Platelet Research Articles

PI3Kδ inhibitor linperlisib combined with gemcitabine and oxaliplatin for relapsed or refractory diffuse large B-cell lymphoma: a multicenter, single-arm phase Ib/II trial

BackgroundThis investigation assessed the therapeutic potential of combining linperlisib, a targeted inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), with gemcitabine and oxaliplatin (GEMOX) for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).MethodsThis was a multicenter, phase Ib/II clinical study conducted across six sites in China, enrolling 39 individuals with histologically confirmed R/R DLBCL. The treatment protocol included oral linperlisib alongside GEMOX administered intravenously every three weeks for up to six cycles. The primary efficacy endpoint was the objective response rate (ORR).ResultsThe ORR observed in the full study population was 53.8% (95% confidence interval [CI]: 37.2–69.9). The median duration of response was 5.7 months (95% CI: 4.3–9.1), and the median progression-free survival was 5.4 months (95% CI: 1.8–6.7). The 1-year OS rate was 65.5% (95% CI: 48.1–78.3). Frequently observed adverse events included decreases in neutrophil counts (74.4%), white blood cell counts (64.1%) and platelet counts (64.1%).ConclusionsThis study highlights the potential of linperlisib plus GEMOX as a treatment for R/R DLBCL, demonstrating a tolerable safety profile and encouraging efficacy results.Trial registrationNCT04500561.

The value of common blood parameters for the differential diagnosis of respiratory tract infections in children

Mycoplasma pneumoniae and influenza A virus are common pathogens that cause respiratory tract infection in children. Both pathogens present with similar clinical symptoms, and their epidemic periods often overlap. Consequently, it is challenging for clinicians to make a rapid preliminary diagnosis. However, common blood tests is simple and efficient, Therefore, the purpose of this study is to preliminarily distinguish Mycoplasma pneumoniae and influenza A virus infection in children by analyzing the results of common blood tests, thereby guiding clinical diagnosis and treatment.The results showed that, compared with children in the influenza A virus-positive group, children in the Mycoplasma pneumoniae-positive group had higher white blood cell (WBC), red blood cell (RBC), haemoglobin (HGB), platelet (PLT) counts, lymphocyte (LYM) and eosinophil (EOS) counts and ratios, as well as higher concentrations of C-reactive protein (CRP) and serum amyloid A (SAA), while neutrophil (NEU) and monocyte (MONO) counts and ratios, Neutrophil to Lymphocyte ratio( NLR) were lower, in addition, LYM, EOS counts and ratios, and NLR were all more effective in differentiating between the two pathogen infections, A combined analysis of these indicators further improved the differentiation efficacy. Therefore, LYM and EOS counts and ratios, along with NLR, can serve as effective blood parameters for differentiating Mycoplasma pneumoniae infections from influenza A virus infections in children.

Investigating the Effects of Metabolic and Bariatric Surgery on Systemic Immune-Inflammation Index and Its Relationship With Smoking.

The contribution of obesity to inflammation may play a role in the progression of obesity-associated medical problems. The systemic immune inflammation index (SII) has recently been identified as a prognostic indicator for many adverse conditions. The primary purpose of the present study was to investigate the effects of metabolic and bariatric surgeries on white blood cell (WBC), platelet (PLT), lymphocyte (LYN), neutrophil (NEU), neutrophil/lymphocyte (NLR), platelet/neutrophil (PLR), and systemic immune inflammation index (SII). The secondary aim was to evaluate the effects of sleeve gastrectomy (SG) and gastric bypass (GB) surgeries, the most commonly performed metabolic and bariatric procedures, on individual inflammation parameters and their relationship with smoking status. The blood inflammatory markers of the participants who underwent surgery were analyzed using the data evaluated during routine clinic follow-ups in the preoperative period and postoperative 1st, 3rd, 6th, and 12thmonths. The primary result was a statistically significant decrease in WBC, NEU, NLR, and SII values in the 3rd postoperative month in those who underwent metabolic and bariatric surgery (MBS) (p values for each parameter: 0.000, 0.000, 0.028, and 0.006, respectively). A statistically significant decrease in WBC, NEU, and SII values in the 3rd postoperative month compared to preoperative values in nonsmoking individuals with obesity who underwent sleeve gastrectomy surgery was presented as our secondary result (p values for each parameter: 0.000, 0.000, and 0.015, respectively). In our study, MBS provided significant regression in inflammation parameters at 3months after surgery in people smoking less than 10 cigarettes per day, although this effect did not seem to persist long term. ACTRN12623000162617.

