Percentage Of Neutrophils Research Articles

113 Maternal Stress Influences Dam and Progeny Cortisol, Immune, and Behavior

Abstract Maternal stress exposes fetuses to increased cortisol concentrations, resulting in lifelong and multi-generational effects on physiology and behavior, especially if stress occurs during sensitive periods of development. This study aimed to validate the prenatal stress model and characterize the immune phenotype of the dam and the stress responsiveness and behavioral phenotype of her progeny. Gilts were randomly assigned to receive either hydrocortisone acetate (HCA) at mid (MID) or late (LATE) gestation for 21 days or placebo (CON). Blood or saliva samples were taken from gilts during the 21 day- treatment period. Blood samples were taken, and behavior was registered in response to weaning from the progeny. Body weights were also recorded. Data were analyzed using PROC MIXED with repeated measures (SAS 9.4). Significant treatment*day interactions occurred for salivary and plasma cortisol. The MID had the greatest salivary cortisol at 3- and 21-days post-HCA treatment and the least plasma cortisol at 7- and 21-days post-HCA compared with LATE and CON. Also, at 21 days post-HCA, there was a significant treatment effect where LATE gilts had decreased percentage of neutrophils (P = 0.012), increased percentage of lymphocytes (P = 0.012), and decreased neutrophil to lymphocyte ratio (P = 0.0007) compared with their respective controls. Plasma IgG patterns were differentially affected by HCA treatment. At 7 days post-HCA, IgG decreased among MID gilts but increased at d 21, whereas IgG increased at d 7 and then decreased at d 21 among LATE treated gilts. Colostrum IgA was greater in the CON gilts than in MID or LATE-treated gilts (P = 0.032). Among the pigs born to these gilts, plasma cortisol was similar before weaning, but 24-h post-weaning pigs from CON had greater cortisol than those from MID or LATE (P < 0.05), and leukocyte distribution in response to weaning was also affected by maternal treatment (P < 0.01). Finally, behavioral responses, including social interactions, were affected by maternal treatment (P < 0.001). Taken together, these findings imply that HCA treatment differentially affects the immune function and HPA responsiveness of the dam dependent on when stress is experienced within gestation.

Risk factors for short-term mortality in elderly hip fracture patients with complicated heart failure in the ICU: A MIMIC-IV database analysis using nomogram

BackgroundHip fracture is a prevalent and hazardous injury among the elderly population that often results in intensive care unit (ICU) admission due to various complications, despite advanced medical science. One common complication experienced in the ICU by elderly hip fracture patients is heart failure, which significantly impacts short-term survival rates. Currently, there is a deficit of adequate predictive models to forecast the short-term risk of death following heart failure for elderly hip fracture patients in the ICU. This study aims to identify independent risk factors for all-cause mortality within 30 days for elderly patients with hip fractures and heart failure while in the ICU in order to develop a predictive model.MethodA total of 641 elderly patients with hip fractures combined with heart failure were recruited from the Medical Information Mart for Intensive Care IV dataset and randomized to the training and validation sets. The primary outcome was all-cause mortality within 30 days. The least absolute shrinkage and selection operator regression was used to reduce data dimensionality and select features. Multivariate logistic regression was used to build predictive models. Consistency index (C-index), receiver operating characteristic curve, and decision curve analysis (DCA) were used to measure the predictive performance of the nomogram.ResultOur results showed that these variables including MCH, MCV, INR, monocyte percentage, neutrophils percentage, creatinine, and combined sepsis were independent factors for death within 30 days in elderly patients with hip fracture combined with heart failure in the ICU. The C-index was 0.869 (95% CI 0.823–0.916) and 0.824 (95% CI 0.749–0.900) for the training and validation sets, respectively. The results of the area under the curve and decision curve analysis (DCA) confirmed that the nomogram performed well in predicting elderly patients with hip fractures combined with heart failure in the ICU.ConclusionWe developed a new nomogram model for predicting 30-day all-cause mortality in elderly patients with hip fractures combined with heart failure in the ICU, which could be a valid and useful clinical tool for clinicians for targeted treatment and prognosis prediction.

A Universal CRISPR/Cas9n-Mediated Genome Editing Approach for ELANE-Related Severe Congenital Neutropenia

