Peripheral Blood Platelet Counts Research Articles

Psychological and physical side effects during G-CSF mobilization in related donors of allo-HCT.

The psychological side effects of granulocyte colony-stimulating factor mobilization in related donors of allogeneic hematopoietic cell transplantation (allo-HCT) and impacts of psychological/physical side effects on harvest outcomes remain largely unknown. We prospectively analyzed 349 consecutive related peripheral blood stem cell (PBSC) donors for allo-HCT at the First Affiliated Hospital, Zhejiang University, School of Medicine from March 2021 to August 2023. Higher baseline peripheral blood white blood cell counts (p = 0.046), monocyte counts (p < 0.001), platelet counts (p = 0.001), and hemoglobin (p < 0.001) had a positive correlation to CD34+ cell counts in the first leukapheresis, while female donors (male vs. female, p < 0.001) and older age (> 40 vs. < = 40, p = 0.003) were negatively related to CD34+ cell counts. Bone pain was the most observed physical side effect and was more frequent in female donors (p = 0.032). The incidence of fatigue was higher in female donors and older donors (female vs. male, p = 0.016; > 40 vs. < = 40, p = 0.015). Donor depression (pre vs. during mobilization, p < 0.001), anxiety (pre vs. during mobilization, p = 0.043) and insomnia (pre vs. during mobilization, p = 0.011) scores increased during the mobilization period. Donors with higher depression, anxiety and stress scores at admission were more likely to experience nausea. At 1 month after the last leukapheresis, the counts of white blood cell, neutrophil, monocyte and hemoglobin were significant lower than baseline counts, while the platelet counts recovered to baseline. The mobilization and harvest process can increase the depression, anxiety and insomnia scores. Poor psychological status of the donor can aggravate the occurrence of physical side effects.

Intradermal needling and acupuncture in prevention and treatment of leukopenia after chemotherapy with spleen-kidney deficiency: a randomized controlled trial

To compare the clinical effect of intradermal needling and acupuncture in prevention and treatment of leukopenia after chemotherapy with spleen-kidney deficiency. A total of 90 patients with malignant tumor who received chemotherapy were randomly divided into a intradermal needling group (30 cases, 1 case dropped out), an acupuncture group (30 cases, 2 cases dropped out, 1 case was eliminated) and a control group (30 cases). The control group received conventional symptomatic treatment after chemotherapy. On the basis of the treatment in the control group, the intradermal needling group received intradermal needling at Guanyuan (CV 4), Dazhui (GV 14) and bilateral Geshu (BL 17), Zusanli (ST 36)，Shenshu (BL 23), the needles were retained for 48 h, once every other day. On the basis of the treatment in the control group, the acupuncture group received conventional acupuncture at the same acupoints as the intradermal needling group, once every other day. The treatment started from the first day of chemotherapy, for a total of 2 weeks in the three groups. The white blood cell count, neutrophil count, hemoglobin content, platelet count and Karnofsky performance status (KPS) score before treatment and on 3rd, 7th, 14th, and 21st days after treatment were compared among the three groups. The incidence and grading of leukopenia and the usage of leukocyte-boosting drug during chemotherapy cycle was recorded. On 7th day after treatment, the white blood cell count in the intradermal needling group and the acupuncture group was higher than that in the control group (P<0.01, P<0.05). On the 14th day after treatment, the hemoglobin content in the intradermal needling group and the acupuncture group was higher than that in the control group (P<0.01). On the 7th, 14th, and 21st days after treatment, the platelet count in the acupuncture group was higher than that in the control group (P<0.01), on the 14th and 21st days after treatment, the platelet count in the intradermal needling group was higher than that in the control group (P<0.01). There was no statistically significant difference among the three groups after treatment in terms of neutrophil count, KPS score, incidence and grading of leukopenia, and the usage of leukocyte-boosting drug (P>0.05). Both intradermal needling and acupuncture can effectively increase peripheral blood white blood cell count, hemoglobin content and platelet count during chemotherapy cycle, reduce the toxicity of chemotherapy drug to bone marrow hematopoietic function, and alleviate bone marrow suppression after chemotherapy. The two treatments are equally effective.

The development of a prediction model based on random survival forest for the prognosis of non- Hodgkin lymphoma: A prospective cohort study in China

