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Therapeutic Advances in Medical Oncology 2024Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis.
Hetrombopag for the management of chemotherapy-induced thrombocytopenia in patients with advanced solid tumors: a multicenter, randomized, double-blind, placebo-controlled, phase II study.
BACKGROUND
Chemotherapy-induced thrombocytopenia (CIT) increases the risk of bleeding, necessitates chemotherapy dose reductions and delays, and negatively impacts prognosis.
OBJECTIVES
This study aimed to evaluate the efficacy and safety of hetrombopag for the management of CIT in patients with advanced solid tumors.
DESIGN
A multicenter, randomized, double-blind, placebo-controlled, phase II study.
METHODS
Patients with advanced solid tumors who experienced a chemotherapy delay of ⩾7 days due to thrombocytopenia (platelet count <75 × 10/L) were randomly assigned (1:1) to receive oral hetrombopag at an initial dose of 7.5 mg once daily or a matching placebo. The primary endpoint was the proportion of treatment responders, defined as patients resuming chemotherapy within 14 days (platelet count ⩾100 × 10/L) and not requiring a chemotherapy dose reduction of ⩾15% or a delay of ⩾4 days or rescue therapy for two consecutive cycles.
RESULTS
Between 9 October 2021 and 5 May 2022, 60 patients were randomized, with 59 receiving ⩾1 dose of assigned treatment (hetrombopag/placebo arm, = 28/31). The proportion of treatment responders was significantly higher in the hetrombopag arm than in the placebo arm [60.7% (17/28) 12.9% (4/31); difference of proportion: 47.6% (95% confidence interval (CI): 26.0-69.3); odds ratio = 10.44 (95% CI: 2.82-38.65); value (nominal) based on the Cochran-Mantel-Haenszel: <0.001)]. During the double-blind treatment period, grade 3 or higher adverse events (AEs) occurred in 35.7% (10/28) of patients with hetrombopag and 38.7% (12/31) of patients on placebo. The most common grade 3 or higher AEs were decreased neutrophil count [35.7% (10/28) 35.5% (11/31)] and decreased white blood cell count [17.9% (5/28) 19.4% (6/31)]. Serious AEs were reported in 3.6% (1/28) of patients with hetrombopag and 9.7% (3/31) of patients with placebo.
CONCLUSION
Hetrombopag is an effective and well-tolerated alternative for managing CIT in patients with solid tumors.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03976882.
PubMed: 38882443
DOI: 10.1177/17588359241260985 -
ARYA Atherosclerosis Jul 2023The Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) have recently been reported as potentially useful indicators of inflammation. In this...
INTRODUCTION
The Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) have recently been reported as potentially useful indicators of inflammation. In this study, the authors investigated their predictive role for postoperative complications of Coronary Artery Bypass Graft (CABG).
METHOD
This study was conducted on the medical records of patients who had undergone isolated CABG in 2019-2020 in Isfahan, Iran. The baseline clinical characteristics were obtained from medical records. The diagnosis of postoperative Acute Kidney Injury (AKI) was defined based on the Kidney Disease Improving Global Outcomes guideline. The postoperative bleeding amount was measured from the total chest tube output during the Intensive Care Unit (ICU) admission after surgery. NLR and PLR were measured by dividing the neutrophil and platelet counts by the lymphocyte count, respectively. All data were analyzed using the Statistical Package for Social Sciences (SPSS) version 24.
RESULTS
Of 356 patients, data of 280 patients, including 219 males and 61 females, were recruited. The mean age among all patients was 63.78±9.07 years. There were no significant differences between the bleeding group and non-bleeding group regarding NLR (2.33(1.89-2.73) vs. 2.20(1.63-3)) and PLR (119.26(94.41-146.39) vs. 110.26(82.13-136.34)) (p=0.742, p=0.228 respectively). NLR and PLR were significantly higher in AKI-positive patients (P< 0.001 and P=0.002, respectively). Only NLR showed the potential ability to predict postoperative AKI in the crude model (P<0.001) based on the regression tests. Moreover, no significant correlation was seen between both NLR and PLR and hospital stay time, ICU stay time, and in-hospital mortality.
