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Introduction: New tools have been developed to distinguish the COVID‐19 diagnosis from other viral infections presenting similar symptomatology and mitigate the lack of sensitivity of molecular testing. We previously identified a specific "sandglass" aspect on the white blood cells (WBC) scattergram of COVID‐19 patients, as a highly reliable COVID‐19 screening test (sensitivity: 85.9%, specificity: 83.5% and positive predictive value: 94.3%). We then decided to validate our previous data in a multicentric study. Methods: This retrospective study involved 817 patients with flu‐like illness, among 20 centers, using the same CBC instrument (XN analyzer, SYSMEX, Japan). After training, one specialist per center independently evaluated, under the same conditions, the presence of the "sandglass" aspect of the WDF scattergram, likely representing plasmacytoid lymphocytes. Results: Overall, this approach showed sensitivity: 59.0%, specificity: 72.9% and positive predictive value: 77.7%. Sensitivity improved with subgroup analysis, including in patients with lymphopenia (65.2%), patients presenting symptoms for more than 5 days (72.3%) and in patients with ARDS (70.1%). COVID‐19 patients with larger plasmacytoid lymphocyte cluster (>15 cells) more often have severe outcomes (70% vs. 15% in the control group). Conclusion: Our findings confirm that the WBC scattergram analysis could be added to a diagnostic algorithm for screening and quickly categorizing symptomatic patients as either COVID‐19 probable or improbable, especially during COVID‐19 resurgence and overlapping with future influenza epidemics. The observed large size of the plasmacytoid lymphocytes cluster appears to be a hallmark of COVID‐19 patients and was indicative of a severe outcome. Furthers studies are ongoing to evaluate the value of the new hematological parameters in combination with WDF analysis. [ABSTRACT FROM AUTHOR]

Introduction: Falsely elevated synovial white blood cell (WBC) counts using automated hematology analyzers have been reported particularly in the setting of joint arthroplasty. We evaluated the implementation of a laboratory workflow based on Sysmex XN‐1000‐automated cell counting and scattergram interpretation. Methods: WBC and differential were measured for 76 synovial fluid samples (29 native joints and 47 with joint arthroplasties) with Sysmex XN‐1000 and manual methods. All scattergrams were evaluated for possible incorrect WBC and/or differential according to our implemented workflow. A specific finding was the "banana‐shape" scattergram, which indicates possible interferences. The European Bone & Joint Infection Society (EBJIS) criteria were applied to identify possible prosthetic joint infections (PJIs) in patients with joint arthroplasties. Results: Correlation between automated and manual WBC counts, calculated for samples with WBC count <50 000/μL, was higher for native joints (r = 0.938) compared with patients known with arthroplasty (r = 0.906). Scattergrams classified as OK showed overall a higher correlation compared with scattergrams, which were interpreted as NOT OK. "Banana‐shape" scattergrams (n = 19) showed falsely elevated automated WBC count, and the patterns were mainly seen in prosthesis patients (17/19 [89%]). Six of 47 (13%) patients with joint arthroplasties were reclassified from "confirmed" to "unlikely" PJI according to the EBJIS criteria. Conclusion: Our workflow based on scattergram interpretation resulted in accurate WBC counts in synovial fluid using automated/and or manual methods. It is important to identify the presence of "banana‐shape" scattergrams to avoid overestimated automated WBC counts. Overall, automated synovial WBC count can be used, even for patients with arthroplasty, but after visual inspection of the scattergram to exclude possible interferences. [ABSTRACT FROM AUTHOR]

Introduction: For the majority of patients with acute myeloid leukemia (AML) an allogeneic stem cell transplant (SCT) in first complete remission (CR) is preferred. However, whether the number of courses required to achieve CR has a prognostic impact is unclear. It is unknown which factors remain important in patients requiring more than one course of induction to attain remission. Methods: This Acute Leukaemia Working Party study from the European Society for Blood and Marrow Transplantation identified adults who received an allograft in first CR from either a fully matched sibling or 10/10 or 9/10 human leucocyte antigen (HLA)‐matched unrelated donor (HLA‐A, HLA‐B, HLA‐C, HLA‐DR, or HLA‐DQ). Univariate and multivariate analyses were undertaken to identify the prognostic impact of one or two courses of induction to attain CR. Results: A total of 4995 patients were included with 3839 (77%) patients attaining a CR following one course of induction chemotherapy (IND1), and 1116 patients requiring two courses (IND2) to attain CR. IND2 as compared to IND1 was a poor prognostic factor in a univariate analysis and remained so in a multivariate Cox model, resulting in an increased hazard ratio of relapse (1.38; 95% confidence interval [CI], 1.16–1.64; p =.0003) and of death (1.27; 95% CI, 1.09–1.47; p =.002). Adverse prognostic factors in a multivariate analysis of the outcomes of patients requiring IND2 included age, FLT3‐ITD, adverse cytogenetics, and performance status. Pretransplant measurable residual disease retained a prognostic impact regardless of IND1 or IND2. Conclusion: Initial response to chemotherapy as determined by number of courses to attain CR, retained prognostic relevance even following SCT in CR. Patients requiring two courses of induction to attain complete remission (CR) have a higher incidence of relapse and inferior survival as compared to those who require one course. Pretransplant measurable residual disease remains important in predicting outcomes following an allogeneic stem cell transplant in those requiring two courses of induction to achieve CR. [ABSTRACT FROM AUTHOR]

Summary: The degree of anaemia in sickle cell disease (SCD) is a well‐known contributor to morbidity and mortality. We aimed to explore the factors affecting haemoglobin (Hb) level in African SCD patients, considering haemolysis biomarkers (LDH and bilirubin level, and reticulocyte count), leucocyte and platelet counts and socio‐demographic characteristics (gender, age group, country of residence and BMI). The research was part of the CADRE multinational cohort and involved 3699 SCD patients living in Mali, Senegal, Ivory Coast, Democratic Republic of Congo, Gabon and Cameroon: 2936 SS/Sβ0, 587 SC and 176 Sβ + patients with median Hb level of 8, 11.3 and 11.2 g/dL respectively (p < 0.001). In multivariate analysis conducted in 1394 SS/Sβ0 patients, living in Cameroon, female gender, lower BMI, higher haemolysis markers (especially LDH) and higher leucocyte and platelet counts were independently associated with lower Hb level (all p < 0.05). In 497 SC and 156 Sβ + patients, female gender (p < 0.001), lower BMI (p < 0.05) and higher platelet counts (p < 0.001) were independently associated with lower Hb level. Anaemia in African SCD patients is not only associated with haemolysis but also with the country of residence, lower BMI and leucocyte or platelet counts which might reflect inflammation related to infectious burden in the region. [ABSTRACT FROM AUTHOR]

Background: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)–derived and lumbar spinal drain–derived samples. Methods: We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain–derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling. Results: We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4–5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64–618 × 106). The cell ratio and index peaked at 8–9 days (0.90% [IQR 0.35–1.98%] and 2.71 [IQR 1.25–6.73], respectively). In spinal drain–derived samples, the leucocyte count peaked at days 6–7, reaching a median of 238 × 106 (IQR 60–396 × 106). The cell ratio and index peaked at 14–15 days (4.12% [IQR 0.63–10.61%]) and 12–13 days after aSAH (8.84 [IQR 3.73–18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain–derived samples at days 6–17, and the cell ratio as well as the cell index was significantly higher in spinal drain–derived samples compared to EVD samples at days 10–15. Conclusions: CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable. [ABSTRACT FROM AUTHOR]

Aims: Aim of this study was to investigate in type 2 diabetes whether expression level of GALNT2, a positive modulator of insulin sensitivity, is associated with a metabolic signature. Methods: Five different metabolite families, including acylcarnitines, aminoacids, biogenic amines, phospholipids and sphingolipids were investigated in fasting serum of 70 patients with type 2 diabetes, by targeted metabolomics. GALNT2 expression levels were measured in peripheral white blood cells by RT-PCR. The association between GALNT2 expression and serum metabolites was assessed using false discovery rate followed by stepwise selection and, finally, multivariate model including several clinical parameters as confounders. The association between GALNT2 expression and the same clinical parameters was also investigated. Results: GALNT2 expression was independently correlated with HbA1c levels (P value = 0.0052), a finding that is the likely consequence of the role of GALNT2 on insulin sensitivity. GALNT2 expression was also independently associated with serum levels of the aminoacid glycine (P value = 0.014) and two biogenic amines phenylethylamine (P value = 0.0065) and taurine (P value = 0.0011). The association of GALNT2 expression with HbA1c was not mediated by these three metabolites. Conclusions: Our data indicate that in type 2 diabetes the expression of GALNT2 is associated with several serum metabolites. This association needs to be further investigated to understand in depth its role in mediating the effect of GALNT2 on insulin sensitivity, glucose control and other clinical features in people with diabetes. [ABSTRACT FROM AUTHOR]