Background and objectiveThe pathological staging of non-Hodgkin lymphoma (NHL) is complex, the clinical manifestations are varied, and the prognosis differ considerably. To provide a useful reference for early detection and effective treatment of NHL, we developed a random survival forest (RSF) prognostic model based on machine learning (ML) algorithms using prospective cohort data collected from Chongqing Cancer Hospital from Jan 1, 2017 to Dec 31, 2019 (n = 1449) to compare with the traditional cornerstone method Cox proportional hazards (CPH) model and evaluate the predictability of the model. MethodsPatients were randomly split into a training cohort (TC) and validation cohort (VC) based on 65/35 ratio. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to extracted the important features. And the RSF was modeled to explore the prognostic factors impacting the overall survival (OS) of patients with NHLs in the TC and validated in the VC. The C-index, the Integrated Brier Score (IBS), Kaplan-Meir method, the receiver operating characteristic (ROC) curve, and the area under the ROC curve (AUC) were selected to measure performances and discriminations of the models. In addition, individual survival probability predicted for NHL patients. ResultsAccording to the features extracted by LASSO model and univariable Cox model, 16 variables were selected to develop the RSF model with log-rank splitting rule, which were age, ethnicity, medical insurance, Ann Arbor stage, pathology, targeted-therapy, chemo-therapy, peripheral blood neutrophil count to lymphocyte count ratio (NLR), peripheral blood platelet count to lymphocyte count ratio (PLR), serum lactate dehydrogenase (LDH), CD4/CD8, platelet (PLT), absolute neutrophil count (ANC), lymphocyte (LYM), B-symptoms, and (CPR) were important prognostic factors. Compared to the CPH model (C-index = 0.748, IBS = 0.166), the RSF model (C-index = 0.786, IBS = 0.165) is outperformed in predictability and accuracy. The AUC of the RSF model to estimate the 1-, 3-, and 5-year OS in TC were 0.847, 0.847, and 0.809, respectively; while those in the CPH were 0.816, 0.803, and 0.750, respectively. ConclusionsTo provide practical implications for the implementation of individualized therapy, the study constructed a high-performed RSF model and reveal that it outperformed the traditional model CPH. And the RSF model ranked the risk variables. In addition, we stratified the risk of NHL patients and estimated individual survival probability based on the RSF model.

Association between systemic immune-inflammation index and psoriasis: a population-based study.

The systemic immune-inflammation index (SII),as measured by lymphocyte, neutrophil and platelet counts in peripheral blood, is regarded as a favorable indicator of both inflammatory state and immune response. Psoriasis is an immune-mediated disease notable for its chronic inflammation of the entire system. Our research sought to explore the latent link between psoriasis and SII. We performed a cross-sectional investigation utilizing data extracted from the National Health and Nutrition Examination Survey (NHANES, 2009-2014). Employing multivariate linear regression models and subgroup analysis, we sought to uncover the association between SII and psoriasis. This study enrolled a total of 17,913 participants as part of its research cohort. Our multivariate linear regression analysis revealed a notable and positive correlation between SII and psoriasis [1.013 (1.000, 1.026)]. As SII tertiles increased, the risk of psoriasis demonstrated an upward trend. The significant dependence on this positive association were maintained in women, BMI(≥ 30 kg/m2),non-stroke and non-cancer subjects in subgroup analysis and interaction tests. Furthermore, we identified a significant association between SII and psoriasis, characterized by two consecutive inverted U-shaped patterns. Notably, the analysis revealed the most prominent inflection point at a specific value of 797.067. The results indicate a significant correlation between elevated SII levels and the presence of psoriasis. However, to corroborate and strengthen these results, additional large-scale prospective studies are required.

Systemic immune-inflammation index is associated with ulcerative plaque in patients with acute ischemic stroke: A single center exploratory study.

This study explored the correlation between inflammatory markers and ulcerative plaques based on carotid doppler ultrasound (CDU) in individuals with acute ischemic stroke (AIS). A total of 202 cases diagnosed with AIS associated with atherosclerotic plaque (AP) in the carotid artery were enrolled in this research. Collecting clinical baseline data, laboratory data (such as the complete blood count) and imaging data (CDU and Brain magnetic resonance imaging [MRI]). Then the correlation between Systemic immune-inflammation index (SII, SII = P N/L, where P, N, and L were the peripheral blood platelet, neutrophil and lymphocyte counts, respectively), the shape and position of AP, the degree of carotid artery stenosis, and the presence of ulcerative plaques. Cutoff values were determined accordingly. SII and high sensitivity CRP (hs-CRP) were independent risk factors for the presence of vulnerable carotid plaques. SII, type A plaque, plaque above carotid bifurcation, and severe carotid stenosis were independent risk factors for the presence of ulcerative plaque. The AUC value, the sensitivity, specificity, the best cutoff value of SII in predicting the presence of ulcerative plaque was 0.895, 93.3%, 89.2%, and 537.4 (109 /L), respectively. SII at admission was found to be independently associated with the presence of AIS with vulnerable plaque, especially ulcerative plaques. Moreover, plaque ulceration was more likely to form when the area of higher plaque thickness was located in the upstream arterial wall of maximum plaque thickness (WTmax), plaque was above the carotid bifurcation and severe carotid stenosis.

Overall Survival Prediction by Tumor Microenvironment Lymphocyte Distribution in Hepatocellular Carcinoma After Liver Transplantation