CONCLUSION
The authors found that an increased NLR is associated with a higher risk for AKI after CABG. The authors also found no significant correlations between NLR and PLR with bleeding, hospital stay, ICU stay, and mortality.
PubMed: 38881994
DOI: 10.48305/arya.2022.39237.2834 -
Translational Cancer Research May 2024Progression of chronic liver fibrosis and related increased fibrotic markers are associated with functional liver reserves or patient prognosis as well as tumor factors...
BACKGROUND
Progression of chronic liver fibrosis and related increased fibrotic markers are associated with functional liver reserves or patient prognosis as well as tumor factors in hepatocellular carcinoma (HCC) patients. The aim of this study was to newly clarify the relationship between fibrotic markers and HCC malignant behaviors or its long-term postoperative prognosis by the retrospective cohort study.
METHODS
We examined the relationship between tumor-related factors or six liver fibrosis-associated parameters, including platelet count, hyaluronic acid (HA), Mac-2 binding protein glycosylation isomer (M2BPGi), type IV collagen 7S (T4C7), aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 (Fib-4) index, and clinicopathological parameters, surgical records, and postoperative prognosis in 130 HCC who underwent curative hepatectomy.
RESULTS
Histological fibrosis stage 4 as cirrhosis was in 31%. The platelet count significantly decreased in stage 4 fibrosis and correlated with grade B liver damage (P<0.01). HA levels were significantly increased in multiple HCC, stage 4 fibrosis, and grade B liver damage (P<0.01). T4C7 was significantly increased in patients with post-hepatectomy tumor recurrence compared to those without (P<0.01). Additionally, M2BPGi was significantly higher in stage 4 fibrosis and liver damage grade B, and was significantly associated with poor prognosis (P<0.05). Fib-4 index was significantly higher in patients with liver damage B (P<0.05), and T4C7 alone did not correlate with other five fibrosis markers. Stage 4 fibrosis, higher T4C7, higher M2BPGi, and increased tumor size were significantly associated with shorter cancer-free, overall, and cancer-specific survivals. Higher T4C7, non-met Milan criteria, liver damage B, blood transfusion, and curability C were independently associated with cancer-specific survivals (P<0.05).
CONCLUSIONS
Type IV collagen 7S (T4C7) may reflect not only impaired liver function but also HCC malignant behaviors and patient survivals.
PubMed: 38881924
DOI: 10.21037/tcr-24-94 -
Frontiers in Pharmacology 2024Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary...
Current pharmacological treatments for Ulcerative Colitis (UC) have limitations. Therefore, it is important to elucidate any available alternative or complementary treatment, and Chinese herbal medicine shows the potential for such treatment. As a traditional Chinese herbal medicine, Danshen-related preparations have been reported to be beneficial for UC by improving coagulation function and inhibiting inflammatory responses. In spite of this, the credibility and safety of this practice are incomplete. Therefore, in order to investigate whether Danshen preparation (DSP) is effective and safe in the treatment of UC, we conducted a systematic review and meta-analysis. PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Database and CQVIP Database were searched for this review.The main observation indexes were the effect of DSP combined with mesalazine or DSP on the effective rate, platelet count (PLT), mean platelet volume (MPV) and C-reactive protein (CRP) of UC. The Cochrane risk of bias tool was used to assess the risk of bias. The selected studies were evaluated for quality and data processing using RevMan5.4 and Stata17.0 software. A total of 37 studies were included. Among them, 26 clinical trials with 2426 patients were included and 11 animal experimental studies involving 208 animals were included. Meta-analysis results showed that compared with mesalazine alone, combined use of DSP can clearly improve the clinical effective rate (RR 0.86%, 95% CI:0.83-0.88, < 0.00001) of UC. Furthermore it improved blood coagulation function by decreasing serum PLT and increasing MPV levels, and controlled inflammatory responses by reducing serum CRP, TNF-α, IL-6, and IL-8 levels in patients. Combining DSP with mesalazine for UC can enhance clinical efficacy. However, caution should be exercised in interpreting the results of this review due to its flaws, such as allocation concealment and uncertainty resulting from the blinding of the study. : http://www.crd.york.ac.uk/PROSPERO/myprospero.php, identifier PROSPERO: CRD42022293287.
