Lymphocyte Levels Research Articles

A comprehensive investigation into the ranges of laboratory tests present in cerebrospinal fluid across various types of meningitis within different age categories

Background. Diagnosing meningitis requires a lumbar puncture to analyze cerebrospinal fluid (CSF) and determine the causative pathogen. Key diagnostic measures include Glucose and Protein concentrations, cell count, differential leukocyte count, Gram stain, culture, and PCR if necessary. Objective. Our analysis assessed patterns in key biomarkers—neutrophils, lymphocytes, cerebrospinal fluid white blood cell count, and CSF/blood Glucose and Protein ratios—across various types of meningitis, including meningococcemia, meningococcal, tuberculous, pneumococcal, aseptic, and other bacterial meningitis. We examined these biomarkers within distinct age categories: children (0-12 years), adults (13-64 years), and the elderly (≥ 65 years). Methods. Descriptive statistics were used to analyze various types of meningitis across different age groups. We assessed the normality of laboratory biomarkers using the Shapiro-Wilk test, and applied Welch ANOVA to explore potential differences in biomarker levels among various types of meningitis. A Games-Howell post hoc test was used to identify specific pairs of meningitis types with statistically significant differences in biomarker levels. Results. The analysis of variance of cerebrospinal fluid biomarkers revealed significant differences in CSF WCC (cells/mm3), Neutrophils (%), Lymphocytes (%), CSF/blood Glucose and Protein ratios in children and adults (p <0.05). However, differences were observed solely in neutrophil levels among elderly subjects. In bacterial meningitis, neutrophil levels increased across all ages, with adults showing higher levels. For meningococcal meningitis, adults had a median neutrophil level of 78.5% [60%, 90%] compared to 57% [24.5%, 85.25%] in children. The CSF white cell count (WCC) median was also higher in adults (339 cells/mm³) compared to children (224 cells/mm³). Viral meningitis cases exhibited higher lymphocyte levels across all age groups, with medians of 69% [34%, 87%] in children, 82% [61%, 93%] in adults, and 77% [55%, 90%] in the elderly. The glucose ratio was lower in bacterial meningitis (<0.3) and higher in viral cases (>0.5). Protein ratios were elevated in bacterial meningitis, indicating increased blood-brain barrier permeability. These results demonstrate a distinct biological profile for different causative agents, modulated by patient age.

NKG2C/KLRC2 tumor cell expression enhances immunotherapeutic efficacy against glioblastoma

BackgroundActivating and inhibitory receptors of natural killer (NK) cells such as NKp, NKG2, or CLEC are highly relevant to cold tumors including glioblastoma (GBM). Here, we aimed to characterize the...

Developing a mouse model of human coronavirus NL63 infection: comparison with rhinovirus-A1B and effects of prior rhinovirus infection.

Human coronavirus (HCoV)-NL63 causes respiratory tract infections in humans and uses angiotensin-converting enzyme 2 (ACE2) as a receptor. We sought to establish a mouse model of HCoV-NL63 and determine whether prior rhinovirus (RV)-A1B infection affected HCoV-NL63 replication. HCoV-NL63 was propagated in LLC-MK2 cells expressing human ACE2. RV-A1B was grown in HeLa-H1 cells. C57BL6/J or transgenic mice expressing human ACE2 were infected intranasally with sham LLC-MK2 cell supernatant or 1 × 105 tissue culture infectious dose (TCID50) units HCoV-NL63. Wild-type mice were infected with 1 × 106 plaque-forming units (PFU) RV-A1B. Lungs were assessed for vRNA, bronchoalveolar lavage (BAL) cells, histology, HCoV-NL63 nonstructural protein 3 (nsp3), and host gene expression by next-generation sequencing and qPCR. To evaluate sequential infections, mice were infected with RV-A1B followed by HCoV-NL63 infection 4 days later. We report that hACE2 mice infected with HCoV-NL63 showed evidence of replicative infection with increased levels of vRNA, BAL neutrophils and lymphocytes, peribronchial and perivascular infiltrates, and expression of nsp3. Viral replication peaked 3 days after infection and inflammation persisted 6 days after infection. HCoV-NL63-infected hACE2 mice showed increased mRNA expression of IFNs, IFN-stimulated proteins, and proinflammatory cytokines. Infection with RV-A1B 4 days before HCoV-NL63 significantly decreased both HCoV-NL63 vRNA levels and airway inflammation. Mice infected with RV-A1B prior to HCoV-NL63 showed increased expression of antiviral proteins compared with sham-treated mice. In conclusion, we established a mouse model of HCoV-NL63 replicative infection characterized by relatively persistent viral replication and inflammation. Prior infection with RV-A1B reduced HCoV-NL63 replication and airway inflammation, indicative of viral interference.NEW & NOTEWORTHY We describe a mouse model of human coronavirus (HCoV) infection. Infection of transgenic mice expressing human angiotensin-converting enzyme 2 (ACE2) with HCoV-NL63 produced a replicative infection with peribronchial inflammation and nonstructural protein 3 expression. Mice infected with RV-A1B 4 days before HCoV-NL63 showed decreased HCoV-NL63 replication and airway inflammation and increased expression of antiviral proteins compared with sham-treated mice. This research may shed light on human coronavirus infections, viral interference, and viral-induced asthma exacerbations.

