Leukopenia Research Articles

Mediating Role of Platelet Count Increase in Unfractionated Heparin Treatment for Sepsis Patients: A Retrospective Cohort Analysis

Aims/Background The role of heparin in sepsis therapy has been widely debated. The controversy surrounding heparin’s use as an anticoagulant in sepsis may stem from differences in sepsis definitions, study designs, timing and dosage of drug administration, treatment duration, complications, and patient severity. In this study, we aimed to determine the optimal timing and dosage of heparin in patients with sepsis, identify specific subgroups that could benefit from heparin therapy, and explore laboratory markers to assess its efficacy. Methods This retrospective cohort study was conducted using the Medical Information Mart for Intensive Care-IV dataset. Data from patients with sepsis were extracted based on the Sepsis 3.0 criteria. Patients were categorized according to heparin use. The effectiveness of early and appropriate heparin administration was assessed, and a subgroup analysis was performed to identify patients most likely to benefit from heparin therapy. Additionally, factors mediating the improvement in sepsis prognosis following heparin treatment were analyzed. Results We recruited 4149 participants who met the inclusion criteria, with an overall 28-day mortality rate of 19.5%. There were 2192 individuals in the heparin group and 1957 in the non-heparin group. After propensity score matching, heparin therapy demonstrated a significantly greater effect on reducing both 28-day and 90-day mortality compared to the non-heparin treatment (18.1% vs. 10.7%, p < 0.001; 18.8% vs. 12.6%, p < 0.001). However, the heparin group had a higher incidence of major bleeding (10.9% vs. 6.3%, p = 0.001), increased use of mechanical ventilation (54.3% vs. 45.1%, p < 0.001), and a longer intensive care unit stay (3.6 vs. 2.5 days, p < 0.001) compared to the non-heparin group. Early administration of high-dose heparin improved 28-day survival. Early and adequate heparin administration was more effective than late and insufficient dosing (p < 0.01), except in patients with sepsis who had low white blood cell counts, alkalosis, or reduced platelet counts. The increase in platelet count had a significant mediating effect on the entire cohort (p < 0.001 for the causal mediation effect), with a mediation proportion of 14%. Conclusion Early and adequate heparin administration can significantly improve the prognosis of sepsis. An increase in platelet count may serve as a potential indicator of the effectiveness of heparin therapy in sepsis.

Impact of microbial diversity on inflammatory cytokines and respiratory pattern measured in whole-body plethysmography in guinea pig models.

This study investigates the breathing patterns and immune status of guinea pigs raised under specific pathogen-free (SPF) conditions compared to conventionally bred (CON). Breathing pattern parameters were assessed using whole-body plethysmography (WBP) during quiet breathing and saline nebulisation. Blood and bronchoalveolar lavage fluid (BALF) were analysed for white blood cell, neutrophil and eosinophil counts, and cytokine levels (TNF-α, IL-1β, IL-4). SPF guinea pigs exhibited higher tidal volume, expired volume, minute volume, and airflow parameters than CON guinea pigs. The immune analysis revealed lower white blood cell counts and IL-4 levels in SPF guinea pigs. These findings indicate that SPF guinea pigs have different respiratory and immune responses than CON guinea pigs. The study highlights that the maturation processes affecting breathing pattern parameters in SPF guinea pigs differ significantly from those in CON guinea pigs. This suggests potential limitations of SPF animals in respiratory physiology research due to their different immune and respiratory responses.

Study on the clinical characteristics, treatment, and outcome influencing factors of severe pneumonia complicated with ARDS.

To investigate the clinical characteristics, treatment methods, and factors influencing the prognosis of patients with severe pneumonia complicated by Acute Respiratory Distress Syndrome (ARDS), aiming to provide references for clinical decision-making and improve patient outcomes. A retrospective analysis was conducted on 118 patients with severe pneumonia complicated by ARDS treated at our hospital from June 2018 to December 2022. Based on treatment outcomes, patients were divided into a death group (n = 75) and a survival group (n = 43). General data and clinical laboratory indicators, including blood urea nitrogen, serum creatinine, C-reactive protein, procalcitonin, arterial partial pressure of oxygen, and arterial partial pressure of carbon dioxide, were collected and compared between the 2 groups to identify independent factors affecting prognosis. Among the 118 patients, the mortality rate was 63.56%. Patients in the death group had a significantly higher average age (57.15 ± 13.38 years) and a higher proportion of severe ARDS (66.67%) compared to the survival group (40.02 ± 11.41 years, 30.23%, P < .001). The death group had significantly lower white blood cell counts (8.10 ± 1.64 × 109/L), oxygenation index (19.82 ± 2.29), and duration of mechanical ventilation (7.79 ± 2.11 days) compared to the Survival group (8.92 ± 1.22 × 109/L, 13.42 ± 1.82, 12.23 ± 3.05 days, P < .05). Conversely, the death group had significantly higher levels of blood urea nitrogen (6.87 ± 1.80 mmol/L), C-reactive protein (130.55 ± 50.28 mg/L), procalcitonin (5.50 ± 2.11 ng/mL), arterial partial pressure of carbon dioxide (41.12 ± 5.56 mm Hg), and a higher proportion of viral infections (48.00%) compared to the survival group (5.90 ± 1.72 mmol/L, 101.77 ± 55.56 mg/L, 3.98 ± 1.15 ng/mL, 35.59 ± 6.22 mm Hg, 27.91%, P < .05). Logistic regression analysis revealed that age (odds ratios [OR] = 1.990, 95% confidence interval [CI]: 1.306-3.033, P < .001), oxygenation index (OR = 1.426, 95% CI: 1.123-1.649, P < .001), and duration of mechanical ventilation (OR = 0.694, 95% CI: 0.557-0.864, P < .001) were independent factors influencing patient prognosis. This indicates that an increase in age and a decrease in oxygenation index are associated with a significantly higher risk of mortality, while shorter mechanical ventilation duration is related to poorer prognosis. Advanced age, lower oxygenation index, and shorter duration of mechanical ventilation are unfavorable prognostic factors in patients with severe pneumonia complicated by ARDS. These findings aid clinicians in identifying high-risk patients, optimizing treatment plans, and improving patient prognosis.

