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Aims Methods Results Conclusions The aim of this study was to explore the clinical characteristics and risk factors for hypersensitivity reactions induced by antituberculosis drugs.A retrospective analysis was conducted on the medical records of patients with active tuberculosis (TB) treated in the TB ward at West China Hospital, Sichuan University, from November 2010 to April 2020.Out of 7106 patients with active tuberculosis, 205 experienced hypersensitivity reactions to antituberculosis drugs; the incidence of hypersensitivity was 2.9%. The predominant clinical manifestation was a rash, observed in 57.1% (117/205) of these cases. Additionally, 19.0% (39/205) of patients presented with concurrent liver injury. The laboratory parameters white blood cell count, total lymphocyte count, monocyte count, eosinophil count, basophil count, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase were significantly elevated in patients with hypersensitivity compared to those without. In 38 patients who tested positive for oral antituberculosis drug provocation, 14 (36.8%) were allergic to more than two antituberculosis drugs. Significant risk factors included being female (odds ratio [OR] = 1.387, 95% confidence intervals [CI]: 1.016–1.894), under 65 years of age (OR = 1.826, 95% CI: 1.145–2.913), existing liver disease (OR = 2.464, 95% CI: 1.822–3.333) and a history of allergic diseases (OR = 6.633, 95% CI: 2.681–16.406) and were significantly correlated with hypersensitivity to antituberculosis drugs.Hypersensitivity reactions to antituberculosis drugs primarily affect the skin, with significant associations observed with liver injury. Females, individuals younger than 65 years, those with pre‐existing liver disease and patients with a history of allergic diseases are at elevated risk for hypersensitivity. [ABSTRACT FROM AUTHOR]

Background. HIV is one of the most significant worldwide health concerns of the twenty‐first century and a serious threat to human society. Hemoglobin level and CD4 cell count are two of the most important biomarkers of HIV progression and patient survival. The objective of this study was to identify common risk factors associated with CD4 cell count and hemoglobin level among adult female HIV‐positive patients treated with ART at the University of Gondar Comprehensive Specialized Hospital, Ethiopia. Methods. The source of data in this study was secondary data conducted in the University of Gondar Comprehensive Specialized Hospital from September 2015 to March 2022. Data exploration in this study was normal histogram plot, box plot, and Q‐Q plot considered to gain some visions of the data related to CD4 cell count and hemoglobin level. A Bayesian joint model was used in this longitudinal data set to get a wide range of information about adult female HIV‐patients. Results. The mean with a standard deviation of hematocrit (%), red blood cell (106/μl), lymphocyte (%), and weight (kg) of female patients were 37.2 (3.8), 4.0 (1.6), 43.6 (11.8), and 44.9 (9.4), respectively. In this study, the random intercept model for CD4 cell count and the random intercept and slope model for hemoglobin level were considered as the best selected model. Visit time, hematocrit, weight, RBC, lymphocyte count, educational status, marital status, disclosure, and substance use were common risk factors for CD4 cell count and hemoglobin level. Conclusion. This study concluded that, the risk factors visit time, weight, secondary educators, tertiary educators, married patients, patients who disclosed their HIV status to family members were associated with high CD4 cell count and hemoglobin level. While, hematocrit, RBC, lymphocyte count, separated marital status, widowed marital status, and substance‐addicted patients were associated with low CD4 cell count and hemoglobin level. The author recommended that FMOH or other health professionals, program planners, decision makers, project implementers, government, and nongovernmental organizations should be given special attention for adult female patinets to minimize the risk of HIV progression and improve their health status. The author also recommended that health staff should conduct health‐related studies for patients to examine continuous checkups. Health professionals also should give more attention to types of ART medication to reduce the progression of disease when the patients come back again into the hospital. Finally, adult female HIV‐positive patients should be given special attention based on these important factors to improve their CD4 cell count, hemoglobin level, and better health quality. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate preoperative prognostic factors available for intrahepatic cholangiocarcinoma (ICC) patients and propose a new preoperative prognostic scoring system for ICC that combines CA19-9 and neutrophil/lymphocyte ratio (NLR). Methods: In this retrospective analysis, 1728 patients diagnosed with ICC and undergoing curative liver resections were studied. This study employed univariate and multivariate Cox regression to find factors affecting recurrence and overall survival (OS), and furthermore assessed how preoperative models influenced tumor traits and postoperative recurrence. Results: The results of the multivariate Cox regression analysis indicated that two preoperative variables, NLR and Ca19-9, were independent risk factors affecting postoperative recurrence and OS in ICC patients. Based on this data, assigning a score of 0 (NLR ≤ 2.4 and Ca19-9 ≤ 37U/ml) or 1 (NLR > 2.4 and Ca19-9 > 37U/ml) to these two factors, a preoperative prognostic score was derived. According to the scoring model, patients were divided into three groups: 0 points (low-risk group), 1 point (intermediate-risk group), and 2 points (high-risk group). The 5-year recurrence and OS rates for the three groups were 56.6%, 68.2%, 77.8%, and 56.8%, 40.6%, 27.6%, respectively, with all P values < 0.001. Furthermore, high-risk group patients were more prone to early recurrence (early recurrence rates for high-, intermediate-, and low-risk groups were 56.8%, 51.5%, and 37.1%, respectively, P < 0.001) and extrahepatic metastasis (extrahepatic metastasis rates for high-, intermediate-, and low-risk groups were 31.7%, 26.4%, and 15.4%, respectively, P < 0.001). In terms of tumor characteristics, high-risk group patients had larger tumor diameters and were more likely to experience microvascular invasion, lymph node metastasis, and perineural invasion. Conclusions: The predictive capacity of postoperative recurrence and OS rates in ICC patients is effectively captured by the preoperative scoring system incorporating NLR and CA19-9 levels. [ABSTRACT FROM AUTHOR]

Background: The systemic immune-inflammation index (SII) is a novel inflammatory marker used to assess the immune-inflammatory status of the human body. The systemic immune inflammation has an interplay and mutual relationship with neurological disorders. Serum neurofilament light chain (sNfL) is widely regarded as a potential biomarker for various neurological diseases. The study aimed to examine the association between SII and sNfL. Methods: This cross-sectional investigation was conducted in a population with complete data on SII and sNfL from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). The SII was calculated by dividing the product of platelet count and neutrophil count by the lymphocyte count. Multivariate linear regression models and smooth curves were used to explore the linear connection between SII and sNfL. Sensitivity analyses, interaction tests, and diabetes subgroup smoothing curve fitting were also performed. Results: A total of 2,025 participants were included in our present research. SII showed a significant positive association with the natural logarithm-transformed sNfL (ln-sNfL) in crude model [0.17 (0.07, 0.28)], partially adjusted model [0.13 (0.03, 0.22)], and fully adjusted model [0.12 (0.02, 0.22)]. In all participants, the positive association between SII and ln-sNfL served as a linear relationship, as indicated by a smooth curve. Interaction tests showed that age, gender, BMI, hypertension, and diabetes did not have a significant impact on this positive association (p for interaction >0.05). The subgroup analysis of diabetes was conducted using smooth curve fitting. It was found that compared to the group without diabetes and the group in a pre-diabetic state, the effect was more pronounced in the group with diabetes. Conclusion: Our findings suggest that there is a positive association between SII and sNfL. Furthermore, in comparison to individuals without diabetes and those in a pre-diabetic state, the positive association between SII and sNfL was more pronounced in individuals with diabetes. Further large-scale prospective studies are needed to confirm the association between SII and sNfL. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to compare hematological parameters preand early post-chemotherapy, and evaluate their values for predicting febrile neutropenia (FN). Methods: Patients diagnosed with malignant solid tumors receiving chemotherapy were included. Blood cell counts peri-chemotherapy and clinical information were retrieved from the hospital information system. We used the least absolute shrinkage and selection operator (LASSO) method for variable selection and fitted selected variables to a logistic model. We assessed the performance of the prediction model by the area under the ROC curve. Results: The study population consisted of 4,130 patients with common solid tumors receiving a three-week chemotherapy regimen in Sichuan Cancer Hospital from February 2019 to March 2022. In the FN group, change percentage of neutrophil count decreased less (-0.02, CI: -0.88 to 3.48 vs. -0.04, CI: -0.83 to 2.24). Among hematological parameters, lower postchemotherapy lymphocyte count (OR 0.942, CI: 0.934-0.949), change percentage of platelet (OR 0.965, CI: 0.955-0.975) and higher change percentage of post-chemotherapy neutrophil count (OR 1.015, CI: 1.011- 1.018), and pre-chemotherapy NLR (OR 1.002, CI: 1.002-1.002) predicted an increased risk of FN. These factors improved the predicting model based on clinical factors alone. The AUC of the combination model was 0.8275. Conclusion: Peri-chemotherapy hematological markers improve the prediction of FN. [ABSTRACT FROM AUTHOR]

Background: Limited information is available on the use of omalizumab (OMA) updosing since its introduction as a second‐line therapy in chronic spontaneous urticaria (CSU) in 2014. Practical guidelines from health authorities are lacking, and the specific characteristics of patients requiring higher doses remain unknown. Our objectives were to characterize the patterns of OMA updosing (defined as changes in dose and/or injection intervals), to identify the predictive factors associated with updosing, and to improve CSU management. Methods: We conducted a prospective, multicentric, real‐life observational study, including patients diagnosed with CSU and starting OMA. The data were collected at 0, 3, 6, and 9 months. The primary endpoint was the frequency of OMA updosing at 3 months. The secondary endpoints included an analysis of updosed patients' profile, and an assessment of OMA efficacy and safety. Results: We included 153 patients. Twenty percent of patients were updosed at 3 months, and 27% in total during the 9‐month follow‐up. Practitioners mainly chose to increase the frequency of injections (66%). At baseline, the updosed patients were more likely to have more severe CSU (UCT < 4, p < 0.030), a lower lymphocyte count (<2000/mm3, p = 0.037), and low IgE levels (<70 UI/mL, p = 0.024). The side effects of OMA were not more frequent after updosing. Conclusion: One in five patient underwent updosing within just 3 months. OMA updosing is frequent in particular in cases of severe disease and low IgE blood levels. [ABSTRACT FROM AUTHOR]