U-shaped correlation of lymphocyte count with all-cause hospital mortality in sepsis and septic shock patients: a MIMIC-IV and eICU-CRD database study

BackgroundIn sepsis, the relationship between lymphocyte counts and patient outcomes is complex. Lymphocytopenia and lymphocytosis significantly influence survival, illustrating the dual functionality of lymphocytes in responding to infections. This study investigates this complex interaction, focusing on how variations in lymphocyte counts correlate with all-cause hospital mortality among sepsis patients.MethodsThis retrospective cohort study analyzed data from two extensive critical care databases: the Medical Information Mart for Intensive Care IV 2.0 (MIMIC-IV 2.0) from Beth Israel Deaconess Medical Center, Boston, Massachusetts, and the eICU Collaborative Research Database (eICU-CRD), which was Multi-center database from over 200 hospitals across the United States conducted by Philips eICU Research Institute. We included adult patients aged 18 years and older who met the Sepsis-3 criteria, characterized by documented or suspected infection and a Sequential Organ Failure Assessment (SOFA) score of 2 or higher. Sepsis patients were categorized into quartiles based on lymphocyte counts. The primary outcome was all-cause mortality in the hospital, with 90 and 60-day all-cause mortality as the secondary outcomes. Univariable and multivariable Cox proportional hazard regressions were utilized to assess lymphocyte counts' impact on hospital mortality. An adjusted restricted cubic spline (RCS) analysis was performed to elucidate this relationship further. Subgroup analyses were also conducted to explore the association across various comorbidity groups among sepsis and septic shock patients.ResultsOur study included 37,054 patients, with an observed in-hospital mortality rate of 16.6%. Univariable and multivariable Cox proportional hazard regression models showed that lymphocyte counts were independently associated with in-hospital mortality (HR = 1.04, P < 0.01; HR = 1.06, P < 0.01). RCS regression analysis revealed a U-shaped relationship between lymphocyte levels and hospital mortality risk in sepsis and septic shock patients (P for overall < 0.001, P for nonliner < 0.01; P for overall = 0.002, P for nonliner = 0.014). Subgroup analyses revealed that elevated lymphocyte counts correlated with increased hospital mortality among sepsis patients with liver disease and requiring renal replacement therapy (P for overall = 0.021, P for nonliner = 0.158; P for overall = 0.025, P for nonliner = 0.759). These findings suggest that lymphocytes may have enhanced prognostic value in specific subsets of critically ill sepsis patients.ConclusionOur findings demonstrate that lymphocyte counts are a significant independent predictor of hospital mortality in sepsis and septic shock patients. We observed a U-shaped association between lymphocyte levels and mortality risk, indicating that high and low counts are linked to increased mortality. This result highlights the complex role of lymphocytes in sepsis outcomes and suggests the need for further investigation into the underlying mechanisms and potential therapeutic approaches. Integrating lymphocyte count assessment into risk stratification algorithms and clinical decision support tools could enhance the early identification of high-risk sepsis patients.

Predictive clinical indicators of refractory Mycoplasma pneumoniae pneumonia in children: A retrospective cohort study.

To determine the clinical indicators predictive of refractory Mycoplasma pneumoniae pneumonia (RMPP) in children and develop a robust predictive model to aid in early identification and management. A retrospective cohort study was conducted on 338 children diagnosed with RMPP out of a total of 1500 cases of Mycoplasma pneumoniae at a single tertiary hospital from May 2021 to November 2023. Clinical and demographic data analyzed included age, gender, parents' educational level, household income, body mass index, allergic constitution, and laboratory findings such as white blood cell count, neutrophil and lymphocyte counts, platelet count, and levels of C-reactive protein (CRP), D-dimer, and procalcitonin. Univariate and multivariate logistic regression analyses were performed to identify significant predictors of RMPP, and a predictive model was developed. Among the RMPP cohort, 52.4% were female, with a mean age of 6.07 ± 2.78 years. Multivariate analysis identified several significant predictors of poor prognosis, including higher body mass index, longer duration of fever, elevated white blood cell count, neutrophil count, C-reactive protein levels, and increased neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. The model demonstrated outstanding diagnostic performance, with an area under the receiver operating characteristic curve of 0.963 (95% confidence interval: 0.946-0.981). Our study identifies key clinical indicators with significant diagnostic accuracy for predicting RMPP in children. The predictive model established offers a valuable tool for clinicians, potentially improving RMPP outcomes through timely intervention.