Idiopathic Mild Platelet Dysfunction: Baseline Characteristics and Clinical Courses.

The causes of nonsyndromic platelet storage pool disease are still unclear, and whether they are of genetic or acquired origin remains to be defined. The study aimed to describe the characteristics and natural history of this disorder. This mostly retrospective cohort enrolled adults presenting with bleeding from platelet dysfunction. Platelet glycoprotein defects, von Willebrand disease, syndromic inherited platelet disorders and known acquired platelet dysfunctions were excluded. Available patients were retested by lumiaggregometry (Chrono-Log) over 1 year after the initial diagnosis. There was a total of 56 patients; 91% female, with a median diagnostic age of 28 years (interquartile range [IQR]: 24.5-38.5). The subnormal responses to ADP, epinephrine, collagen, and arachidonate were found in 91%, 82%, 55%, and 34%, respectively. Nineteen patients had von Willebrand factor levels measured. Twenty-three subjects underwent repeat tests. Twenty-one of them were female (91%), with a median age and follow-up time of 37 years (IQR: 28-55) and 6 years (IQR: 3-12), respectively. Median ISTH-BAT bleeding scores at diagnosis and follow-up were 5 (IQR: 3-8) and 1 (IQR: 0-2), respectively. The common abnormalities were reduced responses to ADP combined with other agonists (83%). Twelve (52%) and five (22%) showed complete and partial platelet function recovery, respectively. None of the partial and non-recovery groups had a bleeding score over 4 at follow-up. Idiopathic mild platelet dysfunction was female-predominant and showed spontaneous symptom resolution after a long follow-up. Platelet function recovery was observed in most cases. Exogenous factors triggering this condition remain to be identified.

A highly sensitive enzyme‑linked immunosorbent assay allows accurate measurements of brain‑derived neurotrophic factor levels in human saliva

Background Hitherto, BDNF levels in humans have been primarily measured in serum and/or plasma where these levels are readily measurable, but primarily reflect the content of BDNF in blood platelets. By contrast, previous attempts to measure BDNF levels in readily accessible human body fluids such as saliva have been complicated by a lack of sensitivity and/or specificity of BDNF ELISAs (see Discussion). Recently, the suitability of a highly sensitive BDNF ELISA assay was validated using mouse plasma and serum where conventional BDNF ELISA fail to detect BDNF. In this report, we demonstrate that BDNF levels in human saliva are extremely low, in the low pg/mL range, yet detectable in all saliva samples tested. Methods Saliva samples were collected from healthy volunteers by a passive drool method. All samples were aliquoted and immediately frozen to keep at -80°C until use. At the time of use, the samples were thawed, centrifuged to remove any remaining particles and BDNF measurement conducted by using a previously validated BDNF ELISA assay (see below). Recombinant mature BDNF was used as a reference. Results The intra-assay variability was in the range of CV = 1.8 to 4.9%. Saliva samples could be kept frozen at -80°C for 2 months until use for measurements, but more than 4 freeze and thaw cycles caused BDNF losses presumably due to structural change of the antigen. The measurements were not affected by the method of collection provided the samples were diluted at least 2-fold. Conclusions The results indicate that human saliva samples collected in a non-invasive fashion can be used as a source of material to try and correlate BDNF levels with human conditions of interest. These results also confirm those of an independent study published recently using the same BDNF ELISA kit to measure BDNF levels in human saliva samples.