IntroductionOur previous research demonstrated that CD8+ cell density profiling using a hexagonal grid-based digital image analysis method provides predictors of patient outcomes after liver resection due to hepatocellular carcinoma (HCC). Continuing our study, we have further investigated the applicability of the methodology to patients receiving a liver transplant for HCC. MethodsThe retrospective study enrolled patients with HCC who underwent liver transplantation (LT) at the Vilnius University Hospital Santaros Clinics between 2007 and 2020. We determined the density profiles of CD8+ lymphocytes at the interface between HCC and stroma and the interface between the perineoplastic liver parenchyma and stroma. Both digital image analysis and the hexagonal grid-based immunogradient method were applied to CD8+ immunohistochemistry images. Survival statistics based on clinicopathological, peripheral blood analysis, and surgical data determined the prognostic value of these indicators. ResultsUnivariate clinicopathological predictors of worse OS after LT included: patient's age at the time of the transplantation, a higher number of HCC nodules, lower platelet count, longer activated thromboplastin time, lower serum albumin, higher serum total bilirubin, and lower serum creatinine levels. The two independent predictors of overall survival were mean CD8+ cell density at the epithelial edge of the explanted liver parenchyma-stroma interface and peripheral blood platelet count. ConclusionsOur model discloses that preoperative peripheral blood platelet count and mean CD8+ cell density at the epithelial edge of nonmalignant interface in the explanted liver parenchyma are independent predictors of OS for HCC after LT.

Increase of Dnts Correlated with Clinic Outcome after Allogeneic DNT Cells Infusion in r/r AML Patients

Background: The treatment of relapsed/refractory AML (r/r AML) patients are still an unmet medical need in clinic. In recent years, cellular immunotherapy especially CAR-T cell therapy played more important roles in hematological malignancies. Unfortunately, the safety and efficacy of existing cell therapies to r/r AML patients still facing many challenges and needs to be further improved. Our previous studies have demonstrated that Double Negative T cells (DNTs) showed strong cytotoxicity to AML blasts and can improve the prognosis of AML patients relapsed after allogeneic stem cell transplantation. Here, we reported our ongoing phase I clinical trial of RC1012 injection (allogeneic DNT cells) in patients with r/r AML (NCT05471323). This study protocol was approved by Chinese NMPA (National Medical Products Administration). Informed consent was obtained in accordance with the Declaration of Helsinki. Objective: Explore the efficacy indicator in r/r AML patients after allogeneic DNT cells therapy. Methods: 7 patients with r/r AML were enrolled in the trial according to the inclusion and exclusion criteria. DNTs from peripheral blood of healthy donors were manufactured in GMP facility. After lymphodepleting chemotherapy with fludarabine and cyclophosphamide, each patient received three infusions of HLA-mismatched DNT cells at 1.5×10^8 cells/kg with one week interval. The PK data were collected and analyses as well as the checkpoint inhibitors on T cells was monitored. Results: As reported before, DNT cells had shown good safety profile in the treatment of r/r AML. Multiple infusions of allogeneic DNT cells can benefit some patients with r/r AML. Allogeneic DNT cell therapy can stimulate the patient's DNT cells to proliferate, and the DNT cells level in peripheral blood corelated to the disease outcomes. Allogeneic DNT cells can also stimulate the patient's CD4 and CD8 cells to proliferate and is favorite the CD8 cells to grow, indicating its potential to enhance the anti-tumor activities after DNT cells therapy. Allogeneic DNT cells have no toxicity to normal bone marrow cells, and the quick recovery of platelet counts in peripheral blood corelated to the efficacy of the DNT cells therapy. TIGIT, PD-1, CD57 are increased on patients' T cells which may hinder the effect of immunotherapy in r/r AML patients. Conclusions: Allogeneic DNTs therapy are safe in clinical treatment and can reduce tumor burden after infusion with the increase of patient's DNT cells in complete remission and partial remission patients. These findings warrant the allogeneic DNTs as a novel adjuvant therapy with allo-HSCT to enhance the treatment efficacy in r/r AML. The finding of TIGIT, PD-1, CD57 molecules were increased on patients' T cells indicated that the combination of DNTs with immune checkpoint inhibitors may further improve the DNTs efficacy in r/r AML patients. Key words: Double negative T cells (DNTs), AML, Immunotherapy

Predictors of Response to Rituximab in Chronic Immune Thrombocytopenia: Do Race, Gender and ABO Blood Type Matter?