PubMed: 38881869
DOI: 10.3389/fphar.2024.1334474 -
Scientific Reports Jun 2024Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin,...
Myelodysplastic syndrome (MDS) is a heterogeneous spectrum of clonal hematopoietic disorders with varying degrees of cytopenia and morphologic dysplasia. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a prognostic marker in several types of malignant tumors. Prognostic value of HALP score remains unclear for MDS. To determine the prognostic value of baseline HALP score in MDS. We retrospectively analyzed data from 130 newly diagnosed MDS patients evaluated and classified under HALP score. By the receiver operating characteristic (ROC) analysis, the optimal cut-off value of HALP was > 67.5 in predicting mortality. Patients were divided into two groups: with low and high HALP scores, and the characteristics were compared between both groups. Patients' median age was 68 (19-84) years, and 79 (60.8%) were male. Higher HALP score was detected in MDS patients with intermediate-risk under IPSS score, and at high and very high risks under IPSS-R score, and those receiving azacitidine (AZA) treatment. The survival rates of those with a HALP score > 67.5 were significantly lower than those with low HALP score at 17.77 ± 3.98 (median ± SE) (p < 0.001). The 3-, 5- and 10-years survival rates of individuals with HALP scores > 67.5 were found as 25, 18, and 11%, respectively. Median overall survival (OS) was also determined as 33.10 (95% CI 16.34-49.88) months by the Kaplan-Meier method. HALP score has shown an ability to be a useful prognostic biomarker in various cancers, including MDS. The meaningful cut-off value of HALP is disease-specific and largely study-specific. High HALP score is associated with unfavorable clinicopathological characteristics. Also, it may be useful in predicting OS and mortality of MDS.
Topics: Humans; Myelodysplastic Syndromes; Male; Aged; Female; Middle Aged; Prognosis; Aged, 80 and over; Adult; Retrospective Studies; Hemoglobins; Young Adult; ROC Curve; Blood Platelets; Lymphocytes; Platelet Count
PubMed: 38879594
DOI: 10.1038/s41598-024-64166-6 -
Cancer Letters Jun 2024Platelets are small circulating anucleated cells mainly involved in thrombosis and hemostasis processes. Moreover, platelets play an active role in tumorigenesis and... (Review)
Review
Platelets are small circulating anucleated cells mainly involved in thrombosis and hemostasis processes. Moreover, platelets play an active role in tumorigenesis and cancer progression, stimulating angiogenesis and vascular remodelling, and protecting circulating cancer cells from shear forces and immune surveillance. Several reports indicate that platelet number in the blood circulation of cancer patients is associated with prognosis and response to treatment. However, the mechanisms of platelets "education" by cancer cells and the crosstalk between platelets and tumor are still unclear, and the role of "tumor educated platelets" (TEPs) is achieving growing interest in cancer research. TEPs are a biological source of cancer-derived biomarkers, especially RNAs that are protected by platelets membrane from circulating RNases, and could serve as a non-invasive tool for tumor detection, molecular profiling and evolution during therapy in clinical practice. Moreover, short platelet lifespan offers the possibility to get a snapshot assessment of cancer molecular profile, providing a real-time tool. We review and discuss the potential and the clinical utility, in terms of cancer diagnosis and monitoring, of platelet count together with other morphological parameters and of the more recent and innovative TEP profiling.
