Peripheral Platelet Counts Research Articles

Optimizing Response to Enasidenib with Dose Escalation: Case Series

Background: Isocitrate dehydrogenase enzymes catalyze the conversion of isocitrate to alpha-ketoglutarate. Mutated IDH enzymes generate the "oncometabolite" 2-hydroxyglutarate (2-HG), which inhibits TET2 function. IDH2 mutations have been reported in 9% to 19% of acute myeloid leukemia (AML) cases. Inhibition of the mutant IDH2 enzyme led to decreased 2-HG levels and induced myeloid differentiation in IDH2 mutant AML. Enasidenib, a small-molecule inhibitor of mutant IDH2, was approved in 2017, after a successful phase I/II trial showing an overall response rate (ORR) of 40.3% in relapsed/refractory (R/R) disease, with 19.3% of patients achieving complete remission (CR). A Phase III trial is currently ongoing. It targets the mutant IDH2 variants R140Q, R172S, and R172K; at an approved dose of 100 mg oral daily dose. At higher doses the drug was less tolerated, however, few subjects received dose modification at the 650 mg daily dose group; these events did not qualify as a dose-limiting toxicity (DLT). In this descriptive study, we are reporting a case series of R/R AML, with an IDH2 mutation, that are treated with escalated dose enasidenib. Method: This case series is based on retrospective observations of patients with R/R IDH2 mutant AML since January 2017, who are treated with enasidenib. We are reporting two cases treated with an escalated dose of 200 mg daily. We included patients with intermediate to poor-risk AML, who received at least one prior line of therapy, started on standard dose enasidenib (100 mg daily) for a minimum of 6 months and followed until disease relapse or death. We excluded patients who are primarily resistant to enasidenib (AML risk stratification and response evaluation by ELN-Leukemia NET. IDH2 mutations were identified by a local diagnostic laboratory that is regulated under CLIA through PCR which is validated to detect 10% or more mutant allele frequency. To quantify IDH2 variant frequency, confirmatory testing was performed via ARUP next-generation sequencing panel (NGS). Results: Here we report the descriptive outcomes of 2 cases from a single institution, who were treated with escalated dose enasidenib (200 mg oral daily) for R/R AML with an IDH2 mutation. The first case describes a 65-year-old female diagnosed with poor-risk AML in the setting of pancytopenia with bone marrow evaluation consistent with the background of erythroid and granulocytic dysplasia, with normal karyotype analysis. The patient has treated with induction chemotherapy and 2 cycles consolidation that was complicated with bacterial infections, prolonged hospitalization, and profound deconditioning led to stopping treatment. After 18 months of surveillance, repeat bone marrow evaluation for new-onset pancytopenia revealed relapsed AML with evidence of IDH2 mutation at codon 140, with a variant frequency of 36.9% by NGS. The case was started on enasidenib at 100 mg oral daily dose. After 6 months of therapy, the patient continued to be cytopenic, repeated bone marrow evaluation showed residual AML with IDH2 variant frequency of 27.6%. The decision was made to increase the enasidenib dose to 200 mg daily. With follow up for another 5 months on the escalated dose, the patient achieved hematologic complete response (hCR) with normalization of peripheral platelet count and ANC. [Figures 1-2] The patient maintained hCR for another 5 months on 200 mg enasidenib daily until she died from COVID-19 infection. The second case describes a 59-year-old female with poor-risk AML in the setting of leukocytosis, with bone marrow evaluation consistent with the background of megakaryocytic dysplasia and karyotype analysis positive for monosomy 7. The patient was treated with induction chemotherapy and failed to respond. Repeat bone marrow evaluation showed primary refractory disease with positive IDH2 mutation at codon 140 with a variant frequency of 40.7%. Treatment with 100 mg enasidenib was started. The patient maintained a partial response for 6 months, then peripheral blasts counts started to gradually increase. The decision was made to increase enasidenib dose to 200 mg daily, which improved peripheral blasts within one month of escalated dose therapy. [Figure 3] The patient maintained a response to therapy for another 3 months before she relapsed. Conclusion: Our limited data showed that initial response to standard dose enasidenib could potentially be optimized by dose escalation to 200 mg daily. Disclosures No relevant conflicts of interest to declare.