Severe congenital neutropenia (CN) is an inherited bone marrow failure syndrome characterized by impaired maturation of neutrophil granulocytes. Due to the lack or very low levels of neutrophils in the peripheral blood, patients experience severe, life-threatening bacterial infections as early as birth. Autosomal-dominant ELANE mutations are the most common cause of CN. Although most patients respond to daily treatment with recombinant human granulocyte colony-stimulating factor, about 15% of patients do not respond to this cytokine, and approximately 20% of patients develop myelodysplasia or acute myeloid leukemia. The only curative treatment available thus far is allogenic hematopoietic stem cell transplantation, which is associated with serious side effects. Autologous transplantation of gene-edited patients' HSPCs offers a novel curative therapy. Considering the wide range of mutations distributed throughout the ELANE gene, A universal, high-safety-profile approach could be advantageous for all ELANE-CN patients. Our group has already published a universal CRISPR/Cas9-mediated knockout approach for the ELANE gene; however, targeting the coding sequence region (CDS) of the ELANE gene could lead to the introduction of new disease-causing variants, so it may be harmful for patients. In order to address this concern, we reformatted our previously published knockout concept into a clinical-grade gene therapy strategy. We have screened cis-regulatory regions in the ELANE core promoter and, using CRISPR/Cas9n, introduced two nicks on opposing strands of the Goldberg-Hognes box region (TATA-box) to make the transcription starting process inefficient, as transcription factors and RNApol II cannot recognize the modified sequence. Theproposed strategy targets the non-coding region of the ELANE gene and thus does not generate new unwanted variants. Also, by replacing Cas9 with Cas9-ncikase, the off-target activity should decrease by up to 1000-fold. We have observed a markedly elevated neutrophil differentiation in gene-edited ELANE-CN patients HSPCs (n = 2), as assessed by the percentage of CD45 +CD11b +CD15 +, CD45 +CD15 +CD16 +, and CD45 +CD16 +CD66b + myeloid/granulocytic cells, compared to the mock electroporated ELANE-CN group, while no disruption of granulopoiesis in healthy donor HSPCs (n = 2) was detected. Results validated by the CFU assay. To have nucleotide-level resolution of on-target events, we performed targeted next-generation sequencing of edited loci on gene-edited healthy donors and ELANE-CN HSPCs. Next-generation sequencing results showed >90% on-target efficiency. CRISPR/Cas9n-mediated targeting of the TATA box rescued defective granulopoiesis in vivo, as gene-edited ELANE-CN HSPCs (n = 3) were transplanted in NSG mice and assessed by the percentage of neutrophils (hCD19 -hCD3 -hCD66b Int/lowhCD33 +hCD16 high) after 16 weeks. We have also observed efficient engraftment and preserved the multilineage potential of gene edited HSPCs in immunodeficient NSG mice. The strategy also depicted a safe profile upon applying gene editing to healthy donor CD34 + HSPCs and performing GUIDE-seq and CAST-seq. GUIDE-seq highlighted two potential off-target sites after >=6 mismatches, while no chromosomal translocations were detected by CAST-seq. RNA-sequencing of in vitro-generated neutrophils from gene-edited HSPCs of healthy donors (n = 2) confirmed a >9-fold reduction of ELANE gene expression level. Important to note, none of the other serine proteases or neighboring genes were down-regulated. Taken together, ex vivo CRISPR-Cas9n-based gene editing of ELANE's gene promoter in the setting of autologous stem cell transplantation could be a safe therapeutic approach for all ELANE-CN patients.

Development and validation of a predictive model for early diagnosis of neonatal acute respiratory distress syndrome based on the Montreux definition.

Based on the Montreux definition, we aim to develop and validate a predictive model for the early diagnosis of neonatal acute respiratory distress syndrome (ARDS). A retrospective analysis of clinical data on 198 neonates with respiratory distress from January 2018 to January 2022 was conducted. Neonates meeting Montreux definition were classified as ARDS group (n = 79), while the rest were non-ARDS group (n = 119). Univariate analysis identified indicators for neonatal ARDS, followed by logistic regression to construct a predictive model for early diagnosis. The ability of predictors and models to predict neonatal ARDS was evaluated using area under the curve (AUC), and model performance was estimated through bootstrap resampling. Maternal prenatal fever, abnormal fetal heart beat, meconium-stained amniotic fluid (MSAF), white blood cell (WBC), absolute neutrophil count (ANC), neutrophil percentage (NE%), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), creatine kinase (CK), activated partial thromboplastin time (APTT), serum calcium (Ca) and sodium (Na)exhibited significant differences between the ARDS group and the non-ARDS group (P < 0.05). MSAF (OR=5.037; 95% CI: 1.523-16.657; P < 0.05), ANC (OR = 1.324; 95% CI: 1.172-1.495; P < 0.05), PLT (OR = 0.979; 95% CI: 0.971-0.986; P < 0.05), Ca (OR = 0.020; 95% CI: 0.004-0.088; P < 0.05) emerged as independent risk factors for the development of ARDS. The respective AUC values for MSAF, ANC, PLT, Ca, and the combined prediction models were 0.606, 0.691, 0.808, 0.761 and 0.931. Internal validation showed that the C-index for the model was 0.931. Early application of the model combining MSAF, ANC, PLT and Ca may have a good predictive effect on the early diagnosis of neonatal ARDS.

Ahemolytic PNH: Clinical Features of a Distinct Phenotype of Paroxysmal Nocturnal Hemoglobinuria

