Decrease In Platelet Count Research Articles

Association of clinical factors with thrombocytopenia in patients receiving linezolid treatment: a retrospective study.

Linezolid (LZD) plays an important role in the treatment of severe infections caused by Gram-positive bacteria. Thrombocytopenia is regarded as one of the most common side effects of linezolid, which results from the destruction of platelets or myelosuppression. The study aimed to identify the risk factors associated with the development of thrombocytopenia in Vietnamese patients. This retrospective, descriptive cross-sectional study was performed on adult patients who received parenteral LZD therapy (1,200 mg/day) in at least 3 days between January 2020 and June 2021 at a tertiary referral hospital in Vietnam. Thrombocytopenia was defined as either a final platelet count of less than 100 G/L or a 25% decrease in platelet count from baseline. Multivariate logistic regression analysis was applied to predict risk factors associated with LZD-induced thrombocytopenia. In the 208 patients included in the study, the average age was 69 and males accounted for 73.1%. LZD-induced thrombocytopenia occurred in 37% of patients. LZD-induced thrombocytopenia was significantly associated with shock (HR = 8.26, 95% CI 3.82 - 17.84, p < 0.001), baseline creatinine clearance (HR = 1.02, 95% CI [1.01 - 1.03], p = 0.002), and duration of LZD treatment of at least 14 days (HR = 4.45, 95% CI [1.83 - 11.05], p = 0.001). The results showed that thrombocytopenia was fairly common in patients using linezolid. Shock, renal failure, and duration of linezolid therapy of at least 14 days were significant risk factors for the incidence of linezolid-induced thrombocytopenia.

Complex changes in serum protein levels in COVID-19 convalescents

The COVID-19 pandemic, triggered by severe acute respiratory syndrome coronavirus 2, has affected millions of people worldwide. Much research has been dedicated to our understanding of COVID-19 disease heterogeneity and severity, but less is known about recovery associated changes. To address this gap in knowledge, we quantified the proteome from serum samples from 29 COVID-19 convalescents and 29 age-, race-, and sex-matched healthy controls. Samples were acquired within the first months of the pandemic. Many proteins from pathways known to change during acute COVID-19 illness, such as from the complement cascade, coagulation system, inflammation and adaptive immune system, had returned to levels seen in healthy controls. In comparison, we identified 22 and 15 proteins with significantly elevated and lowered levels, respectively, amongst COVID-19 convalescents compared to healthy controls. Some of the changes were similar to those observed for the acute phase of the disease, i.e. elevated levels of proteins from hemolysis, the adaptive immune systems, and inflammation. In contrast, some alterations opposed those in the acute phase, e.g. elevated levels of CETP and APOA1 which function in lipid/cholesterol metabolism, and decreased levels of proteins from the complement cascade (e.g. C1R, C1S, and VWF), the coagulation system (e.g. THBS1 and VWF), and the regulation of the actin cytoskeleton (e.g. PFN1 and CFL1) amongst COVID-19 convalescents. We speculate that some of these shifts might originate from a transient decrease in platelet counts upon recovery from the disease. Finally, we observed race-specific changes, e.g. with respect to immunoglobulins and proteins related to cholesterol metabolism.

A tight interplay between platelet activation and mitochondrial DNA release promotes platelet storage lesion in platelet concentrates.

Platelet storage lesion (PSL) adversely affects the quality of platelet concentrates (PCs). Platelets are prone to activation during storage. Moreover, elevated free mitochondrial DNA (mtDNA) levels in PCs are associated with a higher risk of adverse transfusion reactions. Therefore, we aimed to evaluate the correlation between platelet activation markers and mtDNA release during PC storage. Six PCs prepared by the platelet-rich plasma method were assessed for free mtDNA copy number using quantitative real-time PCR and CD62P (P-selectin) expression by flow cytometry on days 0 (PC collection day), 3, 5 and 7 of storage. Lactate dehydrogenase (LDH) activity, pH, platelet count, mean platelet volume (MPV) and platelet distribution width (PDW) were measured as well. The correlation between free mtDNA and other PSL parameters, and the correlation between all parameters, was determined. Significant increases in free mtDNA, MPV and PDW, and a significant decrease in platelet count and pH were observed. CD62P expression and LDH activity elevated significantly, particularly on storage days 5-7 and 0-3, respectively. Moreover, a moderate positive correlation (r = 0.61) was observed between free mtDNA and CD62P expression. The r values between free mtDNA and LDH, pH, platelet count, MPV and PDW were 0.81, -0.72, -0.49, 0.81 and 0.77, respectively. The interplay between platelet activation and mtDNA release in promoting PSL in PCs may serve as a promising target for future research on applying additive solutions and evaluating the quality of PCs to improve transfusion and clinical outcomes.

