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The aim of the study is to identify and evaluate the general immunological reactivity of patients with COVID-19 and its relationship with gene polymorphism, severity of the clinical course of the disease and combination with comorbidities. A cohort study was conducted involving 204 patients with COVID-19 diagnosed with community-acquired pneumonia of mild, moderate, and severe degrees who also had comorbidities: endocrinopathies (46 patients), cardiovascular diseases (82 patients), and comorbidities of the ENT organs, connective tissue, gastrointestinal tract, chronic kidney disease (CKD), which were grouped into the group "other comorbidities (76 patients). Among the patients there were 51.97% (106) women and 48.03% (98) men. The average age of patients was 55.93±8.75 years. The polymorphism of the NOS3 (rs2070744), FGB (rs1800790) and TMPRSS2 (rs12329760) genes was determined by real-time polymerase chain reaction (qualitative determination). The overall immunological reactivity was detected and evaluated based on the analysis of 14 integral leukocyte indices: leukocyte shift index, absolute leukocyte count/erythrocyte sedimentation rate (ESR) ratio index, lymphocyte-granulocyte index, lymphocyte index, immunological resistance and reactivity index, and others. The overall immunological reactivity of the body of patients with coronavirus infection increases in the presence of the wild-type T-allele of the eNOS gene (rs2070744) in the patient's genotype, especially the CC genotype, by 21.98-57.89% (p≤0.029-0.001), against the background of a decrease in the index of nonspecific reactivity and the ratio of agranulocytes to ESR – by 23.0 (p=0.039) and 15.74% (p=0.044), indicating the onset of specific immunological reactions in the active infectious process. Carriers of the mutational A-allele of the FGB gene (rs1800790) and the TT genotype of the TMPRSS2 gene (rs12329760) showed higher immune reactivity and resistance, which was significantly confirmed by the level of increase in immune reactivity by 6.31-17.21% (p=0.007) and 22.05-35.78% (p≤0.06-0.004), respectively, against the background of a slightly higher rate of allergy (especially in owners of the AG genotype of the FGB gene – by 68.18%, PAG=0.017), a higher ratio of agranulocytes and ESR – by 18.30-21.84% (p≤0.008-0.007) and 19.46-31.07% (p=0.023), with a higher ratio of lymphocytes and eosinophils – by 13.35-19.20% (p≤0.002-0.001). The influence of the wild-type T-allele of the eNOS gene (rs2070744), the A-allele of the FGB gene (rs1800790) and the TT genotype of the TMPRSS2 gene (rs12329760) on the immunological reactivity of the body of a patient with coronavirus infection was revealed. [ABSTRACT FROM AUTHOR]

Inflammation and oxidative stress are 2 factors that play an important role in Chronic Kidney Disease (CKD). Controlling these 2 factors is expected to give better kidney functions outcomes. Statins have anti-inflammatory and antioxidative stress effects apart from their lipid-lowering effect. In this study, we want to analyze that statin might be one of a renoprotective agent through their pleiotropic effect as an anti-inflammation and anti-oxidative in CKD patients. This is a cross-sectional study that enrolled of 40 patients with CKD: 20 patients consumed statin and 20 patients did not consume statin. We compared HDL; inflammatory markers: high sensitive – C reactive protein (hsCRP), absolute neutrophil count, absolute leukocyte count, absolute eosinophil count, and neutrophil-lymphocyte ratio (NLR); and oxidative stress marker malondialdehyde (MDA) with kidney functions (GFR, cystatin c, BUN, albumin urine, and creatinine serum) between groups. Then we analyze the correlation between HDL, inflammatory markers, and oxidative marker with kidney functions. The results are HDL and MDA had a correlation with all the kidney function, hs-CRP correlated with GFR, cystatin c, and BUN, and NLR correlated with GFR, cystatin c, BUN, and creatinine serum. Statin group significantly have lower hs-CRP, NLR, and MDA. HDL, absolute neutrophil, leukocyte, and eosinophil count are lower in the statin group but not significantly. All the kidney function markers significantly have a better outcome in the statin group. This study concludes that lowering inflammation and oxidative stress levels using statin could be one of the strategy therapies in CKD to achieve better kidney function outcomes. Inflammation and oxidative stress are 2 factors that play an important role in Chronic Kidney Disease (CKD). Controlling these 2 factors is expected to give better kidney functions outcomes. Statins have anti-inflammatory and antioxidative stress effects apart from their lipid-lowering effect. In this study, we want to analyze that statin might be one of a renoprotective agent through their pleiotropic effect as an anti-inflammation and anti-oxidative in CKD patients. This is a cross-sectional study that enrolled of 40 patients with CKD: 20 patients consumed statin and 20 patients did not consume statin. We compared HDL; inflammatory markers: high sensitive – C reactive protein (hsCRP), absolute neutrophil count, absolute leukocyte count, absolute eosinophil count, and neutrophil-lymphocyte ratio (NLR); and oxidative stress marker malondialdehyde (MDA) with kidney functions (GFR, cystatin c, BUN, albumin urine, and creatinine serum) between groups. Then we analyze the correlation between HDL, inflammatory markers, and oxidative marker with kidney functions. The results are HDL and MDA had a correlation with all the kidney function, hs-CRP correlated with GFR, cystatin c, and BUN, and NLR correlated with GFR, cystatin c, BUN, and creatinine serum. Statin group significantly have lower hs-CRP, NLR, and MDA. HDL, absolute neutrophil, leukocyte, and eosinophil count are lower in the statin group but not significantly. All the kidney function markers significantly have a better outcome in the statin group. This study concludes that lowering inflammation and oxidative stress levels using statin could be one of the strategy therapies in CKD to achieve better kidney function outcomes. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 variants demonstrate diverse transmission patterns, modifications in infectivity, and immune response. Changes in disease manifestation may be attributed to vaccination and the virus's reduced capacity to induce inflammation. Objectives: To investigate the relationship between the inflammatory response and the characteristics of COVID-19 across successive waves. Methods: A retrospective cross-sectional study was conducted to evaluate sociodemographic, clinical, and laboratory data of Alpha (G1), Delta (G2), and Omicron (G3) variants. Results: A total of 300 patients from a hospital in Madrid, Spain, were included. The groups exhibited similar sociodemographic and baseline characteristics. The Alpha variant predominantly affected younger patients, while the Omicron variant affected patients with a higher prevalence of comorbidities. The Alpha group had the lowest vaccination rate compared to the highest rate in the Omicron group. The Alpha group received a higher proportion of tocilizumab compared to the other groups. Despite these differences, the severity scores were similar among the three variants. Regarding laboratory parameters, differences were observed in haemoglobin, D-dimer, alkaline phosphatase, and potassium levels. The Omicron variant showed higher D-dimer levels (p=0.04). In the multivariate analysis, differences in leukocyte count, haemoglobin, alkaline phosphatase, and potassium levels were consistently observed among patients from different waves. Omicron exhibited a higher absolute leukocyte count than the Alpha variant (p=0.003). Conclusion: No significant differences were found in inflammation biomarkers among the three variants. Furthermore, there were no significant disparities in mortality or disease severity. The level of inflammatory response in patients may be determined by the severity of COVID-19, rather than the specific viral variant. [ABSTRACT FROM AUTHOR]