This article discusses a case of eosinophilic cholecystitis with polyserositis that mimicked malignancy in a 36-year-old man. The patient presented with symptoms of abdominal fullness and poor appetite, and laboratory findings showed elevated inflammatory markers and peripheral eosinophils. Imaging tests indicated peritonitis, pleural and pericardial effusions, and a thickened gallbladder wall. Despite initial suspicions of gallbladder malignancy, cholecystectomy revealed eosinophilic cholecystitis. The patient's condition improved after surgery, with reduced eosinophil count and resolution of symptoms. The article highlights the misleading clinical picture created by the multisystemic manifestations of eosinophilic cholecystitis. [Extracted from the article]

Objective: This study aimed to evaluate the application of choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis (AP) with encapsulated necrosis and analyzed related inflammatory indexes. Methods: Thirty patients with AP with encapsulated necrosis were enrolled and treated with choledochoscopy and double-cannula lavage. Serum white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), and related inflammatory indexes were detected before and after surgery. Results: All of the participants who underwent the surgery recovered well and were discharged without serious complications; no deaths occurred. The serum WBC, PCT, and CRP of patients after surgery decreased compared with before the procedure, and the differences in WBC and CRP were statistically significant (P < 0.05); the difference in PCT was not statistically significant (P > 0.05). Postoperatively, IL-6, IL-8, and TNF-α levels were higher than before surgery, and the differences were statistically significant (P < 0.05). Conclusion: The surgical method presented herein effectively controlled and alleviated the infection of patients; it also did not increase the risk of infection and can thus be considered a safe and effective surgical method. [ABSTRACT FROM AUTHOR]

Sepsis is a potentially fatal syndrome related to severe systemic inflammation developed by infection. Despite different antimicrobial therapies, morbidity and mortality rates remain high. Herbs along with cell therapy have been introduced as a promising option to improve the symptoms of sepsis. The present study aimed to evaluate the therapeutic effect of simultaneous administration of thyme essential oil (TEO) and endothelial progenitor stem cells (EPCs) on lipopolysaccharide (LPS)‐induced sepsis in C57BL/6 mice. Sepsis was induced in C57Bl/6J mice by intraperitoneal injection of LPS, followed 2 h later by an intravenous injection of EPCs or oral administration of TEO or simultaneous administration of TEO and EPCs. After 10 days, the complete blood cell, renal and liver factors, serum levels of inflammatory cytokines, and angiogenic factors were measured. Simultaneous treatment with EPCs and TEO significantly increased the survival of mice with sepsis and modulated the inflammatory response by reducing the serum levels of pro‐inflammatory cytokines. Moreover, this treatment significantly reduced the level of white blood cells and neutrophils and increased the number of red blood cells, the percentage of hematocrit, and hemoglobin. The combination of TEO with EPCs decreased organ injuries and was assessed by lower levels of the liver enzymes alanine aminotransferase and aspartate aminotransferase compared to the sepsis group. Administration of EPCs and TEO also significantly improved angiogenic factors, lung function, and toll‐like receptor 4 expression. EPCs in combination with TEO increase survival in the LPS‐induced sepsis mice model by acting on several targets. Thus, the combination of TEO with EPCs can be a feasible approach for the future clinical treatment and control of sepsis. [ABSTRACT FROM AUTHOR]

Background: We aim to investigate the characteristics of invasive pulmonary aspergillosis (IPA) in patients with HBV-related acute on chronic liver failure (HBV-ACLF). Methods: A total of 44 patients with probable IPA were selected as the case group, and another 88 patients without lung infections were chosen as the control group. Results: HBV-ACLF patients with probable IPA had more significant 90-day mortality (38.6% vs. 15.9%, p = 0.0022) than those without. The white blood cell (WBC) count was the independent factor attributed to the IPA development [odds ratio (OR) 1.468, p = 0.027]. Respiratory failure was associated with the mortality of HBV-ACLF patients with IPA [OR 26, p = 0.000]. Twenty-seven patients received voriconazole or voriconazole plus as an antifungal treatment. Plasma voriconazole concentration measurements were performed as therapeutic drug monitoring in 55.6% (15/27) of the patients. The drug concentrations exceeded the safe range with a reduced dosage. Conclusions: The WBC count might be used to monitor patients' progress with HBV-ACLF and IPA. The presence of IPA increases the 90-day mortality of HBV-ACLF patients mainly due to respiratory failure. An optimal voriconazole regimen is needed for such critical patients, and voriconazole should be assessed by closely monitoring blood levels. [ABSTRACT FROM AUTHOR]

Our previous study suggested that the Mono-ADP ribosylhydrolase 2 (MACROD2) rs6110695 A>G polymorphism is significantly associated with white blood cell (WBC) count in the Korean population. The present study aimed to evaluate the clinical relevance of the MACROD2 rs6110695 A>G polymorphism for predicting WBC count by utilizing plasma metabolites and a single-nucleotide polymorphism (SNP). Two groups were characterized by MACROD2 rs6110695 A>G SNP genotypes among 139 healthy subjects based on the genetic information provided in our previous work: rs6110695 AA genotype group (n = 129) and rs6110695 AG genotype group (n = 10). Plasma global metabolic profiling was performed using ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). To estimate the predictive abilities of WBC count models using the rs6110695 genotype and/or significant differential metabolites, multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were conducted. The AG genotype had greater WBC-to-apolipoprotein (apo) A-I ratios; counts of WBCs, lymphocytes, monocytes, and granulocytes; monocyte-to-lymphocyte ratio (MLR); and monocyte-to-platelet ratio (MPR) than the AA genotype. In terms of metabolic profile, indoleacetic acid, and butyrylcarnitine levels were considerably distinct between the two groups, and these metabolites were considered to be meaningful prognostic variables for the rs6110695 genotype. Finally, ROC curve analysis demonstrated that the model containing the rs6110695 genotype and the two main metabolites was reliable. The present study revealed that individuals carrying the rs6110695 AG genotype with high plasma indoleacrylic acid and butyrylcarnitine levels might have elevated WBC counts. The rs6110695 genotype and the concentrations of indoleacrylic acid and butyrylcarnitine could contribute to reducing the risk of chronic diseases in the future. [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]

This article presents the findings of a study on serum globulin levels in patients with systemic lupus erythematosus (SLE). The study identified two distinct trajectories of serum globulin levels and developed a predictive model for the elevated globulin level trajectory. The model included various blood test values and may be useful for monitoring and managing SLE. The study highlights the importance of monitoring globulin levels in SLE patients for disease progression. [Extracted from the article]

Background: In Amyotrophic Lateral Sclerosis (ALS) patients with SOD1 mutation the intrathecal administration of tofersen slowed down the progression of disease in a controlled clinical study, but results were not statistically significant. Methods: In this multicentre, observational study, we evaluated a cohort of 27 ALS-SOD1 patients who were treated with tofersen, focussing on 17 patients who were followed for at least 48 weeks (median period of 84 weeks, range 48–108). We compared the clinical slopes, as measured by ALSFRS-R, MRC scale and Forced Vital Capacity, during tofersen treatment with retrospective data at 1 year prior to therapy. Cerebrospinal fluid (CSF) and serum neurofilament light chains (NFL) were measured in all patients. Results: Cumulative evaluation of the ALSFRS-R and MRC progression rates showed a statistically significant change during treatment with respect to the period prior to therapy (p = 0.023 and p = 0.007, respectively). The analysis of individual patients showed that nine of the seventeen patients substantially stabilized or slightly improved. Four patients deteriorated during treatment, while in the remaining patients the very slow course did not allow to identify significant changes. CSF and serum NFL concentration markedly decreased in the near totality of patients. Increased levels of white blood cells and proteins in the CSF were found in 60% of patients. Such alterations were clinically asymptomatic in all but two patients who showed an acute pure motor radiculitis, which responded to steroid therapy. Conclusions: Clinical findings and NFL analysis strongly suggest that tofersen may have a disease-modifying effect in a subset of SOD1-ALS patients. [ABSTRACT FROM AUTHOR]