The effect of GM-CSF and predictors of treatment outcome in pediatric septic shock patients

BackgroundPediatric septic shock is a critical condition associated with high mortality rates, largely due to sepsis-induced immunosuppression. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been explored as a therapeutic intervention to counteract this immunosuppression. Despite its potential, the efficacy of GM-CSF in pediatric septic shock has not been clearly established. This study aims to investigate the impact of GM-CSF administration on survival rates and to identify key predictors of treatment outcomes in pediatric septic shock patients.MethodsWe conducted a retrospective cohort study at the Pediatric Intensive Care Unit (PICU) of Children’s Hospital of Fudan University, Shanghai, from January 1, 2019, to December 31, 2023. The study included pediatric patients diagnosed with septic shock, analyzing their demographic data, GM-CSF and adjunctive therapies, laboratory results, and clinical outcomes. We employed univariate and multivariate logistic regression models to assess the influence of GM-CSF on 28-day mortality and identify significant predictors of treatment outcomes.ResultsThe study included 200 pediatric patients, with 66 receiving GM-CSF treatment and 134 not treated with GM-CSF. The initial comparison showed a higher 28-day mortality in the GM-CSF group (59.1%) compared to the non-GM-CSF group (35.1%, P = 0.001). Notably, after adjustment for confounding factors, multivariate analysis revealed that the effect of GM-CSF treatment on 28-day mortality among pediatric septic shock patients did not reach statistical significance, with an odds ratio (OR) of 0.472 and a 95% confidence interval (CI) ranging from 0.153 to 1.457 (P = 0.192). However, the analysis indicated a potential trend suggesting that GM-CSF treatment may contribute to a reduction in 28-day mortality. In addition, significant predictors of treatment outcomes included hematopoietic stem cell transplantation (HSCT), lactic acid (LAC) levels, hospital-acquired septic shock (HASS), red blood cell (RBC) count, and platelet (PLT) count.ConclusionsGM-CSF treatment may benefit pediatric septic shock patients, especially those with higher lactic acid, and lower RBC and platelet counts. These factors, which are significant predictors of outcomes, should be monitored during therapy.

Safety and Efficacy of DPMAS in Patients With Acute-on-Chronic Liver Failure Based on Different Platelet Count Levels.

To investigate the effect of different platelet (PLT) counts on the safety and efficacy of the double-plasma molecular absorption system (DPMAS) in patients with acute-on-chronic liver failure (ACLF). A total of 156 patients with ACLF receiving DPMAS were divided into the observed group (40 × 109/L ≤ PLT < 50 × 109/L) and the control group (PLT ≥ 50 × 109/L) according to PLT count level. The safety and efficacy indices of bleeding-related complications, PLT reduction rate, total bilirubin (TBIL) reduction rate, and 28-days survival rate after DPMAS were analyzed and compared between the two groups. The incidence of bleeding complications during and after DPMAS in the observed and control groups (14.3% vs. 14.9%, p = 0.922), the decline rate of PLT immediately and 24 h after treatment (0.13 vs. 0.11/0.05 vs. 0.09, p = 0.256/0.161), and the 28-days survival rate after treatment (76.2% vs. 75.4%, p = 0.923) were not significantly different. The thromboelastogram before DPMAS showed no significant difference in PLT function between the two groups (p > 0.05). Although the TBIL level of the two groups rebounded 24 h after treatment compared with immediately after treatment, it decreased significantly immediately and 24 h after treatment compared with pre-treatment levels (p < 0.05). There was no significant difference in the rate of decline of serum TBIL immediately after treatment and 24 h after treatment between the two groups (0.33 vs. 0.35/0.14 vs. 0.16, p = 0.193 and 0.653, respectively). DPMAS is safe and effective in patients with ACLF with 40 × 109/L ≤ PLT count < 50 × 109/L.