Salvia officinalis L., commonly known as sage and belonging to the Lamiaceae family, is a medicinal herb indigenous to the Mediterranean region. It is celebrated for its diverse pharmacological properties and traditional uses in folk medicine, particularly in addressing hepatotoxicity. Cisplatin (Cis), a potent chemotherapeutic agent widely employed in cancer treatment, is recognized for its efficacy but often accompanied by adverse effects, including hepatotoxicity. The aim of this study was to assess whether an ethanolic S. officinalis extract (ESOE) could provide protection against Cis -induced hepatotoxicity in an experimental rat model. The ESOE was prepared using standard extraction techniques, and its chemical constituents were elucidated through UPLC-ESI-MS/MS analysis, revealing the presence of bioactive compounds such as alkaloids, phenolic compounds, and flavonoids, which are associated with various therapeutic effects, including hepatoprotection. Adult male albino rats were allocated into four groups: control, ESOE (250 mg/kg), Cis (7.5 mg/kg), and ESOE (250 mg/kg) + Cis (7.5 mg/kg). The treatment duration lasted 21 days, with Cis administration on the 22nd day. Twenty-four hours post-Cis administration, blood and liver samples were collected for analysis. Cis -induced hepatotoxicity was evidenced by alterations in hematological parameters, including erythrocyte, thrombocyte, leukocyte, and lymphocyte counts, alongside elevated serum levels of liver enzymes (ALT, LDH, AST, ALP, and GGT), indicative of liver damage. Furthermore, Cis exposure resulted in increased hepatic malondialdehyde (MDA) and Nitric oxide (NO) levels, oxidative stress markers, coupled with decreased levels of reduced glutathione (GSH), a non-enzymatic antioxidant, and histopathological changes in liver tissue, characterized by necrosis and inflammation. Additionally, Cis treatment led to elevated levels of 8-hydroxy-2′-deoxyguanosine (8-OH-dG), TNF-α, and IL-6, indicating oxidative stress and inflammation. Remarkably, pretreatment with ESOE ameliorated these Cis -induced hepatotoxic effects, as evidenced by improved hematological parameters, reduced liver enzyme activities, alleviated oxidative stress, and ameliorated histopathological alterations. The observed hepatoprotective effects of ESOE against Cis -induced liver injury may be attributed to its antioxidant and anti-inflammatory properties, highlighting its potential as a natural therapeutic agent in mitigating chemotherapy-associated hepatotoxicity. [Display omitted] • Ethanolic Salvia officinalis extract (ESOE) mitigates cisplatin-induced hepatotoxicity. • ESOE restores hematological parameters and hepatic enzyme levels. • ESOE attenuates oxidative stress and inflammatory markers in rat liver. • Histological examination confirms ESOE's protective effect on hepatic architecture. • ESOE suppresses caspase-3 and iNOS expression, indicating anti-apoptotic and anti-inflammatory actions. [ABSTRACT FROM AUTHOR]

Aims: Over 50% of breast cancer cases are "Human epidermal growth factor receptor 2 (HER2) low breast cancer (BC)", characterized by HER2 immunohistochemistry (IHC) scores of 1+ or 2+ alongside no amplification on fluorescence in situ hybridization (FISH) testing. The development of new anti‐HER2 antibody‐drug conjugates (ADCs) for treating HER2‐low breast cancers illustrates the importance of accurately assessing HER2 status, particularly HER2‐low breast cancer. In this study we evaluated the performance of a deep‐learning (DL) model for the assessment of HER2, including an assessment of the causes of discordances of HER2‐Null between a pathologist and the DL model. We specifically focussed on aligning the DL model rules with the ASCO/CAP guidelines, including stained cells' staining intensity and completeness of membrane staining. Methods and Results: We trained a DL model on a multicentric cohort of breast cancer cases with HER2‐IHC scores (n = 299). The model was validated on two independent multicentric validation cohorts (n = 369 and n = 92), with all cases reviewed by three senior breast pathologists. All cases underwent a thorough review by three senior breast pathologists, with the ground truth determined by a majority consensus on the final HER2 score among the pathologists. In total, 760 breast cancer cases were utilized throughout the training and validation phases of the study. The model's concordance with the ground truth (ICC = 0.77 [0.68–0.83]; Fisher P = 1.32e‐10) is higher than the average agreement among the three senior pathologists (ICC = 0.45 [0.17–0.65]; Fisher P = 2e‐3). In the two validation cohorts, the DL model identifies 95% [93% ‐ 98%] and 97% [91% ‐ 100%] of HER2‐low and HER2‐positive tumours, respectively. Discordant results were characterized by morphological features such as extended fibrosis, a high number of tumour‐infiltrating lymphocytes, and necrosis, whilst some artefacts such as nonspecific background cytoplasmic stain in the cytoplasm of tumour cells also cause discrepancy. Conclusion: Deep learning can support pathologists' interpretation of difficult HER2‐low cases. Morphological variables and some specific artefacts can cause discrepant HER2‐scores between the pathologist and the DL model. [ABSTRACT FROM AUTHOR]

Negative symptoms in the context of psychosis are still poorly understood and diagnosed, which impairs the treatment efficacy of current therapies and patient's integration in society. In this study, we aimed to test hypothesis-based and exploratory associations of negative symptom domains, as defined by the Brief Negative Symptom Scale (BNSS), with hormonal and hematological variables, and, complementarily, with standard psychological/cognitive and psychopathological measures. Fifty-one male patients diagnosed with a psychotic disorder underwent a structured interview and blood collection. Standard Spearmen bivariate correlations were used for data analysis. We obtained evidence of hypothesis-based associations between specific negative symptoms and oxytocin, thyroid stimulating hormone levels and neutrophil-to-lymphocyte ratio; as well as novel and hypothesis-free associations with erythrocyte and lymphocyte count, mean corpuscular volume and red cell distribution width. Complementarily, we also obtained some validation of previous associations of negative symptoms with illness resolution, cognitive symptom severity and social performance, and a novel association with anger contagion. We hope our results can generate new hypotheses in psychosis research. Our work suggests further avenues in research on erythrocytic, inflammatory, thyroid and oxytocin-related markers and abnormalities in psychosis, especially in regards to specific negative symptoms, towards more precise and comprehensive etiological, diagnostic and therapeutic models. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the dynamic changes and interrelationships between leukocyte components and inflammatory markers in the early stages and sepsis stage in severe burns, and explore their potential clinical significance. This is a 5-year retrospective cohort study involving 107 patients with severe burns (the total body surface area of burn (TBSA) > 50%), in which, neutrophil count, lymphocyte count, monocyte count, the ratio of the product of monocyte and lymphocyte count to neutrophil count (MLPN), procalcitonin (PCT), C-reactive protein (CRP), capillary leakage index (CLI) and creatinine (Scr) were investigated. Within one week after injury, the leukocyte components and MLPN showed a V-shaped change, with a peak immediately after injury and a trough on the 4th or 5th day after injury, while CRP showed a continuous upward trend, and the leukocyte compositions of all patients were negatively correlated with CRP values. The counts of leukocytes components and CRP values in deceased patients were higher than those in surviving patients within 2 days after injury. In the resorption stage, although no significant difference in lymphocyte and monocyte counts between surviving and deceased patients was found, the monocyte and lymphocyte counts in deceased patients were lower than those in surviving patients on the 5th to 7th day after injury, while neutrophils counts and CRP values remained higher than those in surviving patients. And the dynamic changes of MLPN were consistent with those of leukocyte compositions and opposite to those of PCT values. Moreover, MLPN were negatively correlated with CRP, CLI, and Scr values in the early stage of severe burns. In sepsis stage, as the condition worsened, the values of CRP, PCT and neutrophil counts continuously increased with varying degree, while lymphocyte and monocyte counts, and MLPN showed continuously decrease, but rebounded to increase before death. And the occurrence of the trough of monocyte counts was earlier than that of lymphocyte counts, a negative correlation between neutrophil counts and PCT values was found. The results of this study revealed the dynamic interrelationships between leucocyte components and inflammatory indicators in the early stages and sepsis stage in severe burns, reflecting the different weightings of inflammatory responses and immune dysfunction in different disease stages and its correlation with outcomes, which providing useful clinical information for dynamic immunomodulatory therapy. Moreover, dynamic monitoring of MLPN value can provide timely information for clinical evaluation. ● Within one week after injury, the leukocyte components were negatively correlated with CRP values. ● The trend of changes in MLPN values was similar to leukocyte components in the early stage after injury. ● A negative correlation between neutrophil counts and PCT values was found in sepsis stage. ● The occurrence of lowest value of monocyte count was earlier than that of lymphocyte count in sepsis stage. ● Lymphocyte and monocyte counts, and MLPN values rebounded to increase before death in sepsis stage. [ABSTRACT FROM AUTHOR]

Pilot tends to have a high prevalence of dyslipidemia. The present study aimed to identify key factors of pilot hyperlipidemia through thorough analysis of physical examination data, and to provide pilot-targeted health guidance to manage hyperlipidemia risks. The physical examination data of 1,253 pilot inpatients from January 2019 to June 2022, were evaluated and divided into two groups based on whether or not the pilot had hyperlipidemia. A total of three multivariate analysis models including logistic model, multilevel model and boosting propensity score were applied to find the risk factors of pilot hyperlipidemia. In the group of pilots with hyperlipidemia, four risk factors, including thrombin time, carbohydrate antigen 199, lymphocyte count and rheumatoid factor, were significantly different from pilots without hyperlipidemia, which might be positively associated with the incidence of hyperlipidemia. In future studies regarding pilots, whether hyperlipidemia is connected to abnormalities in thrombin time, carbohydrate antigen 199 and rheumatoid factor should be further explored. Based on the findings of the present study, pilot health management should be more refined and personalized, and attention should be paid to the risk factors of hyperlipidemia including diet and lifestyle. [ABSTRACT FROM AUTHOR]