The role of baker's yeast in poultry performance when fed a standard diet is well known. However, its effect on broiler chickens fed low-nutrient diets is lacking in literature. The aim of this study is to evaluate the performance, haematology, and blood chemistry of broiler chickens fed a reduced energy and protein (REP) diet with or without baker's yeast supplementation. Two hundred (200) Ross 308 broiler chickens were used in a 6-week feeding trial. The birds were divided into four groups having five replicates of ten birds each. Each group was assigned to one experimental diet in a completely randomized design. The four experimental groups include the control group fed a diet having recommended energy and protein without baker's yeast; the REPY0 group fed REP diet without baker's yeast; the REPY0.2 group fed REP diet with 0.20% baker's yeast; and the REPY0.4 group fed REP diet with 0.40% baker's yeast. The REPY0 and REPY0.2 groups had the poorest (p < 0.05) average daily feed intake (ADFI), final live weight (FLW), average daily weight gain (ADWG), and FCR compared to those in the control and the REP0.4 groups. There was no difference in the mortality recorded across the treatment groups. There were no significant (p > 0.05) differences in white blood cell, red blood cell, heamoglobin, lymphocyte, heterophils, H/L ratio, platelets, mean corpuscular volume, mean corpuscular heamoglobin concentration, and mean corpuscular heamoglobin values across the dietary groups. There was a significant (p < 0.05) decrease in packed cell volume (PCV) of birds fed REPY0 and REPY0.2 diets. However, this decrease in values was improved in the REPY0.4 group. There was a decrease (p < 0.05) in the total protein, globulin, and glucose values of birds in the REPY0 and REPY0.2 groups compared to the control group. However, an improvement was noticed when 0.40% baker's yeast was added to the REP diet. It was concluded that the addition of 0.40% baker's yeast could ameliorate the decrease observed in performance as well as PCV, serum total protein, globulin, and glucose values of finisher broiler chickens fed REP diet. [ABSTRACT FROM AUTHOR]

Dog leukocyte antigen (DLA) polymorphisms have been found to be associated with inter-individual variations in the risk, susceptibility, and severity of immune-related phenomena. While DLA class II genes have been extensively studied, less research has been performed on the polymorphisms of DLA class I genes, especially in beagle dogs commonly used as laboratory animals for safety evaluations in drug development. We genotyped four DLA class I genes and four DLA class II genes by locus-specific Sanger sequencing using 93 laboratory beagle dogs derived from two different strains: TOYO and Marshall. The results showed that, for DLA class I genes, 11, 4, 1, and 2 alleles, including a novel allele, were detected in DLA-88, DLA-12/88L, DLA-64, and DLA-79, while, for DLA class II genes, 1, 10, 6, and 7 alleles were detected in DLA-DRA, DLA-DRB1, DLA-DQA1, and DLA-DQB1, respectively. It was estimated that there were 14 DLA haplotypes, six of which had a frequency of ≥ 5%. Furthermore, when comparing the DLA diversity between TOYO and Marshall strains, the most common alleles and haplotypes differed between them. This is the first study to genotype all DLA loci and determine DLA haplotypes including all DLA class I and class II genes in dogs. Integrating information on the DLA diversity of laboratory beagle dogs should reinforce their benefit as an animal model for understanding various diseases associated with a specific DLA type. [ABSTRACT FROM AUTHOR]

Background Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. Objectives To understand optimal initial treatment of candidaemia. Methods We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. Results A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P  = 0.87; immunocompromised: 57% versus 59%, P  = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P  = 0.002) and time to antifungal (P  = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P  < 0.001) and Candida isolated from a non-blood site (P  = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P  = 0.003) and Candida isolated from a non-blood site (P  = 0.026) were associated with not meeting the primary outcome. Conclusions These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes. [ABSTRACT FROM AUTHOR]

Aims: To examine whether nursing diagnoses were associated with delirium in patients with sepsis. Background: Nursing diagnosis is a nurse's clinical judgement about clients' current or potential health conditions. Delirium is regarded as an important nurse‐sensitive outcome. Nonetheless, nursing diagnoses associated with delirium have not yet been identified. Design: Retrospective correlational study. Methods: This study was carried out from December 2021 to January 2023. We analysed electronic health records of patients with sepsis admitted to the intensive care units (ICUs) of a tertiary hospital in Seoul, South Korea. Delirium was defined based on the Intensive Care Delirium Screening Checklist score. Nursing diagnoses established within 24 h of admission to the ICU were included and were based on the North American Nursing Diagnosis Association diagnostic classification. The data were analysed using logistic regression. Demographics, comorbidities, procedures and physiological measures were adjusted. Regression model was evaluated via receiver operating characteristic curve, Nagelkerke R2, accuracy and F1 score. Results: The prevalence of delirium in patients with sepsis was 51.8%. Ineffective breathing patterns, decreased cardiac output and impaired skin integrity were significant nursing diagnoses related to delirium. Age ≥ 65 years, Acute Physiology and Chronic Health Evaluation II score, mechanical ventilation, continuous renal replacement therapy, physical restraint and comatose state were also associated with delirium in patients with sepsis. The area under the receiver operating characteristic curve was 0.806. Conclusion: Ineffective breathing patterns, decreased cardiac output and impaired skin integrity could manifest as prodromal symptoms of delirium among patients with sepsis. Impact: The prodromal symptoms of delirium revealed through nursing diagnoses can be efficiently used to identify high‐risk groups for delirium. The use of nursing diagnosis system should be recommended in clinical practice caring for sepsis patients. Reporting Methods: STROBE checklist. Patient or Public Contribution: No patient or public involvement. [ABSTRACT FROM AUTHOR]

Qualitative urinalysis using the Sternheimer stain is a common method in Japan for identifying bacteriuria, but there is a lack of studies examining its test characteristics. In this study, we aimed to investigate the sensitivity and specificity of the Sternheimer stain for urine culture results and compare it with the sensitivity and specificity of the Gram stain. Our goal was to determine the usefulness of the Sternheimer stain in identifying bacteriuria. Among 986 patients aged 16 years or older from whom samples for both urinalysis and urine culture were obtained at the emergency room of Tenri Hospital from January 2019 to December 2019, 342 patients with pyuria, defined as the presence of 10 or more white cells per cubic millimeter in a urine specimen, who had not received prior antimicrobial therapy were included. Urine cultures were used for comparison to determine the sensitivity and specificity of Sternheimer and Gram stain in this patient group. A positive Sternheimer stain result was defined as bacteriuria ≥ (1+), and that of Gram stain was defined as ≥ 1/1 field of high-power (× 1000) oil immersion. Using urine culture results for comparison, the sensitivity of Sternheimer stain was 92.2%, the specificity was 48.5%, the positive likelihood ratio was 1.79, and the negative likelihood ratio was 0.16. Sternheimer stain is a rapid and useful method to exclude bacteriuria in a group of patients with pyuria in the emergency department. [ABSTRACT FROM AUTHOR]

This article discusses the use of dupilumab, a biologic medication, for the treatment of atopic dermatitis (AD) in pediatric and young adult patients with inborn errors of immunity (IEIs). The medication has been approved for use in children with moderate to severe AD who have inadequate control with topical therapies. The article presents case studies of patients with IEIs and AD who were treated with dupilumab, showing significant clinical improvement as early as week 4 of treatment. However, further studies are needed to evaluate the long-term safety and efficacy of dupilumab in this patient population. [Extracted from the article]

