Low Lymphocyte Count Research Articles

Outbreak of Trypanosoma vivax in Dairy Cows: Hematologic, Immunological and Antioxidant Responses Before and After Treatment with Isometamidium Chloride

Trypanosoma vivax infection is an emerging condition that causes damage and mortality among cattle and is transmitted by mechanical vectors or contaminated fomites. This disease has been spreading in southern Brazil, causing anemia, weight loss, diarrhea, abortion, and infertility; however, its behavior and host–parasite relationships are not yet fully understood. To clarify this issue, animals that presented clinical signs were subjected to an immunochromatographic screening test. An indirect immunofluorescence test was then performed on samples collected before treatment (the gold standard test), which showed that in the herd of 20 cows, we had 14 seropositive for T. vivax. Blood samples were collected before and after treatment to study the effects of the disease and treatment, with the cows divided into two groups: infected and uninfected. Cows were evaluated for hematologic, biochemical, and antioxidant responses, comparing them with uninfected and infected animals, as well as pre- and post-treatment (isometamidium chloride—1 mg/kg body weight [BW]). There was no difference (p > 0.05) between groups in milk production and feed intake; however, ten days after treatment, there was an increase of 1.72 kg of milk in cows diagnosed as infected with T. vivax. Seropositive cows had lower erythrocyte counts, hemoglobin concentrations, hematocrit, platelet counts, and lymphocyte and granulocyte counts. In seropositive cows, the higher total protein concentration is due to increased globulins, which the protein profile by electrophoresis showed to be related to higher levels of immunoglobulins (IgA and other heavy-chain immunoglobulins), ceruloplasmin, haptoglobin, ferritin, C-reactive protein; associated with lower transferrin levels. The activity of the enzymes aspartate aminotransferase, gamma-glutamyl transferase, cholinesterases, and creatine kinase were compared in seronegative and seropositive cows for T. vivax. Lower serum calcium levels were observed in seropositive cows. Cows diagnosed with trypanosomosis presented high levels of reactive oxygen species, lipid peroxidation, protein oxidation, nitrite/nitrate activity, superoxide dismutase, and glutathione peroxidase. The enzymes catalase and glutathione S-transferase presented lower activity in the blood of seropositive cows compared to the control on the day of diagnosis, which was no longer observed ten days after treatment. The animals exhibited hypogalactia, anemia, thrombocytopenia, leukopenia, and acute phase response accompanied by liver and muscle tissue damage and oxidative stress, demonstrating the effect of T. vivax infection in naturally infected Jersey cows.

Severe Lymphopenia Predicts Poorer Survival in Patients With Rectal Cancer Undergoing Neoadjuvant Chemoradiation.

Chemoradiation-induced lymphopenia is common and associated with poorer survival in multiple solid malignancies. However, the association between chemoradiation-related lymphopenia and survival outcomes in rectal cancer is yet unclear. The objective of this study was to evaluate the prognostic impact of lymphopenia and its predictors in patients with rectal cancer undergoing neoadjuvant chemoradiation. The inclusion criteria for this single-institution retrospective study were as follows: (1) biopsy-proven diagnosis of rectal adenocarcinoma, (2) receipt of neoadjuvant chemoradiation followed by surgery, and (3) absolute lymphocyte count available prior to and within 12 weeks of chemoradiation. In general, chemoradiation consisted of 5-fluorouracil or capecitabine and radiotherapy with 50.4 Gy over 28 fractions. Lymphopenia was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The primary variable of interest was absolute lymphocyte count nadir within 12 weeks of chemoradiation, dichotomized by <500/μL (grade 3 or worse lymphopenia). The primary endpoint was overall survival. Cox modeling and Kaplan-Meier methods were used to perform survival analyses. A total of 193 patients were identified with a median follow-up of 68 months. Overall clinical stage was 2 in 21% and 3 in 76%. Median baseline lymphocyte count for the entire cohort was 1700/μL. One hundred ten patients (57%) experienced chemoradiation-related severe lymphopenia. Pathologic complete response rate was 21%; 83% received adjuvant chemotherapy. Lower baseline lymphocyte count was significantly associated with increased risk for chemoradiation-related severe lymphopenia (odds ratio, 1.71). On multivariable Cox regression analysis, chemoradiation-related severe lymphopenia was significantly associated with worse disease-free survival (hazard ratio, 2.64) and overall survival (hazard ratio, 4.32). Five-year overall survival was 79% versus 92%, and 5-year disease-free survival was 70% versus 86% in the cohort that experienced versus did not experience severe lymphopenia, respectively. Chemoradiation-induced lymphopenia is common and a prognostic marker of poorer survival in rectal cancer. Closer observation in high-risk patients and treatment modifications may be potential approaches to mitigating treatment-related lymphopenia. Our findings also suggest an important role of the host immunity in rectal cancer outcomes and support future studies investigating ways to reduce treatment-induced lymphopenia.

