Lymphocyte Count Research Articles

Impact of neoadjuvant radiation therapy modalities on post-surgical lymphopenia in operable pancreatic cancer.

710 Background: Recent advances in therapeutic vaccines show promise for KRAS -mutated pancreatic cancer (PC), with ongoing clinical trials exploring their potential further. Lymphocytes are essential in generating vaccine-induced immune response. Patients who develop lymphopenia following neoadjuvant radiation therapy (RT) are frequently excluded from these vaccine trials. We aimed to assess how different modalities of neoadjuvant RT impact the severity and incidence of lymphopenia. Methods: We identified patients with PC who received neoadjuvant therapy including RT followed by surgery at our institution between March 2009 and June 2024. Patients were stratified by the type of RT they received: conventional long-course chemo-RT (LCRT) with 50.4 Gy over 28 fractions (Fr), short-course chemo-RT (SCRT) with 36 Gy over 15 Fr, and stereotactic body RT (SBRT) with 30 Gy over 5 Fr. The absolute lymphocyte count (ALC, 10 3 cells/µL) was compared at various timepoints: baseline, during RT, 6-weeks after surgery (post-op), and every 3-month interval up to 1 year post-op. Moderate lymphopenia was defined as ALC <1.0 and severe lymphopenia as ALC <0.5. Results: Among the 627 patients included in the study, 522 had baseline pre-RT ALC data available for analysis. There was no difference in baseline ALC among the different RT groups (Table). During RT, patients receiving LCRT experienced a higher incidence of severe lymphopenia (86.1%; median ALC (mALC) nadir 0.28) compared to SCRT (41.9%; mALC nadir 0.50) or SBRT (20.0%; mALC nadir 0.72, p<0001). No difference in the mALC or rates of lymphopenia was observed beyond 6 weeks post-op. Notably, 53% of the patients experienced lymphopenia for as long as 1 year after surgery. Conclusions: LCRT resulted in more severe lymphopenia compared to SCRT or SBRT during RT, but this difference in severity diminished 6 weeks after surgery. Alternatives in treatment sequencing for operable pancreatic cancer can have profound effects on patterns of disease recurrence. When applying multiple treatments in series, toxicities such as lymphopenia may impact receipt of therapy. Techniques to mitigate such toxicities, while maximizing response, will be important to consider. Absolute lymphocyte count (ALC, 10 3 cells/µL) at different time point. Patients with baseline ALC LCRT (n=454) SCRT (n=34) SBRT (n=34) P-value Baseline ALC, median (IQR) 1.48 (0.74) 1.27 (0.94) 1.51 (0.74) 0.74 6-week lymphopenia, n (%) No Moderate Severe 173 (37)219 (46)79 (17) 13/27 (48)11/27 (41)3/27 (11) 18/35 (51)16/35 (46)1/35 (3) 0.10 1-year lymphopenia, n (%) No Moderate Severe 101/217 (47)90/217 (41)26/217 (12) 3/8 (37)5/8 (63)0/8 (0) 9/13 (69)1/13 (8)3/13 (23) 0.054

The immunomodulatory and antioxidative effects of curcumin-supplemented diets against the isolated Aeromonas hydrophila in Oreochromisniloticus.

Worldwide, Aeromonas hydrophila (A. hydrophila) has become a significant foodborne pathogen, causing gastrointestinal and extra-intestinal infections in humans as well as severe economic losses in fish farms. Thus, we conducted this research in two experiments. The experiment 1 investigated the prevalence of A. hydrophila among Nile tilapia in different farms in Kafrelsheikh province and its pathogenicity by detecting some of its virulence genes before being used in the in vivo experiment. The experiment 2 was done to investigate the effect of dietary curcumin on growth performance, humoral immunity, antioxidants, and histopathology of Nile tilapia through a sixty-day feeding trial. Nile tilapia was divided into 3 groups, each in 3 replicates. Fish were given diets that included 0.0 (C, control), 1% (10g curcumin/kg diet; G1), and 2% curcumin/kg diet (20g curcumin/kg diet; G2). Moreover, the antibacterial effect of dietary curcumin against isolated bacteria in experiment 1 was investigated through experimental infection. The study's findings of experiment 1 indicated that the incidence of isolated A. hydrophila was 28%. Moreover, the virulence aerolysin (aerA) and haemolysin (hlyA) genes were found in 100% and 50% of the isolates, respectively. The experiment 2 outcomes demonstrated that the growth-modulating impacts of dietary curcumin were notably noticed in final weight, feed intake, weight gain%, and specific growth rate without pathological lesions in the different organs. In addition, the white blood cell and lymphocyte counts significantly (P<0.05) increased in Nile tilapia fed dietary curcumin. Similar improvements in humoral immunity (lysozyme and phagocytic activity) and antioxidants (catalase and superoxide dismutase) were seen in the 1% curcumin group (G1). The experimental infection with a virulent strain of A. hydrophila that was previously isolated in experiment 1 showed a significant decrease in the morbidity and mortality rates in the 1% curcumin treatment group (G1), followed by the 2% group (G2). The present study concluded that under current experimental conditions, dietary curcumin at a dose of 10g/kg diet proves effective, but the dose of 1% may not be optimal for tilapia.