Introduction: Immune thrombocytopenia (ITP)is characterized by immune mediated destruction of platelets causing isolated thrombocytopenia with a peripheral blood platelet count &amp;lt;100,000/microL in the absence of other causes that may be associated with thrombocytopenia. It remains a diagnosis of exclusion. Corticosteroids are the first-line treatment for ITP and more than 75% of adults with ITP will respond to them. However, approximately 70-80% of adult patients with ITP will experience treatment failure with corticosteroids or become dependent on them and require second-line therapy. Various options in the second line setting include thrombopoietin receptor agonists, rituximab, and splenectomy. In one study rituximab was noted to result in an overall platelet count response in 62.5% of adults. However not all patients remain in remission and clinical factors that are predictive of response are lacking. Racial disparities are known to predict response to rituximab in other hematologic disorders such as immune mediated thrombotic thrombocytopenic purpura (Mezapa et al, 2022). Herein, we are examining the effect of race, gender and ABO blood type on response to rituximab in patients diagnosed with ITP. Methods: This retrospective cohort study included adult patients, aged 18 and above, with a diagnosis of ITP who had received single agent rituximab within a multihospital academic healthcare system between January 2015 and December 2022. Initially 196 patients were identified but only 127 of those were included in the study. We excluded patients with missing response data, and those with combined rituximab and other therapies (stable or decreasing doses of steroids were allowed). Our primary end point was any response to rituximab by day 180 after starting rituximab. Any response was defined as complete response or partial response. Complete response was defined as platelet count ≥ 100,000 /microL and absence of bleeding. Partial response was defined as platelet count of at least 30,000/microL after week 4 from rituximab administration or doubling of platelet count from baseline without administration of any platelet increasing therapy. Our secondary end point was relapse rate which was defined as platelet count below 100,000/microL if complete response had been attained or below 30,000/microL or less than 2 fold increase of baseline platelet count. We also investigated clinical and socioeconomic predictors of response. Exploratory analysis was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Chi square test was used to compare percentages and t-test was used to compare means. Univariate and multivariate regression models were used to analyze the predictors of any response to rituximab. Kaplan-Meier method was used to calculate estimates of relapse-free survival, and log-rank test was used to compare these estimates. Result: We identified 127 patients diagnosed with ITP who received rituximab. The median age was 64 years (IQR 48-74), there were 46.5% females. The majority of the patients were Caucasians (95.3%), and rituximab was most commonly received as a second line therapy (73.2%). Median initial platelet count was 28,000/microL. Complete response was observed in 50% of African American patients compared with 43.0% in Caucasian patients (p-value 0.63). No predictors for any response on univariate or multivariate analyses were found. Race (OR 0.30, 95CI 0.03-3.25, p-value 0.32) and female gender (OR 0.76, 95CI 0.33-1.76, p-value 0.51) did not affect response to rituximab in our patient cohort. Relapse rate was 60% in African American patients versus 67.5% in Caucasians (p-value 0.72), and 68.7% in males versus 64.9% in females (p-value 0.71). ABO blood type also did not predict a response to Rituximab in our patient population (Table 1) Conclusion: In our study, race and gender did not affect response or relapse rates after rituximab treatment in chronic ITP. Patient's ABO blood type also did not predict a difference in response to Rituximab. However, our study was limited by a small sample size and further multi-institutional analysis is warranted to confirm the findings of our study.

Impact of nutritional status and systemic immune-inflammation index on mortality in patients with acute myocardial infarction

Abstract Background It has been known that malnutrition and elevated inflammatory markers are associated with clinical outcome in patients with acute myocardial infarction (AMI). However, few studies have investigated the association between nutritional status, inflammatory markers and survival in patients with AMI. Purpose The aim of this study is to investigate combined impact of nutritional status and systemic immune-inflammatory index (SII) on outcome in patients with AMI. Methods We examined 1,984 patients (mean age = 64 ± 12 year-old, 1,493 males) admitted for AMI. Nutritional assessment was evaluated at the admission by geriatric nutritional risk index (GNRI) calculation. Malnutrition was defined as GRNI &amp;lt;92. We calculated SII from the equation, SII = P x N/L, where P, N and L are peripheral blood platelet, neutrophil and lymphocyte counts per liter at the time of admission, respectively. The primary endpoint was all-cause mortality at 1-year. Results GNRI was significantly correlated with SII (r = -0.135, p&amp;lt;0.001). GNRI (95.2 ± 8.4 versus 102.7 ± 7.3) was significantly lower, whereas SII (1,906.9 ± 2,016.0 x 109 cells/L versus 1,100.9 ± 981.6 x 109 cells/L) was significantly higher in non-survivors. Patients with malnutrition had significantly higher mortality compared with patients without malnutrition (19.2% versus 4.3%, log-rank p &amp;lt;0.001). In receiver operating characteristics curve analysis, area under the curve of SII for predicting all-cause mortality was 0.625. The optimum cut-off point for SII for a favorable prognosis was determined to be 1,425 x 109 cells/L. Patients with high SII had significantly higher mortality (9.6% versus 4.2%, log-rank p&amp;lt;0.001). The patients were divided into four groups based on GNRI &amp; SII; high GNRI &amp;low SII (Group 1), high GNRI &amp; high SII (Group 2), low GNRI &amp; low SII (Group 3), and low GNRI &amp; high SII (Group 4). In Kaplan-Meier survival curve, all-cause mortality was significantly higher in Group 4 compared with Group 1, Group 2, and Group 3 (3.5% versus 6.7% versus 14.1% versus 25.6%, log-rank p&amp;lt;0.001; Figure). In Cox-proportional hazards model, compared with Group 1 (1, reference), Group 2 (HR 1.64, 95% CI 1.02 – 2.63; p=0.038), Group 3 (HR 1.97, 95% CI 1.06 – 3.68; p=0.032), and 4 (HR 4.17, 95% CI 2.40 – 7.24; p&amp;lt;0.001) was an independent predictor of all-cause mortality after adjusting for confounding variables. Conclusion Nutritional status was significantly correlated with immune-inflammatory index. Malnutrition and high SII was independent predictors of overall survival in patients with AMI.

