Higher Percentage Of Lymphocytes Research Articles

Abstract 5206: High level STING expression in tumor and inflammatory cells is linked to microsatellite instability and favorable tumor parameters in a cohort of 1,900 colorectal cancer patients

Abstract Background: The stimulator of interferon genes (STING) is a transmembrane protein expressed on a variety of cell types including epithelial, inflammatory (lymphocytes and macrophages), and endothelial cells. STING expression has been described at variable levels in various tumor types where it might enhance anti-tumoral effects of the immune system and impact tumor angiogenesis. STING activating targeted therapies are currently evaluated in preclinical studies. However, the clinical significance of STING expression in tumor cells as compared to tumor-associated inflammatory cells is not fully resolved. Methods: To evaluate the potential clinical significance of STING expression in different cell types of colorectal cancer (CRC) tissue (tumor cells, lymphocytes, macrophages and endothelial cells), more than 1,900 patients were analyzed by multiplex fluorescence immunohistochemistry (CKpan, STING, CD45, CD68 and CD31) in a tissue microarray format (TMA) in combination with a deep-learning based algorithm for automated cell detection. Results: STING expression on colorectal cancer cells varied markedly. Of 1,905 evaluable cancers, 601 (31.5%) showed a strong expression in virtually all tumor cells and 428 (22.5%) lacked STING staining while 478 (25.1%) showed a weak, and 398 (20.9%) a moderate staining. High STING expression on tumor cells was associated with microsatellite instability (MSI, p<0.0001), low tumor stage (p=0.0013), absence of nodal metastasis (pN0, p=0.0003) and tumor localization in the right colon (p<0.0001). A multivariate analysis revealed that these associations were solely driven by the tight relationship between STING expression in tumor cells and MSI. Accordingly, subgroups of tumors with and without MSI lacked significant associations between STING expression on tumor cells and pT or pN categories. While the total number of lymphocytes and macrophages were related to MSI, low pT, and pN0, there were significant associations between a high percentage of STING positive macrophages and lymphocytes to low pT stage (p<0.0001 each) and absence of nodal metastases for high percentage of STING positive macrophages (p=0.0033). STING was regularly expressed on endothelial cells of small vessels. Although the intensity appeared to be variable, there was no link to tumor phenotype. Conclusion: In summary, the significant link between high STING expression on tumor cells, lymphocytes and macrophages with a favorable tumor phenotype supports the concept of STING representing an enhancer of anti-tumoral effects of the immune system. Citation Format: Elena Bady, Zhihao Huang, Maximilian Lennartz, Claudia Hube-Magg, Julia Ebner, Frank Jacobsen, Stefan Steurer, Christian Bernreuther, Till S. Cauditz, Andreas H. Marx, Till Krech, Eike Burandt, Guido Sauter, Ronald Simon, Sarah Minner, Jan Hendrik Mueller. High level STING expression in tumor and inflammatory cells is linked to microsatellite instability and favorable tumor parameters in a cohort of 1,900 colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5206.

Immunity in the Progeroid Model of Cockayne Syndrome: Biomarkers of Pathological Aging.

Cockayne syndrome (CS) is a rare autosomal recessive disorder that affects the DNA repair process. It is a progeroid syndrome predisposing patients to accelerated aging and to increased susceptibility to respiratory infections. Here, we studied the immune status of CS patients to determine potential biomarkers associated with pathological aging. CS patients, as well as elderly and young, healthy donors, were enrolled in this study. Complete blood counts for patients and donors were assessed, immune cell subsets were analyzed using flow cytometry, and candidate cytokines were analyzed via multi-analyte ELISArray kits. In CS patients, we noticed a high percentage of lymphocytes, an increased rate of intermediate and non-classical monocytes, and a high level of pro-inflammatory cytokine IL-8. In addition, we identified an increased rate of particular subtypes of T Lymphocyte CD8+ CD28- CD27-, which are senescent T cells. Thus, an inflammatory state was found in CS patients that is similar to that observed in the elderly donors and is associated with an immunosenescence status in both groups. This could explain the CS patients' increased susceptibility to infections, which is partly due to an aging-associated inflammation process.