Abstract TP355: Immunohistochemical Confirmation of Neutrophil Extracellular Trap (NET) Enrichment in Stroke Thrombus of Patients with Atrial Fibrillation

Background: Neutrophil Extracellular Traps (NETs) are web-like structures of DNA, histones, and granule proteins that trap pathogens as part of innate immunity but also scaffold red blood cells, fibrin, and platelets in pathological thrombosis. Thrombus NETs have been associated with failed thrombolysis and thrombectomy for acute ischemic stroke (AIS). We previously used mass spectrometry to describe a novel association between NET proteins and atrial fibrillation (AF). This association has not been validated by traditional immunohistochemical methods. Aims/Purpose: We used immunohistochemistry to quantify NETs in AIS thrombus taken from patients with and without comorbid AF. Methods: We selected markers for each of the components of NETS: (1) a granule protein, myeloperoxidase (MPO), (2) citrullinated histone 3 (CitH3), and cellular nucleic acid (NA, using Hoechst 33342). This was a single-blind study using cryopreserved thrombi from 30 patients, 15 with AF. Stroke thrombi were collected over a two-year span, and immediately frozen to -80*C post-thrombectomy. To capture the coverage of NET markers more comprehensively for each patient, we used cryostat to sample four sections (five-micron thickness) from each thrombus. We then fixed sections with 4% formaldehyde in phosphate buffered saline (PBS), performed immunohistological staining, and quantified extent of staining using ImageJ. Data for each NET marker from a single thrombus is represented as the mean percentage of thrombus area staining positively across the four corresponding sections. After performing Shapiro Wilks test for normality, statistical comparisons of NET marker staining coverage between AF and non-AF thrombi were performed with either unpaired T test or Mann-Whitney U test, depending on whether a parametric or non-parametric test was appropriate. Results: Thrombi from patients with AF had greater MPO coverage(17.9 +/- 1.47% versus 11.6 +/- 1.29% in non-AF, p&lt;0.01) and CitH3 coverage(12.6 +/- 1.46% versus 7.4 +/- 1.11% in non-AF, p&lt;0.01). Staining for nucleic acid with Hoechst 33342 trended toward higher coverage in AF but did not reach significance (27.8 +/- 3.35% versus 22.6 +/- 3.20% in non-AF, p=0.30). Conclusion: The present study provides immunohistochemical validation, supporting novel observations in prior proteomic investigations, of increased NETs in stroke thrombi of patients with AF. This can help to identify patient cohorts for future studies of therapies directed at NETs.

Complex gene-dependent and-independent mechanisms control daily rhythms of hematopoietic cells.

The abundance and behaviour of all hematopoietic components display daily oscillations, supporting the involvement of circadian clock mechanisms. The daily variations of immune cell functions, such as trafficking between blood and tissues, differentiation, proliferation, and effector capabilities are regulated by complex intrinsic (cell-based) and extrinsic (neuro-hormonal, organism-based) mechanisms. While the role of the transcriptional/translational molecular machinery, driven by a set of well-conserved genes (Clock genes), in nucleated immune cells is increasingly recognized and understood, the presence of non-transcriptional mechanisms remains almost entirely unexplored. Studies on anucleate hematopoietic components, such as red blood cells and platelets, have shown that auto-sustained redox reaction cycles persist and operate in mammals. This opens to the possibility that transcriptional and non-transcriptional circadian mechanisms might coexist in nucleated immune cell populations, potentially complementing each other. It is becoming increasingly clear that disruption of the circadian rhythm at the central level (core clock) is strongly implicated in a plethora of diseases that are associated with maladaptive immune responses. On the other hand, several evidence imply that dysregulated immune activity (e.g. excessive inflammation) may alter/disrupt the proper functioning of peripheral clocks. This knowledge paves the way to the exploitation of chronobiological concepts in clinical practice. A better comprehension of various transcriptional/translational and biochemical mechanisms that maintain rhythmicity in immune system activities, as well as the many factors (host-derived, microbiota-derived, environment) that can alter or disrupt these processes, will facilitate the development of novel chrono-immunotherapeutic approaches.