Megakaryocytes Have Immune Characteristics in Murine Immune Bone Marrow Failure

Introduction Megakaryocytes (MKs) have familiar roles in the bone marrow (BM) microenvironment, including platelet production, maintenance of hematopoietic stem and progenitor cells (HSPCs) function, and more recent evidence suggests MK engagement in immune responses. Immune aplastic anemia (AA) is characterized by oligoclonal expansion of T-cells and death of HSPCs leading to bone marrow failure (BMF). As MKs demonstrate niche maintenance and immune effector function, we explored the potential roles of MKs in the development of AA in a murine model of immune BMF. Methods BMF was induced in CByB6F1 mice by intravenous infusion of lymph node (LN) cells from major histocompatibility complex mismatched C57BL/B6 (B6) donor mice at a dose of 30-40x10 6 cells/recipient. No irradiation was given to recipients to avoid extra damage to MKs and CByB6F1 recipient mice were sacrificed at D7, D10, D14, and D17 following LN cell infusion (Chen J, et al. Blood. 2004). Peripheral blood (PB) samples, tibias, femurs, and sterna were harvested at each timepoint. Immunophenotyping of MKs and T cells was performed by flow cytometry on flushed BM cells and two-photon excitation microscopy (2P) imaging was performed on fixed sternal samples, using fluorescence-labelled CD41 antibody to visualize the physical location of MKs in BM. To enrich for MKs, BM cells were filtered through a 10 µm pluriStrainer™ through which most lymphocytes, red blood cells, and other small cells were eluted while MKs and other large size cells remained on the strainer. Large cells and residual small cells were subsequently assessed by single cell RNA sequencing (sc-RNAseq) on the Parse Bio Evercode™ platform based on combinatorial barcoding technology, which was able to accommodate the large size of MKs, as no partitioning step is needed in the analysis workflow. Results BMF was successfully induced as measured by decreasing PB counts from point of lymphocyte infusion accompanied by increasing expansion of CD4 and CD8 T-cells and marked reduction of total BM cells. MKs persisted throughout the course of BMF as measured by both flow cytometry and 2P (Figure 1A) despite PB thrombocytopenia and progressive marrow hypocellularity. Concomitantly, MKs identified by large size on forward scatter versus side scatter and CD41+ expression had progressive upregulation of immune effector markers IA-IE and CD53 over the course of BMF. Following sc-RNAseq and bioinformatics analysis of enriched BM cells at D14, cell clustering identified a distinct cell cluster representing MKs (Figure 1B). MK identity was supported by co-expression of transcripts encoding platelet factor 4, TUBB1, Glycoprotein 5, and Itga2b (CD41). This MK cell population was distinct from macrophages which highly expressed Fcgr4, Cd5l, Ccr5, Cd74 and Gbp5 genes. Gene expression profiling demonstrated that MKs in BMF mice showed upregulation of immune pathways such as interferon gamma and interferon alpha response and downregulation of pathways related to platelet activation and platelet homeostasis, as compared with normal mice. Conclusions In a murine model of BMF, using multiple modalities, we demonstrate that MKs cease platelet production, manifested by reduction in peripheral blood platelet count and downregulation of gene expression pathways related to platelet production, while concurrently acquiring characteristics of immune effector cells. This suggests that MKs are active participants in immune BMF.

Molecular characterization of Clostridium perfringens isolates from a tertiary children’s hospital in Guangzhou, China, establishing an association between bacterial colonization and food allergies in infants

BackgroundCow’s milk protein allergy (CMPA) is one of the most common types of food allergy in infants. Faecal pathogen cultures showed that the positive rate of Clostridium perfringens was more than 30%, which was significantly higher than that for other bacteria. Therefore, it is speculated that Clostridium perfringens colonization may be one of the pathogenetic factors for CMPA in infants. We conducted a real-world evidence study. Infants aged 0–6 months with diarrhoea and mucoid and/or bloody stools were recruited from a large tertiary hospital in China. Faecal pathogen cultures for the detection of Clostridium perfringens were confirmed by flight mass spectrometry, and potential toxin genes were identified using PCR. After 12 months of follow-up, the diagnoses of CMPA and food allergy were recorded. The correlation was assessed by Pearson correlation analysis.ResultsIn this study, 358 infants aged 0–6 months with gastrointestinal symptoms and faecal pathogen cultures were recruited. A total of 270 (44.07% girls; mean age, 2.78 ± 2.84 months) infants were followed up for 12 months. Overall, the rate of positivity for Clostridium perfringens in faecal pathogen cultures was 35.75% (128/358) in infants aged ≤ 6 months. The earliest Clostridium perfringens colonization was detected within 2 days after birth. The majority of Clostridium perfringens isolates were classified as type C in 85 stool samples. In the Clostridium perfringens-positive group, 48.21% (54/112) of infants were clinically diagnosed with food allergies after 12 months, including 37.5% (42/112) with CMPA, which was significantly higher than that of the negative group, with 7.59% (12/158) exhibiting food allergies and 5.06% (8/158) presenting CMPA (P < 0.0001). Faecal Clostridium perfringens positivity was significantly correlated with CMPA, food allergy, faecal occult blood, faecal white blood cells, antibiotic use, increased peripheral blood platelet counts, and decreased haemoglobin levels (P < 0.0001).ConclusionsThis study demonstrates that intestinal colonization by Clostridium perfringens is common in infants. The majority of Clostridium perfringens isolates are classified as type C. Colonization of the intestine by Clostridium perfringens is associated with the development of CMPA and food allergy in infants.