Diagnostic accuracy of systemic immune-inflammation index for acute appendicitis in the geriatric population.

This study aimed to evaluate the diagnostic accuracy of the systemic immune-inflammation index (SII) in distinguishing acute appendicitis from non-appendicitis cases in geriatric patients who underwent surgery with a preliminary diagnosis of appendicitis. A retrospective study was conducted on geriatric patients with suspected acute appendicitis at a tertiary healthcare center. Demographic data, clinical features, and laboratory values were obtained from medical records. The SII was calculated based on neutrophil, platelet, and lymphocyte counts, and the patients were classified according to histopathological outcomes. The primary outcome was the diagnostic accuracy of SII in identifying appendicitis in the elderly population. The study included 64 geriatric patients with suspected appendicitis, comprising 45 patients with confirmed appendicitis (70.3%) and 19 patients without appendicitis (29.7%). The mean age of the patients was 71years (interquartile range: 67-76), with no significant difference between the appendicitis and non-appendicitis groups (p = 0.590). Females constituted 50% of the total cohort. The SII was significantly higher in the appendicitis group (median: 3687, interquartile range: 2420-5930) compared to the non-appendicitis group (median: 1589, interquartile range: 1134-2248, p < 0.001). The area under the receiver operating characteristic curve for the index was 0.81 (95% confidence interval: 0.68-0.93, p < 0.001), indicating good diagnostic accuracy. A threshold of greater than 2289 yielded a sensitivity of 0.78 and specificity of 0.79. The positive predictive value was 0.90, while the negative predictive value was 0.60. The SII demonstrated high diagnostic accuracy in differentiating between acute appendicitis and non-appendicitis cases in geriatric patients. SII may be a valuable diagnostic tool in elderly patients with suspected appendicitis, aiding timely and accurate clinical decision-making.

Peripheral Blood Cell Changes And Outcomes After Partial Splenic Embolization For Hypersplenism İn Cirrhotic Patients

Background and Purpose: Partial splenic embolization is a common treatment for hypersplenism in patients with cirrhosis. In this investigation, we evaluated the effectiveness and safety of partial splenic embolization in patients with cirrhosis. Methods: We retrospectively investigated 17 patients with hypersplenism secondary to cirrhosis who underwent partial splenic embolization. Following partial splenic embolization, peripheral blood cell counts were measured at regular intervals over a period of twelve months.Post-procedural complications were recorded. Results: This study included 17 individuals, with a mean age of 54.5 ± 10 years. Hemoglobin, platelet, neutrophil, lymphocyte, and white blood cell counts showed statistically significant increases.when compared to the pre-procedure levels at each time point (pre-procedure vs. 1st day p

Risk factors and machine learning prediction models for intrahepatic cholestasis of pregnancy

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in the second and third trimesters of pregnancy and is associated with a significant risk of fetal complications, including premature birth and fetal death. In clinical practice, the diagnosis of ICP is predominantly based on the presence of pruritus in pregnant women and elevated serum total bile acid. However, this approach may result in missed or delayed diagnoses. Therefore, it is essential to explore the risk factors associated with ICP and to accurately identify affected individuals to enable timely prophylactic interventions. The existing literature exhibits a paucity of studies employing artificial intelligence to predict ICP. Therefore, developing machine learning-based diagnostic and severity classification models for ICP holds significant importance.MethodsThis study included ICP patients and some healthy pregnant women from Jiaxing Maternity and Child Health Care Hospital in China between July 2020 and October 2023. We collected clinical data during their pregnancies and selected the top 11 critical risk factors through univariable and lasso regression analysis. The dataset was randomly divided into training and testing cohorts. Thirteen machine learning techniques, including Random Forest, Support Vector Machine, and Artificial Neural Network, were employed. Based on their various classification performances on the training set, the top five models were selected for internal validation.ResultsThe dataset included 798 participants (300 normal, 312 mild, and 186 severe cases). Through univariable and lasso regression analysis, total bile acid, gamma-glutamyl transferase, multiple pregnancy, lymphocyte percentage, hematocrit, neutrophil percentage, prothrombin time, Aspartate aminotransferase, red blood cell count, lymphocyte count and platelet count were identified as risk factors of ICP. The AUCs of the selected top five models ranged from 0.9509 to 0.9614. The CatBoost model achieved the best performance, with an AUC of 0.9614 (95% confidence interval, 0.9377–0.9813), an accuracy of 0.9085, a precision of 0.8930, a recall of 0.9059, and a F1-score of 0.8981.ConclusionsWe identified risk factors for ICP and developed machine learning models based on these factors. These models demonstrated good performance and can be used to help predict whether pregnant women have ICP and the degree of ICP (mild or severe).