Alterations in Blaood Profiles and Spleen Tissue Following Purple Sweet Pota-to Anthocyanin Extract Treatment in Restraint-Stressed Mice

Stress is associated with broad changes in blood and immune cell dysfunction, which are correlated with the spleen as a secondary lymphoid organ. Anthocyanin, a plant bioactive compound from purple sweet potatoes, has previously been reported to have a beneficial effect on stress response behavior. However, the limited studies evaluated anthocyanin's effect on blood profiles and spleen tissue under stress. Therefore, this study aimed to explore the effect of total anthocyanin extract (ANC) from purple sweet potatoes (PSP) on the blood profiles and spleen tissue of restraint stressed mice. A total of 20 male adult BALB/c mice were divided into control (CTRL), stress (STR), stress + ANC 10 mg/kgBW (STR+ANC10), stress + ANC 20 mg/kgBW (STR+ANC20), and stress + ANC 40 mg/kgBW (STR+ANC10). Restraint stress was applied two hours/day for 14 days. An automatic blood analyzer was used for blood profiling. Immunoblotting of caspase-3 and hematoxylin-eosin-stained histological slides were observed for spleen tissue analysis. Combination of STR and ANC treatment reduced the erythrocyte count, hemoglobin level, and leucocyte count. The ANC-treated groups had a higher percentage of lymphocytes and a lower percentage of granulocytes. The expression of caspase-3 declined among ANC-treated groups. Spleen extramedullary erythropoiesis, vacuolization, and white pulp involution were demonstrated in stress and ANC-treated animals. In summary, restraint stress modified the blood cell profiles and spleen tissue in the mice model. Further research is necessary to evaluate the mechanism of ANC during stress on blood cells and splenic tissue repair enhancement

Evaluation of some immunological markers in co-infection of COVID-19 with thrush candidiasis.

COVID-19 infection poses significant risks, including life-threatening consequences and fungus synchronization, making it a significant concern. This study seeks to assess the effect of concurrent infection of COVID-19 with Thrush Candida albicans on the patient's health state by measuring the proportion of immune cells and certain interleukins such as IL-8, -10, -17, and -33. The study involved 70 patients (30 patients with COVID-19, 17 patients with thrush candidiasis, and 23 patients with Thrush Candida albicans) and 50 healthy individuals as a control group. COVID-19 was identified using RT-PCR, while C. albicans were identified through culture media, biochemical testing, and oral swabs. Ruby equipment and ELISA kits were used for blood counts and interleukin detection. COVID-19, thrush candidiasis, and Thrush Candida albicans infections occur in a wide range of age groups (4-80 years), with no significant differences between sexes (p>0.05). Immunologically, our study found that Thrush Candida albicans patients had the highest rate of neutrophils (89.6%) and basophils (2.01%), while corona patients had the highest percentage of lymphocytes (70.12%) and eosinophils (7.11%), and patients with thrush candidiasis had the highest percentage of monocytes. Thrush Candida albicans patients showed increased IL-8 (56.7 pg/mL) and IL-17 (101.1 pg/mL) concentrations, with the greatest concentration of IL-33 (200.5 pg/mL) in COVID-19, and a decrease in the level of IL-10 in patient groups compared with controls. Patient groups showed increased neutrophils, lymphocytes, monocytes, and IL-8 levels, with a significant linear association between proinflammatory interleukins and these cells.

Corelationship of Lymphocyte Subsets and Prognosis in Juvenile Myelomonocytic Leukemia