Analysis of the clinical value of ultrasound attenuation parameters in evaluating liver steatosis degree in patients with chronic liver disease

Objective: To evaluate the clinical value of ultrasound attenuation parameters (UAP) in diagnosing the liver steatosis degree in patients with chronic liver disease, and to explore the relevant factors that affect UAP detection values. Methods: 130 cases with chronic liver disease diagnosed as liver steatosis by liver biopsy during January 2014 to May 2019 were selected from the Hepatology Department of Integrated Traditional Chinese and Western Medicine of the Third Hospital of Hebei Medical University. UAP and liver stiffness (LSM) were detected by iLivTouch, and the body mass index (BMI) was calculated. Simultaneously, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), total bilirubin (TBil), triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) levels and peripheral platelet (PLT) counts were measured. The correlation between UAP and liver steatosis was analyzed based on the liver histopathological results. SPSS 21.0 statistical software was used for statistical analysis. Receiver operating characteristic curve (ROC) was used to analyze the accuracy and specificity of UAP in the diagnosis of liver steatosis in patients with chronic liver disease. Spearman's rank correlation analysis was used to study the relevant factors affecting UAP value. Results: The histopathological changes of liver biopsy showed that there were 43 cases of grade F1, 47 cases of F2, 32 cases of F3 and 8 cases of F4. UAP and BMI (r = 0.363, P < 0.001), and UAP and liver steatosis degree (r = 0.380, P < 0.001) were positively correlated. BMI and the liver steatosis degree were independent predictors of UAP value. The cut-off points for UAP to diagnose liver steatosis degree were 276 dB/m for F≥2, 288 dB/m for F≥2, 293 dB/m for F≥3, and F = 4, respectively. The sensitivity and specificity was 0.379, 0.500, 0.750, and 0.930, 0.922, 0.836, respectively. Conclusion: Ultrasonic attenuation parameters cannot only determine the presence or absence of liver steatosis in patients with chronic liver disease, but also can better assess the liver steatosis degree.

Clinical Analysis of 269 Ph Chromosome-Negative Myeloproliferative Neoplasms Patients Stratified by Age

To investigate the difference of clinical characteristics between young patients(age≤40 years old) and middle-older patients(age>40 years old) with the myeloproliferative neoplasms（MPN）. The clinical data (gene mutations， peripheral blood routine examinations， imaging examination and past history) of 269 MPN patients was collected and analyzed. In essential thrombocythemia (ET) group, the proportion of triple-negative type in young patients was higher than that in middle-older group, while the peripheral white blood cell（WBC） and platelets（PLT） counts in the first visit were lower. In polycythemia vera (PV) group, the total detection rate of JAK2V617F (80.65%) was lower than that of other research reports. Young patients with PV showed the lower JAK2V617F rate and lower WBC count, compared with the middle-older aged patients. Both CALR and MPL mutations were not found in PV patients. There was only 1 primary myelofibrosis (PMF) patient aged <40 years old. 91.67% of the patients merged splenomegaly and this rate was higher than that of ET or PV patients. It was found that there were a diagnosed familial MPN family and an undiagnosed family， and the youngest patient was only 8 years old. The second-generation gene sequencing detection for them was not carried out. Age is an important reference index in the assessment of risks. The MPN patients with different age and types show much difference in gene mutations, peripheral blood cell counts, thrombotic events and sizes of spleen. The onset ages of patients with familial MPN trends to be generational younger.

Hepatocellular Carcinoma Within the Milan Criteria: A Novel Inflammation-Based Nomogram System to Assess the Outcomes of Ablation.

ObjectivesFew studies based on pretreatment inflammation-based scores focused on assessing the prognosis of hepatocellular carcinoma (HCC) patients within the Milan Criteria after ablation. This study aimed to construct a nomogram based on a novel inflammation-based score for those patients.MethodsA total of 635 HCC patients within the Milan Criteria after ablation meeting the inclusion and exclusion criteria were included in the study. The novel inflammation-based score—Albumin-Platelet Score (APS)—was constructed by Cox proportional-hazards modeling. The nomogram based on APS was constructed by multivariate analysis and the “rms” R package. The performance of the APS and the nomogram were assessed by time-dependent receiver operating characteristic and the concordance index (C-index).ResultsThe APS was an integrated indicator based on peripheral albumin level and platelet counts, which was significantly superior to other inflammation-based scores (neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, Prognostic Nutritional Index, modified Glasgow Prognostic Score, Glasgow Prognostic Score, Prognostic Index, and C-reactive protein/albumin ratio) in predicting the long-term prognosis of those patients undergoing ablation (P < 0.05). An easy-to-use nomogram based on three pretreatment clinical variables (i.e., the APS, tumor size, and age) was constructed and further improved significantly the performance in predicting the prognosis in patients within the Milan Criteria after ablation (P < 0.05). The C-index of nomogram for overall survival was 0.72 (95% CI 0.66, 0.77). The calibration plots with 1000 cycles of bootstrapping were well matched with the idealized 45° line.ConclusionThe APS was a better inflammation-based prognostic system than others. Also, the nomogram based on the APS improved the performance of predicting the prognosis of HCC patients within the Milan Criteria after ablation.