P-1015. Cellular Composition of Bronchoalveolar Lavage Fluid in Patients with Hematologic Malignancies and Invasive Pulmonary Aspergillosis: Significant Associations with Peripheral Blood Cell Counts

Abstract Background Bronchoalveolar lavage (BAL) is frequently performed to diagnose invasive pulmonary aspergillosis (IPA) in patients (pts) with hematologic malignancies (HM). Given the critical role of the pulmonary immune environment for fungal control, BAL might be leveraged for diagnostic and prognostic immune biomarkers in IPA pts. However, data on the concordance of cell counts in peripheral blood (PB) and BAL fluid (BALF) of IPA pts is lacking.Figure 1.Heatmap summarizing Spearman’s rank correlation coefficients between peripheral blood white blood cell counts and differentials and those from bronchoalveolar lavage fluid at diagnosis of invasive pulmonary aspergillosis. * p&amp;lt;0.05, ** p&amp;lt;0.01, *** p&amp;lt;0.001. Methods We retrospectively reviewed 63 culture-positive proven/probable IPA cases in adult pts who underwent bronchoscopy at MD Anderson Cancer Center in 2011–2022. BALF cell counts, microbiology data, PB white blood cell (WBC) differentials on the day of bronchoscopy, and IPA outcomes were analyzed.Figure 2.Comparison of bronchoalveolar lavage fluid cell composition according to neutropenia status (A) and 42-day outcomes (B) in invasive aspergillosis patients with hematologic malignancies. Mann-Whitney U test. ** p&amp;lt;0.01, *** p&amp;lt;0.001. Results The median BALF WBC count at IPA diagnosis was 129/µL (interquartile range [IQR] 54–272/µL) and median neutrophil percentage was 11% (IQR 2–46%). PB total WBC counts significantly correlated with BALF WBC (r=0.55, p&amp;lt; 0.001), neutrophil (r=0.59, p&amp;lt; 0.001), and lymphocyte (r=0.48, p&amp;lt; 0.001) counts. Likewise, PB WBC differentials, i.e., absolute neutrophil and lymphocyte counts, significantly correlated with those in BALF (Fig. 1). Neutropenic pts (&amp;lt; 500/µL) had lower median BALF WBC (66 vs. 140/µL, p=0.005) and neutrophil counts (1 vs. 41/µL, p&amp;lt; 0.001) than non-neutropenic pts (Fig. 2A). BALF neutrophil counts were significantly higher in pts with bacterial coinfections than in those without coinfection (143 vs. 8/µL, p=0.005), while both neutrophil (37 vs. 5/µL, p=0.005) and lymphocyte (20 vs. 8/µL, p=0.021) counts were higher in pts with respiratory viral coinfection. Notably, cellular composition of BALF was not significantly associated with BALF galactomannan positivity or 42-day mortality after IPA diagnosis (Fig. 2B). Conclusion Unlike the well-known association between PB cytopenias and IPA outcome, severity of IPA was not significantly influenced by quantitative BAL cell composition, underscoring the unmet need for reliable qualitative/functional BAL biomarkers to prognosticate fungal control in HM pts. Both PB cytopenias and coinfections significantly affected immune cell mobilization into BALF. Thus, clinical context will be critical for normalization and validation of BAL-based host biomarkers. Disclosures Sebastian Wurster, MD, MSc, Astellas Pharma: Grant/Research Support|Gilead Sciences: Grant/Research Support Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant

High Expression Levels of the Long Non-Coding RNAs Lnc-IRF2-3 and Lnc-KIAA1755-4 Are Markers of Poor Prognosis in Chronic Lymphocytic Leukemia

Long non-coding RNAs (lncRNAs) play complex roles at multiple levels of gene regulation, thus modulating key cellular processes involved in the pathogenesis and progression of cancer. Aberrant expression of lncRNAs has been reported in various malignancies, including chronic lymphocytic leukemia (CLL). We investigated the expression of lnc-IRF2-3 and lnc-KIAA1755-4 in peripheral blood mononuclear cells of 112 previously untreated CLL patients by quantitative reverse-transcriptase polymerase chain reaction. Both lncRNAs were found to be overexpressed in CLL samples in comparison to healthy controls, and their high levels were associated with adverse clinico-biological characteristics of patients at diagnosis. High lnc-IRF2-3 expression was associated with high leukocyte and lymphocyte counts, high β2-microglobulin, advanced Binet stage, unfavorable cytogenetics, CD38-positivity and IGHV-unmutated status. Regarding lnc-KIAA1755-4, its high expression was associated with high leukocyte count, lymphocyte count, β2-microglobulin, lactate dehydrogenase and low hemoglobin, as well as with IGHV-unmutated status. In addition, we observed shorter time to first treatment and overall survival of patients expressing high levels of both lncRNAs in comparison to low-expressing patients. In summary, our study showed that high lnc-IRF2-3 and lnc-KIAA1755-4 expression at diagnosis predicts poor survival in CLL. The mechanisms of their upregulation, as well as their specific targets in CLL cells, remain to be elucidated.

P-57. Durability of SARS-CoV-2 specific Cellular Immune Response after COVID-19 Vaccination in PLWH