Concurrent transarterial chemoembolization plus atezolizumab and bevacizumab in unresectable hepatocellular carcinoma: Interim analysis from a multicenter real-world study (CHANCE 023).

542 Background: Combining transarterial chemoembolization (TACE) with systemic therapies such as atezolizumab and bevacizumab (T+A) has shown potential efficacy in patients with unresectable Hepatocellular carcinoma (HCC) This interim analysis aims to evaluate the efficacy and safety of this combination therapy when administered concurrently within a two-month period. Methods: This multicenter, real-world study included patients diagnosed with unresectable HCC who received TACE combined with T+A from January 2020 to June 2024, across 37 centers in mainland China. The primary endpoint was overall survival (OS). This trial is registered with ClinicalTrials.gov, NCT06024252. Results: Out of a cohort of 335 patients, 293 (259 males) met the inclusion criteria, and 37.5% (112/293) adopted this regimen as second-line therapy. The interim analysis showed a median OS of 29.97 months and a one-year survival rate of 76.50%. The median PFS was 19.23 months, and the objective response rate (ORR) was 41.6%, with 26 complete responses and 96 partial responses. The disease control rate (DCR) was 84.6%. Common adverse events included bone marrow suppression, decreased white blood cell or platelet counts, among others. Serious adverse events occurred in 9.2% of patients (27/293) and were manageable with standard interventions. Conclusions: This study is a real-world analysis to highlight the potential benefits of combining TACE with T+A in this patient population. However, longer follow-up is required to better assess both overall survival and the long-term safety profile of this treatment strategy. Clinical trial information: NCT06024252 .

Abstract TP376: S-nitrosoglutathione Reduced Ischemia/reperfusion Injury by Relieving Thrombo-inflammation in Experimental Stroke Models

Aims: S-nitrosoglutathione (GSNO) is an endogenous low-molecular-weight S-nitrosothiol, involved in storing and transporting of nitric oxide. The study was aimed to test the effects of GSNO in ischemia/reperfusion (I/R) Injury through relieving thrombo-inflammation. Methods: Male C57BL/6 mice (n=160) were 10-week-old (20-25 g) at the time of surgery. Mice were administered with carboplatin (60 mg/kg body weight) intraperitoneally to build thrombocytopenic models. The animals were randomized and coded by an independent researcher who was not involved in the data analysis. Investigators involved in the surgery and evaluation of all parameters were blinded to the experimental groups. The mice were randomly divided into four groups: 1) regular I/R models with iv. normal saline (NS), 2) regular I/R models + 1 mg/kg iv. GSNO, 3) thrombocytopenic I/R models with iv. NS, and 4) thrombocytopenic I/R models +1 mg/kg iv. GSNO. All animals received humane care in compliance with Beijing Tiantan Hospital’s guidance. Levels of P-selectins, interferon (IFN)-γ and infarct volume and were compared. Results: Mean blood platelets count was 177 10^9/L in the mice administrated with carboplatin, and 383 10^9/L in the mice without carboplatin administration (p &lt; 0.05). Comparing with the mice treated with NS, P-selectin in the ischemic brain tissue were significantly decreased after injected with GSNO either at 24 h (1610.5 vs. 863.0 pg/ml, p &lt; 0.05) or at 7 d (1056.8 vs. 590.0 pg/ml, p &lt; 0.05) in regular mice, and in thrombocytopenic mice (2874.2 vs. 2113.0 pg/ml, p &lt; 0.05, at 24 h） and（3088.0 vs. 2373.0 pg/ml, p &lt; 0.001, at 7 d） (Fig1). After treating with GSNO, levels of IFN-γ were decreased in regular mice (24 h: 635.4 vs. 244.8 pg/ml, p &lt; 0.05; at 7 d: 559.2 vs. 100.0 pg/ml, p &lt;0.05）and thrombocytopenic mice（24h: 423.0 vs. 491.8 pg/ml, p &lt; 0.05; 7d: 319.6 vs. 155.4 pg/ml, p &lt; 0.05）(Fig1). GSNO tended to have the effect of decreasing infarct volume in regular mice（24h: 65% vs. 79%, p = 0.11; 7d: 31% vs. 62%, p = 0.05） and thrombocytopenic mice（24h: 42% vs. 79%, p =0.06; 7d: 60% vs. 62%, p =0.69）than NS (Fig2). Conclusions: GSNO reduced inflammation by limiting platelets activation to protect I/R injury in experimental stroke models.