Hemoglobin F% and Complete Blood Count Patterns in Two Independent Sickle Cell Anemia Cohorts from India & the US

Sickle cell anemia (SCA) is among the most common monogenetic diseases affecting approximately 8 million people and 300,000 newborns per year worldwide. In certain regions of India, the hemoglobin (Hb) S mutation is observed in up to 40% of the population with 2% being homozygous (Hb SS). Despite the high prevalence of SCA in India, the characteristics of SCA in this population and the impact of Hb F% on the SCA phenotype are not well understood. We conducted a prospective, observational study to better understand the Hb F% patterns and relationship to complete blood count (CBC) parameters in a tribal region of central India. 575 patients with SCA were recruited between 11/2021 and 4/2024 and blood was collected to determine Hb F%, Hb concentrations, and white blood cell (WBC) counts. We compared our findings to a separate cohort of 240 SCA patients enrolled in a registry from a large urban academic center in the US. The Hb F% from the US cohort were obtained either before initiating hydroxyurea therapy or at the time of recruitment if not on hydroxyurea therapy. The median age of the SCA cohort from India was 16 (interquartile range [IQR], 9 - 25) years old and 284 (49%) were female. The median Hb F% was 26.8% (IQR, 22.3% - 31.2%) and the median Hb concentration was 8.5 g/dL (IQR, 7.3 - 9.6 g/dL). Females had significantly higher Hb F% versus males (25.7% vs. 23.4%, respectively; P = 0.001) while older age was associated with a trend for lower Hb F% (β -0.032 ± 0.027; P = 0.1). A higher Hb F% was associated with improved Hb concentrations (β 0.083 ± 0.012; P &amp;lt; 0.0001) and lower WBC counts (β -0.129 ± 0.035; P &amp;lt; 0.0001). In the US cohort, the median age was 31 (IQR, 23 - 42) years old and 143 (59%) were female. The median Hb F% was 4.4% (IQR, 2.4 - 7.9%) and significantly lower compared to the Hb F% observed in SCA patients from India (age-adjusted P &amp;lt; 0.0001). The median Hb concentration was 8.6 g/dL (IQR, 7.7 - 9.4 g/dL), similar to the Hb concentrations observed in SCA patients from India (P = 0.6). Consistent with the Indian cohort, females had significantly higher Hb F% versus males (5.0% vs. 3.4%, respectively; P = 0.002) while there was no association between age and Hb F% (P = 0.7) in the US SCA cohort. Also similar to the Indian cohort, a higher Hb F% was associated with improved Hb concentrations (β 0.084 ± 0.019; P &amp;lt; 0.0001) and lower WBC counts (β -0.125 ± 0.047; P = 0.008). In conclusion, we demonstrate laboratory phenotyping of a large cohort of patients with SCA from a tribal region in central India. Hb F% were significantly higher in this cohort compared to a cohort of SCA patients from the US. We observed parallel findings between the two cohorts for higher Hb F% in women versus men as well as the protective effects of Hb F% on improved hemoglobin concentrations and reduced WBC counts, a biomarker that predicts vaso-occlusive episodes. Interestingly, although Hb F% were higher in SCA patients from the cohort in India vs. US, the Hb concentrations were similar. This suggests other factors, such as nutritional deficiencies, may be contributing to the anemia in SCA patients from India. Continued research is needed to better understand the phenotype of SCA in India as well as the impact of therapies that augment Hb F%, including gene therapy, in this patient population.