P-771. Demographic and Clinical Characteristics of Adverse Reactions to anti-Tuberculosis Therapy: A Retrospective Analysis

Abstract Background Adverse reactions (AR) to anti-tuberculosis (anti-TB) therapy pose a significant challenge, leading to decreased treatment compliance, increased morbidity and mortality rates, and prolonged hospital length-of-stay. Methods This study examines the demographic, clinical, and laboratory profiles of patients diagnosed with tuberculosis and hospitalized at the Tor Vergata Policlinic in Rome between 2013-2023, who experienced adverse reactions requiring the interruption, suspension, or modification of anti-tuberculosis therapy, in the period 2013-2023. Results Out of 242 patients receiving treatment for tuberculosis, data regarding AR were available for 136 cases. Of these, 35.3% (48/136) experienced an AR attributable to anti-tuberculosis therapy, median age of 39 years (IQR 26.5-57), 72.9% male, 60.4% non-italians, and 41.6% undergoing treatment for pulmonary TB. The most common AR were hypertransaminasemia (52.2%), allergic reaction (25%), and cholestasis (8.3%). Patients with AR characterized by hypertransaminasemia/cholestasis compared to those with allergic reactions were younger (31 years (IQR 25-45) vs. 60.5 (IQR 36-69.5); p=0.012), more frequently of non-italian nationality (74.2% vs. 25.8%; p= 0.013), and had more frequently a negative Quantiferon test (41.9% vs. 8.3%; p= 0.03). Pirazinamide emerged as the drug most frequently linked to AR, being suspended in 62.5% of cases (20/29 due to hypertransaminasemia; 8/12 due to allergic reaction). In 76.2% of cases, the drug responsible for the AR was discontinued in favor of a fluoroquinolone. All ARs resolved upon suspension of the implicated drug. Among patients with AR, 65.3% recovered, and 13% died. Patients with AR had a lower lymphocyte count at treatment initiation compared to patients without AR (median 1150 (IQR 780-1940) vs 1460 (IQR 1035-2020), p=0.04) and had more frequently a negative Quantiferon test (29.2% vs 10.2%; p=0.012). Conclusion AR during TB therapy affected 35% of patients in our sample. Pyrazinamide was the most commonly implicated drug, and the reactions resolved upon discontinuation. A lower lymphocyte count at TB diagnosis in patients with AR might indicate an immune component, similar to IRIS, in their onset. However, further studies are warranted to explore this aspect. Disclosures All Authors: No reported disclosures

P-1904. The Interaction of Serum Biomarkers and Lymphopenia on Pulmonary COVID-19 Illness Progression in Hospitalized Patients

Abstract Background Low absolute lymphocyte count (ALC) as well as elevated levels of plasma nucleocapsid antigen (N-antigen) and C-reactive protein (CRP) are independently associated with COVID-19 clinical outcomes. We evaluated the potential additive interaction of these three prognostic markers on the progression of pulmonary COVID-19 illness. Methods We utilized publicly available data to perform a secondary analysis of hospitalized adults who enrolled into the Therapeutics for Inpatients with COVID-19 platform trial (NCT04501978). Plasma N-antigen level &amp;gt; 1000 ng/L, CRP level &amp;gt; 75 mg/L, and ALC &amp;lt; 1.5x109/L, all measured at baseline, were the three prognostic markers of interest. The outcome of interest was worsened pulmonary status, dichotomized as either worse or same/better than baseline status on a 7-point ordinal scale, at day 5. Estimated coefficients from modified multivariable Poisson regression were utilized to calculate risk ratios. We then calculated relative excess risk due to interaction (RERI) to evaluate departure from additivity. We present a measure of excess risk due to the respective two-way interactions when one of the markers is absent (RERI2), a measure of excess risk due to the three-way interaction (RERI3), and a total summation of excess risk (TotRERI). Results A total of 2,478 enrolled patients were included in our complete-case analysis (Figure 1). The interaction of low ALC, elevated plasma N-antigen level and elevated CRP level on worsened pulmonary status at day 5 may be super-additive (TotRERI = 0.88, 95% confidence interval (CI): -0.71 – 2.48) (Table 1). This 88% excess risk of worsened pulmonary status is mainly due to the explicit three-way interaction (RERI3: 1.56, 95% CI: -0.77 – 3.89). Sensitivity analysis utilizing multiple imputation to address missing data revealed similar estimates: TotRERI: 0.87 (95% CI: -0.79 – 2.53) and RERI3: 1.70 (-0.74 – 4.14). Conclusion Our data suggest that the interaction of low ALC, elevated plasma N-antigen level and elevated CRP level may be associated with excess risk of worsened pulmonary COVID-19 illness among hospitalized patients. Further evaluation regarding the interaction of prognostic markers in identifying patients at high-risk of pulmonary deterioration is supported. Disclosures Eleftherios Mylonakis, MD, PhD, BARDA: Grant/Research Support|Basilea: Advisor/Consultant|Chemic Labs/KODA Therapeutics: Grant/Research Support|Cidara: Grant/Research Support|Leidos Biomedical Research Inc./NCI: Grant/Research Support|NIH SciClone Pharmaceuticals: Grant/Research Support|NIH/NIAID: Grant/Research Support|NIH/NIGMS: Grant/Research Support|Pfizer: Grant/Research Support|Regeneron Pharmaceuticals, Inc.: Grant/Research Support