Ma-Nuo-Xi decoction has an immunostimulating effect in cyclophosphamide-immunosuppressed mice

Ma-Nuo-Xi decoction (MNXD), as well as its hundreds of derivative preparations, has been used in Tibetan medicine since the 14th century. MNXD is in accordance with the theory of treatment determination based on syndrome differentiation. This study aimed to compare the effect of the auxiliary MNXD prescription (MNXD-AD) with that of the basic MNXD prescription (MNXD-BD) on the immunostimulating activity of MNXD. The immunopotentiation of MNXD, MNXD-BD, and MNXD-AD was evaluated using a cyclophosphamide (CTX)-immunosuppressed mouse model. Their influences on non-specific and specific immunity were evaluated using immune organ indexes, peripheral white blood cell (WBC) count, red blood cell (RBC) count, platelet count, phagocytosis, macrophage-secreted nitric oxide (NO) and cytokines, natural killer (NK) cytotoxic activity, lymphocyte proliferation, serum cytokines, splenic T-lymphocyte subpopulations, and quantitative hemolysis of sheep red blood cell (QHS SRBC) assays. MNXD, MNXD-BD, and MNXD-AD increased the spleen and thymus indexes, as well as the peripheral WBC, RBC, and platelet counts. They also promoted phagocytosis, NO and cytokine secretion from macrophages, NK cytotoxic activity, and lymphocyte proliferation, and also raised the CD4+ /CD8+ T-cell ratio, serum cytokine concentrations, and haemolysin formation in CTX-treated immunosuppressed mice. Compared with MNXD-BD and MNXD-AD, MNXD was superior in restoring the phagocytic index, concanavalin A (ConA)-induced T-lymphocyte proliferation, NO secretion from macrophages, and haemolysin formation, as well as the levels of interleukin 1 beta (IL-1β), and serum interleukin-2 (IL-2) and interferon gamma (INF-γ). MNXD, MNXD-BD, and MNXD-AD have excellent immunostimulating and myelosuppression-restoring activities on CTX-immunosuppressed mice. Among them, MNXD-AD might be an immunomodulator, which may happen to be in line with the clinical experience of Tibetan medicine physicians of using it to promote the efficacy of MNXD-BD.

Prognostic value of platelet recovery degree before and after achieving minimal residual disease negative complete remission in acute myeloid leukemia patients

BackgroundRisk stratification and prognosis prediction of acute myeloid leukemia (AML) are largely dependent on pre-treatment information. However, post-treatment data also provides much useful information. In this retrospective study, we explored whether the level of blood count recovery before and after the first minimal residual disease (MRD) negative complete remission (CR) is relevant to clinical outcomes of AML patients.MethodsFor each included patient, peripheral platelet counts were measured on the day before initial treatment (PLTpre), whereas platelet peak values (PLTpeak) were recorded after marrow recovery following the chemotherapy course inducing the first MRD-negative CR. The difference (DPLT) between these two values (DPLT = PLTpeak−PLTpre) was calculated. X-tile software was utilized to establish the optimal cut-point for DPLT, which was expected to distinguish CR patients with different clinical outcomes. A cross validation analysis was conducted to confirm the robustness of the established cut-point. The results were further tested by a Cox multivariate analysis.ResultsThe optimal cut-point of DPLT was determined as 212 × 109/L. Patients in high DPLT group were observed to have a significantly better PFS (p = 0.016) and a better OS (without statistical significance, p = 0.106). Cox multivariate analysis showed that higher DPLT was associated with longer PFS (HR = 2.894, 95% CI: 1.320–6.345, p = 0.008) and longer OS (HR = 3.077, 95% CI: 1.130–8.376, p = 0.028).ConclusionPlatelet recovery degree before and after achieving MRD-negative CR (DPLT) is a potential predictor of clinical outcomes in CR patients. Higher DPLT value is associated with longer PFS and OS. Our findings may help to develop simple methods for AML prognosis evaluation.

Anxiety and depression in COVID-19 survivors: Role of inflammatory and clinical predictors

Infection-triggered perturbation of the immune system could induce psychopathology, and psychiatric sequelae were observed after previous coronavirus outbreaks. The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. We investigated the psychopathological impact of COVID-19 in survivors, also considering the effect of clinical and inflammatory predictors.We screened for psychiatric symptoms 402 adults surviving COVID-19 (265 male, mean age 58), at one month follow-up after hospital treatment. A clinical interview and a battery of self-report questionnaires were used to investigate post-traumatic stress disorder (PTSD), depression, anxiety, insomnia, and obsessive-compulsive (OC) symptomatology. We collected sociodemographic information, clinical data, baseline inflammatory markers and follow-up oxygen saturation levels.A significant proportion of patients self-rated in the psychopathological range: 28% for PTSD, 31% for depression, 42% for anxiety, 20% for OC symptoms, and 40% for insomnia. Overall, 56% scored in the pathological range in at least one clinical dimension. Despite significantly lower levels of baseline inflammatory markers, females suffered more for both anxiety and depression. Patients with a positive previous psychiatric diagnosis showed increased scores on most psychopathological measures, with similar baseline inflammation. Baseline systemic immune-inflammation index (SII), which reflects the immune response and systemic inflammation based on peripheral lymphocyte, neutrophil, and platelet counts, positively associated with scores of depression and anxiety at follow-up.PTSD, major depression, and anxiety, are all high-burden non-communicable conditions associated with years of life lived with disability. Considering the alarming impact of COVID-19 infection on mental health, the current insights on inflammation in psychiatry, and the present observation of worse inflammation leading to worse depression, we recommend to assess psychopathology of COVID-19 survivors and to deepen research on inflammatory biomarkers, in order to diagnose and treat emergent psychiatric conditions.