PubMed: 38876385
DOI: 10.1016/j.canlet.2024.217044 -
Medicine Jun 2024The neutrophil lymphocyte ratio (NLR) and red blood cell distribution width (RDW) have been repeatedly demonstrated to be associated with risk of severity, progression,... (Observational Study)
Observational Study
The neutrophil lymphocyte ratio (NLR) and red blood cell distribution width (RDW) have been repeatedly demonstrated to be associated with risk of severity, progression, and prognosis of chronic obstructive pulmonary disease (COPD), but data on respiratory failure (RF) in patients with COPD are very limited. This study aimed to examine the relationship between NLR and RDW and the incident RF in patients with COPD. This is a retrospective study that reviewed data by examining the hospitalization medical records to identify those who were admitted with a diagnosis of COPD. Based on whether RF occurred during index hospitalization, patients were classified as COPD group and COPD combined with RF group. Also, healthy controls of the same age and sex were enrolled in a 1:1 ratio as the COPD group. Univariate comparisons were performed between three groups to examine differences. With the COPD group as reference, multivariable logistic regression was formed to identify the relationship between NLR and RDW and RF, with adjustment for multiple covariates. There were 136 healthy controls, 136 COPD patients and 62 patients with COPD combined with RF included for analysis. There was a significant difference for eight variables, including age, WBC, neutrophil, NLR, RDW, platelet, PLR, and CRP. The Spearman test showed the significant correlation between NLR and WBC (correlation coefficient, 0.38; P = .008), NLR and RDW (correlation coefficient, 0.32; P = .013), and NLR and CRP level (correlation coefficient, 0.54; P < .001). The multivariable logistic regression showed that age (every additional 10 years) (OR, 1.785), NLR (OR, 1.716), RDW (OR, 2.266), and CRP (OR, 1.163) were independently associated with an increased risk of RF. This study demonstrated the independent associative effect of NLR and RDW with RF in patients with COPD, exhibiting the potential clinical role in evaluating the progress of COPD to RF.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Retrospective Studies; Erythrocyte Indices; Neutrophils; Middle Aged; Aged; Lymphocytes; Respiratory Insufficiency; Lymphocyte Count; Prognosis
PubMed: 38875435
DOI: 10.1097/MD.0000000000038512 -
Medicine Jun 2024Preoperative laboratory data indicators significantly affect the prognosis of a variety of tumors. Nevertheless, the combined effect of systemic immune-inflammation... (Observational Study)
Observational Study
Preoperative laboratory data indicators significantly affect the prognosis of a variety of tumors. Nevertheless, the combined effect of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) on overall survival (OS) in patients with esophageal carcinoma remains unclear. Thus, we examined these associations among patients with postoperative staged T3N0M0 esophageal carcinoma. The data of 246 patients with postoperative staged T3N0M0 esophageal carcinoma from January 1, 2010, to December 31, 2022, were retrospectively analyzed. OS was measured from the date of pathological diagnosis until either death or the last follow-up. The Kaplan-Meier method and multivariate Cox regression model were used to analyze the relationship between neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Platelet-to-lymphocyte ratio (LMR), SII, PNI, and OS. The predictive value of SII and PNI as a combined index was analyzed by the receiver operating characteristic curve (ROC). A total of 246 patients aged 65.5 ± 7.4 years were included in this study and 181 (73.6%) were male. The univariate analysis revealed that differentiation, vessel involvement, postoperative treatment, NLR, SII, PLR, LMR, PNI were predictors of OS (P < .05). After adjusted for potential confounds, multivariate Cox regression analysis showed that the differentiation, SII, PNI, and postoperative treatment were independent prognostic factors correlated with OS in patients with postoperative staged T3N0M0 esophageal carcinoma (P < .05). SII and PNI, as a combined indicator, have a higher predictive value for OS. The NLR, SII, PLR, LMR, and PNI could all be used as independent predictors of OS in patients with postoperative staged T3N0M0 esophageal carcinoma. The combination of SII and PNI can significantly improve the accuracy of prediction.
Topics: Humans; Esophageal Neoplasms; Male; Female; Aged; Retrospective Studies; Prognosis; Middle Aged; Neutrophils; Nutrition Assessment; Lymphocyte Count; Kaplan-Meier Estimate; Preoperative Period; Platelet Count; ROC Curve; Lymphocytes; Proportional Hazards Models; Neoplasm Staging
PubMed: 38875403
DOI: 10.1097/MD.0000000000038477 -
PloS One 2024The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were...