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem/progenitor cell disorder caused by PIGA mutations. All hematopoietic lineages derived from the affected clone exhibit the PNH phenotype [deficiency of glycosyl phosphatidylinositol linked membrane proteins (GPI-APs)]. Diagnosis is made by flow cytometric analysis of red blood cells (RBC), granulocytes, and monocytes. The percentage of granulocytes and monocytes with absent expression of GPI-APs is a measure of the size of the PNH clone. Typically, the percentage of GPI-AP deficient RBCs is somewhat less than that of granulocytes and monocytes due to selective destruction by complement-mediated intravascular hemolysis, manifested by high LDH, bilirubin, reticulocyte count and low haptoglobin. Herein, we report five patients with large PNH clones based on percentage of GPI-AP deficient neutrophils and monocytes, but with absent or near absent PNH RBCs and no biochemical evidence of hemolysis. We call this unique disease subtype, ahemolytic PNH. Methods: The medical records of PNH patients (174 patients with PNH granulocytes &amp;gt;20%) at the University of Texas Southwestern, Cleveland Clinic Foundation, and National Institutes of Health from 2000 to 2022 were examined. Information pertaining to their clinical, laboratory, and molecular attributes (NGS sequencing) was collected. Five patients with granulocyte clones &amp;gt;50% and RBC clones &amp;lt;5% were identified (Table). Results: Patient 1 is a 63-year-old male with a remote history of non-severe aplastic anemia (AA) diagnosed at 11 years old. The first PNH flow cytometry, obtained at age 61 years, showed 0.02% type II PNH RBC, 0.5% type III PNH RBC, 96% PNH monocyte and 97% PNH granulocytes (Table). There was no biochemical evidence of hemolysis at the time of diagnosis or in the preceding 5 years. Patient 2 is a 50-year-old male who presented with pancytopenia and was diagnosed with acute myeloid leukemia with myelodysplastic-related mutations. Flow cytometry showed 85% PNH monocytes and 59% PNH with no detectable PNH RBCs and no biochemical evidence of hemolysis at diagnosis or in 3 years of follow-up (Table). Patient 3 is a 73-year-old female who presented with pancytopenia and marrow aplasia with unremarkable morphology, and a PNH granulocyte clone of 93.6% with 1.3% type III PNH RBCs and 1.3% and 0.5% type II PNH RBCs, with no evidence of hemolysis (Table). Patient 4 is a 21-year-old female who presented with Budd-Chiari syndrome. Flow cytometry showed 73% PNH granulocytes with 3.6% type III PNH RBCs and 1.8% type II PNH RBCs. There was no biochemical evidence of hemolysis, but because of thrombosis, she was treated complement inhibitor therapy (Table). Patient 5 is a 61-year-old female with history of severe aplastic anemia treated with immunosuppression (IST) and eltrombopag. PNH flow cytometry showed PNH granulocytes of 92.4% and 2.1% PNH type II RBCs 2.1% post IST treatment with no biochemical evidence of hemolysis (Table). Conclusion: Herein, we present five patients with a distinct PNH phenotype that we call ahemolytic PNH. Except for the absence or near absence of PNH erythrocytes, this entity shares clinical and pathophysiological features with classic PNH, including thrombophilia (Budd-Chiari Syndrome, Table). The basis of this phenotype is speculative but may be determined by the genotype of the affected HSPC in which the somatic mutation of PIGA first occurred. According to this hypothesis, somatic mutations other than PIGA skew differentiation toward granulocyte/monocyte lineages. The International PNH Interest Group recognizes the following three categories of PNH: classic PNH, PNH in the setting of another define bone marrow abnormality, and subclinical PNH. Like ahemolytic PNH, subclinical PNH has no biochemical evidence of hemolysis. In this case, however, the absence of hemolysis is due to the small size of the PNH clone (median clone size &amp;lt;1%) as determined by flow cytometry analysis of peripheral blood granulocytes and monocytes. We propose that ahemolytic PNH, defined as patients having less than &amp;lt;5% PNH red cells and &amp;gt;50% PNH granulocytes/monocytes, be recognized as a distinct category of PNH.

CRISPR/Cas9 Strategy for Correcting ELANE Mutations and Restoring Neutrophil Differentiation in Severe Congenital Neutropenia: Insights from Patient-Derived iPSCs

Introduction The ELANE gene, encoding neutrophil elastase (NE), has been identified as the primary causative gene for more than half of patients with severe congenital neutropenia (SCN). For patients refractory to standard therapy (G-CSF), the only available option is an allogeneic hematopoietic stem cell transplant. Therefore, there is a great clinical interest in the development of novel gene therapies, including CRISPR/Cas9, which has shown promise for the correction of ELANE mutations and the restoration of neutrophil function. Here, we introduce a gene editing strategy using CRISPR/Cas9 to repair ELANE gene mutations in patient-derived induced pluripotent stem cells (iPSCs), aiming to restore proper neutrophil development and function. Methods We utilized a targeted NGS panel composed of 725 genes related to hematological disorders to sequence 282 pediatric patients suffering from chronic neutropenia. Patient-derived epithelial cells collected from urine were reprogrammed into iPSCs using the EBV-derived oriP/EBNA-1 system carrying transcription factors. CRISPR-Cas9 technology was employed to repair mutations in patient-derived iPSCs. The efficiency of transfection and gene editing was subsequently assessed by analyzing the targeted region by Sanger sequencing. Control iPSCs (healthy donors) and iPSCs from patients were differentiated into neutrophils with specific cytokine cocktail (BMP4, CHIR99021, VEGF, SCF, bFGF, SB431542, SCF, IL-3, TPO, Flt-3, G-CSF). Cells were harvested at day 25 and analyzed for surface markers resembling the distinct myeloid progenitors. Flow cytometry antibody panel (CD14, CD45, CD49d, Siglec-8, CD101, CD11b, CD35, CD16) and gating strategy allowed to identify myeloid populations such as proNeu1, preNeu, immature-Neu and mature Neu representing myeloblasts, promyelocytes, myelocytes/metamyelocytes and band/segmented neutrophils, respectively. The morphology of myeloid precursors and mature neutrophils as well as the localization of neutrophil elastase in control iPSCs were evaluated by confocal microscopy. Results From a sequenced cohort of 282 patients, causative mutations were identified in 49 individuals, including 17 with ELANE mutations, and 9 novel variants were discovered. For this study, we selected two patients exhibiting different phenotypes for further investigation. One patient carries the NM_001972.3:c.[163T&amp;gt;C];[=], NP_001963:p.[(Cys55Arg)];[(=)] ELANE mutation and presents severe neutropenia (ANC=100/µL), currently undergoing G-CSF treatment. The second patient carries the NM_001972.3:c.[597+5G&amp;gt;A];[=], NP_001963:p.[(Val190_Phe199del)];[(=)] ELANE mutation which demonstrates in the fluctuating blood neutrophil counts characteristic for cyclic neutropenia. iPSCs were generated from both patients. Alkaline phosphatase and immunocytochemical staining confirmed that the reprogrammed cells express pluripotent stem cell markers and can differentiate into the three germ layers. Genetic defect repair was observed in 13.3% of tested cell colonies from the patient with the c.163T&amp;gt;C Cys55Arg ELANE mutation and in 30% of sequenced colonies from the patient with the c.597+5G&amp;gt;A V190_F199del ELANE mutation. Molecular cytogenetics (SNP-array) showed no significant genomic rearrangements or off-targets in iPSCs selected for differentiation. iPSC cells from healthy donors, derived from c.597+5G&amp;gt;A V190_F199del ELANE patient and the repaired clone were successfully differentiated into neutrophils (CD16+ CD35+) and their myeloid precursors (CD49d+ CD11b+). The percentage of immature and mature neutrophils (CD16+ and CD35+) derived from control or corrected iPSC was significantly higher compared to patient-derived neutrophils (Figure 1). Conclusions Our study demonstrates the successful use of CRISPR/Cas9 to repair ELANE gene mutations in patient-derived iPSCs, aiming to restore proper neutrophil development. Patient-derived iPSCs exhibit impaired differentiation at the myelocytes/metamyelocytes stage, as evidenced by a notably lower population of immature and mature neutrophils when compared to CRISPR/Cas9 repaired and healthy donor iPSCs. This observation aligns with the bone marrow phenotype observed in patients with SCN. Our findings indicate that iPSCs generated from patients' epithelial cells serve as a valuable cellular model for further research.