A comprehensive meta-analysis on the composition of circulating immune cells from both the myeloid and the lymphoid lines including specialized subsets in blood and cerebrospinal fluid (CSF) of patients with psychotic disorders compared with healthy control participants has been lacking. Multiple databases (PubMed, EMBASE, Cochrane Library, Web of Science, ClinicalTrials.gov, and PsycINFO) were searched for eligible studies up until October 18, 2022. All studies investigating circulating immune cells in the blood and CSF from patients with psychotic disorders (ICD-10: F20 and F22-29) compared with healthy control participants were included. A total of 86 studies were included in the meta-analysis. In the blood, the following categories of immune cells were elevated: leukocyte count (31 studies, standardized mean difference [SMD] = 0.35; 95% CI, 0.24 to 0.46), granulocyte count (4 studies, SMD = 0.57; 95% CI, 0.12 to 1.01), neutrophil granulocyte count (21 studies, SMD = 0.32; 95% CI, 0.11 to 0.54), monocyte count (23 studies, SMD = 0.40; 95% CI, 0.23 to 0.56), and B lymphocyte count (10 studies, SMD = 0.26; 95% CI, 0.04 to 0.48). Additionally, the neutrophil/lymphocyte ratio (23 studies, SMD = 0.40; 95% CI, 0.19 to 0.60), the monocyte/lymphocyte ratio (9 studies, SMD = 0.31; 95% CI, 0.04 to 0.57), and the platelet/lymphocyte ratio (10 studies, SMD = 0.23; 95% CI, 0.03 to 0.43) were elevated. The CSF cell count showed a similar tendency but was not significantly elevated (3 studies, SMD = 0.14; 95% CI, −0.04 to 0.32). The results indicate a broad activation of the immune system in psychotic disorders, with cells from both the myeloid and the lymphoid line being elevated. However, CSF analyses were lacking in most of the studies, and many studies were hampered by insufficient adjustment for confounding factors such as body mass index and smoking. [ABSTRACT FROM AUTHOR]

Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS. MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian–Laird method. Risk of bias assessment was done using the Newcastle–Ottawa Scale. Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L−1 higher C-reactive protein (95% confidence interval [CI] 12.7–56.2 mg L−1; P <0.01), a 4.4 g L−1 lower albumin (95% CI 0.5–8.3 g L−1; P <0.01), and a 0.36×109 L−1 lower lymphocyte count (95% CI 0.25–0.47×109 L−1; P =0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly. While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions. International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749). [ABSTRACT FROM AUTHOR]

Background: The immunological background responsible for the severe course of COVID-19 and the immune factors that protect against SARS-CoV-2 infection are still unclear. The aim of this study was to investigate immune system status in persons with high exposure to SARS-CoV-2 infection. Methods: Seventy-one persons employed in the observation and infectious diseases unit were qualified for the study between November 2020 and October 2021. Symptomatic COVID-19 was diagnosed in 35 persons. Anti-SARS-CoV-2 antibodies were also found in 8 persons. Peripheral blood mononuclear cells subpopulations were analyzed by flow cytometry, and the concentrations of cytokines and anti-SARS-CoV-2 antibodies were determined by ELISA. Results: The percentages of cytotoxic T lymphocytes (CTLs), CD28+ and T helper (Th) cells with invariant T-cell receptors were significantly higher in persons with symptomatic COVID-19 than in those who did not develop COVID-19' symptoms. Conversely, symptomatic COVID-19 persons had significantly lower percentages of: a) CTLs in the late stage of activation (CD8+/CD95+), b) NK cells, c) regulatory-like Th cells (CD4+/CTLA-4+), and d) Th17-like cells (CD4+/CD161+) compared to asymptomatic COVID-19' persons. Additionally, persons with anti-SARS-CoV-2 antibodies had a significantly higher lymphocyte count and IL-6 concentration than persons without these antibodies. Conclusion: Numerous lymphocyte populations are permanently altered by SARS-CoV-2 infection. High percentages of both populations: NK cells—as a part of the non-specific response, and T helper cells' as those regulating the immune response, could protect against the acute COVID-19 symptoms development. Understanding the immune background of COVID-19 may improve the prevention of this disease by identifying people at risk of a severe course of infection. Trial registration: This is a retrospective observational study without a trial registration number. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) has been less deadly since the advent of corticosteroid-sparing medications. SLE patients still have a higher mortality rate than the general population. Infectious disease is reported as one of the major causes of death in patients with SLE. Although bacteria are the most often isolated pathogens from patients with SLE, Pneumocystis jirovecii pneumonia (PJP) is more deadly than bacterial infection. Methods: We retrospectively enrolled consecutive patients with SLE concurrent with PJP (SLE-PJP) in our center between January 2014 and December 2022. The participants were classified into two groups: survivors and non-survivors. Cox regression models and Kaplan‒Meier survival analyses were conducted to explore prognostic factors for survival. Results: There were 57 patients with SLE (42.0 ± 15.8 years old, 78.9% female) complicated with PJP, 22 (38.6%) of whom died. Compared with the survival group, the non-survival group had more patients with hyperglycemia or diabetes mellitus, invasive ventilation (p < 0.01), respiratory failure, intensive care unit admission, non-invasive ventilation, and hospital-acquired pneumonia (p < 0.05). The non-survival group showed a higher neutrophil percentage, lactate dehydrogenase, D-dimer (p < 0.001), urea, high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), and ferritin (p < 0.05). It also had lower minimal albumin, hemoglobin (p < 0.001), immunoglobulin G, complement 3, peripheral lymphocyte count, platelet, NK cell count, and CD4+ T-cell count (p < 0.05). Multivariate analysis indicated that hyperglycemia or diabetes mellitus (HR = 4.25, p < 0.01, 95% CI: 1.51–11.97), thrombocytopenia (HR = 4.22, p < 0.01, 95% CI: 1.63–10.91) and lower complement 3 (C3) (HR = 4.06, p < 0.01, 95% CI: 1.60-10.33) were independent risk factors for the survival of SLE-PJP patients. Conclusions: The mortality rate of patients with SLE-PJP is still high. Hyperglycemia, decreased C3, and thrombocytopenia are independent survival risk factors. [ABSTRACT FROM AUTHOR]

Background: The relationship between peripheral immune cells and immunoglobulin A nephropathy (IgAN) is widely known; however, causal evidence of this link is lacking. Here, we aimed to determine the causal effect of peripheral immune cells, specifically total white blood cells, lymphocytes, monocytes, basophils, eosinophils, and neutrophils, as well as lymphocyte subset traits, on the IgAN risk using a Mendelian randomization (MR) analysis. Methods: The inverse-variance weighted (IVW) method was used for the primary analysis. We applied three complementary methods, including the weighted median, MR-Egger regression, and MR-PRESSO, to detect and correct for the effect of horizontal pleiotropy. Additionally, we performed a multivariable MR (MVMR) analysis, adjusting for the effects of C-reactive protein (CRP) levels. The roles of specific lymphocyte subtypes and their significance have garnered interest. Bidirectional two-sample MR analysis was performed to test the potential causal relationships between immune traits, including median fluorescence intensities (MFIs) and the relative cell count (AC), and IgAN. Results: The IVW-MR analysis suggested a potential causal relationship between lymphocyte counts and IgAN in Europe (OR per 1-SD increase: 1.43, 95% CI: 1.08-1.88, P = 0.0123). The risk effect of lymphocytes remained even after adjusting for CRP levels using the MVMR method (OR per 1-SD increase: 1.44, 95% CI: 1.05-1.96, P = 0.0210). The other sensitivity analyses showed a consistent trend. The largest GWAS published to date was used for peripheral blood immunophenotyping to explore the potential causal relationship between peripheral immune cell subsets and IgAN. Six AC--IgAN and 14 MFI--IgAN pairs that reached statistical significance (P < 0.05) were detected. Notably, CD3, expressed in eight subsets of T cells, consistently showed a positive correlation with IgAN. The bidirectional MR analysis did not reveal any evidence of reverse causality. According to the sensitivity analysis, horizontal pleiotropy was unlikely to distort the causal estimates. Conclusions: Genetically determined high lymphocyte counts were associated with IgAN, supporting that high lymphocyte counts is causal risk factor for IgAN. [ABSTRACT FROM AUTHOR]

Background: In 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. Methods: This 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. Results: Our 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. Conclusion: Our 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. [ABSTRACT FROM AUTHOR]

While previous observational studies have suggested a link between leukocyte counts and vascular dementia (VD), the causal relationship between leukocyte counts and various subtypes of VD remains elusive. This study aimed to investigate the causal relationship between five types of leukocyte counts and VD, with the goal of improving prevention and treatment strategies. In this study, leukocyte counts were used as the exposure variable, with genome-wide association study (GWAS) data sourced from both the UK Biobank and the Blood Cell Consortium. Additionally, GWAS data for five subtypes of vascular dementia were obtained from the FinnGen database. We conducted rigorous statistical analysis and visualization using Mendelian randomization (MR) to elucidate the potential causal relationship between leukocyte counts and vascular dementia. This study, utilizing MR analysis with data from the UK Biobank and Blood Cell Consortium, identified significant causal associations between increased lymphocyte counts and VD. Specifically, lymphocyte counts were found to be causally related to multiple and mixed VD subtypes. Sensitivity analyses, including MR-Egger regression and MR-PRESSO tests, confirmed the robustness of these findings, with no evidence of reverse causality or significant horizontal pleiotropy detected. The results underscore a potential inflammatory or immunological mechanism in the pathogenesis of VD, highlighting lymphocytes as a key component in their etiology. This investigation establishes a robust association between elevated lymphocyte and leukocyte counts and an increased risk of VD, emphasizing the roles of inflammation, immune activation, and hematological factors in disease pathogenesis. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusions Peripheral inflammation is probably involved in the pathogenesis of progressive supranuclear palsy (PSP) and it may be a common feature with Parkinson's disease (PD). The peripheral immune profile in PSP remains unclear, as well as whether the inflammatory pathways differ from those in PD. The neutrophil‐to‐lymphocyte ratio (NLR) has been proven to be a well‐established biomarker of systemic inflammation. This study aimed to evaluate the peripheral immune profile in PSP compared with PD.A cross‐sectional study was conducted including patients with PSP and PD and healthy controls (HCs). Leukocyte subpopulations and the NLR were measured in peripheral blood. Multivariate linear regression and post hoc tests were applied. Electronic databases were searched in November 2023 to perform meta‐analyses to clarify the peripheral immune profile in PSP.Our cohort included 121 patients with PSP, 127 patients with PD and 266 HCs. The NLR was higher in PSP and PD compared with HCs. PSP had a higher neutrophil count compared with HCs. Whilst a lower lymphocyte count was found in PD compared with HCs, the lymphocyte count did not differ between PSP and HCs. The meta‐analyses supported this immune profile.PSP and PD show an increased peripheral inflammation and a higher NLR compared with HCs. Different pathogenic inflammatory mechanisms are probably involved in PSP and PD, since in PSP this altered peripheral immune profile is mainly driven by neutrophils. Understanding the neutrophils' role in PSP may allow for the development of targeted therapies. [ABSTRACT FROM AUTHOR]