Objective: Juvenile Myelomonocytic Leukemia (JMML) is a rare hematopoietic stem cell malignant clonal disease in children and has the characteristics of MDS/MPN. Due to the poor response of JMML to chemotherapy, hematopoietic stem cell transplantation (HSCT) is currently the only cure method for JMML. Currently, there are some reports on the distribution of lymphocyte subsets in MDS. A significant lymphocytopenia was observed in MDS patients compared with similarly aged healthy people. Another study form Polish found patients with MDS have more CD3+T cells than healthy donors. But there are few related reports in JMML. The objective of this study is to analyze relationship between the distribution of lymphocyte subsets and prognosis in JMML patients, and explore new risk stratification indicatorsfor JMML personalized therapy. Method: This study retrospectively collected JMML patients clinical data from Institute of Hematology & Blood Diseases Hospital of CAMS during Jan 2008 and Nov 2022. All completed complete blood count and peripheral blood classification, fetal hemoglobin (HbF), granulocyte colony-stimulating factor (GM-CSF) high sensitivity, bone marrow morphology, immune typing, molecular biology, cytogenetics and other tests. We analyzed the relationship between distribution of lymphocyte and prognosis in these patients. Result: 96 newly diagnosed JMML patients were admitted to this study. The median age at diagnosis was 25 (2-82) months, and male to female was 3.8:1. 66 cases underwent lymphocyte subsets by flow cytometry. Median percentage of lymphocytes is 34.3%(1.8%-90.4%, normal range: 20%-40%), median percentage of CD3+T cells is 54.85%(10.3%-91%, normal range: 57%-88%), median percentage of CD3+CD4+ T cells is 30.95%(3.54%-53%, normal range: 27%-58%), median percentage of CD3+CD8+ T cells is 18.4%(2%-49.1%, normal range: 16%-45%), median percentage of NK cells is 13.95%(2.3%-50.3%, normal range: 3%-32%), and median percentage of B cells is 23.25%(4%-69.6%, normal range: 4%-18%). These cases were followed-up to Jan 2023, with a median follow-up time of 12 months (1-104 months). The overall survival (OS) rate was 52.67%, with a median OS time of 12 months (0-103 months). There were significant differences in the percentage of CD3+T cells (30.89% ± 9.46% vs 59.05% ± 10%, P<0.01) and CD3+CD4+T cells (14.87% ± 5.82% vs 35% ± 5.41%, P<0.01) between children with single NRAS mutation and compound mutations (≥2 classical five Ras pathway mutation ). In PTPN11 mutation patients, there is a significant positive correlation between OS and the percentage of lymphocytes (P=0.018). Conclusion: Our study shows differences in percentage of CD3+ T cells and CD3+CD4+ T cells between patients with NRAS mutation and compound mutations. Patients with PTPN11 mutation and higher percentage of lymphocytes will have better prognosis.

White blood cells in a healthy adolescent population according to social and health characteristics

BackgroundThe immune system constitutes a sensory system both for heritable and non-heritable factors. Among the latter, social and environmental determinants of health may influence and shape the immune system in early life. To study the relationship between leukocytes and determinants of health in adolescence, we assessed total and differential white blood cells (WBC) according to social and environmental determinants of health in a healthy adolescent population. MethodsAs part of the population-based cohort Epidemiological Health Investigation of Teenagers in Porto (EPITeen), 1213 adolescents were evaluated at the age of 13. Total and differential WBC were evaluated through a venous blood sample using an automated blood counter (Sysmex®XE-5000, Hyogo, Japan). Sociodemographic, behavioral, and clinical data were collected through self-administered questionnaires. ResultsParticipants with better socioeconomic conditions (enrolled at private schools or higher parental education) had significantly lower total WBC levels, and the latter showed a lower percentage of neutrophils and higher percentage of lymphocytes. Those who practiced sports had significantly lower total WBC levels and neutrophil percentage, as well as a significantly higher percentage of eosinophils and lymphocytes. Adolescents with chronic disease, chronic medication, or allergic diseases had a significantly higher percentage of eosinophils and a lower percentage of monocytes. With increasing body mass index and systemic inflammation, we found a significant increase in total WBC levels. ConclusionWBC linked to different immune response patterns are associated with several social and environmental determinants of health in adolescence.

The effect of Psidium guajava Leaves’ extract for mild and asymptomatic corona virus Disease-19

COVID-19 is an emerging disease that attacks the respiratory and systemic systems. Various treatments have been used for COVID-19, but no antiviral agents seemed to be efficacious. Many medicinal plants are commonly used for viral infections in Indonesia, including the guajava leaf. The study aimed to determine the effects of Psidium guajava extract supplementation on inflammation markers of asymptomatic and mild COVID-19 patients. The conversion time of PCR results was also evaluated. This study was an experimental, single-blinded, randomized clinical trial (ClinicalTrials.gov: NCT04810728) comparing the efficacy of P. guajava extract at the dose of 1000 mg/8h on top of standard treatment with the standard treatment only for asymptomatic and mild COVID-19 subjects. The primary endpoints were neutrophil and lymphocyte percentages as well as the neutrophil/lymphocyte ratio (NLR) on day 7 of the treatment. The secondary endpoints were high-sensitivity c-reactive protein (hs-CRP) level, PCR-based conversion time, and recovery rate at weeks 2 and 4. A total of 90 subjects were enrolled, and there were 40 subjects in the P. guajava (experimental) group and 41 subjects in the control group who completed the research. On day 7, significantly lower percentage of neutrophil (52.4% vs 58.9%, p = 0.002), higher lymphocyte percentage (35.5%, vs 29.7%, p = 0.002), and lower NLR (1.5 vs 2.1, p = 0.001) were demonstrated in the experimental versus control group. The PCR-based conversion time was shorter (14 days vs 16 days, p < 0.001), and recovery rate at 2 and 4 weeks were higher (49% vs 27%, p = 0.03 and 100% vs 82%, p = 0.003, respectively) in the experimental group. There were no differences in the baseline characteristics. P. guajava extract supplementation reduced neutrophil and increased lymphocyte percentages which led to reduced NLR, accelerated PCR-based conversion time, and increased recovery rate in subjects with mild and asymptomatic COVID-19 infection.\\