Early-stage predictors of the acute phase duration in uncomplicated COVID-19 pneumonia.

ObjectiveIn this study, we aimed to highlight the common early‐stage clinical and laboratory variables independently related to the acute phase duration in patients with uncomplicated coronavirus disease (COVID‐19) pneumonia.MethodsIn hospitalized patients, the acute phase disease duration was followed using the Brescia‐COVID respiratory severity scale. Noninvasive ventilation was administered based on clinical judgment. Patients requiring oropharyngeal intubation were excluded from the study. For parameters to be measured at the hospital entrance, age, clinical history, National Early Warning Score 2 (a multiparametric score system), partial pressure of oxygen in arterial blood/fraction of inspired oxygen (P/F ratio), C‐reactive protein, and blood cell count were selected.ResultsIn 64 patients, age (direct relationship), P/F, and platelet number (inverse relationship) independently accounted for 43% of the acute phase duration of the disease (P < .001).ConclusionsFor the first time, the present results revealed that the acute phase duration of noncomplicated pneumonia, resulting from severe acute respiratory syndrome coronavirus 2, is independently predicted from a patient's age, as well as based on the hospital entrance values of P/F ratio and peripheral blood platelet count.

Evaluation of risk factors for postoperative complications in rectal cancer patients.

&lt;b&gt;Introduction:&lt;/b&gt; The complications of surgical treatment for rectal cancer, particularly anastomotic leaks after anterior resection, are a significant clinical problem. We retrospectively analysed preoperative factors that may affect the occurrence of complications. &lt;br&gt;&lt;b&gt;Meterial and Methods:&lt;/b&gt; A total of 392 rectal cancer patients were included in a retrospective analysis. A total of 257 anterior resections (AR) and 135 abdominoperineal resections (APR) were performed. The risk factors for early postoperative complications were analysed by logistic regression and receiver operating characteristic curves. &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; The significant risk factors for severe complications (grade 3B and higher on the Clavien-Dindo scale) in the multivariate analysis were neutrophil to lymphocyte ratio &gt; 5 (P = 0.047) in the AR group, age of the patients (P = 0.031) in the APR group, and coronary artery disease in both groups (P = 0.03, P = 0.011, respectively). There were no risk factors for anastomotic leaks in the AR group before the analysis was divided into early and late leaks. In the univariate analysis, the statistically significant risk factors for early leaks were preoperative neutrophil to lymphocyte ratio &gt; 5 and peripheral blood platelet count, while late leaks were associated with coronary artery disease; however, in the multivariate analysis, these factors were not statistically significant. &lt;br&gt;&lt;b&gt;Conclusions:&lt;/b&gt; The risk factors for severe postoperative complications were neutrophil to lymphocyte ratio &gt; 5, advanced age of the patients and coronary artery disease. The different risk factors for early and late anastomotic leaks after anterior resection may indicate their different aetiologies.

The role of AGK in thrombocytopoiesis and possible therapeutic strategies

AbstractAbnormal megakaryocyte development and platelet production lead to thrombocytopenia or thrombocythemia and increase the risk of hemorrhage or thrombosis. Acylglycerol kinase (AGK) is a mitochondrial membrane kinase that catalyzes the formation of phosphatidic acid and lysophosphatidic acid. Mutation of AGK has been described as the major cause of Sengers syndrome, and the patients with Sengers syndrome have been reported to exhibit thrombocytopenia. In this study, we found that megakaryocyte/platelet-specific AGK-deficient mice developed thrombocytopenia and splenomegaly, mainly caused by inefficient bone marrow thrombocytopoiesis and excessive extramedullary hematopoiesis, but not by apoptosis of circulating platelets. It has been reported that the G126E mutation arrests the kinase activity of AGK. The AGK G126E mutation did not affect peripheral platelet counts or megakaryocyte differentiation, suggesting that the involvement of AGK in megakaryocyte development and platelet biogenesis was not dependent on its kinase activity. The Mpl/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (Stat3) pathway is the major signaling pathway regulating megakaryocyte development. Our study confirmed that AGK can bind to JAK2 in megakaryocytes/platelets. More interestingly, we found that the JAK2 V617F mutation dramatically enhanced the binding of AGK to JAK2 and greatly facilitated JAK2/Stat3 signaling in megakaryocytes/platelets in response to thrombopoietin. We also found that the JAK2 JAK homology 2 domain peptide YGVCF617CGDENI enhanced the binding of AGK to JAK2 and that cell-permeable peptides containing YGVCF617CGDENI sequences accelerated proplatelet formation. Therefore, our study reveals critical roles of AGK in megakaryocyte differentiation and platelet biogenesis and suggests that targeting the interaction between AGK and JAK2 may be a novel strategy for the treatment of thrombocytopenia or thrombocythemia.