HIV prevention with pre‐exposure prophylaxis (PrEP) constitutes a major pillar in fighting the ongoing epidemic. While daily oral PrEP adherence may be challenging, long‐acting (LA‐)PrEP in oral or implant formulations could overcome frequent dosing with convenient administration. The novel drug islatravir (ISL) may be suitable for LA‐PrEP, but dose‐dependent reductions in CD4+$$ \mathrm{CD}{4}^{+} $$ T cell and lymphocyte counts were observed at high doses. We developed a mathematical model to predict ISL pro‐drug levels in plasma and active intracellular ISL‐triphosphate concentrations after oral vs. subcutaneous implant dosing. Using phase II trial data, we simulated antiviral effects and estimated HIV risk reduction for multiple dosages and dosing frequencies. We then established exposure thresholds where no adverse effects on immune cells were observed. Our findings suggest that implants with 56–62 mg ISL offer effective HIV risk reduction without reducing lymphocyte counts. Oral 0.1 mg daily, 3–5 mg weekly, and 10 mg biweekly ISL provide comparable efficacy, but weekly and biweekly doses may affect lymphocyte counts, while daily dosing regimen offered no advantage over existing oral PrEP. Oral 0.5–1 mg on demand provided >90%$$ >90\% $$ protection, while not being suitable for post‐exposure prophylaxis. These findings suggest ISL could be considered for further development as a promising and safe agent for implantable PrEP. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to evaluate the clinical effect of mixed nutrition and parenteral nutrition support on postoperative patients with esophageal cancer. Method: By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures until March 2024 about the comparison of randomized controlled Trial (RCT) of mixed nutrition and parenteral nutrition support in postoperative patients with esophageal cancer were screened. The inclusion criteria were that the patients were from randomized controlled trials or clinical trials in China, and the patients were all diagnosed with esophageal cancer by pathological biopsy. The exclusion criteria were the literature other than the above, including repeated published literature, non-Chinese and English literature, incomplete or missing analysis data, etc. After two researchers independently screened the literature, extracted the data and evaluated the risk of bias according to the criteria, Meta-analysis was carried out with RevMan 5.4 software. Results: A total of 11 studies were included, including 1216 patients. Metaanalysis showed that, compared with parenteral nutrition, mixed nutrition can improve the levels of transferrin, serum albumin, prealbumin and lymphocyte counts in patients with esophageal cancer after surgery, shorten the time of anal recovery of exhaust, defecation and hospital stay after surgery, and reduce the incidence of pulmonary infection, abdominal distension, incision infection and anastomotic fistula, with statistical significance between the two groups (P < 0.05). The heterogeneity of individual results in this study is relatively high, the analysis comes from clinical heterogeneity, and the publication bias is analyzed through Funnel plot. Taking the incidence of lung infection as an example, the results are evenly distributed on both sides of the Funnel plot, and the publication bias has little impact on the results of the study. Conclusion: Compared with parenteral nutrition, mixed nutrition can improve the prognosis of postoperative patients with esophageal cancer and reduce the incidence of related adverse events. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the association between stress hyperglycemia ratio (SHR) and poor functional outcomes at 90 days in patients with acute ischemic stroke (AIS). Methods: This study retrospectively collected 1988 AIS patients admitted to two hospitals in the Shenzhen area between January 2022 and March 2023. A total of 1255 patients with Fasting Blood-glucose (FBG) and hemoglobin A1c (HbA1C) values at admission were included in this analysis. SHR, measured by FBG/HbA1C, was evaluated as both a tri-categorical variable (Tertile 1: ≤ 0.83; Tertile 2: 0.84 -0.95; Tertile 3: ≥ 0.96). The outcome was poor functional outcomes (modified Rankin Scale [mRS] score 2–6) at 90 days. We performed univariate analysis, multiple equation regression analysis, stratified analysis, and interactive analysis. Results: Compared with patients in the lowest tertile of SHR, the highest tertile group had significantly lower odds of achieving poor functional outcomes (adjusted odds ratio, OR = 2.84, 95% CI: 2.02–3.99, P < 0.0001) at 90 days after adjusting for potential covariates. Similar results were observed after further adjustment for white blood cell count, neutrophil count, lymphocyte count, fasting blood glucose, stroke type, intravenous thrombolytic therapy, baseline Glasgow score, and baseline NIHSS score. Conclusion: SHR, as measured by the FBG/HbA1C, was associated with an increased odds of achieving poor functional outcomes in patients with AIS at 90 days. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion The prognostic nutritional index (PNI) has been reported as a significant predictor in various diseases. However, the prognostic value of the PNI in geriatric hip fracture patients has not been thoroughly evaluated. This study aimed to investigate the association between admission PNI and 3‐year mortality in those patients.In this post hoc analysis, we included patients aged ≥65 years who underwent surgery for hip fracture between 2018 and 2019. The admission PNI was calculated as serum albumin (g/L) +5 × total lymphocyte count (×109/L). Patients were categorized into four groups based on PNI quartiles (≤ 43.55, 43.55–46.55, 46.55–49.20, and >49.20, respectively). The median follow‐up duration was 3.1 years. Cox proportional hazards models were used to calculate the hazard ratio (HR). Receiver operating characteristic curve (ROC) was conducted for using PNI to predict mortality.Of the 942 eligible patients, 190 (20.2%) patients died during the follow‐up. Compared to patients in the first quartile (Q1), those in the second (Q2), third (Q3), and fourth (Q4) quartiles had significantly lower mortality risks (HRs 0.50, 95% CI 0.35–0.74; 0.41, 95% CI 0.26–0.64; and 0.26, 95% CI 0.15–0.45, respectively). The optimal cutoff of PNI for predicting mortality was set as 45.275 (sensitivity, 0.674; specificity, 0.692; area under the curve (AUC), 0.727). Patients with higher PNI (>45.275) had a significant lower mortality risk (HR 0.39, 95% CI 0.28–0.55) compared to those with lower PNI (≤ 45.275).PNI is a reliable and independent predictor of 3‐year mortality after hip fracture surgery in the elderly. [ABSTRACT FROM AUTHOR]

Simple Summary: An Aeromonas veronii strain, isolated from bronze gudgeon, was identified as a significant cause of morbidity and mortality. Through bacterial isolation, virulence gene analysis, and physiological characterization, we identified this bacterium as containing the act, alt, lip, LuxS, and ascV genes, which are distinct from those reported in infections of other aquatic animals. Designated as strain WH10, this is the first documented instance of Aeromonas veronii infecting bronze gudgeon. Our findings provide new insights into the mechanisms of bacterial transmission and underscore the necessity for further research into Aeromonas veronii pathogenesis. Aeromonas veronii, an opportunistic pathogen toward aquatic organisms, was identified as the causative pathogen (isolate WH10) in diseased bronze gudgeon via bacterial isolation, and morphological, physiological, biochemical, and molecular characterization. WH10 exerted its pathogenicity via five virulence genes, including those encoding cytotoxic enterotoxins (act and alt), lipase (lip), a quorum sensing-controlled virulence factor (LuxS), and a Type III secretion system inner membrane component (ascV). WH10 was shown to be sensitive to compound sulfamethoxazoles, cefothiophene, doxycycline, and sulfamethoxazole. Toward bronze gudgeon, WH10 had a median lethal dose (LD50) of 1.36 × 106 colony forming units/mL. Analysis of blood parameters of diseased fish revealed significant increases in monocytes and neutrophils, but decreased numbers of lymphocytes. Serum aspartate aminotransferase activity and triglyceride concentration were significantly higher in diseased fish than in healthy fish. The reverse was noted for alkaline phosphatase, total protein, albumin, total cholesterol, and glucose. Thus, Aeromonas veronii is implicated as the causative agent of the mass mortality observed in bronze gudgeon, warranting further investigations into the diagnosis, epidemiology, prevention, and treatment of this infectious disease. [ABSTRACT FROM AUTHOR]

Cenerimod is a sphingosine‐1‐phosphate receptor 1 modulator that reduces tissue availability of circulating lymphocytes. The compound is in Phase 3 development for the treatment of systemic lupus erythematosus. Its pharmacokinetic properties are characterized by slow absorption and multiphasic elimination with a long terminal half‐life (t½), potentially caused by enterohepatic circulation (EHC). In this trial in healthy participants, oral cenerimod 0.5 and 4 mg once daily was administered for 50 days, followed by oral administration of activated charcoal (ie, 50 mg every 12 h for 11 days, starting 24 h after the last cenerimod dose), to investigate the potential EHC of cenerimod and assess whether elimination of cenerimod can be accelerated. The multiple‐dose pharmacokinetics, pharmacodynamics, safety, and tolerability of cenerimod were also evaluated. For both doses, peak plasma concentrations were reached 6 and 7 h after dosing. Cenerimod accumulated approximately eightfold and (near) steady‐state conditions were reached after 50 doses, resembling clinically meaningful exposure to cenerimod. The t½ following 0.5 and 4 mg of cenerimod was 767 and 799 h (ie, 32 and 33 days) and 720 and 780 h (ie, 30 and 33 days) with or without administration of charcoal, respectively, indicating no statistically significant difference. Therefore, charcoal did not accelerate cenerimod elimination suggesting that there is no EHC of cenerimod. A reversible, dose‐dependent decrease in total lymphocyte count was observed. No safety concerns were identified; administration of charcoal was well tolerated. [ABSTRACT FROM AUTHOR]