Effect of photodynamic therapy on peripheral immune system for unresectable cholangiocarcinoma

BackgroundPhotodynamic therapy (PDT) has been emerging as a promising treatment for unresectable cholangiocarcinoma (CCA). A number of experiments have demonstrated that PDT could enhance antitumor immunity significantly. However, the impact of PDT on peripheral immune system for unresectable CCA remains unclear. MethodsIn a clinical trial comparing the perioperative and long-term outcomes of PDT+stent treatment and stent alone treatment for unresectable CCA, we tested the levels of lymphocytes (CD4+ T cells, CD8+ T cells, NK cells, B cells and Treg cells) and immune-related cytokines (IL-4, IL-6, IL-10, TNF-α, TGF-β, perforin, GM-CSF and IFN-γ) in peripheral blood before and after PDT+stent treatment or stent alone treatment and analyzed the influence of PDT on peripheral immune system for unresectable CCA. ResultsBefore treatment, the levels of all the immune cells and immune-related cytokines did not show significant differences between the PDT+stent group and stent alone group. The ratio of CD8+ T cells increased significantly after PDT treatment, but other kinds of lymphocytes did not show significant difference. Increased level of IL-6 and decreased level of perforin and TGF-β after PDT treatment were demonstrated, whereas no significant changes were found for other immune-related cytokines. ConclusionPDT altered the levels of immune cells and immune-related cytokines in the peripheral blood of unresectable CCA patients, potentially correlating with the therapeutic efficacy of PDT in unresectable CCA treatment. Future studies could delve deeper into this aspect to explore how PDT can be more effectively utilized in the management of unresectable CCA.

Immunomodulatory effect of tibetan medicine compound extracts against ORFV in vitro by metabolomics

Ovine contagious pustular dermatitis (ORF) is one of the main diseases of sheep and is a zoonotic disease caused by Ovine contagious pustular dermatitis virus (ORFV) infection, posing a significant constraint on sheep breeding industry and human health. The Tibetan medical formulation composed of Polygonum leucoides, Polygonum xanthoxylum and Acanthophora rotunda significantly regulated lymphocyte immune function following ORFV stimulation, although the mechanism remains unclear. In order to study the immunomodulatory effects and mechanism of three Tibetan medicinal extracts (Polygonum leucoides, Polygonum xanthoxylum, and Acanthophora rotunda) against ORFV in vitro, sheep peripheral blood lymphocytes were isolated in vitro and treated with different concentrations of Tibetan medicine compound extract solution after ORFV infection. The cytokine expression levels in lymphocytes were measured at 4 h, 8 h and 12 h. Additionally endogenous metabolites in lymphocytes at 0 h, 4 h, 8 h and 12 h were quantified by untargeted metabolomics method. The results showed that, the extracts could regulate the lymphocyte immune factors altered by ORFV, and regulate the lymphocyte immune function through cysteine and methionine metabolic pathways as well as the pyrimidine metabolic pathways, potentially alleviating the immune evasion induced by ORFV.

Cracking the Codes behind Cancer Cells' Immune Evasion.

Immune evasion is a key phenomenon in understanding tumor recurrence, metastasis, and other critical steps in tumor progression. The tumor microenvironment (TME) is in constant flux due to the tumor's ability to release signals that affect it, while immune cells within it can impact cancer cell behavior. Cancer cells undergo several changes, which can change the enrichment of different immune cells and modulate the activity of existing immune cells in the tumor microenvironment. Cancer cells can evade immune surveillance by downregulating antigen presentation or expressing immune checkpoint molecules. High levels of tumor-infiltrating lymphocytes (TILs) correlate with better outcomes, and robust immune responses can control tumor growth. On the contrary, increased enrichment of Tregs, myeloid-derived suppressor cells, and M2-like anti-inflammatory macrophages can hinder effective immune surveillance and predict poor prognosis. Overall, understanding these immune evasion mechanisms guides therapeutic strategies. Researchers aim to modulate the TME to enhance immune surveillance and improve patient outcomes. In this review article, we strive to summarize the composition of the tumor immune microenvironment, factors affecting the tumor immune microenvironment (TIME), and different therapeutic modalities targeting the immune cells. This review is a first-hand reference to understand the basics of immune surveillance and immune evasion.