Being overweight and obese increases suicide risk, the severity of depression, and the inflammatory response in adolescents with major depressive disorders.

There is a bidirectional relationship between obesity and depression. We investigated whether the coexistence of obesity and depression increases the risk of having severe depression and a high suicide risk in adolescents with major depressive disorder (MDD). Additionally, we explored the potential mechanisms linking the coexistence of obesity and depression to worse outcomes in these patients. The odds of high suicide risk and severe depression were compared among MDD patients based on different body mass index (BMI) groups. Complete blood count (CBC) parameters, inflammatory ratios (neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], and platelet-lymphocyte ratio [PLR]), and cytokine levels (IFN-γ, IL-1β, IL-6, IL-8, MCP-1, TNF-α, and TGF-β1) were evaluated across BMI groups. Additionally, Pearson correlation coefficients (r) were assessed to understand the relationships between the 8Q and 9Q scores, CBC parameters, inflammatory ratios, cytokine levels, and BMI. A total of 135 antidepressant-naive adolescents with MDD were included. Overweight and obese MDD patients had higher odds of having high suicide risk and severe depression than lean individuals. Furthermore, they exhibited significantly higher white blood cell (WBC), and neutrophil counts. The NLR tended to be higher in obese MDD patients than in leans. Overweight and obese MDD patients had elevated levels of interleukin (IL)-1β and IL-6 compared to lean individuals, while TGF-β1 levels appeared to decline as body weight increased. BMI showed weak positive correlations with 8Q score, WBC count, neutrophil count, monocyte count, platelet count, neutrophil percentage, and NLR, and a weak negative correlation with lymphocyte percentage. The 8Q score displayed weak positive correlations with BMI, neutrophil percentage, monocyte percentages, NLR, and MLR, and a weak negative correlation with lymphocyte percentage. The findings suggest that coexistence of overweight or obesity with depression heightened inflammatory responses, leading to worse outcomes and increased suicide risk in adolescents MDD patients.

Lysosome-Related Diagnostic Biomarkers for Pediatric Sepsis Integrated by Machine Learning.

There is currently no biomarker that can reliably identify sepsis, despite recent scientific advancements. We systematically evaluated the value of lysosomal genes for the diagnosis of pediatric sepsis. Three datasets (GSE13904, GSE26378, and GSE26440) were obtained from the gene expression omnibus (GEO) database. LASSO regression analysis and random forest analysis were employed for screening pivotal genes to construct a diagnostic model between the differentially expressed genes (DEGs) and lysosomal genes. The efficacy of the diagnostic model for pediatric sepsis identification in the three datasets was validated through receiver operating characteristic curve (ROC) analysis. Furthermore, a total of 30 normal samples and 35 pediatric sepsis samples were gathered to detect the expression levels of crucial genes and assess the diagnostic model's efficacy in diagnosing pediatric sepsis in real clinical samples through real-time quantitative PCR (qRT-PCR). Among the 83 differentially expressed genes (DEGs) related to lysosomes, four key genes (STOM, VNN1, SORT1, and RETN) were identified to develop a diagnostic model for pediatric sepsis. The expression levels of these four key genes were consistently higher in the sepsis group compared to the normal group across all three cohorts. The diagnostic model exhibited excellent diagnostic performance, as evidenced by area under the curve (AUC) values of 1, 0.971, and 0.989. Notably, the diagnostic model also demonstrated strong diagnostic ability with an AUC of 0.917 when applied to the 65 clinical samples, surpassing the efficacy of conventional inflammatory indicators such as procalcitonin (PCT), white blood cell (WBC) count, C-reactive protein (CRP), and neutrophil percentage (NEU%). A four-gene diagnostic model of lysosomal function was devised and validated, aiming to accurately detect pediatric sepsis cases and propose potential target genes for lysosomal intervention in affected children.