Introduction: Radiation induced lymphopenia (RIL) deteriorate survival and diminishes the benefit of immune checkpoint inhibitors in combined treatment of lung cancer. Given the inconsistent data across various studies on the predictors of RIL, we aim to methodically elucidate these predictors and formulate a practical guide for clinicians. Methods: We conducted observational cohort study in four tertiary cancer centers. Patients with non-small cell lung cancer and small cell lung cancer, without lymphopenia grade >1, who underwent standalone radiotherapy (RT) in minimum 15 fractions were eligible. Dose-volume parameters of structures and clinical factors were comprehensively analyzed using various predictors selection methods and statistical models (Linear Regressors, Elastic Net, Bayesian Regressors, Huber Regression, regression based on k-nearest neighbors, Gaussian Process Regressor, Decision Tree Regressor, Random Forest Regressor, extreme Gradient Boosting, Automated Machine Learning) and were ranked to predict lymphocytes count nadir (alc_nadir). Results: Two hundred thirty eight patients (stage I-3.4%, II-17.6%, III-75.2%, IV- 3.8%) who underwent RT to median dose of 60 Gy were analyzed. Median alc_nadir was 0.68K/mm³. The 60 feature sets were evaluated in 600 models (RMSE 0.27-0.41K/mm³). The most important features were baseline lymphocyte count (alc_1), mean lung_dose, lung v05, lung v10, heart v05 and effective dose to immune cells (edic). In patients with alc_1 < 2.005K/mm³, median alc_nadir predictions were 0.54K/mm³ for lung_v05p > 51.8% and 0.76K/mm³ for lung_v05p ≤ 51.8%. Lymphopenia was rare in patients with alc_1 > 2.005K/mm³. Discussion: RIL was most severe in patients with low early lymphocyte counts, primarily triggered by low RT doses in the heart and lungs. [ABSTRACT FROM AUTHOR]

Background: Since the HIV epidemic in the 1980s, CMV retinitis has been mainly reported in this context. CMV retinitis in persons living with HIV is usually observed when CD4 + cells are below 50 cells/mm3. This study aims to describe the immune markers of non-HIV-related CMV retinitis as well as to describe its clinical manifestations and outcomes. Methods: Retrospective chart review of consecutive patients with CMV retinitis not related to HIV seen at the uveitis clinic of Jules Gonin Eye Hospital between 2000 and 2023. We reported the clinical manifestations and outcomes of the patients. We additionally assessed immune markers during CMV retinitis (leukocyte, lymphocyte, CD4 + cell and CD8 + cell counts as well as immunoglobulin levels). Results: Fifteen patients (22 eyes) were included. Underlying disease was hematologic malignancy in 9 patients, solid organ transplant in 3 patients, rheumatic disease in 2 patients and thymoma in one patient. The median time between the onset of underlying disease and the diagnosis of retinitis was 4.8 years. Lymphopenia was observed in 8/15 patients (mild = 3, moderate = 4, severe = 1), and low CD4 counts were observed in 9/12 patients, with less than 100 cells/mm3 in 4 patients. Hypogammaglobulinemia was detected in 7/11 patients. Retinitis was bilateral in 7/15 patients, and severe visual loss was frequent (5/19 eyes). Disease recurrence was seen in 7/13 patients at a median time of 6 months after initial diagnosis. No differences in immune markers were observed in patients with vs. without recurrence. Conclusion: CMV retinitis is a rare disorder that can affect patients suffering any kind of immunodeficiency. It is associated with a high visual morbidity despite adequate treatment. CD4 + cell counts are usually higher than those in HIV patients, but B-cell dysfunction is common. [ABSTRACT FROM AUTHOR]

Background & objective: About 20% of patients with COVID-19 admitted to the intensive care unit (ICU) need ventilatory support under sedation using dexmedetomidine and ketamine. Ketamine has an anti-inflammatory effect and is expected to suppress immune cells. A high neutrophil-lymphocyte ratio (NLR) is associated with a severe stage of the disease. We compared NLR between COVID-19 patients under sedation with dexmedetomidine alone or with dexmedetomidine combined with ketamine. Methodology: This pre-experimental study involved a control group of patients receiving dexmedetomidine (n = 10) and the intervention group receiving dexmedetomidine and ketamine (n = 10) for sedation. NLR was evaluated before and after 24 h of sedation with the study drugs. Result: The patients' NLR increased significantly at 24 h after sedation using sole dexmedetomidine from 9.01 to 15.62 (P > 0.05). The combination of dexmedetomidine and ketamine significantly reduced NLR from 11.22 to 8.61 (P = 0.026). Both groups experienced a decrease in neutrophil count (P > 0.05). The lymphocyte count increased significantly in the intervention group (P = 0.025) and decreased in the control group. Conclusion: There is a significant NLR difference between a patient receiving dexmedetomidine sedation compared dexmedetomidine combined with ketamine. A combination of dexmedetomidine and ketamine reduces NLR compared to sole dexmedetomidine in critically ill COVID-19 patients. [ABSTRACT FROM AUTHOR]

Objective: To explore significance of eosinophil and eosinophil/lymphocyte ratio （ELR） in predicting allergic asthma in children in different seasons. Methods: Retrospective analysis of children with asthma who visited pediatric respiratory department outpatient clinic and ward of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2021 to December 2021, whose allergen specific IgE （sIgE） and peripheral blood cell analysis were complete. sIgE≥0.35 kUA/L were included in allergic asthma group, sIgE<0.35 kUA/L and total allergen IgE<60 kUA/L were included in non-allergic asthma group. General data and changes in peripheral blood cells of two groups were analyzed. Results: There were 1 378 qualified subjeats, including 999（ 72.5%） in allergic asthma group and 379 （27.5%） in non-allergic asthma group. Number of visits in allergic asthma group varied seasonally, with the most in autumn. Peripheral blood lymphocyte count （LYMPH）, eosinophil count （EOS） and ELR were all higher in children with allergic asthma than in children with non-allergic asthma （P<0.05）, and platelet/lymphocyte ratio （PLR） was lower than that in children with non-allergic asthma （P<0.05）. Peripheral blood LYMPH, PLT, EOS and ELR of children with allergic asthma differed between four seasons, which were higher than those of non-allergic asthma in each season in EOS and ELR, LYMPH was significantly higher than that of children with non-allergic asthma in autumn, and PLT was significantly lower than that of children with non-allergic asthma in spring （P<0.05）. EOS predicted AUC of spring, summer, autumn and winter were 0.79, 0.77, 0.71 and 0.64 in children with allergic asthma, and ELR predicted AUC were 0.72, 0.48, 0.73 and 0.68 in children with allergic asthma. Conclusion: Allergic asthma in children is seasonally variable and peaks in autumn. EOS and ELR in peripheral blood cells in children with allergic asthma are higher than in children with non-allergic asthma in each season of year, LYMPH is significantly higher than children with nonallergic asthma in the fall, and PLT is lower than in children with non-allergic asthma in spring, suggesting that allergic asthma type Ⅱ inflammation persists, and EOS and ELR have predictive value for children's allergic asthma. [ABSTRACT FROM AUTHOR]

Purpose: Accurate height and weight measurement can be challenging in older adults and complicates nutritional status assessment. Other parameters like the neutrophil-to-lymphocyte ratio (NLR) and the lymphocyte count (LC) could be an option to these measurements. We aimed to test these variables as subrogates of body mass index (BMI) or calf-circumference (CC) for malnutrition screening in community-dwelling older adults. Methods: This is a secondary analysis from the Salud, Bienestar y Envejecimiento (SABE) survey from Ecuador (2009). Includes data on demographics, health-related factors, physical assessments, and complete blood count, allowing to calculate NLR and LC to be used as part of the Mini Nutritional Assessment (MNA), instead of the BMI. Consequently, 4 models were included: standard MNA, MNA-CC, MNA-NLR and MNA-LC. Finally, age, sex, and comorbidities were considered as confounding variables. Results: In our analysis of 1,663 subjects, 50.81% were women. Positive correlations with standard MNA were found for MNA-NLR (Estimate = 0.654, p < 0.001) MNA-CC (Estimate = 0.875, p value < 0.001) and MNA-LC (Estimate = 0.679, p < 0.001). Bland-Altman plots showed the smallest bias in MNA-CC. Linear association models revealed varying associations between MNA variants and different parameters, being MNA-NLR strongly associated with all of them (e.g. Estimate = 0.014, p = 0.001 for albumin), except BMI. Conclusion: The newly proposed model classified a greater number of subjects at risk of malnutrition and fewer with normal nutrition compared to the standard MNA. Additionally, it demonstrated a strong correlation and concordance with the standard MNA. This suggests that hematological parameters may offer an accurate alternative and important insights into malnutrition. [ABSTRACT FROM AUTHOR]

Purpose: Systemic inflammatory response markers are reported to be prognostic for patients with cancer. The C-reactive protein (CRP)-albumin-lymphocyte (CALLY) index has been established as an immuno-nutritional scoring system. The aim of this study was to clarify the impact of the preoperative CALLY index on the outcome of patients undergoing gastrectomy for gastric cancer. Methods: We analyzed the data of 826 patients who underwent gastrectomy for stage I, II, or III gastric cancer between 2010 and 2017. The CALLY index was defined as (albumin × lymphocyte)/(CRP × 104). Results: The cut-off of the CALLY index was 2. The 147 patients with a preoperative CALLY index < 2 had significantly worse overall survival (OS) and relapse-free survival (RFS) than those with a CALLY index ≥ 2 (P < 0.01, P < 0.01, respectively). Multivariate analysis identified that a CALLY index < 2 (P = 0.02), intraoperative blood loss (P < 0.01), and stage II or III disease (P < 0.01) were independent and significant predictors of worse RFS. A CALLY index < 2 (P = 0.01), intraoperative blood loss (P < 0.01), postoperative complications (P = 0.02), and stage II or III disease (P < 0.01) were independent and significant predictors of worse OS. Conclusion: The preoperative CALLY index was independently associated with a poor prognosis for patients after gastrectomy for gastric cancer. [ABSTRACT FROM AUTHOR]

