/CT parameters (SUVmax of the primary tumor and mediastinal lymph nodes), and patient characteristics were evaluated for brain metastasis free survival (BMFS). Results. - Median follow-up duration was 25 months (range: 3-130 months). Cut-off values for platelet, NLR, PLR, LDH, CRP, and Hb were 290 x 103/mu L, 2.6, 198, 468 IU/L, 2.5 mg/dL, and 11.5 g/d1. We defined each parameter as low or high according to the cut-off values. 56 patients (26.9%) developed brain metastases during follow-up. In univariate analysis, high NLR (P=0.001), PLR (P=0.037), LDH (P = 0.028), CRP (P = 0.002) values, value >= 7.5 for lymph nodes (P = 0.005) and low ALI value (P = 0.002) were poor prognostic factors for BMFS. In multivariate analysis, high NLR (P= 0.022), PLR (P= 0.017), CRP (P= 0.006), stage >= IIIB disease (P< 0.001), multi-stational N2 disease (P= 0.036), adenocarcinoma histology (P< 0.001) and SUVmax value >= 7.5 (P = 0.035) were poor prognostic factors for BMFS. Conclusions. - High NLR, PLR, LDH, CRP values, SUVmax values for lymph nodes, and low ALI which indicates high tumor burden were additional prognostic factors besides stage, histology, and lymph node status. (C) 2020 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Introduction Although several reports on the risk factors for severe disease of COVID-19 already exist, reports on effective early indicators are still limited, especially from Japan. This study was conducted to clarify the patient’s characteristics whose disease progressed to severe status. Methods The medical records of all consecutive 300 Japanese patients hospitalized at our institution between February and November 2020 were retrospectively reviewed. The clinical characteristics were evaluated to compare between mild (no oxygen needed), moderate (oxygen needs of 1–4 L/min), and severe diseases (oxygen needs of 5 L/min or more). Results The median age was 68 years old, with 123 (41.0%) males and 177 (59.0%) females. Of these, 199 patients (66.3%), 55 patients (18.3%), 46 patients (15.3%) patients were in the mild disease, moderate disease, severe disease groups, respectively. Patients with severe disease were more likely to be older, have more comorbidities, and tended to have higher body mass index. In laboratory data, lymphocyte count, levels of C-reactive protein (CRP), LDH, and AST on admission were significantly associated with the severity. In multivariate analysis, age and CRP were the independent risk factors for severe disease (OR = 1.050, 1.130, respectively). The optimal cut-off value for age was 74 years old and that for CRP was 3.15 mg/dL. Conclusions Age and CRP were independently associated with disease severity of COVID-19 in multivariate analysis. Additionally, the numbers of underlying disease, lymphocyte count, and inflammatory markers such as LDH and D-dimer may also be related to disease severity.

The transplantation field requires the identification of specific risk factors associated with the level of immunosuppression. Here, our aim was to analyze the association between the number of circulating lymphocytes, monitored routinely by complete blood cell counts during outpatient visits, and patient and graft survival. In total, 2,999 kidney or combined kidney-pancreas recipients transplanted between 2000 and 2016, from two University hospitals, were enrolled. We investigated the etiological relationship between time-dependent lymphocyte count beyond one year after transplantation and patient and graft survival, viral infection and cancer risk using time-dependent multivariate Cox models. Model 1 considered kidney function at one year and model 2 as time-dependent variable. At the time of inclusion (one year after transplantation), 584 patients (19.4%) had deep lymphopenia (under 750 /mm3) and 1,072 (35.7%) had a normal count (over 1,500 /mm3). A patient with deep lymphopenia at a given follow-up time had significantly higher risks of graft failure, death and viral infection than comparable patients with a normal lymphocyte count at the same time point. Thus, after the first year of transplantation, the occurrence of deep lymphopenia within a patient's follow-up is a risk factor for long-term graft failure, death and viral infection.