Elevated Platelet Count Predicts Poor Prognosis in Breast Cancer Patients with Supraclavicular Lymph Node Metastasis.

BackgroundMore and more studies show that platelets are closely related to the occurrence and development of tumors. This study aims to explore the predictive value of peripheral blood platelet count on the prognosis of breast cancer patients with ipsilateral supraclavicular lymph node (ISLN) metastasis.MethodsEighty-five breast cancer patients with ISLN metastasis in the Affiliated Cancer Hospital of Zhengzhou University were collected retrospectively in this study. Chi-square test was used to analyze the correlation between clinical pathological data and platelet count. DFS rate was estimated by K-M curve and Log Rank test was performed. Univariate and multivariate Cox regression were used to determine the prognostic value of platelets. Time-dependent Cox regression was used to further analyze the correlation between peripheral blood platelets and prognosis to determine the stability of the results.ResultsThe pathological complete response rate of ISLN after neoadjuvant chemotherapy (NAC) was 51.8%. Platelet count was correlated with PR status of breast cancer at first visit (P=0.01). After a median follow-up of 30 months, multivariate Cox analysis showed that high platelet count (HR=3.18, 95% CI=1.13–8.93, P=0.028), premenopausal status (HR=0.40, 95% CI=0.17–0.97, P=0.043), and ISLN pathological failure (HR=0.25 95%, CI=0.10–0.62, P<0.01) were associated with poor prognosis. K-M curve analysis showed that the prognosis of patients with a high platelet count was worse than that of patients with low platelet count (HR=5.32, 95% CI=2.41–11.75, P<0.01). To further verify the stability of this result, multivariate time-dependent Cox model also suggested that higher platelet level was related to poor prognosis (HR=1.009, 95% CI=1.003–1.016, P<0.01). Meanwhile, menopausal status (HR=0.32, 95% CI=0.14–0.76, P=0.01) and sPCR (HR=0.29, 95% CI=0.12–0.70, P=0.01) were also independent predictors of DFS.ConclusionPlatelets have important predictive value for the prognosis of breast cancer patients with ISLN metastasis, which indicates that platelet count can be used to distinguish high-risk patients so as to obtain clinical benefits.

Systemic Immune-Inflammation Index Predicts Overall Survival in Patients with Gastric Cancer: a Propensity Score–Matched Analysis

BackgroundThe systemic immune-inflammation index (SII), integrated by peripheral lymphocyte, neutrophil, and platelet counts, is used as an objective biomarker that reflects the balance between host inflammatory and immune response status in cancer patients. Herein, we examined the prognostic significance of SII in gastric cancer patients. MethodsWe retrospectively reviewed data of 415 patients who underwent curative laparoscopic gastrectomy using propensity score–matched (PSM) analysis. The prognostic value of SII was compared between two groups based on SII values: low SII group (SII < 661.9) and high SII group (SII ≥ 661.9). ResultsIn multivariate analysis, the American Society of Anesthesiologists physical status (ASA-PS) (p < 0.001), tumor differentiation (p = 0.019), pathological stage (p = 0.046), carcinoembryonic antigen (CEA) level (p < 0.001), SII (p = 0.006), and operative procedure (p = 0.009) were independent prognostic factors of overall survival (OS) in the overall PSM cohort. The log-rank test demonstrated that patients with a high SII had significantly worse OS than did those with low SII (p = 0.002). In age-stratified subgroups analysis (< 65/≥ 65 years), multivariate analysis revealed that ASA-PS (p < 0.001), tumor differentiation (p = 0.019), CEA level (p = 0.008), SII (p = 0.013), and operative procedure (p = 0.026) were independent prognostic factors of OS in the elderly group. Similarly, elderly patients with a high SII had significantly worse OS than did those with a low SII (p = 0.009). Meanwhile, SII was not an independent prognostic factor of OS, and no significant association was observed between SII and OS in non-elderly patients. ConclusionsSII was an independent prognostic indicator in gastric cancer patients, especially in the elderly population.