Background: Asthma is a chronic inflammatory condition characterized by episodes of acute asthma exacerbations (AAEs), in addition to chronic airway inflammation, which has a huge impact on both the affected patients and their parents. The main objective of this study was to explore the utility of available white-blood-cell-derived inflammatory markers in diagnosing AAEs and identifying children at risk for severe exacerbations requiring admission to the pediatric intensive care unit (PICU). Methods: This study was a retrospective cohort study. The medical records of 128 children diagnosed with asthma exacerbation and 131 children with stable asthma between the ages of 2 and 12 years were reviewed. Results: A total of 259 participants were enrolled. Children with AAE demonstrated significantly higher white blood cell counts (WBC: 10.0 ± 4.2 × 103/μL vs. 7.1 ± 2.2 × 103/μL, p < 0.001), absolute neutrophil counts (ANC: 7398.5 ± 4600 cells/μL vs. 2634.8 ± 1448 cells/μL, p < 0.001), and neutrophil-to-lymphocyte ratios (NLR: 7.0 ± 6.8 vs. 0.9 ± 0.7, p < 0.001) but significantly lower absolute lymphocyte counts (ALC: 1794.1 ± 1536 × 103/μL vs. 3552.9 ± 1509 × 103/μL, p < 0.001). Interestingly, blood eosinophil count displayed an opposite trend: children with stable asthma had significantly more eosinophils compared to those experiencing an exacerbation (370.1 ± 342.7 cells/mm3 vs. 0.9 ± 1.9 cells/mm3, p < 0.001). Two criteria that are indicative of AAE were identified: NLR values greater than 1.2, with good discriminative ability (area under the curve [AUC] 0.90; 95% confidence interval [CI] 0.85–0.94; sensitivity 82.5%; specificity 79.5%), and ANC values exceeding 3866, with moderate discriminative ability (AUC 0.86; 95% CI 0.81–0.91; sensitivity 75.0%; specificity 82.3%). Moreover, a comparative analysis of these markers (NLR, ANC, PLR, WBC, AEC, and ALC) in patients with AAE did not demonstrate significant differences between those requiring PICU admission and those who did not require it. Conclusions: This study contributes two major findings. The first is that NLR, ANC, WBC, and PLR are significantly higher in AAE patients compared to those with stable asthma. The second is that children with stable asthma have higher AEC and ALC levels compared to those with AAE. Furthermore, this study has revealed that the studied markers (NLR, ANC, PLR, WBC, AEC, and ALC) did not differentiate between AAE patients requiring PICU admission and those managed in the general ward, suggesting a need for alternative predictive factors. [ABSTRACT FROM AUTHOR]

Background: The inhalation of paraquat (PQ), one of the most widely used herbicides in the world, can result in lung injury. Curcuma longa (Cl) has long history in traditional and folk medicine for the treatment of a wide range of disorders including respiratory diseases. Aim: The aim of the present work was to evaluate the preventive effect of Cl on inhaled PQ‐induced lung injury in rats. Methods: Male Wistar rats were divided into 8 groups (n = 7), one group exposed to saline (control) and other groups exposed to PQ aerosol. Saline (PQ), Cl extract, (two doses), curcumin (Cu), pioglitazone (Pio), and the combination of Cl‐L + Pio and dexamethasone (Dex) were administered during the exposure period to PQ. Total and differential white blood cell (WBC) counts, oxidant and antioxidant indicators in the bronchoalveolar lavage (BALF), interleukin (IL)‐10, and tumor necrosis alpha (TNF‐α) levels in the lung tissues, lung histologic lesions score, and air way responsiveness to methacholine were evaluated. Results: WBC counts (Total and differential), malondialdehyde level, tracheal responsiveness (TR), IL‐10, TNF‐α and histopathological changes of the lung were markedly elevated but total thiol content and the activities of catalase and superoxide dismutase were decreased in the BALF in the PQ group. Both doses of Cl, Cu, Pio, Cl‐L + Pio, and Dex markedly improved all measured variables in comparison with the PQ group. Conclusion: CI, Pio, and Cl‐L + Pio improved PQ‐induced lung inflammation and oxidative damage comparable with the effects of Dex. [ABSTRACT FROM AUTHOR]

Background: Mecapegfilgrastim, a long‐acting granulocyte‐colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. Objective: We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S‐1/capecitabine‐based regimens or the fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Method: Five hundred and sixty‐one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. Results: The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S‐1/capecitabine‐based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S‐1/capecitabine‐based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. Conclusion: In a real‐world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high‐risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

The diagnosis of multiple myeloma requires detection of paraproteinemia and confirmation of monoclonal bone marrow infiltration, along with signs of end-organ damage. Despite the increasing prevalence, serum paraproteinemia is not routinely measured. We examined the relationship between alterations in routine hematological parameters and the development of paraproteinemia in a case-control study. Data was retrieved from a laboratory database in the capital region of Denmark between 01/01/2012 and 31/12/2022. Patients were included if they had a test for paraproteinemia (n = 134,740) and at least one prior hematological parameter (white blood cells, hemoglobin and platelet count) with a minimum follow-up of 1 year. Between 96,999 and 103,590 patients were included in each of the three hematological groups. We found white blood cell count and the presence of paraproteinemia followed an inverse J-shaped curve, with the highest presence below 3 × 109/L and above > 9 × 109/L. The adjusted OR below and above the nadir of 4 × 109/L was 1.61 (95% CI 1.25; 2.08, p < 0.0001) and 1.03 (95% CI 1.03; 1.04, p < 0.0001). Hemoglobin levels were inversely associated the presence of paraproteinemia, with the highest association below 6 mmol/L with an OR of 1.30 (95% CI 1.28; 1.32, p < 0.0001) adjusted for age and gender. Platelet count followed a U-shaped curve with the highest association at < 100 × 109/L. The adjusted OR below and above the nadir of 250 × 109/L was 1.13 (95% CI 1.10; 1.17, p < 0.0001) and 1.10 (95% CI 1.08; 1.12, p < 0.0001) respectively. In conclusion, all three parameters showed significant association with later paraproteinemia. [ABSTRACT FROM AUTHOR]

Background and Objective: Thioguanine (TG), azathioprine (AZA), and mercaptopurine (MP) are thiopurine prodrugs commonly used to treat diseases, such as leukemia and inflammatory bowel disease (IBD). 6-thioguanine nucleotides (6-TGNs) have been commonly used for monitoring treatment. High levels of 6-TGNs in red blood cells (RBCs) have been associated with leukopenia, the cutoff levels that predict this side effect remain uncertain. Thiopurines are metabolized and incorporated into leukocyte DNA. Measuring levels of DNA-incorporated thioguanine (DNA-TG) may be a more suitable method for predicting clinical response and toxicities such as leukopenia. Unfortunately, most methodologies to assay 6-TGNs are unable to identify the impact of NUDT15 variants, effecting mostly ethnic populations (e.g., Chinese, Indian, Malay, Japanese, and Hispanics). DNA-TG tackles this problem by directly measuring thioguanine in the DNA, which can be influenced by both TPMT and NUDT15 variants. While RBC 6-TGN concentrations have traditionally been used to optimize thiopurine therapy due to their ease and affordability of measurement, recent developments in liquid chromatography–tandem mass spectrometry (LC–MS/MS) techniques have made measuring DNA-TG concentrations in lymphocytes accurate, reproducible, and affordable. The objective of this systematic review was to assess the current evidence of DNA-TG levels as marker for thiopurine therapy, especially with regards to NUDT15 variants. Methods: A systematic review and meta-analysis were performed on the current evidence for DNA-TG as a marker for monitoring thiopurine therapy, including methods for measurement and the illustrative relationship between DNA-TG and various gene variants (such as TPMT, NUDT15, ITPA, NT5C2, and MRP4). PubMed and Embase were systematically searched up to April 2024 for published studies, using the keyword "DNA-TG" with MeSH terms and synonyms. The electronic search strategy was augmented by a manual examination of references cited in articles, recent reviews, editorials, and meta-analyses. A meta-analysis was performed using R studio 4.1.3. to investigate the difference between the coefficients (Fisher's z-transformed correlation coefficient) of DNA-TG and 6-TGNs levels. A meta-analysis was performed using RevMan version 5.4 to investigate the difference in DNA-TG levels between patients with or without leukopenia using randomized effect size model. The risk of bias was assessed using the Newcastle–Ottowa quality assessment scale. Results: In this systematic review, 21 studies were included that measured DNA-TG levels in white blood cells for either patients with ALL (n = 16) or IBD (n = 5). In our meta-analysis, the overall mean difference between patients with leukopenia (ALL + IBD) versus no leukopenia was 134.15 fmol TG/µg DNA [95% confidence interval (CI) (83.78–184.35), P < 0.00001; heterogeneity chi squared of 5.62, I2 of 47%]. There was a significant difference in DNA-TG levels for patients with IBD with and without leukopenia [161.76 fmol TG/µg DNA; 95% CI (126.23–197.29), P < 0.00001; heterogeneity chi squared of 0.20, I2 of 0%]. No significant difference was found in DNA-TG level between patients with ALL with or without leukopenia (57.71 fmol TG/µg DNA [95% CI (− 22.93 to 138.35), P < 0.80]). DNA-TG monitoring was found to be a promising method for predicting relapse rates in patients with ALL, and DNA-TG levels are likely a better predictor for leukopenia in patients with IBD than RBC 6-TGNs levels. DNA-TG levels have been shown to correlate with various gene variants (TPMT, NUDT15, ITPA, and MRP4) in various studies, points to its potential as a more informative marker for guiding thiopurine therapy across diverse genetic backgrounds. Conclusions: This systematic review strongly supports the further investigation of DNA-TG as a marker for monitoring thiopurine therapy. Its correlation with treatment outcomes, such as relapse-free survival in ALL and the risk of leukopenia in IBD, underscores its role in enhancing personalized treatment approaches. DNA-TG effectively identifies NUDT15 variants and predicts late leukopenia in patients with IBD, regardless of their NUDT15 variant status. The recommended threshold for late leukopenia prediction in patients with IBD with DNA-TG is suggested to be between 320 and 340 fmol/µg DNA. More clinical research on DNA-TG implementation is mandatory to improve patient care and to improve inclusivity in thiopurine treatment. [ABSTRACT FROM AUTHOR]