The effect of Dipeptidyl peptidase 4 (DPP-4) inhibitors on hemoglobin level in diabetic kidney disease: A retrospective cohort study.

Anemia typically develops early in the course of diabetic kidney disease (DKD). There are data to show that dipeptidyl-peptidase-4 (DPP-4) inhibitors affect hematopoietic growth factor activity and hemoglobin level. We retrospectively reviewed 443 DKD patients who were started on DDP-4 inhibitor therapy in 2019. Their hemoglobin level at baseline (6-12 months before treatment), pretreatment (0-6 months before treatment), and post-treatment periods (within 6 months after DPP-4 inhibitor), concomitant estimated glomerular filtration rate (eGFR), HbA1c, peripheral blood white cell and platelet counts were reviewed. The severity of kidney failure was classified according to the Kidney Disease: Improving Global Outcomes stages. The hemoglobin level had a small but significant decline from 11.98 ± 2.07 to 11.87 ± 2.12 g/dL from pretreatment to post-treatment period (paired Student t test, P < .0001). From the pre- to post-treatment period, the decline of hemoglobin level was 0.10 ± 0.89 g/dL, which was significantly less than that from baseline to pretreatment period (0.24 ± 0.90 g/dL, P = .0008). The change in hemoglobin level had a positive correlation with the change in HbA1c level (R = 0.218, P < .0001), but did not correlate with the type of DPP-4 inhibitor or pretreatment eGFR. There was no significant change in peripheral blood white cell or platelet count during the same period. DPP-4 inhibitor ameliorates hemoglobin decline in DKD. The effect of DPP-4 inhibitor on hemoglobin is statistically significant but clinically modest, and did not correlate with the concomitant change in kidney function.

Identification of Plasma Thrombopoietin Level and Its Significance in Patients with Aplastic Anemia and Myelodysplastic Syndrome.

Objective Our objective was to investigate the concentration of plasma thrombopoietin (TPO) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), as well as its relationship with patients' responses to recombined human TPO (rhTPO) therapy. Methods We detected the concentration of plasma TPO in 31 patients with AA, 27 patients with MDS, and 11 normal controls using enzyme-linked immunosorbent assay. Results The median concentration of plasma TPO in patients with AA, MDS, and controls was (841.08 ± 768.64), (212.41 ± 338.93), and (35.09 ± 18.21) pg/mL, respectively. The TPO concentration in patients with AA and MDS was significantly higher than that in controls ( p < 0.05). The median platelet (PLT) counts were (184 ± 34) ×10 9 /L in the control group and (24 ± 19) ×10 9 /L and (80 ± 71) ×10 9 /L in AA and MDS patients, respectively. Negative correlations were found between plasma TPO concentration and PLT counts as well as megakaryocytes in bone marrow ( p < 0.05). In AA patients treated with rhTPO, a negative correlation was observed between increased PLT counts and pretreatment TPO levels ( p < 0.05). Conclusion Plasma TPO concentration in AA and MDS was significantly higher than that in normal controls. Plasma TPO was negatively correlated with peripheral blood PLT counts and bone marrow megakaryocyte counts. The pretreatment TPO level may serve as a prognostic indicator for the therapeutic effect of rhTPO in AA patients.

Prognostic Significance of Hemoglobin, Albumin, Lymphocyte and Platelet (HALP) Score in Hepatocellular Carcinoma.

HALP score consisting of hemoglobin content, albumin content, lymphocyte count, and platelet count can comprehensively evaluate the inflammatory response and nutritional status. Many researchers have indicated that the HALP score is an effective predictor of the overall prognosis of various tumors. However, there is no relevant research to suggest whether the HALP score can predict the prognosis of patients with hepatocellular carcinoma (HCC). We retrospectively analyzed 273 HCC patients who underwent surgical resection. Hemoglobin content, albumin content, lymphocyte count, and platelet count in peripheral blood were measured for each patient. The relationship between the HALP score and overall survival (OS) was investigated. With a mean of 56.69 ± 1.25 months follow-up, the 1-, 3-, and 5-year OS was 98.9%, 76.9%, and 55.3% for all patients, respectively. HALP scores (HR=1.708, 95% CI=1.192-2.448, P=0.004) were significant independent risk factors of OS. The 1-, 3-, and 5-year OS were 99.3%, 84.3%, and 63.4% for patients with high HALP scores; and 98.6%, 69.8%, and 47.5% for patients with low HALP scores, respectively (P=0.018). In TNM I-II stage patients, compared with high HALP scores, low HALP scores have worse OS (P=0.039). In AFP positive patients, compared with high HALP scores, low HALP scores have worse OS (P=0.042). Our research showed the preoperative HALP score is an independent predictive factor of overall prognosis, and a low HALP score indicates a worse prognosis in HCC patients who underwent surgical resection.

Clinical characteristics and outcomes in febrile infants aged 29-90 days with urinary tract infections and cerebrospinal fluid pleocytosis.