Combination of Low White Blood Cell Count and Impaired Renal Function Is a Risk Factor for Higher Concentrations of Venetoclax and Prolonged Neutropenia in AML Patients with Venetoclax Combined Regimen: Real World Experience in the Japanese Cohort

Combination of Low White Blood Cell Count and Impaired Renal Function Is a Risk Factor for Higher Concentrations of Venetoclax and Prolonged Neutropenia in AML Patients with Venetoclax Combined Regimen: Real World Experience in the Japanese Cohort

Biomarker potential of nuclear Nrf2 activation in the ABC subtype of diffuse large B‑cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma characterized by distinct subtypes and heterogeneous treatment outcomes. Oxidative stress and the dysregulation of related regulatory genes are prevalent in DLBCL, prompting an investigation into the nuclear factor erythroid 2-related factor 2 (Nrf2)-kelch-like ECH-associated protein 1 (Keap1) signaling pathway and associated genes. The present study assessed pathological specimens and clinical data from 43 newly diagnosed patients with DLBCL, comparing the associations and correlations between the expression of Nrf2, Keap1, microtubule-associated protein 1 light chain 3β (LC3B) and nitrotyrosine and the activated B-cell (ABC) and germinal center B-cell (GCB) subtypes of DLBCL using immunohistochemistry and digital image analysis software. Nuclear Nrf2 activation was observed in 33.3% of patients with DLBCL ABC, demonstrating a higher prevalence of hepatitis B surface antigen positivity, calcium ions and significant body weight loss (P<0.05). Total Nrf2 expression was associated with the DLBCL GCB subtype and inversely correlated with Keap1 expression in the DLBCL ABC subtype. Furthermore, a positive correlation was demonstrated between Nrf2 and LC3, indicating that total Nrf2 is inhibited by Keap1 and regulates LC3 expression. The ABC subtype was also associated with lower white blood cell counts and more frequent chemotherapy courses than the GCB subtype. These findings suggest that nuclear Nrf2 could be a biomarker for DLBCL clinical diagnosis.

A discussion of pediatric therapy-related acute myeloid leukemia with a rare t(8;16) translocation

Abstract Introduction/Objective Secondary acute myeloid leukemia is a type of blood cancer that arises after a previous myeloid neoplasm or after exposure to chemotherapy. Certain genetic mutations and chromosomal abnormalities can occur as a result of said cytotoxic drug-related effects. Here, we discuss a case of secondary acute myeloid leukemia with a rare translocation following hemophagocytic lymphohistiocytosis Etoposide treatment in a 13-year-old female. After less than a year into her initial treatment, the patient presented to the emergency department with severe bone pain. A full hematologic workup was performed, including bone marrow biopsy, flow cytometry analysis, and subsequent genetic studies. A diagnosis of therapy-related acute myeloid leukemia was made. Genetic studies revealed a rare t(8;16) translocation which presents with a unique morphology and prognosis that will be discussed here. Methods/Case Report A 13-year-old female presented to the emergency department for evaluation of fever, myalgia, and swelling in her clavicle. The patient’s history was notable for hemophagocytic lymphohistiocytosis with subsequent Etoposide chemotherapy treatment which she received less than a year prior to her visit. CBC was notable for low white blood cell count, low hemoglobin, increased neutrophilic bands, and decreased lymphocytes. Given her past medical history and worsening pain without a clear reason, hematology was consulted. Results (if a Case Study enter NA) A blast count of 61.8% was reported via flow cytometry with the cells seen in the dim CD45+, moderate to bright side-scatter region, co-expressing CD4, CD14 (dim, heterogeneous), CD15, CD16 (dim), CD64, HLA-DR, and MPO. The bone marrow biopsy was described as hypercellular with the predominant cell type as blasts at 66.4%. Numerous hemophagocytic blasts were noted as well. Acute leukemia next generation sequencing panel revealed a t(8;16)(p11;p13.3) KATA6A::CREBBP fusion without other abnormalities in the evaluated genes. This workup as a whole rendered the diagnosis of acute myeloid leukemia with KAT6A::CREBBP. Conclusion Diagnosing acute myeloid leukemia with KATA6A::CREBBP is important for prognostic factors. Knowing the patient’s history regarding her prior chemotherapy with Etoposide is also imperative for distinguishing a de novo presentation of this rare subtype, versus a therapy-related myeloid neoplasm. The patient was started on chemotherapy for her acute myeloid leukemia shortly thereafter the diagnosis.