Abstract Background People living with HIV (PLWH) face the dual challenge of human immunodeficiency virus(HIV) infection and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. It is associated with severe outcomes and a higher risk of mortality. In January 2021, the vaccination campaign against SARS-CoV-2 was launched in India and started mass administration of two types of vaccines. The two vaccines used on a large scale were, a recombinant, replication-deficient chimpanzee adenovirus vectored vaccine/ ChAdOx1 nCoV-19 (Covishield) and whole virion inactivated vaccine/ BBV152 (Covaxin).The study of cellular immune responses to COVID-19 vaccination in PLWH was vital for safeguarding this vulnerable population. Methods Study design: Prospective observational study Study population: The individuals recruited in the study were vaccinated with at least 2 doses and/or booster dose of the COVID-19 vaccine (COVISHIELD/COVAXIN). The individuals were segregated into two groups (PLWH and non-HIV-infected healthy individuals). Testing Method: Peripheral blood mononuclear cell (PBMC) were cultured to test the SARS-CoV-2-specific T cell immune response using activation induced marker/ intracellular cytokine staining (AIM/ICS) assay. Distribution of CD4 T lymphocytes count in HIV patients with mean CD4 count 470 cell/µl. Results We conducted did this study in two phases. The first phase was conducted between August 2022 and December 2022, while the second phase, or the follow-up, took place from January 2023 to December 2023. In the first phase/ first visit (V1), we recruited 50 adult PLWH and 40 adult healthy controls. Subsequently, in phase 2/follow-up/ second visit (V2), we achieved a follow-up rate of 100% in each arm. SARS-CoV2-specific cellular immune response after COVID-19 vaccination was comparable and durable IN PLWH as compared to healthy controls. Conclusion Comparable and durable immune response was observed in PLWH population on regular highly active antiretroviral therapy (HAART), with stable viral suppression and good CD4+ T cell counts. This was consistent over time across 1 year gap in both phases of the study and across different vaccine types. This outcome indicates that the cellular immune responses in our PLWH cohort is comparable and durable to that of the general population, which is a reassuring finding for the public health. SARS-CoV-2-specific CD8 T-cell immune response (scatter plots displaying the results of CD8 T cell assays, specifically evaluating the production of various cytokines (IFNγ (Interferon-gamma), TNFα (Tumor Necrosis Factor-alpha), and IL-2 (Interleukin 2), Granzyme B (Gran-B) at two different time points V1 and V2 (visit 1 and visit 2) with p values mentioned at the top. Disclosures All Authors: No reported disclosures

The clinical features and outcomes of diabetes patients infected with COVID-19: a systematic review and meta-analysis comprising 192,693 patients

ObjectivesWe sought to explore the relevance of analyses that include critical laboratory parameters and drug treatment, clinical characteristics of diabetic patients who are infected with COVID-19, to the development of individualized treatment strategies for diabetic patients infected with COVID-19.MethodsWe searched Cochrane, Embase, FMRS, Pubmed, Springer, Web of Science databases for systematic reviews and meta-analyses to estimate the clinical characteristics and prognosis of confirmed covid-19 infections in patients with and without diabetes.ResultsOur meta-analysis included a total of 32 studies with 192,693 COVID-19 patients. Common comorbidities in the diabetic group were hypertension, cerebrovascular disease, chronic kidney disease and cardiovascular disease. We discovered that white blood cell count, neutrophil count, inflammatory marker levels, D-dimer, urea, precursor of the brain natriuretic peptide (Pro-BNP) increased and lymphocyte count, estimated glomerular filtration rate (eGFR), albumin decreased significantly in the diabetic group in laboratory test results. Compared with the non-diabetic group, the diabetic group had a higher incidence of complications in acute respiratory distress syndrome (ARDS), shock, acute heart injury, acute kidney injury and more regularly used oxygen therapy, invasive ventilation, non-invasive ventilation, continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO) treatment. Mortality and intensive care unit (ICU) hospitalization rates were highest in the diabetic group than in the non-diabetic group (p &amp;lt; 0.05).ConclusionDiabetic patients hospitalized with COVID-19 have an increased risk of death, lower discharge rates, and higher ICU admission rates. Their presence of hypertension, cerebrovascular disease, chronic kidney disease (CKD), higher levels of inflammatory markers. Multiple complications are all predictors of poor outcomes in people with diabetes. Our findings will help identify elevated risk factors in diabetics, which will benefit early prediction.

P-1854. Children with Congenital Heart Disease and PICS (Persistent Inflammation, Immunosuppression, and Catabolism Syndrome) Demonstrate Both Pro- and Anti-Inflammatory Cytokine Profiles

Abstract Background Patients with chronic critical illness have variable recovery from acute events, such as surgery or sepsis, and experience dysregulated inflammation, blunted immune responses, and recurrent infections. The development of persistent inflammation, immunosuppression, and catabolism syndrome (PICS) increases the risk of healthcare associated infections, poor wound healing, and indolent organ failure. The pathophysiology of PICS has not been characterized in critically ill pediatric populations, particularly those with congenital heart disease (CHD). Methods The PICASSO study is an ongoing, observational cohort study of immunologic dysregulation in children with CHD who undergo cardiopulmonary bypass for surgical repair. Three groups were defined in this preliminary analysis. Children with uncomplicated post-operative courses served as control participants. Group 1 includes children who underwent CHD repair and were anticipated to have prolonged recovery (n=6), and Group 2 includes children with culture-confirmed, post-operative infection (n=2). PICS was defined as having at least 2 of the following criteria: lymphocyte count &amp;lt; 1500 cells/mL, CRP &amp;gt; 10 mg/dL, and albumin &amp;lt; 3 mg/dL. Blood samples were collected weekly for up to one month in Groups 1 and 2; controls had one sample collected at discharge. Plasma cytokines were measured using a 25-plex panel (Human Immunotherapy Fixed Panel, Luminex®). Results Thirty-four samples from 15 patients were analyzed. Plasma cytokines analysis across groups is shown in Figure 1. While come cytokines were more abundant in Group 1 compared to Group 2 and controls (e.g., IL-9 and IP-10), no significant differences were observed. Next, we compared cytokine levels in participants with (n=4) and without PICS (n=11). Both IL-1Ra and IP-10 were increased among children with PICS (p=0.007 and p=0.012, respectively). Conclusion In a preliminary analysis of the first 15 patients in the cohort, children with CHD and PICS demonstrate increased plasma levels of both pro-inflammatory (IP-10) and anti-inflammatory (IL-1Ra) cytokines that mirror the clinical phenotype of PICS. Ongoing analysis includes immunophenotyping and immunometabolic profiling of peripheral blood mononuclear cells. Disclosures C. Buddy Creech, MD, MPH, CommenseBio: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant

P-1390. Anorectal Human Papillomavirus (HPV) Infection in HIV-Positive Men who have Sex with Men (MSM) in Nicaragua

Abstract Background HIV-positive men who have sex with men (MSM) are at increased risk for sexually transmitted infections, including anorectal HPV, with the consequent likelihood of neoplasia at that level. There is a complete lack of information on this situation in Nicaragua. This study explores and establishes for the first time the prevalence of anorectal HPV infection in HIV-positive MSM and its correlation with cytological abnormalities, and some associated behavioral, virological, and immunological factors in Nicaragua.Figure 1.Prevalence of HPV Anorectal Infection in MSM HIV Positive Diagnosed by RT-PCR Xpert HPV. Methods A prospective, multicenter cohort study was conducted between January 2023 at December 2023, at Dr. Fernando Vélez Paiz Hospital, Antonio Lenin Fonseca Hospital, and Manolo Morales Hospital in the city of Managua, Nicaragua. HIV-positive MSM patients were enrolled to the study with prior consent. Anorectal swab samples were processed by molecular method for HPV detection (GeneXpert HPV®) of different genotypes individually or grouped into genetic patterns (16, 18/45, P3: 31/32/35/52, P4: 51/59, and P5: 39/56/66/68). In addition, anorectal Pap smears were performed for cytopathology study. All samples were processed in the microbiology and pathology laboratories of the Dr. Fernando Vélez Paiz Hospital, the main center of the research.Figure 2.Different Genotypes Detected by Xpert HPV Anorectal Infection in MSM HIV Positive. Results A total of 44 patients were enrolled in the study. A significant proportion of patients declined to participate in the study. The mean age was 35.2 ± 12.4 years. Most of the patients reported having a passive or versatile sexual role. 22.7% were naïve to antiretroviral therapy (ART). The prevalence of anorectal HPV infection was 86.3% (Figure 1). The most frequent genotype was HPV 16 (21.7%) (Figure 2). In the combined genotype patterns, P3 (31/32/35/52) was observed in 40.5% of patients. All patients were infected with more than one genotype. 31.5% of those infected had cytological abnormalities, the most frequent being low-grade squamous intraepithelial lesion (Table 1). HPV-positive patients were younger, had a higher viral load, and a lower CD4+ lymphocyte count (Table 2).Table 1.Abnormalities in Anal Papanicolau in MSM HIV-positive con HPV Infection Diagnosed by Xpert HPV. Conclusion The prevalence of anorectal HPV infection in this study is high, with serotype 16 being the most frequent. Almost a third of them have altered cytology, with low-grade squamous intraepithelial lesion being the most frequent finding.Table 2.Differences in Age, HIV Viral Load and Count of Lymphocyte CD4+ in MSM HIV-Positive with and wihtout HPV Infection Disclosures All Authors: No reported disclosures

Platelet/lymphocyte ratio levels as a predictor for echocardiographic abnormalities in patients with systemic lupus erythematosus

Abstract Background Platelet/lymphocyte ratio (PLR) has recently been described as a predictor for adverse cardiovascular outcomes, such as heart failure and coronary artery disease. In systemic lupus erythematosus (SLE), PLR has been studied as a marker of disease activity. PLR has not been evaluated as a cardiovascular biomarker in SLE. Purpose To compare the prevalence of echocardiographic abnormalities between normal and high PLR in patients with SLE. Methods Cross-sectional, retrospective, descriptive study. Women older than 18 years who met the ACR/EULAR 2019 classification criteria for the diagnosis of SLE. Patients with a history of cardiovascular disease, other connective tissue diseases, or pregnancy were excluded. The platelet/lymphocyte ratio (PLR) was calculated by dividing the platelet count by the lymphocyte count; a value &amp;gt;172.68 was considered a high PLR. Transthoracic echocardiography was performed by a certified cardiologist blinded to clinical information. Diastolic dysfunction was defined according to the following parameters: mitral flow E/A ratio, septal and lateral E/E' ratio, left atrial volume, and mitral valve deceleration time. The distribution between groups was assessed with the Kolmogorov-Smirnov test. Comparisons were made using the Chi-square test or Fisher's exact test and the Student T test or Mann-Whitney U test, as appropriate. A p-value&amp;gt;0.05 was considered statistically significant. Results A total of 54 patients were included. The mean age was 35.1 ± 11.8 years. Disease activity measured by SLEDAI was similar between groups (8.0 vs 9.0, p=0.434) and disease duration was longer in patients with high PLR (116 months vs 60 months, p=0.023). The median PLR was 157.1 ± 91.2. There was no difference in indexed left ventricular mass or diastolic dysfunction patterns between patients with high PLR and SLE patients with normal PLR. Complete results are shown in Table 2. Conclusion The prevalence of echocardiographic abnormalities is not higher in those with high PLR compared with those with normal PLR in patients with SLE. Prospective studies with serial measurements of PLR are needed to evaluate its prognostic utility in cardiovascular outcomes in patients with SLE.

P-143. Interpreting Prognostic Factors Associated with In-Hospital COVID-19 Mortality in a Peru Sample using Shapley Additive Explanations on Ensemble Learning

Abstract Background COVID-19 has infected over 4.5 million and killed more than 222,000 people in Peru. Research on key factors for in-hospital mortality in these patients is limited. Our study aims to understand prognostic factors linked to the mortality of patients with COVID-19 receiving treatment in Peru. A modified SHapley Additive exPlanations (SHAP) method was proposed. Table 1 Methods Clinical and laboratory data were collected prospectively about all patients that were admitted in the inpatient setting at Hospital De Alta Complejidad Virgen De La Puerta and Hospital víctor Lazarte Echegaray Essalud from March 1st to December 31st 2020 with a COVID-19 diagnosis clinically. Ten base predictors were first implemented using the ML algorithms such as Random Forest. Prediction performance on the area under the receiver operating characteristic (AUC) was computed. The SHAP method was then applied to each predictor based on resampled train sets for 30 trials. Factor importance in each trial was estimated by averaging SHAP scores across all predictors, weighted by AUC. Table 2 (Part 1/3) Results After applying inclusion and exclusion criteria (n=) 1,857 patients were selected from a total of 2,000 admitted patients. Several factors out of 281 in total achieved stable importance scores with statistical significance while others were not. Among poor prognostic factors were low PaO2/FiO2 ratio (SV: 4.135, 95% CI: [4.107, 4.163]), shortness of breath (SV: 4.975, 95% CI: [4.864, 5.086]), and productive cough (SV: 2.037, 95% CI: [1.99, 2.080]). Among favorable factors were high PaO2/FiO2 ratio (SV: 3.832, 95% CI: [3.816, 3.848]), low D dimer (SV: 0.875, 95% CI: [0.859, 0.891]) and lymphocyte counts (SV: 1.319, 95% CI: [1.297, 1.340]). For medications, dexamethasone w. air (SV: 2.186, [2.095, 2.277]) was the most effective. For oxygen support, binasal cannula (SV: 0.841, 95% CI: [0.826, 0.857]) and high flow cannula (SV: 0.663, 95% CI: [0.633, 0.693]) are associated with more favorable prognosis than invasive ones. Table 2 (Part 2/3) Conclusion Clinical symptoms and evidence associating acute respiratory distress and sepsis, as well as immune responses less specific to viruses, suggest a likelihood of COVID-19 mortality, consistent with global findings. Our SHAP variant generated reasonable prognostic interpretation about COVID-19 mortality in Peru. Table 2 (Part 3/3) Disclosures All Authors: No reported disclosures

Peripheral blood immunoinflammatory biomarkers: prospective predictors of postoperative long-term survival and chronic postsurgical pain in breast cancer

BackgroundTumor progression and chronic postsurgical pain (CPSP) in patients with breast cancer are both significantly influenced by inflammation. The associations between immunoinflammatory biomarkers and long-term survival, as well as CPSP, remain ambiguous. This study examined the predictive value of immunoinflammatory biomarkers for both long-term survival and CPSP.MethodsData on the clinicopathological characteristics and perioperative peripheral blood immunoinflammatory biomarkers of 80 patients who underwent breast cancer surgery were retrospectively collected. Optimal cut-off values for preoperative immunoinflammatory biomarkers, including the preoperative systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), and pan-immune-inflammation value (PIV), were established via receiver operating characteristic (ROC) curves. Kaplan−Meier curves and Cox regression analysis were used to evaluate the relationships between preoperative immunoinflammatory biomarkers and long-term survival. The relationships among the perioperative neutrophil count (NEU), monocyte count (MONO), lymphocyte count (LYM), platelet count (PLT), SII, SIRI, NLR, PIV, dynamic changes in peripheral blood cell counts, and CPSP were further assessed using logistic regression analysis.ResultsKaplan−Meier curves revealed a considerable prolongation of disease-free survival (DFS) and overall survival (OS) in the low preoperative SII, SIRI, NLR, and PIV groups. Multivariate Cox regression analysis revealed that only an elevated preoperative SIRI was an independent risk factor for postoperative DFS (HR=8.890, P=0.038). The incidence of CPSP was 28.75%. Univariate logistic regression analysis revealed that body mass index (BMI), postoperative NEU, MONO, SIRI, and PIV were negatively correlated with the occurrence of CPSP, whereas subsequent multivariate logistic regression analysis revealed that only BMI was independently associated with CPSP (OR=0.262, P=0.023).ConclusionElevated preoperative SIRI was an independent risk factor for poor DFS in breast cancer patients after surgery. In contrast, perioperative immunoinflammatory biomarkers had limited potential for predicting CPSP in patients who underwent breast cancer surgery.