Neutrophil extracellular traps - a potential trigger for the development of thrombocytopenia during extracorporeal membrane oxygenation.

Neutrophil extracellular traps (NETs) have recently emerged as a potential link between inflammation, immunity, and thrombosis, as well as other coagulation disorders which present a major challenge in the context of extracorporeal membrane oxygenation (ECMO). By examining blood from ECMO patients for NETs and their precursors and correlating them with clinical and laboratory biomarkers of coagulation and inflammation, this study aims to evaluate the association between the presence of NETs in the bloodstream of ECMO patients and the development of potentially severe coagulation disorders during ECMO therapy. Therefore, blood samples were collected from healthy volunteers (n=13) and patients receiving veno-venous (VV) ECMO therapy (n=10). To identify NETs and their precursors, DNA and myeloperoxidase as well as granulocyte marker CD66b were visualized simultaneously by immunofluorescence staining in serial blood smears. Differentiation of DNA-containing objects and identification of NETs and their precursors was performed semiautomatically by a specific algorithm using the shape and size of DNA staining and the intensity of MPO and CD66b signal. Neutrophil extracellular traps and their precursors could be detected in blood smears from patients requiring VV ECMO. Compared to volunteers, ECMO patients presented significantly higher rates of NETs and NET precursors as well as an increased proportion of neutrophil granulocytes in all detected nucleated cells. A high NET rate prior to the initiation of ECMO therapy was associated with both increased IL-6 and TNF-α levels as an expression of a high cytokine burden. These patients with increased NET release also presented an earlier and significantly more pronounced decrease in platelet counts and ATIII activity following initiation of therapy compared with patients with less elevated NETs. These findings provide further indications for the development of immune-mediated acquired thrombocytopenia in ECMO patients.

Association of a decreased platelet count with poor survival in patients with adult secondary hemophagocytic lymphohistiocytosis.

We aimed to examine the association between baseline platelet count (PLT) and the prognosis of adult secondary hemophagocytic lymphohistiocytosis (sHLH). Data from 292 patients with pretreatment platelet counts were retrospectively analysed from January 2016 to December 2020. We categorized platelet count into quartiles. Multivariable Cox proportional hazards models and restricted cubic splines (RCS) were used to evaluate the relationship between platelet count and mortality. During a median follow-up of 53 (interquartile ranges, 17-223) days, a total of 208 deaths occurred. After adjusting for multiple variables, a non-linear and inverse relationship was observed between platelet count and mortality in sHLH patient (P for nonlinearity=0.002). For non- lymphoma-associated haemophagocytic lymphohistiocytosis (non-LHLH), a similar curve was also observed (P for nonlinearity =0.028). Decreased PLT (PLT Q4) was associated with an increased risk of mortality (adjusted hazard ratio: 1.97; 95% confidence interval: 1.28-3.04; Ptrend =0.005). Similar results were observed in the LHLH subgroup (adjusted hazard ratio: 1.84; 95% confidence interval: 1.05-3.24; Ptrend =0.024) but not in the non-LHLH subgroup (Ptrend =0.266). Baseline platelet count demonstrated a nonlinear and inverse association with an increased risk of mortality among adult sHLH patients. This method is used to identify sHLH patients with inferior overall survival due to its low cost and universal availability.

Autologous stem cell boost improves persistent immune effector cell associated hematotoxicity following BCMA directed chimeric antigen receptor T (CAR T) cell therapy in multiple myeloma.