Screening for gene variants causing inherited platelet disorders: are the cons always cons?

Screening for gene variants causing inherited platelet disorders: are the cons always cons?

An observational study of alveolar-derived autologous blood clot used in regenerative endodontic treatment for immature permanent teeth with pulp necrosis.

This study introduces the alveolar-derived autologous blood (ADAB) clot, obtained by maxillary alveolar bone puncture, as a novel scaffold for regenerative endodontic treatment (RET). The purpose of this study is to verify the feasibility of using ADAB clots in RET by evaluating their cellular content, postoperative pain intensity, and clinical outcomes in the management of immature permanent teeth with pulp necrosis. Blood routine examinations were performed to analyze the cell content of peripheral venous blood (PVB) and ADAB. Postoperative pain intensity scores were recorded using the Numerical Rating Scale (NRS) at four time points: upon complete recovery from anesthesia, and at 12, 24, and 48h postoperatively. Five immature premolars with pulp necrosis were treated by RET with ADAB clots. Radiographic root area (RRA) was analyzed using ImageJ software on oral radiographs obtained immediately after treatment and at the final follow-up (6-18months). The percentage difference in cell types between two groups (n = 8 per group) were not significant, except for blood platelets (PLT). The PLT count in the ADAB group (133.38 ± 119.62) was approximately half that of the PVB group (268.88 ± 52.82). Postoperative pain (n = 9) was predominantly mild upon anesthesia recovery and at 12h postoperatively, while the majority of participants reported no pain at 24 and 48h postoperatively. The mean RRA (0.50 ± 0.11) in the final recall radiographs was significantly larger than that in the immediate postoperative radiographs (0.35 ± 0.16) (P = 0.046 < 0.05). Based on this study, the ADAB clot shows potential as an alternative scaffold for RET. Because it can be obtained via maxillary terminal alveolar bone paracentesis with mild postoperative pain intensity and successfully promotes root regrowth. However, the coagulation time of ADAB may be longer than that of PVB, and root regrowth outcomes appear to depend on the developmental stage of the tooth. Hence, further clinical trials are necessary to comprehensively evaluate the clinical efficacy of the ADAB clot. Compared to autologous platelet concentrates (APCs) derived from PVB, ADAB clots offer advantages in RET, especially in cases where periapical bleeding is insufficient to fill the root canals. ADAB clots can be prepared independently by dentists without the need for a qualified nurse for blood collection or specialized centrifugation equipment. Furthermore, the volume of blood required to fabricate an ADAB clot is less than that needed for APCs from PVB.

Assessment of the Toxicological Effects of Cypermethrin Nanoformulation on &lt;i&gt;Hypselobarbus pulchellus&lt;/i&gt; using Selected Biomarkers