Repeated injection of multivitamins and multiminerals during the transition period enhances immune response by suppressing inflammation and oxidative stress in cows and their calves.

Periparturient dairy cows undergo major physiological and metabolic changes as well as immunosuppression, associated with decrease in plasma concentrations of various minerals and vitamins. The present study was conducted to investigate effects of repeated injections of vitamins and minerals on oxidative stress, innate and adaptive immune response in periparturient dairy cows and their offspring. Experiment was carried out on 24 peripartum Karan-Fries cows, randomly divided into four groups (n=6): control, Multi-mineral (MM), Multi-vitamin (MV) and Multi-minerals and Multi-vitamin (MMMV). Five ml of MM (Zinc 40 mg/ml, Manganese 10 mg/ml, Copper 15 mg/ml, Selenium 5 mg/ml) and five ml of MV (Vitamin E 5 mg/ml, Vitamin A 1000 IU/ml, B-Complex 5 mg/ml, and Vitamin D3 500 IU/ml) were injected intramuscularly (IM) to the MM and MV groups. MMMV group cows were injected with both. In all treatment groups, injections and blood sampling were carried out on 30th, 15th, 7th days before and after expected date of parturition and at calving. In calves, blood was collected at calving and on 1, 2, 3, 4, 7, 8, 15, 30 and 45 days post-calving. Colostrum/milk were collected at calving and at days 2, 4, and 8 post-calving. A lower percentage of total neutrophils and immature neutrophils, higher percentage of lymphocytes together with increased phagocytic activity of neutrophils and proliferative capacity of lymphocytes found in blood of MMMV cows/calves. Lower relative mRNA expression of TLRs and CXCRs and higher mRNA expression of GR-α, CD62L, CD11b, CD25 and CD44 found in blood neutrophils of MMMV groups. Total antioxidant capacity was higher, activity of antioxidant enzymes (SOD and CAT), TBARS levels were lower in the blood plasma of treated cows/calves. In both cows/calves, plasma pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, IL-17A, IFN-γ and TNF-α) increased, whereas anti-inflammatory cytokines (IL-4 and IL-10) decreased in MMMV groups. Total immunoglobulins increased in colostrum/milk of MMMV injected cows and plasma of their calves. Results indicate that repeated injections of multivitamins and multiminerals to peripartum dairy cows could be a major strategy to improve immune response and decrease in inflammation and oxidative stress in transition dairy cows and their calves.

A high high-density lipoprotein level is associated with Gleason score upgrade in Chinese patients diagnosed with high-grade prostate carcinoma

BackgroundThe high incidence of Gleason score upgrading (GSU) made urologists underestimate the disease, leading to the inaccurate therapeutic decision. The study aimed to explore relevant laboratory examination evidence associated with GSU.MethodsPatients diagnosed with prostate carcinoma undergoing radical prostatectomy in our center between January 2015 and December 2019 were included in this retrospective study. Patients were divided into GSU and NGSU groups according to the occurrence of GSU. Medical records were reviewed and analyzed between groups.ResultsA total of 130 patients were enrolled, including 52 patients diagnosed with GS = 6 (20 NGSU and 32 GSU) and 78 patients with GS = 7 (36 NGSU and 42 GSU). No significant differences in demographic characteristics were found between groups. An increased neutrophil count (OR = 1.326, 95% CI = 1.005–1.748) and a decreased percentage of lymphocytes (OR = 0.951, 95% CI = 0.904–1) were associated with GSU in the GS = 6 group, whereas a high HDL level (OR = 7.735, 95% CI = 0.998–59.957) was associated with GSU in GS = 7 group. Preoperative high neutrophile count and low lymphocyte percentage were correlated with GSU in patients with low-grade prostate cancer. In contrast, high HDL level was associated with GSU in patients with high-grade prostate cancer.ConclusionsThese laboratory examination data could provide urologists with information before making a therapeutic protocol.