P-2108. Risk Factors for Indeterminate Tuberculosis (TB) Testing Results Among Immunocompromised Children in an Area of Low TB Endemicity

Abstract Background Tumor necrosis factor α inhibitors (TNFαi) are immunosuppressants used to treat autoimmune (AI) conditions and inflammatory bowel disease (IBD). TNFαi initiation requires tuberculosis infection (TBI) screening, often performed by interferon-γ release assays (IGRA) including the QuantiFERON Gold Plus (QFT) and T-SPOT.TB (T-SPOT). The rate of and risk factors for indeterminate (IND) testing results, as well as the optimal TBI screening assay, among immunocompromised children (ICC) with AI or IBD in an area of low TB endemicity remain poorly defined. We performed a retrospective analysis of QFT testing at our institution to identify rates of and risk factors for IND results. We also prospectively evaluated the performance of QFT versus T-SPOT in an area of low TB endemicity. Methods A retrospective analysis of children (ages 0-21 years) with AI or IBD on immunosuppression cared for at Nationwide Children’s Hospital (NCH) from 1/2010-12/2023 who underwent TBI screening with QFT. Patients were excluded if they had prior TBI, BCG vaccine, and organ or stem cell transplant. Demographic, laboratory results, and medication history were recorded. Prospectively, QFT-eligible patients were consented for concurrent testing utilizing the T-SPOT test, run in parallel. Single variable statistical analysis was performed. Results 662 patients (372 (56.2%) male) had 2011 unique QFT tests performed. 148 patients (22.4%) had a total 191 (9.5%) IND QFT result at any time in the study interval. Younger age, lower absolute lymphocyte counts (ALC), and corticosteroid exposure at testing were observed more frequently in those with IND QFT results [TABLE 1]. At an interim assessment of the prospective study, 117 patients underwent tandem screening by QFT and T-SPOT; 5 total IND results were observed [QFT (n=4), T-SPOT (n=1)] [TABLE 2]. Conclusion Younger age, lower ALC, and corticosteroid exposure at time of testing were observed more frequently in those with IND QFT results. While interim assessment of T-SPOT vs. QFT does not yield a difference, this may be driven by a high proportion of individuals with adequate disease control. Ongoing prospective assessment may better define an optimal screening IGRA assay for TBI among ICC with AI or IBD in an area of low TB endemicity. Disclosures Jennifer L. Dotson, MD, MPH, Pfizer: Grant/Research Support Christopher Ouellette, MD, Oxford Immunotec: Grant/Research Support|UpToDate: Royalties

Association of Circulating Basophil Count with Gastric Cancer Prognosis.

Basophils play a crucial role in immunoglobulin E-mediated allergic reactions and parasitic infections. Recently, a low basophil count was reported to be a poor prognostic indicator in patients with malignant tumors. This study aimed to investigate the cut-off value to evaluate the clinicopathological and prognostic significance of the basophil count in patients with gastric cancer. This study enrolled 1192 gastric cancer patient who underwent surgery without preoperative chemotherapy between 2001 and 2020. The cutoff value was 26/μl based on the receiver of characteristics curves for overall survival, and 606 patients were classified as the low basophil group. The clinicopathological and prognostic significance of the low basophil count was assessed by univariate and multivariate analyses. Elderly age (p < 0.001), high C-reactive protein level (p < 0.001), low lymphocyte count (p = 0.044), and low neutrophil count (p < 0.001) are independently associated with low basophil count. The low basophil group demonstrated a significantly worse overall survival than the high basophil group (p = 0.005). Although there was no significant difference in stage I, the low basophil group demonstrated poor overall survival in stage II/III/IV. In stage II, low basophil count was independently associated with poor OS. In stage III/IV, low basophil group tended to have poor overall survival rate. Including all stages, low basophil count was an independent risk factor for poor overall survival (hazard ratio (HR) = 1.29, 95% CI: 1.03-1.61, p = 0.027). Low basophil count was significantly associated with elderly age, high C-reactive protein level, and low neutrophil count (<26/μl). In addition, low basophil count was an independent poor prognostic factor in patients with gastric cancer. Thus, preoperative circulating basophil count assessment may be useful for predicting the postoperative survival of patients with gastric cancer.

The effect of immunosuppression on outcomes in elderly patients with community-acquired pneumonia

BackgroundThe effect of immunosuppression on clinical manifestations and outcomes was unclear in elderly patients with CAP.MethodsElderly hospitalised patients with CAP were consecutively enrolled and were divided into immunocompromised hosts (ICHs) or non-ICHs groups. Clinical manifestations, severity, and outcomes were compared. The logistic regression model was used to determine the association between immunosuppression and outcomes. The primary outcome was 30-day mortality.ResultsA total of 822 patients were enrolled, of whom 133 (16.2%) were immunocompromised. There were no differences between the two groups in vital signs, oxygenation, admission laboratory tests, need for mechanical ventilation and intensive care unit admission, except for a lower lymphocyte count in the ICH group (0.9*10^9/L, IQR 0.6–1.3*10^9/L [ICH group] vs. 1.2*10^9/L, IQR 0.8–1.7*10^9/L [non-ICH group]; p < 0.001). The 30-day mortality in ICHs was 15.8%, significantly higher than the 5.1% in non-ICHs (p < 0.001). The risk distribution of severity was similar between the two groups when assessed by CURB-65 on admission; however, the significant difference was found when assessed by PSI. Notably, in the CURB-65 low-risk group, the 30-day mortality was significantly higher in ICHs than in non-ICHs (9.7% vs. 1.1%, p < 0.001); but there was no difference between ICHs and non-ICHs in PSI low-risk group (3.7% vs. 0.6%; p > 0.05). After adjusting for age, sex, and comorbidities, immunosuppression was significantly associated with a higher risk of 30-day mortality (odds ratio 5.004, 95% CI [2.618–9.530]).ConclusionsImmunosuppression was independently associated with an increased risk of 30-day mortality. CURB-65 may underestimate the mortality risk of ICHs.