Little information exists on YKL-40—a key protein in tissue remodeling—and complete blood count (CBC) parameters during acute exacerbations of advanced chronic obstructive pulmonary disease (COPD). This pilot exploratory study (August 2020–January 2021) investigated the connection between serum YKL-40 levels and CBC profile in sex- and age-matched individuals with severe COPD (GOLD stage III, n = 23, median age = 66 years, 65.21% males) and very severe COPD (GOLD stage IV, n = 24, median age = 66.5 years, 74.81% males). The measured parameters were serum YKL-40, absolute leukocyte count (ALLC), absolute neutrophil count (ANC), neutrophil percentage, absolute lymphocyte count (ALC), lymphocyte percentage, neutrophil-to-lymphocyte ratio (NLR), absolute eosinophil count (AEC), eosinophil percentage, absolute monocyte count (AMC), monocyte percentage, absolute basophil count (ABC), basophil percentage, hemoglobin levels, and hematocrit concentrations. No significant inter-group differences were observed. However, high YKL-40 subjects (n = 23)—as stratified via median YKL-40 (3934.5 pg/mL)—showed significantly increased neutrophil percentage and NLR but significantly lower lymphocyte-, eosinophil-, and basophil-related parameters compared to low YKL-40 patients (n = 24). These results reveal multidimensional, YKL-40-associated changes in leukocyte profile of patients with advanced COPD during acute exacerbations, with potential implications for personalized treatment. [ABSTRACT FROM AUTHOR]

Background: Early and accurate prognosis prediction of the patients was urgently warranted due to the widespread popularity of COVID-19. We performed a meta-analysis aimed at comprehensively summarizing the clinical characteristics and laboratory abnormalities correlated with increased risk of mortality in COVID-19 patients. Methods: PubMed, Scopus, Web of Science, and Embase were systematically searched for studies considering the relationship between COVID-19 and mortality up to 4 June 2020. Data were extracted including clinical characteristics and laboratory examination. Results: Thirty-one studies involving 9407 COVID-19 patients were included. Dyspnea (OR = 4.52, 95%CI [3.15, 6.48], P < 0.001), chest tightness (OR = 2.50, 95%CI [1.78, 3.52], P<0.001), hemoptysis (OR = 2.00, 95%CI [1.02, 3.93], P = 0.045), expectoration (OR = 1.52, 95%CI [1.17, 1.97], P = 0.002) and fatigue (OR = 1.27, 95%CI [1.09, 1.48], P = 0.003) were significantly related to increased risk of mortality in COVID-19 patients. Furthermore, increased pretreatment absolute leukocyte count (OR = 11.11, 95%CI [6.85,18.03], P<0.001) and decreased pretreatment absolute lymphocyte count (OR = 9.83, 95%CI [6.72, 14.38], P<0.001) were also associated with increased mortality of COVID-19. We also compared the mean value of them between survivors and non-survivors, and found that non-survivors showed significantly raise in pretreatment absolute leukocyte count (WMD: 3.27×109/L, 95%CI [2.34, 4.21], P<0.001) and reduction in pretreatment absolute lymphocyte count (WMD = -0.39×109/L, 95%CI [-0.46, -0.33], P<0.001) compared with survivors. The results of pretreatment lactate dehydrogenase (LDH), procalcitonin (PCT), D-Dimer and ferritin showed the similar trend with pretreatment absolute leukocyte count. Conclusions: Among the common symptoms of COVID-19 infections, fatigue, expectoration, hemoptysis, dyspnea and chest tightness were independent predictors of death. As for laboratory examinations, significantly increased pretreatment absolute leukocytosis count, LDH, PCT, D-Dimer and ferritin, and decreased pretreatment absolute lymphocyte count were found in non-survivors, which also have an unbeneficial impact on mortality among COVID-19 patients. Motoring these indicators during the hospitalization plays a very important role in predicting the prognosis of patients. [ABSTRACT FROM AUTHOR]

Background: Data are lacking on the role of cellular components of hematological system as biomarkers for prognosis of sepsis. We planned to identify if these parameters measured at admission to ICU and at 72 hours can be useful as prognostic marker in septic critically ill patients. Materials and methods: In this prospective observational study, 130 adult patients with sepsis were recruited. Various hematological study parameters (total, differential, and absolute leukocyte count, platelet count, platelet distribution width, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio) were noted at day 1 and day 3 of admission. Primary outcome was 28-day mortality, and secondary outcomes were duration of mechanical ventilation, vasopressor requirement, ICU length of stay, and requirement of renal replacement therapy. The variables were compared between two groups and using binary regression model and were evaluated as prognostic markers for 28-day mortality. Results: Data from n = 129 were analyzed. At day-28, n = 58 (44.96%) patients survived. Baseline and demographic parameters were comparable between survivors and nonsurvivors. Admission Sequential Organ Failure Assessment score was more in nonsurvivors than survivors [8 (6--8) vs 6 (4--8); p = 0.002]. In nonsurvivors, monocyte, lymphocyte, basophil, eosinophil, and platelet count were significantly less at day 1 and lymphocyte, eosinophil, basophil and platelet count were significantly less at day 3. NLR and PLR at day 3 were significantly more in nonsurvivors. On logistic regression analysis, age, thrombocytopenia on day 1, and low eosinophil count on day 3 predicted 28-day mortality (p = 0.006, p = 0.02, and p = 0.04, respectively). Conclusion: Thrombocytopenia on day 1 and eosinopenia on day 3 may predict 28-day mortality in sepsis. [ABSTRACT FROM AUTHOR]

There is a need for a quick assessment of severely ill patients presenting to the hospital. The objectives of this study were to identify clinical, laboratory and imaging parameters that could differentiate between influenza and COVID-19 and to assess the frequency and impact of early bacterial co-infection. A prospective observational cohort study was performed between February 2019 and April 2020. A retrospective cohort was studied early in the COVID-19 pandemic. Patients suspected of sepsis with PCR-confirmed influenza or SARS-CoV-2 were included. A multivariable logistic regression model was built to differentiate COVID-19 from influenza. In total, 103 patients tested positive for influenza and 110 patients for SARS-CoV-2, respectively. Hypertension (OR 6.550), both unilateral (OR 4.764) and bilateral (OR 7.916), chest X-ray abnormalities, lower temperature (OR 0.535), lower absolute leukocyte count (OR 0.857), lower AST levels (OR 0.946), higher LDH (OR 1.008), higher ALT (OR 1.044) and higher ferritin (OR 1.001) were predictive of COVID-19. Early bacterial co-infection was more frequent in patients with influenza (10.7% vs. 2.7%). Empiric antibiotic usage was high (76.7% vs. 84.5%). Several factors determined at presentation to the hospital can differentiate between influenza and COVID-19. In the future, this could help in triage, diagnosis and early management. Clinicaltrial.gov Identifier: NCT03841162 [ABSTRACT FROM AUTHOR]