Compromised T-cell immunity in patients with spinal cord injury and its relationship with injury characteristics.

The aim of this study was to investigate in vivo and in vitro cellular immune responses in patients with chronic (spinal cord injury; SCI), determine the effects of autonomic dysfunction on cellular immune response, and determine the effect of completeness of the injury at different levels on cellular immune response. Forty-nine patients (42 males, 7 females; mean age: 35.5±13.4 years; range, 18 to 68 years) with chronic (time since injury >6 months) traumatic SCI were included in this cross sectional study between March 2013 and December 2013. Patients were allocated into two groups: Group 1, patients with an injury at T7 or below, and Group 2, patients with an injury at T6 or above. All patients in Group 2 had a history of autonomic dysreflexia and orthostatic hypotension. Intradermal skin tests were applied to the participants to reveal delayed T-cell responses. The percentages of cluster of differentiation (CD)3+ T cells and CD3+ T cells expressing CD69 and CD25 were analyzed by flow cytometry for the detection of activated T cells including all T-cell subsets. When patients with complete injuries were compared, the CD45+ cell percentage was found to be significantly higher in patients in Group 2. Patients with an incomplete SCI had increased skin response to candida antigens compared to complete SCI patients. Incomplete SCI patients also had higher percentages of lymphocytes and CD3+CD25+ and CD3+CD69+ T cells compared to patients with complete SCI. T-cell activity is impaired in chronic SCI patients with higher levels of injury, and the completeness of injury and autonomic dysfunction gain prominence as compromising factors in T-cell immunity.

Peripheral double negative T: A look at senescent Cubans

IntroductionAge-related changes in the immune system are called immunosenescence. Within the T lymphocytes is the subpopulation of double negative (DNT) peripheral lymphocytes that are immunomodulators of the immune response, based on their ability to suppress the functions of simple positive T cells and their cytotoxicity for tumor cells and those infected by viruses. ObjectiveTo determine the frequency of peripheral DNT lymphocytes in older Cuban adults. MethodsA cross-sectional study was carried out in 30 older adults, residents in Cuba. DNT lymphocytes in peripheral blood were quantified by flow cytometry. A Beckman Coulter Gallios flow cytometer was used for data reading and analysis. Percentage values mean and standard deviation were used. The Chi-square was used to relate the percentage values of DNT and comorbidities. It was considered statistically significant if p ≤ 0.05. ResultsThere was a predominance of women who represented 70 %. No older adult with low values of DNT lymphocytes was reported. Women with high percentage and absolute values of DNT lymphocytes prevailed in relation to men. In the group ≥80 years, high values in % and absolute values of DNT lymphocytes predominated. The high percentage values of DNT cells were mainly related to cardiovascular disease, and predominated in the elderly of ≥80 years old; who presented respiratory and skin infections, fundamentally. The percentage normal value in the group < 80 years was significant (p = 0.0198). The Chi-square value was 0,5995. ConclusionsMost older adults who exhibited high percentage and absolute values of DNT lymphocytes, or a tendency to them, had some associated comorbidity, an idea that suggests that DNT cells participate in immune surveillance, defense and homeostasis based on their double identity, that is, its pathogenic or immunosuppressive phenotype according to the specific immunological microenvironment.

Mendelian randomization reveals causal effects of kidney function on various biochemical parameters

The kidney is a vital organ with diverse biological effects and the burden of kidney function impairment is increasing in modern medicine. As the effects from kidney function on diverse biochemical parameters are yet fully understood, additional investigation to reveal the causal effects is warranted. Here we show the causal estimates from kidney function parameter, estimated glomerular filtration rate (eGFR), on 60 biochemical parameters by performing two-sample Mendelian randomization (MR) study in 337,138 white British UK Biobank participants. A higher genetically predicted eGFR was significantly associated with higher lymphocyte percentage, HDL cholesterol, and alanine aminotransferase. The causal estimates indicated that a higher genetically predicted eGFR was associated with lower urea, urate, insulin growth factor-1, and triglycerides levels. The parameters with significant but non-linear causal estimates were hemoglobin concentration, calcium, vitamin D, and urine creatinine values, identified by non-linear MR. Healthcare providers should understand that changes in eGFR may affect the identified biochemical parameters in diverse patterns. Future study is warranted to expand the knowledge of the mechanisms and clinical implications of the causal effects of eGFR on various biochemical parameters.