Activating α7nAChR suppresses systemic inflammation by mitigating neuroinflammation of the medullary visceral zone in sepsis in a rat model.

Our previous studies have shown that activating α7nAChRs suppresses systemic inflammation and immunity through the cholinergic anti-inflammatory pathway (CAP) in early sepsis. Now that the medullary visceral zone (MVZ) is the center of CAP and responsible for regulating systemic inflammation, what changes will occur in MVZ's pathology and function in sepsis, especially when interfering with α7nAChRs? Does activation of MVZ's α7nAChRs contribute to the inhibition of systemic inflammation? To clarify these issues, we explored the systemic inflammation and immunity state by detecting serum levels of TNF-α, IL-6, HMGB1, sCD14, and CD4+CD25+Treg and TH17 lymphocytes percentage, meanwhile, we analyzed the apoptosis of cholinergic and catecholaminergic neurons and the expressions of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) in MVZ in sepsis and the interfering effects on α7nAChRs. In this study, we found that in sepsis, serum TNF-α, IL-6, HMGB1, sCD14, CD4+CD25+Treg, and TH17 lymphocytes significantly increased and the ratio of Treg/TH17 significantly decreased, cholinergic and catecholaminergic neurons underwent apoptosis with low expressions of TH and CHAT in MVZ; activation of α7nAChRs not only significantly decreased the levels of septic serum TNF-α, IL-6, HMGB1, sCD14, and TH17 lymphocytes (P ＜ 0.05), but also significantly reduced cholinergic and catecholaminergic neurons' apoptosis, and promoted expressions of TH/CHAT. Our study reveals that sepsis undermines MVZ through neuroinflammation which contributes to the uncontrolled systemic inflammation. Activating central α7nAChRs is not only helpful to restore MVZ's structure and function but also beneficial to subside the inflammatory storm in sepsis. Even if MVZ is damaged in sepsis, cholinergic neurons in MVZ still regulate the systemic inflammation stably.

Interleukin-6 and Interleukin-10 as a Predictor of Mortality in Elderly with COVID-19.

The age group at the most high risk for mortality due to SARS-CoV-2 infection was the elderly. This study aims to analyze markers that can predict the severity and mortality of elderly COVID-19 patients. This study used a cohort retrospective design. We include adult and elderly COVID-19 patients at Universitas Airlangga Hospital from March to August 2021. The sample used was 48 COVID-19 patients with positive real-time polymerase chain reaction swab results. We check the complete blood count and serum levels of interleukin-6 (IL-6) and IL-10 using enzyme-linked immunosorbent assay during admission. Data were analyzed using t -test, Mann-Whitney, Chi-square, Pearson, and Kendall Tau correlation. Leukocyte level (6.6 ± 2.5) was lowest in the severe-critical elderly group. Neutrophil level (75.3 ± 10.2) was highest in the mild-moderate elderly group. Lymphocyte level (18.8 ± 8.7) was highest in mild-moderate nonelderly group. Platelet level (279.0 ± 117.7) was highest in the mild-moderate elderly group. Neutrophil to lymphocyte ratio level (9.1 ± 9.4) was highest in the severe-critical nonelderly group, IL-6 level (98.6 ± 144.1) was highest in the severe-critical elderly group, IL-10 level (107.7 ± 47.7) was highest in the severe-critical elderly group and highest IL-6/IL-10 level (1.4 ± 1.7) was found in the mild-moderate elderly group no significant differences in biomarkers identification between the elderly and nonelderly groups. There was a substantial relationship between IL-10 levels and gender, IL-10 level, and hospital discharge condition. Female elderly patients and alive elderly patients were correlated with increased levels of IL-10.

Cholecalciferol combined with Satureja rechingeri essential oils improves growth performance and immune response of broiler chickens.