Persistent Immune Effector Cell Associated Hematotoxicity (ICAHT) is a significant side effect of BCMA CAR T-Cell therapy in patients with relapsed multiple myeloma (MM). The use of stem cell boosts in ICAHT has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience of ICAHT, defined by an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia with a platelet count ≤ 50,000 or/and anemia as hemoglobin (hgb) ≤9 g/dL, in patients who received BCMA CAR T therapy, and the effects of subsequent stem cell boost on hematopoietic reconstitution and clinical outcome. In this study, ICAHT was observed in 60% (n = 61/101) of patients at D + 21, and risk factors for its development included history of a prior ASCT, higher number of prior lines of therapy, a decreased platelet count prior to lymphodepletion and history of ICANS. 28% of patients with ICAHT received a stem cell boost at a median of 116 days due to profound and prolonged cytopenias often requiring ongoing transfusion support. Stem cell boost significantly improved cytopenias at 3 and 6 months follow up without any adverse effects on PFS and OS, underscoring the safety of this procedure.

Thrombocytopenia among Patients Undergoing Aortic Valve Replacement Using the Sutureless Perceval S Bioprosthesis: A Retrospective Study.

The sutureless Perceval S bioprosthesis is associated with postoperative thrombocytopenia. Our objectives were to compare the incidence, severity, and clinical implications of thrombocytopenia after aortic valve replacement (AVR) using the Perceval S or the Trifecta bioprosthesis. Patients who underwent AVR between March 2016 and August 2019 using the Perceval or Trifecta were retrospectively included. The primary endpoint was the nadir in platelet counts within 15 days after surgery. Secondary endpoints included postoperative hemolysis and inflammatory parameters, as well as clinical and echocardiographic outcomes. Overall, 156 patients were included (Perceval, n = 103; Trifecta, n = 53). Preoperatively, there was no difference in platelet counts between the two groups. Postoperatively, the Perceval S bioprosthesis was associated with a greater decrease in platelet counts. The nadir was reached at Day 3 for both groups, but thrombocytopenia was more severe for the Perceval S (Perceval S vs. Trifecta, 89.2 ± 37.7 × 109/L vs. 106.5 ± 34.1 × 109/L, p = 0.01). No difference regarding lactate dehydrogenase, C-reactive protein, and white blood cells count was found. All-cause 30-day mortality rates (both valves, 2%, p = 0.98), hospital lengths of stay, and re-operation rates were similar. The Perceval S bioprosthesis was associated with more severe postoperative thrombocytopenia. This did not translate into higher short-term morbidity or mortality.

Assessing the Safety of Mechanically Fibrillated Cellulose Nanofibers (fib-CNF) via Toxicity Tests on Mice: Single Intratracheal Administration and 28 Days' Oral Intake.

Mechanically fibrillated cellulose nanofibers, known as fib-CNF (fiber length: 500 nm; diameter: 45 nm), are used in composites and as a natural thickener in foods. To evaluate their safety, we conducted a 28-day study in mice with inhalation exposure at 0.2 mg/body and oral administration of 400 mg/kg/day. Inhalation exposure to fib-CNF caused transient weight loss, changes in blood cell counts, and increased lung weights. These changes were attributed to adaptive responses. The oral administration of fib-CNF for 28 days resulted in no apparent toxic effects except for a slight decrease in platelet counts. The fib-CNF administration using the protocols studied appears to be safe in mice.

Factors influencing delayed high-dose methotrexate excretion and its correlation with adverse reactions after treatment in children with malignant hematological tumors.

High-dose methotrexate (HDMTX) is crucial in treating pediatric malignant hematological tumors. However, its use is often complicated by delayed excretion and associated adverse reactions, which can significantly affect treatment outcomes and patient safety. Identifying risk factors is essential for safer, more effective therapy. This study aimed to investigate the influencing factors for delayed excretion and their correlation with adverse reactions in children with malignant hematological tumors after receiving HDMTX chemotherapy. From April to October 2021, the clinical information of children who had undergone HDMTX chemotherapy and had their blood tested for drug concentration was gathered by the Department of Hematology and Oncology at Shanghai Children's Medical Center. Via univariate and multivariate logistic regression, the factors affecting the delayed excretion of HDMTX were examined, and the relationship between delayed excretion and unfavorable effects in children was determined. This study included 99 patients comprising 199 courses of HDMTX. The occurrence rate of HDMTX delayed excretion was 20.1%. Age ≥9 years and a 24-hour methotrexate (MTX) concentration of 64 µmol/L were independent risk factors for delayed MTX excretion according to multivariate logistic regression analysis (P<0.05). Negative side effects, such as fever, infection, mucositis, gastrointestinal response, and decreased platelet count in children with delayed excretion were statistically significant when compared to those of children with normal excretion. White blood cell reduction, hemoglobin levels below 65 g/L, MTX excretion delay, and concomitant etoposide treatment were all independent risk factors for infection in children. To estimate the risk of delayed MTX excretion during HDMTX therapy, patient laboratory data should be scrutinized, especially for patients ≥9 years or those with a 24-hour MTX concentration of greater than 64 µmol/L.