Objectives The aim of this study was to assess the impact of COVID-19 on the morbidity and mortality on vasooclusive crisis (VOC) in sickle cell anaemia (SCA) patients. Methods One hundred patients with(fifty) or without COVID-19 PCR positivity(fifty), were enrolled in a prospective cohort study after signing a written informed consent. Results The COVID-19 positive patients had significantly higher median VOC episodes/year i.e 3 /year (IQR, 1-6 /year) v/s 2 /year (IQR, 2-12 /year) (p

To describe the kinetics of the peripheral blood components after radiotherapy, to examine radiation exposure vs. End-of-Radiation-Therapy (EoRT) counts and to associate the EoRT lymphocyte count with death and cancer treatment failure.Cohort study of patients who received curative intent radiotherapy for solid tumor diagnoses from 2009-2016 at Rigshospitalet, Copenhagen and had available 3D radiation exposure data. We illustrated peripheral blood count kinetics within 12 months before and after radiotherapy start and analyzed the impact of the irradiated body volume. We investigated overall survival and cancer treatment failure according to EoRT lymphopenia using Cox regression analyses.We analyzed 4055 patients with both pre-treatment and EoRT platelet counts and 2318 patients who also had neutrophil and lymphocyte counts. Only the lymphocyte decline after radiotherapy start was clinically relevant and remained low one year after radiotherapy. The higher the volume of the body exposed to radiation, the lower the EoRT blood counts. Female gender (p 0.001), number of fractions (p = 0.010), dose-volume (p 0.001) and concomitant use of chemotherapy, particularly the platinum compounds (p 0.001) were independently associated with a lower EoRT lymphocyte count. Patients with head and neck cancer had the lowest EoRT lymphocyte count. Patients with lymphopenia had a higher risk of death in the year after radiotherapy, compared with patients with no lymphopenia.Radiation schemes with fewer fractions and radiation techniques allowing reduction of the volume of the body exposed to radiation could be expected to better preserve patients' immune function.

Background Some patients with glioblastoma multiforme (GBM) survive 3–5 years (or longer) after diagnosis. The goal of this study was to identify differences between the long-term survivors (LTS) and those who had a shorter overall survival (non-LTS groups). Methods This study was a retrospective analysis of prospectively maintained surgical databases. All patients who underwent safe maximal resection for GBM were included. Demographic, clinical, radiologic, and pathologic data were obtained from electronic medical records. Values of the biomarkers of systemic inflammation were computed from the preoperative hemogram reports. Patients with an overall survival (OS) ≥36 months were defined as the LTS group and were compared with the non-LTS groups (OS Results Patients in the LTS group were younger, had a better baseline performance status, and were more likely to have undergone near- or gross-total resection. LTS was associated with lower Ki67 labeling, MGMT methylation, IDH mutation, and lack of p53 overexpression. Several novel findings were generated by this study. A longer pretreatment duration of symptoms was associated with a longer OS. Higher pretreatment levels of the absolute neutrophil count, neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, derived neutrophil-lymphocyte ratio and systemic index of inflammation, and lower levels of the absolute eosinophil count and eosinophil-lymphocyte ratio all correlated with a shorter OS. Conclusions Several differences were identified between the LTS and non-LTS groups. These differences will likely be incorporated into future prognostic models. They may also aid in differentiation between recurrent disease and treatment-related changes.