This article discusses a rare case of meningitis caused by Moraxella osloensis, a bacterium that is difficult to identify due to its similarities to other species. The patient initially presented with symptoms of headache, fever, and cranial nerve injury, leading to a diagnosis of viral meningitis. However, antiviral therapy did not improve the patient's condition, and conventional diagnostic methods were inconclusive. The use of metagenomic next-generation sequencing (mNGS) allowed for the accurate identification of the pathogen and guided appropriate antibiotic treatment. The patient ultimately recovered. The article emphasizes the importance of mNGS in cases where traditional diagnostic methods are ineffective and highlights the need for further research on susceptible groups for M. osloensis infection. [Extracted from the article]

Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, which promotes a sustained inflammatory environment in the central nervous system. Regulatory T cells (Tregs) play an important role in the control of inflammation and might play a neuroprotective role. Indeed, a decrease in Treg number and function has been reported in PD. In this context, pramipexole, a dopaminergic receptor agonist used to treat PD symptoms, has been shown to increase peripheral levels of Treg cells and improve their suppressive function. The aim of this work was to determine the effect of pramipexole on immunoregulatory Treg cells and its possible neuroprotective effect on human dopaminergic neurons differentiated from human embryonic stem cells. Methods: Treg cells were sorted from white blood cells of healthy human donors. Assays were performed with CD3/CD28‐activated and non‐activated Treg cells treated with pramipexole at concentrations of 2 or 200 ng/mL. These regulatory cells were co‐cultured with in vitro‐differentiated human dopaminergic neurons in a cytotoxicity assay with 6‐hydroxydopamine (6‐OHDA). The role of interleukin‐10 (IL‐10) was investigated by co‐culturing activated IL‐10‐producing Treg cells with neurons. To further investigate the effect of treatment on Tregs, gene expression in pramipexole‐treated, CD3/CD28‐activated Treg cells was determined by Fluidigm analysis. Results: Pramipexole‐treated CD3/CD28‐activated Treg cells showed significant protective effects on dopaminergic neurons when challenged with 6‐OHDA. Pramipexole‐treated activated Treg cells showed neuroprotective capacity through mechanisms involving IL‐10 release and the activation of genes associated with regulation and neuroprotection. Conclusion: Anti‐CD3/CD28‐activated Treg cells protect dopaminergic neurons against 6‐OHDA‐induced damage. In addition, activated, IL‐10‐producing, pramipexole‐treated Tregs also induced a neuroprotective effect, and the supernatants of these co‐cultures promoted axonal growth. Pramipexole‐treated, activated Tregs altered their gene expression in a concentration‐dependent manner, and enhanced TGFβ‐related dopamine receptor regulation and immune‐related pathways. These findings open new perspectives for the development of immunomodulatory therapies for the treatment of PD. [ABSTRACT FROM AUTHOR]

Introduction: Nuclear medicine infection imaging is routinely performed with the use of leukocytes radiolabelled with technetium-99m hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO) and single-photon emission computed tomography (SPECT). Positron emission tomography (PET) is more sensitive than SPECT and results in higher-quality images. Zirconium-89 (89Zr) is a positron emitter with a half-life of 78.4 h, which translates to the biological half-life and slow biodistribution of intact cells and allows delayed PET imaging for more accurate biodistribution of the labelled leukocytes to infection foci. A first-in-human study with [89Zr]Zr-oxine-leukocytes in four healthy volunteers was reported in 2022. Our first-in-human study utilising the cell surface labelling approach aimed to image infection in patients with the use of 89Zr-labelled leukocytes, using p-isothiocyanatobenzyl-desferrioxamine B (Df-Bz-NCS) as a bifunctional chelating agent, and to compare the scan quality and biodistribution of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes on PET images to SPECT images obtained with [99mTc]Tc-HMPAO-labelled leukocytes. Methods: Leukocytes were isolated from whole-blood samples of eight patients with clinically and/or radiologically confirmed infection. Isolated leukocytes were labelled with [99mTc]Tc-HMPAO according to standardised methods, and [89Zr]Zr-Df-Bz-NCS according to our previously published radiolabelling method. Whole-body SPECT imaging was performed 2 and 18 h post injection of [99mTc]Tc-HMPAO-labelled leukocytes, and whole-body PET/CT was performed 3 and 24 h post injection of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in seven patients. Results: Successful [89Zr]Zr-Df-Bz-NCS-leukocyte labelling was achieved. High labelling efficiencies were obtained (81.7% ± 3.6%; n = 8). A mean high viability of [89Zr]Zr-Df-Bz-NCS-labelled leukocytes was observed (88.98% ± 12.51%). The [89Zr]Zr-Df-Bz-NCS-leukocyte labelling efficiency was not significantly affected by the white blood cell count of the patient. The performance of [99mTc]Tc-HMPAOand [89Zr]Zr-Df-Bz-NCS-labelled leukocytes, in terms of the ability to accurately detect infection, were similar in two out of seven patients, and [99mTc]Tc-HMPAOlabelled leukocytes outperformed [89Zr]Zr-Df-Bz-NCS-labelled leukocytes in one patient with femoral osteomyelitis. However, in two cases of pulmonary pathology, [89Zr]Zr-Df-Bz-NCS-labelled leukocytes demonstrated improved pathological uptake. No skeletal activity was observed in any of the patients imaged with [89Zr] Zr-Df-Bz-NCS-labelled leukocytes, illustrating the in vivo stability of the radiolabel. Discussion: Although the [89Zr]Zr-Df-Bz-NCS-leukocyte labelling aspect of this study was noteworthy, infection imaging did not yield convincingly positive results due to the pulmonary trapping of intravenously administered [89Zr]Zr-Df-Bz-NCS-labelled leukocytes. [ABSTRACT FROM AUTHOR]

Introduction: The independent diagnostic value of inflammatory markers neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) and the diagnostic efficacy of NLR, derived neutrophil to lymphocyte ratio (dNLR), PLR, and lymphocyte-to-monocyte ratio (LMR) in glioma cases remain unclear. We investigated the correlation of preoperative peripheral blood inflammatory markers with pathological grade, Ki-67 Proliferation Index, and IDH-1 gene phenotype in patients with glioma, focusing on tumor grade and prognosis. Methods: We retrospectively analyzed the clinical, pathological, and laboratory data of 334 patients with glioma with varying grades and 345 with World Health Organization (WHO I) meningioma who underwent initial surgery at the Affiliated Hospital of Jining Medical University from December 2019 to December 2021. The diagnostic value of peripheral blood inflammatory markers for glioma was investigated. Results: The proportion of men smoking and drinking was significantly higher in the glioma group than in the meningioma group (P <.05); in contrast, the age and body mass index (Kg/m2) were significantly lower in the glioma group (P =.01). Significant differences were noted in the pathological grade (WHO II, III, and IV), Ki-67 Proliferation Index, and peripheral blood inflammatory markers such as lymphocyte median, NLR, dNLR, and PLR between the groups (P <.05). No significant correlation existed between peripheral blood inflammatory factors and IDH-1 gene mutation status or tumor location in patients with glioma (P >.05). LMR, NLR, dNLR, and PLR, varied significantly among different glioma types (P <.05). White blood cell (WBC) count, neutrophil, NLR, and dNLR correlated positively with glioma risk. Further, WBC, neutrophil, NLR, dNLR, and LMR had a high diagnostic efficiency. Conclusion: Peripheral blood inflammatory markers, serving as noninvasive biomarkers, offer high sensitivity and specificity for diagnosing glioma, differentiating it from meningioma, diagnosing GBM, and distinguishing GBM from low-grade glioma. These markers may be implemented as routine screening tools. [ABSTRACT FROM AUTHOR]