Utility of Atypical Lymphocytes and Large Immature Cells in Prediction of Dengue Severity.

Background: There is a clinical imperative to devise metrics to prognosticate dengue severity. Our objective was to determine the association between longitudinal trends in atypical lymphocytes and large immature cell count with platelet count and dengue severity. Materials and methods: Retrospective analysis of longitudinally measured clinical and hematological data from (n = 79) hospitalized dengue patients was done. Results: The cohort consisted of patients with dengue fever without warning signs (DFWOWS) (n = 40, females = 14, and age = 19.9 ± 14.6 years), dengue fever with warning signs (DFWWS) (n = 36, females = 13, and age = 16.1 ± 14.1 years) and severe dengue (n = 3, females = 2, and age = 5.3 ± 4 years). Platelet count increased at a rate of 11,524 cells/mm3/day, with a slower rate of rise as the severity increased (p = 0.001***). Concurrently hematocrit and neutrophil percentage decreased, while the lymphocyte percentage and white blood cell (WBC) count increased during the hospital stay. Every 1% increase in atypical lymphocyte count (ATY) was associated with a fall in platelet count by 16,963 cells/mm3 (p = 0.001***). A similar but weaker trend was found for large immature cells (LICs). Conclusion: The data support the usefulness of longitudinal tracking of atypical lymphocyte and large immature cell count for dengue prognosis. The time trends of the hematological parameters indicate the progression of patients from the critical to the recovery phase. How to cite this article: Peraka R, Koppula A, Muppala BS, et al. Utility of Atypical Lymphocytes and Large Immature Cells in Prediction of Dengue Severity. J Assoc Physicians India 2023;71(11):19-24.

Construction and evaluation of a nomogram prediction model for aspiration pneumonia in patients with acute ischemic stroke

BackgroundAspiration Pneumonia (AP) is a leading cause of death in patients with Acute Ischemic Stroke (AIS). Early detection, diagnosis and effective prevention measures are crucial for improving patient prognosis. However, there is a lack of research predicting AP occurrence after AIS. This study aimed to identify risk factors and develop a nomogram model to determine the probability of developing AP after AIS. MethodA total of 3258 AIS patients admitted to Jinshan Hospital of Fudan University between January 1, 2016, and August 20, 2022, were included. Among them, 307 patients were diagnosed with AP (AP group), while 2951 patients formed the control group (NAP group). Univariate and multivariate logistic regression analyses were conducted to identify relevant risk factors for AP after AIS. These factors were used to establish a scoring system and develop a nomogram model using R software. ResultsUnivariate analysis revealed 20 factors significantly associated (P < 0.05) with the development of AP after AIS. These factors underwent multivariate logistic regression analysis, which identified age (elderly), National Institute of Health Stroke Scale (NIHSS) score, dysphagia, atrial fibrillation, cardiac insufficiency, renal insufficiency, hepatic insufficiency, elevated Fasting Blood Glucose (FBG), elevated C-Reactive Protein (CRP), elevated Neutrophil percentage (NEUT%), and decreased prealbumin as independent risk factors. A nomogram model incorporating these 11 risk factors was constructed, with a C-index of 0.872 (95 % CI: 0.845–0.899), indicating high accuracy. Calibration and clinical decision analyses demonstrated the model's reliability and clinical value. ConclusionA nomogram model incorporating age, NIHSS score, dysphagia, atrial fibrillation, cardiac insufficiency, renal insufficiency, hepatic insufficiency, FBG, CRP, NEUT%, and prealbumin effectively predicts AP risk in AIS patients. This model provides guidance for early intervention strategies, enabling the identification of high-risk individuals for timely preventive measures.

PSVI-1 Effect of Soy co-Products in Supplements for Growing Cattle on Hemocytology Following a Lipopolysaccharide Challenge

Abstract The objective of this study was to determine the effect of including soy co-products (soybean meal and soy oil) in the diet on the hemocytology of cattle after an endotoxin challenge. For the growing phase, crossbred Angus steers (n = 36; initial body weight = 289 ± 31 kg) were stratified by body weight and sire and randomly assigned to pastures (n = 9; 0.45 ha mixed grass). Pastures were assigned randomly to 1 of 3 dietary treatments: 1) a control supplement containing no soy co-products (CON); 2) a supplement containing soybean meal (SBM); or 3) a supplement containing soy oil (SBO). All supplements were isonitrogenous and isoenergetic. Cattle were fed supplements (2.45 kg DM/day) for 56 days. At the conclusion of the growing phase, cattle were assigned randomly to 1 of 2 groups for a lipopolysaccharide (LPS) challenge (i.v. infusion of 0.5 µg LPS/kg of body weight). A minimum of 18 hours before sampling, cattle were fitted with jugular vein catheters and placed into stanchions. Blood was collected starting 2 hours before LPS infusion (-2 hr), immediately prior to LPS infusion (0 hr), and at 2, 4, 6, and 8 hr. Statistical analyses were performed using the MIXED procedure of SAS 9.4 as repeated measures with treatment, time, and treatment × time interaction as fixed effects, challenge group as random effect, and calf specified as the subject. Statistical significance was declared at P ≤ 0.05 and tendencies declared at 0.05 &amp;lt; P ≤ 0.1. There were treatment × time interactions for neutrophils (P = 0.003), percentage of neutrophils (P = 0.002), percentage of lymphocytes (P = 0.006), and neutrophil/lymphocyte ratio (NE:LY ratio; P = 0.001). Briefly, neutrophils, percentage of neutrophils, and NE:LY ratio were decreased in cattle on CON diets compared with SBM at -2 h and 0 h (P &amp;lt; 0.01). Also, the percentage of neutrophils were greater at 8 h for cattle on SBO diets than SBM diets (P = 0.018). The percentage of lymphocytes were greater in cattle on the CON diets compared with the SBM diets at 0 and -2 h (P &amp;lt; 0.015). There was a treatment effect for percentage of monocytes (P = 0.035), as the CON diet had greater monocyte percentage compared with the SBM diet, and the SBO diet tended to have greater monocyte percentage compared with SBM diet. There was a time effect for all other hematology variables (P &amp;lt; 0.0001), as leukocytes were typically greater pre-administration of LPS, sharply decreased at 2 and 4 h post-administration of LPS and began to increase at 6 and 8 h. Preliminary results indicated that the inclusion of soy co-products in growing cattle diets influenced hemocytology.