Background/Objectives: As COVID-19 can be severe, early predictive markers of both severity and onset of secondary bacterial infections are needed. This study first examined changes over time in the levels of plasma neopterin (NP) and biopterins (BPs), among others, in patients with COVID-19 and then in those with secondary bacterial infection complications. Methods: Fifty-two patients with COVID-19 admitted to two tertiary care centers were included. They were divided into a severe group (intubated + mechanical ventilation) (n = 10) and a moderate group (non-intubated + oxygen administration) (n = 42), and changes over time in plasma NP, plasma BPs, IFN-γ, lymphocyte count, CRP, and IL-6 were investigated. Four of the patients in the severe group (n = 10) developed secondary bacterial infections during treatment. Plasma NP and plasma BPs of patients with bacterial sepsis (no viral infection) (n = 25) were also examined. Results: The plasma NP, IL-6, CRP, and SOFA levels were significantly higher in the severe group, while the IFN-γ level and lymphocyte count were significantly lower. The higher plasma NP in the severe group persisted only up to 1 week after symptom onset. The plasma BPs were higher in complications of bacterial infection. Conclusions: The timing of sample collection is important for assessing severity through plasma NP, while plasma BPs may be a useful diagnostic tool for identifying the development of secondary bacterial infection in patients with COVID-19. Further investigation is needed to clarify the mechanism by which NP and BPs, which are involved in the same biosynthetic pathway, are differentially activated depending on the type of pathogen. [ABSTRACT FROM AUTHOR]

Gliomas are associated with high rates of disability and mortality, and currently, there is a lack of specific and sensitive biomarkers for diagnosis. The ideal biomarkers should be detected early through noninvasive methods. Our research aims to develop a rapid, convenient, noninvasive diagnostic method for gliomas, as well as for grading and differentiation. We retrospectively collected data from patients who underwent surgery for glioma, trigeminal neuralgia/hemifacial spasmschwannoma, and those diagnosed with multiple sclerosis at our institution from January 2018 to December 2020. Inflammatory markers and coagulation factor levels were collected on admission, and neutrophil count (NLR), (WBC count minus neutrophil count) / lymphocyte count, platelet count / lymphocyte count, lymphocyte count / monocyte count, and albumin count [g/L] + total lymphocyte count × 5 were calculated for patients. Analyze the significance of biomarkers in the diagnosis and grading of gliomas, the diagnosis of MS, and the differential diagnosis of them. We evaluated 155 healthy individuals, 64 trigeminal neuralgia/hemifacial spasm patients, 47 MS patients, 316 schwannoma patients, and 814 with glioma patients. Compared with healthy controls and MS group, the preoperative levels of NLR, (WBC count minus neutrophil count) / lymphocyte count, D-dimer, Fibrinogen, Antithrobin, and Factor VIII of glioma patients were significantly higher in glioma patients and positively correlated with the grade of glioma. Conversely, 0020 lymphocyte count / Monocyte count and albumin count [g/L] + total lymphocyte count × 5 were significantly lower and negatively correlated with glioma grading. ROC curves confirmed that for the diagnosis of glioma, NLR showed a maximum area under the curve value of 0.8616 (0.8322–0.8910), followed by D-dimer and Antithrombin, with area under the curve values of 0.8205 (0.7601–0.8809) and 0.8455 (0.8153–0.8758), respectively. NLR and d-dimer also showed great sensitivity in the diagnosis of MS and differential diagnosis with gliomas. Our study demonstrated that multiple inflammatory markers and coagulation factors could be utilized as biomarkers for the glioma diagnosis, grading, and differential diagnosis of MS. Furthermore, the combination of these markers exhibited high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke (AIS) is a cerebrovascular disease that seriously affects the physical and mental health and quality of life of patients. However, there is a lack of reliable prognostic prediction methods. The main objective of this study was to investigate the prognostic value of long non-coding RNA (lncRNA) H19 in lymphocytes of patients with AIS, and to construct a prognostic prediction model for AIS including lncRNA H19 in lymphocytes, which would provide new ideas for the prognostic evaluation of AIS. Poor prognosis was defined when the patient's modified Rankin scale (mRS) score at 3 months after AIS onset was greater than 2. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the level of lncRNA H19 in lymphocytes. Spearman correlation analysis revealed a positive correlation between lncRNA H19 and mRS score at 3 months after AIS onset (r = 0.1977, p = 0.0032), while lncRNA H19 was negatively correlated with white blood cells counts, lymphocytes counts, and neutrophils counts. Logistic regression analysis identified lncRNA H19 as an independent predictor of poor prognosis (OR = 3.062 [1.69–5.548], p < 0.001). Moreover, a nomogram prediction model incorporating lncRNA H19 in lymphocytes demonstrated effective discrimination, calibration, and clinical applicability in predicting AIS outcomes. The findings suggest that lncRNA H19 in lymphocytes could be a valuable prognostic indicator and a potential pharmacological target for AIS patients, and might be a novel pathway for enhanced prognostic evaluation and targeted therapeutic strategies. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to stratify preoperative immune cell counts by cancer specific outcomes in patients with renal cell carcinoma (RCC) and a tumor thrombus after radical nephrectomy with tumor thrombectomy. Methods: Patients with a diagnosis of RCC with tumor thrombus that underwent radical nephrectomy with thrombectomy across an international consortium of seven institutions were included. Patients who were metastatic at diagnosis and those who received preoperative medical treatment were also included. Retrospective chart review was performed to collect demographic information, past medical history, preoperative lab work, surgical pathology, and follow up data. Neutrophil counts, lymphocyte counts, monocyte counts, neutrophil to lymphocyte ratios (NLR), lymphocyte to monocyte ratios (LMR), and neutrophil to monocyte ratios (NMR) were compared against cancer-specific outcomes using independent samples t -test, Pearson's bivariate correlation, and analysis of variance. Results: One hundred forty-four patients were included in the study, including nine patients who were metastatic at the time of surgery. Absolute lymphocyte count preoperatively was greater in patients who died from RCC compared to those who did not (2 vs 1.4; p < 0.001). Patients with tumor pathology showing perirenal fat invasion had a greater neutrophil count compared to those who did not (7.5 vs 5.5; p = 0.010). Patients with metastatic RCC had a lower LMR compared to those without metastases after surgery (2.5 vs 3.2; p = 0.041). Tumor size, both preoperatively and on gross specimen, had an interaction with multiple immune cell metrics (p < 0.05). Conclusions: Preoperative immune metrics have clinical utility in predicting cancer-specific outcomes for patients with RCC and a tumor thrombus. Additional study is needed to determine the added value of preoperative serum immune cell data to established prognostic risk calculators for this patient population. [ABSTRACT FROM AUTHOR]

Background: Differences in radiation-induced lymphopenia and prognosis between methods of radiotherapy (RT) for brain metastases remain unclear. Methods: In this retrospective analysis of patients who underwent whole-brain radiotherapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS/SRT) for brain metastases, baseline total lymphocyte count (TLC) data were obtained within 2 weeks before RT initiation. Follow-up TLC data were evaluated at 0–2, 2–4, and 4–8 weeks after RT completion. Persistent lymphopenia was defined as <800/μL at any time point. Results: Overall, 138 RT courses in 128 patients were eligible (94 WBRT; 44 SRS/SRT). In the WBRT courses, the median baseline TLC was 1325/μL (IQR: 923–1799). Follow-up TLC decreased significantly to 946/μL (626–1316), 992/μL (675–1291), and 1075/μL (762–1435) (p < 0.001). SRS/SRT courses showed no significant TLC decrease. Multivariate analysis revealed female sex, prior RT, baseline TLC < 800/μL, and WBRT use were significantly associated with persistent lymphopenia. In the WBRT group, overall survival was significantly different between those with and without persistent lymphopenia (median, 2.6 and 6.1 months; p < 0.001). However, there was no significant difference in survival in the SRS/SRT group (p = 0.60). Conclusion: This study suggests SRS/SRT might be preferable for lymphocyte preservation in brain metastasis patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Nutritional status is closely related to the outcomes of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). However, the prognostic value of the Controlling Nutritional Status (CONUT) score in CRS-HIPEC has not yet been investigated. This study evaluated the predictive power of the CONUT score for mortality and postoperative complications after CRS-HIPEC. We found that patients with high CONUT score exhibited significantly higher 1-year mortality and postoperative complication rates than those with low CONUT score. Notably, a high CONUT score was identified as an independent risk factor for 1-year mortality and postoperative complications. These results suggest the potential of the CONUT score as a robust risk stratification tool for identifying high-risk patients within the CRS-HIPEC surgical demographic. The Controlling Nutritional Status (CONUT) score is a novel nutritional index that integrates the serum albumin level, peripheral blood lymphocyte count, and total cholesterol level. This retrospective study explores its prognostic significance in patients undergoing cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). We included 436 patients who underwent CRS-HIPEC, categorized into low (0–3) and high (4–12) CONUT score groups, and performed logistic regression analysis to predict one-year mortality and postoperative morbidity. Our findings revealed that high CONUT scores correlate with increased one-year mortality (47.1% vs. 20.3%, p < 0.001) and morbidity (39.2% vs. 18.2%, p < 0.001) compared to low CONUT scores. Multivariable regression analysis confirmed high CONUT scores as independent predictors of one-year mortality (odds ratio: 2.253, 95% CI: 1.014–5.005, p = 0.046) and postoperative morbidity (odds ratio: 2.201, 95% CI: 1.066–4.547, p = 0.033). These results underscore the CONUT score's effectiveness as an independent marker for evaluating risks associated with CRS-HIPEC, emphasizing its potential to improve risk stratification. [ABSTRACT FROM AUTHOR]