Complete blood counts as potential risk factors of early dissemination to liver and lungs in resected colorectal cancer: a retrospective cohort study

PurposeLiver and lung metastases demonstrate distinct biological, particularly immunological, characteristics. We investigated whether preoperative complete blood count (CBC) parameters, which may reflect the immune system condition, predict early dissemination to the liver and lungs in colorectal cancer (CRC).MethodsIn this retrospective single-centre study, we included 268 resected CRC cases with complete 2-year follow-up and analysed preoperative CBC for association with early liver or lung metastasis development. Next, selected CBC and clinicopathological parameters were analysed with uni- and multivariable Cox regression. Independent factors affecting liver or lung metastasis-free survival were incorporated into composite scores, which were further evaluated with receiver operating characteristic (ROC) curves and dichotomised using a modified, specificity-focused, Youden approach to identify particularly high-risk patients.ResultsCompared to metastasis-free patients, early liver metastases were related to decreases in red blood cells, haematocrit, lymphocytes and elevated monocyte-to-lymphocyte ratio, while lung metastases to lower eosinophil counts. A composite score of independent factors (erythrocytopenia, lower lymphocyte count and pN) yielded HR of 8.01 (95% CI 3.45–18.57, p < 0.001) for liver-specific metastasis-free survival (MFS). For lung-specific MFS, the combination of eosinopenia, pN and primary tumour location showed HR of 13.69 (95% CI 4.34–43.20, p < 0.001).ConclusionEarly CRC metastases to the liver and lungs are associated with partially divergent clinicopathological and peripheral blood features. We propose simple, clinically implementable scores, based on routinely assessed parameters, to identify patients with an increased risk of early dissemination to the liver or lungs. After validation in independent cohorts, these scores may provide easily available prognostic information.

Clinical characteristics and prognostic analysis of concurrent Pneumocystis jirovecii pneumonia in patients with idiopathic inflammatory myopathy

Objective: To describe the clinical characteristics and to explore the prognostic factors of concurrent pneumocystis jirovecii pneumonia (PJP) in patients with idiopathic inflammatory myopathy (IIM). Methods: We retrospectively enrolled consecutive IIM patients diagnosed with PJP at our center between January 2014 and December 2022. Fifty-eight IIM-PJP patients were enrolled in our study, with the age of 26-79 (56.3±12.1) years. There were 19 males (32.9%) and 39 females (67.1%). The participants were classified into survival group (21 patients) and non-survival group (37 patients) according to the clinical outcome. Cox regression models were used to analyze the prognostic factors. Results: Compared with the survival group, there were more patients with anti- melanoma differentiation-associated gene (MDA5) positive, respiratory failure, hospital-acquired pneumonia, second-line PJP treatment, and caspofungin treatment in non-survival group (P<0.05). Meanwhile, the time from onset of IIM, corticosteroid therapy, and immunosuppressant medication to diagnosis of PJP was significantly shorter in non-survival patients than survival patients (P<0.05). Additionally, non-survival patients had higher neutrophil percentage and creatine kinase (P<0.05), and lower lymphocyte count and percentage, platelets, minimal albumin, NK cell count, T cell count, and CD8+T cell count (P<0.05). Multivariate analysis showed that anti-MDA5 positive (HR=3.54, P<0.05, 95%CI: 1.27-9.89), oral candidiasis infection (HR=2.62, P<0.05, 95%CI: 1.07-6.43) and thrombocytopenia (HR=5.00, P<0.01, 95%CI: 1.88-13.32) were independent risk factors for IIM-PJP patients. Conclusions: Middle-aged females were the main IIM-PJP in our group, and the mortality rate was 63.8%. Anti-MDA5 antibody positive, oral candidiasis infection, and thrombocytopenia were independent survival risk factors for them.

Helicobacter pylori Infection as a Cause of Dyspepsia in the Pakistani Population: An Experience From a Large Tertiary Care Center.