First-line treatment with camrelizumab plus famitinib in advanced or metastatic NSCLC patients with PD-L1 TPS ≥1%: results from a multicenter, open-label, phase 2 trial

BackgroundThe combination of immune-checkpoint inhibitors and antiangiogenic agents can synergistically modulate the tumor microenvironment and represents a promising treatment option. Here, we evaluated the efficacy and safety of camrelizumab plus...

Severe Hepatotoxicity in Mushroom Poisoning by Lepiota brunneoincarnata from Complete Recovery to Liver Transplantation: A Case Series with Review on Liver Function Tests and Liver Histopathology.

In spite of the scientific evidence supporting health advantages of mushrooms, some of them are seriously poisonous. The clinical picture of mushroom intoxication ranges from minor gastrointestinal symptoms to organ failure, such as liver failure and death. We provided demographics, clinicopathological characteristics, applied treatments, and outcomes of mushroom poisoning by Lepiota species in a series of 18 cases that were referred from Kermanshah and Lorestan provinces to Abu-Ali-Sina Hospital, Shiraz, Iran. Clinical and paraclinical data were collected by taking history and reviewing of medical documents. Pathologic findings were extracted through a review of hematoxylin and eosin pathologic slides. The patients were between the ages of 18 and 67 years, composed of ten females and eight males. The most frequent clinical manifestations were nausea and vomiting followed by abdominal pain. Four cases presented decreased consciousness on admission. One of them passed away. Three other cases underwent liver transplantation, two of them died after transplantation, and one fully recovered without any major issues. All instances had elevated ALT levels, which ranged from 44 to 9,140 IU/L (mean: 3259 ± 2476), with most of them also having concurrent AST elevations (mean: 1,361 ± 1,532). Only few patients had modest elevations in alkaline phosphatase. Total and direct bilirubin elevations up to 47.6 and 24 mg/dL, respectively, were found in most cases. Decreased total protein and albumin concentrations and increased BUN and creatinine levels were observed in some patients. In addition, some instances revealed increased LDH, increased WBC, decreased hemoglobin, and decreased platelet count. Most patients had increased prothrombin time; hematuria and positive stool occult blood were observed in few patients. Histopathologic examination of three explanted livers revealed massive necrosis with moderate to severe macrovesicular steatosis, significant ductular reaction, and parenchymal inflammation. Other patients followed a recovery process with a considerable drop in liver enzymes, especially ALT, during hospitalization utilizing conservative treatment. They had no liver problems or relevant issues after a two-year follow-up. In our study, highly elevated liver enzymes with a significantly high ALT/AST ratio were observed in cases of mushroom poisoning by Lepiota species, leading to fulminant liver failure and death in some cases. These laboratory findings were correlated with liver necrosis and macrovesicular steatosis in explanted livers.

First safety and efficacy data from phase Ib/IIa study of fostroxacitabine bralpamide (fostrox, MIV-818) in combination with lenvatinib in patients with hepatocellular carcinoma (HCC).