Fever without a focus is a common reason for medical evaluations, hospitalizations, and the antimicrobial treatment of infants younger than 90 days. The presence of cerebrospinal fluid (CSF) pleocytosis could be challenge for clinicians who treat febrile young infants with urinary tract infection (UTI). We evaluated the factors associated with sterile CSF pleocytosis and the clinical outcomes of the patients. A retrospective review of patients aged 29-90 days with febrile UTIs who underwent a non-traumatic lumbar puncture (LP) at Pusan National University Hospital from January 2010 to December 2020 was conducted. CSF pleocytosis was defined as white blood cell (WBC) counts ≥9/mm3. A total of 156 patients with UTI were eligible for this study. Four (2.6%) had concomitant bacteremia. However, no patients had culture-proven bacterial meningitis. In correlation analysis, although weak strength, CSF WBC counts were positively correlated with C-reactive protein (CRP) level (Spearman r = 0.234; P = 0.003). Thirty-three patients had CSF pleocytosis [21.2%; 95% confidential interval (CI), 15.5-28.2]. The time from fever onset to the hospital visit, peripheral blood platelet counts, and CRP level at admission were statistically significant in patients with sterile CSF pleocytosis compared to those without CSF pleocytosis. In the multiple logistic regression, only CRP was independently associated with sterile CSF pleocytosis (cutoff, 3.425 mg/dl; adjusted odds ratio, 2.77; 95% CI, 1.19-6.88). The proportion of fever defervescence by hospital day 2 was 87.9% in patients with CSF pleocytosis and 89.4% in those without CSF pleocytosis (P = 0.759). There was no statistical difference in the fever defervescence curves between the two patient groups (P = 0.567). No patients had neurological manifestations or complications. Coexisting sterile CSF pleocytosis among febrile infants with UTIs suggest a systemic inflammatory response. However, the clinical outcomes between the two groups were similar. A selective LP should be considered in young infants with evidence of UTI, and inappropriate antibiotic therapy for sterile CSF pleocytosis should be avoided.

Correlation of systemic immune-inflammation index and moderate/major depression in patients with depressive disorders: a large sample cross-sectional study.

To evaluate the clinical value of systemic immune-inflammation index (SII) based on peripheral blood neutrophil, lymphocyte, and platelet count in evaluating the subtype and severity of depression in patients with depressive disorder. This retrospective cohort study was conducted in the Third People's Hospital of Fuyang City from January 1, 2020 to December 31, 2022. The data included sociodemographic information at admission, clinical data, discharge diagnosis and inflammatory markers. Patients were divided into low SII group and high SII group according to the optimal threshold of SII determined by receiver operating characteristic curve (ROC curve). Binary logistic regression was used to analyze the correlation between moderate/major depression and SII level. Compared to the low SII group, the high SII group had a higher age level (χ2 = 7.663, p = 0.006), more smokers (χ2 = 9.458, p = 0.002), more moderate/major depression patients (χ2 = 45.645, p < 0.001), and a higher proportion of patients with accompanying somatic symptoms (χ2 = 14.867, p < 0.001). In the final logistic regression model, after controlling for confounding factors, SII at admission was significantly associated with moderate/major depression [β =1.285, p < 0.001; odds ratio (95% confidence intervals) = 3.614 (2.693-4.850)]. Patients with high SII scores were 3.614 times more likely to have moderate/severe depression than those with low SII scores. We propose a cut-off value of SII =540.78 (sensitivity = 36.4% and specificity = 80.3%) according to the maximum Youden index. Our research indicates that SII may be a useful, repeatable, convenient, and affordable index to identify moderate/major depression in depressive disorder.

The effects of large-volume leukapheresis on hemoglobin, platelet and coagulation in patients with hyperleukocytic leukemia.

This study retrospectively analyzed a total of 86 leukapheresis treatments in 55 patients with hyperleukocytic leukemia (HLL). In the leukapheresis treatments, the monitoring collection (MNC) program in COBE spectra continuous flow centrifuge (CFC) for blood component separator was used. In this study, the white blood cell (WBC) suspension volume collected in leukapheresis treatment were 870.72±208.40 mL, and significantly larger than that reported in previous study. Compared with before leukapheresis, there were no difference in patient with HLL on the peripheral blood platelet (PLT) count and hemoglobin (HGB) levels. The index plasma fibrinogen (FIB) concentration was slightly reduced by leukapheresis, however, it did not affect a lot the maintenance of normal hemostatic function in patients with HLL. Our data provided evidences that large-volume leukapheresis had no obvious effects on HGB level and coagulation functions in patient with HLL. So large-volume leukapheresis by CFC could be widely used in clinic.

Platelet Abnormalities after Splenectomy for Hypersplenism in Decompensated Cirrhosis: A Case Report

Patients in the decompensated stage of cirrhosis are usually associated with hepatic decompensation and portal hypertension, splenomegaly, hypersplenism, and abnormal or significantly reduced blood counts in at least one of the three blood cell lines, mainly platelets. At present, surgical removal of the spleen is still an essential treatment for hypersplenism. The majority of patients who undergo splenectomy can effectively improve the decrease in peripheral blood platelet count. In order to provide some reference value for the diagnosis and treatment of similar clinical cases in the future, we report a case of platelet reduction in hypersplenism in cirrhosis after splenectomy, in which platelets first rose to normal and then decreased abnormally.