Host Factors Independently Associated With Prognosis in Patients With Oral Cavity Cancer

The association and interaction of host characteristics with prognosis in patients with oral cavity squamous cell carcinoma (OSCC) are poorly understood. There is increasing evidence that host characteristics are associated with treatment outcomes of many cancers. To examine the host factors associated with prognosis in patients with OSCC and their interactions to create a numerical index that quantifies the prognostic capacity of these host characteristics. This retrospective cohort study included patients with OSCC treated surgically at a tertiary care center from January 1, 1998, to December 31, 2015. From a departmental OSCC database of 1377 previously untreated patients, 68 patients with missing data on any host variable of interest within a month before the start of treatment were excluded, leaving 1309 patients. Data analysis was performed from October 21, 2019, to December 10, 2019. Primary surgery for OSCC. Overall survival (OS) was the primary end point, and disease-specific survival (DSS) was the secondary end point. Optimal cutoffs for each variable were identified using recursive-partitioning analysis with the classification and regression tree method using OS as the dependent variable. Body mass index (BMI) and pretreatment peripheral blood leukocyte count, platelet count, hemoglobin level, and albumin level were analyzed. A host index (H-index) was developed using independent factors associated with OS. A total of 1309 patients (731 [55.8%] male; mean [SD] age, 62 [14.3] years) participated in the study. When including all the host-related factors in a multivariable analysis, all except BMI (hazard ratio [HR], 1.14; 95% CI, 0.80-1.63) were independently associated with outcomes. For example, compared with a hemoglobin level of 14.1 g/dL or greater, the HR for a level of 12.9 to 14.0 g/dL was 1.42 (95% CI, 1.13-1.77) and for a level of 12.8 g/dL or less was 1.51 (95% CI, 1.18-1.94), and compared with an albumin level of 4.3 g/dL or greater, the HR for a level of 3.7 to 4.2 g/dL was 1.18 (95% CI, 0.95-1.45) and for a level of 3.6 g/dL or less was 3.64 (95% CI, 2.37-5.58). An H-index of 1.4 or less was associated with a 74% 5-year OS, an H-index of 1.5 to 3.5 with a 65% 5-year OS, and an H-index of 3.6 or higher with a 38% 5-year OS; for DSS, the 5-year survival was 84%, 80%, and 64%, respectively. Compared with patients with an H-index score of 1.4 or less, patients with H-index scores of 1.5 to 3.5 (hazard ratio, 1.474; 95% CI, 1.208-1.798) and 3.6 or higher (hazard ratio, 3.221; 95% CI, 2.557-4.058) had a higher risk of death. The findings suggest that pretreatment values of neutrophils, monocytes, lymphocytes, hemoglobin, and albumin are independently associated with prognosis in patients with OSCC. The interactions between these host factors were incorporated into a novel H-index that quantified the prognostic capacity of host characteristics associated with OSCC.

Signification of Systemic Immune-Inflammation Index for prediction of prognosis after resecting in patients with colorectal cancer.

Systemic inflammatory response has been reported to be associated with prognosis in cancer patients. The aim of this study is to investigate the association between Systemic Immune-Inflammation Index (SII), a novel inflammation-based prognostic score and long-term outcomes among patients with colorectal cancer (CRC) after resection. We retrospectively investigated 733 patients who underwent resection for CRC between January 2010 and December 2014 at the Jikei University Hospital and explored the relationship between SII, calculated by multiplying the peripheral platelet count by neutrophil count and divided by lymphocyte count, and overall survival. In survival analyses, we conducted Cox proportional hazards models, adjusting potential confounders including TNM stage, serum CEA, serum CA 19-9, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and platelet count. In multivariate analysis, age ≥ 65years (p = 0.003), tumor location (p = 0.043), advanced TNM stage (p < 0.001), serum CA 19-9 > 37mU/ml (p < 0.001), and SII (P for trend = 0.017) were independent and significant predictors of poor patient survival. Compared to patients with low SII, those with high and intermediate SII patients had poorer survival (Hazard ratio 2.48; 95% CI 1.31-4.69, Hazard ratio 1.65; 95% CI 0.83-3.27, respectively). The Systemic Immune-Inflammation Index might be an independent and significant indicator of poor long-term outcomes in patients with CRC after resection.