Impact of Latent Tuberculosis on Severity and Outcomes in Admitted COVID-19 Patients.

BackgroundThere is limited data on coronavirus disease 2019 (COVID-19) and latent tuberculosis infection (LTBI).MethodologyWe analyzed data of admitted COVID-19 patients evaluated for LTBI to examine the impact of LTBI on severity, laboratory parameters, and COVID-19 outcome. Prospectively collected data were analyzed for 60 patients who were administered the Mantoux tuberculosis skin test (TST) using five tuberculin units of purified protein derivative. All patients were administered TST irrespective of Bacille Calmette-Guérin (BCG) vaccination status. Comorbidities, clinical features, radiologic involvement, laboratory parameters, and clinical course were analyzed concerning LTBI.ResultsThe mean age was 45.9 (±15.2) years, and 35 (58.3%) patients had non-severe disease. The vast majority (n = 56/60; 93.3%) had been vaccinated with single-dose BCG in infancy or early childhood, as per national immunization guidelines. LTBI was diagnosed in 15 (25%) patients. LTBI prevalence was lower in severe (n = 1/25; 4%) than non-severe (n = 14/35; 40%) COVID-19 (p = 0.01) patients. LTBI patients had lower percentage neutrophil count, higher lymphocyte percentage, higher monocyte count, lower neutrophil-lymphocyte (NL) ratio, lower alanine aminotransferase, lower C-reactive protein, and lesser radiologic involvement compared to those without LTBI (p < 0.05). Similarly, among the mild COVID-19 subgroup, those with LTBI had higher lymphocyte and monocyte counts and lesser radiologic involvement than those without LTBI (p < 0.05).ConclusionsLTBI patients appear to have milder disease, higher lymphocyte and monocyte count, higher NL ratio, and lesser radiographic involvement. This observation needs to be studied in larger studies using interferon release assays.

Chronic Lymphocytic Leukemia in a Cockatiel (Nymphicus hollandicus).

A 24-year-old, female cockatiel (Nymphicus hollandicus) was diagnosed and treated for chronic lymphocytic leukemia. Diagnosis was based on a persistent lymphocytosis, with counts increasing 10 times from reference intervals with a high percentage of well-differentiated lymphocytes in the bone marrow. Immunohistochemical staining confirmed neoplastic cells of T-cell origin. Specific treatment for the disease was initially withheld but commenced based on an increasing lymphocytosis and decreasing packed cell volume. Therapeutic management of the cockatiel's chronic lymphocytic leukemia was based on human protocols. Treatment with chlorambucil stabilized the disease but did not result in a significant regression of the neoplasm. The bird was euthanatized 15 months after the initial diagnosis and 8 months after treatment commenced. On the postmortem examination, extensive T-cell lymphocytic infiltration was found throughout the internal organs.

The application of machine learning algorithms in predicting the length of stay following femoral neck fracture

PurposeFemoral neck fracture is a frequent cause of hospitalization, and length of stay is an important marker of hospital cost and quality of care provided. As an extension of traditional statistical methods, machine learning provides the possibility of accurately predicting the length of hospital stay. The aim of this paper is to retrospectively identify predictive factors of the length of hospital stay (LOS) and predict the postoperative LOS by using machine learning algorithms. MethodBased on the admission and perioperative data of the patients, linear regression was used to analyze the predictive factors of the LOS. Multiple machine learning models were developed, and the performance of different models was compared. ResultStepwise linear regression showed that preoperative calcium level (P = 0.017) and preoperative lymphocyte percentage (P = 0.007), in addition to intraoperative bleeding (p = 0.041), glucose and sodium chloride infusion after surgery (P = 0.019), Charlson Comorbidity Index (p = 0.007) and BMI (P = 0.031), were significant predictors of LOS. The best performing model was the principal component regression (PCR) with an optimal MAE (1.525) and a proportion of prediction error within 3 days of 90.91%. ConclusionExcessive intravenous glucose and sodium chloride infusion after surgery, preoperative hypocalcemia, preoperative high percentages of lymphocytes, excessive intraoperative bleeding, lower BMI and higher CCI scores were related to prolonged LOS by using linear regression. Machine learning could accurately predict the postoperative LOS. This information allows hospital administrators to plan reasonable resource allocation to fulfill demand, leading to direct care quality improvement and more reasonable use of scarce resources.