Vitamin D possesses an important role in the maintenance and health of broiler chickens. Herbal essential oils (EOs) have been proposed as a suitable alternative to chemical drugs in intensive production management systems for better performance of broilers with slight side effects and admirable therapeutic properties. This experiment was conducted to investigate the effects of feeding cholecalciferol (VD) in combination of Satureja rechingeri EO (SREO) on growth performance, haematological indicators and immunological response of broilers. A total of 540 1-day-old mixed-sex broiler chickens (Ross 308) were used in a completely randomized design with a 3×3 factorial arrangement of treatments. Experimental treatments included different concentrations of cholecalciferol (VD) (0, 2000 and 4000IU/kg=0, 0.05 and 0.1mg/kg) and SREO (0, 200 and 400mg/kg) on growth performance, haematological indicators and immunological responses of broiler chickens were investigated. The results showed that the chicken fed diet supplemented with 0.1mg/kg VD (VD0.1) in combination of 200mg/kg SREO (SREO200) increased the feed intake during the overall and first 14-day periods of the trial when compared with other dietary treatments. Interaction of VD0.1×SREO200 led to more body weight gain (BWG) in the grower and finisher phases than all other feed treatment groups. The blood level of lymphocyte at day 42, heterophil at days 28 and 42 and heterophil/lymphocyte (H/L) ratio at 14 and 28 days of age were affected by VD0.1+SREO200 in comparison with VD0+SREO0 group. Feeding VD and/or SREO decreased triglyceride, cholesterol and low-density lipoprotein concentrations at days 28 and 42 of the study, especially in VD0.1+SREO200 treatment. Feeding VD0.1+SREO200 also resulted in higher serum status of immunoglobulin M, lysozymes and phagocytic percentage among all treatments. Considering the outcomes, it is suggested that the combination of suitable concentration of VD and EO of the plant had favourable effects on the immune system and performance criteria of broiler chickens.

Association of clinicopathologic and sonographic features with stromal tumor-infiltrating lymphocytes in triple-negative breast cancer

BackgroundIncreased level of stromal tumor-infiltrating lymphocytes (sTILs) are associated with therapeutic outcomes and prognosis in triple-negative breast cancer (TNBC). This study aimed to investigate the associations of clinicopathologic and sonographic features with sTILs level in TNBC.MethodsThis study included invasive TNBC patients with postoperative evaluation of sTILs after surgical resection. Tumor shape, margin, orientation, echo pattern, posterior features, calcification, and vascularity were retrospectively evaluated. The patients were categorized into high-sTILs (≥ 20%) and low-sTILs (< 20%) level groups. Chi-square or Fisher’s exact tests were used to assess the association of clinicopathologic and sonographic features with sTILs level.ResultsThe 171 patients (mean ± SD age, 54.7 ± 10.3 years [range, 22‒87 years]) included 58.5% (100/171) with low-sTILs level and 41.5% (71/171) with high-sTILs level. The TNBC tumors with high-sTILs level were more likely to be no special type invasive carcinoma (p = 0.008), higher histologic grade (p = 0.029), higher Ki-67 proliferation rate (all p < 0.05), and lower frequency of associated DCIS component (p = 0.026). In addition, the TNBC tumors with high-sTILs level were more likely to be an oval or round shape (p = 0.001), parallel orientation (p = 0.011), circumscribed or micro-lobulated margins (p < 0.001), complex cystic and solid echo patterns (p = 0.001), posterior enhancement (p = 0.002), and less likely to have a heterogeneous pattern (p = 0.001) and no posterior features (p = 0.002).ConclusionsThis preliminary study showed that preoperative sonographic characteristics could be helpful in distinguishing high-sTILs from low-sTILs in TNBC patients.

Mitochondrial Pathogenic Mutations and Expression Pattern of Oxidative Phosphorylation Genes in COVID-19 Patients

Mitochondrial missense mutations and pathogenic variants have been implicated in the pathogenesis of COVID‐19. This study evaluated the role of mitochondrial DNA (mtDNA) mutations and changes in gene expression in the progression of COVID-19 and their correlation with clinical characteristics. Next‐generation sequencing with high throughput was used to identify mtDNA mutations in 30 COVID-19 patients compared to 20 healthy controls. The potential impact of identified mutations on protein structure and stability was predicted using bioinformatic tools. Quantitative real-time polymerase chain reaction was employed to assess the expression levels of mtDNA-encoded genes involved in oxidative phosphorylation in COVID-19 patients and healthy controls. Correlations between gene expression levels, clinical parameters, including leukocyte, lymphocyte, neutrophil, and platelet count, as well as creatinine, alanine transaminase (ALT), aspartate transaminase (AST), and blood urea nitrogen (BUN) levels, and disease severity were analyzed. We found 8 different mtDNA mutations in ND1, ND5, CO3, ATP6, and CYB genes, which were predicted to alter amino acids and decrease protein stability. Two missense unique mutations, C9555T in CO3 and A12418T in ND5 were identified and correlated with Complexes I and IV, respectively. This downregulation was correlated with age, elevated levels of leukocytes, lymphocytes, neutrophils, platelets, creatinine, ALT, AST, and BUN, as well as disease severity. These findings suggest that mtDNA mutations and altered expression of oxidative phosphorylation genes contribute to mitochondrial dysfunction in COVID-19. Targeting mitochondrial dysfunction may represent a promising therapeutic strategy for COVID-19 treatment.