A major health outbreak in March 2024 with renal impairments occurred by ingested food supplements made from beni-koji (red yeast rice) in Japan, which has been considered as major health issue. A troponoid compound puberulic acid (PA) that was produced by contaminated Penicillium spp. is attracting attention as a causative agent of this health disaster occurred by beni-koji (red yeast rice). Regarding toxicity, it was reported that PA showed weak cytotoxicity against fetal human lung fibroblastlike MRC-5 cells with an IC50 value of about 289 µM (Iwatsuki et al., 2011). However, understandings about the physiological effects of PA against human tissues and cells still remain poor and insufficiently studied. Therefore, in this study, we investigated the effect of PA on the viability and the all-trans retinoic acid (ATRA)-induced superoxide anion (O2 -)-generating ability of human leukemia U937 cells. PA remarkably showed a strong cytotoxicity accompanied by apoptosis, which was enhanced by ATRA. Furthermore, PA dramatically down-regulated the ATRA-induced O2 --generating activity in a dose-dependent manner. Quantitative RT-PCR and immunoblot analyses showed that PA significantly reduces the ATRAinduced O2 --generating activity via down-regulating gene expression levels of gp91-phox, which is an essential factor for the O2 --generating activity of leukocytes. These findings revealed that PA has not only the strong ATRA-enhancible cytotoxic effect but also the drastic reducing effect on the ATRA-induced O2 --generating activity through down-regulating transcription of gp91-phox gene. We expect that our findings will contribute to resolve the large-scale health disaster caused by beni-koji (red yeast rice). [ABSTRACT FROM AUTHOR]

Background and Aims: Blood, vital for transporting nutrients and maintaining balance, comprises red blood cells, white blood cells, and platelets, each pivotal. Imbalances lead to issues—low red cells cause fatigue (anemia), high white cells hint at infection, low counts raise infection risks. Using trendy statistical approaches, investigating the complex link between platelet counts and numerous blood components. Our investigation, leveraging count regression approaches, revealed deep insights into the interaction between platelet counts and other important hematological markers. Methods: A cross‐sectional study utilized data from 3120 individuals, including both male and female participants, who visited these hospitals between June 16, 2022 and December 17, 2022, to assess their blood samples through testing by using convenience non‐parametric sampling framework. Platelet count was taken into account as a measure of outcome in this research. This specific study region was chosen for its easy accessibility, which helped the seamless execution of the data‐gathering technique. Count regression, negative binomial regression, and quasi‐Poisson regression techniques have been employed for examining relationship of the data sets. Results: Three different count regression models were utilized to assess the proper association between the response and the relevant covariates and we found negative binomial count regression model (Akaike information criterion = 76.55, Bayesian information criterion = 76.59, and deviance = 3.14) was providing comparatively better performance than others. Based on the chosen model we found white blood cell, erythrocyte sedimentation rate, and eosinophils are significant but neutrophil, monocyte, and lymphocyte are not significant. We have also gone through proper model adequacy checking for our selected model and we found enough evidence to justify our model. Conclusion: From the result, we found insightful remarks into the mechanisms involved in platelet production and regulation, which can aid in developing increased effective treatments and interventions to maintain optimal platelet levels and prevent health problems related to abnormal platelet counts. [ABSTRACT FROM AUTHOR]

This study determines the effects of probiotics - Saccharomyces cerevisiae on oocysts shedding, haematology and serum proteins of broilers infected with mixed Eimeria oocysts. 120-day-old broiler chicks were randomly assigned to four groups (Groups A - D) of 30 birds each. Group A - was fed a plain diet and not infected, Group B - was fed a supplemented diet and infected, Group C - was fed a plain diet and infected, and Group D - was fed a supplemented diet and not infected. S. cerevisiae was supplemented at 0.1 %/kg of feed. At week 3, Groups B and C were infected with sporulated mixed Eimeria oocysts orally, followed by a daily faecal examination of all groups. The rate of oocyst shedding, packed cell volume (PCV), haemoglobin concentration (Hb), red blood cell (RBC) count, total white blood cell (WBC) count, differential WBC count and serum levels of total protein, albumin and globulin were determined at five days' intervals. The data collected were analyzed using a one-way analysis of variance at a 95% confidence interval (p<0.05). Group C had the significantly higher (p<0.05) number of oocysts in faeces, total WBC count and globulin levels, with the lowest PCV, Hb, RBC count, total protein and albumin levels. Group D had significantly higher (p<0.05) heterophil, eosinophil and monocyte counts. In conclusion, dietary supplementation with S. cerevisiae (1 g/kg) ameliorated the effect of Eimeria infection in broilers, by reducing the rate of oocyst shedding, anaemia and hypoproteinaemia due to the activity of the parasite. [ABSTRACT FROM AUTHOR]

Purpose: We investigated the Epidemiology, risk factors and outcomes of Candida bloodstream infection. Methods: The electronic laboratory records data of patients with candidemia (2015– 2022) were collected. We used univariate and multivariate logistic regression to determine the risk factors of candidemia. Results: Of the 134 patients with candidemia, the most prevalent species were Candida albicans (37.2%), followed by Candida glabrata (27.7%), Candida parapsilosis (18.9%), and others. The mean annual incidence was 0.33/1000 admissions. The overall resistance rate of Candida spp. against fluconazole and voriconazole were 4.9% (7/142) and 5.9% (6/101), while Candida tropicalis showed high resistance to fluconazole (38.8%) and voriconazole (27.8%). The 30-day mortality rate was 32.8%. On multivariate analysis, age ≥ 65 (odds ratio [OR] = 3.874, 95% confidence interval [CI]: 1.146, 13.092; P = 0.029), high Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR = 12.384, 95% CI: 2.963, 51.762; P = 0.001), shock (OR = 3.428, 95% CI: 1.097, 10.719; P = 0.034), initial antifungal therapy (OR = 0.057, 95% CI: 0.011, 0.306; P = 0.001) and White blood cells (OR = 1.129, 95% CI: 1.016, 1.255; P = 0.024) were the independent risk factors with mortality within 30 day in patients with candidemia. Conclusion: The incidence rate and the mortality rate of candidemia are high, and lower azole susceptibility was found in Candida tropicalis. Age≥ 65 years, Shock, high APACHE II score, Antifungal therapy and White blood cells count were independently associated with 30-day mortality. [ABSTRACT FROM AUTHOR]

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Objective: Trauma is a leading cause of morbidity and mortality in children. One in every four patients with trauma has abdominal trauma. Abdominal trauma is the third leading cause of death associated with trauma. Mortality increases in patients with inflammation because of the body's reaction to trauma. The systemic immune-inflammation index (SIII) is a test indicative of body inflammation based on complete blood count alone. Index value may indicate prognosis of pediatric patients with blunt abdominal trauma. Materials and Methods: The present study was designed as a retrospective, single-center research. The study included pediatric patients with isolated blunt abdominal trauma who were admitted to the emergency department between June 01, 2021 and June 01, 2022 and met the inclusion criteria. Patient demographic data; medical history; leukocytes, platelet, and neutrophil count; SIII; and outcome status were captured in the case form. Results: The study included 103 patients, of whom 64.1% were male and the mean age was 7.32±5.12 years. Mortality was noted in 6.8% of the patients included in the study. The sensitivity and specificity for a cut-off value of 890.47×103/L SIII were 95.7% and 62.5%, respectively (area under the curve: 0.832; 95% confidence interval: 0.820-0.944, p<0.003), in pediatric patients with blunt abdominal trauma. Conclusion: High SIII scores, a rapid, inexpensive, reliable, and radiation-free test, could be used as a predictor of mortality in pediatric patients admitted to the emergency department with blunt abdominal trauma. [ABSTRACT FROM AUTHOR]

The origins and evolution of the eosinophilic leukocyte have received only scattered attention since Paul Ehrlich first named this granulocyte. Studies suggest that myeloperoxidase, expressed by granulocytes, and eosinophil peroxidase diverged some 60 to 70 million years ago, but invertebrate to vertebrate evolution of the eosinophil lineage is unknown. Vertebrate eosinophils have been characterized extensively in representative species at light microscopic, ultrastructural, genetic, and biochemical levels. Understanding of eosinophil function continues to expand and includes to date regulation of "Local Immunity And/Or Remodeling/Repair" (the so-called LIAR hypothesis), modulation of innate and adaptive immune responses, maintenance of tissue and metabolic homeostasis, and, under pathologic conditions, inducers of tissue damage, repair, remodeling, and fibrosis. This contrasts with their classically considered primary roles in host defense against parasites and other pathogens, as well as involvement in T-helper 2 inflammatory and immune responses. The eosinophils' early appearance during evolution and continued retention within the innate immune system across taxa illustrate their importance during evolutionary biology. However, successful pregnancies in eosinophil-depleted humans/primates treated with biologics, host immune responses to parasites in eosinophil-deficient mice, and the absence of significant developmental or functional abnormalities in eosinophil-deficient mouse strains under laboratory conditions raise questions of the continuing selective advantages of the eosinophil lineage in mammals and humans. The objectives of this review are to provide an overview on evolutionary origins of eosinophils across the animal kingdom, discuss some of their main functions in the context of potential evolutionary relevance, and highlight the need for further research on eosinophil functions and functional evolution. [ABSTRACT FROM AUTHOR]