Background: Many coronavirus disease 2019 (COVID-19) vaccines were approved worldwide. Their safety was the primary concern. In Egypt, Oxford-AstraZeneca (AZ) vaccine was the first approved vaccine initially for healthcare workers (HCWs). Objective: We aim to determine adverse events and hematological abnormalities following the COVID-19 AZ vaccine and estimate the infection rate of the candidates by COVID-19 between the first and second doses of vaccination. Methods: Within 8-10 days of receiving their initial dose of the AZ vaccine, 909 HCWs were assessed for adverse events as part of a prospective longitudinal study. Complete blood counts (CBCs) were evaluated before and one month after vaccination. Results: 37.2% of the candidates experienced side effects following vaccination. Pain at the injection site was the most common (25.4%) and more frequent in participants between 20 and 40 years (27.9%). The mean total leukocyte count (TLC), absolute leukocyte count (ALC), absolute neutrophil count (ANC), and absolute monocyte count (AMC) increased one month following vaccination (P < 0. 001). Sixty-six vaccinated HCWs were infected with COVID-19 between the two vaccine doses. 82% were infected after 14 days of the first dose, while 18% were infected before 14 days (P < 0.0001). Conclusions: Most of the vaccinated personnel did not experience any side effects after the first dose of the vaccine. Furthermore, the most common complaints were pain at the injection site, fatigue, fever, headache, arthralgia, myalgia, and chills. Infected people with COVID-19 after the first dose had significantly more severe disease if they were infected before 14 days than those who got infected later on. [ABSTRACT FROM AUTHOR]

Introduction: Asthma is a heterogenic disease, commonly divided into allergic and nonallergic asthma. It affects people of all age group and is associated with impaired lung function. Previously, it was thought that asthma is a disease of developed countries but at present, world scenario has changed and its prevalence in developing countries is rapidly increasing. Asthma shows large geographical variations in terms of prevalence, severity and mortality. Aim: To establish the prevalence of allergic and nonallergic asthma in adults of Kumaun region of Uttarakhand (India) and to evaluate whether the peripheral blood cell count is associated with the severity of lung impairment in both the subtypes (allergic and nonallergic) of asthma. Materials and Methods: This cross-sectional study was carried out jointly in Department of Physiology and Department of Respiratory Medicine, Government Medical College, Haldwani, Uttarakhand (India), during the period from October 2015 to January 2017. A total of 125 patients of both sexes age above 18 years, who attended the OPD of Respiratory Medicine and diagnosed asthma by the physician were enrolled in the study. The patients associated with tuberculosis, worm infestations, other allergic diseases and systemic diseases were excluded. History of Allergic Rhino-Conjunctivitis (ARC) was used for allergic sensitisation and to define allergic asthma. Classification of severity of airflow limitation was done according to Global Initiative for Asthma (GINA) guidelines. Absolute Leukocyte Counts was determined by using the formula: Absolute leukocyte count=Differential leukocyte count/100×Total leukocyte count. One-way ANOVA followed by Tukey HSD post-hoc analysis and Chi-square was done. Level of statistical significance was set at p-value <0.05. Results: The prevalence of allergic asthma was more in 79 patients (63.2%), in comparison to nonallergic asthma in 46 (36.8%) and it (allergic asthma) was more common in males than females (54:25). Mean age of allergic and nonallergic group asthma patients were 51.00±14.31 and 56.11±13.14 years, respectively. In allergic asthma patients, blood eosinophil count increased significantly (p=0.001) the severity of lung impairment increased and no significant changes were observed in other blood cell counts while in nonallergic asthma over-all neutrophil count was significantly high (p=0.044) with increase in severity. Nonallergic asthma also showed increasing trend of eosinophil count as the severity of airway obstruction increased but there were no significant changes in other counts. Conclusion: The prevalence of allergic asthma is high in comparison to nonallergic asthma among adults of Kumaun region of Uttarakhand, India and it is more prevalent among males in both the groups. Peripheral blood leukocyte count might be used as biological marker to differentiate allergic asthma from nonallergic asthma. [ABSTRACT FROM AUTHOR]

Purpose: To describe 5-fluorouracil (5FU) pharmacokinetics, myelotoxicity and respective covariates using a simultaneous nonlinear mixed effect modelling approach.Methods: Thirty patients with gastrointestinal cancer received 5FU 650 or 1000 mg/m2/day as 5-day continuous venous infusion (14 of whom also received cisplatin 20 mg/m2/day). 5FU and 5-fluoro-5,6-dihydrouracil (5FUH2) plasma concentrations were described by a pharmacokinetic model using NONMEM. Absolute leukocyte counts were described by a semi-mechanistic myelosuppression model. Covariate relationships were evaluated to explain the possible sources of variability in 5FU pharmacokinetics and pharmacodynamics.Results: Total clearance of 5FU correlated with body surface area (BSA). Population estimate for total clearance was 249 L/h. Clearances of 5FU and 5FUH2 fractionally changed by 77%/m2 difference from the median BSA. 5FU central and peripheral volumes of distribution were 5.56 L and 28.5 L, respectively. Estimated 5FUH2 clearance and volume of distribution were 121 L/h and 96.7 L, respectively. Baseline leukocyte count of 6.86 × 109/L, as well as mean leukocyte transit time of 281 h accounting for time delay between proliferating and circulating cells, was estimated. The relationship between 5FU plasma concentrations and absolute leukocyte count was found to be linear. A higher degree of myelosuppression was attributed to combination therapy (slope = 2.82 L/mg) with cisplatin as compared to 5FU monotherapy (slope = 1.17 L/mg).Conclusions: BSA should be taken into account for predicting 5FU exposure. Myelosuppression was influenced by 5FU exposure and concomitant administration of cisplatin. [ABSTRACT FROM AUTHOR]

Introduction: Epstein-Barr virus (EBV) infection has been linked to cervical cancer (CC), but few have described the clinical and outcome features of patients with CC and EBV infection. Methods: We conducted a single-center matched cohort study on 94 patients with CC. Real-time Polymerase chain reaction (RT-PCR) was used to detect EBNA-1 (Epstein-Barr nuclear antigen 1) and LMP-1 (Latent membrane protein 1). We used Kaplan-Meier and Cox regression analysis to evaluate the effect of EBV infection on overall survival (OS) and progression-free survival (PFS). Females with a positive EBV status were matched to those without infection using a propensity score. Results: Of the 94 patients in our cohort, 21 (22%) had a positive EBV status. Before and after matching, there were no differences in baseline clinical and sociodemographic features between patients diagnosed with CC with and without EBV infection. Most patients received concurrent chemoradiotherapy (73%) as frontline treatment. With a median follow-up of 67 months, the 5-year OS was 42% (95% CI: 33–55%) and the 5-year PFS was 37% (95% CI: 37–49%) in the entire population. Patients with EBV-positive status had comparable 5-year OS (50% vs. 37%, p-value=0.490; Hazard Ratio [HR] 0.77, 95% CI 0.36-1.62) and 5-year PFS (44% vs. 37%, p-value=0.750; HR 0.89, 95% CI 0.43-1.83) to those with EBV-negative CC, respectively. Conclusion: Females with CC and EBV infection have similar clinical features and outcomes compared to those without EBV infection. [ABSTRACT FROM AUTHOR]