This work aimed to analyze the value of serum platelet/lymphocyte ratio (PLR), carbohydrate antigen 125 (CA125), and diffusion-weighted imaging (DWI) in the diagnosis of recurrent ovarian cancer.Forty-three patients with suspected recurrence of ovarian cancer were deemed as research objects, and 5 healthy people were set as controls. PLR, DWI, and CA125 level before surgery were analyzed. Pearson correlation analysis was implemented to explore the correlation between CA125 and lymphocyte count, platelet count, and PLR. Neuropathic Pain Scale was adopted to analyze the analgesic effect of patients with recurrent ovarian cancer before treatment and 7 days after treatment. Moreover, the quality of life scores of patients with recurrent ovarian cancer were evaluated before treatment and 30 days after treatment.The platelet and PLR values of patients with recurrent ovarian cancer were significantly higher relative to healthy people (P0.001), while the lymphocyte count was relatively lower (P = 0.002). There were considerable differences in PLR and CA125 levels in patients with recurrent ovarian cancer before and after treatment (P0.001). The single detection of CA125 was significantly better than that of DWI and PLR (P = 0.034). The sensitivity and specificity of CA125 detection alone was 77.3% and 81.8%, respectively, while those of the joint detection of DWI + PLR + CA125 was 92.4% and 79.9%, respectively. PLR was proved to be positively correlated with CA125 before and after treatment (r = 0.687, P0.001). Pain scores in all aspects of patients with recurrence of ovarian cancer after treatment were lower than that before treatment (P0.001), and the quality of life score was significantly higher than that before treatment (P0.001).CA125 and PLR combined with DWI had the best diagnostic effect for patients with recurrent ovarian cancer. After treatment, the levels of PLR and CA125 were reduced and the quality of life of patients was improved.

SARS-CoV-2 infection is associated with lower blood oxygen levels, even in patients without hypoxia requiring hospitalization. This discordance illustrates the need for a more unifying explanation as to whether SARS-CoV-2 directly or indirectly affects erythropoiesis. Here, we show significantly enriched CD71+ erythroid precursors/progenitors in the blood circulation of COVID-19 patients. We found that these cells have distinctive immunosuppressive properties. In agreement, we observed a strong negative correlation between the frequency of these cells with T and B cell proportions in COVID-19 patients. The expansion of these CD71+ erythroid precursors/progenitors was negatively correlated with the hemoglobin levels. A subpopulation of abundant erythroid cells, CD45+ CD71+ cells, co-express ACE2, TMPRSS2, CD147, and CD26, and these can be infected with SARS-CoV-2. In turn, pre-treatment of erythroid cells with dexamethasone significantly diminished ACE2/TMPRSS2 expression and subsequently reduced their infectivity with SARS-CoV-2. This provides a novel insight into the impact of SARS-CoV-2 on erythropoiesis and hypoxia seen in COVID-19 patients., In this article Elahi and colleagues show that COVID-19 infection is associated with significant expansion of erythroid precursors/progenitors in the blood of patients. These cells suppress patients' immune response against SARS-CoV-2 infection. Also, they express ACE2 and TMPRSS2 and get infected with SARS-CoV-2. In turn, pre-treatment with dexamethasone significantly diminishes ACE2/TMPRSS2 expression and subsequently reduces their infectivity with SARS-CoV-2.

Vitamin D deficiency represents a pandemic health problem with a broad spectrum of clinical implications. Several studies have involved lower levels of vitamin D with inflammatory disorders including cardiovascular, autoimmune and infectious disease. Indeed, the pathophysiological mechanisms are still poorly ascertained. We aimed at evaluating the impact of cholecalciferol (25(OH)D) levels on the biomarkers of acute-phase response and inflammation in a large cohort of patients with cardiovascular disease.Consecutive patients undergoing coronary angiography were included. Main clinical features and chemistry parameters were assessed at admission. 25(OH)D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc, Stillwater, US). Hypovitaminosis D was defined for 25(OH)D 10 ng/ml.A total of 3974 patients were included, of whom 29.4% had hypovitaminosis D. 25(OH)D deficiency was associated to age, female gender, diabetes mellitus, renal failure, previous percutaneous coronary intervention and smoke, acute presentation, severe coronary disease, higher glycemia and cholesterol and lower hemoglobin and ejection fraction (p 0.001), higher platelet count (p = 0.004) and BMI (p = 0.05). 25(OH)D significantly directly related with white blood cells count and the different components of leukocytes formula, Neutrophils-to-Lymphocytes Ratio, Monocytes-to-Lymphocytes Ratio and C-reactive protein, but not with lymphocytes levels. In fact, hypovitaminosis D predicted levels above the median for both Neutrophils-to-Lymphocytes Ratio (≥2.56; 57.3% vs. 47.6%; p 0.001; adjusted OR[95%CI] = 1.28[1.07-1.52; p = 0.007) and Monocytes -to-Lymphocytes Ratio (≥0.33; 59.1% vs. 49.8%; p 0.001; adjusted OR[95%CI] = 1.3[1.1-1.54; p = 0.002), results were confirmed in major subgroups of patients.The present study demonstrates that, among patients with cardiovascular disease, 25(OH)D deficiency is associated with a higher metabolic and clinical risk profile and with an elevation of cellular and humoral inflammatory parameters. Future dedicated studies should be, therefore, advocated in order to define whether 25(OH)D supplementation can modulate the mediators of the acute phase response and therefore potentially offer clinical and prognostic advantages on a broad spectrum of inflammatory disease.