Characteristics of long-term survivors with malignant pleural mesothelioma

Pleural mesothelioma (PM) is a cancer with usually a dismal prognosis. However, long-term survivors do exist. Herein, we analyzed long-term survivors (>5 years after surgery) from high-volume centres around the world. This is a multicenter retrospective descriptive analysis of long-term survivors (overall survival ≥ 5 years from surgery) treated within a multimodality therapy approach including macroscopic complete resection. Overall survival was calculated with Kaplan Meier analysis and cases were matched by center and surgery year and compared with a control group of short-term survivors (<2 years) in a conditional logistic regression analysis. There were 276 long-term survivors, most were male (n=166, 63%) with a median age of 59 (range 21-83) years at time of diagnosis. The histology for 246 was epithelioid and non-epithelioid for 30 patients. The disease was on the right side in 58% of the patients. As of this analysis, 148 patients were dead, 104 were alive and 10 were lost to follow-up. Pathological tumor stages were: pT1 (n=50), pT2 (n=63), pT3 (n=90) or pT4 (n=16), pN0 (n=150), pN1 (n=20) and pN2 (n=39). The matched control dataset included 333 patients, 95 cases and 238 controls. Comparing short- with long-term survivors, there was moderate evidence that a low white blood cell (WBC) count before surgery was more often observed in long-term survivors. The data show that long-term survival in PM is possible in a subgroup of surgically treated patients; histological subtype and WBC count seem to be prognosticators for longer survival.

High Polygenic Risk Scores Positively Associated with Gastric Cancer Risk Interact with Coffee and Polyphenol Intake and Smoking Status in Korean Adults.

This study investigated the relationship between single nucleotide polymorphisms (SNPs) and gastric cancer (GC) risk, while also examining the interaction of genetic factors with lifestyle variables including the nutrient and bioactive compound intake in Korean adults of a large hospital-based cohort. We conducted a genome-wide association study (GWAS) comparing GC patients (n = 312) with healthy controls without cancers (n = 47,994) to identify relevant genetic variants. Generalized multifactor dimensionality reduction (GMDR) was employed to detect SNP interactions between diets and lifestyles. We utilized polygenic risk scores (PRSs) to assess individuals' GC risk based on multiple SNP loci. Among the selected SNPs, since SEMA3C_rs1527482 was a missense mutation, bioactive compounds which decrease the binding energy were found with its wild and mutated proteins by molecular docking analysis. Individuals with high PRSs exhibited a 4.12-fold increased risk of GC compared to those with low PRSs. Additional factors associated with elevated GC risk included a low white blood cell count (OR = 5.13), smoking (OR = 3.83), and low coffee consumption (OR = 6.30). The SEMA3C_rs1527482 variant showed a positive correlation with GC risk. Molecular docking analyses suggested that certain polyphenols, including theaflavate, rugosin E, vitisifuran B, and plantacyanin, reduced the binding free energy in both wild-type and mutated SEMA3C_rs1527482. However, some polyphenols exhibited differential binding energies between its wild and mutated forms, suggesting they might modulate wild and mutated proteins differently. High PRSs and SEMA3C_rs1527482 interact with immune function, coffee intake, polyphenol consumption, and smoking status to influence GC risk. These findings could contribute to developing personalized nutrition and lifestyle interventions to reduce GC risk.

PSX-27 Growth performance and immune response dynamics in weaned lambs with subclinical Haemonchus contortus parasite infection

Abstract Parasite infections, particularly from Haemonchus contortus, hinder sheep production in Canada by reducing weight gain and immunity. Current diagnosis and treatment methods rely on observing symptoms and the blind administration of anthelmintic drugs, resulting in escalating costs and the development of drug-resistant parasites. This study aimed to identify the exact time-point when subclinical H. contortus parasite infection affects growth performance and triggers an immune response. A total of 60 Rideau Arcott ewe lambs (~7-8 mo old), confirmed to be parasite-free, were randomly assigned in a 2 x 2 factorial design assessing inoculation treatment (TRT): oral inoculation (IN) with a solution containing 5,000 L3 strain of H. contortus or sham inoculation (CT) using water solution as control; and drench (DRENCH) administration: oral drench (D), 28-days post-inoculation, with a combination of 0.08% ivermectin solution (200 mcg per kg of BW; Durvet®) and 10% oral suspension of fenbendazole (2.5 mL per 50 kg of BW; Safe-guard®), or water solution (non-drenched, ND), resulting in four treatment groups: IN-D, IN-ND, CT-D, and CT-ND (n=15/treatment). Lambs were equally assigned to four feedlot pens (two replicates/treatment) for 57 days (d) with ad libitum access to a grain-based total mixed ration and water. Animals were individually weighed (BW) and blood sampled on days -1 and 0 (baseline), as well as on days 7, 21, 28, 35, 42, 56, and 57 post-inoculations (DAY); average daily gain (ADG) was calculated for the entire experimental period. White blood cells count (WBC) was used as an indicator of infection and red blood cell count (RBC) as indicator of anemia. Data was analyzed using a mixed-effects model including TRT, DRENCH, DAY (and their interactions) as fixed effects. Overall, CT lambs were heavier (TRT effect; P &amp;lt; 0.05) and had a tendency of greater (TRT effect; P = 0.08) ADG than IN lambs. The IN lambs had a tendency of greater (TRT*DAY; P = 0.07) WBC on d 7 than CT lambs. Additionally, IN-ND had lower (TRT*DRENCH; P &amp;lt; 0.05) WBC than IN-D lambs (1.9 and 2.0 ± 0.042 x 109/L, respectively). A significant (TRT*DRENCH*DAY; P &amp;lt; 0.01) interaction was found on RBC. The CT-D had lower (P &amp;lt; 0.05) RBC on d 7 and greater (P &amp;lt; 0.05) on d 28, 35, 42, and 57 than IN-ND as well as on d 28 than IN-D. Furthermore, CT-ND had greater (P &amp;lt; 0.05) RBC on d 21, 28 and 35 than IN-D and from d 21 to 57 than IN-ND. The IN-D had greater (P &amp;lt; 0.01) RBC from d 35 to 57 than IN-ND. These findings suggest compromised growth in both drenched and non-drenched infected groups. Infection slightly peaked in the infected lambs on d 7 post-inoculation, but drench administration was effective at mitigating overall infection by day 21 and the anemia by day 35.

Development and validation of a nomogram based on Lasso-Logistic regression for predicting splenomegaly secondary to acute pancreatitis

PurposeInvestigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression.MethodsA retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation.ResultsThe prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P < 0.05 for all). There were 185 and 79 patients in the training and internal validation cohorts, respectively. Variables screened by Lasso regression, including platelet count, white blood cell (WBC) count, local complications, and modified CT severity index (mCTSI), were incorporated into the Logistic model. Multivariate analysis showed that WBC count ≦9.71 × 109/L, platelet count ≦140 × 109/L, mCTSI ≧8, and the presence of local complications were independently associated with the occurrence of SSAP. The area under the receiver operating characteristic curve was 0.790. The Hosmer-Lemeshow test showed that the model had good fitness (P = 0.954). Additionally, the nomogram performed well in the internal validation cohorts.ConclusionsSSAP is relatively common, and patients with this condition often have a worse clinical prognosis. Patients with low WBC and platelet counts, high mCTSI, and local complications in the early stages of the illness are at a higher risk for SSAP. A simple nomogram tool can be helpful for early prediction of SSAP.

Unraveling the influence of childhood emotional support on adult aging: Insights from the UK Biobank

BackgroundExploring the association between Childhood Emotional Support (CES) and the mechanisms of aging is pivotal for understanding its potential to lessen the incidence of age-related pathologies and promote a milieu for healthy aging. MethodsUtilizing data from the UK Biobank comprising nearly 160,000 individuals, comprehensive analyses were conducted to explore associations between CES levels and age-related diseases, biological age and aging hallmarks. Cox proportional hazards regression models were used to investigate the relationship between CES and the risk of hospitalization for age-related diseases. Linear regression models were employed to explore the associations between CES and the frailty index (FI), Klemera-Doubal method (KDM) biological age acceleration, homeostatic dysregulation (HD), C-reactive protein (CRP), white blood cell (WBC) count, and telomere length. ResultsThe analyses revealed a significant association between higher CES levels and a decreased risk of hospitalization for age-related diseases in later life. After adjustments for covariates, the hazard ratio for age-related diseases was 0.87 (95 % confidence interval, 0.83–0.91, p < 0.001) in those with the highest CES level compared to those with the lowest CES level. Participants with the highest CES level exhibited lower FI scores (coefficient = -0.033, p < 0.001), reduced CRP level (coefficient = -0.097, p < 0.05) and lower WBC counts (coefficient = -0.034, p < 0.05). Stratified analyses based on genetic susceptibility further elucidated the protective role of CES against age-related diseases. ConclusionThese findings underscore the potential of early interventions targeting CES to promote healthy aging and alleviating the burden of age-related diseases.

Predictors of gentamicin therapy failure in neonates with sepsis.

Sepsis is a common disease with high morbidity and mortality among newborns in intensive care units world-wide. Gram-negative bacillary bacteria are the major source of infection in neonates. Gentamicin is the most widely used aminoglycoside antibiotic in empiric therapy against early-onset sepsis. However, therapy failure may result due to various factors. The purpose of this study was to identify predictors of gentamicin therapy failure in neonates with sepsis. This was a prospective cross-sectional study at the Neonatal Intensive Care Unit at Windhoek Central Hospital over a period of 5 months in 2019. Neonates received intravenous gentamicin 5 mg/kg/24 h in combination with either benzylpenicillin 100 000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Logistic regression modeling was performed to determine the predictors of treatment outcomes. 36% of the 50 neonates were classified as having gentamicin treatment failure. Increasing treatment duration by 1 day resulted in odds of treatment failure increasing from 1.0 to 2.41. Similarly, one unit increase in CRP increases odds of gentamicin treatment failure by 49%. The 1 kg increase in birthweight reduces the log odds of treatment failure by 6.848, resulting in 99.9% decrease in the odds of treatment failure. One unit increase in WBC reduces odds of gentamicin treatment failure by 27%. Estimates of significant predictors of treatment failure were precise, yielding odds ratios that were within 95% confidence interval. This study identified the following as predictors of gentamicin therapy failure in neonates: prolonged duration of treatment, elevated C-reactive protein, low birthweight, and low white blood cell count.