Background: Patients treated with immune checkpoint inhibitors (ICIs) are at risk of considerable adverse events, and the ongoing struggle is to accurately identify the subset of patients who will benefit. Lymphocyte subsets play a pivotal role in the antitumor response, this study attempted to combine the absolute counts of lymphocyte subsets (ACLS) with the clinicopathological parameters to construct nomograms to accurately predict the prognosis of advanced non-small cell lung cancer (aNSCLC) patients treated with anti-PD-1 inhibitors. Methods: This retrospective study included a training cohort (n = 200) and validation cohort (n = 100) with aNSCLC patients treated with anti-PD-1 inhibitors. Logistic and Cox regression were conducted to identify factors associated with efficacy and progression-free survival (PFS) respectively. Nomograms were built based on independent influencing factors, and assessed by the concordance index (C-index), calibration curve and receiver operating characteristic (ROC) curve. Result: In training cohort, lower baseline absolute counts of CD3+ (P < 0.001) and CD4+ (P < 0.001) were associated with for poorer efficacy. Hepatic metastases (P = 0.019) and lower baseline absolute counts of CD3+ (P < 0.001), CD4+ (P < 0.001), CD8+ (P < 0.001), and B cells (P = 0.042) were associated with shorter PFS. Two nomograms to predict efficacy at 6-week after treatment and PFS at 4-, 8- and 12-months were constructed, and validated in validation cohort. The area under the ROC curve (AUC-ROC) of nomogram to predict response was 0.908 in training cohort and 0.984 in validation cohort. The C-index of nomogram to predict PFS was 0.825 in training cohort and 0.832 in validation cohort. AUC-ROC illustrated the nomograms had excellent discriminative ability. Calibration curves showed a superior consistence between the nomogram predicted probability and actual observation. Conclusion: We constructed two nomogram based on ACLS to help clinicians screen of patients with possible benefit and make individualized treatment decisions by accurately predicting efficacy and PFS for advanced NSCLC patient treated with anti-PD-1 inhibitors. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of a feed additive (FA) containing a probiotic consortium, fructooligosaccharide and yeast extract on growth performance, humoral immune responses, hepatic antioxidant parameters and intestine digestive enzymes, morphology and transcripts in rainbow trout, Oncorhynchus mykiss. The fish were reared for 8 weeks, feeding on diets containing 0 (CNT), 0.3 (0.3FA), 1 (1FA) and 2 (2FA) g/kg FA. The results showed that fish growth parameters were significantly and quadratically related to FA levels and FA treatments had better growth performance than CNT treatment. Intestinal amylase activity significantly increased in 2FA, whereas, intestinal protease activity increased in all FA treatments. Intestinal villus length and muscular layer thickness significantly increased in 0.3FA treatment. Blood leucocyte and lymphocyte counts, plasma lysozyme activity and hepatic glutathione content significantly increased in 0.3FA and 1FA treatments; whereas hepatic malondialdehyde significantly decreased in these treatments. Blood neutrophil and monocyte counts significantly increased in 0.3FA treatment, while plasma alternative complement activity significantly increased in 1FA treatments. Plasma bactericidal activities against Aeromonas hydrophila, Yersinia ruckeri and Streptococcus iniae, and intestinal expression of heat shock protein 70 and beta‐defensin significantly increased in all FA treatments. The abundance of A. hydrophila, Y. ruckeri and S. iniae in fish gut significantly decreased in 0.3FA treatment; these bacteria were absent in the intestines of 1FA and 2FA treatments. The present results suggest that dietary 0.3–1 g/kg of FA can significantly improve growth performance, immune response, intestinal health and hepatic antioxidant capacity in rainbow trout. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Abnormalities in the peripheral immune system in ALS have been paid attention; however, the results of changes in peripheral immune parameters were inconsistent. A total of 1109 ALS patients were enrolled in the study. All patients received clinical evaluation and peripheral immune parameters measurement. The outcomes were analyzed by correlation analysis, multiple linear regression and cox survival analysis. We found that ALS patients had significantly higher percentage of CD4+ T cells (39.3 vs. 37.1%, p < 0.001) and CD4+/CD8+ ratio (1.88 vs. 1.72, p = 0.011), significantly lower IgG (11.73 vs.12.82, p < 0.001) and IgA (2130.70 vs. 2284.8, p = 0.013) compared with the health controls. In the multivariate linear model, we found that each increase of 1.262, 0.278, and 4.44E-4 in ALSFRS-R scores were significantly associated with each increment of lymphocyte count, IgG, and IgA, respectively. However, each decrease of 0.341, 0.068, and 0.682 in ALSFRS-R score was associated with each increment in neutrophils, CD4+ T cells, and CD4+/CD8+ ratio, respectively. Cox survival regression analysis showed that the death risk of ALS patients was related to the levels of C3 (HR 0.592, 95% CI 0.361–0.973). We found that there were differences in peripheral immune parameters of ALS patients with the severity of the disease, especially neutrophil, lymphocyte, CD4+ T, and IgG; C3 is an independent predictor of survival in ALS patients. More studies are needed to elucidate the mechanisms associated with altered immune parameters in ALS. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid diseases (AITDs), mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune disorders characterized by abnormal immune responses targeting the thyroid gland. We conducted a bidirectional two-sample MR analysis using the largest dataset of peripheral immune cell phenotypes from Sardinia, and the AITD dataset from the 10th round of the FinnGen and the UK Biobank project. Instrumental variables (IVs) were rigorously selected based on the three assumptions of MR and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were performed using Cochrane's Q, the Egger intercept, the MR-PRESSO, and the leave-one-out (LOO) method to ensure the robustness of the results. The Steiger test was utilized to identify and exclude potential reverse causation. The results showed that 3, 3, and 11 immune cell phenotypes were significantly associated with the risk of AITD. In GD, the proportion of naive CD4-CD8- (DN) T cells in T cells and the proportion of terminally differentiated CD4+T cells in T cells showed the strongest inducing and protective effects, respectively. In HT, lymphocyte count and CD45 on CD4+T cells showed the strongest inducing and protective effects, respectively. In autoimmune hypothyroidism, CD127 CD8+T cell count and terminally differentiated DN T cell count exhibited the strongest inducing and protective effects, respectively. Through MR analysis, our study provides direct genetic evidence of the impact of immune cell traits on AITD risk and lays the groundwork for potential therapeutic and diagnostic target discovery. [ABSTRACT FROM AUTHOR]

Introduction: Endovascular aortic repair (EVAR) is commonly used for abdominal aortic aneurysms, but its mortality rate remains high. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score, which measures hemoglobin, albumin, lymphocyte, and platelet levels, provides prognostic value by reflecting the nutritional status and systemic inflammation. This study aimed to explore the relationship between the HALP score upon admission and long-term mortality in patients with EVAR. Methods: Consecutive patients with EVAR at our tertiary center from October 2010 to August 2021 were retrospectively analyzed. HALP scores were calculated using the following formula: hemoglobin (g/L) x albumin (g/L) x lymphocyte count (/L)/platelet count (/L). In-hospital and long-term mortality data were extracted. Receiver operating characteristic curve analysis identified predictors of in-hospital mortality. Multivariate Cox regression analysis was performed to examine determinants of long-term mortality. Results: Among the 162 participants (mean age: 69.4±8.2 years, 90.1% male), the HALP score was the most significant predictor of in-hospital mortality (area under the curve: 0.752, 95% confidence interval: 0.674-0.830; p<0.001). Multivariate Cox regression analysis revealed HALP (p=0.001) and C-reactive protein (p=0.004) as independent determinants of long-term mortality. Conclusion: This study is the first to investigate the association between the HALP score and in-hospital and long-term mortality in EVAR patients. The HALP score is a robust prognostic tool compared with its components and other parameters in this patient population. [ABSTRACT FROM AUTHOR]

In the event of a nuclear or radiation accident, rapid identification is required for those who exposed to potentially lethal dose irradiation. However, existing techniques are not adequate for the classification of lethal injury. Several studies have explored the potential of miRNAs as biomarkers for ionizing radiation injury, however, there are few miRNAs with specific expression for lethal radiation injury. Therefore, the aim of this study was to screen and validate the possibility of serum miRNAs as biomarkers of lethal radiation injury. We found the specific expression of mmu-miR-374c–5p / mmu-miR-194–5p on first day and mmu-miR-192–5p / mmu-miR-223–3p on third day in the mouse serum only under 10 Gy irradiation by miRNA sequencing and all significantly correlated with lymphocyte counts by Pearson's correlation analysis. In addition, it was found that among the 4 candidate serum miRNAs, only highly-expressed mmu-miR-192–5p in mouse serum irradiated at lethal doses was returned to sham-like expression levels at 3 days post-irradiation with amifostine pretreatment and closely correlated with survival rate. We demonstrated for the first time that mmu-miR-192–5p screened from lethally irradiated mice sera can be used as a potential biomarker for lethal irradiation injury, which will be helpful to improve efficiency of medical treatment to minimize casualties after a large-scale nuclear accident. • mmu-miR-374c-5p, mmu-miR-194–5p, mmu-miR-192–5p and mmu-miR-223–3p was specially expressed only under lethal irradiation. • mmu-miR-192–5p was significantly increased on third day only after lethal irradiation. • mmu-miR-192–5p expression was negatively correlated with lymphocyte counts. • mmu-miR-192–5p expression could return to sham-like level on third day post-irradiation with amifostine pretreatment. • mmu-miR-192–5p expression was related to the ability to survive (or the degree of damage suffered). [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the correlation between changes in bone mineral density (BMD) in postmenopausal women and circulating inflammatory markers. Methods: This retrospective study focused on postmenopausal women admitted to the orthopedic department of Suzhou Benq Medical Center from June 2022 to December 2023, following predetermined inclusion and exclusion criteria. We retrospectively collected data on initial blood routine test results and bone density measurements for all study subjects upon admission, including parameters such as white blood cell count (WBC), C‐reactive protein, interleukin‐6 (IL‐6), and procalcitonin (PCT). Additionally, the systemic immune‐inflammation index (SII) was calculated using neutrophil count, lymphocyte count, and platelet count. Statistical analyses using SPSS and GraphPad software were performed to assess the correlation between bone density and inflammatory markers. Results: Patients were classified into three groups based on BMD results, including 60 individuals in the osteoporosis (OP) group, 127 individuals in the osteopenia group, and 37 individuals in the Normal group, respectively. Principal component analysis analysis suggested that WBC, SII, and postmenopausal OP (PMOP) held significant feature values. Correlation analysis indicated a correlation between WBC (p = 0.021), IL‐6 (p = 0.044), SII (p = 0.034), and PMOP. One‐way ANOVA analysis revealed significant differences in IL‐6 (p = 0.0179), SII (p = 0.0210), and PCT (p = 0.0200) among the three groups. Finally, ROC curve analysis demonstrated that SII (area under the curve = 0.716) has predictive value for PMOP. Conclusion: This study identified a certain predictive value for PMOP through the assessment of inflammatory markers in peripheral blood using routine blood tests. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive impairment (CI) is common in both end‐stage kidney disease (ESKD) and alcohol‐related liver cirrhosis. The aim of this study was to assess the prevalence and patterns of CI in patients awaiting kidney and liver transplantation, and to identify its determinants. Methods: In this cross‐sectional, prospective study, 31 consecutive patients with ESKD and 31 consecutive patients with alcohol‐related liver cirrhosis, all currently on transplant waiting lists, were screened for cognitive decline using the Addenbrooke's Cognitive Examination. Medical history, demographics, and laboratory test results were also collected. Results: The prevalence of CI among patients with ESKD and alcohol‐related liver cirrhosis was 26% and 90%, respectively. In both groups, memory was the most affected cognitive domain, along with verbal fluency in patients with ESKD, and visuospatial abilities in patients with alcoholic cirrhosis. The most statistically significant increase in the prevalence of CI was found in patients with lower educational attainment, in both alcohol‐related liver cirrhosis and ESKD populations as well as in older patients with alcoholic cirrhosis. Furthermore, better cognitive functioning in ESKD patients was associated with higher levels of total lymphocyte count and alanine transaminase (ALT), and in alcohol‐related liver cirrhosis patients with higher levels of ALT and aspartate transaminase. A nonsignificant trend toward lower memory domain scores was also observed with increasing ammonia levels and increasing severity of liver disease (higher Child–Pugh scores). Finally, suboptimal performance on the screening test was correlated with the severity of liver disease as assessed by the Model for End‐Stage Liver Disease Sodium (MELD‐Na), but not at the statistically significant level. Conclusions: The prevalence of CI, especially in patients with alcohol‐related liver cirrhosis, is high and can be a significant clinical problem, negatively affecting the transplantation process. Routine screening tests in this group would contribute to the implementation of appropriate management, such as rehabilitation program or psychosocial treatments and facilitate the provision of specialized health care. [ABSTRACT FROM AUTHOR]