Pesticides are widely used in aquaculture farms against ectoparasites. However, due to the development of resistance in ectoparasites against the traditional pesticide formulations, pesticides are being applied at a higher dose or in combinations. Nano formulation of pesticides with enhanced properties is a viable option to reduce the volume of traditional pesticides applied in aquaculture. Hence, the present study developed a nano formulation of the pesticide cypermethrin and evaluated the toxic effects in the fish Hypselobarbus pulchellus. The acute toxicity study recorded the mortalities at 24h intervals for 96h. The 96h LC50 value was estimated to be 0.003 mg L-1. Chronic toxicity studies were also conducted exposing H. pulchellus to sublethal concentrations for 45 days. The brain acetylcholine esterase activity was significantly reduced (p ˂ 0.05) in the cypermethrin nano formulation exposed fish. The nano formulation exposure also caused a significant increase in the liver and kidney superoxide dismutase activity. Elevated catalase and glutathione-s-transferase levels were observed in the liver and gills, with no conspicuous change in the kidneys. The serum enzymes aspartate aminotransferase and alanine aminotransferase were elevated significantly by cypermethrin exposure. The serum triglycerides, cholesterol, and protein content were reduced significantly. Similarly, the red blood cell, haematocrit, haemoglobin, and platelet count also showed significant reduction on cypermethrin exposure. These findings on the toxic impacts may help to understand the effect of micro-formulated antiparasitic drugs in fin fish.

The ability of CD4dimCD8+ T cells to distinguish between Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis and pediatric infectious mononucleosis.

Epstein-Barr virus (EBV)-related hemophagocytic lymphohistiocytosis (EBV-HLH) and infectious mononucleosis (IM) are characterized by fever, hepatomegaly, and splenomegaly, but HLH has a 50% lethality rate. Therefore, this study aimed to compare the laboratory findings in differentiating EBV-HLH children from IM children who have fever, hepatomegaly, or splenomegaly. A total of 131 IM patients and 29 EBV-HLH pediatric patients with fever, hepatomegaly, or splenomegaly were enrolled in our study. The clinical traits and laboratory findings were analyzed, and a predictive regression analysis was also performed. EBV-HLH patients had a lower set of diagnostic markers, which included fibrinogen (FIB), white blood cells (WBC), hemoglobin (Hb), and platelet (PLT), compared to IM patients. Triglyceride (TG) and ferritin were elevated obviously in EBV-HLH patients compared to IM patients. CD4dimCD8+ T cells are highly activated T cells. EBV-HLH patients experienced a significant decrease in the absolute number and ratio of CD4dimCD8+T cells (CD4dimCD8+T#, CD4dimCD8+T%) compared to IM patients in our study. The AUC of CD4dimCD8+ T # in the diagnosis of EBV-HLH was 0.920 with a sensitivity of 86.2% and a specificity of 90.1%. A logistic regression analysis was developed to improve sensitivity. The results revealed that lower levels of Hb, FIB, and CD4dimCD8+T cells were risk factors for EBV-HLH. The regression model for separating EBV-HLH from EBV-IM had an AUC of was 0.996 with a sensitivity of 100% and a specificity of 95.3%. The ratio and absolute number of CD4dimCD8+T cells were decreased in IM and EBV-HLH patients. EBV-HLH can be identified in IM patients with fever, hepatomegaly, or splenomegaly by detecting Hb, FIB, and the absolute number of CD4dimCD8+T cells.

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).

Correlation Red Blood Inidces to Hemogloblin Levels In Addolescent At SMK-TI High School, Badung, Bali

The Complete Blood Count (CBC) or hemogram is a panel of test results on the cellular components of blood: the Red Blood Cells (RBCS), White Blood Cells (WBCS), and platelets (PLTS). Each of the portions can be interpreted separately in a methodical fashion and the interpretation has two aims for laboratorians. parameter that is quite sensitive to testing errors and interferences (often flagged) is the Mean Cell Hemoglobin Concentration (MCHC). The purpose of checking Hemoglobin levels is to assess the level of anemia, response to anemia therapy, or the development of diseases related to anemia and polycythemia. Other uses for checking Hemoglobin include assessing the level of anemia, the response to anemic women and the development of diseases related to anemia. This research used a crosssectional analytic method with the aim of finding a correlation red blood indices to Hemoglobin. Teenagers are the most prominent investors and the next generation of the nation's ideals. However, in adolescence, many problems can have a negative impact on health, such as adolescent nutrition. The quality and quantity of nutritional intake consumed during adolescence is an important factor in the emergence of nutritional problems in adolescents.