PD-L1 expression and immune stromal features in HPV-independent cervical adenocarcinoma.

Human papilloma virus (HPV)-independent cervical adenocarcinoma (CA) is usually diagnosed at an advanced stage, while the therapeutic options are limited. Therefore, effective treatment options are required. The programmed cell death 1 (PD-1) inhibitor pembrolizumab has been approved for the treatment of patients with recurrent or metastatic cervical squamous cell carcinoma expressing PD-ligand 1 (PD-L1). However, no data regarding PD-L1 expression in HPV-independent CA are available. Thus, we evaluated the association between PD-L1 expression and the clinicopathological characteristics and survival of patients with HPV-independent CA. We evaluated PD-L1, mismatch repair (MMR) protein expression and the immune stromal features of 44 patients with HPV-independent CA. PD-L1 expression was defined as a combined positive score (CPS) ≥1 and a tumour proportion score (TPS) ≥1%. PD-L1 expression was observed in 14 cases (31.8%) with CPS ≥1 and 12 cases (27.3%) with TPS ≥1%. PD-L1 expression, based on either the CPS or the TPS, was associated with a high tumour-infiltrating lymphocyte percentage (CPS=P<0.001; TPS=P<0.001). Patients with a PD-L1 CPS ≥1 showed worse progression-free survival and overall survival than PD-L1-negative patients (P=0.004 and P=0.023, respectively). Forty-two cases demonstrated intact MMR expression and two cases demonstrated loss of MSH2/MSH6. Our data demonstrated that PD-L1 was expressed in HPV-independent CA, especially in clear cell carcinoma, and that PD-L1 expression is a negative prognostic marker. Our data support the role of PD-L1 in HPV-independent CA and its potential as an immunotherapeutic target.

Immunophenotypic characterization of double positive T lymphocytes in Cuban older adults.

Immunosenescence is the functional deterioration of the immune system during natural aging that mainly affects T lymphocytes, within which is the subpopulation of peripheral double positive T lymphocytes that are immunomodulators of the immune response. They are increased in older adults and play a fundamental role in the immunopathogenesis of autoimmune diseases, viral infections and neoplasms. To characterize the immunophenotype of peripheral double positive T lymphocytes in Cuban older adults. A cross-sectional study was carried out in 30 older adults residing in Cuba. Peripheral blood double positive T lymphocytes were quantified by flow cytometry. The reading was done on a Beckman Coulter Gallios flow cytometer. A Beckman Coulter Gallios flow cytometer was used for data analysis. Percentage values, median and standard deviation were used. There was a predominance of women who represented 70%. No older adults with low values of double positive T lymphocytes were reported. Women with high percentage and absolute values of DPT lymphocytes predominated in relation to men. Among the high percentage values and the absolute value of DPT lymphocytes, the group ≥80years prevailed. Most of the older adults who exhibited high percentage and absolute values of DPT lymphocytes had some associated comorbidity, an idea that suggests that CD4+CD8+ T cells seem to play an important role in peripheral sites as powerful immunosuppressants or as cells with high cytotoxic potential.

Prognostic significance of bronchoalveolar lavage cellular analysis in patients with acute exacerbation of interstitial lung disease

BackgroundAcute exacerbation (AE) of interstitial lung disease (ILD) is an acute respiratory deterioration of unknown etiology, associated with high mortality. Currently, bronchoalveolar lavage (BAL) has been no longer required for the diagnosis of AE-ILD; however, the clinical utility of BAL fluid (BALF) cellular analysis in AE-ILD remains unclear. MethodsA retrospective study of 71 patients who underwent BAL at our institution between 2005 and 2019 and were diagnosed with AE-ILD was conducted. We performed BALF cellular analysis and evaluated its prognostic significance. ResultsThere were 26 patients with AE of idiopathic pulmonary fibrosis (IPF) and 45 with AE of non-IPF, including idiopathic interstitial pneumonias/non-IPF (n = 22), ILD associated with collagen tissue disease (n = 20) and fibrotic hypersensitivity pneumonia (n = 3). All patients were treated with high-dose corticosteroids, and the 90-day mortality after AE was 31%. Most patients showed a high percentage of lymphocytes and/or neutrophils in BALF regardless of the underlying ILD. There was a significant negative correlation between BALF neutrophils and the PaO2/FiO2 ratio, and patients with UIP pattern or diffuse AE pattern on HRCT had a significantly higher percentage of BALF neutrophils than those with other patterns. Multivariate analysis revealed that lower and higher percentage of lymphocytes and neutrophils, respectively, in BALF were independent poor prognostic factors for 90-day survival. BALF lymphocyte and neutrophil count ≥25% and <20%, respectively, predicted favorable survival after AE. ConclusionsCellular analysis of BALF in AE-ILD is a potential biomarker for predicting prognosis after AE.