476 Background: Fostrox is an orally administered troxacitabine-based nucleotide prodrug in clinical development in combination with lenvatinib (NCT03781934). Fostrox is rapidly metabolized by human hepatocytes, directing high levels of the active metabolite to the liver. Phase I fostrox monotherapy demonstrated selective intra-tumoral activity in on-treatment liver biopsies. The anti-angiogenic activity of lenvatinib has the potential to synergize with fostrox by hypoxia-induced increase in the enzymatic generation of the active metabolite of fostrox in the tumor. Methods: In a phase Ib/IIa study with an inter-patient dose escalation 3+3 cohort design followed by a dose expansion phase, fostrox was administered orally QD for 5 days in 21-day cycles in combination with lenvatinib according to local prescription information. Patients (pts) with &lt;2 prior lines systemic treatment for advanced, unresectable HCC were recruited at 10 sites in Spain, South Korea and UK. Pts with histologically, radiologically, or cytologically confirmed HCC, Child-Pugh A, ≥18 years, ECOG PS ≤ 1 and adequate organ function were eligible. The primary objective was to assess safety and tolerability. Key secondary endpoints were ORR based on RECIST 1.1 and mRECIST. Exploratory endpoints included pharmacokinetics (PK) and pharmacodynamic effects of fostrox in combination with lenvatinib. Results: At interim data cut-off 18 pts (6 pts in Ib and 12 pts in IIa) were enrolled at fostrox QD doses of 20mg (3 pts) and 30mg (15 pts) in combination with lenvatinib. Median age was 63 years (range: 42-82). No DLTs and only 1 discontinuation of fostrox due to AEs with a median FU of 3.8 months, were observed. Most common grade 3/4 AEs were transient neutrophil count decrease, platelet count decrease and hypertension. No febrile neutropenia, bleeding events or proteinuria were reported. The safety profile was consistent with each individual agent. In phase Ib, central independent review based on RECIST 1.1 showed SD in 5/6 pts, while mRECIST showed CR in 1 pt, PR in 2 pts and SD in 2 pts. Updated phase Ib data and efficacy data from phase IIa by central independent review, together with PK for fostrox and lenvatinib, and liver biopsy biomarker data, will be presented. Conclusions: Fostrox in combination with lenvatinib, in pts with HCC who progressed on previous systemic treatment, had an acceptable safety and tolerability profile with promising interim efficacy results from the completely enrolled phase Ib/IIa study. Clinical trial information: NCT03781934 .

An Assessment of the Viability of Haematological and Haemostatic Parameters of Blood under certain Storage Conditions at the Rivers State University Teaching Hospital Blood Bank in Port Harcourt, Nigeria

Introduction: Despite significant advances in transfusion medicine, concerns about the inherent risks of blood transfusion persist, even under optimal temperature and duration of storage. This makes the evaluation of blood viability a global task (1). Maintenance of adequate temperature is considered a key factor in the viability and quality of stored blood in healthcare institutions. Evaluating the haematological and haemostatic functionality of blood elements at different storage temperature and duration is therefore imperative for improving patient care and resource utilization in Rivers State University Teaching Hospital (RSUTH) blood bank in Port Harcourt.&#x0D; Methods: In this cohort study design, a total of sixteen (16) male and female blood donors in equal proportion of sex and ABO blood groups were randomly selected from the Port Harcourt blood donors' population and recruited as study subjects for this research. A well-structured questionnaire and the immunoassays were used to assess the donors' health and serological status respectively. Also the sample obtained were analayzed by automation and data statistically analyzed using ANOVA.&#x0D; Results: The results of this study shows a statistically significant decrease in white blood cell count from 4.93×109/L ± 0.33 to 2.79×109/L ± 1.68 (p=0.00) and platelet count from 227.38×109/L ± 32.17 to 153.75×109/L ± 58.39 (p=0.00) at day 7. Also, a significant decrease in platelet count from 227.38×109/L ± 32.17 to 141.50±60.92 at day 14. A significant decrease in Fibrinogen from 340.75mg/L±18.69 to 281.2575 mg/L ±46.41 at day 1 and day 14 respectively, and rise in PT and aPTT from 17.02s ±1.28 to 24.31s ±6.67 and 41.25s±3.23 to 46.63s±6.28 at day 14th to day 21 respectively (p=0.00).&#x0D; Conclusion and Implications for Translation: Pooled plasma at 4-60C contain clinically significant amount of coagulation factors up to day 21 in storage. The WBC and platelet is lost within seven day of storage at 4-60C. Lower temperatures, especially freezing at -60°C accelerate the loss of haematological viability of blood especially the depletion of white blood cells and platelets (p=0.00). Antihaemophilic factor and fibrinogen is maintained in FFP at 180 day in storage at -600C.