BCG vaccination is known to reduce neonatal mortality from infections in a pathogen-agnostic manner. In this observational study we report on whether an emergency granulopoietic response is elicited in term babies from a developed country following BCG vaccination. We studied a cohort of neonates re-admitted to the hospital from home for feeding support separated into 2 groups dependent on whether they had received BCG vaccination. Clinical data including gender, weight, gestational age, method of feeding and full blood count results were retrieved retrospectively. While lymphocyte counts increase following BCG vaccination irrespective of gender and in proportion with the time elapsed after vaccination, the increase in neutrophil counts, is only observed in boys. This increase appears to be temporary. Our results confirm the presence of emergency granulopoiesis following BCG vaccination in a neonatal cohort from a developed country. However, this effect appears to be gender-specific and is present only in boys.

Highlights • EBV reactivation was observed in patients with COVID-19. • NK + and CD8 + T cell reduction was related to the severity of COVID-19 infection. • An increase of B cells in patients with severe symptoms was documented., Objectives The immunologic profile and opportunistic viral DNA increase were monitored in Italian patients with COVID-19 in order to identify markers of disease severity. Methods A total of 104 patients infected with SARS-CoV-2 were evaluated in the study. Of them, 42/104 (40.4%) were hospitalized in an intensive care unit (ICU) and 62/104(59.6%) in a sub-intensive care unit (SICU). Human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV), Parvovirus B19 and Human Herpesvirus 6 virus reactivations were determined by real-time PCR, and lymphocyte subpopulation counts were determined by flow cytometry. Results Among opportunistic viruses, only EBV was consistently detected. EBV DNA was observed in 40/42 (95.2%) of the ICU patients and in 51/61 (83.6%) of the SICU patients. Comparing the two groups of patients, the EBV DNA median level among ICU patients was significantly higher than that observed in SICU patients. In parallel, a significant reduction of CD8 T cell and NK count in ICU patients as compared with SICU patients was observed (p

Background The prediction of COVID-19 disease behavior in the early phase of infection is challenging but urgently needed. MuLBSTA score is a scoring system that predicts the mortality of viral pneumonia induced by a variety of viruses, including coronavirus, but the scoring system has not been verified in novel coronavirus pneumonia. The aim of this study was to validate this scoring system for estimating the risk of disease worsening in patients with COVID-19. Methods This study included the patients who were treated between April 1 st and March 13 th , 2020. The patients were classified into mild, moderate, and severe groups according to the extent of respiratory failure. MuLBSTA score was applied to estimate the risk of disease worsening in each severity group and we validated the utility of the scoring system. Results A total of 72 patients were analyzed. Among the 46 patients with mild disease, 17 showed disease progression to moderate or severe disease after admission. The model showed a sensitivity of 100% and a specificity of only 34.5% with a cut-off value of 5 points. Among the 55 patients with mild or moderate disease, 6 deteriorated to severe disease, and the model showed a sensitivity of 83.3% and a specificity of 71.4% with a cut-off value of 11 points. Conclusions This study showed that MuLBSTA score is a potentially useful tool for predicting COVID-19 disease behavior. This scoring system may be used as one of the criteria to identify high-risk patients worsening to life-threatening status.