The effect of long-standing lymphopenia after radiation therapy on survival in rectal cancer

BackgroundLymphopenia and high neutrophil-to-lymphocyte ratio are known negative prognostic factors in rectal cancer. Until recently, however, lymphopenia was regarded as a minor sequela following radiation therapy (RT). The immune system's influence on rectal cancer treatment outcomes led us to evaluate the impact of lymphopenia at various time points, before, during, and following radiotherapy. We hypothesized that chronic lymphopenia following radiotherapy might negatively influence the survival of patients, and pre-treatment lymphopenia may be predictive of poor outcomes. MethodsThis retrospective study involved 110 patients treated for rectal cancer between 2015 and 2019. The oncological outcomes are defined as alive without disease (AWOD), alive with disease (AWD), and death. These outcome probabilities tested against variables of lymphopenia before RT, during RT, and at several post-RT follow-up time points. ResultsAt the end of the study, 69 patients were AWOD (63 %), 13 were AWD (12 %) and 28 had died (25 %). Treatment results were assessed with according level of lymphocytes measured one year following RT: 35 out of 39 patients (89.7 %) with normal values were AWOD. In 65 patients with sustained lymphopenia, 52 % were AWOD, 18.5 % AWD and 29 % died. A similar difference was found at all time-points up to 2 years following RT (p < 0.004).The results of our study shows that pre-existing lymphopenia (prior to RT) is associated with a 3 times greater chance of death compared to patients with normal lymphocyte levels prior to RT. The PFS significantly affected by lymphopenia at all time-points after RT. An NLR of more than 4 was associated with a 3-time higher risk of recurrence than lower NLR scores (p = 0.0054). ConclusionOur results support the relevance of lymphopenia and NLR in the prognosis of rectal cancer. We believe this is the first study showing a negative correlation between sustained lymphopenia and OS following RT.

White blood cell counts, ratios, and C-reactive protein among individuals with schizophrenia spectrum disorder and associations with long-term outcomes: a population-based study

BackgroundImmune mechanisms are associated with adverse outcomes in schizophrenia; however, the predictive value of various peripheral immune biomarkers has not been collectively investigated in a large cohort before. ObjectiveTo investigate how white blood cell (WBC) counts, ratios, and C-Reactive Protein (CRP) levels influence the long-term outcomes of individuals with schizophrenia spectrum disorder (SSD). MethodsWe identified all adults in the Central Denmark Region during 1994–2013 with a measurement of WBC counts and/or CRP at first diagnosis of SSD. WBC ratios were calculated, and both WBC counts and ratios were quartile-categorized (Q4 upper quartile). We followed these individuals from first diagnosis until outcome of interest (death, treatment resistance and psychiatric readmissions), emigration or December 31, 2016, using Cox regression analysis to estimate adjusted hazard ratios (aHRs). ResultsAmong 6,845 participants, 375 (5.5 %) died, 477 (6.9 %) exhibited treatment resistance, and 1470 (21.5 %) were readmitted during follow-up. Elevated baseline levels of leukocytes, neutrophils, monocytes, LLR, NLR, MLR, and CRP increased the risk of death, whereas higher levels of lymphocytes, platelets, and PLR were associated with lower risk. ROC analysis identified CRP as the strongest predictor for mortality (AUC=0.84). Moreover, elevated levels of leukocytes, neutrophils, monocytes, LLR, NLR and MLR were associated with treatment resistance. Lastly, higher platelet counts decreased the risk of psychiatric readmissions, while elevated LLR increased this risk. ConclusionsElevated levels of WBC counts, ratios, and CRP at the initial diagnosis of SSD are associated with mortality, with CRP demonstrating the highest predictive value. Additionally, certain WBC counts and ratios are associated with treatment resistance and psychiatric readmissions.