Association between platelet count and neonatal acute kidney injury: a cohort study using the medical information mart for intensive care III database

Objective A decrease in platelet count has been reported to be associated with several neonatal inflammatory diseases, including sepsis and necrotizing enterocolitis; while its association with neonatal acute kidney injury (AKI) has not been reported. This study aims to explore the association between platelet count and neonatal AKI. Methods This was a retrospective cohort study based on the Medical Information Mart for Intensive Care III (MIMIC-III) database. Data were extracted based on baseline characteristics, comorbidities, vital signs, laboratory parameters, and intervention measures. Logistic regression analysis was used to assess the association between platelet count and AKI, and results were shown as odds ratios (OR) with 95% confidence intervals (CI). Results A total of 1,576 neonates were finally included in the analysis. After adjusting birth weight, sepsis, patent ductus arteriosus, hematocrit, percentage of neutrophils, and vasopressor use, we found that platelet count in the lowest quartile (Q1) was significantly associated with the higher odds of AKI than platelet count in the highest quartile (Q4) (OR = 1.70, 95% CI: 1.01-2.87). Conclusions Low platelet count was associated with the high odds of AKI in the neonatal intensive care unit (NICU), indicating that platelet count might be a biomarker for neonatal AKI. Large-scale multicenter studies should be performed to verify the results.

Roselle Calyx (Hibiscus sabdariffa L.) Ethyl Acetate Fraction Lowering Malondialdehyde and TNF-α and Reducing Hypercoagulability in Diabetic Model

Introduction: Traditionally and empirically, Hibiscus sabdariffa L. has been used in treating diabetes mellitus due to its antioxidant activity. This study aimed to investigate the effect of administering the ethyl acetate fraction of hibiscus calyxes (EAFHCs) on malondialdehyde (MDA) levels, tumor necrosis factor-α (TNF-α) levels, bleeding time, and platelet count in male white rats induced with streptozotocin-induced diabetes. Method: Thirty-six Wistar Kyoto rats were induced with intraperitoneal streptozotocin at 55 mg/kg BW and stabilized for 5 days to obtain diabetic conditions. Diabetic animals were divided into four groups; the diabetic group was given vehicle, the glibenclamide group was given 0.45 mg/kg BW of glibenclamide, and two groups were administered the EAFHCs at doses of 100 mg/kg BW and 200 mg/kg BW for 5 days. Subsequently, the MDA, TNF-α, bleeding time and platelet count levels were examined on days 1, 3, and 5, respectively. All data were analyzed using two-way ANOVA followed by the Duncan Multiple Range Test (DMRT). Results: EAFHC significantly reduced MDA and TNF-α levels (p < 0.05). Additionally, this fraction appeared to shorten bleeding time and decrease platelet count in diabetic rats. Administration of the EAFHC for 5 days effectively lowered MDA and TNF-α levels significantly, decreased platelet counts and prolonged coagulation (p < 0.05) in diabetic rats. Conclusion: This study demonstrates that EAFHC effectively reduces MDA and TNF-α levels and reduces the risk of hypercoagulability in diabetic model.

Holter ECG monitoring and platelets characteristics in patients with coronary artery disease and atrial fibrillation.

Aim: To check the relationships between platelet characteristics and Holter ECG monitoring results in patients with atrial fibrillation (AF) and coronary artery disease (CAD). Materials and Methods: 300 investigated patients were separated into three groups: I (CAD) - 149 patients with CAD without arrhythmias, II (CAD and AF) - 124 patients with CAD and AF paroxysm, and the control group (CG) - 27 patients without CAD and arrhythmias. Results: In the II group was detected an increase in mean platelet volume (MPV) (9.30%) and platelet-to-leucocyte ratio (PLR) (41.12%) and a decrease in platelet count (PC) (12.20%) in comparison with the I group, P<0.05. Also, in the II group was found an increase in platelet leucine (12.63%), isoleucine (10.73%), and a decrease in serine (5.06%), threonine (23.05%), valine (30.83%), glycine (32.21%) levels in comparison with the I group, P<0.05. PC, MPV, and PLR ratios were correlated with supraventricular extrasystoles per hour (r=-0.352, r=0.308, and r=0.359, consequently), P<0.05. Platelets distribution width (PDW) was correlated with ST-segment changes (r=0.371), P<0.05. Platelet threonine, serine, glycine, alanine, and valine levels were correlated with total supraventricular extrasystoles (r=-0.374, r=-0.358, r=-0.402, r=-0.307, r=-0.312, consequently) and supraventricular extrasystoles per hour (r=-0.374, r=-0.358, r=-0.402, r=-0.307, r=-0.312, consequently), P<0.05. Platelet lysine, taurine, cysteine, and phenylalanine levels were correlated with ST-segment changes (r=-0.319, r=-0.344, r=-0.376, and r=0.317, consequently), P<0.05. Conclusions: Platelet features (PC, MPV, PDW, PLR, and amino acid spectrum) are significantly correlated with supraventricular arrhythmias and ST-segment episodes, which shows their role in AF and CAD pathogenesis.