Age, gender, and infectious status-wise assessments of hematological parameters among patients with dengue infection

BackgroundThe aim of this study was to examine the impact of different stages of dengue infection on immune cell counts among dengue patients and to compare them with cases of non-dengue febrile illness. MethodsThe recruited patients were divided into two groups: the first group served as a control (n = 55), representing non-dengue febrile illness, and the second group was identified as dengue febrile illness (n = 149), which was further divided into three groups based on infection stage. Blood samples were collected from the selected patients and subjected to blood cell component analysis. To find IgG and IgM as well as the dengue virus non-structural antigen-1 (NS1), an immunochromatographic test (ICT) kit was utilized. Additionally, a hematological analyzer was used to determine complete blood cell counts (CBC). Data was thoroughly analyzed using Graph Pad Prism 6 software. The differences in means of different groups were calculated by applying the student's t-test. ResultsThe findings revealed the presence of severe leucopenia and thrombocytopenia at stages 1 and 2, accompanied by lymphopenia at stage 1. Group comparisons indicated that only teenagers exhibited a significantly lower white blood cell count compared to older individuals, while no significant differences were observed in lymphocytes, platelets, and monocytes across all age groups. Comparing different age groups of normal individuals to dengue-infected patients, the results unveiled that leucopenia was most severe in adults, followed by teenagers and children, with no significant difference in the elderly. Furthermore, adults showed the greatest degree of thrombocytopenia, followed by teens and kids, with the elderly showing the greatest degree of thrombocytopenia. Adults and teens showed extreme neutrophilia, whereas young children and the elderly showed no discernible abnormalities. Elderly patients experienced a marked decrease in monocyte count, a phenomenon not observed in other age groups. ConclusionIn conclusion both, leucopenia & thrombocytopenia, are most severe in stages 1 and 2, whereas neutrophilia & lymphopenia are predominantly severe in stage 1. These results imply that the consequences associated with dengue infection are more severe in the early stages and tend to ameliorate as the patient progresses toward recovery.

Predictive Value of C-reactive Protein in the Spontaneous Passage of Lower Ureteric Stones: A Prospective Single-Centre Study.

Ureteric stones, characterised by their presence in the ureter, present a common yet often painful urological condition requiring timely intervention. As C-reactive protein (CRP) emerges as a potential biomarker, its correlation with the spontaneous stone passage(SSP) offers valuable insights into patient management and treatment strategies. The present study aimed to assess if CRP levels can predict SSP in symptomatic lower ureteric calculi of size 5 mm-10 mm. This prospective observational study, conducted at the Indira Gandhi Institute of Medical Sciences in Patna, India, from July 2022 to June 2023, focused on individuals aged 13 to 60 years presenting with ureteric colic and single distal ureteral stones (5 mm-10 mm). Patients underwent comprehensive initial assessment and monitoring, including diagnostic procedures such as a complete blood count, urinalysis, CRP levels, and renal function evaluations. Treatment consisted of hydration encouragement, tamsulosin (0.4 mg) daily administration, and diclofenac (50 mg) as needed. Follow-up assessments at one-month post-treatment involved clinical examination and imaging studies to evaluate treatment efficacy. This study analysed 157 patients with ureteric stones, finding that 76% experienced SSP. Lower CRP levels (≤6 mg/L), along with other laboratory parameters like low white blood cell counts, low neutrophil levels, absence of leukocyturia, absence of hematuria, and lower urine specific gravity, were associated with higher SSP rates. C-reactive protein levels ≤6 mg/L emerged as a strong predictor of SSP in multiple regression analysis. The findings underscore the potential utility of CRP as a predictive biomarker in guiding the management and treatment strategies for ureteric stones.

Crosstalk between circBMI1 and miR-338-5p/ID4 inhibits acute myeloid leukemia progression.