Graft-versus-host disease (GVHD) is the most frequent complication after allogeneic hematopoietic stem cell transplantation (HSCT), and is one of the major causes of non-relapse mortality. Transferred mature lymphocytes are thought to be responsible for GVHD based on the findings that mice transplanted with lymphocyte-depleted bone marrow (BM) cells from MHC-mismatched donors do not develop GVHD. However, we found that overexpression of signal-transducing adaptor protein (STAP)-2 in lymphoid cells could induce GVHD after lymphocyte-depleted BM transplantation. To examine the function of STAP-2, which has been shown to play an important role in development and function of lymphocytes, in GVHD, we transplanted BM cells from STAP-2 deficient, or Lck promoter/IgH enhancer-driven STAP-2 transgenic (Tg) mice into MHC-mismatched recipients. Unexpectedly, mice transplanted with lymphocyte-depleted BM cells from STAP-2 Tg mice developed severe acute GVHD with extensive colitis and atrophy of thymus, while no obvious GVHD developed in mice transplanted with the wild type or STAP-2 deficient graft. Furthermore, mice transplanted with lymphocyte-depleted BM cells from the syngeneic STAP-2 Tg mice developed modest GVHD with colitis and atrophy of thymus. These results suggest that STAP-2 overexpression may enhance survival of allo-, and even auto-, reactive lymphocytes derived from engrafted hematopoietic progenitor cells in lethally irradiated mice, and that clarification of the mechanism may help understanding induction of immune tolerance after HSCT.

The global burden of death due to sepsis is considerable. Early diagnosis is essential to improve the outcome of this deadly syndrome. Yet, the diagnosis of sepsis is fraught with difficulties. Patients with blood stream infection (BSI) are at an increased risk of complications and death. The aim of this study was to determine the diagnostic accuracy of four readily available biomarkers to diagnose BSI in patients with suspected sepsis.In this retrospective, observational, Electronic Medical Record based study we compared the accuracy of procalcitonin (PCT), serum lactate concentration, total white blood cell (WBC) count and the neutrophil-lymphocyte count ratio (NLCR) to diagnose BSI in adult patients presenting to hospital with suspected sepsis. Based on the blood culture results patients were classified into 1 of the following 5 groups: i) negative blood cultures, ii) positive for a bacterial pathogen, iii) positive for a potential pathogen, iv) fungal pathogen and v) potential contaminant. Group 2 was further divided into Gram -ve and Gram +ve pathogens. Receiver operating characteristic (ROC) curves were constructed to compare the diagnostic performance of the biomarkers.There were 1767 discreet patient admissions. The median PCT concentration differed significantly across blood culture groups (p 0.0001). The highest median PCT concentration was observed in patients with a Gram-negative pathogen (17.1 ng/mL; IQR 3.6-49.7) and the lowest PCT in patients with negative blood cultures (0.6 ng/mL; IQR 0.2-2.8). The AUROC was 0.83 (0.79-0.86) for PCT, 0.68 (0.64-0.72) for the NLCR, 0.55 (0.51-0.60) for lactate concentration and 0.52 (0.48-0.57) for the WBC count. The AUROC for PCT was significantly greater than that of the NLCR (p 0.0001). A PCT less than 0.5 ng/mL had a negative predictive value of 95% for excluding BSI. The best cut-off value of PCT for predicting BSI was 1.5 ng/ml.Our results suggest that PCT of less than 0.5 ng/mL may be an effective screening tool to exclude BSI as the cause of sepsis, while the diagnosis of BSI should be considered in patients with a PCT above this threshold. The total WBC count and blood lactate concentration may not be reliable biomarkers for the diagnosis of BSI. The NLCR may be a useful screening test for BSI when PCT assays are not available.