PREDICTORS OF HEMORRHAGIC AND THROMBOTIC COMPLICATIONS OF HEPATOSPLENOMEGALY SYNDROME

Summary. Goal. Investigation of the interactions of coagulation, anticoagulant and fibrinolytic systems with factors of immunoresistance in hepatosplenomegaly syndrome (SHSM).&#x0D; Materials and methods. Materials — сells and blood serum of 58 patients with SHSM against the background of liver cirrhosis complicated by portal hypertension, with the etiological factor — HCV / HBV virus infection (group I, 22 people) and the etiological factor — CMV / VEB virus infection (group II, 36 people), who were admitted to the hospital for bleeding from esophageal varicose veins. Methods - photometric on a biochemical analyzer Stat Fax 1904 Plus (USA). (C3 and C4 components of complement, antithrombin III and plasminogen, concentration of circulating immune complexes (CIC), determination of the coagulation time of venous blood Lee-White, calculation of the prothrombin index, fibrinogen content by the Rutberg gravimetric method. Protein C activity (PrS) by the clotting method on a coagulometer K 3002 Spectramed (Poland). Peripheral blood platelet counts were performed using immersion microscopy according to the Fonio method.&#x0D; Results. Multidirectional changes in the functions of the hemostasis system were revealed: a decrease in antithrombin III activity, protein C content, fibrinogen concentration, a decrease in plasminogen activity, a decrease in platelet counts, an increase in platelet antibodies, an increase in the concentration of the C3 component and a decrease in the C4 component of complement.&#x0D; Conclusions. Hemorrhagic and thrombotic complications of HCV, life-threatening and affecting the tactics and results of surgical and minimally invasive treatment, can occur both in the HCV group on the background of HBV/HCV viral hepatitis, and in the HCV group on the background of herpes virus CMV/VEB infection, but in group I both hemorrhagic and thrombotic complications were dominated by plasma risk factors for and in group II - platelet and immunological (complement component C3) risk factors for hemorrhagic complications, plasma factors of thrombotic complications.

Radiosensitivity-Related Genes and Clinical Characteristics of Nasopharyngeal Carcinoma

Background and purpose: Radioresistance is one of the main obstacles limiting the therapeutic efficacy of chemoradiotherapy (CRT) and favorable patient prognoses, and the molecular mechanisms underlying this type of resistance remain unclear. The purpose of this study was to identify characteristic genes involved in chemoradiotherapy resistance in nasopharyngeal carcinoma (NPC). Materials and methods: Clinicopathological data of 185 patients with NPC treated at Nanfang Hospital of Southern Medical University between January 2013 and December 2014 were retrospectively analyzed. SPSS statistical software was used to analyze the clinicopathological data related to radiotherapy efficacy. Three patients who achieved complete remission and three with disease progression after CRT were selected. Differentially expressed genes (DEGs) were screened via mRNA microarray analysis of primary diagnostic endoscopy specimens. Results: The peripheral blood leukocyte count, platelet count and EBV-DNA copy number in NPC patients who were resistant to radiotherapy were higher than those in NPC patients who were sensitive to radiotherapy. The RobustRankAggreg (RRA) analysis method identified 392 DEGs, and the 66 most closely related genes among the DEGs were identified from the PPI network. Conclusion: The results of this study indicate that screening for DEGs and pathways in NPC using integrated in silico analyses can help identify a series of genetic and clinical signatures for NPC patients treated with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy. Funding Statement: This work was supported by the Clinical Research Startup Program of Southern Medical University by High-level University Construction Funding of Guangdong Provincial Department of Education (LC2019ZD008); the Clinical Research Startup Program of Nanfang Hospital (2018CR021);the National Natural Science Foundation of China (Grant Nos. 81602685 and 81672992); the Science and Technology Projects in Guangdong Province (Grant Nos. 2018-1201-SF-0019 ); the Health & Medical Collaborative Innovation Project of Guangzhou City, China (201803040003); and the Natural Science Foundation of Guangdong Province (Grant No. 2017A030313486); the Natural Science Foundation of Fujian Province (Grant No. 2017J01245). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: The protocol was approved by the ethics committee of Nanfang Hospital and implemented in accordance with the principles of the Declaration of Helsinki. All participants provided informed consent.

Diagnostic Value of miR-34a in Bone Marrow Mononuclear Cells of Acute Myeloid Leukemia Patients.

The current study aims to analyze the expression of miR-34a in bone marrow mononuclear cells (BMMCs) of acute myeloid leukemia (AML) patients and its possible role in the development of leukemia. Real-time fluorescent quantitative PCR was used to detect the expression of miR-34a in bone marrow of 40 patients with initial treatment of AML, 22 patients with complete remission AML, 13 patients with refractory recurrence, 20 patients with non-hematological tumors and healthy persons. Pearson's correlation was performed to analyze the correlation between the expression level of miR-34a and clinical indicators in patients. The expression of miR-34a in the initial treatment group, complete remission group and refractory relapse group of AML patients was higher than that in the control group. In addition, the expression of miR-34a in the complete remission group was higher than that in the initial treatment group. Moreover, the expression of miR-34a in the refractory relapse group was lower than that in the initial treatment group. The expression level of miR-34a in initial treatment AML group was negatively correlated with the number of bone marrow primary immature cells, but not with the number of peripheral blood leukocytes, platelet count, hemoglobin content, age, gender, and chromosomal abnormalities. The expression of miR-34a in bone marrow mononuclear cells of patients with AML was down-regulated and related to tumor load. It may play an important role in the occurrence and development of leukemia and may become a new molecular marker for the diagnosis of AML.