Copyright of Jornal Brasileiro de Patologia e Medicina Laboratorial is the property of Sociedade Brasileira de Patologia Clinica and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Currently, the evaluation of mutational status of variable region of immunoglobulin heavy chain gene (IGHV) makes up one of the key prognostic and predictive tests in patients with chronic lymphocytic leukaemia (CLL), performed before the initiation of first line therapy. This publication presents the first edition of the Polish recommendations of the Molecular Haematology Section of the Polish Society of Human Genetics (PTGC) concerning the methodology of IGHV mutation status determination and the principles of reporting the results based on the recognised international standards. [ABSTRACT FROM AUTHOR]

Background: Adolescent group may be prone to a variety of behavioral disorders, one of which is nonsuicidal self-injury (NSSI), NSSI intervention is limited for its unknown mechanism, so this study aimed to explore the factors associated with and pathological mechanism underlying NSSI from the perspective of family dysfunction, alexithymia, circRNA_103636 in a sample of Chinese adolescents. Methods: A total of 200 MDD adolescents with NSSI and 200 healthy controls were enrolled via a convenient sampling method in clinical settings. The Family APGAR Index (APGAR), Toronto Alexithymia Scale (TAS-20), and Adolescent Nonsuicidal Self-injury Assessment Questionnaire (ANSSIAQ) were used for mental assessment of the study group and control group participants. Real-time quantitative reverse transcription PCR (qRT–PCR) was utilized to detect circRNA_103636 expression in peripheral blood mononuclear cells (PBMCs). Results: There were significant between-group differences of 134 patients (67%) in the study group and 42 patients in the control group (21%) with moderate or severe family dysfunction (P< 0.01). The APGAR score was lower, and the difficulty identifying feeling (DIF), difficulty describing feeling (DDF) and externally oriented thinking (EOT) scores of the TAS-20 and ΔCt value of circRNA_103636 were greater in the study group than in the control group. NSSI behavior and NSSI function were negatively correlated with the APGAR score and positively correlated with DIF, DDF, and the EOT of TAS-20 and the ΔCt value of circRNA_103636. Multiple regression analysis confirmed that EOT, circRNA_103636 expression, and APGAR were predictors of ANSSIAQ, which could explain 40.5% of the variance. Similarly, the alexithymia and circRNA_103636 expression mediated the correlation between family dysfunction and NSSI in the study group, and these mediating effects accounted for 27.25% and 23.33%, respectively, of the total effect. Taken together, family dysfunction, alexithymia, and circRNA_103636 expression have predictive effects on NSSI and alexithymia, circRNA_103636 expressions are mediators between family dysfunction and NSSI in Chinese adolescent. Conclusion: Here, we established a new model for NSSI in which exposure to family dysfunction could induce pathological process by modulating personality traits and epigenetic regulators. [ABSTRACT FROM AUTHOR]

Background: Interferon-beta (IFN-β) still plays a fundamental role in immunomodulation of people with multiple sclerosis (MS) with low disease activity and in clinically isolated syndrome (CIS). In 2014, pegylated (PEG) interferon was licensed by the European Medicines Agency (EMA) for relapsing-remitting MS (RRMS), enabling a lower dosing frequency. Objectives: Our retrospective study compares laboratory findings and adverse events between subcutaneous (sc.) PEG-IFN-β-1a and IFN-β-1a in RRMS and CIS patients. Design: Patients with CIS or RRMS fulfilling the revised McDonald criteria from 2017 visiting the neurology department of the University Medical Center of the Johannes Gutenberg University Mainz from 2010 to 2019 and treated with sc. PEG-IFN-β-1a or sc. IFN-β-1a (n = 202) were screened for eligibility. Patients who underwent regular laboratory controls in-house were included in our analysis (n = 128). Methods: We evaluate disease progression through clinical examination, relapse history, and magnetic resonance imaging (MRI) disease activity (gadolinium-enhancing or new T2 lesions). Relevant laboratory findings such as leukopenia (leukocyte count < 3.5/nl) and neutropenia (neutrophil count <43% of lymphocytes or <1500/µl) were assessed. Telephone interviews evaluated the side effects of the respective medication. A subgroup of patients was analyzed regarding neutrophil quantities and qualities. Results: Patients treated with sc. PEG-IFN-β-1a had significantly lower leukocyte counts (p = 0.046) and higher incidences of leukopenia (p = 0.006) and neutropenia (p = 0.03) compared to sc. IFN-β-1a. Clinical and MRI disease activity showed no significant differences, but people treated with sc. PEG-IFN-β-1a reported more common adverse events such as joint/muscle pain, injection-site reaction, and infections. No serious adverse events were reported. Conclusion: Treatment with sc. PEG-IFN-β-1a compared to unpegylated sc. IFN-β resulted in a significantly greater reduction in leukocyte and neutrophil levels with a higher incidence of side effects. We suggest mandatory monitoring of differential blood counts before and during treatment. Plain language summary: Possible risk factors for the occurrence of leukopenia in patients with multiple sclerosis treated with interferon beta In our study, we compared two medications used to treat multiple sclerosis (MS): pegylated interferon-beta-1a (PEG-IFN-beta-1a) and interferon-beta-1a (IFN-beta-1a). The pegylated form needs to be taken less often. We looked at patients' medical history, physical exams, lab results, and MRI scans to see how these drugs affected them. We also asked about side effects during phone interviews. We found that PEG-IFN-beta-1a caused lower levels of certain blood cells, like leukocytes, and more side effects such as skin rashes and infections compared to IFN-beta-1a. However, there were no differences in disease activity as seen in clinical exams and MRI scans. We recommend regular blood tests for patients using these medications to monitor their health. [ABSTRACT FROM AUTHOR]

Background: To evaluate the diagnostic characteristics of tryptophanyl tRNA synthetase (WRS) for the diagnosis of septic arthritis of the knee joint and to determine whether it is a reliable and sensitive synovial biomarker for discriminating septic arthritis from other types of arthritis. Methods: Patients joint effusions for which septic arthritis was suspected were prospectively recruited between January 2019 and September 2020. A total of 9 patients had septic arthritis, 6 had acute gout attack, 1 had an acute flare of chronic rheumatic arthritis, and 46 had pseudogout or reactive arthropathy. Traditional inflammatory markers were measured, and their diagnostic abilities were compared. Neutrophil count, C-reactive protein (CRP) level, WRS, and human neutrophil α-defensin levels were assessed in the synovial fluids. Demographic parameters and biomarkers with a P < 0.05 in differentiating septic from nonseptic arthritis were included in a multivariable model. A multivariable logistic regression with a stepwise selection was performed to build the final combined model. Receiver operating characteristic curves were used to establish optimal thresholds for the diagnosis of septic arthritis of the knee joint, and the area under the curve was calculated to determine the overall accuracy of these tests compared with patients with nonseptic inflammatory arthritis. Results: Patients with septic arthritis were more likely to display higher serum WBC and CRP levels, synovial neutrophil counts, and levels of two synovial biomarkers, including WRS and α-defensin. WRS showed the highest specificity (87.5%) and sensitivity (83.3%) with α-defensin among the three synovial biomarkers. Conclusions: Synovial fluid WRS is a relevant biomarker in discriminating septic arthritis from other inflammatory arthritis and should be tested in an independent cohort. Level of evidence: prospective observational study, III. [ABSTRACT FROM AUTHOR]