P-2311. Logical Versus Absolute Lymphocyte Count-guided Preemptive Therapy for CMV Prevention in Solid Organ Transplant Recipients: A Randomized Controlled Trial

Abstract Background A preemptive approach using plasma CMV DNA load monitoring is recommended among CMV-seropositive (R+) solid organ transplant recipients (SOTr). Lately, absolute lymphocyte count (ALC) has been proposed as a surrogate marker to predict CMV infection in SOTr. We hypothesized that a preemptive approach guided by immune assessment, using low ALC, could effectively prevent CMV infection, akin to the proposed routine preemptive therapy. We aimed to assess the efficacy of logical preemptive therapy (LOG) versus ALC-guided preemptive therapy for CMV infection in CMVR+ SOTr, along with cost-effectiveness. Methods A 1:1 open-labeled randomized controlled trial was conducted at a single transplant center from February to November 2023. All adult CMVR+ SOTr not receiving anti-thymocyte globulin were randomly assigned to two groups: the LOG Group, where patients underwent plasma CMV DNA load testing every 4 weeks for 12 weeks after transplantation, and the ALC group, where the quantity of CMV DNA load was initiated when the ALC was &amp;lt; 1,000 cells/mm3. Patients were then followed for 6 months after SOT to compare the occurrence of CMV infection and the CMV DNA load testing-related cost. Results A total of 98 eligible SOTr were included and assigned into two groups, 49 patients each. They all underwent kidney transplantation (KT) with a mean+SD age of 46+11 years old; 66.3% were male. Demographic data between the two groups were comparable. Twenty-five (25.5%) participants developed CMV infection within 6 months after KT. CMV infection was comparably observed in 13 (26.5%) participants in the LOG group vs. 12 (24.5%) participants in the ALC group, p=0.82. Of those, there were no significant differences in terms of asymptomatic CMV infection, CMV disease, and clinically significant CMV infection (p=NS, all). The total cost of plasma CMV DNA load testing (68 USD per test) was significantly lower in the ALC group compared to the LOG group (2,320 vs.10,014 USD, p&amp;lt; 0.01), respectively. Conclusion Immune-guided preemptive therapy directed by low ALC appears to be effective in preventing early CMV infection after SOT. A simple and universally available ALC test could potentially be used as a personalized and cost-effective marker to initiate preemptive therapy in moderate-risk CMVR+ SOTr. TCTR20220720007. Disclosures All Authors: No reported disclosures

P-2362. Risk Factors for Persistent and Recurrent CMV DNAemia in a Real-World Cohort of SOT and HSCT Patients Receiving Maribavir

Abstract Background Refractory/resistant (R/R) CMV infection, defined by persistent symptoms or DNAemia after at least two weeks of antiviral therapy, is associated with high rates of rejection and mortality in transplant patients. Maribavir (MBV) is a newer agent with demonstrated efficacy in achieving DNAemia clearance without the bone marrow suppression associated with conventional first line therapy. However, there is less data on the risk factors for treatment failure with MBV. We sought to evaluate clinical outcomes of MBV in transplant patients in a real-world patient cohort.Table 1:Demographic Characteristics Methods A retrospective chart review was conducted of adult solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients who received MBV for R/R CMV infection at a high-volume transplant center from 2021-2023. The main treatment outcome was failure (defined as persistence of DNAemia requiring a switch in therapy).Table 2:Risk Factors for Maribavir Failure Results Nineteen patients received MBV for CMV DNAemia or tissue-invasive disease. Overall, 84% were SOT, 63% had high-risk CMV serostatus, and 90% had asymptomatic DNAemia. Twenty-six percent of patients experienced MBV failure. The median absolute lymphocyte count (ALC) was 852 µL at MBV switch in those with successful treatment compared with 262 µL in those with MBV failure, although this did not reach statistical significance. Peak viral load was also not significantly associated with MBV failure. Five patients later developed MBV resistance by commercial genotype sequencing. Conclusion Real world use of MBV demonstrated comparable rates of viral clearance with clinical trial data in SOT and HSCT patients. While not statistically significant, there was a trend towards MBV failure in patients with lower ALC. Future studies may be useful to determine if switching to MBV before onset of worsening lymphopenia related to first line therapy would impact the rate of treatment failure and MBV resistance. The lack of association between VL and virologic response also suggests that MBV may be safely used in patients regardless of viral load. Disclosures Joanna M. Schaenman, MD, PhD, FAST, Eurofins Viracor: Honoraria|F2G: Grant/Research Support|MedCure: Advisor/Consultant|Moderna: Clinical trial support to institution|OneLegacy: Advisor/Consultant

Handgrip strength as a potential indicator of aging: insights from its association with aging-related laboratory parameters

IntroductionThe aging process is frequently associated with a decline in functional capacity, endurance, muscle quality, and overall quality of life. Examining aging-related biomarkers often requires significant time and financial resources, underscoring the need for a straightforward and practical indicator. This study aims to investigate the association between handgrip strength and aging-related laboratory parameters in the elderly population of Indonesia.MethodsA cross-sectional study was conducted involving 109 participants aged 60–82 years. Handgrip strength was measured using a Jamar hydraulic hand dynamometer and Jamar PLUS+ digital dynamometer. Aging-related laboratory biomarkers were defined as those indicating physiological aging processes.ResultsThe study revealed a significant association between handgrip strength and several aging-related laboratory parameters, including leukocyte count, absolute neutrophil count, absolute lymphocyte count, neutrophil/lymphocyte ratio, and erythrocyte sedimentation rate.DiscussionThese findings suggest that handgrip strength could serve as a cost-effective, non-invasive predictor of aging-related health status in older adults. Its practical utility highlights its potential for guiding health interventions targeting the elderly population.