Introduction: In EVOLVE-MS-1 (NCT02634307), mean absolute lymphocyte count (ALC) on diroximel fumarate (DRF) declined from baseline by approximately 28% in year 1, then stabilized, similar to ALC decline observed with dimethyl fumarate (DMF). Prior studies reported that clinical efficacy of DMF was not substantially different in patients with and without lymphopenia. Methods: EVOLVE-MS-1—an open-label, 96-week, phase 3 study—assessed DRF safety and exploratory efficacy in patients with relapsing–remitting multiple sclerosis. This study analyzes efficacy-related outcomes comparing (1) patients with lymphopenia (≥ 1 ALC below lower limit of normal [LLN]) and without (all ALCs ≥ LLN); (2) across quartiles stratified by week 96 ALC decline from baseline: Q1 (≥ 47% decline); Q2 (30% to < 47% decline); Q3 (12% to < 30% decline); Q4 (< 12% decline). Results: Baseline characteristics were similar between patients without (n = 593) and with lymphopenia (n = 452). At week 96, adjusted annualized relapse rate (ARR; 95% confidence interval) was 0.14 (0.11–0.17) without lymphopenia and 0.12 (0.09–0.15) with lymphopenia. Estimated proportions with 12-week confirmed disability progression (CDP12) at week 96 were 10.2% without and 9.3% with lymphopenia. When stratified by quartiles (Q1–Q4), ARR at week 96 was 0.11 (Q1), 0.09 (Q2), 0.13 (Q3), and 0.17 (Q4). Estimated proportions with CDP12 at week 96 were 9.6% (Q1), 10.2% (Q2), 5.7% (Q3), and 10.9% (Q4). At week 96, no evidence of disease activity was achieved by 47.2% (Q1), 47.8% (Q2), 45.4% (Q3), and 37.3% (Q4) of patients. Conclusion: In DRF-treated patients in EVOLVE-MS-1, clinical and radiological measurements indicated reduced disease activity regardless of lymphopenia or magnitude of ALC decline from baseline; however, patients who had greater ALC declines appeared to have numerically lower ARR and higher proportions free from relapses and gadolinium-enhancing lesions compared with those with smallest decline. This supports prior evidence that, while lymphopenia may contribute to fumarate efficacy outcomes, it is not the primary mechanism of action. Trial Registration: ClinicalTrials.gov identifier NCT02634307. [ABSTRACT FROM AUTHOR]

Aims: To investigate the relationship between peripheral blood lymphocyte subsets and prognosis in patients with acute ischemic stroke (AIS). Methods: We enrolled 294 patients with AIS and collected peripheral blood samples for analysis of lymphocyte subsets. Prognosis was assessed at 3 months using the modified Rankin Scale (mRS). Association between lymphocyte count and poor outcomes (mRS score >2) was assessed using logistic regression. Individualized prediction models were developed to predict poor outcomes. Results: Patients in the mRS score ≤2 group had higher T‐cell percentage (odds ratio [OR] = 0.947; 95% confidence interval [CI]: 0.899–0.998; p = 0.040), CD3+ T‐cell count (OR = 0.999; 95% CI: 0.998–1.000; p = 0.018), and CD4+ T‐cell count (OR = 0.998; 95% CI: 0.997–1.000; p = 0.030) than those in the mRS score >2 group 1–3 days after stroke. The prediction model for poor prognosis based on the CD4+ T‐cell count showed good discrimination (area under the curve of 0.844), calibration (p > 0.05), and clinical utility. Conclusion: Lower T cell percentage, CD3+, and CD4+ T‐cell counts 1–3 days after stroke were independently associated with increased risk of poor prognosis. Individualized predictive model of poor prognosis based on CD4+ T‐cell count have good accuracy and may predict disease prognosis. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to assess the impact of physical activity on both therapeutic efficacy and immune-related adverse events (irAEs) during immunotherapy for non-small cell lung cancer (NSCLC). Methods: Physical activity was divided into three groups: light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) for laboratory indexes, efficacy, and irAEs. A multivariate logistic regression was employed to analyze the relationship between sedentary behavior with efficacy and irAEs. Results: The study included 121 patients. The three levels of physical activity were not significantly associated with efficacy or irAEs. However, noteworthy disparities were observed in base-hemoglobin levels (F = 3.4, P = 0.037) and base-lymphocyte levels (χ2 = 6.13, P = 0.047) among the three groups. After treatment, we identified statistically significant variations in albumin levels (P = 0.012) and lymphocyte counts (P = 0.035). Furthermore, a negative correlation emerged between pre-treatment sedentary behavior duration and immune-efficacy (β: −0.005, P = 0.027). Conclusions: In summary, within the cohort of NSCLC patients undergoing single immunotherapy or a combination of immunotherapy and chemotherapy, physical activity is closely related to immune and inflammatory indicators in patients, and prolonged sitting will reduce the therapeutic effect. [ABSTRACT FROM AUTHOR]

Background: Patients with head and neck squamous cell carcinoma (HNSCC) frequently develop synchronous esophageal cancer (ESCC), but there is a lack of clinical predictors. The neutrophil to lymphocyte (NLR), platelet to lymphocyte (PLR), and lymphocyte to monocyte ratios (LMRs), reflect the balance between pro‐cancer inflammation and anti‐cancer immune responses, but their role in HNSCC and synchronous cancer remain uncertain. Method: The study consecutively enrolled a total of 717 patients with newly diagnosed HNSCC who received pre‐treatment esophageal endoscopic screening. The pretreatment NLR, LMR and PLRs were calculated and analyzed in comparison with the clinical factors. Results: A total of 103 patients (14.4%) were found to have synchronous ESCCs, and were associated with a significantly lower absolute lymphocyte count (p < 0.001), higher NLRs (p = 0.044) and lower LMRs (p = 0.001), but not PLRs (p = 0.49). The ROC curve for the presence of synchronous ESCC verified the optimal cutoff value as 2.5 for NLRs and 4.0 for LMRs. Multivariable logistic regression revealed that a LMR <4 (OR 2.22; 95% CI 1.27–3.88, p = 0.005), alcohol consumption (OR 4.19; 95% CI 1.47–11.91, p = 0.007), tumor location over the pharynx (OR 1.68; 95% CI 1.07–2.64, p = 0.025), and low body mass index (OR 0.94; 95% CI 0.88–0.99, p = 0.039) were risk factors for developing synchronous ESCC. A low‐LMR was significantly associated with decreases in overall survival (p < 0.0001), in both synchronous and non‐synchronous groups. Multivariate analysis demonstrated that LMR <4 (HR 1.97; 95% CI 1.38–2.81, p < 0.001), a low‐BMI (HR 0.96; 95% CI 0.93–0.99, p = 0.044) and presence of synchronous ESCC (HR 1.56; 95% CI 1.10–2.22, p = 0.013) were independent prognostic factors for HNSCC patients. Conclusion: Incorporation of LMR into other identified risk factors, such as alcohol consumption, tumor location over pharynx, and low‐BMI, may establish a more efficient screening program for esophageal exploration in HNSCC patients. The significances of LMR also suggest that anti‐cancer immunity may play a role in the filed cancerization to initiate multiple cancers, and the immunotherapy may have potentials for prevention or as an adjuvant treatment for synchronous SCC in the future. [ABSTRACT FROM AUTHOR]

Objective Design Setting Animals Interventions Measurements and Main Results Conclusion To investigate the utility of the neutrophil‐to‐lymphocyte ratio (NLR) as a prognostic marker in cats with blunt trauma.Retrospective study from January 2018 to December 2021.University teaching hospital.Medical records of 177 cats admitted with blunt trauma were evaluated. History, clinical findings, blood cell count‐based ratios, thoracic radiographs on presentation, and outcome were reviewed. The Animal Trauma Triage (ATT) score was assessed in each cat and classified as mild (1–3), moderate (4–7), and severe trauma (≥8). Forty‐eight healthy blood donor cats served as the control population. NLR, neutrophil counts, and lymphocyte counts were compared between cats with blunt trauma and controls, and among trauma patients.NoneNLR, neutrophil counts, and lymphocyte counts significantly differ in cats with blunt trauma compared to controls (p < 0.001), and NLR was higher in patients with thoracic trauma (p = 0.044). Nonsurvivors had lower lymphocyte counts (p = 0.041), although those values do not appear to be clinically relevant. A significant increase in NLR was observed with increasing severity of trauma (p < 0.001). The NLR was not associated with the length of hospitalization, intensive care assistance, or mortality.NLR is a widely available diagnostic tool, which can be used in addition to ATT to assess trauma severity, although in our study it was not predictive of the outcome. [ABSTRACT FROM AUTHOR]