Interleukin-8 and neutrophil extracellular traps in children with lupus nephritis and vitamin C deficiency.

Vitamin C is a potent scavenger of reactive oxygen species, which induce neutrophil extracellular trap (NET) formation. NETs are a major source of autoantigens and are involved in systemic lupus erythematosus (SLE) pathogenesis. We determined vitamin C status and evaluated NET formation and inflammatory cytokines in children with lupus nephritis. Serum vitamin C was measured in 46 patients (82.6% females, mean age 14.5 ± 0.3years). Vitamin C levels < 0.3mg/dL indicated vitamin C deficiency. Patients were divided into two groups according to serum vitamin C levels: normal and low (< 0.3mg/dL). We compared NET formation and levels of SLE-related cytokines, including interleukin (IL)-8, IL-10, and tumor necrosis factor-α (TNF-α), between groups. NET formation was determined through measurement of serum citrullinated histone 3 levels and mRNA expression of peptidyl arginine deiminase-4 and assessment of the percentage of neutrophils with NETs by immunofluorescence. Nine patients (19.6%) had vitamin C deficiency. Kidney pathology assessment at disease onset revealed that histological activity index and number of kidney biopsies containing crescentic glomeruli were higher in vitamin C-deficient patients, but chronicity index was not. NET formation and serum IL-8 were more prominent in vitamin C-deficient patients. Serum IL-8 levels were 12.9 ± 5.2pg/mL in low vitamin C group and 5.2 ± 0.9pg/mL in normal vitamin C group (p = 0.03). Serum IL-10 and TNF-α were similar between groups. Our study demonstrated correlation among vitamin C deficiency, increased NET formation, and IL-8 upregulation in children with lupus nephritis. A prospective study is required to evaluate cause‒effect relationships of vitamin C status, NET formation and IL-8 expression.

Clinical Characteristics and Immune Responses in Children with Primary Ciliary Dyskinesia during Pneumonia Episodes: A Case-Control Study.

This study explored the clinical features and immune responses of children with primary ciliary dyskinesia (PCD) during pneumonia episodes. The 61 children with PCD who were admitted to hospital because of pneumonia were retrospectively enrolled into this study between April 2017 and August 2022. A total of 61 children with pneumonia but without chronic diseases were enrolled as the control group. The clinical characteristics, levels of inflammatory indicators, pathogens, and imaging features of the lungs were compared between the two groups. The PCD group had higher levels of lymphocytes (42.80% versus 36.00%, p = 0.029) and eosinophils (2.40% versus 1.25%, p = 0.020), but lower neutrophil counts (3.99 versus 5.75 × 109/L, p = 0.011), percentages of neutrophils (46.39% versus 54.24%, p = 0.014), CRP (0.40 versus 4.20 mg/L, p < 0.001) and fibrinogen (257.50 versus 338.00 mg/dL, p = 0.010) levels. Children with PCD and children without chronic diseases were both most commonly infected with Mycoplasma pneumoniae (24.6% versus 51.9%). Children with PCD had significantly more common imaging features, including mucous plugging (p = 0.042), emphysema (p = 0.007), bronchiectasis (p < 0.001), mosaic attenuation (p = 0.012), interstitial inflammation (p = 0.015), and sinusitis (p < 0.001). PCD is linked to immune system impairment, which significantly contributes to our understanding of the pathophysiology of this entity.

Hemogram Parameters and Hemogram-Derived Ratios in Covid-19 Severity

Background: Understanding the hematological manifestations of the COVID-19, is of paramount importance in terms of patient management and prognosis. Aim: To review the fundamental hemogram parameters and their clinical significance. Methods: This is a retrospective, cross-sectional, and observational investigation. Hemogram findings of the participants within 30 days following the onset of symptoms were analyzed. Participants were categorized into moderate and severe groups based on the assessment of disease severity. Results: Both erythrocyte sedimentation rate and C-reactive protein are considerably elevated in both groups, with higher levels observed in the severe group compared to the moderate group. The percentage of neutrophils, is elevated above normal in both groups, with the severe group demonstrating higher values. The statistical difference between the groups is significant. Conclusion: Hemogram-derived ratios would be beneficial to include them in common laboratory practices.