Highlights • T cell-induced immune responses during acute SARS-CoV-2 infection have barely been reported • The importance of CD4+ T cells (but not CD8+ and CD3+ T cells) in SARS-CoV-2-associated pneumonia • CD4+ T cells might be important for the control of SARS-CoV-2. Ideally, this information will contribute to the development of novel treatment methods for SARS-CoV-2, Background The world is facing the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). T cell-induced immune responses during acute SARS-CoV-2 infection have rarely been reported. Methods We use cell counting chips and PCR arrays to offer the first insights into the T cell involved in the course of acute SARS-CoV-2 infection. All consecutive patients with suspected SARS-CoV-2 infection treated at the designated hospital between January 2020 and February 2020 were recruited for the study, and cases were confirmed by real-time RT-PCR. Baseline characteristics for inpatients were prospectively collected and analyzed. Results 96 patients with suspected SARS-CoV-2 infection in our center were screened for inclusion in the study. The median age of the patients was 39.0 years, and 47 (49.0%) were female. Multivariate logistic regression analysis showed that only the CD4+ cell counts were significantly lower in the infection group and slightly higher in the control group. Receiver operating characteristic curve analysis showed good discrimination power between subjects with and subjects without infection. Limitations This is a single-center study of patients with a specific ethnic background and lacks a mechanism. Conclusions These findings imply the importance of CD4+ T cells (but not CD8+ and CD3+ T cells) in SARS-CoV-2 infection associated pneumonia and indicate that CD4+ T cells might be important for the control of SARS-CoV-2.

To discover immune factors that can predict the progression of COVID-19, we evaluated circulating immune cells and plasma cytokines in COVID-19 patients. We found that T cells, including CD4+ T cells and CD8+ T cells, were significantly decreased in severe COVID-19 symptoms but not in mild symptoms, in comparison with healthy people. T cells remained at a low level after recovery from severe COVID-19. CD4+CD25+CD127low Treg-enriched cells were significantly increased in either mild or severe COVID-19 patients, regardless of recovery or not. Moreover, in either mild or severe COVID-19 patients, Treg-enriched cells up-regulated CD25 and down-regulated CD127. After recovery, CD25 was partially down-regulated but still higher than the normal level, while CD127 returned to the normal level in mild patients but not severe patients. B cells were decreased in mild patients and further decreased in severe patients, and remained low after recovery. NK cells were decreased only in severe COVID-19, with a tendency to return to the normal level after recovery. Plasma IL-6 and IL-10 were both elevated in severe patients but not in mild patients. After recovery, IL-6 remained higher than its normal level, while IL-10 returned to the normal level. Binary logistic regression analysis indicated that CD4+ T cells, B cells, IL-6, and IL-10 were significantly associated with COVID-19 severity. Therefore, these parameters are indicators of COVID-19 severity. Dynamic monitoring of these parameters would benefit therapy planning and prognosis evaluation.

The relationship between NK cell counts during primary infection and disease progression or immune restoration after antiretroviral treatment (ART) was explored. We followed 462 individuals with HIV infection and measured their NK, CD4+ T, CD8+ T cell counts and viral loads. Our data showed that individuals with high NK cell counts had much lower viral loads and higher CD4+ T cell counts. NK cell counts during primary infection were negatively correlated with viral set-point and viral loads at one-year-infection point, and positively correlated with CD4+ T cell counts at one-year-infection and one-year-ART point. Moreover, the NK cell counts during primary infection can predict HIV disease progression and immune restoration after ART. In conclusion, NK cell counts during primary infection represents a potential predictive biomarker to predict HIV disease prognosis in the clinic.