Background Dyspepsia is one of the most common worldwide gastrointestinal disorders, more prevalent in developing countries like Pakistan. One of the most common causes of dyspepsia is Helicobacter pylori. Therefore, this study aimed to determine the frequency of H. pylori infection among dyspeptic patients presenting to a tertiary care hospital in Karachi, Pakistan. Methodology This cross-sectional study was conducted from January 2021 to March 2022 at Medical Ward VII, Jinnah Postgraduate Medical Center, Karachi. In this study, 370 patients aged 18 years or higher of either gender presenting with symptoms of dyspepsia for more than four weeks were recruited. Patients who received antibiotics within the last four weeks and those with suspected gastric malignancies or liver disease were excluded from the study. Clinical assessment, upper gastrointestinal endoscopy, and histopathological examination of gastric biopsies were performed. Statistical analysis was done using SPSS version 25 (IBM Corp., Armonk, NY, USA), and p-values <0.05 were considered statistically significant. Results H. pylori infection was diagnosed in 64.8% of patients presenting with dyspepsia. Dominant dyspeptic symptoms included upper abdominal pain in 92.4% of the cases and heartburn in 82.2%. Significant associations with H. pylori infection included male gender (p = 0.03), low socioeconomic status (p ≤ 0.01), consumption of outside food (p = 0.012), low hemoglobin levels (p = 0.02), low lymphocyte count (p = 0.017), and decreased lymphocyte count (p = 0.039). Conclusions H. pylori infection is a very common cause of dyspepsia in Pakistan, and much needs to be done at the public health level to improve hygiene and dietary practices. Longitudinal outcomes, antibiotic resistance, and treatment efficacy are further areas that need to be researched to define an optimal management strategy.

Neutrophil-to-Lymphocyte Ratio and System Score Could Predict the Occurrence of Macrophage Activation Syndrome in Patients with Adult-Onset Still's Disease.

To investigate the characteristics of Adult-onset Still's disease (AOSD) patients with macrophage activation syndrome (MAS) and explore the risk factors for the development of MAS. A case-control study. Place and Duration of the Study: Department of Rheumatology and Immunology, the Second Hospital of Anhui Medical University, Anhui, China, from January 2008 to June 2024. AOSD patients with MAS (AOSD-MAS) and without MAS (AOSD-nonMAS) were compared. Clinical features and laboratory results from two groups were analysed using the independent samples t-test or Mann-Whitney U test. Fisher's exact test or Pearson's Chi-square test was used to compare the variables between the two groups. The multivariable logistic regression analysis was applied to identify AOSD with MAS-associated factors. The value of risk factors in predicting MAS occurrence was carried out by a receiver operating characteristic validation analysis. MAS patients showed higher prevalence of sore throat, splenomegaly and abnormal liver function, a lower prevalence of arthrodynia and higher levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio, alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase, serum ferritin, D-Dimer levels, and a higher AOSD system score, along with a lower lymphocyte count (p <0.05). Multivariate logistic regression analysis identified NLR and AOSD system scores as predictors of MAS. An optimised threshold of 17.455 and 5.500 for NLR and AOSD system score yielded a sensitivity of 84.60% (38.50) and a specificity of 91.00%, (47.40). Early detection of MAS in AOSD may be facilitated by monitoring these factors, particularly NLR and AOSD system scores. Adult-onset still's disease, Macrophage activation syndrome, Risk factor.

Whole blood concentrations of fingolimod and its pharmacologically active metabolite fingolimod phosphate obtained during routine health care of patients with multiple sclerosis.

Fingolimod is a first-in-class, orally administered drug indicated for the treatment of relapsing-remitting multiple sclerosis. It acts as an immunomodulator, is classified as a "disease-modifying therapy", and its main mechanism of action is the modulation of sphingosine-1-phosphate receptors. In this prospective pilot study, whole blood concentrations of fingolimod and fingolimod phosphate obtained during routine health care were measured. In this study, we aimed to determine whether therapeutic monitoring of fingolimod and fingolimod phosphate concentrations can help personalise pharmacotherapy for patients with multiple sclerosis. The study group consisted of 73 patients treated with oral fingolimod (0.5 mg) once daily. Blood samples were collected between July 2021 and January 2022. The whole blood concentrations of fingolimod and fingolimod phosphate were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The relationship between the measured concentrations and the absolute peripheral blood lymphocyte count was evaluated. Fingolimod concentrations ranged from 0.61 to 6.21 µg/L, and fingolimod phosphate concentrations from 0.48 to 4.28 µg/L. Significantly higher concentrations of the active metabolite, fingolimod phosphate, and a significantly higher fingolimod phosphate/fingolimod concentration ratio were observed in women. The sum of fingolimod and fingolimod phosphate concentrations was significantly higher in the subgroup of patients with a lower absolute peripheral blood lymphocyte count. Although all patients were treated with the same dose of fingolimod (0.5 mg orally daily), a 10-fold difference was observed in the achieved whole blood concentrations of fingolimod and fingolimod phosphate. This wide inter-individual variability may lead to potential toxicity or suboptimal concentrations, with the risk of further deterioration in the clinical condition of patients with multiple sclerosis. Therefore, fingolimod is a suitable candidate for therapeutic drug monitoring, including monitoring patient adherence to treatment.