This study investigated how Rhus toxicodendron (RT) (6C, 30C, and 200C) can boost the immune system of BALB/c mice that were given cyclophosphamide (CPM), which is an anticancer drug that weakens the immune system. RT, known for its historical use in traditional homeopathic remedies, has demonstrated immunomodulatory and anti-inflammatory effects in various experimental models. To test the immune-boosting effects of RT, CPM (80 mg/kg) was given intraperitoneally to mice on days 4, 8, and 12 of the study but not to the normal control group. CPM-induced immunosuppression led to significant decreases in red blood cell (RBC), white blood cell (WBC), and hemoglobin (Hb) levels, and reduced spleen and thymus indices. Phagocytic activity, cytokine concentrations, and spleen architecture were also adversely affected. RT treatment, particularly at 200C, significantly ameliorated these effects, improving RBC, WBC, and Hb levels. Furthermore, RT partially prevented CPM-induced atrophy of immune organs. Treatment positively influenced cytokine production at both the protein and mRNA levels, restoring immune balance. Histopathological results confirmed that RT stimulated the immune system. The cells were more stable, and the white pulp in the spleen was arranged in a regular pattern. These findings suggest that RT may serve as an adjunctive immunostimulant therapy for conditions characterized by immunosuppression. However, further investigations in other immunocompromised states must validate these results before considering human clinical trials. [ABSTRACT FROM AUTHOR]

The Aedes aegypti mosquito is a vector of many infectious agents, including flaviviruses such as Zika virus. Components of mosquito saliva have pleomorphic effects on the vertebrate host to enhance blood feeding, and these changes also create a favorable niche for pathogen replication and dissemination. Here, we demonstrate that human CD47, which is known to be involved in various immune processes, interacts with a 34-kilodalton mosquito salivary protein named Nest1. Nest1 is up-regulated in blood-fed female A. aegypti and facilitates Zika virus dissemination in human skin explants. Nest1 has a stronger affinity for CD47 than its natural ligand, signal regulatory protein α, competing for binding at the same interface. The interaction between Nest1 with CD47 suppresses phagocytosis by human macrophages and inhibits proinflammatory responses by white blood cells, thereby suppressing antiviral responses in the skin. This interaction elucidates how an arthropod protein alters the human response to promote arbovirus infectivity. Editor's summary: Aedes aegypti mosquitos can transmit arboviruses during blood feeding, and components of mosquito saliva may enhance both blood feeding and virus transmission. Marin-Lopez et al. identified a 34-kDa mosquito salivary protein called Nest1, highly expressed in the saliva of female A. aegypti mosquitos, as a high-affinity binder to human CD47. In human skin explants infected with Zika virus, Nest1 increased virus burden and inhibited some CD47-governed immune functions like phagocytosis and proinflammatory responses in immune cells, thus inhibiting antiviral responses. These findings provide insight into how mosquito salivary proteins can potentially facilitate arbovirus infection. —Christiana Fogg [ABSTRACT FROM AUTHOR]

Peri-implantitis (PI) is a current concern whose understanding and resolution are ongoing. We aimed to evaluate in vivo a new treatment with antibacterial properties, based on bacterial lysates obtained from the strains of Aggregatibacter actinomycetemcomitans, Streptococcus oralis, and Fusobacterium nucleatum. This research was conducted on 30 rats with PI which were divided into three groups and treated with antibiotic and anti-inflammatory (AAi) drugs, bacterial lysates (BLs), and saline (C), respectively. The monitoring period included the clinical and paraclinical examination where hematological, immunological, imaging, and histopathological analysis were performed. No particular clinical signs were observed, but the radiological examination showed the loss of all implants in group C, in contrast to group BL which had the highest survival rate of devices. White cells showed a decrease from the PI period, as did the immunological analysis. Only IL-6 showed an increase in the AAi and BL groups. Histopathologically, the C group presented a high degree of bone destruction, and in the BL group, many attenuated inflammatory phenomena appeared compared to the AAi animals. Bacterial lysates have similar effects to antibiotic-based therapeutic regimens for PI, and their future use may help to improve the current therapeutic management of the disease. [ABSTRACT FROM AUTHOR]

Purpose: The main aim of this study was to compare and analyze hematological profiles using menstrual blood, as an alternative to peripheral blood. Patients and Methods: This study used menstrual and peripheral blood samples from women who were menstruating. The design of this research is analytical observational. Results: Menstrual blood can show an overall hematological profile similar to peripheral blood. Data shows the detection of blood component parameters, white blood cells and reticulocytes in MB with a range within and outside normal blood. Data on MB that show higher values (WBC, MCH, MCHC, PLT, RDW-CV, PDW, MPV, P-LCR, PCT, neutrophils, lymphocytes, monocytes, basophils, reticulocytes, LFR, Ret-He) and lower values lower (RBC, HGB, HCT, MVC, RDW-SD, Eosinophils, IRF, MFR, HFR) when compared with peripheral blood controls. The hematological profiles of Menstrual and peripheral blood showed significant differences (p < 0.01) for several parameters, while several other parameters did not show significant differences (p > 0.05) according to the Wilcoxon test. Conclusion: All hematological profile parameters were detected in menstrual blood. The new concept that menstrual blood can be used as a supporting medium for hematological examinations opens up opportunities for developing independent hematological detection tools in productive women. [ABSTRACT FROM AUTHOR]

Insufficient sleep duration may lead to a series of immune dysfunctions. One of the factors influencing this effect could be physical activity (PA). The study aimed to assess the impact of deprivation of sleep (DS) on selected inflammatory parameters. Seventy-seven participants completed the protocol consisting of polysomnography (PSG) conducted in a sleep laboratory and DS, monitored with an actigraph. PA was assessed with actigraphy, which categorized participants as active or inactive. White blood cells (WBC) values negatively correlated with sleep efficiency based on sleep diaries and PSG parameters (total sleep time, sleep efficiency, and REM duration), but regression analysis showed that WBC depends only on the sleep diary parameter. Granulocytes (GRA) positively correlated with REM latency, and negatively with sleep efficiency. After DS, all participants exhibited an elevated GRA count. The number of WBC and GRA increased also in the active group; inactive participants showed no changes in inflammatory parameters. The overall number of WBC depends primarily on the quality of sleep over a period of several days. Under the influence of sleep deprivation, the number of GRA increases, but the number of leukocytes depends on the level of physical activity during DS. [ABSTRACT FROM AUTHOR]

A hemocytometer is a key piece of laboratory equipment typically used in diagnostic and immunology research laboratories to enumerate white blood cells. The accurate quantification of cell density is essential to ensure accurate numbers of cells are added to assays to generate valid data. Hence, learning to correctly use a hemocytometer is a critical skill for all undergraduate immunology students. However, this skill can be challenging to learn because of students’ unfamiliarity with correct cell identification, differentiating viable versus dead cells and mathematical proficiency in calculating cell density and viability. To address these issues, we developed an interactive computer simulation that replicated all aspects of a Neubauer‐style hemocytometer. This simulation was used to teach second‐year undergraduate immunology students before a face‐to‐face (F‐2‐F) laboratory exercise where these skills were applied. Using a mixed methods approach, student performance and feedback were collected on broad aspects of the intervention and its benefits to the F‐2‐F setting. The approach was found to be extremely successful with all measures indicating a significant impact of the virtual hemocytometer on student learning, understanding and confidence. We suggest that integrating an online simulation to teach students the fundamentals of hemocytometer use and calculations is a valuable educational aid for learning this important skill. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2‐high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate‐1 (INT1) patients, with scarce information on responses and outcome.The authors investigated the benefit of RUX in 1055 MF patients, included in the “RUX‐MF” retrospective study.At baseline (BL), 595 (56.2%) patients were at INT1‐risk according to DIPSS (PMF) or MYSEC‐PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9%, 47.4%, and 39.7% of patients, respectively; 300 (54.1%) were highly symptomatic (total symptom score ≥20). High‐molecular‐risk (HMR) mutations (IDH1/2, ASXL‐1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2%) patients had ≥1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG‐MRT–defined spleen and symptoms response rates were 26.8% and 67.9%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio [OR], 2.0, p = .05], no cytopenia (OR, 2.10; p = .01), and blasts <1% (OR, 1.91; p = .01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 [1.12–3.76]; p = .01).In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high‐risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less‐responsive INT1 patients, who may benefit for alternative therapeutic strategies. [ABSTRACT FROM AUTHOR]