Persistent headaches one year after bacterial meningitis: prevalence, determinants and impact on quality of life.

Little is known on headaches long-term persistence after bacterial meningitis and on their impact on patients' quality of life. In an ancillary study of the French national prospective cohort of community-acquired bacterial meningitis in adults (COMBAT) conducted between February 2013 and July 2015, we collected self-reported headaches before, at onset, and 12months (M12) after meningitis. Determinants of persistent headache (PH) at M12, their association with M12 quality of life (SF 12), depression (Center for Epidemiologic Studies Depression Scale) and neuro-functional disability were analysed. Among the 277 alive patients at M12 87/274 (31.8%), 213/271 (78.6%) and 86/277 (31.0%) reported headaches before, at the onset, and at M12, respectively. In multivariate analysis, female sex (OR: 2.75 [1.54-4.90]; p < 0.001), pre-existing headaches before meningitis (OR: 2.38 [1.32-4.30]; p < 0.01), higher neutrophilic polynuclei percentage in the CSF of the initial lumbar puncture (OR: 1.02 [1.00-1.04]; p < 0.05), and brain abscess during the initial hospitalisation (OR: 8.32 [1.97-35.16]; p < 0.01) were associated with M12 persistent headaches. Neither the responsible microorganism, nor the corticoids use were associated with M12 persistent headaches. M12 neuro-functional disability (altered Glasgow Outcome Scale; p < 0.01), M12 physical handicap (altered modified Rankin score; p < 0.001), M12 depressive symptoms (p < 0.0001), and M12 altered physical (p < 0.05) and mental (p < 0.0001) qualities of life were associated with M12 headaches. Persistent headaches are frequent one year after meningitis and are associated with quality of life alteration. NCT01730690.

Risk factors and construction of a nomogram model for cirrhotic portal vein thrombosis combined with esophagogastric variceal bleeding

Objective: To investigate the risk factors and construct a nomogram model for predicting the occurrence of cirrhotic portal vein thrombosis in patients combined with esophagogastric variceal bleeding (EVB). Methods: Clinical data on 416 cirrhotic PVT cases was collected from the First Hospital of Lanzhou University between January 2016 and January 2022. A total of 385 cases were included after excluding 31 cases for retrospective analysis. They were divided into an esophagogastric variceal bleeding group and a non-esophagogastric variceal bleeding group based on the clinical diagnosis. The esophagogastric variceal group was then further divided into an EVB group and a non-bleeding group. All patients underwent gastroscopy, serology, and imaging examinations. The risk factors of PVT combined with EVB were identified by univariate analysis using SPSS 26. The prediction model of cirrhotic PVT in patients combined with EVB was constructed by R 4.0.4. The prediction efficiency and clinical benefits of the model were evaluated by the C-index, area under the receiver operating characteristic curve, calibration plots, and decision curve. The measurement data were examined by a t-test or Mann-Whitney U test. The counting data were tested using the χ(2) test or the Fisher exact probability method. Results: There were statistically significant differences in the etiology, Child-Pugh grade,erythrocyte count, hematocrit, globulin, and serum lipids between the esophageal and non-esophageal varices groups (P < 0.05). There were statistically significant differences in etiology, erythrocyte count, hemoglobin, hematocrit, neutrophil percentage, total protein, globulin, albumin/globulin, urea, high-density lipoprotein cholesterol, calcium, and neutrophil lymphocyte ratio (NLR) between the EVB and non-bleeding groups (P < 0.05). Multivariate logistic regression analysis showed that etiology (OR = 3.287, 95% CI: 1.497 ~ 7.214), hematocrit (OR = 0.897, 95% CI: 0.853 ~ 0.943), and high-density lipoprotein cholesterol (OR = 0.229, 95% CI: 0.071 ~ 0.737) were independent risk factors for cirrhotic PVT patients combined with EVB. The constructed normogram model predicted the probability of bleeding in patients. The nomogram model had shown good consistency and differentiation (AUC = 0.820, 95% CI: 0.707 ~ 0.843), as verified by 10-fold cross-validation (C-index = 0.799) and the Hosmer-Lemeshow goodness of fit test (P = 0.915). The calibration plot and the decision curve suggested that the prediction model had good stability and clinical practicability. Conclusion: The risk factors for EVB occurrence include etiology, erythrocyte, hemoglobin, hematocrit, percentage of neutrophils, total protein, globulin, albumin/globulin, urea, high-density lipoprotein cholesterol, calcium, and NLR in patients with cirrhotic liver. The constructed prediction model has good predictive value, and it can provide a reference for medical personnel to screen patients with high bleeding risk for targeted treatment.

CBC Differences between Survived and Deceased COVID-19 Patients: A Cohort Study.

The Coronavirus disease 2019 (COVID-19) pandemic showed the importance of simple, low-cost, and accessible tests for patient triage. Complete Blood Count (CBC) can be considered a good option for predicting the prognosis of COVID-19 and daily follow-up of hospitalized patients. CBC tests of 100 COVID-19 patients admitted to the general ward or intensive care unit (ICU) were monitored for ten days. Routine laboratory tests were also performed. In addition, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated at the time of admission. The WBC count of the ICU-admitted patients was significantly lower than in the non-ICU-admitted group (P = 0.008). The mean lymphocyte percentage of deceased patients was significantly lower than in the survived patients (P = 0.041), whereas the mean neutrophil percentage of the former group was higher than the latter ( P = 0.012). Moreover, the mean monocyte percentage of the survivors was significantly more than that of non-survivors (P = 0.003). However, there was no significant difference in mean platelet counts, hemoglobin levels, and red blood cell count between the studied groups. A lower WBC, lymphocyte percentage, and monocyte percentage, in addition to a higher neutrophil percentage, may indicate a poor prognosis in moderate to severe COVID-19 patients.