Background: Neonatal sepsis is a major cause of neonatal morbidity and mortality, especially in developing countries. Atypical clinical symptoms lead to delays in diagnosis and treatment. Scoring a combination of routine hematology parameters may be able to predict the occurrence of sepsis in preterm neonates. Objective: To formulate a new model for neonatal sepsis scoring from various complete blood count parameters to predict sepsis in preterm neonates. Methods: This analytical cross sectional study using secondary data from the Registry of the Neonatology Division was conducted at the RSUP Dr. Hasan Sadikin, Bandung, West Java. Subjects were neonates diagnosed with sepsis, of gestational age 28-36 weeks, who were born at the RSUP Dr. Hasan Sadikin from January to December 2021. Laboratory results of patients who met the inclusion criteria were recorded. Subjects were divided into either proven sepsis and probable sepsis groups, based on blood culture results. Results: Of 112 subjects, 35.7% had proven sepsis and 64.3% probable sepsis. In the proven sepsis group, 52.5% of subjects were male, median birth weight was 1,490 grams, median gestational age was 32 weeks, 90% were small for gestational age, and 60% were delivered normally. Multivariable analysis by multiple logistic regression revealed that the parameters associated with the incidence of neonatal sepsis were c-reactive protein (CRP) >0.18 mg/dL (score 6), hematocrit <40% (score 4), plateletto- lymphocyte ratio (PLR) <19.623 (score 4); monocytelymphocyte ratio (MLR) <0.461 (score 2); and mean platelet volume (MPV) value >0 (score 2). Score >8 had a sensitivity of 85% and specificity of 70.8%, with area under the ROC curve of 0.865 (P<0.001). Scoring accuracy was 75.8%, with a positive predictive value of 61.8%, a negative predictive value of 89.5%, and Kappa index of 51.5% with moderate agreement. Conclusion: A hematological score >8 can be used as a predictor of sepsis in preterm neonates. [ABSTRACT FROM AUTHOR]

Parvovirus B19 frequently infects children and targets cells of the erythroid lineage. Although healthy children rarely suffer severe disease, children with sickle cell disease (SCD) can experience transient red cell aplasia (TRCA), hospitalization, and life-threatening anemia upon first virus exposure. Given that children with SCD can also suffer chronic inflammation and that parvovirus B19 has been associated with autoimmune disease in other patient populations, we asked if parvovirus B19 infections contributed to acute and chronic immune abnormalities in children with SCD. Nineteen hospitalized patients with SCD and parvovirus B19–induced TRCA were evaluated. Blood tests included CBC, flow cytometry, and total antibody isotype analyses. Cytokine/chemokine analyses were performed on nasal wash (NW) samples, representing a common site of viral entry. Unusually high white blood cell count (WBC) and absolute neutrophil count (ANC) values were observed in some patients. A correlation matrix with Day 0 values from the 19 patients then identified two mutually exclusive phenotype clusters. Cluster 1 included WBC, ANC, absolute reticulocyte count (ARC), absolute lymphocyte count (ALC), lactate dehydrogenase (LDH), NW cytokines/chemokines, % naïve cells among B cell and T cell populations, and parvovirus-specific IgG. This cluster was negatively associated with virus load, suggesting a signature of successful adaptive immunity and virus control. Cluster 2 included virus load, % CD38+CD24− cells among CD19+ B cells (termed 'plasmablasts' for simplicity), % HLA-DRlow cells among CD19+ B cells, IgG4, and % memory phenotypes among B cell and T cell populations. Plasmablast percentages correlated negatively with parvovirus-specific IgG, possibly reflecting a non-specific trigger of cell activation. All patients were released from the hospital within 1 week after admission, and the highest WBC and ANC values were eventually reduced. Nonetheless, a concern remained that the acutely abnormal immune profiles caused by parvovirus B19 infections could exacerbate chronic inflammation in some patients. To avoid the numerous sequelae known to affect patients with SCD following hospitalizations with parvovirus B19, rapid development of a parvovirus B19 vaccine is warranted. [ABSTRACT FROM AUTHOR]

Copyright of Kocatepe Veterinary Journal / Kocatepe Veteriner Dergisi is the property of Afyon Kocatepe University, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims: Absolute polymorphonuclear (PMN) counts in ascites define spontaneous bacterial peritonitis (SBP), a severe form of bacterial infection in liver cirrhosis. Bacterascites, another form of ascites infection, can progress to SBP or may resolve spontaneously but is not reflected by absolute PMN counts. We investigated whether the relative ascites PMN count (the absolute PMN count divided by the absolute leukocyte count) provides additional information to detect bacterascites or predict SBP.Methods: Hospitalized patients with liver cirrhosis requiring paracentesis were stratified with respect to a diagnosis of bacterascites and SBP with a prospective follow-up for 1 year. Diagnostic power of relative PMN counts in ascites was evaluated by receiver operating characteristics curves.Results: At inclusion, we observed 28/269 (10%) and 43/269 (16%) episodes of BA and SBP, respectively. Unlike absolute PMN counts, relative PMN counts in ascites were significantly elevated in bacterascites (p = 0.001). During follow-up, 16 and 30 further episodes of BA and SBP were detected, respectively. Relative PMN counts increased significantly once patients developed BA (p = 0.001). At a threshold of 0.20 for the relative PMN count, sensitivity, specificity, positive and negative predictive values for bacterascites which required antibiotic treatment were 83, 75, 26 and 98%, respectively (p < 0.001). Furthermore, a relative PMN count in ascites ≥0.13 and MELD score >17 was independent factors associated with occurrence of SBP during follow-up.Conclusion: The relative PMN count is a cheap immunological marker linked to bacterascites and future SBP, which may help to stratify patients according to their risk of infection. [ABSTRACT FROM AUTHOR]

The aim of the study was to conduct a comparative analysis of serum lysozyme activity and study its innovativeness in predicting bacterial complications after kidney transplantation. Material and methods. Lysozyme activity was studied in 99 patients after kidney transplantation and 81 practically healthy volunteers. Patients depending on period after surgery were divided into five groups: group 1 – 1st day after kidney transplantation (n = 6); group 2 – 1–5 months (n = 10); group 3 – 6–12 months (n = 21); group 4 – 2–5 years (n = 30); group 5 – 6–10 years (n = 32). An analysis of the correlation between serum lysozyme level, absolute leukocyte count and creatinine content was performed. Lysozyme activity was assessed in bacterial complications, transplant dysfunction and organ rejection. Results and discussion. On the 1st day after kidney transplantation lysozyme activity was minimal – 117.95 [60.80–133.51] µg/ ml (median [lower quartile – upper quartile]) (in healthy volunteers it was 243.80 [190.76–305.69] µg/ml, p < 0,001). One month after surgery, it returned to normal (292.08 [311.66–218.48] μg/ml) and did not differ from the value of the group of practically healthy volunteers for 5 months (p = 0,17). Lysozyme activity in serum of patients after kidney transplantation had inverse moderate correlation with creatinine content (r = –0,32, p < 0,05). The threshold value for the probability of bacterial infections for serum lysozyme was > 321,4 μg/ml (p = 0,003). Creatinine level > 0,11 mmol/l predicts graft dysfunction. Conclusions. On the first day after transplantation a low level of lysozyme indicates high risk of bacterial infection. One month after surgery lysozyme returned to normal which indicates restoration of humoral component of nonspecific immune resistance. Relationship between creatinine content and lysozyme activity as well as an increase in the latter in comparison with healthy group allows to use lysozyme as an additional diagnostic criterion for acute bacterial infection and creatinine – for prognosis of graft dysfunction.