Comparison of the Diagnostic Values of Leukocytes, Neutrophils, Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Distinguishing between Acute Appendicitis and Right Ureterolithiasis.

To compare the diagnostic values of leukocytes, neutrophils, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in distinguishing between acute appendicitis (AA) and right ureterolithiasis (RU). In this retrospective study, 106 patients diagnosed with AA (Appendicitis group) and 33 cases with RU (Ureterolithiasis group) were enrolled due to acute right lower abdominal pain. The levels of peripheral blood leukocyte counts (leukocytes), neutrophil counts (neutrophils), lymphocyte counts (lymphocytes), platelet counts (platelets), NLR and PLR were recorded and compared between the two groups. Student's t-test for independent samples was adopted for comparing the mean between the two groups. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed using the Z-test. The levels of leukocytes, neutrophils, NLR, and PLR were significantly increased in AA compared with RU (all p < 0.01), while there were no significant statistical differences of lymphocytes and platelets (all p > 0.05); moreover, AUC in distinguishing AA from RU was 0.797 (95% confidence interval (CI), 0.721 to 0.861) for leukocytes, 0.814 (95% CI, 0.740 to 0.875) for neutrophils, 0.770 (95% CI, 0.691 to 0.837) for NLR, and 0.608 (95% CI, 0.522 to 0.690) for PLR, and significant differences were observed between PLR and any of the three other parameters (all p < 0.01), while there were no significant statistical differences after pairwise comparison between leukocytes, neutrophils and NLR (all p > 0.05). Finally, the cutoff values were 13.1 × 109/L in distinguishing between AA and RU (specificity 87.88%, sensitivity 63.21%, and Youden index 0.511) for leukocytes, 7.4 x 109/L (specificity 69.70%, sensitivity 83.02%, and Youden index 0.527) for neutrophils, 5.57 (specificity 81.82%, sensitivity 68.87%, and Youden index 0.507) for NLR, and 182.5 (specificity 84.85%, sensitivity 37.74%, and Youden index 0.226) for PLR. Leukocytes, neutrophils, and NLR can demonstrate more accurate and reliable diagnostic values than PLR, suggesting that they are useful and potential biomarkers in distinguishing between AA and RU.

Intraglomerular uptake of platelets in unilateral Masugi nephritis in the rabbit.

The pathogenetic roles of platelets were studied in unilateral progressive Masugi nephritis in the rabbit. On fourteenth day after the injection of anti-kidney serum, peripheral platelet counts, platelet aggregation and platelet aggregation rate were not changed statistically compared with those before the initial injection. The presence of platelet antigen within the glomeruli of the unclamped nephritic kidney suggests the participation in the pathogenesis of glomerular lesion. No significant difference was observed in the intrarenal uptake of 111Indium-labeled platelets between clamped and unclamped kidneys. This is probably due to the possibility of the participation of the very small amount of platelets or the possible decreased renal blood flow in the nephritic side in this model, or the active uptake of platelet not being found in this progressed stage of this model.

Radiolabelling and immunohistochemistry reveal platelet recruitment into lungs and platelet migration into airspaces following LPS inhalation in mice

Platelets are under investigation for their role in host defence and inflammatory lung diseases and have been demonstrated to be recruited to the lung. However, the mechanisms and consequences of platelet recruitment into lungs are poorly understood. We have utilised a murine model to investigate the mechanisms of platelet involvement in lung inflammation induced by intranasal administration of LPS. Our aim was to characterise lung platelet recruitment following LPS inhalation in mice using immunohistochemistry, and non-invasive and invasive radiolabelled platelet tracking techniques. Intranasal administration of LPS caused an increase in lung platelet staining in lung tissue and elicited the recruitment of radiolabelled platelets into the lung. Prior to these responses in the lung, we observed an earlier decrease in blood platelet counts, temporally associated with platelet recruitment to the liver and spleen. Non-invasive measurements of thoracic radioactivity reflected changes in blood counts rather than extravascular lung platelet recruitment. However, both in situ counting of radiolabelled platelets and immunostaining for platelet surface markers showed LPS-induced increases in extravascular platelets into lung airspaces suggesting that some of the platelets recruited to the lung enter air spaces. Intranasal administration of LPS activates the innate immune response which includes a fall in peripheral blood platelet counts with subsequent platelet recruitment to the lung, spleen and liver, measured by immunohistochemistry and radiolabelling techniques.