Healing Potential of Chromolaena odorata Extract: Modulation of Neutrophil, Macrophage, and Lymphocyte Response in Infected Wounds of Mus musculus

Chromolaena odorata has been reported to possess antimicrobial, antibacterial, and anti-inflammatory properties that aid in wound healing. Previous studies demonstrated the significant effects of a 7.5% concentration of C. odorata extract on non-infected wounds. This study aims to investigate its impact on infected wound healing. An experimental study was conducted on 36 mice, divided into two groups. Partial-thickness wounds were created on the dorsal side of each mouse and contaminated with S. aureus (106 CFU/ml). Group 1 was treated with normal saline, while Group 2 was treated with C. odorata aqueous extract at 7.5%. Histopathological analysis was performed on days 3 and 5 to count neutrophils, macrophages, and lymphocytes. Results showed a significantly lower neutrophil, macrophage, and lymphocyte count in Group 2 compared to Group 1 (p &lt; 0.05). On day 3 and 5, Group 2 had lower neutrophil counts (5.6 ± 1.8, 5.8 ± 0.6) compared to Group 1 (9.2 ± 5.2, 15.1 ± 3.9). Macrophage counts were also lower in Group 2 (6.9 ± 1.7, 1.9 ± 0.7) compared to Group 1 (3.7 ± 1.4, 4.3 ± 0.9). Lymphocyte counts followed a similar trend, with Group 2 having fewer lymphocytes on both days (p &lt; 0.05). In conclusion, C. odorata aqueous extract at a 7.5% concentration demonstrates potential as a wound healing agent by reducing inflammatory cells in infected wounds.

The Effects of a Blend of Essential Oils in the Milk of Suckling Calves on Performance, Immune and Antioxidant Systems, and Intestinal Microbiota.

The objective of the present study was to determine whether the addition of a blend based on the essential oils of cinnamon, oregano, and eucalyptus to the liquid diets of calves would stimulate the immune system combined with anti-inflammatory action, minimize oxidative responses, and alter the intestinal microbiota, consequently enhancing animal growth. Twenty-four male Holstein calves (approximately five days old) were suckled for 60 days, underwent a weaning process, and were followed up until day 75 of the experiment. The calves were divided into control (n = 12) and phytobiotic (n = 12) groups, receiving commercial milk replacer and pelleted concentrate ad libitum. For the phytobiotic group, we added the blend to the liquid diet twice daily at 5 mL/feeding in the first 15 days and 10 mL/feeding until day 60. We detected no differences in weight gain, but animals in the phytobiotic group tended to consume less feed. Calves treated with phytobiotics showed better conversion and feed efficiency than the animals in the control group. Lower leukocyte and lymphocyte counts were observed, as was a higher cholesterol concentration. Immunoglobulin A, ceruloplasmin, and transferrin also differed between groups, with higher IgA and lower levels of acute-phase proteins (ceruloplasmin and transferrin) in calves that consumed the phytobiotic. Higher glutathione S-transferase activity was found in the serum of calves in the treatment group. The intestinal microbiota did not differ between the groups; however, the genera Acinetobacter, Pseudomonas, and Psychrobacter were the most abundant regardless of treatment. We concluded that the blend of oils based on cinnamon, oregano, and eucalyptus improved the calves' immune and antioxidant systems, improving feed efficiency without affecting the intestinal microbiota.

The Influence of Age, Sex, and Season on Hematological Parameters in a Captive Population of Former Laboratory Chimpanzees (Pan troglodytes).

This study aimed to establish a baseline hematological profile and examine the influence of age, sex, and season on hematological parameters in captive chimpanzees (Pan troglodytes) living in a humid tropical climate. Hematological parameters are a useful tool for assessing health status and diagnosing diseases in animals. We analyzed 473 blood samples collected from 84 chimpanzees (43 females and 41 males) during annual health checks, conducted under anesthesia for a routine physical examination. The main findings revealed significant sex differences in some hematological parameters: males had higher hematocrit and red blood cell counts than females. Age-related variations have also been noted, with adolescents and adults having lower lymphocyte counts but higher neutrophil and monocyte counts than infants. Adults, in particular, had significantly lower platelet counts compared to other age classes. Seasonal fluctuations were also observed: lymphocyte counts were higher in the rainy season, while neutrophil counts were higher in the dry season. In addition, the general trends in hematological parameters for this captive population of chimpanzees were similar to those reported in captive chimpanzees living in the United States. These results should provide animal health professionals, particularly those working with nonhuman primates, with data to compare and interpret. They will help improve practices for monitoring and managing the health of nonhuman primates in captivity.

Predicting Severe Respiratory Failure in Patients with COVID-19: A Machine Learning Approach.