Pretreatment Pan-Immune-Inflammation Value Efficiently Predicts Survival Outcomes in Glioblastoma Multiforme Patients Receiving Radiotherapy and Temozolomide.

The purpose of this study was to determine the predictive significance of pretreatment pan-immune-inflammation value (PIV) in patients with newly diagnosed glioblastoma multiforme (GBM) who received postsurgical radiation (RT) and concurrent plus adjuvant temozolomide (TMZ). The outcomes of 204 newly diagnosed GBM patients were analyzed retrospectively. Each eligible patient's PIV was calculated using the findings of peripheral blood platelet (P), monocyte (M), neutrophil (N), and lymphocyte (L) counts obtained on the first day of therapy: PIV = P × M × N ÷ L. We used receiver operating characteristic (ROC) curve analysis to discover the ideal cutoff values for PIV concerning progression-free (PFS) and overall survival (OS) outcomes. The primary and secondary end-points were the OS and PFS divergences across the PIV groups. In ROC curve analysis, the optimal PIV cutoff was 385, which substantially interacted with PFS and OS results and categorized patients into low PIV (L-PIV; N = 75) and high PIV (H-PIV; N = 129) groups. Comparative survival analyses showed that the patients in the H-PIV group had significantly shorter median PFS (6.0 vs. 16.6 months; P < 0.001) and OS (11.1 vs. 22.9 months; P < 0.001) durations than those in the L-PIV group. The results of multivariate Cox regression analysis indicated an independent and significant connection between an H-PIV measure and shorter PFS and OS outcomes. The novel PIV was able to independently stratify newly diagnosed GBM patients into two groups with fundamentally different PFS and OS outcomes following RT and concurrent plus adjuvant TMZ.

Phase II Study of a JAK1/2 Inhibitor Ruxolitinib for Systemic Chronic Active Epstein-Barr Virus Disease: An Investigator-Initiated Trial

Background: Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare EBV-positive T- or NK-lymphoproliferative disease. Although the only curative treatment for sCAEBV available now is allogeneic hematopoietic stem cell transplantation (allo-HSCT), the presence of disease activity, persistent inflammation, at the time of allo-HSCT is associated with poor outcomes (Am J Hem.2022, 97, p780). STAT3 is constitutively activated contributing to cytokine production and cell survival of EBV-infected cells in sCAEBV (Oncotarget. 2019, 9, p31077). Thus, STAT3 inhibition by ruxolitinib, a JAK1/2 inhibitor, may be effective against disease activity of sCAEBV. Methods: We conducted an investigator-initiated trial of open-label, phase 2, prospective and multicenter to assess the efficacy and safety of ruxolitinib in sCAEBV patients with disease activity. The diagnostic criteria were as follows: elevated EBV-DNA load in the peripheral blood (PB) (>102.5 copies/µg DNA); EBV infected T or NK cells detected in affected tissues or PB; systemic inflammatory symptoms persisting for more than three months; exclusion of other possible diagnoses, such as immune deficiencies, autoimmune diseases, or lymphoma (Blood adv. 2021, 4, p2918). sCAEBV patients ≥13 y.o. with fever (≥ 37.5 ºC), and/or liver dysfunction (ALT ≥ 2.0 × ULN) were enrolled. Anti-VCA-IgM-positive patients were excluded. The initiation dose of ruxolitinib was 5-20 mg twice a day determined by the platelet count in PB. The treatment effects were classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). CR was defined as the disappearance of all the elements of disease activity such as fever, liver dysfunction, uveitis, progressive skin lesions, and vasculitis. PR was defined as the disappearance of at least one of the elements listed above. PD was defined as the conversion to active disease, exacerbation of active disease, or the development of overt T- or NK-cell lymphoma. SD was defined as presenting no progression. Ruxolitinib was administered for eight weeks. If CR was observed and allo-HSCT was scheduled, ruxolitinib was terminated early even if these events had occurred within less than eight weeks after initiating investigational drug administration. The primary endpoint of efficacy assessments was CR rate at eight weeks after the initiation of drug administration or at the time of early termination. Safety was assessed based on the frequency of adverse events defined by Common Terminology Criteria for Adverse Events, version 4.0. Results: Nine patients were enrolled between January 2019 and August 2021; five males and four females aged 13-64 y.o.; median age of 40 y.o. The types of EBV-infected cells were as follows: four were CD4, one was CD8, and four were CD56. Seven patients completed the study. Five among them received ruxolitinib for eight weeks and were treated as outpatients. Two patients fulfilled the criteria of early termination and each was treated for 35 and 12 days. The responses are shown in the figure. CR rate and OR rate after eight weeks or at early termination, the primary and the secondary endpoints were 28.6% (2/7) and 42.9% (3/7), respectively. No one showed progressive disease. One patient developed a grade 4 adverse event of oral bleeding during the treatment and resulted in discontinuing the administration of ruxolitinib on day 13. Seven patients received allo-HSCT. Five patients achieved undetectable level of EBV-DNA PB after allo-HSCT. Conclusion: The results indicate that ruxolitinib has demonstrated encouraging effects and is a potent therapeutic reagent against sCAEBV with active disease. Further analysis shall complete its assessment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal