Peripheral Platelet Counts Research Articles

Associations of subcutaneous fat area and Systemic Immune-inflammation Index with survival in patients with advanced gastric cancer receiving dual PD-1 and HER2 blockade

BackgroundSystemic Immune-inflammation Index (SII) and body composition parameters are easily assessed, and can predict overall survival (OS) in various cancers, allowing early intervention. This study aimed to assess the correlation...

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.

Loss of P2Y1 receptor desensitization does not impact hemostasis or thrombosis despite increased platelet reactivity in vitro

BackgroundThe hemostatic plug formation at sites of vascular injury is strongly dependent on rapid platelet activation and integrin-mediated adhesion and aggregation. However, to prevent thrombotic complications, platelet aggregate formation must be a self-limiting process. The second-wave mediator adenosine diphosphate (ADP) activates platelets via Gq-coupled P2Y1 and Gi-coupled P2Y12 receptors. After ADP exposure, the P2Y1 receptor undergoes rapid phosphorylation-induced desensitization, a negative feedback mechanism believed to be critical for limiting thrombus growth. ObjectiveThe objective of this study was to examine the role of rapid P2Y1 receptor desensitization on platelet function and thrombus formation in vivo. MethodsWe analyzed a novel knock-in mouse strain expressing a P2Y1 receptor variant that cannot be phosphorylated beyond residue 340 (P2Y1340-0P), thereby preventing the desensitization of the receptor. ResultsP2Y1340-0P mice followed a Mendelian inheritance pattern, and peripheral platelet counts were comparable between P2Y1340-0P/340-0P and control mice. In vitro, P2Y1340-0P/340-0P platelets were hyperreactive to ADP, showed a robust activation response to the P2Y1 receptor-selective agonist, MRS2365, and did not desensitize in response to repeated ADP challenge. We observed increased calcium mobilization, protein kinase C substrate phosphorylation, alpha granule release, activation of the small GTPase Rap1, and integrin inside-out activation/aggregation. This hyperreactivity, however, did not lead to increased platelet adhesion or excessive plug formation under physiological shear conditions. ConclusionOur studies demonstrate that receptor phosphorylation at the C-terminus is critical for P2Y1 receptor desensitization in platelets and that impaired desensitization leads to increased P2Y1 receptor signaling in vitro. Surprisingly, desensitization of the P2Y1 receptor is not required for limiting platelet adhesion/aggregation at sites of vascular injury, likely because ADP is degraded quickly or washed away in the bloodstream.

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.

Associations between dietary and blood inflammatory indices and their effects on cognitive function in elderly Americans.

To determine the correlations between dietary and blood inflammation indices in elderly Americans and their effects on cognitive function. This research extracted data from the 2011-2014 National Health and Nutrition Examination Survey for 2,479 patients who were ≥60 years old. Cognitive function was assessed as a composite cognitive function score (Z-score) calculated from the results of the Consortium to Establish a Registry for Alzheimer's Disease Word Learning and Delayed Recall tests, the Animal Fluency test, and the Digit Symbol Substitution Test. We used a dietary inflammatory index (DII) calculated from 28 food components to represent the dietary inflammation profile. Blood inflammation indicators included the white blood cell count (WBC), neutrophil count (NE), lymphocyte count (Lym), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), neutrophil-albumin ratio (NAR), systemic immune-inflammation index [SII, calculated as (peripheral platelet count) × NE/Lym], and systemic inflammatory response index [SIRI, calculated as (monocyte count) × NE/Lym]. WBC, NE, Lym, NLR, PLR, NAR, SII, SIRI, and DII were initially treated as continuous variables. For logistic regression, WBC, NE, Lym, NLR, PLR, NAR, SII, and SIRI were divided into quartile groups, and DII was divided into tertile groups. After adjusting for covariates, WBC, NE, NLR, NAR, SII, SIRI, and DII scores were markedly higher in the cognitively impaired group than in the normal group (p < 0.05). DII was negatively correlated with the Z-score when combined with WBC, NE, and NAR (p < 0.05). After adjusting for all covariates, DII was positively correlated with SII in people with cognitive impairment (p < 0.05). Higher DII with NLR, NAR, SII, and SIRI all increased the risk of cognitive impairment (p < 0.05). DII was positively correlated with blood inflammation indicators, and higher DII and blood inflammation indicators increased the risk of developing cognitive impairment.

Predictive Role of the Systemic Immune Inflammation Index for Intravesical BCG Response in Intermediate- and High-Risk Non-Muscle-Invasive Bladder Cancer

Introduction: In this study, we aimed to explore using the predictive role of systemic immune inflammation index (SII) for responses of intravesical Bacillus Calmette-Guérin (BCG) therapy in patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). Methods: From 9 centers, we reviewed the data of patients treated for intermediate- and high-risk NMIBC between 2011 and 2021. All patients enrolled in the study presented with T1 and/or high-grade tumors on initial TURB had undergone re-TURB within 4–6 weeks after initial TURB and had received at least a 6-week course of intravesical BCG induction. SII was calculated with the formula SII = (P × N)/L, where P, N, and L refer to peripheral platelet, neutrophil, and lymphocyte counts, respectively. In patients with intermediate- and high-risk NMIBC, the clinicopathological features and follow-up data were evaluated to compare SII with other systemic inflammation-based prognostic indices. These included the neutrophil-to-lymphocyte ratio (NLR), platelet-to-neutrophil ratio (PNR), and platelet-to-lymphocyte ratio (PLR). Results: A total of 269 patients were enrolled in the study. Median follow-up time was 39 months. Disease recurrence and progression were observed in 71 (26.4%) and 19 (7.1%) patients, respectively. For groups with and without disease recurrence in terms of NLR, PLR, PNR, and SII calculated prior to intravesical BCG treatment, no statistically significant differences were observed (p = 0.470, p = 0.247, p = 0.495, and p = 0.243, respectively). Moreover, there were also no statistically significant differences between the groups with and without disease progression in terms of NLR, PLR, PNR, and SII (p = 0.504, p = 0.165, p = 0.410, and p = 0.242, respectively). SII did not show any statistically significant difference between early (<6 months) and late (≥6 months) recurrence (p = 0.492) and progression groups (p = 0.216). Conclusion: For patients with intermediate- and high-risk NMIBC, serum SII levels do not present as an appropriate biomarker for the prediction of disease recurrence and progression following intravesical BCG therapy. A possible explanation for the failure of SII to predict BCG response may be found in the impact of Turkey’s nationwide tuberculosis vaccination program.

Research on the mechanism of prednisone in the treatment of ITP via VIP/PACAP-mediated intestinal immune dysfunction

RationaleImmune thrombocytopenia (ITP) is thought to be a result of immune dysfunction, which is treated by glucocorticoids such as prednisone. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) have immunomodulatory properties, but their role in intestinal immune control is unclear. The major goal of this study was to look at the effects of prednisone on platelet, VIP, and PACAP levels in ITP mice, as well as the regulatory system that controls intestinal immunity.MethodsEighteen BALB/c mice were randomly divided into three groups: blank control group, model control group, and prednisone group, with six mice in each group. The ITP animal model control group and the prednisone group were injected with anti-platelet serum (APS) to replicate the ITP animal model. The prednisone group began prednisone intervention on the 8th day. Platelet count was dynamically measured before APS injection, on the 4th day of injection, on the 1st day of administration, on the 4th day of administration, and at the end of the experiment. After the experiment, the expression of p53 protein in mouse mesenteric lymph node lymphocytes was detected by immunohistochemistry. The changes in lymphocyte apoptosis rate in mouse mesenteric lymph nodes were detected by in situ terminal transferase labeling (TUNEL). The contents of VIP and PACAP in the mouse brain, colon, and serum were detected by enzyme-linked immunosorbent assay (ELISA). The contents of IFN-γ, IL-4, IL-10, IL-17A in the mouse spleen were detected by ELISA.Results①Changes of peripheral platelet count: there was no significant difference in platelet count among the three groups before modeling; on the 4th day, the platelet count decreased in the model control group and prednisone group; on the 8th day, the number of platelets in model control group and prednisone group was at the lowest level; on the 12th day, the platelet count in prednisone group recovered significantly; on the 15th day, the platelet count in prednisone group continued to rise. ②Changes of VIP, PACAP: compared with the blank control group, VIP and PACAP in the model control group decreased significantly in the brain, colon, and serum. Compared with the model control group, the levels of VIP and PACAP in the brain, colon, and serum in the prednisone group were increased except for serum PACAP. ③Changes of mesenteric lymphocytes: the expression of p53 protein in the mesenteric lymph nodes of model control group mice was significantly higher than that of blank control group mice. After prednisone intervention, the expression of p53 protein decreased significantly.④Changes of cytokines in spleen: compared with blank control group, IFN- γ, IL-17A increased and IL-4 and IL-10 decreased in model control group. After prednisone intervention, IFN- γ, IL-17A was down-regulated and IL-4 and IL-10 were upregulated.ConclusionsPrednisone-upregulated VIP and PACAP levels decreased P53 protein expression and apoptosis rate in mesenteric lymph node lymphocytes and affected cytokine expression in ITP model mice. Therefore, we speculate that the regulation of intestinal immune function may be a potential mechanism of prednisone in treating ITP.

A study on the diagnostic value of GP73 in liver fibrosis among patients with chronic liver disease

Objective: This study aimed to evaluate the diagnostic value of serum Golgi protein 73(GP73) alone and GP73 combined with liver stiffness measurement (LSM), aspartate aminotransferase/platelet ratio index (APRI), and 4-factor-based fibrosis index (FIB4) in diagnosing liver fibrosis in patients with chronic liver disease of different etiologies. Methods: A diagnostic test. A total of 68 patients who underwent liver biopsy in the Department of Traditional and Western Medical Hepatology of the Third Hospital of Hebei Medical University from October 2019 to December 2020 were selected to detect serum GP73 levels. iLivTouch was used to assess liver stiffness measurement (LSM). In addition, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), total bilirubin (TBil), direct bilirubin (DBil), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels, and peripheral platelet (PLT) counts were assayed. The correlation between GP73 and the above indexes was assessed, and APRI and FIB-4 were calculated. SPSS 21.0 statistical software was used for statistical analysis. The area under the receiver operating characteristic curve was calculated to evaluate diagnostic efficacy of GP73 in identifying hepatic fibrosis stages. Furthermore, the difference between GP73 and liver stiffness, as well as APRI and FIB4 in diagnosing significant fibrosis was assessed. Results: Based on liver biopsy, 13, 18, 17, and 20 cases were diagnosed as stages S0-1, S2, S3, and S4, respectively. The AUC of GP73 diagnosing hepatic fibrosis stage S≥3 and S=4 were 0.806 and 0.844 at cut-off points of 2.06 and 3.27 μg/L, and the sensitivity and specificity were 93.5%, 61.5%, 90.0%, 70.3%, respectively. In addition, GP73 levels were positively correlated with the degree of liver fibrosis (r=0.547, P<0.001). Conclusions: The efficacy of serum GP73 level in diagnosing the degree of liver fibrosis in patients with chronic liver disease from different causes was significantly higher than that of APRI, FIB4, and LSM. The combination of GP73 and FIB4 can further improve the accuracy of diagnosis of liver fibrosis staging S≥3 and S=4, which is a reliable serological marker for the diagnosis of fibrosis in patients with chronic liver disease.

Dual specificity tyrosine phosphorylation regulated kinase 1B inhibition promotes megakaryocyte polyploidization and platelet production.

Platelets are produced from mature megakaryocytes which undergo polyploidization and proplatelet formation. Cell cycle regulation plays a crucial role in megakaryocyte terminal differentiation especially in polyploidization. Dual specificity tyrosine phosphorylation regulated kinase 1B (DYRK1B) controls cell cycle progression in cancer cells. The objective of this study was to determine DYRK1B function in megakaryocyte maturation and platelet production. A DYRK1B knock out mouse (DYKO) was generated with increased peripheral platelet count compared to the wild type (WT) mouse without affecting megakaryocyte numbers in bone marrow. Polyploidy and proplatelet formation were significantly enhanced when DYRK1B was depleted in vitro. DYRK1B inhibition promoted megakaryocyte maturation by simultaneously upregulating cyclin D1 and downregulating P27. Furthermore, there was platelet restoration in two mice disease models of transient thrombocytopenia. In summary, DYRK1B plays an important role in megakaryocyte maturation and platelet production by interacting with cyclin D1 and P27. DYRK1B inhibition has potential therapeutic value in transient thrombocytopenia treatment.

The Relationship between Speed of Platelet Recovery and Its R-squared and Efficacy after First Induction Chemotherapy in Acute Myeloid Leukemia

To calculate the cut-off values of speed of platelet recovery and its R-squared in patients with acute myeloid leukemia (AML) after initial induction chemotherapy, which were used to predict the complete remission (CR) of the first induction chemotherapy, and guide the clinic to choose the next appropriate chemotherapy regimen as soon as possible. A total of 117 patients with newly diagnosed AML in the Second Hospital of Shanxi Medical University were included. Patients were diagnosed by morphology, immunology, cytogenetics, and molecular biology (MICM) classification, and the risk stratification was evaluated in combination with the clinical situations of the patients at the time of admission. The peripheral platelet counts after the first induction chemotherapy were detected and the linear regression equation was used to calculate the recovery speed of platelet counts in 5 consecutive blood cell analysis before discharge. According to the ROC curve, the cut-off value between the recovery speed and the R-squared was calculated, and the cut-off value was used to divide the patients into different groups. The differences between groups were compared by Pearson χ2 test to observe the remission effect of the first induction chemotherapy. ROC curve analysis showed that the cut-off value for predicting the platelet recovery speed and its R-squared of the first induction chemotherapy to achieve remission was 4.059 5×109/(L·d) and 72.7%, the sensitivity was 77% and 63.9%, the specificity was 62.5% and 67.9%, and the Youden index was 0.395 and 0.318, respectively. The patients were divided into different groups and compared according to the above cut-off values, and the results showed statistical differences (P<0.001, P=0.001). The cut-off value of platelet recovery speed and its R-squared after the first induction chemotherapy calculated by peripheral platelet count and ROC curve in AML patients can be used as an index to evaluate the remission. The faster the platelet recovery speed after chemotherapy is, the more likely patients achieve remission. The more stable the platelet recovery tendency is, the more likely patients achieve remission too.

Therapeutic Effect of Single Intramuscular Administration of Recombinant Human Thrombopoietin on Rhesus Monkeys with Acute radiation Sickness

To confirm the therapeutic effect of recombinant human thrombopoietin (rhTPO) on rhesus monkeys irradiated with 5.0 Gy 60Co γ-ray, and provide experimental basis for clinical treatment of similar patients. Fourteen adult rhesus monkeys were irradiated with 60Co γ-ray on both sides at the dose of 5.0 Gy (dose rate 69.2 cGy/min) to establish the acute radiation sickness model. The monkeys were divided into irradiation group (n=5), rhTPO 5 μg/kg group (n=4) and rhTPO 10 μg/kg group (n=5). Two hours after irradiation, the three groups of monkeys were injected with saline 0.1 ml/kg, rhTPO 5 μg/kg（0.1 ml/kg） and rhTPO 10 μg/kg(0.2 ml/kg), respectively. The general signs, survival, peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation, and the differences between rhTPO group and irradiation control group were compared. After total body irradiation with 5.0 Gy60Co γ-ray, rhesus monkeys successively showed fever, hemorrhage, sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes. Compared with the irradiated control group, a single intramuscular injection of rhTPO 5 μg/kg or 10 μg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding, increase the nadir of peripheral red blood cells and platelets counts, shorten the duration of hemocytopenia, and advance the time for blood cells to return to the pre-irradiation level. The serum biochemical results showed that rhTPO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent. Compared with the two administration groups, the therapeutic effect of rhTPO 10 μg/ kg was better. A single injection of rhTPO 5 μg/ kg or 10 μg/ kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gy γ-ray. It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.

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.

Outcomes of Older Patients with Aplastic Anemia Treated with Frontline Anti-Thymocyte Globulin (ATG)-Based Immunosuppressive Therapy

Background: Advances in the treatment of aplastic anemia (AA), such as the addition of eltrombopag (EPaG) to immunosuppressive therapy (IST) and the expanded use of unrelated and haploidentical stem cell transplant (SCT) have steadily improved outcomes. However, little is known about the characteristics and outcomes of patients (pts) ≥ 60 years (yrs) of age with newly diagnosed AA who have been treated with an ATG-based regimen. Presumed low bone marrow (BM) reserves, higher frequency of underlying clonal hematopoiesis, intolerance to therapy, comorbidities, and challenges in proceeding to salvage SCT have led to the speculation that response and survival of these pts to IST may be inferior than their younger counterparts. Methods: We retrospectively analyzed the characteristics and outcomes of pts ≥ 60 yrs of age (OLDER) at the time of diagnosis of AA treated with frontline (F/L) ATG based therapy at our center and compared them to pts < 60 yrs of age (YOUNG) treated with F/L ATG over the same time period. We captured their clinical characteristics, cytogenetic abnormalities, mutations in DNMT3A (D), ASXL1 (A) and TET2 (T), exposure to EPaG, response, time to response (TTR) and survival. Overall response included complete and partial response per the standard definitions. Relapse free survival (RFS) was tabulated from the time of best response to loss of response, 2nd ATG infusion, salvage SCT or death (whichever was earlier) and overall survival was tabulated from the time of response to death from any cause. Results: From Jan 2011-May 2012, 43 OLDER pts were treated as F/L for AA of whom 41 (95%) received ATG based therapy; 68 YOUNG pts were treated as F/L for AA over the same time period of whom 62 (91%) received ATG based regimen. Four YOUNG pts vs. no pts in the OLDER group received upfront SCT, and 2 pts in each group were treated with non ATG based therapy: single agent CSA, EPaG, or alemtuzumab. Comparative baseline characteristics are depicted in Table 1. There were no differences in the baseline WBC, peripheral blood lymphocyte percentage and platelet counts between the ATG treated OLDER and YOUNG groups. Both groups had similar frequencies of cytogenetic abnormalities and PNH clones, though OLDER pts had mutations in D-A-T genes compared to the YOUNG group (62% vs. 38%, p=0.05). Both groups had equal concurrent exposure to EPaG with ATG. Cumulatively 23/41 (56%) pts in the OLDER group had an overall response (OR) compared to 43/62 (70%) pts in the YOUNG group (p=0.1); 11/23 (48%) and 23/43 (53%) responders in each group attained CR respectively. There were no differences in OR rates in both groups based on concurrent EPaG exposure: 61% vs. 46% with and without EPaG, respectively, in the OLDER group (p=0.5) and 74% vs 60%, respectively, (p=0.38) in the YOUNG group. On logistic regression analysis using baseline platelet counts, PB lymphocyte (%), D-A-T mutations, karyotype, and EPaG use as covariates, none affected the odds of OR in the 2 groups. The median TTR was 111 days (range, 10-323 days) and 177 days (51-410) in YOUNG AND OLDER groups, respectively; and this was not affected by EPaG use in either group. At a median follow of 38 months (mos) from ATG initiation (53 mos for the OLDER group and 32 mos for the YOUNG group), the median RFS was 49 mos and 39 mos (p=0.6) and median OS 55 vs. not reached (NR) (p <0.0001) in OLDER and YOUNG groups respectively (Fig.1). Significantly more pts in the YOUNG group underwent a subsequent SCT (19% vs. 5%) due to loss of response/ no response, possibly accounting for the higher OS rates. Rates of transformation to MDS or AML was 5% in both groups. Conclusion: Frontline ATG based IST in older pts with AA is a feasible and safe treatment option with promising response rates of 56% and median RFS more than 4 years; figures which are comparable to younger pts with AA treated with IST. The overall risks of transformation to MDS/AML on long term follow-up remain low (≈5%). Further studies assessing the response of the ATG+EPaG combination in these pts and the possibilities of clonal evolution with time needs to be conducted. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Elevated systemic immune inflammation level increases the risk of total and cause-specific mortality among patients with chronic kidney disease: a large multi-center longitudinal study.

Chronic kidney disease (CKD) is inherently a complex immune-inflammatory condition, and heightened inflammation and immune dysfunction are closely related to an increased risk of death. However, evidence regarding the relationship between immune-inflammatory levels and all-cause, cardiovascular, and cancer mortality among patients with CKD is scarce. Patients with non-dialysis dependent CKD undergoing coronary angiography (CAG) were included from five Chinese tertiary hospitals. Systemic immune inflammation index (SII) was calculated by multiplying peripheral platelet count with neutrophil-to-lymphocyte ratio, and patients were categorized into four groups by SII quartiles. Cox regression models and competing risk Fine and Gray models were used to examining the relationships between SII levels and all-cause, cardiovascular, and cancer mortality. A total of the 19,327 patients (68.8 ± 10.03years, female 32.0%) were included in this study. During a median follow-up of 4.5years, 5,174 deaths occurred, including 2,861 cardiovascular deaths and 375 cancer deaths. Controlling for confounders, all-cause mortality (Q2, Q3, Q4: hazard ratio(HR) [95 CI%] = 1.15 [1.06-1.26], 1.30 [1.19-1.42], 1.48 [1.35-1.62], respectively; p for trend < 0.001) and cardiovascular mortality (Q2, Q3, Q4: HR [95 CI%] = 1.16 [1.03-1.31], 1.40 [1.24-1.58], 1.64 [1.44-1.85], respectively; p for trend < 0.001) increased with higher SII levels, and SII levels was related to cancer mortality comparing last quartile to first quartile of SII (Q2, Q3, Q4: HR [95 CI%] = 1.12 [0.83-1.52], 1.22 [0.90-1.67], 1.50 [1.09-2.08], respectively; p for trend < 0.001). Elevated immune inflammation level on admission was an independent risk factor for all-cause, cardiovascular, and cancer mortality among CKD patients. Further research is needed to validate the predictive value of SII for mortality risk among CKD patients.

L1CAM expression in either metastatic brain lesion or peripheral blood is correlated with peripheral platelet count in patients with brain metastases from lung cancer.

Systemic immune-inflammation states across the heterogeneous population of brain metastases from lung cancer are very important, especially in the context of complex brain-immune bidirectional communication. Previous studies from our team and others have shown that the L1 cell adhesion molecule (L1CAM) is deeply involved in the aggressive phenotype, immunosuppressive tumor microenvironment (TME), and metastasis during multiple malignancies, which may lead to an unfavorable outcome. However, little is known about the relationship between the L1CAM expression and the systemic immune-inflammation macroenvironment beyond the TME in brain metastases from lung cancer. Two cohorts of patients with brain metastases from lung cancer admitted to the National Cancer Center, Cancer Hospital of Chinese Academy of Medical Sciences, were studied in the present research. The L1CAM expression in cranial metastatic lesions by immunohistochemistry was explored in patients treated with neurosurgical resection, whereas the L1CAM expression in peripheral blood by ELISA was tested in patients treated with non-surgical antitumor management. Furthermore, based on peripheral blood cell counts in the CBC test, six systemic immune-inflammation biomarkers [neutrophil count, lymphocyte count, platelet count, systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio] were calculated. Then, the relationship between the L1CAM expression and these systemic immune-inflammation biomarkers was analyzed. In addition, these systemic immune-inflammation biomarkers were also used to compare the systemic immune-inflammation states in two cohorts of patients with brain metastases from lung cancer. Positive L1CAM expressions in the metastatic brain lesions were accompanied with significantly increased peripheral platelet counts in patients treated with neurosurgical tumor resection (P < 0.05). Similarly, in patients treated with non-surgical antitumor management, L1CAM expressions in the peripheral blood were positively correlated with peripheral platelet counts (P < 0.05). In addition, patients prepared for neurosurgical tumor resection were presented with poorer systemic immune-inflammation states in comparison with the one with non-surgical antitumor management, which was characterized by a significant increase in peripheral neutrophil counts (P < 0.01), SII (P < 0.05), and NLR (P < 0.05) levels. The L1CAM expression in either the metastatic brain lesion or peripheral blood is positively correlated with the peripheral platelet count in patients with brain metastases from lung cancer. In addition, brain metastases that are prepared for neurosurgical tumor resection show poor systemic immune-inflammation states.

Administration of recombinant human thrombopoietin is associated with alleviated thrombocytopenia in adult intensive care unit patients with pneumonia: A single-center retrospective study.

Background: Recombinant human thrombopoietin (rhTPO) is reported to stimulate platelet production and increase peripheral platelet counts; it is primarily used to manage chemotherapy-induced thrombocytopenia and idiopathic thrombocytopenic purpura. However, the effect of rhTPO in patients with pneumonia and thrombocytopenia remains uncertain. Objective: To assess the association of rhTPO and platelet counts in ICU patients with pneumonia and thrombocytopenia. Materials and Methods: A retrospective cohort study was performed in the ICU department, Nanfang Hospital, Southern Medical University, Guangzhou, China. From January 2016 to April 2021, patients with pneumonia and thrombocytopenia were allocated to two groups—the rhTPO and no-rhTPO groups—according to whether they received rhTPO treatment or not during their ICU stay. Demographical and clinical data were collected and analyzed using statistical software; p < 0.05 was considered statistically significant. Results: Out of 327 patients, 149 were in the rhTPO group and 178 were in the no-rhTPO group. Within the first 7 days, platelet counts increased more for patients in the rhTPO group compared with those in the no-rhTPO group (99.21 ± 102.613 vs. 2.08 ± 43.877, p = 0.000). The clinical recovery rate of platelets increased within 7 days (65.8 vs. 18.5%, p = 0.000) and, after 7 days of enrollment, hemorrhagic scores decreased more apparently in the rhTPO group (2.81 ± 2.856 vs. 1.16 ± 2.123, p = 0.000). Further, bleeding events ceased in 66.7% of the patients in the rhTPO group compared with 37.3% of the patients in the no-rhTPO group (p = 0.000). Less red-blood-cells transfusions were needed in the rhTPO group (3.639 ± 4.630 vs. 5.818 ± 6.858, p = 0.009). Furthermore, through logistic regression, rhTPO administration was found to be an independent indicator that affected the platelet recovery rate within 7 days. Conclusion: This study finds that rhTPO administration is associated with increased platelet counts, alleviated bleeding, and reduced blood transfusion. For patients with pneumonia and thrombocytopenia, rhTPO may be an effective therapeutic drug; however, more RCT trails are needed to confirm our observation.

Reticulocyte Count and Platelet Count as Predictors of Morphological Remission/Hemopoitic Recovery in Acute Lymphoblastic Leukemia (ALL) after Induction Chemotherapy

Objectives: To determine the predictive values of reticulocyte and platelet count for remission in cases of acute lymphoblastic leukemia after induction therapy. Materials and Methods:This cross-sectional observational study was conducted in the department of hematology, MTI Hayatabad Medical Complex, Peshawar. All cases of ALL referred to the department for remission after taking induction therapy, irrespective of age and gender were included. Relevant information wascollected on a predesigned proforma prepared in accordance with the objectives of the study. Results: A total of 84 cases referred for remission were included, 56(66.7%) were males and 28 (33.3%) were females. 50(59.5%) cases were in the age range of 5-18 years. The mean with a standard deviation of the age of patients was 15+ 4 years. 75(89.3%) of the cases were classified into ALL-1) by FAB classification. 50(59.5%) of the referred cases had achieved morphological remission by bone marrow aspiration. There was a statistically significant rise in Platelet count of the remission vs non-remission cases (p-0.001). Again there was a statistically significant difference in the retic count of the cases with remission (p-0.05). We observed a statically significant downhill moderate correlation ofretic count with remission (in termsof blast count of BM aspiration) (p-0.04, r:-0.32). Platelet count also had an inverse significant correlation with remission ( p-0.01, r:-0.37). The diagnostic roles of the peripheral platelet count and retic yielded an area under curves of (0.768 and 0.648 respectively) to predict remission.We observed that the retic count and platelet count havebeen shown to have strong predictive valuesfor remission in ALL with interaction values of (R= 0.28**, ΔR²=0.02, p=0.08). Similarly, an increase in platelet also has a strong predictive value for remission in ALL cases with interaction values of (R= 0.41**, ΔR²=0.16, p=0.001) Conclusion: In ALL cases of post-induction therapy, The peripheral blood reading for an increase in Retic and platelet count predictsremission with 95% confidence. These values if strictly observed can reduce the frequency of invasive procedures like bone marrow aspiration. Keywords: ALL, Remission, Reticulocyte count, Platelet count.

Clinical characteristics in immune thrombocytopenia patients after COVID-19 vaccination

ABSTRACT It is well documented that COVID-19 vaccines greatly reduce the severity and complications of SARS-CoV-2 infection. However, it has been reported that COVID-19 related vaccines may induce or exacerbate autoimmune hematological disorders, for example, a decrease in platelet numbers characteristic of immune thrombocytopenia (ITP). To investigate this, we retrospectively reported, for the first time, the clinical characteristics of 42 ITP patients after COVID-19 vaccination in southwest China. Of the 42 patients, 28 patients were historically diagnosed ITP, and their platelet counts (PC) decrease mainly occurred after the first-dose vaccinations. The average PC after vaccination was 39.5 × 109/L and recovered to an average of 80.6 × 109/L after treatment. Efficacy of treatment was 90%, and only 10% maintained low PC at the third month of treatment. More interestingly, of the 42 patients, 14 were newly diagnosed ITP following vaccination. Of these 14 patients, 6 patients (43%) were found PC deterioration after the first vaccine dose, and 7 patients (50%) after the second dose. Fortunately, the peripheral PC of all 14 patients recovered significantly after treatment, and the average PC was 139.4 × 109/L, including 8 CRs (complete response) and 6 PRs (partial response). Notably, 9 of the 14 cases were found to have abnormal immune indices when thrombocytopenia diagnosed. No severe organ hemorrhage was found in either subgroup. These results are reassuring the vaccine safety for ITP patients, in that the risks of aggravating thrombocytopenia by COVID-19 vaccination do exist, but it was transient and can be effectively controlled through intensive clinical monitoring and management.