P-914. Clinical Outcomes and Predictors of Mortality among Hospitalized HIV/ AIDS Adult Patients Diagnosed with Central Nervous System Infections in a National Tertiary Referral Hospital in the Philippines: A 5-year Retrospective Study

Abstract Background HIV infection remains a significant global health concern despite the major advances in its understanding and treatment. Central nervous system (CNS) infections are common complications among HIV-infected patients. In the Philippines, limited local data on the clinical profile and outcome among HIV-infected patients with CNS infections is available. Case Distribution of CNS Infections among HIV-infected patients in the Philippines Methods This is a 5-year retrospective study of confirmed HIV-infected patients hospitalized and managed as CNS Infections at San Lazaro Hospital, Manila Philippines between 2018 and 2022. Demographics and clinical data were extracted from medical records and the association with clinical outcome and length of hospital stay were analyzed. Incidence and Case Fatality Rate of CNS Infections among HIV-infected patients in the Philippines Results One hundred twenty-eight (128) HIV-infected patients, mostly male (95%), were included, with a mean age of 31 years, and a mean CD4 lymphocyte count of 56.8 (0-282) cells/mm3. Forty-one patients (32%) were newly diagnosed with HIV, and 51% (n=65) were not on antiretroviral therapy (ART). The mean duration of HIV diagnosis among those known to have HIV before admission was 1.4 years. The most common CNS infection was Tuberculous Meningitis (TBM) (35%), followed by Cryptococcal Meningitis (CM) (29%), and Toxoplasma Encephalitis (TE) (17%). The presence of dual CNS Infection was diagnosed among 20 patients (15.6%), of which a total of 16 (12.5%) had co-infection of TBM and TE, while 4 (3.1%) had co-infection of TBM and CM. The most common clinical manifestations were headache (87.5%), fever (61%), and sensorial changes (60%). The overall in-hospital mortality rate was 30.4% (n=39), with the highest case-fatality rate among those infected with Cryptococcal Meningitis at 53% (n=19). Among those diagnosed with CM, 23 patients (62%) had concomitant Cryptococcal Fungaemia. Those with CM and dual CNS infection had a longer hospital stay of &amp;gt;31 days ( &amp;gt;1 month). Conclusion In the Philippines, the most common CNS infection among HIV-infected patients was Tuberculous Meningitis, followed by Cryptococcal Meningitis, and Toxoplasma Encephalitis. Early diagnosis of HIV infection with timely initiation of ART, together with an effective diagnostic and management approach to these conditions is needed to decrease the risk of further complications and death. Disclosures All Authors: No reported disclosures

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

Early mortality predictors in COVID-19 pneumonia complicated with pulmonary embolism- unicentre analysis

Abstract Background Covid-19 took an huge death-toll in the era of its pandemic widespread in scale of the whole world imposing a new and still not completely understood not resolved threat to public health. Beyond the severity of lungs affliction and the subsequent respiratory failure thromboembolic complications with their crucial form of pulmonary embolism (PE) are seen as responsible of this high numbers of fatalities. Aim We aim to find predictors of in hospital death in subgroup of patients with COVID-19 pneumonia diagnosed simultaneously with CT-angiography of pulmonary embolism. Methods Our group included 39 patients from 42 to 95 year old (mean age 67±13, 27 males and 12 females) hospitalized in Internal Disease and Clinical Pharmacology Department since October 2020 to June 2021 with the diagnosis of SARS COV2 pneumonia and pulmonary embolism detected with CT angiography during the analysed hospitalization. We compared clinical, laboratory and treatment data between group who died during hospitalization (G1) and those who survived the early period of at least 1 month after disease onset (G2). Results During hospitalization and in extended to 1 month follow-up 12 deaths occurred, 8 in men (30%) and 4 in women (33%), however this difference did not reach statistical significance and moreover women were older than men among all PE patients (73±12 vs 64±13 years respectively, p=0.049). The compared groups did not differ significantly according to age (although some trend to higher age in G1), the prevalence of hypertension, diabetes, chronic obstructive pulmonary disease as well as provided treatment including heparin, oxygen therapy, remdesivir, tocilizumab and dexamethasone or heart rate, creatinine, troponin or NT-proBNP level, see Table. They differ, however, according to IL-6 concentration significantly higher in group with fatal outcome (108 (77-240) vs 52 (41-98) pg/ml, p =0.0162) as well as according to surprisingly higher lymphocyte count (0.95 (0.75-1.55) vs 0.6 (0.4-0.7) count X 1000, p=0.0058). Both these parameter showed significant predictive value of early death in studied group with sensitivity of 75% for both parameters and specificity of 74% for IL-6 &amp;gt; 91 and 78% for lymphocytes above 700/µl.