Prognostic Value of Absolute Lymphocyte count, Lymphocyte percentage, Serum albumin, Aberrant Expression of CD7, CD19 and the Tumor Suppressors (PTEN and p53) in Patients with Acute Myeloid Leukemia

Background: Acute myeloid leukemia (AML) is a hematopoietic neoplasm. Tumor suppressors have a magnificent role in preventing the AML process. The absolute lymphocyte count is a simple yet statistically powerful estimate in patients with acute leukemia besides the lymphocyte’s percentage. Aim: Investigating the prognostic value of absolute lymphocyte count, lymphocyte percentage, serum albumin, the aberrant expression of CD7and CD19 and the tumor suppressor genes (PTEN and p53) in patients with AML. Methods: 35 de novo AML patients were included. They received the standard induction chemotherapy (3+7 protocol) and were followed up for one year after treatment. 15 normal healthy individuals, age and sex matched constituted the controls.Results: The mean overall survival of patients with lymphocyte percentage ≤25 was low compared to those with high lymphocyte percentage (&gt;25%) (χ2 =5.808, P=0.016). AML patients with low levels of ALC showed significantly shorter overall survival than patients with high levels (χ2 =4.587, P= 0.032). AML patients with low serum albumin were of low overall survival compared to those with normal level (χ2 =8.698, P=0.003). Patients with aberrant CD7 expression showed short survival and unresponsiveness to treatment than CD7 negative patients. PTEN gene expression and p53 protein level were significantly lower in AML patients compared to the control group.Conclusion: The decrease in ALC, lymphocyte percentage, albumin concentration and the increase in monocyte percentage indicates bad prognosis in AML patients. The Aberrant CD7 expression, very low expression of PTEN and low level of p53 could estimate the unresponsiveness to standard chemotherapy.

IMMU-21. INVESTIGATION OF WHITE BLOOD CELL CHARACTERISTICS IN CSF SAMPLES AT PEDIATRIC BRAIN TUMOR DIAGNOSIS

BACKGROUNDThere has been a recent surge in investigation of immunity and immunotherapy, but their role in pediatric brain tumors is incompletely defined. We hypothesized that investigating an understudied dataset, WBC and differential results in CSF drawn at the time of pediatric brain tumor diagnosis to look for microscopic metastases, would provide insight into the role of immunology and potential for immunotherapy in these diseases and correlate with prognosis and/or metastasis.METHODSWe conducted a retrospective comparison analysis of CSF values in 349 patients at our institution from samples drawn within 60 days of initial CNS tumor diagnosis from 1998–2018. We examined total nucleated cell count, absolute counts and percentages for WBC subtypes. We compared CSF values by tumor cell presence, patient vital status, and disease group: atypical teratoid rhabdoid tumor, ependymoma, germinoma, high-grade glioma (HGG), low-grade glioma (LGG), medulloblastoma, non-germinomatous germ cell tumor, and other embryonal tumors (OET). We used Wilcoxon and Kruskal-Wallis tests for comparisons.RESULTSOverall, higher lymphocyte percentage (p=0.002) and lower monocyte percentage (p=0.007) were associated with survival. WBC characteristics did not differ significantly based on tumor cell presence. Compared to medulloblastoma, ependymoma showed a more active CSF immune response, while LGG, HGG, and OET showed a less active response, based on total WBC and/or absolute neutrophil count (p=0.001–0.007).CONCLUSIONSHigher lymphocyte and lower monocyte percentages in CSF correlated with better prognosis overall; causality requires further investigation. Tumor subtypes varied in their immune stimulation, offering potential insight into which will be amenable to immunotherapy.