Features of T-cell and humoral immunity of patients with acute coronary syndrome, with and without COVID-19, depending on/peripheral blood B-lymphocytes with the phenotype CD3–CD19+CD5+ level

The aim of the work was to assess the T-cell and humoral immune arms in patients with acute coronary syndrome (ACS) recovered from or not exposed to COVID-19. 86 men with ACS aged 40 to 65 years old, who suffered or not exposed to COVID-19, which required stenting of coronary arteries, were examined. Depending on the peripheral blood B-lymphocyte CD3–CD19+CD5+ level and the former COVID-19 history, all patients were divided into 6 groups. Of the previously COVID-19 exposed subjects CD3–CD19+CD5+ lymphocytes were at: reduced (group 1), normal (group 2), increased (group 3) level. COVID-19 unexposed subjects had CD3–CD19+CD5+ lymphocyte level: reduced (group 4), normal (group 5), increased (group 6). The most severe clinical manifestations were observed in group 1: with a larger rate of stent thrombosis and increased mortality. In absolute numbers, T-lymphocytes were significantly lower in group 1 compared to other groups, except group 4. The lowest both relative and absolute T-helper cell counts were recorded in covid-19 patients, with reduced CD3–CD19+CD5+ cell level. NK-lymphocytes both in relative and absolute level were significantly (p 0.05) higher in patients who suffered from COVID-19 as compared to those in patients unexposed to previous COVID-19. Percentage of late-activation T-regulatory cells was minimal in patients with former COVID-19 along with high B-lymphocyte CD3–CD19+CD5+ level, which significantly (p 0.05) differed from those in subjects lacking former COVID-19 history. In addition, significantly lower B-lymphocyte CD3–CD19+CD5– level was found in group 1 and 4. The IgM level peaked in group 5 — subjects lacking former COVID-19 history and having normal CD3–CD19+CD5+ cell level that significantly differed in comparison with that of in group 1, 2, 3. At the same time, the maximum value of IgG level was recorded in COVID-19 patients with normal CD3–CD19+CD5+ cells, and significantly differed from those found in group 5 and 6. C1-inhibitor level was higher in group 3 that significantly differed from that in other groups. SARS-CoV-2-specific IgG and IgM levels were significantly higher in COVID-19-positive vs. COVID-19-negative patients. Conclusion. In patients who have suffered COVID-19 with low B-lymphocyte CD3–CD19+CD5+ level, a significantly compromised immune protection was noted in comparison with other groups: a decline in total T-lymphocyte, T-helper, early- and late-activation T-lymphocyte, T-regulatory cell, B-lymphocyte CD3–CD19+CD5– levels, which was associated with a more severe disease course characterized by stent thrombosis and large mortality.

The effectiveness of HALP score in predicting mortality in non-ST-elevation myocardial infarction patients.

The HALP score, measured based on hemoglobin, albumin, lymphocyte, and platelet levels, is regarded as a novel scoring system that indicates the status of systemic inflammation and nutritional health. Our study aimed to evaluate the relationship between HALP score and prognosis in non-ST-elevation myocardial infarction (NSTEMI) patients. Between 1 January 2020 and 1 January 2022, 568 consecutive patients diagnosed with NSTEMI from a single center were included in the study retrospectively. The patients were divided into two equal groups according to the median HALP cutoff value of 44.05. Patients were followed for at least 1 year from the date of admission. The average age of the patients was 62.3 ± 10.6 years and 43.7% were female. In-hospital and 1-year mortality were found to be significantly higher in the group with low HALP scores (6.0 vs. 2.1%, P = 0.019 and 22.5 vs. 9.9%, P < 0.001, respectively). In receiver operating characteristic curve analysis, a cutoff level of 34.6 of the HALP score predicted 1-year mortality with 71% sensitivity and 65% specificity (area under the curve: 0.707, 95% confidence interval: 0.651-0.762, P < 0.001). In Kaplan-Meier analysis, higher mortality rates were observed over time in the group with lower HALP scores (log-rank test=16.767, P < 0.001). In Cox regression analysis, the HALP score was found to be an independent predictor of 1-year mortality (odds ratio: 0.969, 95% confidence interval: 0.958-0.981, P < 0.001). We found that a low HALP score could predict in-hospital and 1-year mortality in patients admitted to the hospital with a diagnosis of NSTEMI.

Clinical Characteristics of Overweight Patients With Acute Exacerbation Chronic Obstructive Pulmonary Disease (AECOPD).