Objective: Neutrophil-to-lymphocyte ratio (NLR) has been shown to be an independent predictor for cardiovascular diseases and metabolic diseases. The role of NLR in metabolic syndrome (MS) has also been explored albeit with conflicting results. The objective of this study was to assess the predictive role of NLR in MS. Methods: We conducted a meta-analysis of observational studies to evaluate the predictive role of NLR in MS. Cochrane library, PubMed, Medline, Embase, and Scopus were systematically searched from their inception to December 2023. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines was followed. The statistical analysis was performed using RevMan 5.3 software. A randomeffect model was used. Results: Twenty six studies enrolling 70,937 individuals were included in this meta-analysis. Compared with the individuals without MS, NLR value was significantly higher in the patients of MS (mean difference (MD) 0.40, 95% confidence intervals (CI): 0.27–0.52, P < 0.00001, I2 = 97%). The derived NLR value also was significantly higher in participants with MS than those without MS (MD 0.48, 95%CI: 0.13–0.84, P = 0.007, I2 = 96%). There was no statistically significant association for NLR between the patients with 4 metabolic risk factors (MRF) and those with 3 MRF, or between patients with 5 MRF and those with 4 MRF (MD 0.16, 95%CI: -0.02-0.35, P = 0.10, I2 = 84%; MD 0.12, 95%CI: -0.06-0.29, P = 0.20, I2 = 68%). However, MS patients with 5 MRF had a significantly higher mean NLR value than those with 3MRF (MD 0.37, 95%CI: 0.05–0.68, P = 0.02, I2 = 92%). Compared with the individuals with low NLR, incidence of MS was significantly higher in those with high NLR (OR 2.23, 95%CI: 1.25–3.98, P = 0.006, I2 = 97%). Conclusion: The findings of our meta-analysis suggested that the value of NLR and derived NLR were higher in MS patients. MS patients with 5 MRF had a significantly higher mean NLR value. High NLR also demonstrated a significantly increased the incidence of MS. NLR may be a good predictive biomarker in MS. [ABSTRACT FROM AUTHOR]

Background: T-cell leukemia originating from large granular lymphocytes (T-LGL leukemia) is a rare lymphoid neoplasia characterized by clonal proliferation of large granular T lymphocytes expressing αβ or γδ T-cell receptor (TCR) on the cell membrane. γδT-LGL leukemia, accounting for approximately 17% of all T-LGL leukemia cases, is associated with autoimmune diseases. However, the features of γδT-LGL leukemia in patients with rheumatologic diseases are still insufficiently characterized. Methods: In this retrospective study, 15 patients with rheumatologic diseaseassociated γδT-LGL leukemia were included. The patients were obtained from a single center from 2008 to 2023. Data related to clinical characteristics and rheumatologic diagnoses were collected. Immunophenotype evaluations as well as T-lymphocyte clonality (based on TCR-γ, TCR-β, and TCR-δ gene rearrangements), and signal transducer and activator of transcription (STAT) three and STAT5B mutation analyses (by next-generation sequencing) were performed on blood, bone marrow, and spleen samples. Results: All but one patient had rheumatoid arthritis (RA). In 36% of patients, manifestations of γδT-LGL leukemia were present before or concurrently with clinical manifestations of RA. Splenomegaly was observed in 60% of patients and neutropenia (<1.5 × 109/L) was detected in 93% of cases. CD4-/CD8- and CD4-/CD8+ subtypes were detected in seven cases each. Mutations in STAT3 were detected in 80% of patients; however, STAT5B mutations were not detected. Evaluations of T-cell clonality and variant allele frequencies at STAT3 in the blood, bone marrow, and spleen tissue revealed an unusual variant of CD4-/CD8- γδT-LGL leukemia with predominant involvement of the spleen, involvement of the bonemarrow to a less extent, and no tumor cells in peripheral blood. Conclusion: The mechanism by which γδT-LGL leukemia may induce the development of RA in some patients requires further investigation. Cases of RA-associated γδT-LGL leukemia with neutropenia and splenomegaly but no detectable tumor-associated lymphocytes in peripheral blood (the so-called splenic variant of T-LGL leukemia) are difficult to diagnose and may be misdiagnosed as Felty syndrome or hepatosplenic T-cell lymphoma. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of noncystic fibrosis bronchiectasis in adults is complex, and the relevant molecular mechanisms remain unclear. In this study, we constructed a panoramic map of bronchiectasis mRNA, explored the potential molecular mechanisms, and identified potential therapeutic targets, thus providing a new clinical perspective for the preventive management of bronchiectasis and its acute exacerbation. Methods: The mRNA profiles of peripheral blood and bronchiectasis tissues were obtained through transcriptome sequencing and public databases, and bioinformatics methods were used to screen for differentially expressed genes (DEGs). The DEGs were then subjected to biological function and pathway analyses. Some DEGs were validated using a real-time quantitative polymerase chain reaction (RT-qPCR) in peripheral blood. Spearman's correlation analysis was used to analyse the correlation between DEGs and clinical indicators. Results: Based on transcriptome sequencing and public databases, the mRNA profile of bronchiectasis was determined. DEGs were obtained from the peripheral blood sequencing dataset (985 DEGs), tissue sequencing dataset (2919 DEGs), and GSE97258 dataset (1083 DEGs). Bioinformatics analysis showed that upregulated DEGs had enriched neutrophil-related pathways, and downregulated DEGs had enriched ribosome-related pathways. RT-qPCR testing confirmed the upregulated expression of VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 in bronchiectasis. These genes were related to many clinical parameters, such as neutrophils, C-reactive protein, and procalcitonin (P < 0.05). Conclusions: Transcriptomic methods were used to construct a panoramic map of bronchiectasis mRNA expression. The findings showed that neutrophil activation, chronic inflammation, immune regulation, impaired ribosomal function, oxidative phosphorylation, and energy metabolism disorders are important factors in the development of bronchiectasis. VCAN, SESTD1, SLC12A1, CD177, IFI44L, SIGLEC1, and RSAD2 may play important roles in the pathogenesis of bronchiectasis and are potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: The clinical spectrum of fibrotic interstitial lung diseases (ILDs) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for the improvement of lung function in patients with fibrotic ILDs. Methods: This registry-based study included 142 patients with fibrotic ILDs as defined by the presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as a relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. Results: At one year, 44 patients showed improvement while 73 showed disease progression. Multivariate analyses found prognostic significance for age < 60 years (OR 5.4; 95%CI 1.9–15.4; p = 0.002), lactate dehydrogenase (LDH) >250 U/L (OR 2.5; 95%CI 1.1–5.8; p = 0.043) and blood monocyte count < 0.8 G/L (OR 3.5; 95%CI 1.1–11.3; p = 0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age < 60 years (OR 8.5 (95%CI 2.1–33.4; p = 0.002) as the only significant variable. Conclusion: Younger age, a higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications. [ABSTRACT FROM AUTHOR]