Population dynamics analysis of the interaction between tacrolimus and voriconazole in renal transplant recipients

BackgroundThe concurrent administration of tacrolimus and voriconazole in kidney transplant recipients can lead to drug interactions, potentially resulting in severe adverse reactions. This study aimed to establish a robust population pharmacokinetic model to explore the interaction between tacrolimus and voriconazole in greater depth.MethodsTacrolimus blood samples and laboratory data were prospectively collected from eligible patients enrolled between April 2023 and April 2024, following predefined inclusion and exclusion criteria. Using Phoenix (version 8.1), a pharmacokinetic prediction model was developed. Model performance was assessed using model fitting plots, bootstrap analysis, and visual predictive checks (VPC).ResultsThis study ultimately included 51 eligible patients, with a total of 281 blood samples collected. Analysis revealed a significant negative correlation between voriconazole concentration (Cvrc) and tacrolimus volume of clearance rate (CL), a significant positive correlation between platelets (PLT) and tacrolimus clearance (CL), and a significant negative correlation between blood cells (RBC) and tacrolimus clearance (CL).ConclusionThis study successfully established a population pharmacokinetic model for renal transplant patients concurrently receiving tacrolimus and voriconazole. The model demonstrated good predictive performance and offers valuable insights to clinicians for optimizing tacrolimus dosing in this patient population.

Platelet-white cell ratio is more strongly associated with mortality than other common risk ratios derived from complete blood counts

Complete blood count indices and their ratios are associated with adverse clinical outcomes for many acute illnesses, but the mechanisms generating these associations are not fully understood. Recent identification of a consistent pattern of white blood cell and platelet count co-regulation during acute inflammatory recovery provides a potentially unifying explanation. Here we show that the platelet-to-white-cell ratio, which was selected based on this conserved recovery pattern, is more strongly associated with mortality than other blood count markers and ratios in four important illnesses involving acute inflammation: COVID-19, acute heart failure, myocardial infarction, and stroke. Patients recovering well from these acute illnesses tend to follow a joint white cell and platelet trajectory that can be reduced to this one-dimensional ratio. The platelet-to-white-cell ratio’s association with prognosis is consistent with recently identified inflammatory dynamics and may provide a convenient and interpretable summary of patient inflammatory state.

Association Between Plasmodium Infection and Blood Count Values: Implications for Malaria Diagnosis in Resource-Limited Settings

PurposeMalaria remains a major global health challenge, particularly in sub-Saharan Africa and low- and middle-income countries (LMICs), contributing substantially to mortality and morbidity rates. In resource-limited settings, access to specialized diagnostic tests is often restricted, making basic blood analysis a valuable diagnostic tool. This study investigated the correlation between malaria infection and full blood count values in a rural region of Ghana during the 2022 rainy season, aiming to highlight diagnostic insights available from routine blood analyses.MethodsA retrospective case-control analysis was conducted on 544 confirmed malaria cases, comparing their blood values with those of matched malaria-negative controls.ResultsParasitaemia levels peaked during the rainy season, with July showing the highest values. Malaria-positive patients exhibited lower levels of haemoglobin, white blood cells, lymphocytes, and platelets, but higher neutrophil counts compared to controls. Middle-aged women had significantly lower haemoglobin levels than men, and younger individuals showed higher parasitaemia levels. A negative correlation was found between Plasmodium density and haemoglobin and platelet counts, while positive correlations were observed with white blood cell and neutrophil counts.ConclusionThis study highlights the significant burden of malaria in rural Ghana during the rainy season and underscores the impact of infection on blood values. Routine full blood count analysis provides a practical and accessible diagnostic tool in resource-limited settings. The findings emphasise the importance of targeted interventions for high-risk groups, particularly children and women, to improve patient management and reduce malaria-related morbidity.Graphical