Background Pancreatic cancer remains one of the most lethal cancers. Objective This study aimed to analyze T cell-related biomarkers and their molecular network in pancreatic cancer. Methods RNAseq sequencing data and clinical data of pancreatic cancer were obtained from TCGA database. The STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) algorithm was used to screen the DEGs related to the tumor immune cells. The pearson correlation analysis were used to analyze the relationships between DEGs and T cells. Additionally, the T cell-related DEGs were subjected to protein-protein interaction, competing endogenous RNA (ceRNA), and chemical small molecule-target network construction. Furthermore, the prognosis-associated DEGs were screened. Results A total of 412 stromal score-associated and 312 immune score-associated DEGs were obtained. From these DEGs, 50 CD4+ T cell-related genes and 13 CD8+ T cell-related genes were selected. The PPI networks associated with immune cell-related genes were constructed and found that CD22, SELL, and OLR1 had higher degrees in the PPI network. The number of ceRNA regulatory relation pairs obtained from CD4+ T cells and CD8+ T cells were 59 and 48, respectively. Additionally, both CD4+ T cell- and CD8+ T cell-related genes predicted 29 small molecules. CXCL9 and GIMAP7 were screened out from CD4+ T cell-related genes, which were related with the survival of pancreatic cancer. Conclusion We mapped T cell-related gene profile in pancreatic cancer and constructed their potential regulatory network.

Immune function (e.g. absolute lymphocyte count (ALC)) and modifiable predictors thereof (e.g. volume of the heart/lungs receiving low-dose radiation) impact outcomes of cancer patients, but this has not been well-studied in the immunotherapy era. This investigation of metastatic lung cancer assessed the interaction of dosimetric parameters (e.g. lung/heart V5), radiotherapy technique (e.g. stereotactic (SBRT) or traditional radiotherapy), lymphopenia, and survival outcomes.Patients were collected from three institutional phase I/II trials of combined immunotherapy and lung irradiation. SBRT referred to 50 Gy/4 fractions or 60 Gy/10 fractions, and traditional RT as 45 Gy/15 fractions. Blood collections were standardized on the first and last day of radiotherapy and each cycle of immunotherapy. Statistics included multivariable linear regression to identify variables associated with ALC decline, Kaplan-Meier analysis of overall and progression-free survival (PFS), and Cox multivariate analysis.The median follow-up of the 165 patients was 21 months. The only factor independently predictive of ALC decline was traditional RT (p 0.001). Therefore, the analysis was repeated for traditional RT and SBRT separately; lung V5 was associated with lymphopenia for traditional RT (p 0.001) but not SBRT (p = 0.12). Pre-radiotherapy ALC was independently associated with PFS in both cohorts (p 0.05 for both); post-RT ALC predicted for PFS in the traditional RT (p = 0.048) but not the SBRT (p = 0.90) group. Neither heart nor lung V5 was independently associated with PFS.When combined with immunotherapy, SBRT may better preserve lymphocytes (and hence improve outcomes) than traditional RT. When administering traditional RT, constraining the lung V5 may indirectly impact outcomes by means of ALC preservation.

Introduction Recently, the lymphocyte to monocyte ratio (LMR) has been proposed as an easily determinable prognostic factor in patients with cancer, including lymphomas. The objective of this study was the evaluation of the impact of baseline absolute lymphocyte count (ALC), absolute monocyte count (AMC), and the LMR on the treatment response and prognosis in follicular lymphoma (FL). Patients and Methods The data of 100 patients with a FL variant, admitted and treated between January 2009 and June 2018, were analyzed. Results The area under the receiver operator characteristic curve and cutoff values of ALC, AMC, and LMR for discrimination between survival times using receiver operating characteristic curves showed 0.57 × 109/L as the most discriminative ALC cutoff value, 1.235 ×109/L as the most discriminative AMC cutoff value, and 1.63 as the most discriminative LMR cutoff value. Progressive disease and stable disease after first-line therapy and mortality rate were significantly associated with lower ALC, higher AMC, and higher LMR. Shorter overall survival (OS) was significantly associated with patients with lower ALC when compared with those having higher ALC. Shorter OS and progression-free survival (PFS) were significantly associated with higher AMC when compared with those having lower AMC. Shorter OS and PFS were significantly associated with lower LMR when compared with those having higher LMR. High-risk Follicular Lymphoma International Prognostic Index as well as low LMR were considered as risk factors for prediction of OS in all the studied patients with FL in univariate analysis and multivariate analysis. Conclusion ALC, AMC, and LMR at diagnosis are simple indices, which reflect the host systemic immunity and can predict the clinical outcomes in FL.