Background: Seasonal fluctuation in incidence of invasive pneumococcal disease, pulmonary embolism, deep vein thrombosis and coronary heart disease etc has been reported since long time. So, the present study was conducted to evaluate the seasonal variation in hematological and hemodynamic parameters, heart rate and blood pressure in the month of November, February and May. Materials and methods: 15 male subjects in the age group of 18.5±1 year were matched on haematological parameters, heart rate and blood pressure in three different seasons and the results were compared. Results: Packed cell volume in winter (February), Erythrocyte Sedimentation Rate in summer (May) were increased (P< 0.001) as compared to basal level in November month with non significant variation in Hemoglobin concentration and Red Blood Cell count. Total Leukocyte count significantly increased (p <0.001) in winter, while on differential and absolute leukocyte count Eosinophil, Basophil, Monocyte, Lymphocyte (%) were elevated (p <0.001) and Neutrophil (%) decreased (p <0.001) in summer. Total Protein concentration, serum Albumin level was higher in winter. Heart rate shows insignificant seasonal changes but blood pressure, both systolic and diastolic was lower (p< 0.001) in summer and rate pressure product (RPP) was higher (p<0.05) in winter. Conclusion: So, these findings indicate that variations in different parameters do occur to adapt to the environmental conditions which may be responsible for susceptibility to different diseases e.g. asthma and ischemic heart diseases in different seasons. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis continues to be a leading cause of mortality and prolonged hospitalisation. The conventional method of blood culture, while considered the gold standard, has limitations such as contamination and delayed reporting. The examination of peripheral smears has uncovered signs suggestive of septicaemia; however, these findings suffer from inter-observer variability and reliance on staining quality. Aim: To investigate the variation of neutrophil and monocyte parameters, including Volume, Conductivity, and Scatter (VCS), in sepsis compared to healthy controls. Materials and Methods: A cross-sectional analytical study was conducted at the Himalayan Institute of Medical Sciences, Swami Rama Himalayan University in Dehradun, Uttarakhand, over the course of one year, from January 2021 to December 2021, involving patients over 18 years of age categorised into sepsis group based on clinical suspicion, sepsis screen, blood culture, and Sequential Organ Failure Assessment (SOFA) score (n=117). A group of healthy controls was also included (n=140). Haematological investigations were performed using the DXH 800 Haematology Analyser (Beckman Coulter, CA, USA) with VCS Technology. Categorical variables were analysed using the Chi-square test, while non parametric data was compared using the Mann-Whitney U test. Results: The average age in the sepsis group was 50.17±13.17 years, while in the control group, it was 38.14±8.78 years. The results revealed higher White Blood Cell (WBC) counts (16.76±7.39)×103/cumm in the sepsis group compared to healthy controls (6.68±1.42)×103, absolute neutrophil counts (13.74±7.280)×103 in sepsis patients, and eosinopenia in the sepsis group (0.0114±0.0104)×103 compared to controls (0.23±0.116)×103. Moreover, mean neutrophilic volumes (158.00±14.840) and monocytic volumes (182.58±18.64) were higher in the sepsis group, while they were lower in healthy controls, which were (149.52±5.23 and 171.17±6.28), respectively. Axial light loss for neutrophil and monocyte was 142.40±11.78 and 121.50±17.93, respectively, while it was lower in healthy controls showing a value of 135.51±7.63 and 119.45±8.25, respectively. Furthermore, mean neutrophilic and monocytic conductivity and scatter were decreased in sepsis. The observed higher WBC counts and absolute neutrophil counts in sepsis patients suggest a premature release of neutrophils from the bone marrow. The alterations in cell volume reflect an immune response. Additionally, the overall scatter of neutrophils and monocytes was reduced, accompanied by increased cellular transparency. Conclusion: The present study contributes valuable insights into the pathophysiological mechanisms underlying sepsis, emphasising the dynamic interplay between immune cells and their functional characteristics. Understanding these variations in cellular parameters could potentially aid in the development of more targeted diagnostic and therapeutic approaches for sepsis, ultimately improving patient outcomes. Further research is warranted to delve deeper into the specific mechanisms driving these observed changes and to explore their clinical implications in the context of sepsis management. [ABSTRACT FROM AUTHOR]

Background and Objectives: episodes of acute decompensation in chronic heart failure (ADHF), a common health problem for the growing elderly population, pose a significant socio-economic burden on the public health systems. Limited knowledge is available on both the endothelial function in and the cardio-metabolic health profile of old adults hospitalized due to ADHF. This study aimed to investigate the connection between asymmetric dimethylarginine (ADMA)—a potent inhibitor of nitric oxide—and key health biomarkers in this category of high-risk patients. Materials and Methods: this pilot study included 83 individuals with a known ADHF history who were admitted to the ICU due to acute cardiac decompensation. Selected cardiovascular, metabolic, haemogram, renal, and liver parameters were measured at admission to the ICU. Key renal function indicators (serum creatinine, sodium, and potassium) were determined again at discharge. These parameters were compared between patients stratified by median ADMA (114 ng/mL). Results: high ADMA patients showed a significantly higher incidence of ischemic cardiomyopathy and longer length of hospital stay compared to those with low ADMA subjects. These individuals exhibited significantly higher urea at admission and creatinine at discharge, indicating poorer renal function. Moreover, their lipid profile was less favorable, with significantly elevated levels of total cholesterol and HDL. However, no significant inter-group differences were observed for the other parameters measured. Conclusions: the present findings disclose multidimensional, adverse ADMA-related changes in the health risk profile of patients with chronic heart failure hospitalized due to recurrent decompensation episodes. [ABSTRACT FROM AUTHOR]