The present study investigated the association between cerebrovascular diseases and sepsis, including its occurrence, progression, and impact on mortality. However, there is currently a lack of predictive models for 28-day mortality in patients with cerebrovascular disease associated with sepsis. The objective of this study is to examine the mortality rate within 28 days after discharge in this population, while concurrently developing a corresponding predictive model. The data for this retrospective cohort study were obtained from the MIMIC-IV database. Patients with sepsis and cerebrovascular disease in the ICU were included. Laboratory indicators, vital signs, and demographic data were collected within 24 hours of ICU admission. Mortality rates within 28 days after discharge were calculated based on patient death times. Logistic regression analysis was used to identify potential variables for a predictive model. A nomogram visualized the prediction model. The performance of the model was evaluated using ROC curves, Calibration plots, and DCA. The study enrolled a total of 2660 patients diagnosed with cerebrovascular disease complicated by sepsis, consisting of 1434 males (53.91%) with a median age of 70.97 (59.60, 80.73). Among this cohort of patients, a total of 751 fatalities occurred within 28 days following discharge. The multivariate regression analysis revealed that age, creatinine, arterial oxygen partial pressure (Pa O2), arterial carbon dioxide partial pressure (Pa CO2), respiratory rate, white blood cell (WBC) count, Body Mass Index (BMI), and race demonstrated potential predictive variables. The aforementioned model yielded an area under the ROC curve of 0.744, accompanied by a sensitivity of 66.2% and specificity of 71.2%. Furthermore, both calibration plots and DCA demonstrated robust performance in practical applications. The proposed prediction model allows clinicians to promptly assess the mortality risk in patients with cerebrovascular disease complicated by sepsis within 28 days after discharge, facilitating early intervention strategies. Consequently, clinicians can implement additional advantageous medical interventions for individuals with cerebrovascular disease and sepsis. [ABSTRACT FROM AUTHOR]

Sweet syndrome is an acute febrile neutrophilic dermatosis characterized by the infiltration of neutrophils into the skin. It may occur idiopathically or be linked to malignancies, inflammatory or autoimmune diseases. Leukocyte adhesion deficiency type I (LAD-I) is an inborn error immunity wherein leukocytes lack adhesion molecules necessary for migration to infection sites due to mutations in the CD18 gene encoding β2 integrins. We present a case of a 16-month-old female initially diagnosed and treated for Sweet syndrome based on histopathological findings with recurrent flare episodes. Subsequent workup revealed LAD-I, making this case the first documented association between Sweet syndrome and LAD-I. Moreover, we reviewed the pertinent literatures detailing the concurrence of neutrophilic dermatosis and immunodeficiency disorders. This case underscores the significance of comprehensive evaluation for Sweet syndrome patients who are refractory to conventional treatments. [ABSTRACT FROM AUTHOR]

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To develop and validate a diagnostic prediction model based on blood parameters for predicting the pertussis in children. A retrospective study of 477 children with suspected pertussis at Zigong First People's Hospital was performed between January 2020 and December 2021. The patients were randomly divided into training cohort and validation cohort. Stepwise regression and R software was performed to develop and validate the model. Stepwise regression analysis showed that white blood cell (WBC), hematocrit (HCT), lymphocyte (LYMPH), C-reactive protein (CRP) and platelet distribution width to mean platelet volume ratio (PDW-MPV-R) were found to be independent factors associated with pertussis. The model containing WBC, CRP and PDW-MPV-R had the best performance. The area under curve (ROC, 0.77 for the training cohort and 0.80 for the validation cohort) of the model indicated satisfactory discriminative ability. The sensitivity and specificity of the model were 72.1% and 72.6% in training cohort and 74% and 72.1%, respectively, in validation cohort. Based on the ROC analysis, calibration plots, and decision curve analysis, we concluded that the model exhibited excellent performance. A model based on blood parameters is sufficiently accurate to predict the probability of pertussis in children, and may provide some reference for clinical decisions. [ABSTRACT FROM AUTHOR]

Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a valuable experimental tool to study the immune state in health and following immune challenges such as infectious diseases, (auto)immune diseases, and cancer. Several tools have been developed to reconstruct B cell and T cell receptor sequences from AIRR-seq data and infer B and T cell clonal relationships. However, currently available tools offer limited parallelization across samples, scalability or portability to high-performance computing infrastructures. To address this need, we developed nf-core/airrflow, an end-to-end bulk and single-cell AIRR-seq processing workflow which integrates the Immcantation Framework following BCR and TCR sequencing data analysis best practices. The Immcantation Framework is a comprehensive toolset, which allows the processing of bulk and single-cell AIRR-seq data from raw read processing to clonal inference. nf-core/airrflow is written in Nextflow and is part of the nf-core project, which collects community contributed and curated Nextflow workflows for a wide variety of analysis tasks. We assessed the performance of nf-core/airrflow on simulated sequencing data with sequencing errors and show example results with real datasets. To demonstrate the applicability of nf-core/airrflow to the high-throughput processing of large AIRR-seq datasets, we validated and extended previously reported findings of convergent antibody responses to SARS-CoV-2 by analyzing 97 COVID-19 infected individuals and 99 healthy controls, including a mixture of bulk and single-cell sequencing datasets. Using this dataset, we extended the convergence findings to 20 additional subjects, highlighting the applicability of nf-core/airrflow to validate findings in small in-house cohorts with reanalysis of large publicly available AIRR datasets. Author summary: We have created nf-core/airrflow, a workflow to help researchers study the immune system in healthy and disease states, such as infections, autoimmunity, and cancer. The adaptive immune system is responsible for the third line of defense responses, specific to each particular threat, after physical barriers have been compromised and the nonspecific innate immune response has failed to clear the danger. Two types of white blood cells are central players in the adaptive response, namely B cells and T cells. These cells have surface receptors that recognize suspicious elements (antigens). Learning what receptors bind to which antigens is of utmost interest to understand immune responses. Adaptive Immune Receptor Repertoire sequencing (AIRR-seq) is a technique that allows to determine the genetic sequence of these receptors. The amount of data generated in these experiments is large, and the analysis complex. nf-core/airrflow simplifies running a comprehensive analysis connecting tools from Immcantation, a specialized software project to analyze AIRR-seq data. The workflow can efficiently process large datasets on multiple computing platforms. We analyzed immune responses to COVID-19 in 97 infected individuals and 99 healthy people, and confirmed previous findings and provided new insights, demonstrating the workflow's applicability to reanalyzing large publicly available datasets. [ABSTRACT FROM AUTHOR]

The first few days of life are characterized by rapid external and internal changes that require substantial immune system adaptations. Despite growing evidence of the impact of this period on lifelong immune health, this period remains largely uncharted. To identify factors that may impact the trajectory of immune development, we conducted stringently standardized, high‐throughput phenotyping of peripheral white blood cell (WBC) populations from 796 newborns across two distinct cohorts (The Gambia, West Africa; Papua New Guinea, Melanesia) in the framework of a Human Immunology Project Consortium (HIPC) study. Samples were collected twice from each newborn during the first week of life, first at Day of Life 0 (at birth) and then subsequently at Day of Life 1, 3, or 7 depending on the randomization group the newborn belongs to. The subsequent analysis was conducted at an unprecedented level of detail using flow cytometry and an unbiased automated gating algorithm. The results showed that WBC composition in peripheral blood changes along patterns highly conserved across populations and environments. Changes across days of life were most pronounced in the innate myeloid compartment. Breastfeeding, and at a smaller scale neonatal vaccination, were associated with changes in peripheral blood neutrophil and monocyte cell counts. Our results suggest a common trajectory of immune development in newborns and possible association with timing of breastfeeding initiation, which may contribute to immune‐mediated protection from infection in early life. These data begin to outline a specific window of opportunity for interventions that could deliberately direct WBC composition, and with that, immune trajectory and thus ontogeny in early life. This trial is registered with NCT03246230. [ABSTRACT FROM AUTHOR]