Predictors of in-hospital appendiceal perforation in patients with non- perforated acute appendicitis with appendicolithiasis at presentation

IntroductionAppendicolithiasis is a risk factor for perforated acute appendicitis. There is limited inpatient data on predictors of progression in appendicolithiasis-associated non-perforated acute appendicitis.MethodsWe identified adults presenting with appendicolithiasis-associated non-perforated acute appendicitis (on computed tomography) who underwent appendectomy. Logistic regression was used to investigate predictors of in-hospital perforation (on histopathology).Results296 patients with appendicolithiasis-associated non-perforated acute appendicitis were identified; 48 (16.2%) had perforation on histopathology. Mean (standard deviation [SD]) age was 39 (14.9) years. The mean (SD) length of stay (LOS) was 1.5 (1.8) days. LOS was significantly longer with perforated (mean [SD]: 3.0 [3.1] days) vs. non-perforated (mean [SD]: 1.2 [1.2] days) appendicitis (p < 0.001). On multivariate analysis, in-hospital perforation was associated with age > 65 years (OR 5.4, 95% CI: 1.4- 22.2; p = 0.015), BMI > 30 kg/m2 (OR 3.5, 95% CI: 1.3–8.9; p = 0.011), hyponatremia (OR 3.6, 95% CI: 1.3–9.8; p = 0.012). There was no significant association with age 25–65 years, gender, race, steroids, time-to- surgery, neutrophil percentage, or leukocyte count.ConclusionGeriatric age, obesity, and hyponatremia are associated with progression to perforation in appendicolithiasis-associated non-perforated acute appendicitis.

Predicting prognosis in patients with stroke treated with intravenous alteplase through blood pressure changes: A machine learning-based approach.

The use of machine learning (ML) in predicting disease prognosis has increased, and researchers have adopted different methods for variable selection to optimize early screening for AIS to determine its prognosis as soon as possible. We aimed to improve the understanding of the predictors of poor functional outcome at three months after discharge in AIS patients treated with intravenous thrombolysis and to construct a highly effective prognostic model to improve prediction accuracy. And four ML methods (random forest, support vector machine, naive Bayesian, and logistic regression) were used to screen and recombine the features for construction of an ML prognostic model. A total of 352 patients that had experienced AIS and had been treated with intravenous thrombolysis were recruited. The variables included in the model were NIHSS on admission, age, white blood cell count, percentage of neutrophils and triglyceride after thrombolysis, tirofiban, early neurological deterioration, early neurological improvement, and BP at each time point or period. The model's area under the curve for predicting 30-day modified Rankin scale was 0.790 with random forest, 0.542 with support vector machine, 0.411 with naive Bayesian, and 0.661 with logistic regression. The random forest model was shown to accurately evaluate the prognosis of AIS patients treated with intravenous thrombolysis, and therefore they may be helpful for accurate and personalized secondary prevention. The model offers improved prediction accuracy that may reduce rates of misdiagnosis and missed diagnosis in patients with AIS.

Disease progression in patients with usual interstitial pneumonia and probable UIP patterns on computed tomography with various underlying etiologies: a retrospective cohort study.

Usual interstitial pneumonia (UIP) is a pattern of interstitial pneumonia that is caused by different etiologies. This study aimed to investigate the transplant-free survival (TFS) and the decline in forced vital capacity (FVC) of the patients with UIP and probable UIP patterns on CT caused by various underlying conditions. A retrospective cohort study was conducted, enrolling patients with interstitial lung disease exhibiting a CT pattern consistent with UIP or probable UIP. Clinical and prognostic data of patients categorized by the etiology were compared. A total of 591 patients were included and classified into the following groups: idiopathic pulmonary fibrosis (IPF) (n = 320), connective tissue disease (CTD)-UIP (n = 229), asbestosis-UIP (n = 28), and hypersensitivity pneumonitis (HP)-UIP (n = 14). Advanced age, elevated levels of serum cytokeratin fraction 21-1 and percentage of neutrophils in bronchoalveolar lavage were observed in all groups. IPF patients showed a more rapid decline in FVC (133.9 mL/year) compared to CTD-UIP (24.5 mL/year, p = 0.001) and asbestosis-UIP (61.0 mL/year, p = 0.008) respectively. Sub-analysis of CTD-UIP revealed that patients with rheumatoid arthritis (RA)-UIP (88.1 mL/year) or antineutrophil cytoplasmic antibody-associated vasculitis (AAV)-UIP (72.9 mL/year) experienced a faster deterioration in FVC compared to those with primary Sjögren's syndrome (pSS)-UIP (25.9 mL/year, p < 0.05). Kaplan-Meier curves showed that IPF had the poorest TFS (median 55.9 months), followed by HP-UIP (57.5 months), CTD-UIP (66.7 months), and asbestosis-UIP (TFS not reached). RA-UIP or AAV-UIP did not exhibit any prognostic advantages compared to IPF, while asbestosis-UIP and pSS-UIP showed better survival rates. Patients with UIP caused by different underlying conditions share certain common features, but the trajectories of disease progression and survival outcomes differ.