Background The neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) have been associated with the prognosis in breast cancer (BC). The relationship of the NLR and PLR with chemotherapy sensitivity and prognosis in luminal B-like (human epidermal growth factor receptor 2-negative [HER2−]) BC are not well studied. Patients and Methods The clinical data from 980 patients with luminal B-like (HER2−) BC from June 2012 to June 2016 were collected. The differences among the variables were calculated using the χ2 test. The associations among the clinicopathologic factors, pretreatment NLR, pretreatment PLR, and disease-free survival (DFS) were analyzed using Kaplan-Meier curves and Cox analyses. Results The median follow-up was 37 months (range, 5-77 months). For the 480 patients who had received neoadjuvant chemotherapy, low pretreatment PLR values were associated with higher pathologic complete response (pCR) rates compared with the high PLR group (15.8% for low vs. 9.2% for high PLR group; P = .027). Multivariate analyses showed that larger tumors, a greater number of lymph nodes involved, a high Ki-67 score, and a high PLR were independent prognostic factors of worse outcomes for the patients with luminal B-like (HER2−) BC. The risk of metastasis and/or recurrence was greater for the high PLR group than for the low PLR group (hazard ratio, 1.576; 95% confidence interval, 1.039-2.390; P = .032). The pretreatment NLR showed no such associations among this cohort of patients. Conclusions The results of the present study have shown that the pretreatment PLR is superior to the NLR as a predictor of pCR and DFS outcomes in patients with luminal B-like (HER2−) BC. A low pretreatment PLR was associated with higher pCR rates after neoadjuvant chemotherapy and was an independent predictive factor for better DFS outcomes among patients with luminal B-like (HER2−) BC.

Highlights • COVID-19 can deteriorate at the 2nd week of illness despite of decreasing viral loads • We analyzed PBMCs of severe or mild COVID-19 cases at the 1st and 3rd week of illness • Cellular responses were not different between two groups at the 1st week of illness • Higher T-cell proliferation, activation, and cytotoxicity was noted in severe cases at the 3rd week • Aberrant hyperactivation of cytotoxic T-cell may contribute to severe COVID-19 pneumonia, Objectives We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. Methods We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤ 93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. Results The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8 + T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in severe group. Conclusions Severe COVID-19 had higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.

Objective To investigate the clinical features of COVID-19 cases in Suzhou China. Biomarkers were screened out of hematological parameters for risk stratification. Method Confirmed COVID-19 adult patients in Suzhou were included. The patient data was collected, and the results of laboratory examinations were compared between the mild/moderate and severe COVID-19 groups. A ROC was calculated to compare the diagnostic performance of candidate indexes, and dynamic levels of hematological indexes were compared between the two groups. Result 75 patients were enrolled, with a mean age of 46.6 ± 14 years, and 45 patients were male. All patients were classified into two groups: the mild/moderate group and the severe group. WBC, neutrophil to lymphocyte ratio (NLR), D-dimer, and fibrinogen levels of the severe group were significantly higher (P, Highlights • Most common symptoms of Suzhou COVID-19 are fever, cough and sore throat. • COVID-19 has characteristics of abnormal hematological indexes. • NLR and D-dimer can be used as valuable biomarkers for risk stratification of COVID-19.