Low body weight in patients with COPD is associated with a poor prognosis and more comorbidities. However, the impact of increased body weight in patients with COPD remains controversial. The aim of this study was to explore the clinical features of overweight patients with AECOPD. In this multicenter cross-sectional study, a total of 647 AECOPD patients were recruited. Finally, 269 normal weight and 162 overweight patients were included. Baseline characteristics and clinical and laboratory data were collected. The least absolute shrinkage and selection operator (LASSO) regression was performed to determine potential features, which were substituted into binary logistic regression to reveal overweight-associated clinical features. The nomogram and its associated curves were established to visualize and verify the logistic regression model. Six potential overweight-associated variables were selected by LASSO regression. Subsequently, a binary logistic regression model identified that the rates of type 2 diabetes (T2DM) and hypertension and levels of lymphocytes (LYM)%, and alanine aminotransferase (ALT) were independent variables of overweight in AECOPD patients. The C-index and AUC of the ROC curve of the nomogram were 0.671 and 0.666, respectively. The DCA curve revealed that the nomogram had more clinical benefits if the threshold was at a range of 0.22~0.78. Collectively, we revealed that T2DM and hypertension were more common, and LYM% and ALT were higher in AECOPD patients with overweight than those with normal weight. The result suggests that AECOPD patients with overweight are at risk for additional comorbidities, potentially leading to worse outcomes.

Association of Serum Vitamin D Levels with Inflammatory Markers in Hospitalized COVID-19 Patients

Background: In recent years, global concern has focused on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Multiple studies have suggested a potential connection between 1,25-dihydroxy Vitamin D levels and patient prognosis. Inflammatory markers have been identified as useful indicators for assessing the prognosis of hospitalized patients. This study aimed to evaluate the relationship between Vitamin D levels, inflammatory markers, and patient prognosis in cases of COVID-19. Methods: This descriptive-analytical study included 906 patients with COVID-19. Serum Vitamin D levels were measured and categorized into three groups: less than 20 ng/mL, between 20–30 ng/mL, and more than 30 ng/mL. Additionally, inflammatory markers, such as C-reactive protein (CRP) and Lactate Dehydrogenase (LDH), were evaluated. The study also addressed the analysis of CT scan findings and patient prognosis. Results: Of the total patients, 497 (54.9%) were male and 409 were female. The mean serum Vitamin D level was 40.10 ± 37.06 ng/mL, while the mean LDH and mean WBC levels were recorded at 696.38 ± 610.19 U/L and 9058.46 ± 6309.80 per microliter, respectively. CRP levels were classified as +1 in 296 patients (32.7%), +2 in 260 patients (28.7%), and +3 in 7 patients (0.8%). In terms of patient prognosis, 62 patients (6.8%) required intubation, and the mortality rate was 18.0% (163 patients). A statistically significant relationship was found between serum Vitamin D and LDH levels (p = 0.015). The findings indicated an insignificant relationship of serum Vitamin D levels with lymphocyte levels (p = 0.619), body mass index (BMI; p = 0.225), and CRP levels (p = 0.985). Furthermore, no relationship was found between patient mortality and serum Vitamin D levels (p = 0.5). Conclusion: Although Vitamin D has confirmed immunomodulatory effects in many studies, this study found no significant relationship between serum Vitamin D levels and mortality or other inflammatory markers in hospitalized COVID-19 patients. However, a statistically significant correlation was observed between LDH levels and serum Vitamin D.

High Probability of Lynch Syndrome Among Colorectal Cancer Patients Is Associated With Higher Occurrence of KRAS and PIK3CA Mutations.

In Indonesia, early-onset colorectal cancer (EOCRC) rates are higher in patients < 50 years old compared to Western populations, possibly due to a higher frequency of Lynch syndrome (LS) in CRC patients. We aimed to examine the association of KRAS and PIK3CA mutations with LS. In this retrospective cross-sectional single-center study, the PCR-HRM-based test was used for screening of microsatellite instability (MSI) mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1), MLH1 promoter methylation, and oncogene mutations of BRAF (V600E), KRAS (exon 2 and 3), and PIK3CA (exon 9 and 20) in FFPE DNA samples. All the samples (n = 244) were from Dr. Sardjito General Hospital Yogyakarta, Indonesia. KRAS and PIK3CA mutations were found in 151/244 (61.88%) and 107/244 (43.85%) of samples, respectively. KRAS and PIK3CA mutations were significantly associated with MSI status in 32/42 (76.19%) and 25/42 (59.52%) of samples, respectively. KRAS mutation was significantly associated with LS status in 26/32 (81.25%) of samples. The PIK3CA mutation was present in a higher proportion in LS samples of 19/32 (59.38%), but not statistically significant. Clinicopathology showed that KRAS mutation was significantly associated with right-sided CRC and higher histology grade in 39/151 (25.83%) and 24/151 (16.44%) samples, respectively. PIK3CA mutation was significantly associated with female sex and lower levels of tumor-infiltrating lymphocytes in 62/107 (57.94%) and 26/107 (30.23%) samples, respectively. KRAS and PIK3CA mutations did not significantly affect overall survival (120 months) in LS and non-LS patients. The high probability of LS in Indonesian CRC patients is associated with KRAS and PIK3CA mutations.