Simple Summary: Melanoma patients with high neutrophil counts often show impaired clinical response and poor prognosis, indicating that neutrophils can support melanoma progression. The precise mechanism responsible for this correlation, especially in the context of targeted therapy, still requires clarification. We show that peripheral blood neutrophils of patients with advanced melanoma are characterized by lower CD16 surface expression compared to healthy donors, which has been reported to be associated with tumor promotion. We provide evidence that melanoma cells under dual-targeted therapy can be protected in vitro by neutrophils from both patients and healthy donors. In addition, this protective effect is dependent on cell–cell contact, as well as on culture conditions, and is observed under nonadherence. Unraveling the mechanism, the interference with the protease activity of neutrophils reduced protection. Understanding the complex interaction of neutrophils and melanoma cells might aid in discovering methods to prevent the tumor-promoting effects by neutrophils in patients. Elevated levels of peripheral blood and tumor tissue neutrophils are associated with poorer clinical response and therapy resistance in melanoma. The underlying mechanism and the role of neutrophils in targeted therapy is still not fully understood. Serum samples of patients with advanced melanoma were collected and neutrophil-associated serum markers were measured and correlated with response to targeted therapy. Blood neutrophils from healthy donors and patients with advanced melanoma were isolated, and their phenotypes, as well as their in vitro functions, were compared. In vitro functional tests were conducted through nonadherent cocultures with melanoma cells. Protection of melanoma cell lines by neutrophils was assessed under MAPK inhibition. Blood neutrophils from advanced melanoma patients exhibited lower CD16 expression compared to healthy donors. In vitro, both healthy-donor- and patient-derived neutrophils prevented melanoma cell apoptosis upon dual MAPK inhibition. The effect depended on cell–cell contact and melanoma cell susceptibility to treatment. Interference with protease activity of neutrophils prevented melanoma cell protection during treatment in cocultures. The negative correlation between neutrophils and melanoma outcomes seems to be linked to a protumoral function of neutrophils. In vitro, neutrophils exert a direct protective effect on melanoma cells during dual MAPK inhibition. This study further hints at a crucial role of neutrophil-related protease activity in protection. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to elucidate the role of peripheral inflammation in Huntington's disease (HD) by examining the correlation of peripheral inflammatory markers with clinical manifestations and disease prognosis. Methods: This investigation involved 92 HD patients and 92 matched healthy controls (HCs). We quantified various peripheral inflammatory markers and calculated their derived metrics including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII). Clinical assessments spanning cognitive, motor, and disease severity were administered. Comparative analysis of inflammatory markers and clinical correlations between HD and controls was performed. Kaplan--Meier survival analysis and Cox regression model were used to assess the effect of inflammatory markers on survival. Results: The study revealed that HD patients had significantly reduced lymphocyte counts, and LMR. Conversely, NLR, PLR, and SII were elevated compared to HCs. Lymphocyte levels inversely correlated with the age of onset and monocyte levels inversely correlated with the UHDRS-total functional capacity (TFC) scores. After adjusting for age, sex, and CAG repeat length, lymphocyte count, NLR, PLR, and SII were significantly correlated with the progression rate of TFC scores. Elevated levels of white blood cells and monocytes were associated with an increased risk of disability and mortality in the HD cohort. Conclusion: Our findings indicate that HD patients display a distinct peripheral inflammatory profile with increased NLR, PLR, and SII levels compared to HCs. The peripheral inflammation appears to be linked with accelerated disease progression and decreased survival in HD. [ABSTRACT FROM AUTHOR]

Locally advanced or metastatic head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis. The introduction of PD-1 inhibitors has led to a significant improvement in survival, but only a subpopulation of patients responds to therapy. Current biomarkers cannot reliably identify these patients. The identification of biomarkers for the prediction and monitoring of immunotherapy is therefore of great importance. In this study, we characterized lymphocyte subsets in the peripheral blood of HNSCC patients under PD-1 inhibition. Patients with primary response (n=11) to PD-1 inhibition showed an increase of the CD3+ effector memory (CD3/EM) population and an elevated expression of the activation marker CD69 in CD3+ T cells, particularly in the CD3/EM subpopulation at 3 months when treatment response was assessed. In contrast, patients with primary treatment failure and progressive disease (n=9) despite PD-1 inhibition had lower absolute lymphocyte counts and an increased expression of CTLA-4 in CD3+ T cells at the time of treatment failure compared with baseline, particularly in CD4+ and CD8+ effector memory populations. Our results demonstrate that HNSCC patients' response to immune checkpoint inhibition shows a distinct immune signature in peripheral blood, which could help identify refractory patients earlier. Furthermore, strategies to overcome primary therapy failure by inducing a beneficial T cell phenotype or adding alternative immune checkpoint inhibitors could improve response rates and survival of HNSCC patients. [ABSTRACT FROM AUTHOR]

Objectives: Acute appendicitis is the most common non-gynaecological indication for surgical intervention during pregnancy. The aim of this study was to compare perioperative and postoperative results of surgical treatment of acute appendicitis in the early and late stage of pregnancy. Material and methods: This is a retrospective study focused on the evaluation of perioperative and postoperative results of appendectomy in pregnancy. The study included all pregnant patients who underwent laparoscopic or open appendectomy at the University Hospital Ostrava during the observed 10-year period (January 2012–December 2021). The patients were divided into two subgroups according to the stage of pregnancy in relation to the expected viability of the foetus (the viability limit was defined as the 23rd week of pregnancy). Results: In the monitored 10-year period, a total of 25 pregnant patients underwent appendectomy. Comparing the two subgroups of patients, there were no statistically significant differences in any of the admission parameters. Laparoscopy was performed in 100% of the patients in the lower stage of pregnancy (< 23 g.w.) and in 61% of the subgroup of patients with more advanced pregnancy (> 23 g.w.); this difference was statistically significant (p = 0.039). Differences in subgroups regarding duration of surgery, risk of revision and 30-day postoperative morbidity were not statistically significant. In the subgroup of patients < 23 g.w., uncomplicated forms of appendicitis predominated (66%), whereas in the subgroup > 23 g.w., complicated forms predominated (69%); this difference was statistically significant (p = 0.026). When comparing the two subgroups of patients, there was a statistically significant difference in the length of hospitalization (p = 0.006). The mortality rate of the group was zero. Conclusions: The results of the study confirm the fact that advanced pregnancy may be related to complicated forms of appendicitis. Therefore, early appendectomy is still the method of choice. In accordance with the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) recommendations, laparoscopic approach is preferred in pregnant patients, even in advanced pregnancy. [ABSTRACT FROM AUTHOR]

Background: Persistentneutrophiliais a well-recognized phenomenon in some chronic cigarette smokers. In contrast, persistentpolyclonal B-cell lymphocytosis (PPBL) is considered a rare entity affecting this patient population. Methods: We analyzed a cohort of 21 patients with chronic smoking histories presenting with persistent leukocytosis. None of the patients was on steroids, lithium preparations, or other medications known to increase the white blood cell (WBC) counts. We excluded any myeloproliferative or lymphoproliferative conditions in our patient cohort. WBC differential was obtained during repeated visits and the mean values calculated. The results were subsequently compared to known upper normal limits and tested for statistical significance. Results: The absolute leukocyte count in our cohort was 17.8 ± 3.2 x 109/L and the absolute neutrophil count was 12.0 ± 2.8 x 109/L. The difference proved statistically significant for both values when compared to upper normal limits (P < 0.001). Six patients (five females and one male) were also found to have a significant and persistent lymphocytosis at 5.1 ± 0.5 x 109/L (P < 0.001). Conclusions: We have identified the presence of ~29% PPBL cases in a series of consecutive patients with persistent leukocytosis/neutrophilia related to chronic cigarette smoking. Similar to the results obtained by other investigators, our PPBL patients showed a younger female predominance. Given the findings in our cohort, we believe that PPBL might be more common than previously thought and discuss further its potential implications for general and specialty practice. [ABSTRACT FROM AUTHOR]