Background/Objectives: Studies attempting to predict the development of severe respiratory failure in patients with a COVID-19 infection using machine learning algorithms have yielded different results due to differences in variable selection. We aimed to predict the development of severe respiratory failure, defined as the need for high-flow oxygen support, continuous positive airway pressure, or mechanical ventilation, in patients with COVID-19, using machine learning algorithms to identify the most important variables in achieving this prediction. Methods: This retrospective, cross-sectional study included COVID-19 patients with mild respiratory failure (mostly receiving oxygen through a mask or nasal cannula). We used XGBoost, support vector machines, multi-layer perceptron, k-nearest neighbor, random forests, decision trees, logistic regression, and naïve Bayes methods to accurately predict severe respiratory failure in these patients. Results: A total of 320 patients (62.1% male; average age, 54.67 ± 15.82 years) were included in this study. During the follow-ups of these cases, 114 patients (35.6%) required high-level oxygen support, 67 (20.9%) required intensive care unit admission, and 43 (13.4%) died. The machine learning algorithms with the highest accuracy values were XGBoost, support vector machines, k-nearest neighbor, logistic regression, and multi-layer perceptron (0.7395, 0.7395, 0.7291, 0.7187, and 0.75, respectively). The method that obtained the highest ROC-AUC value was logistic regression (ROC-AUC = 0.7274). The best predictors of severe respiratory failure were a low lymphocyte count, a high computed tomography score in the right and left upper lung zones, an elevated neutrophil count, a small decrease in CRP levels on the third day of admission, a high Charlson comorbidity index score, and a high serum procalcitonin level. Conclusions: The development of severe respiratory failure in patients with COVID-19 could be successfully predicted using machine learning methods, especially logistic regression, and the best predictors of severe respiratory failure were the lymphocyte count and the degree of upper lung zone involvement.

Quantitative analysis of chest CT in coronavirus infected patients and its correlation with clinical features

To explore the quantitative analysis results of different patterns of chest computed tomography (CT) in patients with coronavirus infection and its relationship with viral load and pathophysiological status. A retrospective clinical cohort study was conducted. Patients with coronavirus infection admitted to Qingdao Municipal Hospital from June 9 to 15, 2023 (all patients underwent chest CT examination within 24 hours after diagnosis) were enrolled. The patients were divided into coronavirus infection non-pneumonia group and coronavirus infection associated pneumonia group according to CT findings. Relevant baseline data, such as demographic characteristics, chest CT characteristics, and laboratory indicators within 12 hours before and after CT examination were collected from each group. Spearman correlation test was used to quantitatively analyze the correlation between CT features and laboratory indicators. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of each laboratory index for pneumonia in patients infected with coronavirus. Multiple linear regression analysis was used to explore the relationship between different CT patterns such as ground-glass opacity (GGO) and consolidation and ventilatory oxygenation status. A total of 171 patients were enrolled, including 44 patients in the coronavirus infection non-pneumonia group and 127 patients in the coronavirus infection associated pneumonia group (the incidence of pneumonia was 74.3%). Compared with patients with coronavirus infection alone, patients with coronavirus infection associated pneumonia had significantly lower lymphocyte count (LYM), oxygenation index (PaO2/FiO2), total lung capacity, GGO volume and GGO ratio, and significantly higher C-reactive protein (CRP), neutrophil/lymphocyte ratio (NLR), D-dimer, fraction of inspired oxygen (FiO2) level, real volume variation and consolidation ratio, the differences were all statistically significant. There were no statistically significant differences in the nucleocapin protein (N) gene cycle threshold (Ct) value and open reading frame (ORF) gene Ct value between the two groups. ROC curve analysis showed that, after adjusting for age, gender, CRP level and other related factors, compared with N gene Ct value, ORF gene Ct value, N gene Ct value+LYM, ORF gene Ct value+LYM, the LYM had the most potential diagnosis power for coronavirus infection associated pneumonia. The area under the ROC curve (AUC) of LYM for predicting coronavirus infection was 0.703. When the cut-off value of LYM was 0.7×109/L, the sensitivity was 55.5%, and the specificity was 79.5%, respectively. Multiple linear regression analysis showed that, when adjusted for consolidation ratio, age, gender, Hb and D-dimer levels, the GGO ratio in patients with coronavirus infection associated pneumonia was correlated with PaO2/FiO2 (β = -2.18, P < 0.001). When adjusted for GGO ratio, age, sex, Hb and D-dimer levels, the proportion of consolidation in patients with coronavirus infection associated pneumonia was correlated with PaCO2 (β = 0.36, P = 0.004). When adjusted for GGO ratio, the proportion of consolidation in patients with coronavirus infection associated pneumonia was also associated with NLR (β = 0.79, P = 0.006). LYM could be a potential marker for predicting coronavirus associated pneumonia, and the correlation seems to be independent of viral load. In addition, in the analysis of imaging features, GGO is associated with hypoxia, while consolidation is associated with PaCO2 level and inflammation. The increased proportion of consolidation in the whole lung may be detrimental to lung ventilation.

Predictors of lethal COVID-19 in patients of intensive care unit

Goal This study aimed to identify potential independent routine laboratory predictors of lethal COVID-19 in critically ill patients admitted to the ICU from August 1st to October 31st 2021, when the SARS-COV-2 delta variant prevailed in the region. Materials and Methods A retrospective single-center study case-control included 120 patients hospitalized to ICU №2 of the Samara Regional Clinical Hospital named after Seredavin from August 1st to October 31st 2021. The infection with SARS-COV-2 virus was verified with a real-time PCR test of the samples obtained from the nasopharynx. Results The study included 120 patients hospitalized to ICU with a severe form of ARDS caused by COVID-19-associated pneumonia. The results of the comparative analysis showed significant differences between the groups of survived and died patients when they were admitted to ICU. Died patients were older, had lower lymphocyte count, higher levels of glucose, ASAT, CPK, LDH, creatinine, BUN, and potassium, had lower cardiac output, and severe pulmonary lesions. Conclusion The single-center study included 120 patients with a severe form of COVID-19 that required their hospitalization to ICU. Univariate and multivariate regression analysis showed that the levels of LDH, BUN, glucose, ASAT, and lymphocyte count can act as independent predictors of the lethal outcome and have to be taken into account by ICU specialists during the evaluation of the clinical condition of patients for timely indication of the relevant therapy. The obtained data agree with previous studies that aimed to identify predictors of the severe course of COVID-19. However, further multi-center studies on larger cohorts of patients should be conducted for the identification of more precise associations between various predictors of lethality. It will help to reveal patients with a high risk of unfavorable outcomes after admission to ICU.