BMI1 polycomb ring finger proto-oncogene (BMI1) is involved in the pathogenesis of different cancers, including acute myeloid leukemia (AML). However, the role of the circular RNA of BMI1 (circBMI1) has not been studied. Our study aimed to investigate the role and mechanism of circBMI1 in AML. circBMI1 was significantly decreased in bone marrow mononuclear cells aspirated from patients with AML. Receiver operating characteristic curve analysis showed that circBMI1 could distinguish patients with AML from controls. By overexpressing and knocking down circBMI1 in HL-60 cells, we found that circBMI1 inhibited cell proliferation, promoted apoptosis, and increased chemotherapeutic drug sensitivity in AML. Experiments using severe combined immune-deficient mice and circBMI1 transgenic mice showed that mice with circBMI1 overexpression had lower white blood cell counts, which suggested less severe AML invasion. RNA immunoprecipitation and dual-luciferase reporter assay revealed binding sites among circBMI1, miR-338-5p, and inhibitor of DNA-binding protein 4 (ID4). Rescue experiments proved that circBMI1 inhibited AML progression by binding to miR-338-5p, which affected the expression of ID4. By coculturing exosomes extracted from circBMI1-HL-60 and small interfering circBMI1-HL-60 cells with HL-60 cells, we found that exosomes from circBMI1-HL-60 cells showed tumor-suppressive effects, namely inhibiting HL-60 proliferation, promoting apoptosis, and increasing chemotherapeutic drug sensitivity. Exosomes from small interfering circBMI1-HL-60 cells showed the opposite effects. circBMI1 may act as an exosome-dependent tumor inhibitor. circBMI1, a potential biomarker for clinical diagnosis, acts as a tumor suppressor in AML by regulating miR-338-5p/ID4 and might affect the pathogenesis of AML by exosome secretion.

Outcomes of patients who received CAR T cell therapy and developed IEC-HS treated with cytokine directed therapy.

7516 Background: Immune effector cell hemophagocytic lymphohistiocytosis IEC-HS is a complication of CAR T cell therapy (CART). This study aims to look at the outcomes of CART patients who develop IEC-HS. Methods: Patients who developed IEC-HS after receiving CART and patients who developed IEC-HS without (nonCART) between December 2020 and March 2022 were included. Results: The 20 CART patients were older than the 25 nonCART patients. Peak ferritin, fibrinogen, CRP, serum creatinine and transaminases were similar between the 2 group. CART patients had lower white blood cell count and platelets and bilirubin than the nonCART patients. CART patients were more like to have markedly elevated IL-6 levels (&gt; 315 mg/ml), higher IL-18, higher MCP-1, and suppressed IL-1β and GMCSF than nonCART patients (Table). Treatment of IEC-HS included tocilizumab (n = 19), anakinra (n = 18) siltuximab (n = 4) and basiliximab (n = 4), dexamethasone (n = 18) methylprednisolone (n = 6), etoposide (n = 1) and ruxolitinib (n = 1). A significant response defined by a 90% reduction or normalization of the cytokine was observed with IL-10 and IFN-ϒ in 92.3% and 84.6% of the CART patients respectively. An intermediate response was noted with TNF, IL-6, MCP-1 and MIP-1 in 38.4%, 30.8% and 61.6% and 38.5% of the patients respectively. No patient had a significant response in IL-2Rα or IL-1β and only 7.7% had a significant response in IL-18. Of the 5 patients who had a MIP-1 response, 4 were on basiliximab +/- high flow continuous venovenous hemofiltration and the only patient that had an IL-18 response was on both modalities. The 100-day mortality after IEC-HS in the CART patients was 40% and was associated with higher peak and lower best ferritin but not the percentage reduction (Table). Higher TNF (90.3 pg/ml vs 37.2 pg/ml, p = 0.05), markedly elevated levels of IL-6 (92% vs 50%, p = 0.03) and IL-10 (33% vs 0%) and an IL-6 response (44.4% vs 0%) were associated with survival at day 100. IL-6 responders had lower peak ferritin vs IL-6 nonresponders (14066 mcg/L vs 45051 mcg/L, p = 0.08). Enterococcus faecium bacteremia developed in 75% of the nonsurvivors vs 16.6% of the 100-day survivors (p = 0.009). Survivors cleared the enterococcus bacteremia within days while nonsurvivors had protracted bacteremia. Conclusions: IEC-HS is devastating complication of CART. Anti-cytokine therapy can reduce some cytokines and ferritin but overimmunosuppression may lead infectious complication, in particular with E. faecium. Better biomarkers are needed to finetune immunosuppressive therapy in order to avoid over-immunosuppression. [Table: see text]

Clinical comparative study of laparoscopic partial splenectomy and open partial splenectomy.

The aim of the article was too investigate and compare the feasibility, safety, and early postoperative recovery associated with laparoscopic partial splenectomy (LPS) and open partial splenectomy (OPS) in patients with benign splenic tumours and traumatic splenic rupture. A retrospective analysis was conducted on clinical data from 110 patients undergoing splenic resection at our hospital between March 2019 and May 2022. Among them, 35 patients underwent OPS, 25 underwent LPS for traumatic splenic rupture, while 50 patients with benign splenic tumours underwent either OPS (n = 20) or LPS (n = 30). Preoperative, intraoperative, and postoperative data were collected and compared. Statistical analysis was conducted using SPSS software. There was no significant difference in the general data between the 2 groups of patients with benign splenic tumours and those with splenic trauma. Among patients with traumatic splenic rupture, the OPS group had a shorter operation time (p < 0.05). Regardless of whether they had traumatic splenic rupture or benign splenic tumours, the LPS group required less postoperative analgesia and had a shorter defecation recovery time (p < 0.05). Additionally, the LPS group displayed lower white blood cell count, white blood cell/lymphocyte ratio (WLR), neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), C-reactive protein (CRP), calcitonin (PCT), and interleukin-6 (IL-6) than the OPS group on the first and third days post-surgery (p < 0.05). In comparison to OPS, LPS presents significant advantages, including minimal surgical trauma, a reduced early postoperative inflammatory response, milder wound pain, and a faster recovery of gastrointestinal function.