Risk Factors for Thrombocytopenia Induced by Capecitabine Plus Oxaliplatin Therapy in Patients With Colorectal Cancer.

Capecitabine plus oxaliplatin (CapeOX) therapy is used as an adjuvant chemotherapy regimen for patients with colorectal cancer (CRC). Although oxaliplatin induces thrombocytopenia, the risk factors for thrombocytopenia in oxaliplatin-treated patients with CRC are not well established. We aimed to investigate the risk factors for thrombocytopenia in CapeOX-treated patients with CRC. In addition, we evaluated platelet counts and non-invasive liver fibrosis indices, specifically the aspartate aminotransferase-to-platelet ratio index (APRI) and the fibrosis-4 index (FIB-4), during CapeOX therapy in these patients. Between July 2017 and June 2020, we enrolled CapeOX-treated patients with high-risk stage II or stage III CRC at seven hospitals collaborating with the Division of Oncology, Aichi Prefectural Society of Hospital Pharmacists (Aichi prefecture, Japan). In this retrospective study, we investigated patients' backgrounds, laboratory data, concomitant medications, number of cycles of CapeOX and oxaliplatin, cumulative dose of oxaliplatin, and administration period. The cut-off values were calculated using receiver operating characteristic analysis of platelet counts and APRI and FIB-4 scores. Fifty-five patients without thrombocytopenia and 44 patients with thrombocytopenia were enrolled. During CapeOX therapy, the thrombocytopenia group showed a significant decrease in platelet count and a significant increase in APRI and FIB-4 scores compared to the non-thrombocytopenia group. Baseline albumin level ≤3.5 g/dl and platelet count ≤238×103/μl were independently associated with ≥grade 2 thrombocytopenia in CapeOX-treated patients. Baseline albumin level and platelet count may be useful for predicting thrombocytopenia in CapeOX-treated patients with high-risk stage II or stage III CRC.

Niraparib in Japanese patients with heavily pretreated, homologous recombination-deficient ovarian cancer: final results of a multicenter phase 2 study.

To evaluate the long-term efficacy and safety of niraparib in Japanese women with heavily pretreated ovarian cancer. This was the follow-up analysis of a phase 2, multicenter, open-label, single-arm study in Japanese women with homologous recombination-deficient, platinum-sensitive, relapsed, high-grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who had completed 3-4 lines of chemotherapy and were poly(ADP-ribose) polymerase inhibitor naïve. Participants received niraparib (starting dose, 300 mg) once daily in continuous 28-day cycles until objective disease progression, unacceptable toxicity, or consent withdrawal. The primary endpoint was confirmed objective response rate (ORR), as assessed using Response Evaluation Criteria in Solid Tumors version 1.1. Safety evaluations included treatment-emergent adverse events (TEAEs). 20 patients were enrolled in the study and included in both efficacy and safety analyses. Median total study duration was 759.5 days. Median dose intensity was 201.3 mg/day. Confirmed ORR was 60.0% (90% confidence interval [CI]=39.4-78.3); 2 patients had complete response and 10 patients had partial response. Median duration of response was 9.9 months (95% CI=3.9-26.9) and the disease control rate was 90.0% (95% CI=68.3-98.8). The most common TEAEs were anemia (n=15), nausea (n=12), and decreased platelet count (n=11). TEAEs leading to study drug dose reduction, interruption, or discontinuation were reported in 16 (80.0%), 15 (75.0%), and 2 patients (10.0%), respectively. The long-term efficacy and safety profile of niraparib was consistent with previous findings in the equivalent population in non-Japanese patients. No new safety signals were identified. ClinicalTrials.gov Identifier: NCT03759600.