PURPOSE
The relationship between the levels of Systemic Immune-inflammation Index (SII) and chronic obstructive pulmonary disease (COPD), lung function, and COPD severity were not fully understood. We conducted this cross-sectional, population-based study to investigate the complex association between SII and COPD, lung function, and COPD severity among the US adults.
METHODS
Overall, 18,349 participants were included in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. The exposure variable was SII, calculated from platelet counts, neutrophil counts, and lymphocyte counts. Weighted univariable and multivariable logistic regression, subgroup analysis, and restricted cubic spline (RCS) regression were performed to assess the relationship between COPD, lung function, COPD severity and SII. Last, we used a propensity score matching (PSM) analysis to reduce selective bias and validate these relationships.
RESULTS
Approximately 1,094 (5.96%) of the participants were diagnosed as COPD. The multivariable-adjusted odds ratio (OR) (95% confidence interval, CI) for the Q2 group (Log-SII > 2.740) was 1.39 (1.16 to 1.68). Before and after matching, multivariable logistic regression models revealed that increased Log-SII levels (SII Logarithmic transformation) associated positively with the risk of COPD. The subgroup analysis showed no interaction between Log-SII and a variety of variables (P for interaction > 0.05). RCS showed a reversed L-shaped relationship between Log-SII with COPD (P for nonlinear = 0.001) in individuals. In addition, we observed negative significant correlations between forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) %, FEV1/FVC% predicted and SII, and reversed U-shaped curve relationships between FEV1, FEV1% predicted and SII. High SII level is associated with severity of COPD, especially at Global Initiative on Obstructive Lung Disease (GOLD) 1 and GOLD 3.
CONCLUSIONS
In summary, the Log-SII level is associated with COPD risk, lung function, and COPD severity.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Male; Female; Middle Aged; Cross-Sectional Studies; Severity of Illness Index; Inflammation; Nutrition Surveys; Aged; Lung; Adult; Risk Factors; Forced Expiratory Volume; Neutrophils; Respiratory Function Tests; Platelet Count
PubMed: 38875233
DOI: 10.1371/journal.pone.0303286 -
Frontiers in Pharmacology 2024The purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug...
OBJECTIVE
The purpose of this study is to investigate the drug safety of three Transthyretin (TTR) inhibitors in the real world using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.
METHODS
This study extracted reports received by the FAERS database from the first quarter of 2018 to the third quarter of 2023 for descriptive analysis and disproportionality analysis. Safety signal mining was conducted at the Preferred Term (PT) level and the System Organ Class (SOC) level using reporting odds ratio (ROR). The characteristics of the time-to-onset curves were analyzed using the Weibull Shape Parameter (WSP). The cumulative incidence of TTR inhibitors was evaluated using the Kaplan-Meier method. Subgroup analyses were conducted based on whether the reporter was a medical professional.
RESULTS
A total of 3,459 reports of adverse events (AEs) caused by TTR inhibitors as the primary suspect (PS) drug were extracted. The top three reported AEs for patisiran were fatigue, asthenia, and fall, with the most unexpectedly strong association being nonspecific reaction. The top three reported AEs for vutrisiran were fall, pain in extremity and malaise, with the most unexpectedly strong association being subdural haematoma. The top three reported AEs for inotersen were platelet count decreased, blood creatinine increased, and fatigue, with the most unexpectedly strong association being blood albumin decreased. Vitamin A decreased, arthralgia, and dyspnea were the same AEs mentioned in the drug labels of all three drugs, while malaise and asthenia were the same unexpected significant signals. This study offers evidence of the variability in the onset time characteristics of AEs associated with TTR inhibitors, as well as evidence of differences in adverse event reporting between medical professionals and non-medical professionals.
CONCLUSION
In summary, we compared the similarities and differences in drug safety of three TTR inhibitors in the real world using the FAERS database. The results indicate that not only do these three drugs share common AEs, but they also exhibit differences in drug safety profiles. This study contributes to enhancing the understanding of medical professionals regarding the safety of TTR inhibitors.
PubMed: 38873427
DOI: 10.3389/fphar.2024.1368244