Cross-sectional analysis of blood leukocyte responsiveness to interleukin-10 and interleukin-6 across age and physical activity level.

To determine how the anti-inflammatory actions of interleukin-10 (IL-10) and IL-6 differ across age and physical activity levels. Using a cross-sectional design, fasted blood samples were obtained from younger physically inactive (YI:n=10, age: 22.7 ± 3.7 years, BMI: 24.8 ± 4.8 kg/m2, <150 min of weekly moderate-to-vigorous physical activity [MVPA]), younger highly active (YA: n=11 varsity cross country running athletes, 20.7 ± 2.7 years, 21.1 ± 1.8 kg/m2, >300 min of weekly MVPA), and older highly active (OA: 12, 56.0 ± 10.3 years, 22.8 ± 3.2 kg/m2, >300 min of weekly MVPA) individuals and analyzed for leukocyte counts, IL-10 and IL-6-related signaling, and cytokine secretion ex vivo. Total white blood cells and monocytes were similarbetween groups (p=0.8) but YA and OA had lower lymphocyte counts than YI (p<0.01). The ability of IL-10 (1 ng/mL) to phosphorylate signal transducer and activator of transcription 3 (STAT3) in CD14 monocytes was greater in YA vs. YI (p<0.03) despite YA having lower IL-10 receptor expression (p<0.01). IL-6 (10 ng/mL) mediated STAT3 phosphorylation in CD4 lymphocytes was higher in OA compared YI (p<0.01), with a similar tendency observed forYA vs. YI (p=0.08). Despite enhanced responsiveness of STAT3 to IL-10/6 in active individuals, the ability of IL-10/6 toinhibit tumor necrosis factor-alpha (TNF-⍺) secretion fromlipopolysaccharide-stimulated whole-blood was similar between groups. Highly active younger and older individuals demonstrate enhanced IL-10- and IL-6-mediated activation of immune cell STAT3. Although the ability of IL-10/6 to inhibit TNF-⍺ secretion appeared unimpacted by activity level, anti-inflammatory cytokine actions were preserved in older active individuals.

Hematological Changes in Newly Diagnosed Pulmonary Tuberculosis Patients on Standard Anti-TB Treatment Regimen and their Influence on Smear Conversion

Pulmonary tuberculosis (PTB) mortality remains high despite the availability of effective anti-TB therapy. Disease and treatment-associated hematological derangements at diagnosis and during therapy might contribute to this high TB mortality rate. This paper aims to determine hematological changes in newly diagnosed pulmonary tuberculosis patients on standard anti-TB treatment regimen and their influence on smear conversion. The study adopted a longitudinal design in which 55 newly diagnosed HIV negative PTB patients were followed up to the fifth month of anti-TB therapy. Blood samples (5ml) were collected for diagnosis during the second and fifth months and analyzed using automated HumaCount 5D hematology analyzer. Data was analyzed using Kruskal-wallis test with Dunn’s multiple comparisons test in Graph-Pad prism version 6.0. Throughout therapy, there was a statistically significant time-dependent decrease in median total white blood cell counts from 6.82x103/ uL at diagnosis to 5.87x103/ uL at the fifth month (P=0.0358). This decrease in total WBC count was majorly driven by significant decrease in the neutrophil numbers from 4.31x103/ uL at diagnosis to 2.97x103/ uL at the fifth month. The proportion of patients who had anemia at the fifth month of treatment increased compared to the second month post intensive phase. There was also a significant decrease in MCV, MCH and MCHC at the second month compared to diagnosis. Moreover, the median platelet count, MPV, PDW and PCT% decreased from 314x103/ uL, 8.9 fL, 10.4 fL and 0.273 at diagnosis to 232x103/ uL, 10.15 fL, 12.5 fL and 0.235 at the fifth month, respectively. High WBC count, high platelet count, low lymphocyte count and low HGB at the end of month two of therapy were shown to increase the likelihood of sputum non-conversion (OR-2.42 (95% Ci 2.07-2.82)), (OR-1.5 (95% Ci 1.01-2.22)), (OR-1 (95% Ci 1-1)) and (OR-2.58 (95% Ci 1.68-3.95)), respectively (P&lt;0.05). A significant number of PTB patients presented with anemia, thrombocytosis and leukocytosis. The proportion of patients with anemia increased over time. The study recommends screening for hematological abnormalities in patients for tailored patient interventions for better clinical outcomes.