Clinical features of COVID-19-related encephalitis: comparison with the features of herpes virus encephalitis and autoimmune encephalitis

IntroductionIdentifying coronavirus disease 2019 (COVID-19)-related encephalitis without clear etiological evidence is clinically challenging. The distinctions between this condition and other prevalent encephalitis types remain unknown. Therefore, we aimed to explore the similarities and differences in the clinical characteristics of COVID-19-related encephalitis and other encephalitis types.MethodsAdult patients with encephalitis admitted to the neurology department at Xuanwu Hospital were enrolled and categorized into the following six groups based on the results of metagenomic next-generation sequencing and autoimmune antibody detection in cerebrospinal fluid (CSF): COVID-19-related encephalitis (n = 36), herpes simplex virus type 1 encephalitis (HSV-1 encephalitis; n = 28), human herpesvirus 3 encephalitis (HHV-3 encephalitis; n = 10), NMDAR-antibody encephalitis (n = 18), LGI1-antibody encephalitis (n = 12), and GABAB-antibody encephalitis (n = 8).ResultsThe predominant characteristics of COVID-19-related encephalitis include a low incidence of seizures (38.9%), cognitive defects (30.6%), and meningeal irritation signs (8.3%). Compared with HSV-1 and HHV-3 encephalitis, COVID-19-related encephalitis exhibited lower white blood cell count (2.5 count/mm3), protein (32.2 mg/dL), and immunoglobulin M, G, and A levels (0.09, 3.2, and 0.46 mg/dL, respectively) in the CSF tests. Abnormal imaging findings were present in only 36.1% of COVID-19-related encephalitis cases, mostly showing diffuse inflammation scattered in various parts, which differed from HSV-1 encephalitis. Additionally, COVID-19-related encephalitis exhibited significant differences in clinical symptoms and CSF white blood cell counts compared with NMDAR-antibody encephalitis; however, it showed limited differences compared with LGI1-antibody and GABAB-antibody encephalitis.DiscussionCOVID-19-related encephalitis and herpes virus or autoimmune encephalitis differ clinically. Symptoms and auxiliary examinations can be used as distinguishing tools.

The clinical significance of TAT, PIC, TM, and t-PAIC in vascular events of BCR/ABL-negative myeloproliferative neoplasms

Predicting the likelihood vascular events in patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN) is essential for the treatment of the disease. However, effective assessment methods are lacking. Thrombin-antithrombin complex (TAT), plasmin-α2- plasmininhibitor complex (PIC), thrombomodulin (TM), and tissue plasminogen activator-inhibitor complex (t-PAIC) are the new direct indicators for coagulation and fibrinolysis. The aim of this study was to investigate the changes of these four new indicators in thrombotic and hemorrhagic events in BCR/ABL1-negative MPN. The study cohort of 74 patients with BCR/ABL negative myeloproliferative disorders included essential thrombocythemia, polycythemia vera, and primary myelofibrosis (PMF). A panel of 4 biomarkers, including TAT, PIC, TM, and t-PAIC were determined using Sysmex HISCL5000 automated analyzers, whereas fibrin/fibrinogen degradation products (FDP), D-dimer and Antithrombin III (ATIII) were analyzed using Sysmex CS5100 coagulation analyzer. A total of 24 (32.4%) patients experienced thrombotic events and hemorrhagic events occurred in 8 patients (10.8%). Compared to patients without hemorrhagic-thrombotic events, patients with thrombotic events had higher fibrinogen (FIB) level, FDP level and lower ATIII activity, while patients with hemorrhagic events had lower white blood cell count and hemoglobin level, higher FDP level (P < 0.05). Patients with a JAK2V617F mutation were more likely to experience thrombotic events (P < 0.05). In addtion, patients with thrombotic events had higher TAT, PIC, TM, and t-PAIC levels than patients without hemorrhagic-thrombotic events (P < 0.05), whereas patients with hemorrhagic events had a lower median value in TAT and TM (no statistical difference, P > 0.05). Patients with higher TAT, TM and t-PAIC were more likely to experience thrombotic events (P < 0.05), and only TAT was positively correlated with thrombotic events (Spearman r =0.287, P = 0.019). TAT, PIC, TM, and t-PAIC combined with ATIII and FDP have a certain value for predicting thrombosis in patients with BCR/ABL1-negative MPN. These 6 parameters are worth further exploration as predictive factors and prognostic markers for early thrombotic events.