Adverse event profile differences between pralsetinib and selpercatinib: a real-world study based on the FDA adverse events reporting system.

The objective of this study is to compare the adverse events (AEs) associated with pralsetinib and selpercatinib. To evaluate the imbalance of AEs linked to pralsetinib and selpercatinib in real-world data, the reporting odds ratio (ROR) was utilized to detect potential signals of AEs. Stratified analysis was conducted to examine the differences in AEs occurring among different genders and age groups taking pralsetinib and selpercatinib. FAERS received 891 reports for pralsetinib and 569 reports for selpercatinib. Our analysis confirmed expected AEs like hypertension, fatigue, and elevated transaminase levels. Unexpected AEs such as rhabdomyolysis, myocardial injury and cognitive disorder were associated with pralsetinib, while selpercatinib was linked with pulmonary embolism, deep vein thrombosis, and pericardial effusion. The risk of AEs such as decreased platelet count, anemia, decreased white blood cell count, pneumonitis, asthenia, and edema caused by pralsetinib is significantly higher than that of selpercatinib. In contrast, the risk of AEs such as ascites, elevated alanine aminotransferase, and elevated aspartate aminotransferase caused by selpercatinib is significantly higher than that of pralsetinib. Women treated with pralsetinib experience higher rates of hypertension, pulmonary embolism, and blurred vision than men, who are more susceptible to rhabdomyolysis. Adults between 18 and 65years are more likely to experience taste disorder, edema, and pulmonary embolism than individuals older than 65, who are particularly vulnerable to hypertension. For patients treated with selpercatinib, males demonstrate a significantly higher incidence of QT prolongation, urinary tract infection, and dysphagia. Individuals aged 18 to 65 are more likely to experience pyrexia and pleural effusion than those older than 65, who are more prone to hypersensitivity. In the clinical administration of pralsetinib and selpercatinib, it is crucial to monitor the effects of gender and age on AEs and to be vigilant for unlisted AEs.

Phase I/II study of the clinical activity and safety of GSK3326595 in patients with myeloid neoplasms.

GSK3326595 is a potent, selective, reversible protein arginine methyltransferase 5 (PRMT5) inhibitor under investigation for treatment of myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). In preclinical models of AML, PRMT5 inhibition decreased proliferation and increased cell death, supporting additional clinical research in myeloid neoplasms. To determine the clinical activity, safety, tolerability, dosing, additional measures of clinical activity, pharmacokinetics, and pharmacodynamics of GSK3326595. In part 1 of this open-label, multicenter, multipart, phase I/II study, adults with relapsed/refractory myeloid neoplasms (e.g., MDS, CMML, and AML) received monotherapy with 400 or 300 mg oral GSK3326595 once daily. Study termination occurred prior to part 2 enrollment. Clinical activity was determined by the clinical benefit rate (CBR; proportion of patients achieving complete remission (CR), complete marrow remission (mCR), partial remission, stable disease (SD) >8 weeks, or hematologic improvement). Adverse events (AEs) were assessed by incidence and severity. Exploratory examination of spliceosome mutations was performed to determine the relationship between genomic profiles and clinical response to GSK3326595. Thirty patients with a median age of 73.5 years (range, 47-90) were enrolled; 13 (43%) and 17 (57%) received 400 and 300 mg of GSK3326595, respectively. Five (17%) patients met CBR criteria: 4 (13%) with SD >8 weeks and 1 (3%) achieving mCR. Of five patients with clinical benefit: three had SRSF2 mutation, one U2AF1, and one was splicing factor wild-type. Frequent GSK3326595-related AEs were decreased platelet count (27%), dysgeusia (23%), fatigue (20%), and nausea (20%). GSK3326595 had rapid absorption, with a T max of approximately 2 h and a terminal half-life of 4-6 h. GSK3326595 monotherapy had limited clinical activity in heavily pretreated patients despite robust target engagement. The safety profile was broadly consistent with other published PRMT5 inhibitor studies. ClinicalTrials.gov: NCT03614728.